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دانلود کتاب Nelson Textbook of Pediatrics, 2-Volume Set, 20e
دانلود کتاب کتاب درسی کودکان نلسون ، مجموعه 2 جلدی ، 20e
مشخصات کتاب
Nelson Textbook of Pediatrics, 2-Volume Set, 20e
دسته بندی: اطفال ویرایش: 20 نویسندگان: Robert M. Kliegman MD, Bonita M.D. Stanton MD, Joseph St. Geme MD, Nina F Schor MD PhD سری: ISBN (شابک) : 1455775665, 9781455775668 ناشر: Elsevier سال نشر: 2015 تعداد صفحات: 5315 زبان: English فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود) حجم فایل: 172 مگابایت
قیمت کتاب (تومان) : 52,000
کلمات کلیدی مربوط به کتاب کتاب درسی کودکان نلسون ، مجموعه 2 جلدی ، 20e: اورژانس اطفال پریناتولوژی نوزادان داخلی پزشکی بالینی علوم بهداشتی جدید کتاب های درسی اجاره ای استفاده شده بوتیک تخصصی
در صورت تبدیل فایل کتاب Nelson Textbook of Pediatrics, 2-Volume Set, 20e به فرمت های PDF، EPUB، AZW3، MOBI و یا DJVU می توانید به پشتیبان اطلاع دهید تا فایل مورد نظر را تبدیل نمایند.
توجه داشته باشید کتاب کتاب درسی کودکان نلسون ، مجموعه 2 جلدی ، 20e نسخه زبان اصلی می باشد و کتاب ترجمه شده به فارسی نمی باشد. وبسایت اینترنشنال لایبرری ارائه دهنده کتاب های زبان اصلی می باشد و هیچ گونه کتاب ترجمه شده یا نوشته شده به فارسی را ارائه نمی دهد.
توضیحاتی در مورد کتاب کتاب درسی کودکان نلسون ، مجموعه 2 جلدی ، 20e
پس از بیش از 75 سال، کتاب درسی نلسون درسی اطفال لازم منبع شما برای قطعی است ، پاسخ های پیشرفتهدر مورد هر جنبه ای از مراقبت های کودکان. این مرجع کلاسیک با استقبال از پیشرفت‌های جدید در علم و همچنین هنر قدیمی تمرین اطفال، اطلاعات اساسی را ارائه می‌دهد که پزشکان و سایر ارائه‌دهندگان مراقبت‌های مرتبط با مراقبت‌های بهداشتی کودکان در سراسر جهان باید بدانند. به طور موثر به طیف عظیمی از مشکلات زیستی، روانی و اجتماعی که کودکان و جوانان ما ممکن است با آن مواجه شوند، رسیدگی کنید. فصل‌های کاملاً جدید و بازنگری‌های جامع در سراسر این اطمینان را می‌دهد که جدیدترین اطلاعات را در مورد تشخیص و درمان بیماری‌های کودکان بر اساس آخرین توصیه‌ها و روش‌ها در اختیار دارید.
- تشکیل تشخیص قطعی و ایجاد بهترین برنامه های درمانی ممکن با استفاده از پزشکی مبتنی بر شواهد و تجارب بالینی زیرکانه از نویسندگان برجسته بین المللی - بسیاری جدید به این نسخه است.
- یک طرح بندی دو جلدی جدید قابلیت حمل و نقل عالی و سهولت استفاده استثنایی را فراهم می کند.
- دیدگاه کامل تری به دست آورید. همراه با تاکید گسترده تر بر تصویربرداریو تشخیص های مولکولی و مرجعات به روز شده، ویرایش جدید شامل تمرکز فزاینده ای بر مسائل بین المللی برای اطمینان از ارتباط در عمل اطفال در سراسر جهان است. < b>
- به‌طور مؤثر جدیدترین تکنیک‌ها و رویکردها را با به‌روزرسانی‌های کامل در 35 فصل جدید، از جمله: نوآوری‌ها در رسیدگی به سلامت و بقای کودکان در تنظیمات کم درآمد، به کار ببرید. ; حوزه های رشدی و نظریه های شناخت. رویکرد آموزشی رجیو امیلیا کاتاتونیا; سندرم تغذیه مجدد؛ بیماری مرتبط با ارتفاع؛ رویکردهای ژنتیکی به بیماری های نادر و تشخیص داده نشده؛ عفونت های مرتبط با مراقبت های بهداشتی؛ عفونت های داخل و حین زایمان؛ نمک حمام و سایر داروهای سوء مصرف؛ پلی نوروپاتی فیبر کوچک؛ میکروبیوم؛ Kingella kingae; انسفالومیوپاتی عصبی میتوکندریایی گوارشی؛ بیماری کبد چرب غیر الکلی؛ پلاژیوسفالی؛ واسکولیت CNS؛ پارگی رباط صلیبی قدامی؛ و آسیب مغزی تروماتیک مرتبط با ورزش.
- شناخت، تشخیص و مدیریت شرایط ژنتیکی و اکتسابی موثرتر. بخش جدید توانبخشی با 10 فصل جدید، شامل: ارزیابی کودک برای خدمات توانبخشی. آسیب شدید تروماتیک مغزی؛ آسیب نخاعی و مدیریت بحران اتونومیک؛ اسپاستیسیتی؛ فلج شبکه بازویی هنگام تولد. آسیب های تروماتیک و ورزشی؛ مننگومیلوسل؛ سلامت و تندرستی برای کودکان دارای معلولیت.
- مدیریت گذار به مراقبت های بهداشتی بزرگسالان برای کودکان مبتلا به بیماری های مزمن از طریق بحث در مورد نیازهای کلی سلامت بیماران مبتلا به نقایص مادرزادی قلب، دیابت و فیبروز کیستیک.
- اصول درمان را بدانید و اینکه چه داروها و دوزهایی را برای هر بیماری تجویز کنید.
- نسخه کتاب الکترونیکی با کارشناسان مشاوره همراه با خرید ارائه شده است. این تجربه کتاب الکترونیکی پیشرفتهبه شما امکان می‌دهد تمام متن، شکل‌ها و مراجع کتاب را در دستگاه‌های مختلف جستجو کنید.
توضیحاتی درمورد کتاب به خارجی
After more than 75 years, Nelson Textbook of Pediatrics remains your indispensable source for definitive, state-of-the-art answers on every aspect of pediatric care. Embracing the new advances in science as well as the time-honored art of pediatric practice, this classic reference provides the essential information that practitioners and other care providers involved in pediatric health care throughout the world need to understand to effectively address the enormous range of biologic, psychologic, and social problems that our children and youth may face. Brand-new chapters and comprehensive revisions throughout ensure that you have the most recent information on diagnosis and treatment of pediatric diseases based on the latest recommendations and methodologies.
- Form a definitive diagnosis and create the best treatment plans possible using evidence-based medicine and astute clinical experiences from leading international authors-many new to this edition.
- A NEW two-volume layout provides superior portability and exceptional ease of use.
- Gain a more complete perspective. Along with a broader emphasis on imaging and molecular diagnoses and updated references, the new edition includes an increased focus on international issues to ensure relevance in pediatrics practice throughout the world.
- Effectively apply the latest techniques and approaches with complete updates throughout 35 new chapters, including: Innovations in Addressing Child Health and Survival in Low Income Settings; Developmental Domains and Theories of Cognition; The Reggio Emilia Educational Approach Catatonia ; Refeeding Syndrome; Altitude-associated Illness; Genetic Approaches to Rare and Undiagnosed Diseases; Healthcare-Associated Infections; Intrapartum and Peripartum Infections; Bath salts and other drugs of abuse; Small Fiber Polyneuropathy; Microbiome; Kingella kingae; Mitochondrial Neurogastrointestinal Encephalomyopathy; Nonalcoholic Fatty Liver Disease; Plagiocephaly; CNS Vasculitis; Anterior Cruciate Ligament Rupture; and Sports-Related Traumatic Brain Injury.
- Recognize, diagnose, and manage genetic and acquired conditions more effectively. A new Rehabilitation section with 10 new chapters, including: Evaluation of the Child for Rehabilitative Services; Severe Traumatic Brain Injury; Spinal Cord Injury and Autonomic Crisis Management; Spasticity; Birth Brachial Plexus Palsy; Traumatic and Sports-Related Injuries; Meningomyelocele; Health and Wellness for Children with Disabilities.
- Manage the transition to adult healthcare for children with chronic diseases through discussions of the overall health needs of patients with congenital heart defects, diabetes, and cystic fibrosis.
- Understand the principles of therapy and which drugs and dosages to prescribe for every disease.
- Expert Consult eBook version included with purchase. This enhanced eBook experience allows you to search all of the text, figures, and references from the book on a variety of devices.
فهرست مطالب
Nelson Textbook of Pediatrics, 2-Volume Set Copyright page Dedication Contributors Preface Videos The Field of Pediatrics 1 Overview of Pediatrics 1 Overview of Pediatrics Vital Statistics About Child Health (See Also Chapter 1.1) The Changing Pediatric World Morbidities among Children Situational Special-Risk Populations Children in Urban Settings Children in Poverty Children of Immigrants and Racial Minority Groups Including U.S. Native Americans Children of Migrant Workers Homeless Children Runaway and Thrown-Away Children Children Directly Affected By War and Other Forms of Direct Violence Inherent Strengths in Vulnerable Children and Interventions Global Warming The Challenge to Pediatricians Patterns of Healthcare Planning and Implementing a System of Care Health Services for At-Risk Populations Evaluation of Healthcare The Information Explosion of the 21St Century Organization of the Profession and the Growth of Specialization Bibliography 1.1 Innovations in Addressing Child Health and Survival in Low-Income Settings Global Burden and Mortality Trends Causes of Newborn and Child Deaths Understanding Social Determinants and Barriers for Care Evidence-Based Interventions and Innovations to Address Inequities Community Health Workers for Newborn and Child Health The Role of Information Technology and mHealth Platforms Cash Transfers to Reduce Poverty Barriers and Improve Child Health Other Technologies and Innovations Bibliography 2 Quality and Safety in Healthcare for Children 2 Quality and Safety in Healthcare for Children The Need for Quality Improvement What is Quality? Definitions of Quality-Related Terms Framework for Quality Developing Guidelines to Establish the Standard for Quality Improving Quality Model for Improvement Six Sigma LEAN Management Sciences Measuring Quality Analyzing Quality Data Comparing and Reporting Quality Quality and Patient Safety Medical Errors in Children’s Healthcare Key Issues in Patient Safety Systems Approach Developing a Culture of Safety Communication. Teamwork and Authority Gradients. Human Factors Engineering. Reliability. Implications of the U.S. Healthcare Reform for Quality The Evolution of Quality to Outcomes to Value Information Technology and Quality Improvement Quality Improvement or Research? Expanding Individual Quality Improvement Initiatives to Scale International Efforts for Quality Improvement Bibliography 3 Ethics in Pediatric Care 3 Ethics in Pediatric Care Assent and Parental Permission Treatment of Critically ILL Children Transitioning the Goals of Care Withholding and Withdrawing Life-Sustaining Treatment Advance Directives. Artificial Hydration and Nutrition. The Doctrine of Double Effect. Care of Disabled Newborns Declaring Death and Organ Donation Death by Neurologic Criteria Circulatory Death Religious or Cultural Objections to Treatment Pediatric Ethics Committees and Ethics Consultation Newborn Screening and Genetic Testing Adolescent Healthcare Adolescent Assent and Consent Chronic Illness Decisions in Terminally Ill Adolescents Research Balancing Maternal and Fetal Interests Justice and Pediatric Ethics Emerging Issues Bibliography 4 Cultural Issues in Pediatric Care 4 Cultural Issues in Pediatric Care The Importance of Culture to Medical Practice Newly Recognized Cultural Groups The Culture of the Medical Profession Cultural Competence Cultural Awareness Cultural Knowledge Cultural Skill Cultural Encounters Cultural Desire Bibliography 5 Maximizing Children’s Health: 5 Maximizing Children’s Health: Periodicity Guidelines Tasks of Well-Child Care Infancy and Early Childhood Middle Childhood and Adolescence Office Intervention for Behavioral and Mental Health Issues Strength-Based Approaches and Framework Office System Change for Quality Improvement Evidence Caring for the Child and Youth in the Context of the Family and Community Bibliography 5.1 Injury Control Injury Control (Formerly Called Accident Prevention) Scope of the Problem Mortality Nonfatal Injuries Global Child Injuries Principles of Injury Control Risk Factors for Childhood Injuries Age Gender Race and Ethnicity Socioeconomic Status Rural–Urban Location Environment Mechanisms of Injury Motor Vehicle Injuries Occupants Teenage Drivers All-Terrain Vehicles. Bicycle Injuries. Pedestrian Injuries. Ski- and Snowboard-Related Head Injuries. Fire- and Burn-Related Injuries. Poisoning. Drowning. Traumatic Brain Injury. Firearm Injuries. Falls. Violent Behavior and Aggression. Psychosocial Consequences of Injuries Bibliography Growth, Development, and Behavior 6 Overview and Assessment of Variability 6 Overview and Assessment of Variability Biopsychosocial Model and Ecobiodevelopmental Framework: Models of Development Biologic Influences Psychologic Influences: Attachment and Contingency Social Factors: Family Systems and the Ecologic Model Unifying Concepts: The Transactional Model, Risk, and Resilience Developmental Domains and Theories of Emotion and Cognition Psychoanalytic Theories Cognitive Theories Behavioral Theory Theories Commonly Employed in Behavioral Interventions Statistics Used in Describing Growth and Development Bibliography 7 Cognitive Development: 7 Cognitive Development: Methodologies Physical Knowledge Development Social Knowledge Development Theories of Cognitive Development Bibliography 7.1 The Reggio Emilia Educational Approach and Child Development and Learning The Emotional Component The Ethical Component The Aesthetic Component Pedagogic Thinking: Core Concepts Around 3 Major Areas The Image of the Child The Image of the Educator The Image of the Contextual Community The Developmental Theories of Greenspan, Vygotsky, and Malaguzzi Greenspan on Well-Being and the Sense of Self Vygotsky and the Reggio Emilia Approach Reggio Approach and Relationships with Parents Bibliography 8 Assessment of Fetal Growth and Development 8 Assessment of Fetal Growth and Development Somatic Development Embryonic Period Fetal Period Neurologic Development Behavioral Development Psychologic Changes in Parents Threats to Fetal Development Bibliography 9 The Newborn 9 The Newborn Parental Role in Mother–Infant Attachment Prenatal Factors Peripartum and Postpartum Influences The Infant’s Role in Mother–Infant Attachment Physical Examination Interactional Abilities Modulation of Arousal Behavioral States Mutual Regulation Implications for the Pediatrician Optimal Practices Assessing Parent–Infant Interactions Teaching About Individual Competencies Bibliography 10 The First Year 10 The First Year Age 0-2 Months Physical Development Cognitive Development Emotional Development Implications for Parents and Pediatricians Age 2-6 Months Physical Development Cognitive Development Emotional Development and Communication Implications for Parents and Pediatricians Age 6-12 Months Physical Development Cognitive Development Emotional Development Communication Implications for Parents and Pediatricians Bibliography 11 The Second Year 11 The Second Year Age 12-18 Months Physical Development Cognitive Development Emotional Development Linguistic Development Implications for Parents and Pediatricians Age 18-24 Months Physical Development Cognitive Development Emotional Development Linguistic Development Implications for Parents and Pediatricians Bibliography 12 The Preschool Years 12 The Preschool Years Structural Development of the Brain Physical Development Implications for Parents and Pediatricians Language, Cognition, and Play Language Cognition Play Implications for Parents and Pediatricians Emotional and Moral Development Implications for Parents and Pediatricians Bibliography 13 Middle Childhood 13 Middle Childhood Physical Development Implications for Parents and Pediatricians Cognitive Development Implications for Parents and Pediatricians Social, Emotional, and Moral Development Social and Emotional Development Moral Development Implications for Parents and Pediatricians Bibliography 14 Adolescence 14 Adolescence 15 Assessment of Growth 15 Assessment of Growth Procedures for Accurate Measurement Derivation and Interpretation of Growth Charts Analysis of Growth Patterns Other Indices of Growth Body Proportions Skeletal Maturation Dental Development Bibliography 16 Developmental-Behavioral Screening and Surveillance 16 Developmental-Behavioral Screening and Surveillance Measurable Delays Psychosocial Risk Early Intervention Services and Eligibility Criteria Primary Care Challenges in Early Detection Policies of the American Academy of Pediatrics Overcoming Logistical Challenges in Primary Care Early Detection and Intervention Evidence-Based Tools A Workable Process: Step-By-Step Bibliography 17 Childcare: 17 Childcare: Provision and Regulation of Childcare in America Childcare Settings Childcare Licensing, Regulation, and Accreditation Sick Children Childcare’s Role in Child Health and Development Characteristics of Childcare and Associations with Child Developmental Outcomes Childcare and Child Health Childcare and Children with Special Needs Role of Pediatric Providers in Childcare Advising Parents on Childcare Selection Advising Parents on Childcare Health Issues Helping Children with Special Needs Consulting and Partnering with Childcare Providers Bibliography 18 Loss, Separation, and Bereavement 18 Loss, Separation, and Bereavement Separation and Loss Divorce Move/Family Relocation Separation Because of Hospitalization Military Families Parental/Sibling Death Grief and Bereavement Developmental Perspective Role of the Pediatrician in Grief Treatment Spiritual Issues Bibliography 19 Sleep Medicine 19 Sleep Medicine Common Sleep Disorders Insomnia of Childhood Obstructive Sleep Apnea Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Parasomnias Etiology Epidemiology Clinical Manifestations Treatment Sleep-Related Movement Disorders: Restless Legs Syndrome/Periodic Limb Movement Disorder and Rhythmic Movements Etiology Epidemiology Clinical Manifestations Treatment Narcolepsy Etiology Epidemiology Clinical Manifestations and Diagnosis Treatment Delayed Sleep Phase Disorder Etiology Epidemiology Clinical Manifestations Treatment Health Supervision Evaluation of Pediatric Sleep Problems Bibliography Behavioral and PsychiatricDisorders 20 Assessment and Interviewing 20 Assessment and Interviewing Aims of Assessment Presenting Problems General Principles of the Psychosocial Interview Indications for Referral Psychiatric Diagnostic Evaluation Special Considerations in the Diagnostic Evaluation of Infants and Young Children Bibliography 21 Psychological Treatment of Children and Adolescents 21 Psychological Treatment of Children and Adolescents Bibliography 21.1 Psychopharmacology Stimulants and other Adhd Medications Antidepressants Antipsychotics Mood Stabilizers Medication Use in Physical Illness Hepatic Disease Gastrointestinal Disease Kidney Disease Heart Disease Respiratory Disease Neurologic Disease Neuroleptic Malignant Syndrome Serotonin Syndrome Bibliography 21.2 Psychotherapy Behavior Therapy Cognitive-Behavioral Therapy Family Therapy Psychodynamic Psychotherapy Supportive Psychotherapy Parenting Interventions Bibliography 21.3 Psychiatric Hospitalization Bibliography 22 Somatic Symptom and Related Disorders 22 Somatic Symptom and Related Disorders Epidemiology Risk Factors Family and Environmental Genetic Symptom Modeling Parental Responses School and Family Stressors Trauma Individual Childhood Physical Illness Temperament/Coping Styles Learned Behavior Psychiatric Comorbidity Other Biologic Factors Assessment Medical Psychological Differential Diagnoses Management Treatment Treatment Setting Bibliography 23 Rumination and Pica 23 Rumination and Pica 23.1 Rumination Disorder Epidemiology Etiology and Differential Diagnosis Treatment Bibliography 23.2 Pica Epidemiology Etiology and Differential Diagnosis Treatment Bibliography 23.3 Enuresis (Bed-Wetting) 23.4 Encopresis 24 Motor Disorders and Habits 24 Motor Disorders and Habits 24.1 Tic Disorders Description Clinical Course Epidemiology Differential Diagnosis Comorbidities Etiology Sequelae Screening Assessment Treatment 24.2 Stereotypic Movement Disorder Description Clinical Course Epidemiology Comorbidity Differential Diagnosis Etiology Treatment Habits Thumb Sucking Bruxism Bibliography 25 Anxiety Disorders 25 Anxiety Disorders Anxiety Associated with Medical Conditions Safety and Efficacy Concerns About SSRIs Bibliography 26 Mood Disorders 26 Mood Disorders 26.1 Major and Other Depressive Disorders Description Epidemiology Clinical Course Differential Diagnosis Comorbidity Sequelae Etiology and Risk Factors Prevention Screening/Case Finding Stepped Management Early Intervention Treatment Level of Care Bibliography 26.2 Bipolar and Related Disorders Description Epidemiology Clinical Course Differential Diagnosis Comorbidity Sequelae Etiology/Risk Factors Prevention Case Finding Treatment Level of Care Bibliography 27 Suicide and Attempted Suicide 27 Suicide and Attempted Suicide Epidemiology Suicidal Ideation and Attempts Suicide Completions Risk Factors Preexisting Mental Disorder Cognitive Distortions Biologic Factors Social, Environmental, and Cultural Factors Protective Factors Assessment and Intervention Prevention Bibliography 28 Eating Disorders 28 Eating Disorders Definitions Epidemiology Pathology and Pathogenesis Clinical Manifestations Differential Diagnosis Laboratory Findings Complications Treatment Principles Guiding Primary Care Treatment Nutrition and Physical Activity Primary Care Treatment Referral to Mental Health Services Referral to an Interdisciplinary Eating Disorder Team Supportive Care Prognosis Prevention Bibliography 29 Disruptive, Impulse-Control, and Conduct Disorders 29 Disruptive, Impulse-Control, and Conduct Disorders Description Epidemiology Clinical Course Differential Diagnosis Comorbidity Sequelae Etiology and Risk Factors Prevention Screening/Case Finding Stepped Management Early Intervention Treatment Level of Care Bibliography 29.1 Age-Specific Behavioral Disturbances Infancy and Toddlerhood Childhood and Adolescence Lying Stealing Truancy and Running Away Fire Setting Aggression and Bullying Cutting and Other Self-Injurious Behaviors Bibliography 30 Autism Spectrum Disorder 30 Autism Spectrum Disorder Description Social Communication and Interaction Deficits Restricted and Repetitive Patterns Severity Specifiers/Associated Features Epidemiology Etiology/Risk Factors Genetic and Familial Factors Neurobiologic Factors Neuropathology Factors Clinical Course Differential Diagnosis Comorbidities Sequelae Screening/Case Finding Assessment Treatment Psychosocial Interventions Pharmacotherapy Bibliography 31 Childhood Psychoses 31 Childhood Psychoses 31.1 Schizophrenia Spectrum and Other Psychotic Disorders Description Epidemiology Clinical Course Differential Diagnosis Comorbidity Sequelae Etiology and Risk Factors Genetic Factors Environmental Factors Neuroanatomical Abnormalities Prevention Screening/Case Finding Assessment Treatment Pharmacotherapy Bibliography 31.2 Psychosis Associated with Epilepsy Bibliography 31.3 Catatonia in Children and Adolescents Diagnosis and Treatment Bibliography 31.4 Acute Phobic Hallucinations of Childhood Clinical Manifestations Diagnosis and Differential Diagnosis Treatment Bibliography Learning Disorders 32 Neurodevelopmental Function and Dysfunction in the School-Age Child 32 Neurodevelopmental Function and Dysfunction in the School-Age Child Terminology and Epidemiology Etiology and Pathogenesis Core Neurodevelopmental Functions Sensory and Motor Development Language Visual–Spatial/Visual–Perceptual Function Intellectual Function Frontal Lobe Functioning Attention Executive Functioning Memory Social Cognition Clinical Manifestations Reading Spelling and Writing Mathematics Nonacademic Problems Assessment and Diagnosis Treatment Demystification Bypass Strategies (Accommodations) Interventions (Remediation of Skills) Developmental Therapy Curriculum Modifications Strengthening of Strengths Individual and Family Counseling Controversial Therapies Medication Bibliography 33 Attention-Deficit/Hyperactivity Disorder 33 Attention-Deficit/Hyperactivity Disorder Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis and Differential Diagnosis Clinical Interview and History Behavior Rating Scales Physical Examination and Laboratory Findings Differential Diagnosis Treatment Psychosocial Treatments Behaviorally Oriented Treatments Medications Prognosis Prevention Bibliography 34 Dyslexia 34 Dyslexia Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Management Prognosis Bibliography 35 Language Development and Communication Disorders 35 Language Development and Communication Disorders Normal Language Development Receptive Language Development Expressive Language Development Variations of Normal Language and Communication Disorders Epidemiology Etiology Pathogenesis Clinical Manifestations Classification Specific Language Impairment Higher-Level Language Disorder Intellectual Disability Autism and Pervasive Developmental Disorders Asperger Syndrome Selective Mutism Isolated Expressive Language Disorder Motor Speech Disorders Dysarthria Childhood Apraxia of Speech Phonologic Disorder Hearing Impairment Hydrocephalus Rare Causes of Language Impairment Hyperlexia Landau-Kleffner Syndrome (Verbal Auditory Agnosia) Metabolic and Neurodegenerative Disorders Screening Noncauses of Language Delay Diagnostic Evaluation Psychologic Evaluation Cognitive Assessment Evaluation of Social Behaviors Relationship of Language and Social Behaviors to Mental Age Speech and Language Evaluation Medical Evaluation Treatment Prognosis Academic Disorders Comorbid Disorders Emotional and Behavioral Difficulty Motor and Coordination Delays Bibliography 35.1 Childhood-Onset Fluency Disorder: Dysfluency (Stuttering, Stammering) Epidemiology and Etiology Diagnosis Treatment Bibliography 36 Intellectual Disability 36 Intellectual Disability Definition Etiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Differential Diagnosis Diagnostic Psychologic Testing Complications Prevention Treatment Supportive Care and Management Primary Care Interdisciplinary Management Periodic Reevaluation Educational Services Leisure and Recreational Activities Family Counseling Prognosis Bibliography Children with Special Needs 37 Adoption 37 Adoption Role of Pediatricians Preadoption Medical Record Reviews Postadoption Medical Care Arrival Visit–International Adoption Developmental Delays Growth Delays Language Development Eating Concerns Sleep Concerns Social and Emotional Development Racial Identity Development Toxic Stress Family Support Adoption Narrative Bibliography 37.1 Medical Evaluation of Immigrant (Foreign-Born) Children for Infectious Diseases Commonly Encountered Infections Hepatitis B Hepatitis A Hepatitis C Intestinal Pathogens Tuberculosis Congenital Syphilis HIV Infection Immunizations Bibliography 38 Foster and Kinship Care 38 Foster and Kinship Care Epidemiology Legislation in the United States Early Childhood Trauma Leads to Poor Health Outcomes Health Issues Healthcare for Children and Adolescents in Foster Care Bibliography 39 Impact of Violence on Children 39 Impact of Violence on Children Impacts of Violence Diagnosis and Follow-up Bibliography Websites 39.1 Bullying, Cyberbullying, and School Violence Bullying (“Traditional Bullying”) Cyberbullying Epidemiology Health Outcomes School Violence Epidemiology Risk Factors Treatment and Prevention of Bullying and School Violence Bibliography Website Resources 39.2 Effects of War on Children Susceptibility of Children in Times of War Psychologic Impact of War Efforts to Protect Children From the Effects of War International Conventions Humanitarian Efforts The Role of Pediatricians and Allied Health Professionals Bibliography 40 Abused and Neglected Children 40 Abused and Neglected Children Definitions Incidence and Prevalence Global Situation Situation in the United States Etiology Clinical Manifestations General Principles for Assessing Possible Abuse and Neglect General Principles for Addressing Child Maltreatment Outcomes of Child Maltreatment Prevention of Child Abuse and Neglect Advocacy Bibliography General References Physical Abuse Neglect Prevention Professional Issues American Academy of Pediatrics Policy Statements 40.1 Sexual Abuse Definition Presentation of Sexual Abuse The Role of the General Pediatrician in the Assessment and Management of Possible Sexual Abuse Physical Examination of the Child with Suspected Sexual Abuse Sexual Abuse Prevention Bibliography 40.2 Medical Child Abuse (Factitious Disorder by Proxy, Munchausen Syndrome by Proxy) Clinical Manifestations Diagnosis Treatment Bibliography 41 Failure to Thrive 41 Failure to Thrive Clinical Manifestations Etiology and Diagnosis Treatment Prognosis Bibliography 42 Chronic Illness in Childhood 42 Chronic Illness in Childhood Epidemiology Enhanced Needs of Children with Chronic Illness and Their Families Financial Costs Complex Clinical Management Pain Behavioral and Adjustment Issues Impact on Families Comprehensive Care and the Medical Home Preventive Services Continuity of Care Access to Urgent Care Access to Specialty Care Enhanced Information Systems Linkage to Schools, Support Groups, and Community Services Logistic Access Cultural Sensitivity and Language Concordance Nondiscrimination in Access and Clinical Decision Making Bibliography 43 Pediatric Palliative Care 43 Pediatric Palliative Care Care Settings Primary and Subspecialty Palliative Care Communication, Advance Care Planning, and Anticipatory Guidance The Parents The Child The Siblings The Staff Goals of Care and Decision Making Resuscitation Status Symptom Management Intensive Symptom Management The Terminal Phase The Pediatrician Bibliography Nutrition 44 Nutritional Requirements 44 Nutritional Requirements Dietary Reference Intakes Energy Fat Proteins Carbohydrates Fiber Micronutrients Water Measuring Nutritional Adequacy Bibliography 45 Feeding Healthy Infants, Children, and Adolescents 45 Feeding Healthy Infants, Children, and Adolescents Feeding During the First Year of Life Breastfeeding Nipple Pain Engorgement Mastitis Inadequate Milk Intake Jaundice Collecting Breast Milk Growth of the Breastfed Infant Formula Feeding (Fig. 45-1) Cow Milk Protein–Based Formulas Soy Formulas Protein Hydrolysate Formula Amino Acid Formulas Milk and Other Fluids Complementary Feeding Feeding Toddlers and Preschool-Age Children Feeding Practices Eating in the Daycare Setting Feeding School-Age Children and Adolescents MyPlate Eating at Home Eating at School Eating Out Nutrition Issues of Importance Across Pediatric Ages Food Environment Using Food as Reward Cultural Considerations in Nutrition and Feeding Vegetarianism Organic Foods Nutrition as Part of Complementary and Alternative Medicine, Functional Foods, Dietary Supplements, Vitamin Supplements, and Botanical and Herbal Products Food Safety Nutritional Programming Preventive Nutrition Counseling in Pediatric Primary Care Food Assistance Programs in the USA Bibliography 46 Nutrition, Food Security, and Health 46 Nutrition, Food Security, and Health Malnutrition as the Intersection of Food Insecurity and Health Insecurity Food Security Measuring Food Insecurity Nutrition, Food Security, and Poverty Food Security and Nutrition Targets Future Food Security Undernutrition Measurement of Undernutrition Prevalence of Undernutrition Consequences of Undernutrition Key Interventions Clinical Manifestations and Treatment of Undernutrition Severe Acute Malnutrition Clinical Manifestations of Severe Acute Malnutrition (Table 46-6) Pathophysiology Principles of Treatment 46.1 Refeeding Syndrome Bibliography 47 Overweight and Obesity 47 Overweight and Obesity Epidemiology Body Mass Index Etiology Environmental Changes Genetics Endocrine and Neural Physiology Comorbidities Identification Evaluation Intervention Prevention Bibliography 48 Vitamin A Deficiencies and Excess 48 Vitamin A Deficiencies and Excess Overview of Vitamin A Metabolism of Vitamin A Vitamin A Status in Neonates Inflammation as a Cause of Low Plasma Retinol Functions of Vitamin a and Mechanisms of Action Vitamin a Deficiency Clinical Manifestations of Vitamin A Deficiency Diagnosis Epidemiology and Public Health Issues Dietary Reference Intakes for the Healthy Population Vitamin A for Treatment of Deficiency Hypervitaminosis A Bibliography 49 Vitamin B Complex Deficiencies and Excess 49 Vitamin B Complex Deficiencies and Excess 49.1 Thiamine (Vitamin B1) Deficiency Clinical Manifestations Diagnosis Prevention Treatment Toxicity Bibliography 49.2 Riboflavin (Vitamin B2) Deficiency Clinical Manifestations Diagnosis Prevention Treatment Toxicity Bibliography 49.3 Niacin (Vitamin B3) Deficiency Clinical Manifestations Diagnosis Prevention Treatment Toxicity Bibliography 49.4 Vitamin B6 (Pyridoxine) Deficiency Clinical Manifestations Diagnosis Prevention Treatment Toxicity Bibliography 49.5 Biotin Bibliography 49.6 Folate Deficiency Clinical Manifestations Diagnosis Prevention Treatment Toxicity Bibliography 49.7 Vitamin B12 (Cobalamin) Deficiency Clinical Manifestations Diagnosis Treatment Prevention Bibliography 50 Vitamin C (Ascorbic Acid) 50 Vitamin C (Ascorbic Acid) Dietary Needs and Sources Deficiency Clinical Features Laboratory Findings and Diagnosis Differential Diagnosis Treatment Prevention Toxicity Bibliography 51 Rickets and Hypervitaminosis D 51 Rickets and Hypervitaminosis D Rickets Etiology Clinical Manifestations Radiology Diagnosis Clinical Evaluation Vitamin D Disorders Vitamin D Physiology Nutritional Vitamin D Deficiency Etiology Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Prognosis Prevention Congenital Vitamin D Deficiency Secondary Vitamin D Deficiency Etiology Treatment Vitamin D–Dependent Rickets, Type 1 Treatment Vitamin D–Dependent Rickets, Type 2 Treatment Chronic Kidney Disease (See Chapter 535.2) Treatment Calcium Deficiency Pathophysiology Clinical Manifestations Diagnosis Treatment Phosphorous Deficiency Inadequate Intake Fibroblast Growth Factor-23 X-Linked Hypophosphatemic Rickets Pathophysiology Clinical Manifestations Laboratory Findings Treatment Prognosis Autosomal Dominant Hypophosphatemic Rickets Autosomal Recessive Hypophosphatemic Rickets Hereditary Hypophosphatemic Rickets with Hypercalciuria Pathophysiology Clinical Manifestations Laboratory Findings Treatment Overproduction of FGF-23 Fanconi Syndrome Dent Disease (See Chapter 531.3) Rickets of Prematurity (See Chapter 106) Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis Prevention Treatment Distal Renal Tubular Acidosis (See Chapter 530) Hypervitaminosis D Etiology Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Prognosis Bibliography 52 Vitamin E Deficiency 52 Vitamin E Deficiency Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Prognosis Prevention Bibliography 53 Vitamin K Deficiency 53 Vitamin K Deficiency Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Prevention Bibliography 54 Micronutrient Mineral Deficiencies 54 Micronutrient Mineral Deficiencies Bibliography Fluid and Electrolyte Disorders 55 Electrolyte and Acid-Base Disorders 55 Electrolyte and Acid-Base Disorders 55.1 Composition of Body Fluids Total Body Water Fluid Compartments Electrolyte Composition Osmolality Bibliography 55.2 Regulation of Osmolality and Volume Regulation of Osmolality Regulation of Volume Bibliography 55.3 Sodium Sodium Metabolism Body Content and Physiologic Function Intake Excretion Hypernatremia Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Hyponatremia Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 55.4 Potassium Potassium Metabolism Body Content and Physiologic Function Intake Excretion Hyperkalemia Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Hypokalemia Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 55.5 Magnesium Magnesium Metabolism Body Content and Physiologic Function Intake Excretion Hypomagnesemia Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Hypermagnesemia Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 55.6 Phosphorus Phosphorus Metabolism Body Content and Physiologic Function Intake Excretion Hypophosphatemia Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Hyperphosphatemia Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 55.7 Acid–Base Balance Acid–Base Physiology Introduction and Terminology Physiologic Buffers Normal Acid–Base Balance Renal Mechanisms Clinical Assessment of Acid–Base Disorders Terminology Diagnosis Metabolic Acidosis Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Metabolic Alkalosis Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Respiratory Acidosis Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Respiratory Alkalosis Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 56 Maintenance and Replacement Therapy 56 Maintenance and Replacement Therapy Maintenance Therapy Maintenance Water Intravenous Solutions Glucose Selection of Maintenance Fluids Variations in Maintenance Water and Electrolytes Replacement Fluids Bibliography 57 Deficit Therapy 57 Deficit Therapy Clinical Manifestations Laboratory Findings Calculation of the Fluid Deficit Approach to Severe Dehydration Monitoring and Adjusting Therapy Hyponatremic Dehydration Hypernatremic Dehydration Bibliography 58 Fluid and Electrolyte Treatment of Specific Disorders 58 Fluid and Electrolyte Treatment of Specific Disorders Acute Diarrhea Pyloric Stenosis Perioperative Fluids Pediatric Drug Therapy 59 Pediatric Pharmacogenetics, Pharmacogenomics, and Pharmacoproteomics 59 Pediatric Pharmacogenetics, Pharmacogenomics, and Pharmacoproteomics Pharmacogenetics, Pharmacogenomics, and the Concept of Personalized Medicine Definition of Pharmacogenetic Terms Developmental or Pediatric Pharmacogenetics and Pharmacogenomics Pharmacogenetic, Pharmacogenomic, and Pharmacoproteomic and Metabolomic Tools Developmental Pharmacogenetics of Drug Biotransformation: Applications to Pediatric Drug Therapy Practice CYP2D6 CYP2C9 CYP2C19 CYP3A4, CYP3A5, and CYP3A7 Glucuronosyltransferases Arylamine N-Acetyltransferases Thiopurine S-Methyltransferase Pharmacogenetics of Drug Transporters The Adenosine Triphosphate–Binding Cassette Superfamily Organic Anion Transporting Polypeptides Organic Cation Transporters Pharmacogenetics of Drug Response: Polymorphisms in Drug Receptors, Ion Channels, and Other Drug Targets During Growth and Development Current and Future Applications for Pharmacogenetics and Pharmacogenomics in Pediatrics Bibliography 60 Principles of Drug Therapy 60 Principles of Drug Therapy General Pharmacokinetic and Pharmacodynamic Principles The Impact of Ontogeny on Drug Disposition Drug Absorption Peroral Absorption Extravascular Drug Absorption Drug Distribution Drug Metabolism Renal Drug Elimination Impact of Ontogeny on Pharmacodynamics Surrogate End Points Additional Considerations in Pediatric Therapeutics Drug-Level Monitoring Drug Formulation and Administration Peroral Drug Administration Parenteral Drug Administration Other Routes for Drug Administration Adherence and Compliance Drug–Drug Interactions Adverse Drug Reactions Personalized Medicine Bibliography 61 Anesthesia, Perioperative Care, and Sedation 61 Anesthesia, Perioperative Care, and Sedation General Anesthesia Analgesia Hypnosis and Amnesia Akinesia (Immobility or Muscular Relaxation) Physiologic Support Vigilance Induction of General Anesthesia Inhalational Anesthetics Respiratory Effects Cardiovascular Effects Specific Anesthetics Sevoflurane Isoflurane Desflurane Nitrous Oxide Intravenous Anesthetic Agents Propofol Barbiturates Etomidate Ketamine Opioids Benzodiazepines Dexmedetomidine Complications During Induction of Anesthesia Parental Presence During Induction of Anesthesia Maintenance of Anesthesia Fluid Maintenance During Surgery and Anesthesia Recovery from Anesthesia Postanesthesia Care Unit Complications in the Postanesthesia Care Unit Respiratory Depression Awareness During Anesthesia Postoperative Nausea and Vomiting Thermoregulation and Malignant Hyperthermia Postoperative Apnea Preanesthetic Evaluation Airway Evaluation Mediastinal Masses Down Syndrome Cardiovascular System Neurobehavioral Considerations Preoperative Preparation Preoperative Fasting The Full Stomach Postoperative Pain Management Regional Anesthesia Bibliography 61.1 Sedation and Procedural Pain Bibliography 61.2 Anesthetic Neurotoxicity Bibliography 62 Pediatric Pain Management 62 Pediatric Pain Management Definition and Categories of Pain The Assessment and Measurement of Pain in Children Age-Specific and Developmentally Specific Measures The Newborn and Infant The Older Child The Cognitively Impaired Child A Conceptual Framework for the Treatment of Pediatric Pain Pharmacologic Treatment of Pain Developmental Pharmacology Acetaminophen, Aspirin, Nonsteroidal Antiinflammatory, and Coxib Drugs Opioids Local Anesthetics Unconventional Medications in Pediatric Pain Antidepressant Medications Tricyclic Antidepressants Serotonin and Serotonin-Norepinephrine Reuptake Inhibitors Antiepileptic Drugs Benzodiazepines Antipsychotics and Major Sedatives Nonpharmacologic Treatment of Pain Other Psychologic or Psychiatric Treatment Invasive Interventions in Treating Pain Head and Neck Blocks Upper-Extremity Blocks Trunk and Abdominal Visceral Blocks Lower-Extremity Blocks Sympathetic Blocks Epidural Anesthesia (Thoracic, Lumbar, and Caudal) Intrathecal Analgesia Nerve Ablation and Destruction Considerations for Special Pediatric Populations Pain Perception and Effects of Pain on Newborns and Infants Children with Cancer Pain Children with Pain Associated with Advanced Disease Examples of Chronic and Recurrent Pain Syndromes Complex Regional Pain Syndromes Myofascial Pain Disorders and Fibromyalgia Erythromelalgia Other Chronic Pain Conditions in Children Managing Complex Chronic Pain Problems Bibliography 63 Poisoning 63 Poisoning Prevention Approach to the Poisoned Patient Initial Evaluation History Description of the Exposure Symptoms Past Medical History Social History Physical Examination Laboratory Evaluation Additional Diagnostic Testing Principles of Management Supportive Care Antidotes Decontamination Syrup of Ipecac Gastric Lavage Single-Dose Activated Charcoal Whole-Bowel Irrigation Enhanced Elimination Urinary Alkalinization Hemodialysis Multiple-Dose Activated Charcoal Intralipid Emulsion Therapy Selected Compounds Commonly Involved in Pediatric Poisonings Pharmaceuticals Analgesics Acetaminophen. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Salicylates. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Ibuprofen and Other Nonsteroidal Antiinflammatory Drugs. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Oral Opioids. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Cardiovascular Medications β-Adrenergic Receptor Blockers. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Calcium Channel Blockers. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Clonidine. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Digoxin. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Iron. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Oral Hypoglycemics Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Psychiatric Medications: Antidepressants Tricyclic Antidepressants. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Selective Serotonin Reuptake Inhibitors. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Atypical Antidepressants. Clinical and Laboratory Manifestations. Treatment. Monoamine Oxidase Inhibitors. Psychiatric Medications: Antipsychotics Pathophysiology. Clinical and Laboratory Manifestations. Management. Household Products Caustics Pathophysiology. Clinical Manifestations. Treatment. Cholinesterase-Inhibiting Insecticides Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Hydrocarbons Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Toxic Alcohols Methanol. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Ethylene Glycol. Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Plants Toxic Gases Carbon Monoxide Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Hydrogen Cyanide Pathophysiology. Clinical and Laboratory Manifestations. Treatment. Some Miscellaneous Toxic Agents Found in the Home Single-Use Detergent Sacs Electric Dishwasher Detergent Magnets Batteries Bibliography 64 Complementary Therapies and Integrative Medicine 64 Complementary Therapies and Integrative Medicine Dietary Supplements Dietary Supplement Safety Dietary Supplement Efficacy Massage and Chiropractic Mind–Body Therapies Acupuncture Bibliography Internet Resources The Acutely Ill Child 65 Evaluation of the Sick Child in the Office and Clinic 65 Evaluation of the Sick Child in the Office and Clinic History Physical Exam Risk Factors Management Disposition Bibliography 66 Emergency Medical Services for Children 66 Emergency Medical Services for Children The Primary Care Physician and Office Preparedness Staff Training and Continuing Education Protocols Resuscitation Equipment Transport Pediatric Prehospital Care Access to the EMS System Provider Capability Destination Determination The Emergency Department Emerging Issues in EMSC Disaster Preparedness Bibliography 66.1 Interfacility Transport of the Seriously Ill or Injured Pediatric Patient Communications and Dispatch Center Medical Control Physician Transport Team Ground Versus Air Ambulance Transport Physiology Safety Family-Centered Care Referring Hospital Responsibilities Educational Outreach Bibliography 66.2 Outcomes and Risk Adjustment Outcome Measures in Emergency Medical Services for Children Risk Adjustment Risk Adjustment Tools in EMSC Pediatric Risk of Admission II Revised Pediatric Emergency Assessment Tool Bibliography 66.3 Principles Applicable to the Developing World EMSC and the Continuum of Care Model Applying the Continuum of Care Model to the Developing World Prevention Infectious Diseases Injuries Out-of-Hospital Care Access to Care Prehospital Care Methods of Transport Hospital-Based Care Triage Pediatric-Specific Emergency Centers Practitioners Clinical Guidelines Trauma Equipment Inpatient Services Humanitarian Disasters Exchange and Dissemination of Information Bibliography 67 Pediatric Emergencies and Resuscitation 67 Pediatric Emergencies and Resuscitation Approach to the Emergency Evaluation of a Child General Assessment Primary Assessment Airway and Breathing Circulation Disability The Alert, Verbal, Pain, Unresponsive Pediatric Response Scale. The Glasgow Coma Scale. Exposure Secondary Assessment Tertiary Assessment Recognition and Treatment of Respiratory Distress and Failure Airway Obstruction Airway Narrowing Parenchymal Lung Disease Advanced Airway Management Techniques Bag-Valve-Mask Positive Pressure Ventilation Endotracheal Intubation Recognition and Management of Shock Recognition of Bradyarrhythmias and Tachyarrhythmias Bradyarrhythmias Tachyarrhythmias Recognition and Management of Cardiac Arrest Vascular Access Venous Access Intraosseous Access Arterial Access Nonvascular Emergency Procedures Thoracentesis and Chest Tube Placement Pericardiocentesis Postresuscitation Care Bibliography 68 Neurologic Emergencies and Stabilization 68 Neurologic Emergencies and Stabilization Neurocritical Care Principles Traumatic Brain Injury Etiology Epidemiology Pathology Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Supportive Care Prognosis Bibliography 68.1 Brain Death Epidemiology Clinical Manifestations and Diagnosis Coma Brainstem Reflexes Apnea Observation Periods Ancillary Studies Documentation Supportive Care Objections to the Idea of Brain Death Bibliography 69 Syncope 69 Syncope Epidemiology Mechanisms Evaluation Treatment Bibliography 69.1 Disorders of Orthostatic Intolerance Bibliography 70 Shock 70 Shock Epidemiology Definition Pathophysiology Clinical Manifestations Diagnosis Laboratory Findings Treatment Initial Management Additional Early Considerations Considerations for Continued Therapy Prognosis Bibliography 71 Respiratory Distress and Failure 71 Respiratory Distress and Failure Respiratory Distress Respiratory Disease Manifesting as Respiratory Distress Respiratory Distress without Respiratory Disease Cardiovascular Disease Manifesting as Respiratory Distress Neurologic Disease Manifesting as Respiratory Distress Toxic-Metabolic States Manifesting as Respiratory Distress Other Nonpulmonary Entities Manifesting as Respiratory Distress Respiratory Failure Pathophysiology of Respiratory Failure Ventilation–Perfusion Mismatch, Venous Admixture, Intrapulmonary Shunt Diffusion Monitoring a Child in Respiratory Distress and Respiratory Failure Clinical Examination Blood Gas Abnormalities in Respiratory Distress and Respiratory Failure Acid–Base Abnormalities in a Child with Respiratory Distress and Respiratory Failure Metabolic Acidosis with Respiratory Compensation Respiratory Acidosis with Metabolic Compensation Assessment of Oxygenation and Ventilation Deficits Management Oxygen Administration Airway Adjuncts Inhaled Gases Positive-Pressure Respiratory Support Endotracheal Intubation and Mechanical Ventilation Transient Manual Ventilation in the Immediate Preintubation and Postintubation Periods Bibliography 71.1 Mechanical Ventilation Basic Concepts of Ventilator Management Equation of Motion Functional Residual Capacity Time Constant Critical Opening Pressure Phases of Mechanical Ventilation Initiation of Inspiration and the Control Variable (Mode) Control Modes Intermittent Mandatory Ventilation Mode Assist-Control Mode Control Variable Support Modes Inspiratory Phase Characteristics Termination of Inspiration (Cycle) Expiratory Phase Maneuvers Additional Ventilatory Modalities Airway Pressure Release Ventilation High-Frequency Ventilation Conventional Ventilator Settings Fio2 Mode Tidal Volume and Rate Inspiratory Time and Expiratory Time Positive End-Expiratory Pressure Patient-Ventilator Asynchrony Triggering the Ventilator Selection of Appropriate Inspiratory Time Selection of Inspiratory Flow Pattern Use of Support Modes Use of Sedation and Pharmacologic Paralysis Cardiopulmonary Interactions Monitoring Respiratory Mechanics Exhaled Tidal Volume Peak Inspiratory Pressure Respiratory System Dynamic Compliance and Static Compliance Assessment of Auto-PEEP Assessment of Dead Space Ventilation Ventilator-Induced LUNG Injury Ventilator-Associated Pneumonia Weaning Bibliography 71.2 Long-Term Mechanical Ventilation 72 Acute Care of the Victim of Multiple Trauma 72 Acute Care of the Victim of Multiple Trauma Epidemiology Regionalization and Trauma Teams Primary Survey Airway/Cervical Spine Breathing Circulation Neurologic Deficit Exposure and Environmental Control Secondary Survey Head Trauma Cervical Spine Trauma Thoracic Trauma Abdominal Trauma Pelvic Trauma Lower Genitourinary Trauma Extremity Trauma Radiologic and Laboratory Evaluation Psychological and Social Support Bibliography 72.1 Care of Abrasions and Minor Lacerations Lacerations and Cuts Epidemiology Evaluation Treatment Abrasions Treatment Bibliography 73 Altitude-Associated Illness in Children (Acute Mountain Sickness) 73 Altitude-Associated Illness in Children (Acute Mountain Sickness) Etiology Definitions Environmental Considerations General Effects of Hypobaric Hypoxia Acclimatization Acute Mountain Sickness Epidemiology and Risk Factors Pathophysiology Diagnosis Periodic Breathing Management Prevention High Altitude Cerebral Edema Epidemiology and Risk Factors Pathophysiology Diagnosis Management High Altitude Pulmonary Edema Epidemiology and Risk Factors Physiology Diagnosis Management Special Considerations Reentry HAPE Symptomatic High-Altitude Pulmonary Hypertension Travel With Young Infants Sickle Trait/Disease Prevention Bibliography 74 Drowning and Submersion Injury 74 Drowning and Submersion Injury Etiology Epidemiology Children Younger Than 1 Year of Age Children 1-4 Years of Age School-age Children Adolescents Underlying Conditions Alcohol Use Sports and Recreation Global Impact of Drowning Pathophysiology Anoxic–Ischemic Injury Pulmonary Injury Cold Water Injury Management Initial Evaluation and Resuscitation Hospital-Based Evaluation and Treatment Cardiorespiratory Management Neurologic Management Other Management Issues Hypothermia Management Prognosis Prevention Bibliography 75 Burn Injuries 75 Burn Injuries Epidemiology Prevention Acute Care, Resuscitation, and Assessment Indications for Admission First Aid Measures Emergency Care Classification of Burns Estimation of Body Surface Area for a Burn Treatment Outpatient Management of Minor Burns Fluid Resuscitation Prevention of Infection and Surgical Management of the Burn Wound Nutritional Support Topical Therapy Inhalational Injury Pain Relief and Psychologic Adjustment Reconstruction and Rehabilitation School Reentry and Long-Term Outcome Special Situations Electrical Burns Bibliography Useful Links 76 Cold Injuries 76 Cold Injuries Pathophysiology Etiology Clinical Manifestations Frostnip Immersion Foot (Trench Foot) Frostbite Hypothermia Chilblain (Pernio) Cold-Induced Fat Necrosis (Panniculitis) Bibliography Human Genetics 77 Integration of Genetics Into Pediatric Practice 77 Integration of Genetics Into Pediatric Practice Diagnostic Testing Predictive Testing Predispositional Testing Pharmacogenetic Testing 77.1 Genetic Counseling Talking to Families Genetic Counseling Specific Condition or Conditions Knowledge of the Diagnosis of the Particular Condition Natural History of the Condition Genetic Aspects of the Condition and Recurrence Risk Prenatal Diagnosis and Prevention Therapies and Referral Support Groups Follow-up Nondirective Counseling 77.2 Management and Treatment of Genetic Disorders Physiologic Therapies Replacement Therapies Enzyme Replacement Transplantation Bibliography 78 The Genetic Approach in Pediatric Medicine 78 The Genetic Approach in Pediatric Medicine The Burden of Genetic Disorders in Childhood The Changing Paradigm of Genetics in Medicine Ethics Issues Bibliography 79 The Human Genome 79 The Human Genome Fundamentals of Molecular Genetics Genetic Variation Genotype-Phenotype Correlations in Genetic Disease Human Genome Project Bibliography 80 Patterns of Genetic Transmission 80 Patterns of Genetic Transmission Family History and Pedigree Notation Mendelian Inheritance Autosomal Dominant Inheritance Autosomal Recessive Inheritance Pseudodominant Inheritance X-Linked Inheritance Y-Linked Inheritance Digenic Inheritance Pseudogenetic Inheritance and Familial Clustering Nontraditional Inheritance Mitochondrial Inheritance Triplet Repeat Expansion Disorders Genetic Imprinting Multifactorial and Polygenic Inheritance Bibliography 81 Cytogenetics 81 Cytogenetics 81.1 Methods of Chromosome Analysis Bibliography 81.2 Down Syndrome and Other Abnormalities of Chromosome Number Aneuploidy and Polyploidy Down Syndrome Bibliography 81.3 Abnormalities of Chromosome Structure Translocations Inversions Deletions and Duplications Insertions Isochromosomes Marker and Ring Chromosomes Bibliography 81.4 Sex Chromosome Aneuploidy Turner Syndrome Klinefelter Syndrome 47,XYY Bibliography 81.5 Fragile Chromosome Sites Bibliography 81.6 Mosaicism Pallister-Killian Syndrome Hypomelanosis of Ito 81.7 Chromosome Instability Syndromes 81.8 Uniparental Disomy and Imprinting Uniparental Disomy Imprinting Bibliography 82 Genetics of Common Disorders 82 Genetics of Common Disorders 82.1 Major Genetic Approaches to the Study of Common Pediatric Disorders Linkage Mapping Genetic Association Bibliography 83 Genetic Approaches to Rare and Undiagnosed Diseases 83 Genetic Approaches to Rare and Undiagnosed Diseases Scope of Genetic Disease Clinical Evaluation Available Commercial Laboratory Genetic Studies Single-Nucleotide Polymorphism Arrays Exome Sequencing Gene Function Studies Pediatric Issues Considerations for Families of Undiagnosed Children The Diagnostic Spectrum Bibliography Metabolic Disorders 84 An Approach to Inborn Errors of Metabolism 84 An Approach to Inborn Errors of Metabolism Common Characteristics of Genetic Disorders of Metabolism Mass Screening of Newborn Infants Clinical Manifestations of Genetic Metabolic Diseases Treatment Bibliography 85 Defects in Metabolism of Amino Acids 85 Defects in Metabolism of Amino Acids 85.1 Phenylalanine Classic Phenylketonuria Clinical Manifestations Nonphenylketonuria Hyperphenylalaninemias (Milder Forms of Hyperphenylalaninemia) Diagnosis Neonatal Screening for Hyperphenylalaninemia Treatment Pregnancy in Women with Hyperphenylalaninemia (Maternal Phenylketonuria) Hyperphenylalaninemia Caused by Deficiency of the Cofactor Tetrahydrobiopterin Clinical Manifestations Diagnosis Treatment Genetics and Prevalence Tetrahydrobiopterin Defects Without Hyperphenylalaninemia Bibliography 85.2 Tyrosine Tyrosinemia Type I (Tyrosinosis, Hereditary Tyrosinemia, Hepatorenal Tyrosinemia) Clinical Manifestations and Natural History Laboratory Findings Treatment and Outcome Genetics and Prevalence Tyrosinemia Type II (Richner-Hanhart Syndrome, Oculocutaneous Tyrosinemia) Tyrosinemia Type III (Primary Deficiency of 4-Hydroxyphenylpyruvate Dioxygenase [4-HPPD]) Hawkinsinuria Transient Tyrosinemia of the Newborn Alkaptonuria Tyrosine Hydroxylase Deficiency Albinism (See also Chapters 622 and 653) Oculocutaneous (Generalized) Albinism OCA1 (Tyrosinase-Deficient Albinism) OCA1 A (Tyrosinase-Negative OCA) OCA1 B OCA2 (Tyrosinase-Positive OCA) OCA3 (Rufous Albinism) OCA4 Ocular Albinism Ocular Albinism 1 (Nettleship-Falls Type) Syndromic Forms of Generalized Albinism Hermansky-Pudlak Syndrome Chédiak-Higashi Syndrome Localized Albinism Piebaldism Waardenburg Syndrome Bibliography 85.3 Methionine Homocystinuria (Homocystinemia) Homocystinuria Caused by Cystathionine β-Synthase Deficiency (Classic Homocystinuria) Homocystinuria Caused by Defects in Methylcobalamin Formation Homocystinuria Caused by Deficiency of Methylenetetrahydrofolate Reductase Hypermethioninemia Primary (Genetic) Hypermethioninemia Acquired (Nongenetic) Hypermethioninemia Cystathioninemia (Cystathioninuria) Bibliography 85.4 Cysteine/Cystine Sulfite Oxidase Deficiency (Molybdenum Cofactor Deficiency) Bibliography 85.5 Tryptophan Hartnup Disorder Bibliography 85.6 Valine, Leucine, Isoleucine, and Related Organic Acidemias Maple Syrup Urine Disease Classic Maple Syrup Urine Disease Intermediate (Mild) Maple Syrup Urine Disease Intermittent Maple Syrup Urine Disease Thiamine-Responsive Maple Syrup Urine Disease Maple Syrup Urine Disease Caused by a Deficiency of E3 Subunit (Maple Syrup Urine Disease Type 3) Genetics and Prevalence of Maple Syrup Urine Disease Isovaleric Acidemia Multiple Carboxylase Deficiencies (Defects in Utilization of Biotin) Holocarboxylase Synthetase Deficiency (Multiple Carboxylase Deficiency Neonatal or Early Form) Biotinidase Deficiency (Multiple Carboxylase Deficiency—Juvenile or Late Form) Multiple Carboxylase Deficiency Because of Dietary Biotin Deficiency Isolated 3-Methylcrotonyl Coenzyme a (CoA) Carboxylase Deficiency 3-Methylglutaconic Aciduria 3-Methylglutaconic Aciduria Type I (3-Methylglutaconyl Coenzyme A Hydratase Deficiency) 3-Methylglutaconic Aciduria Type II (X-Linked Cardiomyopathy, Neutropenia, Growth Retardation, and 3-Methylglutaconic Aciduria with Normal 3-Methylglutaconyl Coenzyme A Hydratase, Barth Syndrome) 3-Methylglutaconic Aciduria Type III (Costeff Optic Atrophy Syndrome) β-Ketothiolase (3-Oxothiolase) Deficiency (Mitochondrial Acetoacetyl Coenzyme a Thiolase [T2] Deficiency) Cytosolic Acetoacetyl Coenzyme a Thiolase Deficiency Mitochondrial 3-Hydroxy-3-Methylglutaryl Coenzyme a Synthase Deficiency 3-Hydroxy-3-Methylglutaric Aciduria Succinyl Coenzyme A:3-Ketoacid Coenzyme a Transferase (SCOT) Deficiency Mevalonic Aciduria Mevalonic Aciduria, Severe Form Periodic Fever with Hyperimmunoglobulinemia D (Mevalonic Aciduria, Mild Form) Treatment Propionic Acidemia (Propionyl Coenzyme a Carboxylase Deficiency) Methylmalonic Acidemia Defects in Metabolism of Vitamin B12 (Cobalamin) Combined Methylmalonic Aciduria and Homocystinuria (cblC, cblD, cblF, cblJ, and cblX Defects) Bibliography 85.7 Glycine Hypoglycinemia Hyperglycinemia Nonketotic Hyperglycinemia, Glycine Encephalopathy Neonatal Hyperglycemia Infantile Nonketotic Hyperglycinemia Late-Onset Nonketotic Hyperglycinemia, Mild Episodic Form Transient Nonketotic Hyperglycinemia Sarcosinemia d-Glyceric Aciduria Trimethylaminuria Hyperoxaluria and Oxalosis Primary Hyperoxaluria Type 1 Primary Hyperoxaluria Type 2 (l-Glyceric Aciduria) Primary Hyperoxaluria Type 3 Creatine Deficiency Bibliography 85.8 Serine 3-Phosphoglycerate Dehydrogenase Deficiency Phosphoserine Aminotransferase Deficiency Bibliography 85.9 Proline Hyperprolinemia Hyperprolinemia Type I Hyperprolinemia Type II Prolidase Deficiency Bibliography 85.10 Glutamic Acid Glutathione Synthetase Deficiency Glutathione Synthetase Deficiency, Severe Form (Pyroglutamic Acidemia, Severe 5-Oxoprolinuria) and Moderate Form Glutathione Synthetase Deficiency, Mild Form 5-Oxoprolinase Deficiency (5-Oxoprolinuria) γ-Glutamylcysteine Synthetase Deficiency Glutathionemia (γ-Glutamyl Transpeptidase Deficiency) Genetic Disorders of Metabolism of γ-Aminobutyric Acid Congenital Glutamine Deficiency Bibliography 85.11 Genetic Disorders of Neurotransmitters Tyrosine Hydroxylase Deficiency (Infantile Parkinsonism, Autosomal Recessive Dopa-Responsive Dystonia, Segawa Syndrome, Autosomal Recessive Form) Aromatic l-Amino Acid Decarboxylase Deficiency Tetrahydrobiopterin Deficiency Tetrahydrobiopterin Deficiency with Hyperphenylalaninemia Tetrahydrobiopterin Deficiency Without Hyperphenylalaninemia Hereditary Progressive Dystonia, Autosomal Dominant Dopa-Responsive Dystonia, Segawa Syndrome, Autosomal Dominant Form Sepiapterin Reductase Deficiency Dopamine β-Hydroxylase Deficiency Monoamine Oxidase (MAO) Deficiency γ-Aminobutyric Acid (GABA) γ-Aminobutyric Acid Transaminase Deficiency Succinic Semialdehyde Dehydrogenase Deficiency (γ-Hydroxybutyric Aciduria) Defects in Neurotransmitters Transporter Proteins Dopamine Transporter Protein Deficiency Dopamine–Serotonin Vesicular Transporter Disease (Vesicular Monoamine Transporter Deficiency) Histidine Decarboxylase Deficiency Hyperprolinemia 3-Phosphoglycerate Dehydrogenase Deficiency Phosphoserine Aminotransferase Deficiency Nonketotic Hyperglycinemia Bibliography 85.12 Urea Cycle and Hyperammonemia (Arginine, Citrulline, Ornithine) Genetic Causes of Hyperammonemia Clinical Manifestations of Hyperammonemia Diagnosis Treatment of Acute Hyperammonemia Long-Term Therapy Carbamyl Phosphate Synthetase and N-Acetylglutamate Synthetase Deficiencies Ornithine Transcarbamylase Deficiency Argininosuccinate Synthetase (ASS) Deficiency (Citrullinemia) Citrullinemia Type I (Classic Citrullinemia) Citrullinemia Resulting From Citrin Deficiency (Citrullinemia Type II) Neonatal Intrahepatic Cholestasis (Citrullinemia Type II—Neonatal Form) Citrullinemia Type II, Adult Form (Adult-Onset Citrullinemia, Citrullinemia Type II—Mild Form) Argininosuccinate Lyase Deficiency (Argininosuccinic Aciduria) Arginase Deficiency (Hyperargininemia) Transient Hyperammonemia of the Newborn Ornithine Gyrate Atrophy of the Retina and Choroid Hyperammonemia-Hyperornithinemia-Homocitrullinemia Syndrome Bibliography 85.13 Histidine Bibliography 85.14 Lysine Pyridoxine (Vitamin B6)-Dependent Epilepsy Antiquitin (α-Aminoadipic Semialdehyde Dehydrogenase) Deficiency Sulfite Oxidase Deficiency (Molybdenum Cofactor Deficiency) Hyperprolinemia Type II Hypophosphatasia Glutaric Aciduria Type I Clinical Manifestations Laboratory Findings Treatment Lysinuric Protein Intolerance (Familial Protein Intolerance) Bibliography 85.15 Aspartic Acid (Canavan Disease) Etiology and Pathology Clinical Manifestations Atypical Canavan Disease Diagnosis Treatment and Prevention Bibliography 86 Defects in Metabolism of Lipids 86 Defects in Metabolism of Lipids 86.1 Disorders of Mitochondrial Fatty Acid β-Oxidation Defects in the β-Oxidation Cycle Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Clinical Manifestations Laboratory Findings Treatment Prognosis Very-Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Short-Chain Acyl-Coenzyme A Dehydrogenase Deficiency Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase/Mitochondrial Trifunctional Protein Deficiency Short-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase Deficiency Defects in the Carnitine Cycle Plasma Membrane Carnitine Transport Defect (Primary Carnitine Deficiency) Carnitine Palmitoyltransferase-IA Deficiency Carnitine:Acylcarnitine Translocase Deficiency Carnitine Palmitoyltransferase-II Deficiency Defects in the Electron Transfer Pathway Electron Transfer Flavoprotein and Electron Transfer Flavoprotein Dehydrogenase Deficiencies (Glutaric Acidemia Type 2, Multiple Acyl-Coenzyme A Dehydrogenation Defects) Defects in Ketone Synthesis Pathway β-Hydroxy-β-Methylglutaryl-Coenzyme A Synthase Deficiency β-Hydroxy-β-Methylglutaryl-Coenzyme A Lyase Deficiency Defects in Ketone Body Utilization Succinyl-Coenzyme A:3-Ketoacid-Coenzyme A Transferase Deficiency β-Ketothiolase Deficiency Bibliography 86.2 Disorders of Very Long Chain Fatty Acids Peroxisomal Disorders Etiology Epidemiology Pathology Pathogenesis Peroxisomal Biogenesis Disorders with Milder or Atypical Phenotypes Rhizomelic Chondrodysplasia Punctata Isolated Defects of Peroxisomal Fatty Acid Oxidation Isolated Defects of Plasmalogen Synthesis Classic Refsum Disease 2-Methylacyl-Coenzyme A Racemase Deficiency Laboratory Findings Level 1: Does the Patient Have a Peroxisomal Disorder? Level 2: What Is the Precise Nature of the Peroxisomal Disorder? Level 3: What Is the Molecular Defect? Diagnosis Complications Treatment Genetic Counseling Adrenoleukodystrophy (X-Linked) Etiology Epidemiology Pathology Pathogenesis Clinical Manifestations Laboratory and Radiographic Findings Neuroimaging Impaired Adrenal Function Diagnosis and Differential Diagnosis Complications Treatment Bone Marrow Transplantation Lorenzo’s Oil Therapy Supportive Therapy Genetic Counseling and Prevention Bibliography Peroxisomal Disorders Adrenoleukodystrophy (X-Linked) 86.3 Disorders of Lipoprotein Metabolism and Transport Epidemiology of Blood Lipids and Cardiovascular Disease Blood Lipids and Atherogenesis Plasma Lipoprotein Metabolism and Transport Transport of Exogenous (Dietary) Lipids Transport of Endogenous Lipids from the Liver High-Density Lipoprotein and Reverse Cholesterol Transport Hyperlipoproteinemias Hypercholesterolemia Familial Hypercholesterolemia Homozygous Familial Hypercholesterolemia Heterozygous Familial Hypercholesterolemia Familial Defective ApoB-100 Autosomal Recessive Hypercholesterolemia Sitosterolemia Polygenic Hypercholesterolemia Hypercholesterolemia with Hypertriglyceridemia Familial Combined Hyperlipidemia Familial Dysbetalipoproteinemia (Type III Hyperlipoproteinemia) Hypertriglyceridemias Familial Chylomicronemia (Type I Hyperlipidemia) Familial Hypertriglyceridemia (Type IV Hyperlipidemia) Hepatic Lipase Deficiency Disorders of High-Density Lipoprotein Metabolism Primary Hypoalphalipoproteinemia Familial Hyperalphalipoproteinemia Familial Apolipoprotein A-I Deficiency Tangier Disease Familial Lecithin–Cholesterol Acyltransferase Deficiency Cholesteryl Ester Transfer Protein Deficiency Conditions Associated with Low Cholesterol Abetalipoproteinemia Familial Hypobetalipoproteinemia Smith-Lemli-Opitz Syndrome Disorders of Intracellular Cholesterol Metabolism Cerebrotendinous Xanthomatosis Wolman Disease and Cholesterol Ester Storage Disease Niemann-Pick Disease Type C Lipoprotein Patterns in Children and Adolescents Blood Cholesterol Screening Risk Assessment and Treatment of Hyperlipidemia Pharmacologic Therapy. Bibliography 86.4 Lipidoses (Lysosomal Storage Disorders) GM1 Gangliosidosis The GM2 Gangliosidoses Gaucher Disease Niemann-Pick Disease Fabry Disease Fucosidosis Schindler Disease Metachromatic Leukodystrophy Multiple Sulfatase Deficiency Krabbe Disease Farber Disease Wolman Disease and Cholesterol Ester Storage Disease Bibliography 86.5 Mucolipidoses I-Cell Disease Pseudo-Hurler Polydystrophy Bibliography 87 Defects in Metabolism of Carbohydrates 87 Defects in Metabolism of Carbohydrates 87.1 Glycogen Storage Diseases Liver Glycogenoses Type I Glycogen Storage Disease (Glucose-6-Phosphatase or Translocase Deficiency, Von Gierke Disease) Clinical Manifestations Diagnosis Treatment Prognosis Type III Glycogen Storage Disease (Debrancher Deficiency, Limit Dextrinosis) Clinical Manifestations Diagnosis Treatment Type IV Glycogen Storage Disease (Branching Enzyme Deficiency, Amylopectinosis, or Andersen Disease) Clinical Manifestations Diagnosis Treatment Type VI Glycogen Storage Disease (Liver Phosphorylase Deficiency, Hers Disease) Type IX Glycogen Storage Disease (Phosphorylase Kinase Deficiency) X-Linked Liver Phosphorylase Kinase Deficiency Autosomal Liver and Muscle Phosphorylase Kinase Deficiency Autosomal Liver Phosphorylase Kinase Deficiency Muscle-Specific Phosphorylase Kinase Deficiency Phosphorylase Kinase Deficiency Limited to Heart Diagnosis Treatment Glycogen Synthase Deficiency Muscle Glycogen Synthase Deficiency Hepatic Glycogenosis with Renal Fanconi Syndrome (Fanconi-Bickel Syndrome) Muscle Glycogenoses Type II Glycogen Storage Disease (Lysosomal Acid α-1,4-Glucosidase Deficiency, Pompe Disease) Clinical Manifestations Laboratory Findings Diagnosis Treatment Glycogen Storage Diseases Mimicking Hypertrophic Cardiomyopathy Type V Glycogen Storage Disease (Muscle Phosphorylase Deficiency, McArdle Disease) Clinical Manifestations Diagnosis Treatment Type VII Glycogen Storage Disease (Muscle Phosphofructokinase Deficiency, Tarui Disease) Clinical Manifestations Diagnosis Treatment Other Muscle Glycogenoses with Muscle Energy Impairment Bibliography 87.2 Defects in Galactose Metabolism Galactose-1-Phosphate Uridyl Transferase Deficiency Galactosemia Clinical Manifestations Diagnosis Genetics Treatment and Prognosis Galactokinase Deficiency Uridine Diphosphate Galactose-4-Epimerase Deficiency Bibliography 87.3 Defects in Fructose Metabolism Deficiency of Fructokinase (Essential or Benign Fructosuria) Deficiency of Fructose-1,6-Bisphosphate Aldolase (Aldolase B, Hereditary Fructose Intolerance) Epidemiology and Genetics Clinical Manifestations Diagnosis Treatment Bibliography 87.4 Defects in Intermediary Carbohydrate Metabolism Associated with Lactic Acidosis Disorders of Gluconeogenesis Deficiency of Glucose-6-Phosphatase (Type I Glycogen Storage Disease) Fructose-1,6-Diphosphatase Deficiency Phosphoenolpyruvate Carboxykinase Deficiency Disorders of Pyruvate Metabolism Pyruvate Dehydrogenase Complex Deficiency Clinical Manifestations Treatment Deficiency of Pyruvate Carboxylase Deficiency of Pyruvate Carboxylase Secondary to Deficiency of Holocarboxylase Synthase or Biotinidase Mitochondrial Respiratory Chain Defects (Oxidative Phosphorylation Disease) Leigh Disease (Subacute Necrotizing Encephalomyelopathy) Bibliography 87.5 Defects in Pentose Metabolism Essential Pentosuria Transaldolase Deficiency Ribose-5-Phosphate Isomerase Deficiency Bibliography 87.6 Disorders of Glycoprotein Degradation and Structure Sialidosis and Galactosialidosis Aspartylglucosaminuria α-Mannosidosis Congenital Disorders of Glycosylation Bibliography 88 Mucopolysaccharidoses 88 Mucopolysaccharidoses Clinical Entities Mucopolysaccharidosis I Hurler Disease Hurler-Scheie Disease Scheie Disease Mucopolysaccharidosis II Mucopolysaccharidosis III Mucopolysaccharidosis IV Mucopolysaccharidosis VI Mucopolysaccharidosis VII Mucopolysaccharidosis IX Diagnosis and Differential Diagnosis Treatment Bibliography 89 Disorders of Purine and Pyrimidine Metabolism 89 Disorders of Purine and Pyrimidine Metabolism Gout Genetics Treatment Abnormalities in Purine Salvage HPRT Deficiency Genetics Pathology Clinical Manifestations Diagnosis Treatment Adenine Phosphoribosyltransferase Deficiency (Dihydroxyadeninuria) Genetics Clinical Manifestations Laboratory Treatment Disorders Linked to Purine Nucleotide Synthesis Phosphoribosylpyrophosphate Synthetase Superactivity and Deficiency Genetics Clinical Manifestations Laboratory Treatment Adenylosuccinate Lyase Deficiency (Succinylpurinuria) Genetics Clinical Manifestations Pathology Treatment Aminoimidazole Carboxamide Ribotide Transformylase/Inosine Monophosphate Cyclohydrolase Deficiency Genetics Clinical Features Laboratory Treatment Disorders Resulting from Abnormalities in Purine Catabolism Myoadenylate Deaminase Deficiency (Muscle Adenosine Monophosphate Deaminase Deficiency) Clinical Manifestations Genetics Laboratory Treatment Adenosine Deaminase Deficiency Purine Nucleoside Phosphorylase Deficiency Xanthine Oxidoreductase Deficiency (Hereditary Xanthinuria/Molybdenum Cofactor Deficiency) Genetics Laboratory Treatment Disorders of Pyrimidine Metabolism Uridine Monophosphate Synthase Type 1 Deficiency (Hereditary Orotic Aciduria) Genetics Clinical Laboratory Treatment Dihydropyrimidine Dehydrogenase Deficiency (Thymine-Uraciluria, Pyrimidinuria) Genetics Laboratory Treatment Dihydropyrimidinase Deficiency (Dihydropyrimidinuria) Genetics Clinical Laboratory Deficiency of β-Ureidopropionase (N-Carbamyl-β-Amino Aciduria) Genetics Clinical Laboratory Treatment Pyrimidine 5’-Nucleotidase Deficiency Genetics Laboratory Treatment Overactive Cytosolic 5’-Nucleotidase (Pyrimidine Nucleotide Depletion) Clinical Treatment Thymidine Phosphorylase Deficiency (Mitochondrial Neurogastrointestinal Encephalomyopathy) Genetics Clinical Manifestations Laboratory Treatment Thymidine Kinase 2 Deficiency Genetics Clinical Treatment Acknowledgments Bibliography Gout Abnormalities in Purine Salvage Adenine Phosphoribosyltransferase Deficiency (Dihydroxyadeninuria) Disorders Linked to Purine Nucleotide Synthesis Adenylosuccinate Lyase Deficiency (Succinylpurinuria) Aicar Transformylase/Imp Cyclohydrolase (ATIC) Deficiency (Aica-Ribosiduria) Disorders Resulting from Abnormalities in Purine Catabolism Xanthine Oxidoreductase Deficiency (Hereditary Xanthinuria/Molybdenum Cofactor Deficiency) Disorders of Pyrimidine Metabolism Dihydropyrimidine Dehydrogenase Deficiency (Thymine-Uraciluria, Pyrimidinuria) Dihydropyrimidinase Deficiency (Dihydropyrimidinuria) Deficiency of Beta-Ureidopropionase (N-Carbamyl-Beta-Amino Aciduria) Pyrimidine 5′-Nucleotidase Deficiency Overactive Cytosolic 5′ Nucleotidase (Pyrimidine Nucleotide Depletion) Thymidine Phosphorylase Deficiency (Mitochondrial Neurogastrointestinal Encephalomyopathy-MNGIE) Thymidine Kinase 2 (TK2) Deficiency 90 Hutchinson-Gilford Progeria Syndrome 90 Hutchinson-Gilford Progeria Syndrome Clinical Manifestations Dermatologic Changes Failure to Thrive Ocular Abnormalities Dental Abnormalities Bone and Cartilaginous Abnormalities Hearing Cardiovascular Disease Cerebrovascular Arteriopathy and Stroke Normally Functioning Systems Laboratory Findings Molecular Pathogenesis Diagnosis and Differential Diagnosis Prognosis, Treatment, and Patient Resources Bibliography 91 The Porphyrias 91 The Porphyrias The Heme Biosynthetic Pathway Classification and Diagnosis of Porphyrias First-Line Laboratory Diagnostic Testing Blistering Cutaneous Porphyrias Nonblistering Cutaneous Porphyria Second-Line Testing Testing for Subclinical Porphyria δ-Aminolevulinic Acid Dehydratase Porphyria Etiology Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Prognosis Prevention and Genetic Counseling Acute Intermittent Porphyria Etiology Pathology and Pathogenesis Neurologic Mechanisms Epidemiology Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Hemin General and Supportive Measures Carbohydrate Loading Other Therapies Seizures and Other Complications Safe and Unsafe Drugs Other Situations Prognosis Prevention Genetic Counseling Congenital Erythropoietic Porphyria Etiology Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Prognosis Prevention and Genetic Counseling Porphyria Cutanea Tarda Etiology Epidemiology Pathology and Pathogenesis Susceptibility Factors Iron Hepatitis C HIV Ethanol Smoking and Cytochrome P450 Enzymes Antioxidant Status Estrogens Clinical Manifestations Cutaneous Manifestations Liver Abnormalities Other Findings and Associations Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Prognosis Prevention and Genetic Counseling Hepatoerythropoietic Porphyria Etiology Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment and Prognosis Prevention and Genetic Counseling Hereditary Coproporphyria Etiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment and Prognosis Prevention and Genetic Counseling Variegate Porphyria Etiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Prognosis and Prevention Genetic Counseling Erythropoietic Protoporphyria Etiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Prognosis Prevention Genetic Counseling Dual Porphyria Porphyria Resulting from Tumors Bibliography General Acute Porphyrias Congenital Erythropoietic Porphyria Porphyria Cutanea Tarda Erythropoietic Protoporphyria 92 Hypoglycemia 92 Hypoglycemia Definition Significance and Sequelae Substrate, Enzyme, and Hormonal Integration of Glucose Homeostasis In the Newborn In Older Infants and Children Clinical Manifestations Classification of Hypoglycemia in Infants and Children Neonatal, Transient, Small for Gestational Age, and Premature Infants Infants Born to Diabetic Mothers Persistent or Recurrent Hypoglycemia in Infants and Children Hyperinsulinism Endocrine Deficiency Substrate Limited Ketotic Hypoglycemia Branched-Chain Ketonuria (Maple Syrup Urine Disease) Glycogen Storage Disease Glucose-6-Phosphatase Deficiency (Type I Glycogen Storage Disease) Amylo-1,6-Glucosidase Deficiency (Debrancher Enzyme Deficiency; Type III Glycogen Storage Disease) Liver Phosphorylase Deficiency (Type VI Glycogen Storage Disease) Glycogen Synthetase Deficiency Disorders of Gluconeogenesis Fructose-1,6-Diphosphatase Deficiency Defects in Fatty Acid Oxidation Acute Alcohol Intoxication Salicylate Intoxication Phosphoenolpyruvate Carboxykinase Deficiency Pyruvate Carboxylase Deficiency Other Enzyme Defects Galactosemia (Galactose-1-Phosphate Uridyl Transferase Deficiency) Fructose Intolerance (Fructose-1-Phosphate Aldolase Deficiency) Defects in Glucose Transporters Glut-1 Deficiency Glut-2 Deficiency Systemic Disorders Diagnosis and Differential Diagnosis Treatment Prognosis Bibliography The Fetus and theNeonatal Infant 93 Overview of Mortality and Morbidity 93 Overview of Mortality and Morbidity Bibliography 94 The Newborn Infant 94 The Newborn Infant 94.1 History in Neonatal Pediatrics 94.2 Physical Examination of the Newborn Infant General Appearance Skin Skull Face Eyes Ears Nose Mouth Neck Chest Lungs Heart Abdomen Genitals Anus Extremities Neurologic Examination Bibliography 94.3 Routine Delivery Room and Initial Care Maintenance of Body Heat Antiseptic Skin and Cord Care Other Measures Bibliography 94.4 Nursery Care Bibliography 94.5 Parent–Infant Bonding Nurseries and Breastfeeding Drugs and Breastfeeding Contraindications to Breastfeeding Bibliography 95 High-Risk Pregnancies 95 High-Risk Pregnancies Genetic Factors Maternal Factors Bibliography 96 The Fetus 96 The Fetus 96.1 Fetal Growth and Maturity Bibliography 96.2 Fetal Distress Bibliography 96.3 Maternal Disease and the Fetus Infectious Diseases Noninfectious Diseases Bibliography 96.4 Maternal Medication and Toxin Exposure and the Fetus Bibliography 96.5 Teratogens Bibliography 96.6 Radiation Bibliography 96.7 Intrauterine Diagnosis of Fetal Disease Bibliography 96.8 Treatment and Prevention of Fetal Disease Bibliography 97 The High-Risk Infant 97 The High-Risk Infant 97.1 Multiple-Gestation Pregnancies Incidence Etiology Monozygotic Versus Dizygotic Twins Examination of the Placenta Postnatal Identification Prognosis Treatment Bibliography 97.2 Prematurity and Intrauterine Growth Restriction Definitions Incidence Very Low Birthweight Infants Factors Related to Premature Birth and Low Birthweight Assessment of Gestational Age at Birth Spectrum of Disease in Low-Birthweight Infants Nursery Care Thermal Control Fluid Requirements Parenteral Nutrition Feeding Initiation of Feeding Vitamins Prevention of Infection Immaturity of Drug Metabolism Prognosis Predicting Neonatal Mortality Discharge From the Hospital Home Care Bibliography 97.3 Postterm Infants Clinical Manifestations Prognosis Management 97.4 Large-for-Gestational-Age Infants 97.5 Infant Transport Bibliography 98 Clinical Manifestations of Diseases in the Newborn Period 98 Clinical Manifestations of Diseases in the Newborn Period Congenital Anomalies Bibliography 99 Nervous System Disorders 99 Nervous System Disorders 99.1 The Cranium 99.2 Traumatic, Epidural, Subdural, and Subarachnoid Hemorrhage 99.3 Intracranial–Intraventricular Hemorrhage and Periventricular Leukomalacia Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Prognosis Prevention Treatment Bibliography 99.4 Brain Injury from Inflammation, Infection, and Medications Bibliography 99.5 Hypoxic–Ischemic Encephalopathy Etiology Pathophysiology and Pathology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 99.6 Spine and Spinal Cord Bibliography 99.7 Peripheral Nerve Injuries Brachial Palsy Phrenic Nerve Paralysis Facial Nerve Palsy Bibliography 100 Delivery Room Emergencies 100 Delivery Room Emergencies Respiratory Distress and Failure Failure to Initiate or Sustain Respiration Neonatal Resuscitation Meconium Shock Pneumothorax Airway Obstruction Abdominal Wall Defects Injury during Delivery Central Nervous System Viscera Fractures Clavicle Extremities Nose Bibliography 101 Respiratory Tract Disorders 101 Respiratory Tract Disorders 101.1 Transition to Pulmonary Respiration The First Breath Breathing Patterns in Newborns 101.2 Apnea Clinical Manifestations Treatment Prognosis Apnea and Sudden Infant Death Syndrome Bibliography 101.3 Respiratory Distress Syndrome (Hyaline Membrane Disease) Incidence Etiology and Pathophysiology Clinical Manifestations Diagnosis Prevention Treatment Pharmacologic Therapies Complications of Respiratory Distress Syndrome and Intensive Care Prognosis Bibliography 101.4 Transient Tachypnea of the Newborn Bibliography 101.5 Aspiration of Foreign Material (Fetal Aspiration Syndrome, Aspiration Pneumonia) 101.6 Meconium Aspiration Clinical Manifestations Prevention Treatment Prognosis Bibliography 101.7 Persistent Pulmonary Hypertension of the Newborn (Persistent Fetal Circulation) Pathophysiology Clinical Manifestations Diagnosis Treatment Extracorporeal Membrane Oxygenation Prognosis Bibliography 101.8 Diaphragmatic Hernia Congenital Diaphragmatic Hernia (Bochdalek) Pathology and Etiology Epidemiology Diagnosis and Clinical Presentation Treatment Initial Management Ventilation Strategies Extracorporeal Membrane Oxygenation Novel Strategies for Infants with Congenital Diaphragmatic Hernia Surgical Repair Outcome and Long-Term Survival Bibliography 101.9 Foramen of Morgagni Hernia 101.10 Paraesophageal Hernia 101.11 Eventration Bibliography 101.12 Extrapulmonary Air Leaks (Pneumothorax, Pneumomediastinum, Pulmonary Interstitial Emphysema, Pneumopericardium) Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 101.13 Pulmonary Hemorrhage Bibliography 102 Digestive System Disorders 102 Digestive System Disorders Vomiting Diarrhea Constipation Meconium Plugs 102.1 Meconium Ileus in Cystic Fibrosis Meconium Peritonitis 102.2 Necrotizing Enterocolitis Pathology and Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 102.3 Jaundice and Hyperbilirubinemia in the Newborn Etiology Clinical Manifestations Differential Diagnosis Physiologic Jaundice (Icterus Neonatorum) Pathologic Hyperbilirubinemia Jaundice Associated with Breast-Feeding Neonatal Hepatitis Congenital Atresia of the Bile Ducts Inspissated Bile Syndrome Bibliography 102.4 Kernicterus Clinical Manifestations Incidence and Prognosis Prevention Treatment of Hyperbilirubinemia Phototherapy Intravenous Immunoglobulin Metalloporphyrins Exchange Transfusion Bibliography 103 Blood Disorders 103 Blood Disorders 103.1 Anemia in the Newborn Infant Bibliography 103.2 Hemolytic Disease of the Newborn (Erythroblastosis Fetalis) Hemolytic Disease of the Newborn Caused by Rh Incompatibility Pathogenesis Clinical Manifestations Laboratory Data Diagnosis Antenatal Diagnosis Postnatal Diagnosis Treatment Treatment of an Unborn Infant Treatment of a Liveborn Infant Exchange Transfusion Intravenous Immunoglobulin Late Complications Prevention of Rh Sensitization Hemolytic Disease of the Newborn Caused by Blood Group a and B Incompatibility Clinical Manifestations Diagnosis Treatment Other Forms of Hemolytic Disease Bibliography 103.3 Plethora in the Newborn Infant (Polycythemia) Bibliography 103.4 Hemorrhage in the Newborn Infant Hemorrhagic Disease of the Newborn Neonatal Thrombocytopenic Purpura Bibliography 104 Genitourinary System 104 Genitourinary System Renal Vein Thrombosis Circumcision Bibliography 105 The Umbilicus 105 The Umbilicus Umbilical Cord Congenital Omphalocele Tumors Hemorrhage Granuloma Infections Umbilical Hernia Bibliography 106 Metabolic Disturbances 106 Metabolic Disturbances Hyperthermia in the Newborn Neonatal Cold Injury Edema Hypocalcemia (Tetany) Metabolic Bone Disease Hypomagnesemia Hypermagnesemia Substance Abuse and Neonatal Abstinence (Withdrawal) Treatment 106.1 Maternal Selective Serotonin Reuptake Inhibitors and Neonatal Behavioral Syndromes 106.2 Fetal Alcohol Syndrome Bibliography 107 The Endocrine System 107 The Endocrine System 107.1 Infants of Diabetic Mothers Pathophysiology Clinical Manifestations Treatment Prognosis Bibliography Bibliography 108 Dysmorphology 108 Dysmorphology Classification of Birth Defects Malformations and/or Dysplasias Deformations Multiple Anomalies: Syndrome and Sequence Disruption Molecular Mechanisms of Malformations Inborn Errors of Development Sonic Hedgehog Pathway as Model Chromosomal Imbalances Approach to the Dysmorphic Child History Physical Examination Imaging Studies Laboratory Studies Diagnosis Management and Counseling Bibliography 109 Infections of the Neonatal Infant 109 Infections of the Neonatal Infant 109.1 Pathogenesis and Epidemiology Bibliography 109.2 Modes of Transmission and Pathogenesis Pathogenesis of Intrauterine Infection Pathogenesis of Ascending Bacterial Infection Pathogenesis of Late-Onset Postnatal Infections Bibliography 109.3 Immunity Immunoglobulin Complement Neutrophils Neutrophil Function Neutrophil Number Natural Killer Cells Cytokines/Inflammatory Mediators Bibliography 109.4 Etiology of Fetal and Neonatal Infection Bibliography 109.5 Epidemiology of Early- and Late-Onset Neonatal Infections Prematurity Bibliography 109.6 Healthcare–Associated Infections (HAI) Bibliography 109.7 Clinical Manifestations of Transplacental Intrauterine Infections Bacterial Sepsis Systemic Inflammatory Response Syndrome Fever Rash Omphalitis Tetanus Pneumonia Bibliography 109.8 Intrapartum and Peripartum Infections Suspected Intrauterine Infection Bibliography 109.9 Suspected Bacterial or Fungal Infections Pneumonia and Pneumonitis Meningitis Bibliography 109.10 Management Empiric Therapy Directed Therapy Antimicrobial Resistance Bacteremia Pneumonia Meningitis Adjunctive Therapies Bibliography 109.11 Complications and Prognosis Bibliography 109.12 Prevention Maternal Strategies Antifungal Prophylaxis Other Strategies for Prevention of Healthcare-Associated Infections Antimicrobial Stewardship Bibliography Adolescent Medicine 110 Adolescent Development 110 Adolescent Development 110.1 Adolescent Physical and Social Development Physical Development Sexual Development Somatic Growth (See Also Fig. 13-1) Neurologic, Cognitive, and Moral Development Psychosocial Development Implications for Providers and Parents Bibliography 110.2 Sexual Identity Development Terms and Definitions Sex and Sexual Identity Sex Assigned at Birth Gender Identity, Gender Role, and Social Sex Role Sexual Orientation and Behavior Gender Variant and Transgender Factors That Influence Sexual Identity Development Gender Variance/Gender Role Nonconformity among Children and Adolescents Prevalence Etiology of Gender-Variant Behavior Stigma, Stigma Management, and Advocacy Gender-Variant and Transgender Identity Among Children and Adolescents Prevalence Etiology of a Gender Variant Identity Clinical Presentation The Diagnosis of Gender Dysphoria: Criteria and Critique Transgender Identity Development Interventions and Treatment Bibliography 110.3 Gay, Lesbian, and Bisexual Adolescents Definitions Prevalence of Homosexuality and Bisexuality in Youth Development of Sexual Orientation in Childhood and Adolescence Stigma, Risk, and Resilience Health and Mental Health Depression and Suicidality Sexually Transmitted Infections Substance Abuse Obesity and Disordered Eating Psychosocial Problems Recommendations for Care Evaluation Medical and Sexual Health Mental Health Bibliography 111 The Epidemiology of Adolescent Health Problems 111 The Epidemiology of Adolescent Health Problems Access to Healthcare Bibliography 112 Delivery of Healthcare to Adolescents 112 Delivery of Healthcare to Adolescents 112.1 Legal Issues Bibliography 112.2 Screening Procedures Interviewing the Adolescent Psychosocial Assessment Physical Examination Vision Testing Audiometry Blood Pressure Determination Scoliosis Breast Examination Scrotum Examination Pelvic Examination Laboratory Testing Bibliography 112.3 Transitioning to Adult Care Bibliography Bibliography 113 Violent Behavior 113 Violent Behavior Epidemiology Etiology Clinical Manifestations Diagnosis Treatment Prevention Bibliography 114 Substance Abuse 114 Substance Abuse Etiology Epidemiology Clinical Manifestations Screening for Substance Abuse Disorders Diagnosis Complications Treatment Prognosis Prevention Bibliography 114.1 Alcohol Pharmacology and Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 114.2 Tobacco Cigarettes Pharmacology Clinical Manifestations Electronic Cigarettes (E-Cigarettes) Smokeless Tobacco Treatment Bibliography 114.3 Marijuana Clinical Manifestations Synthetic Marijuana Bibliography 114.4 Inhalants Clinical Manifestations Complications Diagnosis Treatment Bibliography 114.5 Hallucinogens Lysergic Acid Diethylamide Clinical Manifestations Treatment Methylenedioxymethamphetamine Clinical Manifestations Phencyclidine Clinical Manifestations Treatment Bibliography 114.6 Cocaine Clinical Manifestations Treatment Bibliography 114.7 Amphetamines Clinical Manifestations Treatment Bibliography 114.8 Opiates Clinical Manifestations Withdrawal Overdose Syndrome Treatment Bibliography 114.9 Bath Salts Bibliography 115 The Breast 115 The Breast Female Disorders Male Disorders Bibliography 116 Menstrual Problems 116 Menstrual Problems Normal Menstruation Menstrual Irregularities Bibliography 116.1 Amenorrhea History and Physical Examination Laboratory Studies Treatment Bibliography 116.2 Abnormal Uterine Bleeding (AUB) Irregular Menstrual Bleeding Heavy and Prolonged Menstrual Bleeding Laboratory Findings Treatment Bibliography 116.3 Dysmenorrhea Bibliography 116.4 Premenstrual Syndrome and Premenstrual Dysphoric Disorder Bibliography 117 Contraception 117 Contraception Epidemiology Sexual Activity Contraceptive Use Contraceptive Counseling Bibliography 117.1 Long-Acting Reversible Contraception Intrauterine Devices Implants Bibliography Product Information 117.2 Other Progestin-Only Methods Depo-Provera Progestin-Only Pills Bibliography 117.3 Combined Hormonal Contraceptives Combined Oral Contraceptives Transdermal Patch Vaginal Ring Bibliography 117.4 Emergency Contraception Copper IUD Ulipristal Acetate Levonorgestrel Bibliography 117.5 Dual Protection Condoms Bibliography 117.6 Other Barrier Methods Diaphragm, Cervical Cap, and Sponge 117.7 Other Methods Spermicides Withdrawal Fertility Awareness–Based Methods Lactational Amenorrhea Method Bibliography 118 Adolescent Pregnancy 118 Adolescent Pregnancy Epidemiology Etiology Clinical Manifestations Diagnosis Pregnancy Counseling and Initial Management Characteristics of Teen Parents Medical Complications of Mothers and Babies Psychosocial Outcomes/Risks for Mother and Child Educational Substance Use Repeat Pregnancy Behavioral, Educational, and Social Outcomes of Children Born to Teen Mothers Prevention of Teen Pregnancies Bibliography 119 Adolescent Rape 119 Adolescent Rape Epidemiology Types of Rape Clinical Manifestations Interview and Physical Examination Laboratory Data Treatment Prevention Bibliography 120 Sexually Transmitted Infections 120 Sexually Transmitted Infections Etiology Epidemiology Pathogenesis Sexually Transmitted Infection Screening Definitions, Etiology, and Clinical Manifestations Urethritis Epididymitis Vaginitis Cervicitis Pelvic Inflammatory Disease Genital Ulcer Syndromes Genital Lesions and Ectoparasites HIV Disease and Hepatitis B Diagnosis Treatment Prevention Bibliography 121 Chronic Fatigue Syndrome 121 Chronic Fatigue Syndrome Epidemiology Pathogenesis Clinical Manifestations Diagnosis Management Prognosis Bibliography Immunology 122 Evaluation of Suspected Immunodeficiency 122 Evaluation of Suspected Immunodeficiency B Cells T Cells Natural Killer Cells Phagocytic Cells Complement Bibliography 123 T Lymphocytes, B Lymphocytes, and Natural Killer Cells 123 T Lymphocytes, B Lymphocytes, and Natural Killer Cells Lymphopoiesis in the Fetus Origin of the Lymphoid System T-Cell Development and Differentiation B-Cell Development and Differentiation Natural Killer–Cell Development Immune Cell Interactions Postnatal Lymphopoiesis T Cells and T-Cell Subsets B Cells and Immunoglobulins Natural Killer Cells Lymphoid Organ Development Inheritance of Abnormalities in T-, B-, and Natural Killer–Cell Development Prenatal Diagnosis and Carrier Detection Bibliography 124 Primary Defects of Antibody Production 124 Primary Defects of Antibody Production X-Linked Agammaglobulinemia Genetics and Pathogenesis Clinical Manifestations Diagnosis Common Variable Immunodeficiency Genetics and Pathogenesis Clinical Manifestations Selective IgA Deficiency Clinical Manifestations IgG Subclass Deficiencies Immunoglobulin Heavy- and Light-Chain Deletions Hyper-IgM Syndrome X-Linked Hyper-IgM Caused By Mutations in the CD40 Ligand: Hyper-IgM Type 1 Genetics and Pathogenesis Clinical Manifestations X-Linked Hyper-IgM Caused By Mutations in the Gene Encoding Nuclear Factor κB Essential Modulator; XHM-ED Autosomal Recessive Hyper-IgM Caused By Mutations in the Gene for Activation-Induced Cytidine Deaminase: Hyper-IgM Type 2 Genetics and Pathogenesis Clinical Manifestations Autosomal Recessive Hyper-IgM Caused By Mutations in the Gene for Uracil DNA Glycosylase; Hyper-IgM Type 5 Genetics and Pathogenesis Autosomal Recessive Hyper-IgM Caused By Mutations in CD40: Hyper-IgM Type 3 Genetics and Pathogenesis Hyper-IgM Type 4 X-Linked Lymphoproliferative Disease Genetics and Pathogenesis Clinical Manifestations CD27 Deficiency Bibliography 124.1 Treatment of B-Cell Defects Bibliography 125 Primary Defects of Cellular Immunity 125 Primary Defects of Cellular Immunity Thymic Hypoplasia (Digeorge Syndrome) Genetics and Pathogenesis Clinical Manifestations Treatment Defective Expression of the T-Cell Receptor–CD3 Complex T-Cell Activation Defects CD8 Lymphocytopenia Caused by Mutations in the Gene Encoding Zeta-Associated Protein 70 T-Cell Defects Characterized By Epstein-Barr Virus Lymphoproliferation/Lymphoma RhoH Deficiency MST1/STK4 Deficiency ITK Deficiency Coronin-1a Deficiency LCK Deficiency Chronic Mucocutaneous Candidiasis Autoimmune Polyendocrinopathy-Candidiasis Ectodermal Dysplasia Bibliography 126 Primary Combined Antibody and Cellular Immunodeficiencies 126 Primary Combined Antibody and Cellular Immunodeficiencies 126.1 Severe Combined Immunodeficiency Pathogenesis Clinical Manifestations Treatment X-Linked Severe Combined Immunodeficiency Caused by Mutations in the Gene Encoding the Common Cytokine Receptor γ Chain Autosomal Recessive Severe Combined Immunodeficiency Adenosine Deaminase Deficiency Jak3 Deficiency IL-7Rα Deficiency RAG1 or RAG2 Deficiencies Artemis Deficiency CD45 Deficiency CD3δ, CD3ε, and CD3ζ Deficiencies Reticular Dysgenesis 126.2 Combined Immunodeficiency Purine Nucleoside Phosphorylase Deficiency Cartilage Hair Hypoplasia Genetics and Pathogenesis Clinical Manifestations Defective Expression of Major Histocompatibility Complex Antigens Major Histocompatibility Complex Class I Antigen Deficiency Major Histocompatibility Complex Class II Antigen Deficiency Immunodeficiency with Thrombocytopenia and Eczema (Wiskott-Aldrich Syndrome) Genetics and Pathogenesis Clinical Manifestations Treatment Ataxia-Telangiectasia Genetics and Pathogenesis Clinical Manifestations 126.3 Defects of Innate Immunity Interferon-γ Receptors 1 and 2, IL-12 Receptor β1, and IL-12P40 Mutations Germline STAT-1 Mutation IL-1R–Associated Kinase 4 Deficiency and Myeloid Differentiation Factor 88 Natural Killer Cell Deficiency Hyper-IgE Syndromes Autosomal Dominant Hyper-IgE Syndrome Genetics and Pathogenesis Clinical Manifestations Autosomal Recessive Hyper-IgE Syndrome Genetics and Pathogenesis Clinical Manifestations Treatment 126.4 Treatment of Cellular or Combined Immunodeficiency 126.5 Immune Dysregulation with Autoimmunity or Lymphoproliferation Autoimmune Lymphoproliferative Syndrome Clinical Manifestations Diagnosis Treatment Immune-Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome Clinical Manifestations Treatment Bibliography 127 Neutrophils 127 Neutrophils The Phagocytic Inflammatory Response Hematopoiesis Neutrophil Maturation and Kinetics Neutrophil Function Bibliography 128 Monocytes, Macrophages, and Dendritic Cells 128 Monocytes, Macrophages, and Dendritic Cells Development Activation Functional Activities Dendritic Cells Abnormalities of Monocyte-Macrophage or Dendritic Cell Function Bibliography 129 Eosinophils 129 Eosinophils Diseases Associated with Eosinophilia Allergic Diseases Infectious Diseases Hypereosinophilic Syndrome Miscellaneous Diseases Bibliography 130 Disorders of Phagocyte Function 130 Disorders of Phagocyte Function Leukocyte Adhesion Deficiency Genetics and Pathogenesis Clinical Manifestations Laboratory Findings Treatment Prognosis Chédiak-Higashi Syndrome Genetics and Pathogenesis Clinical Manifestations Laboratory Findings Treatment Myeloperoxidase Deficiency Clinical Manifestations Laboratory Findings Treatment Chronic Granulomatous Disease Genetics and Pathogenesis Clinical Manifestations Laboratory Findings Treatment Genetic Counseling Prognosis Bibliography 131 Leukopenia 131 Leukopenia Neutropenia Clinical Manifestations of Neutropenia Laboratory Findings Acquired Neutropenia Infection-Related Neutropenia. Drug-Induced Neutropenia. Nutrition-Related Neutropenia. Immune-Mediated Neutropenia. Neutropenia Secondary to Bone Marrow Replacement. Neutropenia Secondary to Reticuloendothelial Sequestration. Inherited Neutropenia Primary Disorders of Granulocytopoiesis. Disorders of Molecular Processing. Vesicular Trafficking Disorders. Disorders of Metabolism. Neutropenia in Disorders of Immune Dysfunction. Unclassified Neutropenic Disorders. Treatment Lymphopenia Acquired Lymphopenia Inherited Lymphopenia Bibliography 132 Leukocytosis 132 Leukocytosis Neutrophilia Acute Acquired Neutrophilia Chronic Acquired Neutrophilia Lifelong Neutrophilia Monocytosis Lymphocytosis Basophilia Bibliography 133 The Complement System 133 The Complement System Classical and Lectin Pathways Alternative Pathway Membrane Attack Complex Control Mechanisms Participation in Host Defense Bibliography 134 Disorders of the Complement System 134 Disorders of the Complement System 134.1 Evaluation of the Complement System Bibliography 134.2 Genetic Deficiencies of Complement Components Bibliography 134.3 Deficiencies of Plasma, Membrane, or Serosal Complement Control Proteins Bibliography 134.4 Secondary Disorders of Complement Bibliography 134.5 Treatment of Complement Disorders Bibliography 135 Principles and Clinical Indications of Hematopoietic Stem Cell Transplantation 135 Principles and Clinical Indications of Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cell Transplantation From an HLA-Identical Sibling Donor Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Chronic Myelogenous Leukemia Juvenile Myelomonocytic Leukemia Myelodysplastic Syndromes Other Than Juvenile Myelomonocytic Leukemia Non-Hodgkin Lymphoma and Hodgkin Disease Acquired Aplastic Anemia Constitutional Aplastic Anemia Thalassemia Sickle Cell Disease Immunodeficiency Disorders Bibliography 136 Hematopoietic Stem Cell Transplantation from Alternative Sources and Donors 136 Hematopoietic Stem Cell Transplantation from Alternative Sources and Donors Unrelated Donor Transplants Umbilical Cord Blood Transplants Haploidentical Transplants Donor Versus Recipient Natural Killer–Cell Alloreactivity Autologous Hematopoietic Stem Cell Transplantation Bibliography 137 Graft-Versus-Host Disease, Rejection, and Venoocclusive Disease 137 Graft-Versus-Host Disease, Rejection, and Venoocclusive Disease Acute Graft-Versus-Host Disease Chronic Graft-Versus-Host Disease Venoocclusive Disease Bibliography 138 Infectious Complications of Hematopoietic Stem Cell Transplantation 138 Infectious Complications of Hematopoietic Stem Cell Transplantation 139 Late Effects of Hematopoietic Stem Cell Transplantation 139 Late Effects of Hematopoietic Stem Cell Transplantation Bibliography Allergic Disorders 140 Allergy and the Immunologic Basis of Atopic Disease 140 Allergy and the Immunologic Basis of Atopic Disease Key Elements of Allergic Diseases Allergens T Cells Antigen-Presenting Cells Immunoglobulin E and its Receptors Eosinophils Mast Cells Mechanisms of Allergic Tissue Inflammation Genetic Basis of Atopy Bibliography 141 Diagnosis of Allergic Disease 141 Diagnosis of Allergic Disease Allergy History Physical Examination Diagnostic Testing In Vitro Tests In Vivo Tests Bibliography 142 Principles of Treatment of Allergic Disease 142 Principles of Treatment of Allergic Disease Environmental Control Measures Pharmacologic Therapy Adrenergic Agents Anticholinergic Agents Antihistamines Chromones Glucocorticoids Leukotriene-Modifying Agents Theophylline Lodoxamide Tromethamine Combination Mast Cell Stabilizer and Antihistamine Antiimmunoglobulin E Nasal Saline Irrigation New Therapies Allergen Immunotherapy Indications and Contraindications Allergen Extracts Allergen Extract Administration Efficacy Bibliography 143 Allergic Rhinitis 143 Allergic Rhinitis Etiology and Classification Pathogenesis Clinical Manifestations Differential Diagnosis Complications Laboratory Findings Treatment Prognosis Bibliography 144 Childhood Asthma 144 Childhood Asthma Etiology Genetics Environment Epidemiology Types of Childhood Asthma Pathogenesis Clinical Manifestations and Diagnosis Differential Diagnosis Laboratory Findings Pulmonary Function Testing Radiology Treatment Component 1: Regular Assessment and Monitoring Component 2: Patient Education Adherence Component 3: Control of Factors Contributing to Asthma Severity Eliminating and Reducing Problematic Environmental Exposures Treating Comorbid Conditions Component 4: Principles of Asthma Pharmacotherapy “Step-Up, Step-Down” Approach Referral to Asthma Specialist Long-Term Controller Medications Inhaled Corticosteroids Systemic Corticosteroids Long-Acting Inhaled β-Agonists Leukotriene-Modifying Agents Nonsteroidal Antiinflammatory Agents Theophylline Anti–Immunoglobulin E (Omalizumab) Quick-Reliever Medications Short-Acting Inhaled β-Agonists Anticholinergic Agents Delivery Devices and Inhalation Technique Asthma Exacerbations and Their Management Home Management of Asthma Exacerbations Emergency Department Management of Asthma Exacerbations Hospital Management of Asthma Exacerbations Special Management Circumstances Management of Infants and Young Children. Asthma Management in Pregnancy. Asthma Management During Surgery. Prognosis Prevention Bibliography 145 Atopic Dermatitis (Atopic Eczema) 145 Atopic Dermatitis (Atopic Eczema) Etiology Pathology Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Cutaneous Hydration Topical Corticosteroids Topical Calcineurin Inhibitors Tar Preparations Antihistamines Systemic Corticosteroids Cyclosporine Antimetabolites Phototherapy Unproven Therapies Interferon-γ Omalizumab Allergen Immunotherapy Probiotics Chinese Herbal Medications Vitamin D Avoiding Triggers Irritants Foods Aeroallergens Infections Complications Prognosis Prevention Bibliography 146 Insect Allergy 146 Insect Allergy Etiology Pathogenesis Clinical Manifestations Diagnosis Treatment Venom Immunotherapy Inhalant Allergy Prevention Bibliography 147 Ocular Allergies 147 Ocular Allergies Clinical Manifestations Allergic Conjunctivitis Vernal Keratoconjunctivitis Atopic Keratoconjunctivitis Giant Papillary Conjunctivitis Contact Allergy Diagnosis Treatment Bibliography 148 Urticaria (Hives) and Angioedema 148 Urticaria (Hives) and Angioedema Etiology and Pathogenesis Physical Urticaria Cold-Dependent Disorders Cholinergic Urticaria Dermatographism Pressure-Induced Urticaria and Angioedema Solar Urticaria Aquagenic Urticaria Chronic Idiopathic Urticaria and Angioedema Diagnosis Treatment Hereditary Angioedema Bibliography 149 Anaphylaxis 149 Anaphylaxis Etiology Epidemiology Pathogenesis Clinical Manifestations and Diagnosis Laboratory Findings Diagnosis Treatment Prevention Bibliography 150 Serum Sickness 150 Serum Sickness Etiology Pathogenesis Clinical Manifestations Differential Diagnosis Diagnosis Treatment Prevention Bibliography 151 Food Allergy and Adverse Reactions to Foods 151 Food Allergy and Adverse Reactions to Foods Pathogenesis Clinical Manifestations Gastrointestinal Manifestations Skin Manifestations Respiratory Manifestations Anaphylaxis Diagnosis Treatment Prevention Bibliography 152 Adverse Reactions to Drugs 152 Adverse Reactions to Drugs Epidemiology Pathogenesis and Clinical Manifestations Drug Metabolism and Adverse Reactions Risk Factors for Hypersensitivity Reactions Diagnosis Treatment β-Lactam Hypersensitivity Sulfonamides Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Hypersensitivity to Antiretroviral Agents Chemotherapeutic Agents Biologics Vaccines Perioperative Agents Local Anesthetics Insulin Drug-Induced Hypersensitivity Syndrome Red Man Syndrome Radiocontrast Media Narcotic Analgesics Aspirin and Nonsteroidal Antiinflammatory Drugs Bibliography Rheumatic Diseasesof Childhood 153 Evaluation of Suspected Rheumatic Disease 153 Evaluation of Suspected Rheumatic Disease Symptoms Suggestive of Rheumatic Disease Signs Suggestive of Rheumatic Disease Laboratory Testing Imaging Studies Bibliography 154 Treatment of Rheumatic Diseases 154 Treatment of Rheumatic Diseases Pediatric Rheumatology Teams and Primary Care Physicians Therapeutics Nonsteroidal Antiinflammatory Drugs Nonbiologic Disease-Modifying Antirheumatic Drugs Methotrexate Hydroxychloroquine Leflunomide Sulfasalazine Mycophenolate Mofetil Glucocorticoids Biologic Agents Tumor Necrosis Factor-α Antagonists Modulator of T-Cell Activation B-Cell Depletion Interleukin-1 Antagonists Interleukin-6 Receptor Antagonist Intravenous Immunoglobulin Cytotoxics Cyclophosphamide Other Drugs Bibliography 155 Juvenile Idiopathic Arthritis 155 Juvenile Idiopathic Arthritis Epidemiology Etiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Laboratory Findings Treatment Prognosis Bibliography 156 Ankylosing Spondylitis and Other Spondyloarthritides 156 Ankylosing Spondylitis and Other Spondyloarthritides Epidemiology Etiology and Pathogenesis Clinical Manifestations and Diagnosis Enthesitis-Related Arthritis Psoriatic Arthritis Juvenile Ankylosing Spondylitis Arthritis with Inflammatory Bowel Disease Laboratory Findings Imaging Differential Diagnosis Treatment Prognosis Bibliography 157 Reactive and Postinfectious Arthritis 157 Reactive and Postinfectious Arthritis Pathogenesis Clinical Manifestations and Differential Diagnosis Diagnosis Treatment Complications and Prognosis Bibliography 158 Systemic Lupus Erythematosus 158 Systemic Lupus Erythematosus Etiology Epidemiology Pathology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Laboratory Findings Treatment Complications Prognosis Bibliography 158.1 Neonatal Lupus Bibliography 159 Juvenile Dermatomyositis 159 Juvenile Dermatomyositis Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Laboratory Findings Treatment Complications Prognosis Bibliography 160 Scleroderma and Raynaud Phenomenon 160 Scleroderma and Raynaud Phenomenon Etiology and Pathogenesis Classification Epidemiology Clinical Manifestations Localized Scleroderma Systemic Scleroderma Raynaud Phenomenon Diagnosis Differential Diagnosis Laboratory Findings Treatment Prognosis Bibliography 161 Behçet Disease 161 Behçet Disease Epidemiology Etiology and Pathogenesis Clinical Manifestations and Diagnosis Diagnosis Treatment and Prognosis Bibliography 162 Sjögren Syndrome 162 Sjögren Syndrome Epidemiology Etiology and Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Complications and Prognosis Bibliography 163 Hereditary Periodic Fever Syndromes and Other Systemic Autoinflammatory Diseases 163 Hereditary Periodic Fever Syndromes and Other Systemic Autoinflammatory Diseases Familial Mediterranean Fever Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Complications and Prognosis Hyperimmunoglobulinemia D with Periodic Fever Syndrome The Tumor Necrosis Factor Receptor-Associated Periodic Syndrome Cryopyrin-Associated Periodic Fever Syndromes Other Mendelian Autoinflammatory Diseases The Syndrome of Pyogenic Arthritis with Pyoderma Gangrenosum and Acne Deficiency of the Interleukin-1 Receptor Antagonist Blau Syndrome Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature Autoinflammation with Phospholipase Cγ2-Associated Antibody Deficiency and Immune Dysregulation Deficiency of Adenosine Deaminase 2 Genetically Complex Autoinflammatory Diseases Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Chronic Recurrent Multifocal Osteomyelitis Bibliography 164 Amyloidosis 164 Amyloidosis Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Laboratory Findings Treatment Complications and Prognosis Prevention Bibliography 165 Sarcoidosis 165 Sarcoidosis Etiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis Differential Diagnosis Treatment Prognosis Bibliography 166 Kawasaki Disease 166 Kawasaki Disease Etiology Epidemiology Pathology Clinical Manifestations Laboratory and Radiology Findings Diagnosis Differential Diagnosis Treatment Complications Prognosis Bibliography 167 Vasculitis Syndromes 167 Vasculitis Syndromes 167.1 Henoch-Schönlein Purpura Epidemiology Pathology Pathogenesis Clinical Manifestations Diagnosis Laboratory Findings Treatment Complications Prognosis Bibliography 167.2 Takayasu Arteritis Epidemiology Pathology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Laboratory Findings Treatment Complications Prognosis Bibliography 167.3 Polyarteritis Nodosa and Cutaneous Polyarteritis Nodosa Epidemiology Pathology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Laboratory Findings Treatment Complications Prognosis Bibliography 167.4 Antineutrophilic Cytoplasmic Antibody–Associated Vasculitis Epidemiology Pathology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Laboratory Findings Treatment Complications Prognosis Bibliography 167.5 Other Vasculitis Syndromes Bibliography Bibliography 168 Musculoskeletal Pain Syndromes 168 Musculoskeletal Pain Syndromes Clinical Manifestations Diagnosis and Differential Diagnosis Treatment Complications and Prognosis 168.1 Growing Pains 168.2 Small Fiber Polyneuropathy Bibliography 168.3 Fibromyalgia Bibliography 168.4 Complex Regional Pain Syndrome Bibliography 168.5 Erythromelalgia Bibliography 169 Miscellaneous Conditions Associated with Arthritis 169 Miscellaneous Conditions Associated with Arthritis Relapsing Polychondritis Mucha-Habermann Disease/Pityriasis Lichenoides Et Varioliformis Acuta Sweet Syndrome Hypertrophic Osteoarthropathy Plant Thorn Synovitis Pigmented Villonodular Synovitis Bibliography Infectious Diseases 170 Diagnostic Microbiology 170 Diagnostic Microbiology Specimen Collection Laboratory Diagnosis of Bacterial and Fungal Infections Microscopy Isolation and Identification Blood Culture Cerebrospinal Fluid Culture Urine Culture Genital Culture Throat and Respiratory Culture Detection of Enteric Pathogens Culture of Other Fluids and Tissues Screening Cultures Antimicrobial Susceptibility Testing Fungal Cultures Point-of-Care Diagnostics Laboratory Detection of Parasitic Infections Serologic Diagnosis Laboratory Diagnosis of Viral Infections Specimens Antigen Detection Tests Viral Culture Molecular Diagnostics Bibliography 171 The Microbiome and Pediatric Health 171 The Microbiome and Pediatric Health Measuring the Microbiome Early-Childhood Development of the Microbiome The Microbiome and Physiologic Development Microbiome and Metabolism Microbiome, Inflammation, and Immunity Microbiome-Neurobiologic Connections Contributions of Microbiome to Disease Microbiome of Premature Birth Changes in the Microbiome with Necrotizing Enterocolitis Microbiome and Allergic Disorders Airway Microbiome of Cystic Fibrosis Microbiome During Antibiotic-Associated Diarrhea and Clostridium difficile Colitis Microbiome and Association with Inflammatory Bowel Disease Microbiome of Obesity Microbiome During Malnutrition Therapeutic Manipulation of the Microbiome Prebiotics Probiotics Bibliography 172 Immunization Practices 172 Immunization Practices Passive Immunity Intramuscular Immunoglobulin Intravenous Immunoglobulin Subcutaneous Immunoglobulin Hyperimmune Animal Antisera Preparations Monoclonal Antibodies Active Immunization Vaccination System in the United States Vaccine Development Vaccine Production Vaccine Policy Vaccine Financing Vaccine Safety Monitoring Vaccine Delivery Recommended Immunization Schedule Vaccines Recommended in Special Circumstances Precautions and Contraindications Improving Immunization Coverage Bibliography 172.1 International Immunization Practices Bibliography 173 Infection Prevention and Control 173 Infection Prevention and Control Hand Hygiene Standard Precautions Isolation Additional Measures Surgical Prophylaxis Employee Health Bibliography 174 Childcare and Communicable Diseases 174 Childcare and Communicable Diseases Epidemiology Respiratory Tract Infections Gastrointestinal Tract Infections Skin Diseases Invasive Organisms Herpesviruses Blood-borne Pathogens Antibiotic Use and Bacterial Resistance Prevention Standards Bibliography 175 Health Advice for Children Traveling Internationally 175 Health Advice for Children Traveling Internationally The Pediatric Travel Medicine Consultation Pediatric Travelers Visiting Friends and Relatives Safety and Preventive Counseling Topics Health and Evacuation Insurance, Underlying Health Conditions, and Medications Safety and Injury Prevention Animal Contact Routine Childhood Vaccinations Required for Pediatric Travel Diphtheria-Tetanus-Pertussis Haemophilus influenzae Type B Hepatitis A Hepatitis B Influenza and Avian Influenza Measles-Mumps-Rubella Pneumococcal Vaccines Polio Vaccine Varicella Specialized Pediatric Travel Vaccinations Cholera Hepatitis A Vaccination and Preexposure Immunoglobulin Japanese Encephalitis Meningococcal Vaccines Rabies Tuberculosis Typhoid Yellow Fever Traveler’s Diarrhea Guidance on Prevention of Traveler’s Diarrhea Management of Traveler’s Diarrhea Presumptive Antibiotic Treatment Insect-Borne Infections Malaria Chemoprophylaxis The Returning Traveler Bibliography 176 Fever 176 Fever Definition Pathogenesis Etiology Clinical Features Evaluation Management Bibliography 177 Fever Without a Focus 177 Fever Without a Focus Fever Without Localizing Signs Neonates 1 to 3 Months of Age 3 to 36 Months of Age Fever of Unknown Origin Etiology Diagnosis History Physical Examination Laboratory Evaluation Management Prognosis Bibliography 178 Infections in Immunocompromised Persons 178 Infections in Immunocompromised Persons 178.1 Infections Occurring with Primary Immunodeficiencies Abnormalities of the Phagocytic System Defective Splenic Function, Opsonization, or Complement Activity B-Cell Defects (Humoral Immunodeficiencies) T-Cell Defects (Cell-Mediated Immunodeficiencies) Combined B-Cell and T-Cell Defects Bibliography 178.2 Infections Occurring with Acquired Immunodeficiencies Acquired Immunodeficiency From Infectious Agents Malignancies Fever and Neutropenia Transplantation Stem Cell Transplantation Pretransplantation Period Preengraftment Period Postengraftment Period Late Posttransplantation Period Solid-Organ Transplantation Timing Bacterial and Fungal Infections Viral Infections Opportunistic Pathogens Bibliography 178.3 Prevention of Infection in Immunocompromised Persons Bibliography 179 Infection Associated with Medical Devices 179 Infection Associated with Medical Devices Intravascular Access Devices Catheter Types Catheter-Associated Skin and Soft Tissue Infection Catheter-Related Bloodstream Infection Prevention of Infection Cerebrospinal Fluid Shunts Prevention of Infection Urethral Catheters Prevention of Infection Peritoneal Dialysis Catheters Prevention of Infection Orthopedic Prostheses Bibliography 180 Principles of Antibacterial Therapy 180 Principles of Antibacterial Therapy Age- and Risk-Specific Use of Antibiotics in Children Neonates Older Children Immunocompromised and Hospitalized Patients Infections Associated with Medical Devices Antibiotics Commonly Used in Pediatric Practice Penicillins Cephalosporins Carbapenems Glycopeptides Aminoglycosides Tetracyclines Sulfonamides Macrolides Lincosamides Quinolones Streptogramins and Oxazolidinones Daptomycin Miscellaneous Agents Bibliography 181 Staphylococcus 181 Staphylococcus 181.1 Staphylococcus aureus Etiology Epidemiology Pathogenesis Clinical Manifestations Newborn Skin Respiratory Tract Sepsis Muscle Bones and Joints Central Nervous System Heart Kidney Toxic Shock Syndrome Intestinal Tract Diagnosis Differential Diagnosis Treatment Prognosis Prevention Bibliography 181.2 Toxic Shock Syndrome Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prevention Bibliography 181.3 Coagulase-Negative Staphylococci Epidemiology Pathogenesis Clinical Manifestations Bacteremia Endocarditis Central Venous Catheter Infection Cerebrospinal Fluid Shunts Urinary Tract Infection Diagnosis Treatment Prognosis Prevention Bibliography 182 Streptococcus pneumoniae (Pneumococcus) 182 Streptococcus pneumoniae (Pneumococcus) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 183 Group A Streptococcus 183 Group A Streptococcus Etiology Epidemiology Pathogenesis Clinical Manifestations Respiratory Tract Infections Scarlet Fever Impetigo Erysipelas Perianal Dermatitis Vaginitis Severe Invasive Disease Diagnosis Differential Diagnosis Treatment Complications Poststreptococcal Reactive Arthritis Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus pyogenes Prognosis Prevention Bibliography 183.1 Rheumatic Fever Etiology Epidemiology Pathogenesis Clinical Manifestations and Diagnosis The 5 Major Criteria Migratory Polyarthritis Carditis Chorea Erythema Marginatum Subcutaneous Nodules Minor Criteria Recent Group A Streptococcus Infection Differential Diagnosis Treatment Antibiotic Therapy Antiinflammatory Therapy Sydenham Chorea Complications Prognosis Prevention Primary Prevention Secondary Prevention Bibliography 184 Group B Streptococcus 184 Group B Streptococcus Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Laboratory Findings Treatment Prognosis Prevention Chemoprophylaxis Maternal Immunization Bibliography 185 Non–Group A or B Streptococci 185 Non–Group A or B Streptococci Bibliography 186 Enterococcus 186 Enterococcus Etiology Epidemiology Pathogenesis Antimicrobial Resistance Clinical Manifestations Neonatal Infections Infections in Older Children Treatment Treatment of Vancomycin-Resistant Enterococci Prevention Bibliography 187 Diphtheria (Corynebacterium diphtheriae) 187 Diphtheria (Corynebacterium diphtheriae) Etiology Epidemiology Pathogenesis Clinical Manifestations Respiratory Tract Diphtheria Cutaneous Diphtheria Infection at Other Sites Diagnosis Complications Toxic Cardiomyopathy Toxic Neuropathy Treatment Supportive Care Prognosis Prevention Asymptomatic Case Contacts Asymptomatic Carriers Vaccine Bibliography 188 Listeria monocytogenes 188 Listeria monocytogenes Etiology Epidemiology Pathology Pathogenesis Clinical Manifestations Listeriosis in Pregnancy Neonatal Listeriosis Postneonatal Infections Diagnosis Differential Diagnosis Treatment Prognosis Prevention Bibliography 189 Actinomyces 189 Actinomyces Etiology Epidemiology Pathogenesis Clinical Manifestations Cervicofacial Actinomycosis Abdominal and Pelvic Actinomycosis Pulmonary Actinomycosis Other Forms Diagnosis and Differential Diagnosis Treatment Prognosis Bibliography 190 Nocardia 190 Nocardia Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 191 Neisseria meningitidis (Meningococcus) 191 Neisseria meningitidis (Meningococcus) Etiology Epidemiology Pathogenesis and Pathophysiology Immunity Host Factors Clinical Manifestations Diagnosis Differential Diagnosis Treatment Antibiotics Supportive Care Complications Prognosis Prevention Secondary Prevention Vaccination Bibliography 192 Neisseria gonorrhoeae (Gonococcus) 192 Neisseria gonorrhoeae (Gonococcus) Etiology Epidemiology Pathogenesis and Pathology Clinical Manifestations Asymptomatic Gonorrhea Uncomplicated Gonorrhea Disseminated Gonococcal Infection Diagnosis Treatment Adolescent and Adult Infections Infant and Pediatric Infections Pelvic Inflammatory Disease Complications Prognosis Prevention Bibliography 193 Kingella kingae 193 Kingella kingae Etiology Epidemiology Pathogenesis Clinical Disease Septic Arthritis Osteomyelitis Spondylodiscitis Occult Bacteremia Endocarditis Diagnosis Treatment Prevention Bibliography 194 Haemophilus influenzae 194 Haemophilus influenzae Etiology Epidemiology Pathogenesis Antibiotic Resistance Immunity Diagnosis Clinical Manifestations and Treatment Meningitis Cellulitis Preseptal Cellulitis Orbital Cellulitis Supraglottitis or Acute Epiglottitis Pneumonia Suppurative Arthritis Pericarditis Bacteremia Without an Associated Focus Miscellaneous Infections Invasive Disease in Neonates Otitis Media Conjunctivitis Sinusitis Prevention Vaccine Prophylaxis Bibliography 195 Chancroid (Haemophilus ducreyi) 195 Chancroid (Haemophilus ducreyi) Etiology and Epidemiology Clinical Manifestations. Diagnosis Treatment Complications Bibliography 196 Moraxella catarrhalis 196 Moraxella catarrhalis Etiology Epidemiology Pathogenesis of Infection Clinical Manifestations Acute Otitis Media Recurrent Otitis Media and Otitis Media with Effusion Sinusitis Bacteremia Diagnosis Treatment Prevention Bibliography 197 Pertussis (Bordetella pertussis and Bordetella parapertussis) 197 Pertussis (Bordetella pertussis and Bordetella parapertussis) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Antibiotics Adjunct Therapies Isolation Care of Household and Other Close Contacts Complications Prevention DTaP Vaccines Tdap Vaccines Bibliography 198 Salmonella 198 Salmonella 198.1 Nontyphoidal Salmonellosis Etiology Epidemiology Pathogenesis Clinical Manifestations Acute Enteritis Bacteremia Extraintestinal Focal Infections Complications Diagnosis Treatment Prognosis Prevention Bibliography 198.2 Enteric Fever (Typhoid Fever) Etiology Epidemiology Pathogenesis Clinical Features Complications Diagnosis Differential Diagnosis Treatment Prognosis Prevention Bibliography 199 Shigella 199 Shigella Etiology Epidemiology Pathogenesis Immunity Clinical Manifestations and Complications Differential Diagnosis Diagnosis Treatment Prevention Bibliography 200 Escherichia coli 200 Escherichia coli Enterotoxigenic Escherichia Coli Enteroinvasive Escherichia Coli Enteropathogenic Escherichia Coli Shiga Toxin–Producing Escherichia Coli Enteroaggregative Escherichia Coli Diffusely Adherent Escherichia Coli Enteroaggregative Hemorrhagic Escherichia Coli Diagnosis Treatment Prevention of Illness Bibliography 201 Cholera 201 Cholera Etiology Epidemiology Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Prevention Bibliography 202 Campylobacter 202 Campylobacter Etiology Epidemiology Pathogenesis Clinical Manifestations Acute Gastroenteritis Bacteremia Focal Extraintestinal Infections Perinatal Infections Diagnosis Complications Reactive Arthritis Guillain-Barré Syndrome Other Complications Treatment Prognosis Prevention Bibliography 203 Yersinia 203 Yersinia 203.1 Yersinia enterocolitica Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Complications Prevention Bibliography 203.2 Yersinia pseudotuberculosis Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Complications Prevention Bibliography 203.3 Plague (Yersinia pestis) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prevention Bibliography 204 Aeromonas and Plesiomonas 204 Aeromonas and Plesiomonas 204.1 Aeromonas Etiology Epidemiology Pathogenesis Clinical Manifestations Enteritis Skin and Soft-Tissue Infections Septicemia Other Infections Diagnosis Treatment Prevention Bibliography 204.2 Plesiomonas shigelloides Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 205 Pseudomonas, Burkholderia, and Stenotrophomonas 205 Pseudomonas, Burkholderia, and Stenotrophomonas 205.1 Pseudomonas aeruginosa Etiology Epidemiology Pathology Pathogenesis Clinical Manifestations Burns and Wound Infection Cystic Fibrosis Immunocompromised Persons Nosocomial Pneumonia Infants Diagnosis Treatment Supportive Care Prognosis Prevention Bibliography 205.2 Burkholderia cepacia Complex Burkholderia Mallei (Glanders) Burkholderia Pseudomallei (Melioidosis) Bibliography Burkholderia cepacia Complex Burkholderia mallei Burkholderia pseudomallei 205.3 Stenotrophomonas Bibliography 206 Tularemia (Francisella tularensis) 206 Tularemia (Francisella tularensis) Etiology Epidemiology Transmission Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prognosis Prevention Bibliography 207 Brucella 207 Brucella Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prognosis Prevention Bibliography 208 Legionella 208 Legionella Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 209 Bartonella 209 Bartonella 209.1 Cat-Scratch Disease (Bartonella henselae) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Laboratory Findings Treatment Complications Prognosis Prevention Bibliography 209.2 Bartonellosis (Bartonella bacilliformis) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Bibliography 209.3 Trench Fever (Bartonella quintana) Etiology Epidemiology Clinical Manifestations Diagnosis Treatment 209.4 Bacillary Angiomatosis and Bacillary Peliosis Hepatis (Bartonella henselae and Bartonella quintana) Bacillary Angiomatosis Bacillary Peliosis Bacteremia and Endocarditis Diagnosis Treatment Prevention Bibliography Bibliography 210 Botulism (Clostridium botulinum) 210 Botulism (Clostridium botulinum) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Supportive Care Complications Prognosis Prevention Bibliography 211 Tetanus (Clostridium tetani) 211 Tetanus (Clostridium tetani) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Supportive Care Complications Prognosis Prevention Wound Management Bibliography 212 Clostridium difficile Infection 212 Clostridium difficile Infection Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 213 Other Anaerobic Infections 213 Other Anaerobic Infections Clinical Manifestations Bacteremia Central Nervous System Upper Respiratory Tract Lower Respiratory Tract Intraabdominal Infection Genital Tract Skin and Soft Tissue Other Sites Diagnosis Treatment Common Anaerobic Pathogens Clostridium Myonecrosis (Gas Gangrene) Food Poisoning Bacteroides and Prevotella Fusobacterium Veillonella Anaerobic Cocci Bibliography 214 Principles of Antimycobacterial Therapy 214 Principles of Antimycobacterial Therapy Agents Used Against Mycobacterium Tuberculosis Commonly Used Agents Isoniazid Rifamycins Pyrazinamide Ethambutol Less Commonly Used Agents Aminoglycosides Cycloserine Ethionamide Fluoroquinolones Linezolid Paraaminosalicylic Acid Bedaquiline Fumarate Agents Used Against Mycobacterium Leprae Dapsone Clofazimine Agents Used Against Nontuberculous Mycobacteria Cefoxitin Doxycycline Macrolides Trimethoprim-Sulfamethoxazole Bibliography 215 Tuberculosis (Mycobacterium tuberculosis) 215 Tuberculosis (Mycobacterium tuberculosis) Etiology Terminology: Exposure, Infection, Disease Epidemiology Transmission Pathogenesis Immunity Clinical Manifestations Primary Pulmonary Disease Progressive Primary Pulmonary Disease Reactivation Tuberculosis Pleural Effusion Pericardial Disease Lymphohematogenous (Disseminated) Disease Upper Respiratory Tract Disease Lymph Node Disease Central Nervous System Disease Cutaneous Disease Bone and Joint Disease Abdominal and Gastrointestinal Disease Genitourinary Disease Pregnancy and the Newborn Perinatal Disease Disease in HIV-Infected Children Diagnostic Tools Tuberculin Skin Testing Interferon-γ Release Assays Mycobacterial Sampling, Susceptibility and Culture Nucleic Acid Amplification Treatment Drug-Resistant Tuberculosis Corticosteroids Supportive Care Latent Mycobacterium tuberculosis Infection Prevention Bacille Calmette-Guérin Vaccination Prevention of Perinatal Tuberculosis Bibliography 216 Hansen Disease (Mycobacterium leprae) 216 Hansen Disease (Mycobacterium leprae) Etiology Epidemiology Pathogenesis Clinical Manifestations Skin Involvement Nerve Involvement Other Involvement Diagnosis Treatment Long-Term Complications Prevention Bibliography 217 Nontuberculous Mycobacteria 217 Nontuberculous Mycobacteria Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 218 Syphilis (Treponema pallidum) 218 Syphilis (Treponema pallidum) Etiology Epidemiology Clinical Manifestations and Laboratory Findings Congenital Infection Diagnosis Congenital Syphilis Treatment Acquired Syphilis Syphilis in Pregnancy Congenital Syphilis Prevention Congenital Syphilis Bibliography 219 Nonvenereal Treponemal Infections 219 Nonvenereal Treponemal Infections 219.1 Yaws (Treponema pertenue) 219.2 Bejel (Endemic Syphilis; Treponema pallidum endemicum) 219.3 Pinta (Treponema carateum) Bibliography Bibliography 220 Leptospira 220 Leptospira Etiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Anicteric Leptospirosis Icteric Leptospirosis (Weil Syndrome) Diagnosis Treatment Prevention Bibliography 221 Relapsing Fever (Borrelia) 221 Relapsing Fever (Borrelia) Etiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 222 Lyme Disease (Borrelia burgdorferi) 222 Lyme Disease (Borrelia burgdorferi) Etiology Epidemiology Transmission Pathology and Pathogenesis Clinical Manifestations Early Localized Disease Early Disseminated Disease Late Disease Congenital Lyme Disease Laboratory Findings Diagnosis Serology Treatment Prognosis Prevention Bibliography 223 Mycoplasma pneumoniae 223 Mycoplasma pneumoniae The Organism Epidemiology Pathology and Pathogenesis Clinical Manifestations Respiratory Tract Disease Extrapulmonary Disease Diagnosis Treatment Antimicrobial Therapy Adjunctive Therapy Prevention Bibliography 224 Genital Mycoplasmas (Mycoplasma Hominis, Mycoplasma Genitalium, and Ureaplasma Urealyticum) 224 Genital Mycoplasmas (Mycoplasma Hominis, Mycoplasma Genitalium, and Ureaplasma Urealyticum) Etiology Epidemiology Transmission Pathology and Pathogenesis Clinical Manifestations Intrauterine and Neonatal Infections Genitourinary Infections Nongenital Infections Diagnosis Genital Tract Infection Neonates Treatment Adolescents and Adults Neonates Bibliography 225 Chlamydia (Chlamydophila) pneumoniae 225 Chlamydia (Chlamydophila) pneumoniae Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 226 Chlamydia trachomatis 226 Chlamydia trachomatis 226.1 Trachoma Bibliography 226.2 Genital Tract Infections Epidemiology Clinical Manifestations Diagnosis Treatment Complications Prevention Bibliography 226.3 Conjunctivitis and Pneumonia in Newborns Epidemiology Inclusion Conjunctivitis Pneumonia Infections at Other Sites Diagnosis Treatment Prevention Bibliography 226.4 Lymphogranuloma Venereum Clinical Manifestations Diagnosis Treatment Bibliography 227 Psittacosis (Chlamydia psittaci) 227 Psittacosis (Chlamydia psittaci) Etiology Epidemiology Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 228 Spotted Fever Group Rickettsioses 228 Spotted Fever Group Rickettsioses 228.1 Rocky Mountain Spotted Fever (Rickettsia rickettsii) Etiology Epidemiology Transmission Pathology and Pathogenesis Clinical Manifestations Other Laboratory Findings Diagnosis Differential Diagnosis Treatment Supportive Care Complications Prognosis Prevention 228.2 Mediterranean Spotted Fever or Boutonneuse Fever (Rickettsia conorii) Etiology Epidemiology Transmission Pathology and Pathogenesis Clinical Manifestations and Laboratory Findings Diagnosis Differential Diagnosis Treatment and Supportive Care Complications Prevention 228.3 Rickettsialpox (Rickettsia akari) Bibliography 229 Scrub Typhus (Orientia tsutsugamushi) 229 Scrub Typhus (Orientia tsutsugamushi) Etiology Epidemiology Transmission Pathology and Pathogenesis Clinical Manifestations and Laboratory Findings Diagnosis and Differential Diagnosis Treatment and Supportive Care Complications Prevention Bibliography 230 Typhus Group Rickettsioses 230 Typhus Group Rickettsioses 230.1 Murine (Endemic or Flea-Borne) Typhus (Rickettsia typhi) Etiology Epidemiology Transmission Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Supportive Care Complications Prevention 230.2 Epidemic (Louse-Borne) Typhus (Rickettsia prowazekii) Etiology Epidemiology Transmission Clinical Manifestations Treatment Prevention Bibliography 231 Ehrlichiosis and Anaplasmosis 231 Ehrlichiosis and Anaplasmosis Etiology Epidemiology Transmission Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis Differential Diagnosis Treatment Complications and Prognosis Prevention Bibliography 232 Q Fever (Coxiella burnetii) 232 Q Fever (Coxiella burnetii) Etiology Epidemiology Transmission Pathology and Pathogenesis Clinical Manifestations and Complications Acute Q Fever Chronic Q Fever Laboratory Findings Diagnosis and Differential Diagnosis Treatment Prevention Bibliography 233 Principles of Antifungal Therapy 233 Principles of Antifungal Therapy Polyenes Amphotericin B Pyrimidine Analogs 5-Fluorocytosine Azoles Fluconazole Itraconazole Voriconazole Posaconazole Echinocandins Caspofungin Micafungin Anidulafungin Bibliography 234 Candida 234 Candida 234.1 Neonatal Infections Epidemiology Pathogenesis Clinical Manifestations Diagnosis Prophylaxis Treatment Prognosis Bibliography 234.2 Infections in Immunocompetent Children and Adolescents Oral Candidiasis Diaper Dermatitis Ungual and Periungual Infections Vulvovaginitis Bibliography 234.3 Infections in Immunocompromised Children and Adolescents Etiology Clinical Manifestations HIV-Infected Children Cancer and Transplant Patients Catheter-Associated Infections Diagnosis Treatment Primary Immune Defects Bibliography 235 Cryptococcus neoformans 235 Cryptococcus neoformans Etiology Epidemiology Pathogenesis Clinical Manifestations Pneumonia Disseminated Infection Meningitis Sepsis Syndrome Cutaneous Infection Skeletal Infection Ocular Infection Lymph Nodes Diagnosis Treatment Prevention Bibliography 236 Malassezia 236 Malassezia Bibliography 237 Aspergillus 237 Aspergillus 237.1 Allergic Disease (Hypersensitivity Syndromes) Asthma Extrinsic Alveolar Alveolitis Allergic Bronchopulmonary Aspergillosis Allergic Aspergillus Sinusitis Bibliography 237.2 Saprophytic (Noninvasive) Syndromes Pulmonary Aspergilloma Chronic Pulmonary Aspergillosis Sinusitis Otomycosis Bibliography 237.3 Invasive Disease Invasive Pulmonary Aspergillosis Diagnosis Treatment Special Populations Cutaneous Aspergillosis Invasive Sinonasal Disease Central Nervous System Eye Bone Heart Empirical Antifungal Therapy Bibliography 238 Histoplasmosis (Histoplasma capsulatum) 238 Histoplasmosis (Histoplasma capsulatum) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 239 Blastomycosis (Blastomyces dermatitidis) 239 Blastomycosis (Blastomyces dermatitidis) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 240 Coccidioidomycosis (Coccidioides Species) 240 Coccidioidomycosis (Coccidioides Species) Etiology Epidemiology Pathogenesis Clinical Manifestations Primary Coccidioidomycosis Complicated Pulmonary Infection Residual Pulmonary Coccidioidomycosis Disseminated (Extrapulmonary) Infection Diagnosis Culture, Histopathologic Findings, and Antigen Detection Serology Imaging Procedures Treatment Primary Pulmonary Infection Diffuse Pneumonia Disseminated (Extrapulmonary) Infection Meningitis Surgical Management Prevention Bibliography 241 Paracoccidioides brasiliensis 241 Paracoccidioides brasiliensis Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 242 Sporotrichosis (Sporothrix schenckii) 242 Sporotrichosis (Sporothrix schenckii) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 243 Zygomycosis (Mucormycosis) 243 Zygomycosis (Mucormycosis) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 244 Pneumocystis jiroveci 244 Pneumocystis jiroveci Etiology Epidemiology Pathogenesis Pathology Clinical Manifestations Laboratory Findings Diagnosis Treatment Supportive Care Complications Prognosis Prevention Bibliography 245 Principles of Antiviral Therapy 245 Principles of Antiviral Therapy Antivirals Used for Herpesviruses Acyclovir Valacyclovir Penciclovir and Famciclovir Ganciclovir Foscarnet Cidofovir Trifluridine Vidarabine Fomivirsen New Agents Antivirals Used for Respiratory Viral Infections Ribavirin Amantadine and Rimantadine Oseltamivir, Zanamivir, and Peramivir Antiviral Immune Globulins Bibliography 246 Measles 246 Measles Etiology Epidemiology Transmission Pathology Pathogenesis Clinical Manifestations Inapparent Measles Infection Laboratory Findings Diagnosis Differential Diagnosis Complications Subacute Sclerosing Panencephalitis Treatment Vitamin A Prognosis Prevention Vaccine Postexposure Prophylaxis Bibliography 247 Rubella 247 Rubella Etiology Epidemiology Pathology Pathogenesis Clinical Manifestations Laboratory Findings Diagnoses Differential Diagnoses Complications Congenital Rubella Syndrome Treatment Supportive Care Prognosis Prevention Vaccination Bibliography 248 Mumps 248 Mumps Etiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Complications Meningitis and Meningoencephalitis Orchitis and Oophoritis Pancreatitis Cardiac Involvement Arthritis Thyroiditis Treatment Prognosis Prevention Bibliography 249 Polioviruses 249 Polioviruses Etiology Epidemiology Transmission Pathogenesis Clinical Manifestations Abortive Poliomyelitis Nonparalytic Poliomyelitis Paralytic Poliomyelitis Diagnosis Differential Diagnosis Treatment Abortive Poliomyelitis Nonparalytic Poliomyelitis Paralytic Poliomyelitis Complications Prognosis Postpolio Syndrome Prevention Bibliography 250 Nonpolio Enteroviruses 250 Nonpolio Enteroviruses Etiology Epidemiology Pathogenesis Clinical Manifestations Nonspecific Febrile Illness Hand-Foot-and-Mouth Disease Herpangina Respiratory Manifestations Ocular Manifestations Myocarditis and Pericarditis Gastrointestinal and Genitourinary Manifestations Neurologic Manifestations Myositis and Arthritis Neonatal Infections Transplant Recipients and Patients with Malignancies Diagnosis Differential Diagnosis Treatment Complications and Prognosis Prevention Bibliography 251 Parvoviruses 251 Parvoviruses Etiology Epidemiology Parvovirus B19 Human Bocaviruses Pathogenesis Parvovirus B19 Human Bocaviruses Clinical Manifestations Parvovirus B19 Erythema Infectiosum (Fifth Disease) Arthropathy Transient Aplastic Crisis Immunocompromised Persons Fetal Infection Myocarditis Other Cutaneous Manifestations Human Bocaviruses Diagnosis Parvovirus B19 Infection Human Bocavirus Infections Differential Diagnosis Parvovirus B19 Human Bocavirus Treatment Parvovirus B19 Human Bocavirus Complications Parvovirus B19 Human Bocavirus Prevention Parvovirus B19 Human Bocavirus Bibliography 252 Herpes Simplex Virus 252 Herpes Simplex Virus Etiology Epidemiology Pathogenesis Clinical Manifestations Acute Oropharyngeal Infections Herpes Labialis Cutaneous Infections Genital Herpes Ocular Infections Central Nervous System Infections Infections in Immunocompromised Persons Perinatal Infections Diagnosis Laboratory Findings Treatment Acute Mucocutaneous Infections Genital Herpes Ocular Infections Central Nervous System Infections Infections in Immunocompromised Persons Perinatal Infections Prognosis Prevention Bibliography 253 Varicella-Zoster Virus 253 Varicella-Zoster Virus Etiology Epidemiology Pathogenesis Clinical Manifestations Varicella in Unvaccinated Individuals Varicelliform Rashes in Vaccinated Individuals Neonatal Varicella Congenital Varicella Syndrome Complications Bacterial Infections Encephalitis and Cerebellar Ataxia Pneumonia Progressive Varicella Herpes Zoster Diagnosis Treatment Varicella Herpes Zoster Prognosis Prevention Vaccine Vaccine-Associated Adverse Events Postexposure Prophylaxis Bibliography 254 Epstein-Barr Virus 254 Epstein-Barr Virus Etiology Epidemiology Pathogenesis Oncogenesis Clinical Manifestations Diagnosis Differential Diagnosis Laboratory Tests Heterophile Antibody Test Specific Epstein-Barr Virus Antibodies Treatment Complications Prognosis Prevention Bibliography 255 Cytomegalovirus 255 Cytomegalovirus The Virus and Its Interaction with the Host Epidemiology Mechanisms of Disease Associated with Cytomegalovirus Infections Clinical Manifestations Immunocompromised Host Congenital Infection Perinatal Infection Diagnosis Congenital Infections Noncongenital Infections Treatment Prevention Passive Immunoprophylaxis Active Immunoprophylaxis Counseling Bibliography 256 Roseola (Human Herpesviruses 6 and 7) 256 Roseola (Human Herpesviruses 6 and 7) Etiology Epidemiology Pathology/Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis Differential Diagnosis Complications Treatment Prognosis Prevention Bibliography 257 Human Herpesvirus 8 257 Human Herpesvirus 8 Etiology Epidemiology Pathology and Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 258 Influenza Viruses 258 Influenza Viruses Etiology Epidemiology Antigenic Variation Seasonal Influenza Pathogenesis Clinical Manifestations Complications Laboratory Findings Diagnosis and Differential Diagnosis Treatment Supportive Care Prognosis Prevention Vaccines Chemoprophylaxis Bibliography 259 Parainfluenza Viruses 259 Parainfluenza Viruses Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis and Differential Diagnosis Treatment Complications Prognosis Prevention Bibliography 260 Respiratory Syncytial Virus 260 Respiratory Syncytial Virus Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Prevention Passive Immunoprophylaxis Vaccine Bibliography 261 Human Metapneumovirus 261 Human Metapneumovirus Etiology Epidemiology Pathology Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Supportive Care Prognosis Prevention Bibliography 262 Adenoviruses 262 Adenoviruses Etiology Epidemiology Pathogenesis Clinical Manifestations Acute Respiratory Disease Ocular Infections Gastrointestinal Infections Hemorrhagic Cystitis Other Complications Adenoviruses in Immunocompromised Patients Diagnosis Complications Treatment Prevention Bibliography 263 Rhinoviruses 263 Rhinoviruses Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Complications Treatment Prevention Bibliography 264 Coronaviruses 264 Coronaviruses Etiology Epidemiology Pathogenesis Clinical Manifestations Respiratory Infections Nonrespiratory Sequelae Severe Acute Respiratory Syndrome–Associated Coronavirus Middle East Respiratory Syndrome Coronavirus Diagnosis Treatment and Prevention Bibliography 265 Rotaviruses, Caliciviruses, and Astroviruses 265 Rotaviruses, Caliciviruses, and Astroviruses Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Laboratory Findings Differential Diagnosis Treatment Supportive Treatment Prognosis Prevention Vaccines Bibliography 266 Human Papillomaviruses 266 Human Papillomaviruses Etiology Epidemiology Pathogenesis Clinical Manifestations Skin Lesions Genital Warts Squamous Intraepithelial Lesions and Cancers Laryngeal Papillomatosis Diagnosis Differential Diagnosis Treatment Complications Prognosis Prevention Bibliography 267 Arboviral Infections in North America 267 Arboviral Infections in North America Etiology Epidemiology Eastern Equine Encephalitis Western Equine Encephalitis St. Louis Encephalitis West Nile Encephalitis Powassan Encephalitis La Crosse/California Encephalitis Colorado Tick Fever Chikungunya Virus Clinical Manifestations Eastern Equine Encephalitis Western Equine Encephalitis St. Louis Encephalitis West Nile Encephalitis Powassan Encephalitis Lacrosse/California Encephalitis Colorado Tick Fever Chikungunya Virus Diagnosis Treatment Prognosis Eastern Equine Encephalitis Western Equine Encephalitis St. Louis Encephalitis West Nile Encephalitis Powassan Encephalitis La Crosse or California Encephalitis Colorado Tick Fever Chikungunya Prevention Bibliography 268 Arboviral Infections Outside North America 268 Arboviral Infections Outside North America 268.1 Venezuelan Equine Encephalitis Etiology Epidemiology Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 268.2 Japanese Encephalitis Etiology Epidemiology Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 268.3 Tickborne Encephalitis Etiology Epidemiology Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 268.4 West Nile Encephalitis 269 Dengue Fever and Dengue Hemorrhagic Fever 269 Dengue Fever and Dengue Hemorrhagic Fever Etiology Epidemiology Dengue-Like Diseases Dengue Hemorrhagic Fever Pathogenesis Clinical Manifestations Dengue Fever Dengue Hemorrhagic Fever Diagnosis Differential Diagnosis Laboratory Findings Treatment Dengue Hemorrhagic Fever and Dengue Shock Syndrome Complications Prognosis Dengue Fever Dengue Hemorrhagic Fever Prevention Bibliography 270 Yellow Fever 270 Yellow Fever Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Complications Prevention Bibliography 271 Ebola and Other Viral Hemorrhagic Fevers 271 Ebola and Other Viral Hemorrhagic Fevers Etiology Epidemiology and Clinical Manifestations Crimean-Congo Hemorrhagic Fever Kyasanur Forest Disease Omsk Hemorrhagic Fever Rift Valley Fever Argentine Hemorrhagic Fever Bolivian Hemorrhagic Fever Venezuelan Hemorrhagic Fever Lassa Fever Marburg Disease Ebola Hemorrhagic Fever Hemorrhagic Fever with Renal Syndrome Clinical Manifestations Crimean-Congo Hemorrhagic Fever Kyasanur Forest Disease and Omsk Hemorrhagic Fever Rift Valley Fever Argentine, Venezuelan, and Bolivian Hemorrhagic Fevers and Lassa Fever Marburg Disease and Ebola Hemorrhagic Fever Hemorrhagic Fever with Renal Syndrome Diagnosis Differential Diagnosis Treatment Prevention Bibliography 272 Lymphocytic Choriomeningitis Virus 272 Lymphocytic Choriomeningitis Virus Etiology Epidemiology Pathogenesis Clinical Manifestations Acquired (Postnatal) Lymphocytic Choriomeningitis Virus Infection Congenital Lymphocytic Choriomeningitis Virus Infection Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Supportive Care Prognosis Prevention Bibliography 273 Hantavirus Pulmonary Syndrome 273 Hantavirus Pulmonary Syndrome Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Laboratory Findings Differential Diagnosis Treatment Prognosis Prevention Bibliography 274 Rabies 274 Rabies Epidemiology Transmission Pathogenesis Clinical Manifestations Differential Diagnosis Diagnosis Treatment and Prognosis Prevention Immunization and Fertility Control of Animal Reservoirs Postexposure Prophylaxis Preexposure Prophylaxis Bibliography 275 Polyomaviruses 275 Polyomaviruses Bibliography 276 Acquired Immunodeficiency Syndrome (Human Immunodeficiency Virus) 276 Acquired Immunodeficiency Syndrome (Human Immunodeficiency Virus) Etiology Epidemiology Transmission Pathogenesis Clinical Manifestations Infections Central Nervous System Respiratory Tract Cardiovascular System Gastrointestinal and Hepatobiliary Tract Renal Disease Skin Manifestations Hematologic and Malignant Diseases Diagnosis Treatment Combination Therapy Adherence Initiation of Therapy Dosing Changing Antiretroviral Therapy Monitoring Antiretroviral Therapy Resistance to Antiretroviral Therapy Supportive Care Prognosis Prevention Bibliography 277 Human T-Lymphotropic Viruses (1 and 2) 277 Human T-Lymphotropic Viruses (1 and 2) Etiology Epidemiology Diagnosis Clinical Manifestations Adult T-Cell Leukemia/Lymphoma Human T-Cell Lymphotropic Virus-1–Associated Myelopathy Human T-Cell Lymphotropic Virus-2 Prevention Bibliography 278 Transmissible Spongiform Encephalopathies 278 Transmissible Spongiform Encephalopathies Etiology Epidemiology Pathogenesis and Pathology Clinical Manifestations Diagnosis Laboratory Findings Treatment Genetic Counseling Prognosis Family Support Prevention Bibliography 279 Principles of Antiparasitic Therapy 279 Principles of Antiparasitic Therapy Selected Antiparasitic Drugs for Protozoans Nitazoxanide (Alinia) Tinidazole (Tindamax) Atovaquone/Proguanil (Malarone) Artemisinin Derivatives and Artemether/Lumefantrine (Coartem, Artemether, Artesunate) Selected Antiparasitic Drugs for Helminths Albendazole (Albenza) Ivermectin (Stromectol, Mectizan) Praziquantel (Biltricide) 280 Primary Amebic Meningoencephalitis 280 Primary Amebic Meningoencephalitis Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 281 Amebiasis 281 Amebiasis Etiology Epidemiology Pathogenesis Clinical Manifestations Amebic Colitis Amebic Liver Abscess Men Who Have Sex with Men and HIV Coinfection Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Prognosis Prevention Bibliography 282 Giardiasis and Balantidiasis 282 Giardiasis and Balantidiasis 282.1 Giardia lamblia Etiology Epidemiology Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 282.2 Balantidiasis Bibliography 283 Cryptosporidium, Isospora, Cyclospora, and Microsporidia 283 Cryptosporidium, Isospora, Cyclospora, and Microsporidia Cryptosporidium Etiology Epidemiology Clinical Manifestations Diagnosis Treatment Isospora Cyclospora Microsporidia Bibliography 284 Trichomoniasis (Trichomonas vaginalis) 284 Trichomoniasis (Trichomonas vaginalis) Epidemiology Pathogenesis Clinical Manifestations Diagnosis Complications Treatment Prevention Bibliography 285 Leishmaniasis (Leishmania) 285 Leishmaniasis (Leishmania) Etiology Epidemiology Pathology Pathogenesis Clinical Manifestations Localized Cutaneous Leishmaniasis Diffuse Cutaneous Leishmaniasis Mucosal Leishmaniasis Visceral Leishmaniasis Laboratory Findings Differential Diagnosis Diagnosis Treatment Prevention Bibliography 286 African Trypanosomiasis (Sleeping Sickness; Trypanosoma brucei Complex) 286 African Trypanosomiasis (Sleeping Sickness; Trypanosoma brucei Complex) Etiology Life Cycle Epidemiology Pathogenesis Clinical Manifestations Trypanosomal Chancre Hemolymphatic Stage (Stage 1) Meningoencephalitic Stage (Stage 2) Diagnosis Treatment Stage 1 Treatment Stage 2 Treatment Prevention Bibliography 287 American Trypanosomiasis (Chagas Disease; Trypanosoma cruzi) 287 American Trypanosomiasis (Chagas Disease; Trypanosoma cruzi) Etiology Life Cycle Epidemiology Pathogenesis Acute Disease Chronic Disease Clinical Manifestations Immunocompromised Persons Diagnosis Treatment Prevention Bibliography 288 Malaria (Plasmodium) 288 Malaria (Plasmodium) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Plasmodium Falciparum Malaria Plasmodium Vivax, P. Ovale, P. Malariae, or P. Knowlesi Malaria Complications of Plasmodium Falciparum Malaria Prevention Bibliography 289 Babesiosis (Babesia) 289 Babesiosis (Babesia) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Prevention Bibliography 290 Toxoplasmosis (Toxoplasma gondii) 290 Toxoplasmosis (Toxoplasma gondii) Etiology Epidemiology Congenital Toxoplasmosis Pathogenesis Congenital Toxoplasmosis Clinical Manifestations Acquired Toxoplasmosis Ocular Toxoplasmosis Immunocompromised Persons Congenital Toxoplasmosis Systemic Signs Skin Endocrine Abnormalities Central Nervous System Eyes Ears Diagnosis Isolation Serologic Testing Acquired Toxoplasmosis Ocular Toxoplasmosis Immunocompromised Persons Congenital Toxoplasmosis Treatment Acquired Toxoplasmosis Ocular Toxoplasmosis Immunocompromised Persons Congenital Toxoplasmosis Pregnant Women with Toxoplasma gondii Infection Prognosis Prevention Bibliography 291 Ascariasis (Ascaris lumbricoides) 291 Ascariasis (Ascaris lumbricoides) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Bibliography 292 Hookworms (Necator americanus and Ancylostoma Spp.) 292 Hookworms (Necator americanus and Ancylostoma Spp.) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Bibliography 292.1 Cutaneous Larva Migrans Etiology Epidemiology Clinical Manifestations Diagnosis Treatment Bibliography 293 Trichuriasis (Trichuris trichiura) 293 Trichuriasis (Trichuris trichiura) Etiology Epidemiology Clinical Manifestations Diagnosis Treatment Prevention Bibliography 294 Enterobiasis (Enterobius vermicularis) 294 Enterobiasis (Enterobius vermicularis) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Bibliography 295 Strongyloidiasis (Strongyloides stercoralis) 295 Strongyloidiasis (Strongyloides stercoralis) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Bibliography 296 Lymphatic Filariasis (Brugia malayi, Brugia timori, and Wuchereria bancrofti) 296 Lymphatic Filariasis (Brugia malayi, Brugia timori, and Wuchereria bancrofti) Etiology Epidemiology Clinical Manifestations Tropical Pulmonary Eosinophilia Diagnosis Treatment Bibliography 297 Other Tissue Nematodes 297 Other Tissue Nematodes Onchocerciasis (Onchocerca Volvulus) Loiasis (Loa Loa) Infection with Animal Filariae Angiostrongylus Cantonensis Angiostrongylus Costaricensis Dracunculiasis (Dracunculus Medinensis) Gnathostoma Spinigerum Bibliography Onchocerciasis (Onchocerca Volvulus) Loiasis (Loa Loa) Infection with Animal Filariae Angiostrongylus Cantonensis Angiostrongylus Costaricensis Dracunculiasis (Dracunculus Medinensis) Gnathostoma Spinigerum 298 Toxocariasis (Visceral and Ocular Larva Migrans) 298 Toxocariasis (Visceral and Ocular Larva Migrans) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Bibliography 299 Trichinellosis (Trichinella spiralis) 299 Trichinellosis (Trichinella spiralis) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Bibliography 300 Schistosomiasis (Schistosoma) 300 Schistosomiasis (Schistosoma) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prevention Bibliography 301 Flukes (Liver, Lung, and Intestinal) 301 Flukes (Liver, Lung, and Intestinal) Liver Flukes Fascioliasis (Fasciola Hepatica) Clonorchiasis (Clonorchis Sinensis) Opisthorchiasis (Opisthorchis Spp.) Lung Flukes Paragonimiasis (Paragonimus Spp.) Intestinal Flukes Bibliography 302 Adult Tapeworm Infections 302 Adult Tapeworm Infections Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prevention Diphyllobothriasis (Diphyllobothrium Species) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prevention Hymenolepiasis (Hymenolepis) Dipylidiasis (Dipylidium Caninum) Bibliography 303 Cysticercosis 303 Cysticercosis Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prevention Bibliography 304 Echinococcosis (Echinococcus granulosus and Echinococcus multilocularis) 304 Echinococcosis (Echinococcus granulosus and Echinococcus multilocularis) Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prognosis Prevention Bibliography The Digestive System 305 Normal Digestive Tract Phenomena 305 Normal Digestive Tract Phenomena 306 Major Symptoms and Signs of Digestive Tract Disorders 306 Major Symptoms and Signs of Digestive Tract Disorders Dysphagia Regurgitation Anorexia Vomiting Diarrhea Constipation Abdominal Pain Gastrointestinal Hemorrhage Abdominal Distention and Abdominal Masses Jaundice Bibliography 307 Development and Developmental Anomalies of the Teeth 307 Development and Developmental Anomalies of the Teeth Initiation Histodifferentiation–Morphodifferentiation Calcification Eruption Anomalies Associated with Tooth Development Bibliography 308 Disorders of the Oral Cavity Associated with Other Conditions 308 Disorders of the Oral Cavity Associated with Other Conditions 309 Malocclusion 309 Malocclusion Variations in Growth Patterns Crossbite Open and Closed Bites Dental Crowding Digit Sucking 310 Cleft Lip and Palate 310 Cleft Lip and Palate Incidence and Epidemiology Clinical Manifestations Treatment Postoperative Management Sequelae Velopharyngeal Dysfunction Clinical Manifestations Bibliography 311 Syndromes with Oral Manifestations 311 Syndromes with Oral Manifestations Bibliography 312 Dental Caries 312 Dental Caries Etiology Epidemiology Clinical Manifestations Complications Treatment Prevention Fluoride Oral Hygiene Diet Dental Sealant Bibliography 313 Periodontal Diseases 313 Periodontal Diseases Gingivitis Aggressive Periodontitis in Children (Prepubertal Periodontitis) Aggressive Periodontitis in Adolescents (Localized Juvenile Periodontitis) Teething Cyclosporine- or Phenytoin-Induced Gingival Overgrowth Acute Pericoronitis Necrotizing Periodontal Disease (Acute Necrotizing Ulcerative Gingivitis) Bibliography 314 Dental Trauma 314 Dental Trauma Injuries to Teeth Injuries to Periodontal Structures Concussion Subluxation Intrusion Extrusion Avulsion Prevention Additional Considerations Bibliography 315 Common Lesions of the Oral Soft Tissues 315 Common Lesions of the Oral Soft Tissues Oropharyngeal Candidiasis Aphthous Ulcers Herpetic Gingivostomatitis Recurrent Herpes Labialis Bohn Nodules Dental Lamina Cysts Fordyce Granules Parulis Cheilitis Ankyloglossia Geographic Tongue Fissured Tongue 316 Diseases of the Salivary Glands and Jaws 316 Diseases of the Salivary Glands and Jaws Parotitis Ranula Mucocele Congenital Lip Pits Eruption Cyst Xerostomia Salivary Gland Tumors Histiocytic Disorders Tumors of the Jaw Bibliography 317 Diagnostic Radiology in Dental Assessment 317 Diagnostic Radiology in Dental Assessment 318 Embryology, Anatomy, and Function of the Esophagus 318 Embryology, Anatomy, and Function of the Esophagus Embryology Anatomy Function Bibliography 318.1 Common Clinical Manifestations and Diagnostic Aids Common Clinical Manifestations Diagnostic Aids 319 Congenital Anomalies 319 Congenital Anomalies 319.1 Esophageal Atresia and Tracheoesophageal Fistula Presentation Diagnosis Management Outcome Bibliography 319.2 Laryngotracheoesophageal Clefts Bibliography 320 Obstructing and Motility Disorders of the Esophagus 320 Obstructing and Motility Disorders of the Esophagus Extrinsic Intrinsic Bibliography 321 Dysmotility 321 Dysmotility Upper Esophageal and Upper Esophageal Sphincter Dysmotility (Striated Muscle) Lower Esophageal and Lower Esophageal Sphincter Dysfunction (Smooth Muscle) Bibliography 322 Hiatal Hernia 322 Hiatal Hernia 323 Gastroesophageal Reflux Disease 323 Gastroesophageal Reflux Disease Pathophysiology Epidemiology and Natural History Clinical Manifestations Diagnosis Management Bibliography 323.1 Complications of Gastroesophageal Reflux Disease Esophageal: Esophagitis And Sequelae—Stricture, Barrett Esophagus, Adenocarcinoma Nutritional Extraesophageal: Respiratory (“Atypical”) Presentations Apnea and Stridor Bibliography 324 Eosinophilic Esophagitis and Non–Gastroesophageal Reflux Disease Esophagitis 324 Eosinophilic Esophagitis and Non–Gastroesophageal Reflux Disease Esophagitis Eosinophilic Esophagitis Infective Esophagitis “Pill” Esophagitis Bibliography 325 Esophageal Perforation 325 Esophageal Perforation Bibliography 326 Esophageal Varices 326 Esophageal Varices Bibliography 327 Ingestions 327 Ingestions 327.1 Foreign Bodies in the Esophagus Bibliography 327.2 Caustic Ingestions Bibliography 328 Normal Development, Structure, and Function 328 Normal Development, Structure, and Function Development Digestion and Absorption 329 Pyloric Stenosis and Other Congenital Anomalies of the Stomach 329 Pyloric Stenosis and Other Congenital Anomalies of the Stomach 329.1 Hypertrophic Pyloric Stenosis Etiology Clinical Manifestations Differential Diagnosis Treatment Bibliography 329.2 Congenital Gastric Outlet Obstruction Clinical Manifestations Diagnosis Treatment 329.3 Gastric Duplication Bibliography 329.4 Gastric Volvulus Bibliography 329.5 Hypertrophic Gastropathy Pathogenesis Clinical Manifestations Diagnosis and Differential Diagnosis Treatment Bibliography 330 Intestinal Atresia, Stenosis, and Malrotation 330 Intestinal Atresia, Stenosis, and Malrotation 330.1 Duodenal Obstruction Clinical Manifestations and Diagnosis Treatment Bibliography 330.2 Jejunal and Ileal Atresia and Obstruction Clinical Manifestation and Diagnosis Treatment Bibliography 330.3 Malrotation Clinical Manifestations Treatment Bibliography Bibliography 331 Intestinal Duplications, Meckel Diverticulum, and Other Remnants of the Omphalomesenteric Duct 331 Intestinal Duplications, Meckel Diverticulum, and Other Remnants of the Omphalomesenteric Duct 331.1 Intestinal Duplication Clinical Manifestations 331.2 Meckel Diverticulum and Other Remnants of the Omphalomesenteric Duct Clinical Manifestations Diagnosis Bibliography 332 Motility Disorders and Hirschsprung Disease 332 Motility Disorders and Hirschsprung Disease 332.1 Chronic Intestinal Pseudoobstruction Clinical Manifestations Diagnosis Treatment Bibliography 332.2 Mitochondrial Neurogastrointestinal Encephalomyopathy Bibliography 332.3 Encopresis and Functional Constipation Clinical Manifestations Diagnosis Treatment Bibliography 332.4 Congenital Aganglionic Megacolon (Hirschsprung Disease) Pathology Clinical Manifestations Diagnosis Treatment Bibliography 332.5 Intestinal Neuronal Dysplasia Bibliography 332.6 Superior Mesenteric Artery Syndrome (Wilkie Syndrome, Cast Syndrome, Arteriomesenteric Duodenal Compression Syndrome) Bibliography 333 Ileus, Adhesions, Intussusception, and Closed-Loop Obstructions 333 Ileus, Adhesions, Intussusception, and Closed-Loop Obstructions 333.1 Ileus Bibliography 333.2 Adhesions Bibliography 333.3 Intussusception Etiology and Epidemiology Pathology Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prognosis Bibliography 333.4 Closed-Loop Obstructions Bibliography 334 Foreign Bodies and Bezoars 334 Foreign Bodies and Bezoars 334.1 Foreign Bodies in the Stomach and Intestine Bibliography 334.2 Bezoars Bibliography 335 Peptic Ulcer Disease in Children 335 Peptic Ulcer Disease in Children 335 Peptic Ulcer Disease in Children Pathogenesis Acid Secretion Mucosal Defense Clinical Manifestations Diagnosis Primary Ulcers Helicobacter pylori Gastritis Idiopathic Ulcers Secondary Ulcers Aspirin and Other Nonsteroidal Antiinflammatory Drugs “Stress” Ulceration Treatment Treatment of Helicobacter pylori–Related Peptic Ulcer Disease Surgical Therapy Bibliography 335.1 Zollinger-Ellison Syndrome Bibliography 336 Inflammatory Bowel Disease 336 Inflammatory Bowel Disease 336.1 Chronic Ulcerative Colitis Clinical Manifestations Differential Diagnosis Diagnosis Treatment Medical Surgical Support Prognosis Bibliography 336.2 Crohn Disease (Regional Enteritis, Regional Ileitis, Granulomatous Colitis) Clinical Manifestations Differential Diagnosis Diagnosis Treatment Medical 5-Aminosalicylates Antibiotics/Probiotics Corticosteroids Immunomodulators Biologic Therapy Enteral Nutritional Therapy Surgery Support Prognosis Bibliography 337 Eosinophilic Gastroenteritis 337 Eosinophilic Gastroenteritis Bibliography 338 Disorders of Malabsorption 338 Disorders of Malabsorption Clinical Approach 338.1 Evaluation of Children with Suspected Intestinal Malabsorption Investigations for Carbohydrate Malabsorption Investigations for Fat Malabsorption Investigations for Protein-Losing Enteropathy Investigations for Exocrine Pancreatic Function (Fig. 338-2) Investigations for Intestinal Mucosal Disorders Imaging Procedures 338.2 Celiac Disease (Gluten-Sensitive Enteropathy) Etiology and Epidemiology Genetics and Pathogenesis Clinical Presentation and Associated Disorders Diagnosis Treatment Nonceliac Gluten Sensitivity Bibliography 338.3 Other Malabsorptive Syndromes Congenital Intestinal Mucosal Defects Microvillus Inclusion Disease (Congenital Microvillus Atrophy) Tufting Enteropathy (Congenital Tufting Enteropathy) Enteric Anendocrinosis Proprotein Convertase 1/3 Deficiency Carbohydrate-Deficient Glycoprotein Syndrome and Enterocyte Heparan Sulfate Deficiency Syndromic Diarrhea Autoimmune Enteropathy Bile Acid Malabsorption Intestinal Lymphangiectasia Abetalipoproteinemia Homozygous Hypobetalipoproteinemia Chylomicron Retention Disease (Anderson Disease) Wolman Disease DGAT1 Mutation Bibliography 338.4 Intestinal Infections and Infestations Associated with Malabsorption Postinfectious Diarrhea Bacterial Overgrowth Tropical Sprue Whipple Disease Bibliography 338.5 Immunodeficiency Disorders Bibliography 338.6 Immunoproliferative Small Intestinal Disease Bibliography 338.7 Short Bowel Syndrome Treatment Complications Bibliography 338.8 Chronic Malnutrition Bibliography 338.9 Enzyme Deficiencies Carbohydrate Malabsorption Lactase Deficiency Fructose Malabsorption Sucrase–Isomaltase Deficiency Glucose–Galactose Malabsorption Exocrine Pancreatic Insufficiency Enterokinase (Enteropeptidase) Deficiency Trypsinogen Deficiency 338.10 Liver and Biliary Disorders Causing Malabsorption 338.11 Rare Inborn Defects Causing Malabsorption Disorders of Carbohydrate Absorption Disorders of Amino Acid and Peptide Absorption Disorders of Fat Transport Disorders of Vitamin Absorption Disorders of Electrolyte and Mineral Absorption Bibliography 338.12 Malabsorption in Eosinophilic Gastroenteritis Bibliography 338.13 Malabsorption in Inflammatory Bowel Disease Bibliography 339 Intestinal Transplantation in Children with Intestinal Failure 339 Intestinal Transplantation in Children with Intestinal Failure Indications for Intestinal Transplant Paucity of Venous Access Life-Threatening Infections Liver Disease Transplantation Operation Donor Selection Types of Intestinal Grafts The Recipient Operation Postoperative Management Immunosuppression Allograft Assessment Rejection and Graft-Versus-Host Disease Infections Outcomes Bibliography 340 Acute Gastroenteritis in Children 340 Acute Gastroenteritis in Children Epidemiology of Childhood Diarrhea Etiology of Diarrhea Pathogenesis of Infectious Diarrhea Risk Factors for Gastroenteritis Clinical Manifestation of Diarrhea Complications Diagnosis Clinical Evaluation of Diarrhea Stool Examination Treatment Oral Rehydration Therapy Enteral Feeding and Diet Selection Zinc Supplementation Additional Therapies Antibiotic Therapy Prevention Promotion of Exclusive Breastfeeding Improved Complementary Feeding Practices Rotavirus Immunization Improved Water and Sanitary Facilities and Promotion of Personal and Domestic Hygiene Improved Case Management of Diarrhea Bibliography 340.1 Traveler’s Diarrhea Treatment Prevention Bibliography 341 Chronic Diarrhea 341 Chronic Diarrhea Definition and Epidemiology Pathophysiology Etiology Genetic and Molecular Basis of the Protracted Diarrhea Syndrome Evaluation of Patients Investigations Treatment Bibliography 341.1 Diarrhea from Neuroendocrine Tumors 342 Functional Abdominal Pain (Nonorganic Chronic Abdominal Pain) 342 Functional Abdominal Pain (Nonorganic Chronic Abdominal Pain) Pathophysiology Evaluation and Diagnosis Treatment Irritable Bowel Syndrome Bibliography 343 Acute Appendicitis 343 Acute Appendicitis Pathology Clinical Features Physical Examination Diagnostic Studies Laboratory Findings Radiologic Studies Plain Radiographs Ultrasound CT Scan MRI/White Blood Cell Scan Differential Diagnosis Diagnostic Approach Treatment Antibiotics Interval Appendectomy Surgical Technique Complications Incidental Appendicoliths Bibliography 344 Surgical Conditions of the Anus and Rectum 344 Surgical Conditions of the Anus and Rectum 344.1 Anorectal Malformations Embryology Associated Anomalies Manifestations and Diagnosis Low Lesions High Lesions Persistent Cloaca Rectal Atresia Approach to the Patient Operative Repair Outcome 344.2 Anal Fissure Clinical Manifestations Treatment 344.3 Perianal Abscess and Fistula Clinical Manifestations Treatment 344.4 Hemorrhoids Clinical Manifestations Treatment 344.5 Rectal Mucosal Prolapse Clinical Manifestations Treatment 344.6 Pilonidal Sinus and Abscess Bibliography 345 Tumors of the Digestive Tract 345 Tumors of the Digestive Tract Hamartomatous Tumors Juvenile Polyposis Syndrome Peutz-Jeghers Syndrome PTEN Hamartoma Tumor Syndromes Adenomatous Tumors Adenomatous Polyposis Coli-Associated Polyposis Syndromes Carcinoma Other Gastrointestinal Tumors Lymphoma Nodular Lymphoid Hyperplasia Carcinoid Tumor Leiomyoma Gastrointestinal Stromal Cell Tumors Vascular Tumors Bibliography 346 Inguinal Hernias 346 Inguinal Hernias Embryology and Pathogenesis Genetics Pathology Incidence Clinical Presentation Evaluation of Acute Inguinal–Scrotal Swelling Incarcerated Hernia Ambiguous Genitalia Management Operative Management Laparoscopic Inguinal Hernia Repair Contralateral Inguinal Exploration Direct Inguinal Hernia Femoral Hernia Complications Wound Infection Recurrent Hernia Iatrogenic Cryptorchidism Incarceration Injury to the Vas Deferens and Male Fertility Bibliography 347 Embryology, Anatomy, and Physiology 347 Embryology, Anatomy, and Physiology 347.1 Anatomic Abnormalities Bibliography 347.2 Physiology Bibliography Bibliography 348 Pancreatic Function Tests 348 Pancreatic Function Tests Indirect Testing Direct Testing Bibliography 349 Disorders of the Exocrine Pancreas 349 Disorders of the Exocrine Pancreas Disorders Associated with Pancreatic Insufficiency Cystic Fibrosis Shwachman-Diamond Syndrome Pearson Syndrome Johanson-Blizzard Syndrome Isolated Enzyme Deficiencies Other Syndromes Associated with Pancreatic Insufficiency Bibliography 350 Treatment of Pancreatic Insufficiency 350 Treatment of Pancreatic Insufficiency Bibliography 351 Pancreatitis 351 Pancreatitis 351.1 Acute Pancreatitis Clinical Manifestations Mild Acute Pancreatitis Severe Acute Pancreatitis Diagnosis Treatment Prognosis Bibliography 351.2 Chronic Pancreatitis Bibliography 352 Pseudocyst of the Pancreas 352 Pseudocyst of the Pancreas Bibliography 353 Pancreatic Tumors 353 Pancreatic Tumors Bibliography 354 Morphogenesis of the Liver and Biliary System 354 Morphogenesis of the Liver and Biliary System Hepatic Ultrastructure Metabolic Functions of the Liver Carbohydrate Metabolism Protein Metabolism Lipid Metabolism Biotransformation Hepatic Excretory Function Bibliography 355 Manifestations of Liver Disease 355 Manifestations of Liver Disease Pathologic Manifestations Clinical Manifestations Hepatomegaly Jaundice (Icterus) Pruritus Spider Angiomas Palmar Erythema Xanthomas Portal Hypertension Ascites Gastrointestinal Bleeding Encephalopathy Endocrine Abnormalities Renal Dysfunction Pulmonary Involvement Recurrent Cholangitis Miscellaneous Manifestations of Liver Dysfunction Bibliography 355.1 Evaluation of Patients with Possible Liver Dysfunction Biochemical Tests Liver Biopsy Hepatic Imaging Procedures Diagnostic Approach to Infants with Jaundice Bibliography 356 Cholestasis 356 Cholestasis 356.1 Neonatal Cholestasis Mechanisms Evaluation Intrahepatic Cholestasis Neonatal Hepatitis Disorders of Transport, Secretion, Conjugation, and Biosynthesis of Bile Acids Bile Acid–Coenzyme a Ligase Deficiency Disorders of Embryogenesis Biliary Atresia Differentiation of Idiopathic Neonatal Hepatitis from Biliary Atresia Management of Patients with Suspected Biliary Atresia Management of Chronic Cholestasis Prognosis Bibliography 356.2 Cholestasis in the Older Child 357 Metabolic Diseases of the Liver 357 Metabolic Diseases of the Liver 357.1 Inherited Deficient Conjugation of Bilirubin (Familial Nonhemolytic Unconjugated Hyperbilirubinemia) Crigler-Najjar Syndrome Type I (Glucuronyl Transferase Deficiency) Clinical Manifestations Diagnosis Treatment Crigler-Najjar Syndrome Type II (Partial Glucuronyl Transferase Deficiency) Clinical Manifestations Diagnosis Treatment Inherited Conjugated Hyperbilirubinemia Dubin-Johnson Syndrome Rotor Syndrome Bibliography 357.2 Wilson Disease Pathogenesis Clinical Manifestations Pathology Diagnosis Treatment Prognosis Bibliography 357.3 Indian Childhood Cirrhosis Bibliography 357.4 Neonatal Iron Storage Disease Bibliography 357.5 Miscellaneous Metabolic Diseases of the Liver α1-Antitrypsin Deficiency Citrin Deficiency Bibliography 358 Viral Hepatitis 358 Viral Hepatitis Issues Common to All Forms of Viral Hepatitis Differential Diagnosis Pathogenesis Common Biochemical Profiles in the Acute Infectious Phase Hepatitis A Etiology Epidemiology Clinical Manifestations Diagnosis Complications Treatment Prevention Immunoglobulin Vaccine Prognosis Hepatitis B Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Complications Treatment Treatment Strategies Prevention Hepatitis B Immunoglobulin Universal Vaccination Postexposure Prophylaxis Special Populations Prognosis Hepatitis C Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Complications Treatment Newer Treatments Prevention Prognosis Hepatitis D Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Complications Treatment Prevention Hepatitis E Etiology Epidemiology Pathogenesis Clinical Manifestations Complications Diagnosis Prevention Approach to Acute or Chronic Hepatitis Bibliography Hepatitis A Hepatitis B Hepatitis C Hepatitis E 359 Liver Abscess 359 Liver Abscess Bibliography 360 Liver Disease Associated with Systemic Disorders 360 Liver Disease Associated with Systemic Disorders Inflammatory Bowel Disease Bacterial Sepsis Celiac Disease Cardiac Disease Cholestasis Associated with Total Parenteral Nutrition Cystic Fibrosis Bone Marrow Transplantation Hemoglobinopathies Histiocytic Disorders Bibliography 360.1 Nonalcoholic Fatty Liver Disease Bibliography 361 Mitochondrial Hepatopathies 361 Mitochondrial Hepatopathies Epidemiology Clinical Manifestations Primary Mitochondrial Hepatopathies Neonatal Liver Failure Alpers Syndrome (Alpers-Huttenlocher Syndrome or Alpers Hepatopathic Poliodystrophy) Mitochondrial DNA Depletion Syndrome Navajo Neurohepatopathy Pearson Syndrome Villous Atrophy Syndrome GRACILE Syndrome Mutations in Nuclear Translation and Elongation Factor Genes Secondary Mitochondrial Hepatopathies Treatment of Mitochondrial Hepatopathies Bibliography 362 Autoimmune Hepatitis 362 Autoimmune Hepatitis Etiology Pathology Clinical Manifestations Laboratory Findings Diagnosis Treatment Prognosis Bibliography 363 Drug- and Toxin-Induced Liver Injury 363 Drug- and Toxin-Induced Liver Injury Treatment Prognosis Prevention Bibliography 364 Fulminant Hepatic Failure 364 Fulminant Hepatic Failure Etiology Pathology Pathogenesis Clinical Manifestations Laboratory Findings Treatment Prognosis Bibliography 365 Cystic Diseases of the Biliary Tract and Liver 365 Cystic Diseases of the Biliary Tract and Liver Choledochal Cysts Autosomal Recessive Polycystic Kidney Disease Cystic Dilation of the Intrahepatic Bile Ducts (Caroli Disease) Congenital Hepatic Fibrosis Autosomal Dominant Polycystic Kidney Disease Autosomal Dominant Polycystic Liver Disease Bibliography Choledochal Cysts Caroli Disease Congenital Hepatic Fibrosis Polycystic Diseases of the Liver and Kidney 366 Diseases of the Gallbladder 366 Diseases of the Gallbladder Anomalies Acute Hydrops Cholecystitis and Cholelithiasis Biliary Dyskinesia Bibliography 367 Portal Hypertension and Varices 367 Portal Hypertension and Varices Etiology Pathophysiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 368 Liver Transplantation 368 Liver Transplantation Indications Technical Innovations Immunosuppression Complications Outcomes Bibliography 369 Malformations 369 Malformations Bibliography 370 Ascites 370 Ascites 370.1 Chylous Ascites Bibliography Bibliography 371 Peritonitis 371 Peritonitis 371.1 Acute Primary Peritonitis Etiology and Epidemiology Clinical Manifestations Diagnosis and Treatment Bibliography 371.2 Acute Secondary Peritonitis Clinical Manifestations Treatment Bibliography 371.3 Acute Secondary Localized Peritonitis (Peritoneal Abscess) Etiology Clinical Manifestations Treatment Bibliography Bibliography 372 Epigastric Hernia 372 Epigastric Hernia Clinical Presentation Bibliography 372.1 Incisional Hernia Bibliography Respiratory System 373 Respiratory Pathophysiology and Regulation 373 Respiratory Pathophysiology and Regulation 373.1 Lung Volumes and Capacities in Health and Disease Bibliography 373.2 Chest Wall Bibliography 373.3 Pulmonary Mechanics and Work of Breathing in Health and Disease Bibliography 373.4 Airway Dynamics in Health and Disease Bibliography 373.5 Interpretation of Clinical Signs to Localize the Site of Pathology Bibliography 373.6 Ventilation-Perfusion Relationship in Health and Disease Bibliography 373.7 Gas Exchange in Health and Disease Bibliography 373.8 Interpretation of Blood Gases Bibliography 373.9 Pulmonary Vasculature in Health and Disease Bibliography 373.10 Immune Response of the Lung to Injury 373.11 Regulation of Respiration Central Respiratory Controller Sensors Lung Receptors Effectors Sleep States Regulation of Respiration in Special Situations Fetus, Newborns, and Young Infants Chronic Hypoxia and Hypercarbia Bibliography Bibliography 374 Diagnostic Approach to Respiratory Disease 374 Diagnostic Approach to Respiratory Disease History Physical Examination Blood Gas Analysis Transillumination of the Chest Radiographic Techniques Chest X-Rays Upper Airway Film Sinus and Nasal Films Chest Computed Tomography and Magnetic Resonance Imaging Fluoroscopy Barium Swallow Pulmonary Arteriography and Aortograms Radionuclide Lung Scans Pulmonary Function Testing Microbiology: Examination of Lung Secretions Exercise Testing Sleep Studies Airway Visualization and Lung Specimen–Based Diagnostic Tests Laryngoscopy Bronchoscopy and Bronchoalveolar Lavage Thoracoscopy Thoracentesis Lung Tap Lung Biopsy Sweat Testing Bibliography 375 Sudden Infant Death Syndrome 375 Sudden Infant Death Syndrome Epidemiology Pathology Environmental Risk Factors Nonmodifiable Environmental Risk Factors Modifiable Environmental Risk Factors Pregnancy-Related Factors Cigarette Smoking Drug and Alcohol Use Infant Sleep Environment Infant Feeding Care Practices and Exposures Genetic Risk Factors Gene-and-Environment Interactions Infant Groups at Increased Risk for Sudden Infant Death Syndrome Unexplained Apparent Life-Threatening Events Subsequent Siblings of a Sudden Infant Death Syndrome Victim Prematurity Physiologic Studies Clinical Strategies Home Monitoring Reducing the Risk of Sudden Infant Death Syndrome Bibliography 376 Congenital Disorders of the Nose 376 Congenital Disorders of the Nose Normal Newborn Nose Physiology Congenital Disorders Choanal Atresia Clinical Manifestations Diagnosis Treatment Congenital Defects of the Nasal Septum Pyriform Aperture Stenosis Congenital Midline Nasal Masses Diagnosis and Treatment Bibliography 377 Acquired Disorders of the Nose 377 Acquired Disorders of the Nose 377.1 Foreign Body Etiology Diagnosis Treatment Complications Prevention Bibliography 377.2 Epistaxis Anatomy Etiology Clinical Manifestations Treatment Prevention Bibliography 378 Nasal Polyps 378 Nasal Polyps Etiology Clinical Manifestations Diagnosis and Differential Diagnosis Treatment Bibliography 379 The Common Cold 379 The Common Cold Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Laboratory Findings Treatment Antiviral Treatment Supportive Care and Symptomatic Treatment Fever Nasal Obstruction Rhinorrhea Sore Throat Cough Ineffective Treatments Complications Prevention Bibliography 380 Sinusitis 380 Sinusitis Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Complications Prevention Bibliography 381 Acute Pharyngitis 381 Acute Pharyngitis Infectious Etiologies Viruses Bacteria Other Than Group A Streptococcus Group A Streptococcus Diagnosis Treatment Chronic Group a Streptococcus Carriers Recurrent Pharyngitis Complications and Prognosis Prevention Bibliography 382 Retropharyngeal Abscess, Lateral Pharyngeal (Parapharyngeal) Abscess, and Peritonsillar Cellulitis/Abscess 382 Retropharyngeal Abscess, Lateral Pharyngeal (Parapharyngeal) Abscess, and Peritonsillar Cellulitis/Abscess Retropharyngeal and Lateral Pharyngeal Abscess Peritonsillar Cellulitis and/or Abscess Bibliography 383 Tonsils and Adenoids 383 Tonsils and Adenoids Anatomy Normal Function Pathology Acute Infection Chronic Infection Airway Obstruction Tonsillar Neoplasm Clinical Manifestations Acute Infection Chronic Infection Airway Obstruction Tonsillar Neoplasm Treatment Medical Management Tonsillectomy Adenoidectomy Tonsillectomy and Adenoidectomy Complications Poststreptococcal Glomerulonephritis and Acute Rheumatic Fever Peritonsillar Infection Retropharyngeal Space Infection Parapharyngeal Space Infection Recurrent or Chronic Pharyngotonsillitis Chronic Airway Obstruction Tonsillectomy and Adenoidectomy Bibliography 384 Chronic or Recurrent Respiratory Symptoms 384 Chronic or Recurrent Respiratory Symptoms Judging the Seriousness of Chronic Respiratory Complaints Recurrent or Persistent Cough Frequently Recurring or Persistent Stridor Recurrent or Persistent Wheeze Recurrent and Persistent Lung Infiltrates Bibliography 385 Acute Inflammatory Upper Airway Obstruction (Croup, Epiglottitis, Laryngitis, and Bacterial Tracheitis) 385 Acute Inflammatory Upper Airway Obstruction (Croup, Epiglottitis, Laryngitis, and Bacterial Tracheitis) 385.1 Infectious Upper Airway Obstruction Etiology and Epidemiology Clinical Manifestations Croup (Laryngotracheobronchitis) Acute Epiglottitis (Supraglottitis) Acute Infectious Laryngitis Spasmodic Croup Differential Diagnosis Complications Treatment Endotracheal/Nasotracheal Intubation and Tracheotomy Prognosis Bibliography Laryngotracheobronchitis Epiglottitis 385.2 Bacterial Tracheitis Clinical Manifestations Diagnosis Treatment Complications Prognosis Bibliography 386 Congenital Anomalies of the Larynx, Trachea, and Bronchi 386 Congenital Anomalies of the Larynx, Trachea, and Bronchi 386.1 Laryngomalacia Clinical Manifestations Diagnosis Treatment Bibliography 386.2 Congenital Subglottic Stenosis Clinical Manifestations Diagnosis Bibliography 386.3 Vocal Cord Paralysis Clinical Manifestations Diagnosis Treatment 386.4 Congenital Laryngeal Webs and Atresia Bibliography 386.5 Congenital Subglottic Hemangioma Bibliography 386.6 Laryngoceles and Saccular Cysts Bibliography 386.7 Posterior Laryngeal Cleft and Laryngotracheoesophageal Cleft Bibliography 386.8 Vascular and Cardiac Anomalies Bibliography 386.9 Tracheal Stenoses, Webs, and Atresia Bibliography 386.10 Foregut Cysts Bibliography 386.11 Tracheomalacia and Bronchomalacia Bibliography 387 Foreign Bodies in the Airway 387 Foreign Bodies in the Airway Epidemiology and Etiology Clinical Manifestations Diagnosis Treatment 387.1 Laryngeal Foreign Bodies 387.2 Tracheal Foreign Bodies 387.3 Bronchial Foreign Bodies Bibliography 388 Laryngotracheal Stenosis and Subglottic Stenosis 388 Laryngotracheal Stenosis and Subglottic Stenosis 388.1 Congenital Subglottic Stenosis 388.2 Acquired Laryngotracheal Stenosis Clinical Manifestations Diagnosis Treatment Bibliography 389 Bronchomalacia and Tracheomalacia 389 Bronchomalacia and Tracheomalacia Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 390 Neoplasms of the Larynx, Trachea, and Bronchi 390 Neoplasms of the Larynx, Trachea, and Bronchi 390.1 Vocal Nodules 390.2 Recurrent Respiratory Papillomatosis Clinical Manifestations Treatment Bibliography 390.3 Congenital Subglottic Hemangioma Clinical Manifestations Treatment Bibliography 390.4 Vascular Anomalies Bibliography 390.5 Other Laryngeal Neoplasms 390.6 Tracheal Neoplasms 390.7 Bronchial Tumors 391 Wheezing, Bronchiolitis, and Bronchitis 391 Wheezing, Bronchiolitis, and Bronchitis 391.1 Wheezing in Infants: Bronchiolitis Definitions and General Pathophysiology Etiology Acute Bronchiolitis and Inflammation of the Airway Other Causes Clinical Manifestations History and Physical Examination Diagnostic Evaluation Treatment Prognosis Prevention Bibliography 391.2 Bronchitis Acute Bronchitis Clinical Manifestations Differential Diagnosis Treatment Chronic Bronchitis Cigarette Smoking and Air Pollution Bibliography 391.3 Plastic Bronchitis Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Complications and Prognosis Bibliography 392 Emphysema and Overinflation 392 Emphysema and Overinflation Localized Obstructive Overinflation Unilateral Hyperlucent Lung Swyer-James or Macleod Syndrome Congenital Lobar Emphysema Pulmonary Vascular Abnormalities Generalized Obstructive Overinflation Pathology Clinical Manifestations Diagnosis Bullous Emphysema Subcutaneous Emphysema Bibliography 393 α1-Antitrypsin Deficiency and Emphysema 393 α1-Antitrypsin Deficiency and Emphysema Pathogenesis Clinical Manifestations Laboratory Findings Treatment Supportive Therapy Bibliography 394 Other Distal Airway Diseases 394 Other Distal Airway Diseases 394.1 Bronchiolitis Obliterans Epidemiology Pathogenesis Clinical Manifestations and Diagnosis Treatment Prognosis Bibliography 394.2 Follicular Bronchitis Bibliography 394.3 Pulmonary Alveolar Microlithiasis Epidemiology and Etiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 395 Congenital Disorders of the Lung 395 Congenital Disorders of the Lung 395.1 Pulmonary Agenesis and Aplasia Etiology and Pathology Clinical Manifestations and Prognosis Diagnosis and Treatment Bibliography 395.2 Pulmonary Hypoplasia Etiology and Pathology Clinical Manifestations Diagnosis and Treatment Bibliography 395.3 Congenital Cystic Malformation Pathology Etiology Diagnosis Clinical Manifestations Treatment Bibliography 395.4 Pulmonary Sequestration Pathophysiology Clinical Manifestations and Diagnosis Treatment Bibliography 395.5 Bronchogenic Cysts Etiology and Pathology Clinical Manifestations and Treatment Bibliography 395.6 Congenital Pulmonary Lymphangiectasia Etiology and Pathology Clinical Manifestations and Treatment Bibliography 395.7 Lung Hernia Etiology and Pathology Clinical Manifestations and Treatment Bibliography 395.8 Other Congenital Malformations of the Lung Congenital Lobar Emphysema and Pulmonary Cysts Pulmonary Arteriovenous Malformation Bronchobiliary Fistula Bibliography 396 Pulmonary Edema 396 Pulmonary Edema Pathophysiology Etiology Clinical Manifestations Treatment Bibliography 397 Aspiration Syndromes 397 Aspiration Syndromes Gastric Contents Treatment Prevention Hydrocarbon Aspiration Treatment Bibliography 398 Chronic Recurrent Aspiration 398 Chronic Recurrent Aspiration Etiology Diagnosis Treatment Bibliography 399 Immune and Inflammatory Lung Disease 399 Immune and Inflammatory Lung Disease 399.1 Hypersensitivity Pneumonia Etiology Classification and Pathogenesis Clinical Manifestations Laboratory Lung Biopsy Radiology Antigen Challenge By Inhalation Treatment Bibliography 399.2 Occupational and Environmental Lung Disease Classification and Pathogenesis Occupational and Environmental Asthma Reactive Airways Disease Syndrome and Irritant-Induced Asthma Treatment Bibliography 399.3 Granulomatous Lung Disease Granulomatosis with Polyangiitis Etiology and Epidemiology Pathogenesis Clinical Manifestations Laboratory and Pathology Radiology Treatment Sarcoidosis Epidemiology and Pathogenesis Clinical Manifestations Diagnostic Laboratory Testing Histopathology Radiology Treatment Berylliosis Pathogenesis Clinical Manifestations Laboratory Testing Radiography Treatment Granulomatous Lung Disease in Primary Immune Deficiency Pathogenesis Clinical Manifestations of Granulomatous Lung Disease in Primary Immune Deficiency Radiography Laboratory and Pulmonary Function Testing Therapy Bibliography 399.4 Eosinophilic Lung Disease Etiology Pathology and Pathogenesis Clinical Manifestations Chest Imaging Löffler Syndrome Acute Eosinophilic Pneumonia Chronic Eosinophilic Pneumonia Eosinophilic Granulomatosis with Polyangiitis (The Churg-Strauss Syndrome) Allergic Bronchopulmonary Aspergillosis Radiography Treatment Hypereosinophilic Syndrome Bibliography 399.5 Interstitial Lung Disease Classification and Pathology Clinical Manifestations Diagnosis Radiography Pulmonary Function Tests Bronchoalveolar Lavage Treatment Genetic Counseling Prognosis Goodpasture Disease Pathophysiology Immunology Factors Genetic Factors Environmental Factors Clinical Manifestations Laboratory Chest Radiography Pulmonary Function Testing Bronchoscopy and Bronchoalveolar Lavage Lung Biopsy Treatment Bibliography 400 Community-Acquired Pneumonia 400 Community-Acquired Pneumonia Epidemiology Etiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Complications Prevention Bibliography 401 Bronchiectasis 401 Bronchiectasis Pathophysiology and Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 402 Pulmonary Abscess 402 Pulmonary Abscess Pathology and Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 403 Cystic Fibrosis 403 Cystic Fibrosis Genetics Pathogenesis Pathology Clinical Manifestations Respiratory Tract Intestinal Tract Biliary Tract Cystic Fibrosis–Related Diabetes and Pancreatitis Genitourinary Tract Sweat Glands Diagnosis and Assessment Sweat Testing DNA Testing Other Diagnostic Tests Pancreatic Function Radiology Pulmonary Function Microbiologic Studies Heterozygote Detection and Prenatal Diagnosis Newborn Screening Treatment General Approach to Care Pulmonary Therapy Inhalation Therapy Airway Clearance Therapy Antibiotic Therapy Oral Antibiotic Therapy Aerosolized Antibiotic Therapy Intravenous Antibiotic Therapy Bronchodilator Therapy Antiinflammatory Agents Endoscopy and Lavage Other Therapies Emerging Therapies Treatment of Pulmonary Complications Atelectasis Hemoptysis Pneumothorax Allergic Bronchopulmonary Aspergillosis Nontuberculous Mycobacteria Infection Bone and Joint Complications Sleep-Disordered Breathing Acute Respiratory Failure Chronic Respiratory Failure Heart Failure Nutritional Therapy Diet Pancreatic Enzyme Replacement Vitamin and Mineral Supplements Treatment of Intestinal Complications Meconium Ileus Distal Intestinal Obstruction Syndrome (Meconium Ileus Equivalent) and Other Causes of Abdominal Symptoms Gastroesophageal Reflux Rectal Prolapse Hepatobiliary Disease Pancreatitis Hyperglycemia Other Therapy Nasal Polyps Rhinosinusitis Salt Depletion Growth and Maturation Surgery Prognosis Bibliography 404 Primary Ciliary Dyskinesia (Immotile Cilia Syndrome, Kartagener Syndrome) 404 Primary Ciliary Dyskinesia (Immotile Cilia Syndrome, Kartagener Syndrome) Normal Ciliary Ultrastructure and Function Genetics of Primary Ciliary Dyskinesia Clinical Manifestations of Primary Ciliary Dyskinesia Diagnosis of Primary Ciliary Dyskinesia Treatment Prognosis Bibliography 405 Diffuse Lung Diseases in Childhood 405 Diffuse Lung Diseases in Childhood 405.1 Inherited Disorders of Surfactant Metabolism Pathology Deficiency of Surfactant Protein B (Surfactant Metabolism Dysfunction, Pulmonary, 1; SMDP1; OMIM #265120) Clinical Manifestations Genetics Diagnosis Surfactant Protein C Gene Abnormalities (Surfactant Metabolism Dysfunction, Pulmonary, 2; SMDP2; OMIM #610913) Clinical Manifestations Genetics Diagnosis Disease Caused by Mutations in ABCA3 (Surfactant Metabolism Dysfunction, Pulmonary, 3; SMDP3; OMIM #610921) Clinical Manifestations Genetics Diagnosis Disease Caused by Mutations in NKX2-1 (Thyroid Transcription Factor 1, Choreoathetosis, Hypothyroidism, and Neonatal Respiratory Distress, OMIM #600635) Clinical Manifestations Genetics Diagnosis Treatment of Surfactant Dysfunction Disorders Bibliography 405.2 Pulmonary Alveolar Proteinosis Etiology and Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 406 Pulmonary Hemosiderosis 406 Pulmonary Hemosiderosis Etiology Epidemiology Pathology Pathophysiology Diffuse Alveolar Hemorrhage Associated with Pulmonary Capillaritis Diffuse Alveolar Hemorrhage Not Associated with Pulmonary Capillaritis Clinical Manifestations Laboratory Findings and Diagnosis Treatment Prognosis Bibliography 407 Pulmonary Embolism, Infarction, and Hemorrhage 407 Pulmonary Embolism, Infarction, and Hemorrhage 407.1 Pulmonary Embolus and Infarction Etiology Epidemiology Pathophysiology Clinical Manifestations Laboratory Findings and Diagnosis Treatment Prognosis Bibliography 407.2 Pulmonary Hemorrhage and Hemoptysis Etiology Epidemiology Pathophysiology Clinical Manifestations Laboratory Findings and Diagnosis Treatment Bibliography 408 Atelectasis 408 Atelectasis Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 409 Pulmonary Tumors 409 Pulmonary Tumors Etiology Clinical Manifestations and Evaluation Bibliography 410 Pleurisy, Pleural Effusions, and Empyem 410 Pleurisy, Pleural Effusions, and Empyema 410.1 Dry or Plastic Pleurisy (Pleural Effusion) Etiology Pathology and Pathogenesis Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Bibliography 410.2 Serofibrinous or Serosanguineous Pleurisy (Pleural Effusion) Etiology Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Bibliography 410.3 Purulent Pleurisy or Empyema Etiology Epidemiology Pathology Clinical Manifestations Laboratory Findings Complications Treatment Bibliography 411 Pneumothorax 411 Pneumothorax Etiology and Epidemiology Pathogenesis Clinical Manifestations Diagnosis and Differential Diagnosis Treatment Bibliography 412 Pneumomediastinum 412 Pneumomediastinum Etiology Pathogenesis Clinical Manifestations Laboratory Findings Complications Treatment Bibliography 413 Hydrothorax 413 Hydrothorax Etiology Clinical Manifestations Laboratory Findings Treatment Bibliography 414 Hemothorax 414 Hemothorax Etiology Clinical Manifestations Diagnosis Treatment Bibliography 415 Chylothorax 415 Chylothorax Etiology Clinical Manifestations Laboratory Findings Complications Treatment Bibliography 416 Bronchopulmonary Dysplasia 416 Bronchopulmonary Dysplasia Clinical Manifestations Treatment Bibliography 417 Skeletal Diseases Influencing Pulmonary Function 417 Skeletal Diseases Influencing Pulmonary Function 417.1 Pectus Excavatum (Funnel Chest) Etiology Epidemiology Clinical Manifestations Laboratory Findings Treatment Bibliography 417.2 Pectus Carinatum and Sternal Clefts Pectus Carinatum Etiology and Epidemiology Clinical Manifestations Treatment Sternal Clefts Bibliography 417.3 Asphyxiating Thoracic Dystrophy (Thoracic-Pelvic-Phalangeal Dystrophy) Etiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 417.4 Achondroplasia Etiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 417.5 Kyphoscoliosis: Adolescent Idiopathic Scoliosis and Congenital Scoliosis Etiology Clinical Manifestations Diagnosis Treatment Bibliography 417.6 Congenital Rib Anomalies Clinical Manifestations Diagnosis Treatment Bibliography 418 Chronic Severe Respiratory Insufficiency 418 Chronic Severe Respiratory Insufficiency 418.1 Neuromuscular Diseases Pathogenesis Treatment Bibliography 418.2 Congenital Central Hypoventilation Syndrome Genetics Ventilator Dependence Hirschsprung Disease Tumors of Neural Crest Origin Cardiac Asystole Autonomic Nervous System Dysregulation Facial Phenotype Neuropathology Clinical Manifestations Differential Diagnosis Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Management Supported Ventilation—Diaphragm Pacing Monitoring in the Home Bibliography 418.3 Other Conditions Myelomeningocele with Arnold-Chiari Type II Malformation Management Rapid-Onset Obesity, Hypothalamic Dysfunction, and Autonomic Dysregulation Obesity Hypoventilation Syndrome Management Acquired Alveolar Hypoventilation Obstructive Sleep Apnea Epidemiology Pathophysiology Clinical Presentation Treatment Spinal Cord Injury Epidemiology Pathophysiology Management Metabolic Disease Mucopolysaccharidoses Dysplasias Glycogenosis Type Ii Severe Tracheomalacia and/or Bronchomalacia (Airway Malacia) Neuropathy of Severe Illness Hematologic Stem-Cell Transplantation Mitochondrial Diseases Bibliography 418.4 Long-Term Mechanical Ventilation Respiratory Equipment for Home Care Noninvasive Equipment Rocker Bed Cuirasse Iron Lung Diaphragmatic Pacing Positive-Pressure Ventilators Airway Clearance Physical Therapy, Occupational Therapy, and Speech Therapy Infections Monitoring Weaning Off Ventilator Support Discharge Process Outpatient Follow Up Transition of Care Bibliography 419 Extrapulmonary Diseases with Pulmonary Manifestations 419 Extrapulmonary Diseases with Pulmonary Manifestations Evaluation Bibliography The Cardiovascular System 490 Lymphadenopathy Diagnosis Treatment Bibliography 490.1 Kikuchi-Fujimoto Disease (Histiocytic Necrotizing Lymphadenitis) Bibliography 490.2 Sinus Histiocytosis with Massive Lymphadenopathy (Rosai-Dorfman Disease) Bibliography 490.3 Castleman Disease Bibliography 446 Development of the Hematopoietic System Hematopoiesis in the Human Embryo and Fetus Fetal Granulocytopoiesis Fetal Thrombopoiesis Fetal Erythropoiesis Hemoglobins in the Fetus and Neonate Embryonic Hemoglobins Fetal Hemoglobin Adult Hemoglobins Normal Relationships Among the Hemoglobins Alterations of the Hemoglobins by Disease Red Cell Life Span of the Fetus and Neonate Bibliography 420 Cardiac Development 420 Cardiac Development 420.1 Early Cardiac Morphogenesis 420.2 Cardiac Looping 420.3 Cardiac Septation 420.4 Aortic Arch Development 420.5 Cardiac Differentiation 420.6 Developmental Changes in Cardiac Function Bibliography 421 The Fetal to Neonatal Circulatory Transition 421 The Fetal to Neonatal Circulatory Transition 421.1 The Fetal Circulation 421.2 The Transitional Circulation 421.3 The Neonatal Circulation Bibliography 421.4 Persistent Pulmonary Hypertension of the Neonate (Persistence of Fetal Circulatory Pathways) 422 History and Physical Examination 422 History and Physical Examination History General Physical Examination Cardiac Examination Bibliography 423 Laboratory Evaluation 423 Laboratory Evaluation 423.1 Radiologic Assessment 423.2 Electrocardiography Developmental Changes Rate and Rhythm P Waves QRS Complex Right Ventricular Hypertrophy Left Ventricular Hypertrophy Bundle Branch Block P-R and Q-T Intervals ST Segment and T-Wave Abnormalities Bibliography 423.3 Hematologic Data 423.4 Echocardiography M-Mode Echocardiography Two-Dimensional Echocardiography Doppler Echocardiography Three-Dimensional Echocardiography Transesophageal Echocardiography Fetal Echocardiography Bibliography 423.5 Exercise Testing Bibliography 423.6 MRI, MRA, CT, and Radionuclide Studies Bibliography 423.7 Diagnostic and Interventional Cardiac Catheterization Diagnostic Cardiac Catheterization Thermodilution Measurement of Cardiac Output Angiocardiography Interventional Cardiac Catheterization Bibliography 424 Epidemiology and Genetic Basis of Congenital Heart Disease 424 Epidemiology and Genetic Basis of Congenital Heart Disease Prevalence Etiology Genetic Counseling Bibliography 425 Evaluation and Screening of the Infant or Child with Congenital Heart Disease 425 Evaluation and Screening of the Infant or Child with Congenital Heart Disease Acyanotic Congenital Heart Lesions Lesions Resulting in Increased Volume Load Lesions Resulting in Increased Pressure Load Cyanotic Congenital Heart Lesions Cyanotic Lesions with Decreased Pulmonary Blood Flow Cyanotic Lesions with Increased Pulmonary Blood Flow Bibliography 426 Acyanotic Congenital Heart Disease: 426 Acyanotic Congenital Heart Disease: 426.1 Atrial Septal Defect Bibliography 426.2 Ostium Secundum Defect Pathophysiology Clinical Manifestations Diagnosis Complications Treatment Prognosis 426.3 Sinus Venosus Atrial Septal Defect 426.4 Partial Anomalous Pulmonary Venous Return 426.5 Atrioventricular Septal Defects (Ostium Primum and Atrioventricular Canal or Endocardial Cushion Defects) Pathophysiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 426.6 Ventricular Septal Defect Pathophysiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 426.7 Supracristal Ventricular Septal Defect with Aortic Insufficiency 426.8 Patent Ductus Arteriosus Pathophysiology Clinical Manifestations Diagnosis Prognosis and Complications Treatment Patent Ductus Arteriosus in Low Birthweight Infants Bibliography 426.9 Aortopulmonary Window Defect 426.10 Coronary Artery Fistula 426.11 Ruptured Sinus of Valsalva Aneurysm 427 Acyanotic Congenital Heart Disease: 427 Acyanotic Congenital Heart Disease: 427.1 Pulmonary Valve Stenosis with Intact Ventricular Septum Pathophysiology Clinical Manifestations and Laboratory Findings Treatment Prognosis and Complications Bibliography 427.2 Infundibular Pulmonary Stenosis and Double-Chamber Right Ventricle 427.3 Pulmonary Stenosis in Combination with an Intracardiac Shunt 427.4 Peripheral Pulmonary Stenosis 427.5 Aortic Stenosis Pathophysiology Clinical Manifestations Laboratory Findings and Diagnosis Treatment Prognosis Bibliography 427.6 Coarctation of the Aorta Pathophysiology Clinical Manifestations Diagnosis Treatment Postcoarctectomy Syndrome Prognosis Bibliography 427.7 Coarctation with Ventricular Septal Defect 427.8 Coarctation with Other Cardiac Anomalies and Interrupted Aortic Arch 427.9 Congenital Mitral Stenosis Bibliography 427.10 Pulmonary Venous Hypertension 428 Acyanotic Congenital Heart Disease: 428 Acyanotic Congenital Heart Disease: 428.1 Pulmonary Valvular Insufficiency and Congenital Absence of the Pulmonary Valve Bibliography 428.2 Congenital Mitral Insufficiency 428.3 Mitral Valve Prolapse Bibliography 428.4 Tricuspid Regurgitation Bibliography 429 Cyanotic Congenital Heart Disease: 429 Cyanotic Congenital Heart Disease: Cardiac Disease Leading to Cyanosis Differential Diagnosis 430 Cyanotic Congenital Heart Lesions: 430 Cyanotic Congenital Heart Lesions: 430.1 Tetralogy of Fallot Pathophysiology Clinical Manifestations Diagnosis Complications Associated Anomalies Treatment Prognosis Bibliography 430.2 Tetralogy of Fallot with Pulmonary Atresia Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 430.3 Pulmonary Atresia with Intact Ventricular Septum Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 430.4 Tricuspid Atresia Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 430.5 Double-Outlet Right Ventricle 430.6 Transposition of the Great Arteries with Ventricular Septal Defect and Pulmonary Stenosis 430.7 Ebstein Anomaly of the Tricuspid Valve Pathophysiology Clinical Manifestations Diagnosis Prognosis and Complications Treatment Bibliography 431 Cyanotic Congenital Heart Disease: 431 Cyanotic Congenital Heart Disease: 431.1 D-Transposition of the Great Arteries 431.2 D-Transposition of the Great Arteries with Intact Ventricular Septum Clinical Manifestations Diagnosis Treatment 431.3 Transposition of the Great Arteries with Ventricular Septal Defect 431.4 L-Transposition of the Great Arteries (Corrected Transposition) Clinical Manifestations Diagnosis Bibliography 431.5 Double-Outlet Right Ventricle Without Pulmonary Stenosis 431.6 Double-Outlet Right Ventricle with Malposition of the Great Arteries (Taussig-Bing Anomaly) 431.7 Total Anomalous Pulmonary Venous Return Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 431.8 Truncus Arteriosus Pathophysiology Clinical Manifestations Diagnosis Prognosis and Complications Treatment Bibliography 431.9 Single Ventricle (Double-Inlet Ventricle, Univentricular Heart) Pathophysiology Clinical Manifestations Diagnosis Prognosis and Complications Treatment 431.10 Hypoplastic Left-Heart Syndrome Pathophysiology Clinical Manifestations Diagnosis Prognosis and Complications Treatment Prevention Bibliography 431.11 Abnormal Positions of the Heart and the Heterotaxy Syndromes (Asplenia, Polysplenia) Bibliography 432 Other Congenital Heart and Vascular Malformations 432 Other Congenital Heart and Vascular Malformations 432.1 Anomalies of the Aortic Arch Right Aortic Arch Vascular Rings Clinical Manifestations Diagnosis Treatment Bibliography 432.2 Anomalous Origin of the Coronary Arteries Anomalous Origin of the Left Coronary Artery From the Pulmonary Artery Clinical Manifestations Diagnosis Treatment and Prognosis Anomalous Origin of the Right Coronary Artery From the Pulmonary Artery Ectopic Origin of the Coronary Artery From the Aorta with Aberrant Proximal Course Bibliography 432.3 Pulmonary Arteriovenous Fistula Bibliography 432.4 Ectopia Cordis 432.5 Diverticulum of the Left Ventricle 433 Pulmonary Hypertension 433 Pulmonary Hypertension 433.1 Primary Pulmonary Hypertension Pathophysiology Clinical Manifestations Diagnosis Prognosis and Treatment 433.2 Pulmonary Vascular Disease (Eisenmenger Syndrome) Pathophysiology Pathology and Pathophysiology Clinical Manifestations Diagnosis Treatment Bibliography 434 General Principles of Treatment of Congenital Heart Disease 434 General Principles of Treatment of Congenital Heart Disease Postoperative Management Long-Term Management Bibliography 434.1 Congenital Heart Disease in Adults Long-Term Medical Considerations Specific Lesions Left-to-Right Shunts Atrial Septal Defects Late Outcome Following Closure of Atrial Septal Defect Ventricular Septal Defects Complete Atrioventricular Canal Patent Ductus Arteriosus Cyanotic Heart Disease Tetralogy of Fallot Transposition of the Great Arteries Pulmonary Valve Stenosis Left-Sided Obstructive Lesions Coarctation of the Aorta Aortic Valve Stenosis Endocarditis Prophylaxis Pregnancy and Congenital Heart Disease Contraception Adolescent Transition Bibliography 435 Disturbances of Rate and Rhythm of the Heart 435 Disturbances of Rate and Rhythm of the Heart 435.1 Principles of Antiarrhythmic Therapy 435.2 Sinus Arrhythmias and Extrasystoles 435.3 Supraventricular Tachycardia Clinical Manifestations Treatment 435.4 Ventricular Tachyarrhythmias 435.5 Long QT Syndromes 435.6 Sinus Node Dysfunction 435.7 AV Block Bibliography 436 Sudden Death 436 Sudden Death Mechanism of Sudden Death Congenital Heart Disease Cardiomyopathy Cardiac Arrhythmia Miscellaneous Causes Evaluation and Therapy for Resuscitated Patients Medication for Attention-Deficit Disorder Prevention of Sudden Death Bibliography 437 Infective Endocarditis 437 Infective Endocarditis Etiology Epidemiology Clinical Manifestations Diagnosis Prognosis and Complications Treatment Prevention Bibliography 438 Rheumatic Heart Disease 438 Rheumatic Heart Disease Patterns of Valvular Disease Mitral Insufficiency Pathophysiology Clinical Manifestations Complications Treatment Mitral Stenosis Pathophysiology Clinical Manifestations Treatment Aortic Insufficiency Clinical Manifestations Prognosis and Treatment Tricuspid Valve Disease Pulmonary Valve Disease Bibliography 439 Diseases of the Myocardium 439 Diseases of the Myocardium 439.1 Dilated Cardiomyopathy Etiology and Epidemiology Pathogenesis Clinical Manifestations Laboratory Findings Prognosis and Management Bibliography 439.2 Hypertrophic Cardiomyopathy Etiology and Epidemiology Pathogenesis Clinical Manifestations Diagnosis Prognosis and Management Bibliography 439.3 Restrictive Cardiomyopathy Etiology and Epidemiology Pathogenesis Clinical Manifestations Diagnosis Prognosis and Management Bibliography 439.4 Left Ventricular Noncompaction, Arrhythmogenic Right Ventricular Cardiomyopathy, and Endocardial Fibroelastosis Bibliography 439.5 Myocarditis Etiology and Epidemiology Viral Infections Bacterial Infections Pathophysiology Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prognosis Bibliography Bibliography 440 Diseases of the Pericardium 440 Diseases of the Pericardium 440.1 Acute Pericarditis Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Infectious Pericarditis Noninfectious Pericarditis 440.2 Constrictive Pericarditis Bibliography 441 Tumors of the Heart 441 Tumors of the Heart Bibliography 442 Heart Failure 442 Heart Failure Pathophysiology Clinical Manifestations Diagnosis Treatment General Measures Diet Diuretics Afterload Reducers, Including Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Digitalis Glycosides α- and β-Adrenergic Agonists Phosphodiesterase Inhibitors Chronic Treatment with β-Blockers Electrophysiologic Approaches to Heart Failure Management 442.1 Cardiogenic Shock Bibliography 443 Pediatric Heart and Heart-Lung Transplantation 443 Pediatric Heart and Heart-Lung Transplantation 443.1 Pediatric Heart Transplantation Indications Recipient and Donor Selection Perioperative Management Diagnosis and Management of Acute Graft Rejection Complications of Immunosuppression Infection Growth Retardation Hypertension Renal Function Neurologic Complications Tumors Chronic Rejection Other Complications Rehabilitation Bibliography 443.2 Heart-Lung and Lung Transplantation Bibliography 444 Diseases of the Blood Vessels (Aneurysms and Fistulas) 444 Diseases of the Blood Vessels (Aneurysms and Fistulas) 444.1 Kawasaki Disease 444.2 Arteriovenous Fistulas Clinical Manifestations Treatment 444.3 Generalized Arterial Calcification of Infancy/Idiopathic Infantile Arterial Calcification 444.4 Arterial Calcifications Caused by Deficiency of CD73 Bibliography 445 Systemic Hypertension 445 Systemic Hypertension Prevalence of Hypertension in Children Definition of Hypertension Measurement of BP in Children Etiology and Pathophysiology Clinical Manifestations Diagnosis Prevention Treatment Bibliography Diseases of the Blood 447 The Anemias 447 The Anemias History and Physical Examination Laboratory Studies Differential Diagnosis Bibliography 448 Congenital Hypoplastic Anemia (Diamond-Blackfan Anemia) 448 Congenital Hypoplastic Anemia (Diamond-Blackfan Anemia) Etiology Epidemiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Prognosis Bibliography 449 Pearson Syndrome 449 Pearson Syndrome Bibliography 450 Acquired Pure Red Blood Cell Anemia 450 Acquired Pure Red Blood Cell Anemia Transient Erythroblastopenia of Childhood Red Cell Aplasia Associated with Parvovirus B19 Infection Chronic Hemolysis Immunodeficiency Miscarriage and Hydrops Fetalis Other Red Cell Aplasias in Children Bibliography 451 Anemia of Chronic Disease and Renal Disease 451 Anemia of Chronic Disease and Renal Disease 451.1 Anemia of Chronic Disease Etiology Clinical Manifestations Laboratory Findings Treatment Bibliography 451.2 Anemia of Renal Disease Etiology Laboratory Findings Treatment Bibliography 452 Congenital Dyserythropoietic Anemias 452 Congenital Dyserythropoietic Anemias Type I Congenital Dyserythropoietic Anemia Pathogenesis Clinical Manifestations Laboratory Findings Treatment Type II Congenital Dyserythropoietic Anemia Pathogenesis Clinical Manifestations Laboratory Findings Treatment Type III Congenital Dyserythropoietic Anemia Bibliography 453 Physiologic Anemia of Infancy 453 Physiologic Anemia of Infancy Treatment Bibliography 454 Megaloblastic Anemias 454 Megaloblastic Anemias 454.1 Folic Acid Deficiency Etiology Inadequate Folate Intake Decreased Folate Absorption Congenital Abnormalities in Folate Transport and Metabolism Drug-Induced Abnormalities in Folate Metabolism Clinical Manifestations Laboratory Findings Treatment Bibliography 454.2 Vitamin B12 (Cobalamin) Deficiency Metabolism Etiology Inadequate Vitamin B12 Intake Impaired Absorption Absence of Vitamin B12 Transport Protein Inborn Errors of Cobalamin Metabolism Clinical Manifestations Laboratory Findings Diagnosis Treatment Bibliography 454.3 Other Rare Megaloblastic Anemias Bibliography 455 Iron-Deficiency Anemia 455 Iron-Deficiency Anemia Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Prevention Treatment Bibliography 456 Other Microcytic Anemias 456 Other Microcytic Anemias Infantile Poikilocytosis and Hereditary Pyropoikilocytosis Copper Deficiency Defects of Iron Metabolism Bibliography 457 Definitions and Classification of Hemolytic Anemias 457 Definitions and Classification of Hemolytic Anemias 458 Hereditary Spherocytosis 458 Hereditary Spherocytosis Etiology Clinical Manifestations Diagnosis Differential Diagnosis Treatment General Supportive Care Guidelines for Splenectomy Bibliography 459 Hereditary Elliptocytosis 459 Hereditary Elliptocytosis Etiology Clinical Manifestations Laboratory Findings Treatment Bibliography 460 Hereditary Stomatocytosis 460 Hereditary Stomatocytosis Hydrocytosis Pathophysiology Clinical Features Xerocytosis Pathophysiology Clinical Features Intermediate Syndromes Other Disorders Associated with Stomatocytosis Treatment Bibliography 461 Paroxysmal Nocturnal Hemoglobinuria and Acanthocytosis 461 Paroxysmal Nocturnal Hemoglobinuria and Acanthocytosis Paroxysmal Nocturnal Hemoglobinuria Etiology Clinical Manifestations Laboratory Findings Treatment Acanthocytosis Bibliography 462 Hemoglobinopathies 462 Hemoglobinopathies Hemoglobin Disorders 462.1 Sickle Cell Disease Pathophysiology Diagnosis and Epidemiology Clinical Manifestations and Treatment of Sickle Cell Anemia (Hb SS) Fever and Bacteremia Aplastic Crisis Splenic Sequestration Hepatic and Gallbladder Involvement Sickle Cell Pain Avascular Necrosis Priapism Neurologic Complications Transcranial Doppler Ultrasonography Pulmonary Complications Renal Disease and Enuresis Cognitive and Psychological Complications Other Complications Therapeutic Considerations Hydroxyurea Hematopoietic Stem Cell Transplantation Red Blood Cell Transfusions Excessive Iron Stores Other Sickle Cell Syndromes Anticipatory Guidance Spleen Palpation Prophylactic Penicillin Immunizations Transcranial Doppler Ultrasound Hydroxyurea Regular Blood Transfusion Therapy Pulmonary and Asthma Screening Retinopathy Renal Echocardiography Bibliography 462.2 Sickle Cell Trait (Hemoglobin AS) 462.3 Other Hemoglobinopathies Hemoglobin C Hemoglobin E Hemoglobin D 462.4 Unstable Hemoglobin Disorders 462.5 Abnormal Hemoglobins with Increased Oxygen Affinity 462.6 Abnormal Hemoglobins Causing Cyanosis 462.7 Hereditary Methemoglobinemia 462.8 Hereditary Methemoglobinemia with Deficiency of NADH Cytochrome b5 Reductase 462.9 Syndromes of Hereditary Persistence of Fetal Hemoglobin 462.10 Thalassemia Syndromes Epidemiology Pathophysiology Homozygous β-Thalassemia (Thalassemia Major, Cooley Anemia) Clinical Manifestations Laboratory Findings Management and Treatment of Thalassemia Transfusion Therapy Guidelines for Transfusion Therapy. Iron Overload Monitoring Chelation Therapy Hydroxyurea Hematopoietic Stem Cell Transplantation Splenectomy Surgical Asplenia Preventative Monitoring of Thalassemia Patients Cardiac. Endocrine. Psychosocial Support. Other β-Thalassemia Syndromes Nontransfusion-Dependent Thalassemia: β-Thalassemia Intermedia α-Thalassemia Syndromes Bibliography 463 Enzymatic Defects 463 Enzymatic Defects 463.1 Pyruvate Kinase Deficiency Etiology Clinical Manifestations and Laboratory Findings Treatment 463.2 Other Glycolytic Enzyme Deficiencies Deficiencies of Enzymes of the Hexose Monophosphate Pathway 463.3 Glucose-6-Phosphate Dehydrogenase Deficiency and Related Deficiencies Episodic or Induced Hemolytic Anemia Etiology Clinical Manifestations Laboratory Findings Diagnosis Prevention and Treatment Chronic Hemolytic Anemias Associated with Deficiency of G6PD or Related Factors Bibliography 464 Hemolytic Anemias Resulting from Extracellular Factors—Immune Hemolytic Anemias 464 Hemolytic Anemias Resulting from Extracellular Factors—Immune Hemolytic Anemias Autoimmune Hemolytic Anemias Autoimmune Hemolytic Anemias Associated with “Warm” Antibodies Etiology Clinical Manifestations Laboratory Findings Treatment Course and Prognosis Autoimmune Hemolytic Anemias Associated with “Cold” Antibodies Cold Agglutinin Disease Paroxysmal Cold Hemoglobinuria Bibliography 465 Hemolytic Anemias Secondary to Other Extracellular Factors 465 Hemolytic Anemias Secondary to Other Extracellular Factors Fragmentation Hemolysis Thermal Injury Renal Disease Liver Disease Toxins and Venoms Wilson Disease Bibliography 466 Polycythemia 466 Polycythemia Clonal (Primary) Polycythemia (Polycythemia Rubra Vera) Pathogenesis Clinical Manifestations Treatment Bibliography 467 Non-Clonal Polycythemia 467 Non-Clonal Polycythemia Pathogenesis Congenital Polycythemia Acquired Polycythemia Diagnosis Treatment Bibliography 468 The Inherited Pancytopenias 468 The Inherited Pancytopenias Fanconi Anemia Etiology and Epidemiology Pathology Clinical Manifestations Laboratory Findings Complications Diagnosis Treatment Prognosis Shwachman-Diamond Syndrome Etiology and Epidemiology Pathology Clinical Manifestations Laboratory Findings Diagnosis Complications Treatment Prognosis Dyskeratosis Congenita Etiology and Epidemiology Pathology Clinical Manifestations Laboratory Findings Diagnosis Complications Treatment Prognosis Congenital Amegakaryocytic Thrombocytopenia Etiology and Epidemiology Clinical Manifestations Laboratory Findings Diagnosis Complications Therapy and Prognosis Other Inherited Syndromes Down Syndrome Dubowitz Syndrome Seckel Syndrome Reticular Dysgenesis Schimke Immunoosseous Dysplasia Noonan Syndrome Cartilage-Hair Hypoplasia Unclassified Inherited Bone Marrow Failure Syndromes Bibliography 469 The Acquired Pancytopenias 469 The Acquired Pancytopenias Etiology and Epidemiology Pathology and Pathogenesis Clinical Manifestations, Laboratory Findings, and Differential Diagnosis Treatment Complications Prognosis Pancytopenia Caused by Marrow Replacement Bibliography 470 Red Blood Cell Transfusions and Erythropoietin Therapy 470 Red Blood Cell Transfusions and Erythropoietin Therapy Bibliography 471 Platelet Transfusions 471 Platelet Transfusions Bibliography 472 Neutrophil (Granulocyte) Transfusions 472 Neutrophil (Granulocyte) Transfusions Bibliography 473 Plasma Transfusions 473 Plasma Transfusions Bibliography 474 Risks of Blood Transfusions 474 Risks of Blood Transfusions Bibliography 475 Hemostasis 475 Hemostasis The Process Pathology 475.1 Clinical and Laboratory Evaluation of Hemostasis History Physical Examination Laboratory Tests Platelet Count Prothrombin Time and Activated Partial Thromboplastin Time Partial Thromboplastin Time Thrombin Time Reptilase Time Mixing Studies Bleeding Time Platelet Function Analyzer D-Dimer Clotting Factor Assays Platelet Aggregation Testing for Thrombotic Predisposition Elevated Homocysteine Tests of the Fibrinolytic System Developmental Hemostasis Bibliography 476 Hereditary Clotting Factor Deficiencies (Bleeding Disorders) 476 Hereditary Clotting Factor Deficiencies (Bleeding Disorders) 476.1 Factor VIII or Factor IX Deficiency (Hemophilia A or B) Pathophysiology Clinical Manifestations Laboratory Findings and Diagnosis Differential Diagnosis Genetics and Classification Treatment Prophylaxis Supportive Care Chronic Complications Inhibitor Formation Comprehensive Care Bibliography 476.2 Factor XI Deficiency (Hemophilia C) Bibliography 476.3 Deficiencies of the Contact Factors (Nonbleeding Disorders) 476.4 Factor VII Deficiency Bibliography 476.5 Factor X Deficiency 476.6 Prothrombin (Factor II) Deficiency Bibliography 476.7 Factor V Deficiency Bibliography 476.8 Combined Deficiency of Factors V and VIII 476.9 Fibrinogen (Factor I) Deficiency 476.10 Factor XIII Deficiency (Fibrin-Stabilizing Factor or Transglutaminase Deficiency) Bibliography 476.11 Antiplasmin or Plasminogen Activator Inhibitor Deficiency Bibliography 477 Von Willebrand Disease 477 Von Willebrand Disease Pathophysiology Classification Laboratory Diagnosis Treatment Bibliography 478 Hereditary Predisposition to Thrombosis 478 Hereditary Predisposition to Thrombosis Bibliography 479 Thrombotic Disorders in Children 479 Thrombotic Disorders in Children Epidemiology Clinical Manifestations Extremity Deep Vein Thrombosis Pulmonary Embolism Cerebral Sinovenous Thrombosis Renal Vein Thrombosis Peripheral Arterial Thrombosis Stroke Rapidly Progressive Thrombosis/Thrombotic Storm Diagnosis Laboratory Testing Treatment Complications 479.1 Anticoagulant and Thrombolytic Therapy Unfractionated Heparin Heparin Dosing Heparin Complications Low-Molecular-Weight Heparin Enoxaparin Dosing Warfarin Warfarin Dosing Warfarin Complications Direct Thrombin or Factor Xa Inhibitors Thrombolytic Therapy Dosing Monitoring Complications Thromboprophylaxis Antiplatelet Therapy Bibliography 480 Postneonatal Vitamin K Deficiency 480 Postneonatal Vitamin K Deficiency Bibliography 481 Liver Disease 481 Liver Disease Bibliography 482 Acquired Inhibitors of Coagulation 482 Acquired Inhibitors of Coagulation Laboratory Findings Treatment Bibliography 483 Disseminated Intravascular Coagulation 483 Disseminated Intravascular Coagulation Etiology Clinical Manifestations Laboratory Findings Treatment Bibliography 484 Platelet and Blood Vessel Disorders 484 Platelet and Blood Vessel Disorders Megakaryopoiesis Thrombocytopenia Bibliography 484.1 Idiopathic (Autoimmune) Thrombocytopenic Purpura Epidemiology Pathogenesis Clinical Manifestations Outcome Laboratory Findings Diagnosis/Differential Diagnosis Treatment Chronic Autoimmune Thrombocytopenic Purpura Bibliography 484.2 Drug-Induced Thrombocytopenia Bibliography 484.3 Nonimmune Platelet Destruction 484.4 Hemolytic-Uremic Syndrome 484.5 Thrombotic Thrombocytopenic Purpura Bibliography 484.6 Kasabach-Merritt Syndrome 484.7 Sequestration 484.8 Congenital Thrombocytopenic Syndromes Bibliography 484.9 Neonatal Thrombocytopenia Bibliography 484.10 Thrombocytopenia from Acquired Disorders Causing Decreased Production 484.11 Platelet Function Disorders 484.12 Acquired Disorders of Platelet Function 484.13 Congenital Abnormalities of Platelet Function Other Hereditary Disorders of Platelet Function Treatment of Patients with Platelet Dysfunction Bibliography 484.14 Disorders of the Blood Vessels Henoch-Schönlein Purpura Ehlers-Danlos Syndrome Other Acquired Disorders Bibliography 485 Anatomy and Function of the Spleen 485 Anatomy and Function of the Spleen Anatomy Function Bibliography 486 Splenomegaly 486 Splenomegaly Clinical Manifestations Differential Diagnosis Pseudosplenomegaly Hypersplenism Congestive Splenomegaly (Banti Syndrome) Bibliography 487 Hyposplenism, Splenic Trauma, and Splenectomy 487 Hyposplenism, Splenic Trauma, and Splenectomy Hyposplenism Splenic Trauma Splenectomy Bibliography 488 Anatomy and Function of the Lymphatic System 488 Anatomy and Function of the Lymphatic System Bibliography 489 Abnormalities of Lymphatic Vessels 489 Abnormalities of Lymphatic Vessels Bibliography 490 Lymphadenopathy Cancer and Benign Tumors 491 Epidemiology of Childhood and Adolescent Cancer 491 Epidemiology of Childhood and Adolescent Cancer Influencing the Incidence of Cancer Bibliography 492 Molecular and Cellular Biology of Cancer 492 Molecular and Cellular Biology of Cancer Genes Involved in Oncogenesis Syndromes Predisposing to Cancer Other Factors Associated with Oncogenesis Viruses Genomic Imprinting Telomerase Bibliography 493 Principles of Diagnosis 493 Principles of Diagnosis Signs and Symptoms Physical Examination Age-Related Manifestations Early Detection Ensuring the Diagnosis Staging Bibliography 494 Principles of Treatment 494 Principles of Treatment Diagnosis and Staging A Multimodal, Multidisciplinary Approach Discussing the Treatment Plan with the Patient and Family Treatments Chemotherapy Surgery Radiation Therapy Acute Toxic Effects and Supportive Care Late Adverse Effects Palliative Care Bibliography 495 The Leukemias 495 The Leukemias 495.1 Acute Lymphoblastic Leukemia Epidemiology Etiology Cellular Classification Clinical Manifestations Diagnosis Differential Diagnosis Treatment Treatment of Relapse Supportive Care Prognosis Bibliography 495.2 Acute Myelogenous Leukemia Epidemiology Cellular Classification Clinical Manifestations Diagnosis Prognosis and Treatment Bibliography 495.3 Down Syndrome and Acute Leukemia and Transient Myeloproliferative Disorder Bibliography 495.4 Chronic Myelogenous Leukemia Bibliography 495.5 Juvenile Myelomonocytic Leukemia Bibliography 495.6 Infant Leukemia Bibliography 496 Lymphoma 496 Lymphoma 496.1 Hodgkin Lymphoma Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Relapse Prognosis Bibliography 496.2 Non-Hodgkin Lymphoma Epidemiology Pathogenesis Clinical Manifestations Laboratory Findings Treatment Burkitt Lymphoma and Diffuse Large B-cell Lymphoma Lymphoblastic Lymphoma Anaplastic Large Cell Lymphoma Relapsed Non-Hodgkin Lymphoma Complications Prognosis Bibliography 496.3 Late Effects in Children and Adolescents with Lymphoma 497 Brain Tumors in Childhood 497 Brain Tumors in Childhood Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Specific Tumors Astrocytomas Ependymal Tumors Choroid Plexus Tumors Embryonal Tumors Pineal Parenchymal Tumors Craniopharyngioma Germ Cell Tumors Tumors of the Brainstem Metastatic Tumors Complications and Long-Term Management Bibliography 498 Neuroblastoma 498 Neuroblastoma Epidemiology Pathology Pathogenesis Clinical Manifestations Diagnosis Treatment Bibliography 499 Neoplasms of the Kidney 499 Neoplasms of the Kidney 499.1 Wilms Tumor Epidemiology Etiology: Genetics and Molecular Biology Clinical Presentation Diagnosis and Differential Diagnosis Treatment Recurrent Disease Prognosis Late Effects 499.2 Other Pediatric Renal Tumors Mesoblastic Nephroma Clear Cell Sarcoma of the Kidney Rhabdoid Tumor of the Kidney Renal Cell Carcinoma Bibliography 500 Soft Tissue Sarcomas 500 Soft Tissue Sarcomas Rhabdomyosarcoma Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Other Soft Tissue Sarcomas Bibliography 501 Neoplasms of Bone 501 Neoplasms of Bone 501.1 Malignant Tumors of Bone Osteosarcoma Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Ewing Sarcoma Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis 501.2 Benign Tumors and Tumor-Like Processes of Bone Bibliography 502 Retinoblastoma 502 Retinoblastoma Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 503 Gonadal and Germ Cell Neoplasms 503 Gonadal and Germ Cell Neoplasms Epidemiology Pathogenesis Clinical Manifestations and Diagnosis Treatment Prognosis Bibliography 504 Neoplasms of the Liver 504 Neoplasms of the Liver Hepatoblastoma Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Hepatocellular Carcinoma Epidemiology Pathogenesis Clinical Manifestations Treatment Bibliography 505 Benign Vascular Tumors 505 Benign Vascular Tumors 505.1 Hemangiomas Clinical Manifestations Treatment Bibliography 505.2 Lymphangiomas and Cystic Hygromas Bibliography 506 Rare Tumors 506 Rare Tumors 506.1 Thyroid Tumors Benign Thyroid Tumors Malignant Thyroid Tumors Bibliography 506.2 Melanoma Bibliography 506.3 Nasopharyngeal Carcinoma Bibliography 506.4 Adenocarcinoma of the Colon and Rectum Bibliography 506.5 Adrenal Tumors Bibliography 506.6 Desmoplastic Small Round Cell Tumor Bibliography 507 Histiocytosis Syndromes of Childhood 507 Histiocytosis Syndromes of Childhood Classification and Pathology 507.1 Langerhans Cell Histiocytosis Clinical Manifestations Treatment and Prognosis Bibliography 507.2 Hemophagocytic Lymphohistiocytosis Clinical Manifestations Treatment and Prognosis Bibliography 507.3 Other Histiocytoses Bibliography Nephrology 508 Introduction to Glomerular Diseases 508 Introduction to Glomerular Diseases 508.1 Anatomy of the Glomerulus Bibliography 508.2 Glomerular Filtration Bibliography 508.3 Glomerular Diseases Pathogenesis Pathology Bibliography 509 Clinical Evaluation of the Child with Hematuria 509 Clinical Evaluation of the Child with Hematuria Bibliography 510 Isolated Glomerular Diseases with Recurrent Gross Hematuria 510 Isolated Glomerular Diseases with Recurrent Gross Hematuria 510.1 Immunoglobulin A Nephropathy (Berger Nephropathy) Pathology and Pathologic Diagnosis Clinical and Laboratory Manifestations Prognosis and Treatment Bibliography 510.2 Alport Syndrome Genetics Pathology Clinical Manifestations Diagnosis Prognosis and Treatment Bibliography 510.3 Thin Basement Membrane Disease Bibliography 511 Glomerulonephritis Associated with Infections 511 Glomerulonephritis Associated with Infections 511.1 Acute Poststreptococcal Glomerulonephritis Etiology and Epidemiology Pathology Pathogenesis Clinical Manifestations Diagnosis Complications Prevention Treatment Prognosis Bibliography 511.2 Other Chronic Infections Bibliography 512 Membranous Nephropathy 512 Membranous Nephropathy Pathology Pathogenesis Clinical Manifestations Diagnosis Prognosis and Treatment Bibliography 513 Membranoproliferative Glomerulonephritis 513 Membranoproliferative Glomerulonephritis Pathology Pathogenesis Clinical Manifestations Differential Diagnosis Prognosis and Treatment Bibliography 514 Glomerulonephritis Associated with Systemic Lupus Erythematosus 514 Glomerulonephritis Associated with Systemic Lupus Erythematosus Pathogenesis and Pathology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 515 Henoch-Schönlein Purpura Nephritis 515 Henoch-Schönlein Purpura Nephritis Pathogenesis and Pathology Clinical and Laboratory Manifestations Prognosis and Treatment Bibliography 516 Rapidly Progressive (Crescentic) Glomerulonephritis 516 Rapidly Progressive (Crescentic) Glomerulonephritis Classification Pathology and Pathogenesis Clinical Manifestations Diagnosis and Differential Diagnosis Prognosis and Treatment Bibliography 517 Goodpasture Disease 517 Goodpasture Disease Pathology Clinical Manifestations Diagnosis and Differential Diagnosis Prognosis and Treatment Bibliography 518 Hemolytic-Uremic Syndrome 518 Hemolytic-Uremic Syndrome Etiology Pathology Pathogenesis Clinical Manifestations Diagnosis and Differential Diagnosis Prognosis and Treatment Bibliography 519 Upper Urinary Tract Causes of Hematuria 519 Upper Urinary Tract Causes of Hematuria 519.1 Interstitial Nephritis 519.2 Toxic Nephropathy 519.3 Cortical Necrosis 519.4 Pyelonephritis 519.5 Nephrocalcinosis 519.6 Vascular Abnormalities Bibliography 519.7 Renal Vein Thrombosis Epidemiology Pathogenesis Clinical Manifestations Diagnosis Differential Diagnosis Treatment Prognosis Bibliography 519.8 Idiopathic Hypercalciuria Diagnosis Treatment Bibliography 520 Hematologic Diseases Causing Hematuria 520 Hematologic Diseases Causing Hematuria 520.1 Sickle Cell Nephropathy Etiology Pathology Clinical Manifestations Treatment Prognosis Bibliography 520.2 Coagulopathies and Thrombocytopenia 521 Anatomic Abnormalities Associated with Hematuria 521 Anatomic Abnormalities Associated with Hematuria 521.1 Congenital Anomalies 521.2 Autosomal Recessive Polycystic Kidney Disease Pathology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 521.3 Autosomal Dominant Polycystic Kidney Disease Pathology Pathogenesis Clinical Presentation Diagnosis Treatment and Prognosis Bibliography 521.4 Trauma Bibliography 521.5 Renal Tumors 522 Lower Urinary Tract Causes of Hematuria 522 Lower Urinary Tract Causes of Hematuria 522.1 Infectious Causes of Cystitis and Urethritis 522.2 Hemorrhagic Cystitis Bibliography 522.3 Vigorous Exercise Bibliography 523 Introduction to the Child with Proteinuria 523 Introduction to the Child with Proteinuria Normal Physiology Pathophysiology of Proteinuria Measurement of Urine Protein Urine Dipstick Measurement of Protein Urine Protein-to-Creatinine Ratio Measurement Clinical Considerations Bibliography 524 Transient Proteinuria 524 Transient Proteinuria Bibliography 525 Orthostatic (Postural) Proteinuria 525 Orthostatic (Postural) Proteinuria Bibliography 526 Fixed Proteinuria 526 Fixed Proteinuria 526.1 Glomerular Proteinuria Bibliography 526.2 Tubular Proteinuria Bibliography 527 Nephrotic Syndrome 527 Nephrotic Syndrome Etiology Pathogenesis Role of the Podocyte Role of the Immune System Clinical Consequences of Nephrotic Syndrome Edema Hyperlipidemia Increased Susceptibility to Infections Hypercoagulability Bibliography 527.1 Idiopathic Nephrotic Syndrome Pathology Minimal Change Nephrotic Syndrome Clinical Manifestations Diagnosis Recommendations for the Initial Evaluation of Children with Nephrotic Syndrome Confirming the Diagnosis of Nephrotic Syndrome. Treatment Use of Corticosteroids to Treat Minimal Change Nephrotic Syndrome Treatment of Initial Episode of Nephrotic Syndrome Managing the Clinical Sequelae of Nephrotic Syndrome Edema. Dyslipidemia. Infections. Thromboembolism. Obesity and Growth. Relapse of Nephrotic Syndrome. Steroid Resistance. Implications of Steroid-Resistant Nephrotic Syndrome. Alternative Therapies to Corticosteroids in the Treatment of Nephrotic Syndrome. Immunizations in Children with Nephrotic Syndrome. Prognosis Bibliography 527.2 Secondary Nephrotic Syndrome Bibliography 527.3 Congenital Nephrotic Syndrome Bibliography 528 Tubular Function 528 Tubular Function Sodium Potassium Calcium Phosphate Magnesium Acidification and Concentrating Mechanisms Developmental Considerations Bibliography 529 Renal Tubular Acidosis 529 Renal Tubular Acidosis Normal Urinary Acidification 529.1 Proximal (Type II) Renal Tubular Acidosis Pathogenesis Autosomal Recessive Disease Cystinosis Lowe Syndrome Clinical Manifestations of Proximal Renal Tubular Acidosis and Fanconi Syndrome 529.2 Distal (Type I) Renal Tubular Acidosis Pathogenesis Clinical Manifestations 529.3 Hyperkalemic (Type IV) Renal Tubular Acidosis Pathogenesis Clinical Manifestations Diagnostic Approach to Renal Tubular Acidosis Treatment and Prognosis Bibliography 529.4 Rickets Associated with Renal Tubular Acidosis 530 Nephrogenic Diabetes Insipidus 530 Nephrogenic Diabetes Insipidus Pathogenesis Clinical Manifestations Diagnosis Treatment and Prognosis Bibliography 531 Bartter and Gitelman Syndromes and Other Inherited Tubular Transport Abnormalities 531 Bartter and Gitelman Syndromes and Other Inherited Tubular Transport Abnormalities 531.1 Bartter Syndrome Pathogenesis Clinical Manifestations Diagnosis Treatment and Prognosis 531.2 Gitelman Syndrome Pathogenesis Clinical Manifestations Diagnosis Treatment 531.3 Other Inherited Tubular Transport Abnormalities Bibliography 532 Tubulointerstitial Nephritis 532 Tubulointerstitial Nephritis Acute Tubulointerstitial Nephritis Pathogenesis and Pathology Clinical Manifestations Diagnosis Treatment and Prognosis Chronic Tubulointerstitial Nephritis Pathogenesis and Pathology Clinical Manifestations Diagnosis Treatment and Prognosis Bibliography 533 Toxic Nephropathy 533 Toxic Nephropathy Bibliography 534 Cortical Necrosis 534 Cortical Necrosis Etiology Clinical Manifestations Laboratory and Radiologic Findings Treatment Prognosis Bibliography 535 Renal Failure 535 Renal Failure 535.1 Acute Kidney Injury Pathogenesis Clinical Manifestations and Diagnosis Laboratory Findings Treatment Medical Management Dialysis Prognosis Bibliography 535.2 Chronic Kidney Disease Etiology Pathogenesis Clinical Manifestations Laboratory Findings Treatment Nutrition Renal Osteodystrophy Adynamic Bone Disease Fluid and Electrolyte Management Acidosis Growth Anemia Hypertension Immunizations Adjustment In Drug Dose Progression of Disease Bibliography 535.3 End-Stage Renal Disease Bibliography 536 Renal Transplantation 536 Renal Transplantation Incidence and Etiology Indications Characteristics of Donors and Recipients Evaluation and Preparing for Transplantation Immunosuppression Induction Therapy T-Cell Antibodies Interleukin-2 Receptor Antibodies Other Induction Therapies Maintenance Immunosuppression Calcineurin Inhibitors Mycophenolate Mofetil Sirolimus Corticosteroids Fluid Management in Infants and Small Children Renal Biopsy Rejection Graft Survival Complications with Immunosuppression Infections Long-Term Outcome Bibliography Urologic Disorders inInfants and Children 537 Congenital Anomalies and Dysgenesis of the Kidneys 537 Congenital Anomalies and Dysgenesis of the Kidneys Embryonic Development Renal Agenesis Renal Dysgenesis: Dysplasia, Hypoplasia, and Cystic Anomalies Anomalies in Shape and Position Associated Physical Findings Bibliography 538 Urinary Tract Infections 538 Urinary Tract Infections Prevalence and Etiology Clinical Manifestations and Classification Clinical Pyelonephritis Cystitis Asymptomatic Bacteriuria Pathogenesis and Pathology Diagnosis Treatment Imaging Studies in Children with a Febrile UTI Prophylaxis of Recurrent Urinary Tract Infection Bibliography 539 Vesicoureteral Reflux 539 Vesicoureteral Reflux Classification Clinical Manifestations Diagnosis Natural History Treatment Observation Antimicrobial Prophylaxis Surgery Current Vesicoureteral Reflux Guidelines Bibliography 540 Obstruction of the Urinary Tract 540 Obstruction of the Urinary Tract Etiology Clinical Manifestations Diagnosis Imaging Studies Renal Ultrasonography Voiding Cystourethrogram Radioisotope Studies Excretory Urogram Magnetic Resonance Urography Computed Tomography Ancillary Studies Specific Types of Urinary Tract Obstruction and Their Treatment Hydrocalycosis Ureteropelvic Junction Obstruction Midureteral Obstruction Ectopic Ureter Ureterocele Megaureter Prune-Belly Syndrome Bladder Neck Obstruction Posterior Urethral Valves Urethral Atresia Urethral Hypoplasia Urethral Strictures Anterior Urethral Valves and Urethral Diverticula in the Male Male Urethral Meatal Stenosis Bibliography 541 Anomalies of the Bladder 541 Anomalies of the Bladder Bladder Exstrophy Clinical Manifestations Treatment Long-Term Prognosis Other Exstrophy Anomalies Bladder Diverticula Urachal Anomalies Bibliography 542 Neuropathic Bladder 542 Neuropathic Bladder Neural Tube Defects Clinical Manifestations and Diagnosis Renal Damage Urinary Incontinence Complications of Augmentation Cystoplasty Urinary Tract Infection Metabolic Acidosis Spontaneous Perforation Bladder Calculi Malignant Neoplasm Future Management Associated Disorders Constipation Latex Allergy Occult Spinal Dysraphism Sacral Agenesis Imperforate Anus Cerebral Palsy Bibliography 543 Enuresis and Voiding Dysfunction 543 Enuresis and Voiding Dysfunction Normal Voiding and Toilet Training Diurnal Incontinence Overactive Bladder (Diurnal Urge Syndrome) Nonneurogenic Neurogenic Bladder (Hinman Syndrome) Infrequent Voiding (Underactive Bladder) Vaginal Voiding Other Causes of Incontinence in Girls Voiding Disorders without Incontinence Nocturnal Enuresis Epidemiology Pathogenesis Clinical Manifestations and Diagnosis Treatment Bibliography 544 Anomalies of the Penis and Urethra 544 Anomalies of the Penis and Urethra Hypospadias Clinical Manifestations Treatment Chordee Without Hypospadias Phimosis and Paraphimosis Circumcision Penile Torsion Inconspicuous Penis Micropenis Priapism Other Penile Anomalies Meatal Stenosis Other Male Urethral Anomalies Urethral Prolapse (Female) Other Female Urethral Lesions Bibliography 545 Disorders and Anomalies of the Scrotal Contents 545 Disorders and Anomalies of the Scrotal Contents Undescended Testis (Cryptorchidism) Epidemiology Pathogenesis Clinical Manifestations Treatment Scrotal Swelling Clinical Manifestations Laboratory Findings and Diagnosis Testicular (Spermatic Cord) Torsion Etiology Diagnosis Treatment Torsion of the Appendix Testis Epididymitis Varicocele Spermatocele Hydrocele Etiology Diagnosis Treatment Inguinal Hernia Testicular Tumor Bibliography 546 Trauma to the Genitourinary Tract 546 Trauma to the Genitourinary Tract Etiology Diagnosis Treatment Bibliography 547 Urinary Lithiasis 547 Urinary Lithiasis Stone Formation Clinical Manifestations Diagnosis Metabolic Evaluation Pathogenesis of Specific Renal Calculi Calcium Oxalate and Calcium Phosphate Calculi Cystine Calculi Struvite Calculi Uric Acid Calculi Indinavir Calculi Nephrocalcinosis Treatment Bibliography Gynecologic Problemsof Childhood 548 History and Physical Examination 548 History and Physical Examination History Gynecologic Examination Neonates Infants and Prepubertal Girls Indications for Genital Examination Preparation Positioning Documentation Adolescents Pelvic Examination Bibliography 549 Vulvovaginitis 549 Vulvovaginitis Etiology Epidemiology Clinical Manifestations Diaper Dermatitis Physiologic Leukorrhea Genital Ulcers Dermatoses Diagnosis and Differential Diagnosis Treatment and Prevention Bibliography 550 Bleeding 550 Bleeding Bibliography 551 Breast Concerns 551 Breast Concerns Breast Development Breast Examination Breast Self-Examination Abnormal Development Neonatal Breast Abnormalities Precocious Puberty Amastia Polymastia and Polythelia Breast Asymmetry and Hypomastia Juvenile or Virginal Hypertrophy Infections Trauma and Inflammation Nipple Discharge Galactorrhea Bloody Discharge Mastalgia Breast Masses Peripubertal Masses Common Adolescent Breast Masses Malignant Masses Imaging of Breast Masses Recommendations for Daughters of Women with Breast Cancer Risk Reduction Screening Procedures Genetic Testing in Children Cosmetic Surgery Bibliography 552 Polycystic Ovary Syndrome and Hirsutism 552 Polycystic Ovary Syndrome and Hirsutism Polycystic Ovary Syndrome Etiology and Definition Pathology Pathogenesis and Genetics Clinical Manifestations Laboratory Findings, Diagnosis, and Differential Diagnosis Complications and Long-Term Outlook Treatment Lifestyle Changes Hormonal Contraceptives Metformin Antiandrogens Hirsutism Bibliography 553 Neoplasms and Adolescent Screening for Human Papillomavirus 553 Neoplasms and Adolescent Screening for Human Papillomavirus Gynecologic Malignancies Impact of Cancer Therapy on Fertility Ovaries Neonatal and Pediatric Ovarian Cysts Functional Cysts Teratomas Cystadenomas Endometriomas Pelvic Inflammatory Disease and Tuboovarian Abscess Adnexal Torsion Ovarian Carcinoma Uterus Vagina Vulva Cervix Bibliography 554 Vulvovaginal and Müllerian Anomalies 554 Vulvovaginal and Müllerian Anomalies Embryology Epidemiology Clinical Manifestations Laboratory Findings Uterine Anomalies Septate Uterus Bicornuate Uterus Unicornuate Uterus and Rudimentary Horns Uterine Didelphys Arcuate Uterus Uterine Anomalies in Diethylstilbestrol-Exposed Patients Treatment Vaginal Anomalies Abnormalities of the Hymen Congenital Absence of the Vagina and Mayer-Rokitansky-Küster-Hauser Syndrome Longitudinal Vaginal Septa Transverse Vaginal Septa (Vertical Fusion Defects) Treatment Cervical Anomalies Vulvar and Other Anomalies Complete Vulvar Duplication Labial Asymmetry and Hypertrophy Clitoral Abnormalities Cloacal Anomalies Ductal Remnants Bibliography 555 Gynecologic Care for Girls with Special Needs 555 Gynecologic Care for Girls with Special Needs Sexuality and Sexual Education Abuse Pelvic Examination Menstruation Treatment of Menstruation Nonhormonal Methods Estrogen-Containing Methods Oral Contraceptives Contraceptive Ring Contraceptive Patch Estrogen Use, Venous Thromboembolism and Mobility Issues Progestin-Only Methods Intramuscular Medroxyprogesterone Acetate Oral Progestins Progesterone Intrauterine Device Implants Hormones and Antiepileptic Drugs Surgical Methods Contraception Bibliography 555.1 Female Genital Mutilation/Cutting Classifications Management Bibliography The Endocrine System 556 Hormones of the Hypothalamus and Pituitary 556 Hormones of the Hypothalamus and Pituitary Anatomy Embryology Vascular Supply Anterior Pituitary Cell Types Growth Hormone Prolactin Thyroid-Stimulating Hormone Adrenocorticotropic Hormone Luteinizing Hormone and Follicle-Stimulating Hormone Posterior Pituitary Cell Types Antidiuretic Hormone Oxytocin Bibliography 557 Hypopituitarism 557 Hypopituitarism Multiple Pituitary Hormone Deficiency Genetic Forms PROP1 POU1F1 (PIT1) HESX1 LHX3 and LHX4 Other Congenital Forms Acquired Forms Isolated Growth Hormone Deficiency and Insensitivity Genetic Forms of Growth Hormone Deficiency Growth Hormone–Releasing Hormone Receptor GH1 X-Linked Isolated Growth Hormone Deficiency Acquired Forms Growth Hormone Insensitivity Abnormalities of the Growth Hormone Receptor Postreceptor Forms of Growth Hormone Insensitivity IGF-1 Gene Abnormalities Insulin-Like Growth Factor–Binding Protein Abnormalities IGF-1 Receptor Gene Abnormalities Clinical Manifestations Congenital Hypopituitarism Acquired Hypopituitarism Laboratory Findings Radiologic Findings Differential Diagnosis Constitutional Growth Delay Primary Hypothyroidism Psychosocial Causes Treatment Complications and Adverse Effects of GH Treatment Bibliography 558 Diabetes Insipidus 558 Diabetes Insipidus Physiology of Water Balance Approach to the Patient with Polyuria, Polydipsia, and Hypernatremia Causes of Hypernatremia Central Diabetes Insipidus Nephrogenic Diabetes Insipidus Treatment of Central Diabetes Insipidus Fluid Therapy Vasopressin Analogs Aqueous Vasopressin Treatment of Nephrogenic Diabetes Insipidus Bibliography 559 Other Abnormalities of Arginine Vasopressin Metabolism and Action 559 Other Abnormalities of Arginine Vasopressin Metabolism and Action Causes of Hyponatremia Syndrome of Inappropriate Antidiuretic Hormone Secretion Nephrogenic Syndrome of Inappropriate Antidiuresis Systemic Dehydration Primary Salt Loss Decreased Effective Plasma Volume Primary Polydipsia (Increased Water Ingestion) Decreased Free Water Clearance Cerebral Salt Wasting Runners’ Hyponatremia Pseudohyponatremia and Other Causes of Hyponatremia Treatment Emergency Treatment of Hyponatremia Treatment of Syndrome of Inappropriate Antidiuretic Hormone Treatment of Cerebral Salt Wasting Bibliography 560 Hyperpituitarism, Tall Stature, and Overgrowth Syndromes 560 Hyperpituitarism, Tall Stature, and Overgrowth Syndromes Hyperpituitarism Tall Stature Differential Diagnosis of Tall Stature Overgrowth in the Fetus and Neonate Overgrowth in Childhood or Adolescence Sotos Syndrome (Cerebral Gigantism) Treatment of Normal Variant Tall Stature Excess Growth Hormone Secretion and Pituitary Gigantism Diagnosis Treatment Hypersecretion of Other Pituitary Hormones Prolactinoma Corticotropinoma Bibliography 561 Physiology of Puberty 561 Physiology of Puberty Bibliography 562 Disorders of Pubertal Development 562 Disorders of Pubertal Development 562.1 Central Precocious Puberty Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment 562.2 Precocious Puberty Resulting from Organic Brain Lesions Etiology Clinical Manifestations Treatment 562.3 Precocious Puberty Following Irradiation of the Brain Treatment 562.4 Syndrome of Precocious Puberty and Hypothyroidism 562.5 Chorionic Gonadotropin-Secreting Tumors Hepatic Tumors Intracranial Tumors Tumors in Other Locations Peripheral Precocious Puberty 562.6 McCune-Albright Syndrome (Precocious Puberty with Polyostotic Fibrous Dysplasia and Abnormal Pigmentation) Extragonadal Manifestations 562.7 Familial Male Gonadotropin-Independent Precocious Puberty Treatment 562.8 Incomplete (Partial) Precocious Development Premature Thelarche Premature Pubarche (Adrenarche) Premature Menarche 562.9 Medicational Precocity Bibliography 563 Thyroid Development and Physiology 563 Thyroid Development and Physiology Fetal Development Thyroid Physiology Thyroid Regulation Bibliography 563.1 Thyroid Hormone Studies Serum Thyroid Hormones Fetal and Newborn Thyroid Serum Thyroxine-Binding Globulin In Vivo Radionuclide Studies Thyroid Ultrasonographic Studies Bibliography 564 Defects of Thyroxine-Binding Globulin 564 Defects of Thyroxine-Binding Globulin Bibliography 565 Hypothyroidism 565 Hypothyroidism Congenital Hypothyroidism Epidemiology Etiology Primary Hypothyroidism Thyroid Dysgenesis. Defective Synthesis of Thyroxine (Dyshormonogenesis). Defect of Iodide Transport. Thyroid Peroxidase Defects of Organification and Coupling. Defects of Thyroglobulin Synthesis. Defects in Deiodination. Thyrotropin Hormone Unresponsiveness. Defects in Thyroid Hormone Transport. Resistance to Thyroid Hormone Thyrotropin Receptor-Blocking Antibody. Radioiodine Administration. Iodine Exposure. Iodine-Deficiency Endemic Goiter. Central (Hypopituitary) Hypothyroidism Thyrotropin and Thyrotropin-Releasing Hormone Deficiency. Thyrotropin-Releasing Hormone Receptor Abnormality. Thyroid Function in Preterm Babies Clinical Manifestations Laboratory Findings Treatment Prognosis Acquired Hypothyroidism Epidemiology Etiology Clinical Manifestations Diagnostic Studies Treatment and Prognosis Bibliography Congenital Hypothyroidism Acquired Hypothyroidism 566 Thyroiditis 566 Thyroiditis Chronic Lymphocytic Thyroiditis (Hashimoto Thyroiditis, Autoimmune Thyroiditis) Etiology Clinical Manifestations Laboratory Findings Treatment Other Causes of Thyroiditis Bibliography 567 Goiter 567 Goiter 567.1 Congenital Goiter Bibliography 567.2 Intratracheal Goiter 567.3 Endemic Goiter and Cretinism Etiology Clinical Manifestations Pathogenesis Treatment Bibliography 567.4 Acquired Goiter Iodide Goiter Simple Goiter (Colloid Goiter) Multinodular Goiter Toxic Goiter (Hyperthyroidism) Bibliography 568 Hyperthyroidism 568 Hyperthyroidism 568.1 Graves Disease Epidemiology Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Bibliography 568.2 Congenital Hyperthyroidism Etiology and Pathogenesis Clinical Manifestations Treatment Prognosis Bibliography 569 Carcinoma of the Thyroid 569 Carcinoma of the Thyroid Epidemiology Pathogenesis Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 569.1 Solitary Thyroid Nodule Bibliography 569.2 Medullary Thyroid Carcinoma Multiple Endocrine Neoplasia, Type 2A Multiple Endocrine Neoplasia, Type 2B Treatment Bibliography 570 Hormones and Peptides of Calcium Homeostasis and Bone Metabolism 570 Hormones and Peptides of Calcium Homeostasis and Bone Metabolism Parathyroid Hormone Parathyroid Hormone–Related Peptide Vitamin D Calcitonin Bibliography 571 Hypoparathyroidism 571 Hypoparathyroidism Etiology Aplasia or Hypoplasia of the Parathyroid Glands X-Linked Recessive Hypoparathyroidism Autosomal Recessive Hypoparathyroidism with Dysmorphic Features Hypoparathyroidism, Sensorineural Deafness, and Renal Anomaly Syndrome Suppression of Neonatal Parathyroid Hormone Secretion Because of Maternal Hyperparathyroidism Autosomal Dominant Hypoparathyroidism Hypoparathyroidism Associated with Mitochondrial Disorders Surgical Hypoparathyroidism Autoimmune Hypoparathyroidism Idiopathic Hypoparathyroidism Clinical Manifestations Laboratory Findings Treatment Differential Diagnosis Bibliography 572 Pseudohypoparathyroidism (Albright Hereditary Osteodystrophy) 572 Pseudohypoparathyroidism (Albright Hereditary Osteodystrophy) Type Ia Type Ia with Precocious Puberty Type Ib Acrodysostosis with Hormone Resistance Bibliography 573 Hyperparathyroidism 573 Hyperparathyroidism Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Prognosis 573.1 Other Causes of Hypercalcemia Familial Hypocalciuric Hypercalcemia (Familial Benign Hypercalcemia) Granulomatous Diseases Hypercalcemia of Malignancy Miscellaneous Causes of Hypercalcemia Bibliography 574 Physiology of the Adrenal Gland 574 Physiology of the Adrenal Gland 574.1 Histology and Embryology Bibliography 574.2 Adrenal Steroid Biosynthesis Zona Glomerulosa Zona Fasciculata Zona Reticularis Fetoplacental Unit Bibliography 574.3 Regulation of the Adrenal Cortex Regulation of Cortisol Secretion Regulation of Aldosterone Secretion Regulation of Adrenal Androgen Secretion Bibliography 574.4 Adrenal Steroid Hormone Actions Actions of Glucocorticoids Metabolic Effects Circulatory and Renal Effects Growth Immunologic Effects Effects on Skin, Bone, and Calcium Central Nervous System Effects Actions of Mineralocorticoids Actions of the Adrenal Androgens Synthetic Corticosteroids Bibliography 574.5 Adrenal Medulla Bibliography 575 Adrenocortical Insufficiency 575 Adrenocortical Insufficiency 575.1 Primary Adrenal Insufficiency Inherited Etiologies Inborn Defects of Steroidogenesis Adrenal Hypoplasia Congenita Other Genetic Causes of Adrenal Hypoplasia Adrenoleukodystrophy Familial Glucocorticoid Deficiency Type I Autoimmune Polyendocrinopathy Disorders of Cholesterol Synthesis and Metabolism Corticosteroid-Binding Globulin Deficiency and Decreased Cortisol-Binding Affinity Acquired Etiologies Autoimmune Addison Disease Infection Drugs Hemorrhage into Adrenal Glands Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Bibliography 575.2 Secondary and Tertiary Adrenal Insufficiency Etiology Abrupt Cessation of Administration of Corticosteroids Corticotropin (Adrenocorticotropic Hormone) Deficiency Clinical Presentation Laboratory Findings Treatment Bibliography 575.3 Adrenal Insufficiency in the Critical Care Setting Etiology Clinical Manifestations Laboratory Findings Treatment Bibliography 575.4 Altered End-Organ Sensitivity to Corticosteroids Generalized Glucocorticoid Resistance Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Cortisone Reductase Deficiency Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Altered End-Organ Sensitivity to Mineralocorticoids Pseudohypoaldosteronism Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Apparent Mineralocorticoid Excess Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Liddle Syndrome Etiology Clinical Manifestations, Laboratory Findings, and Differential Diagnosis Treatment Bibliography Generalized Glucocorticoid Resistance Cortisone Reductase Deficiency Altered End-Organ Sensitivity to Mineralocorticoids Apparent Mineralocorticoid Excess Liddle Syndrome 576 Congenital Adrenal Hyperplasia and Related Disorders 576 Congenital Adrenal Hyperplasia and Related Disorders 576.1 Congenital Adrenal Hyperplasia Caused by 21-Hydroxylase Deficiency Etiology Epidemiology Genetics Pathogenesis and Clinical Manifestations Aldosterone and Cortisol Deficiency Prenatal Androgen Excess Postnatal Androgen Excess Adrenomedullary Dysfunction Laboratory Findings Differential Diagnosis Prenatal Diagnosis Newborn Screening Treatment Glucocorticoid Replacement Mineralocorticoid Replacement Surgical Management of Ambiguous Genitals Prenatal Treatment Bibliography 576.2 Congenital Adrenal Hyperplasia Caused by 11β-Hydroxylase Deficiency Etiology Epidemiology Clinical Manifestations Laboratory Findings Treatment Bibliography 576.3 Congenital Adrenal Hyperplasia Caused by 3β-Hydroxysteroid Dehydrogenase Deficiency Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Bibliography 576.4 Congenital Adrenal Hyperplasia Caused by 17-Hydroxylase Deficiency Etiology Clinical Manifestations and Laboratory Findings Treatment Bibliography 576.5 Lipoid Adrenal Hyperplasia Etiology Clinical Manifestations Laboratory Findings Treatment Bibliography 576.6 Deficiency of P450 Oxidoreductase (Antley-Bixler Syndrome) Etiology, Pathogenesis, and Clinical Manifestations Epidemiology Laboratory Findings Differential Diagnosis Bibliography 576.7 Aldosterone Synthase Deficiency Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Bibliography 576.8 Glucocorticoid-Suppressible Hyperaldosteronism Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Genetic Counseling Bibliography 577 Cushing Syndrome 577 Cushing Syndrome Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Bibliography 578 Primary Aldosteronism 578 Primary Aldosteronism Etiology Epidemiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Bibliography 579 Adrenocortical Tumors 579 Adrenocortical Tumors Epidemiology Etiology 579.1 Virilizing and Feminizing Adrenal Tumors Clinical Manifestations Laboratory Findings Pathologic Findings Differential Diagnosis Treatment Bibliography 580 Pheochromocytoma 580 Pheochromocytoma Etiology Clinical Manifestations Laboratory Findings Differential Diagnosis Treatment Bibliography 581 Adrenal Masses 581 Adrenal Masses 581.1 Adrenal Incidentaloma 581.2 Adrenal Calcification Bibliography 582 Development and Function of the Gonads 582 Development and Function of the Gonads Genetic Control of Embryonic Gonadal Differentiation Function of the Testes Function of the Ovaries Diagnostic Testing Therapeutic Use of Sex Steroids Bibliography 583 Hypofunction of the Testes 583 Hypofunction of the Testes 583.1 Hypergonadotropic Hypogonadism in the Male (Primary Hypogonadism) Etiology Congenital Anorchia or Testicular Regression Syndrome Chemotherapy and Radiation-Induced Hypogonadism Sertoli Cell–Only Syndrome Other Causes of Testicular Hypofunction Testicular Dysgenesis Syndrome Clinical Manifestations Diagnosis Noonan Syndrome Etiology Clinical Manifestations Treatment Klinefelter Syndrome Etiology Clinical Manifestations Klinefelter Variants and Other Poly-X Syndromes Laboratory Findings Management XX Males 45,X Males 47,XXX Males Bibliography 583.2 Hypogonadotropic Hypogonadism in the Male (Secondary Hypogonadism) Etiology Isolated Gonadotropin Deficiency Hypogonadotropic Hypogonadism Without Anosmia Other Disorders with Hypogonadotropic Hypogonadism Hypogonadotropic Hypogonadism Associated with Other Pituitary Hormone Deficiencies Diagnosis Treatment Bibliography 584 Pseudoprecocity Resulting from Tumors of the Testes 584 Pseudoprecocity Resulting from Tumors of the Testes Bibliography 585 Gynecomastia 585 Gynecomastia Physiologic Forms of Gynecomastia Neonatal Gynecomastia Pubertal Gynecomastia Pathologic Gynecomastia Evaluation of Gynecomastia Treatment Bibliography 586 Hypofunction of the Ovaries 586 Hypofunction of the Ovaries 586.1 Hypergonadotropic Hypogonadism in the Female (Primary Hypogonadism) Turner Syndrome Pathogenesis Clinical Manifestations Laboratory Findings Treatment XX Gonadal Dysgenesis 45,X/46,XY Gonadal Dysgenesis XXX, XXXX, and XXXXX Females XXX Females XXXX and XXXXX Females Noonan Syndrome Other Ovarian Defects Bibliography 586.2 Hypogonadotropic Hypogonadism in the Female (Secondary Hypogonadism) Etiology Hypopituitarism Isolated Deficiency of Gonadotropins Diagnosis Bibliography 587 Pseudoprecocity Resulting from Lesions of the Ovary 587 Pseudoprecocity Resulting from Lesions of the Ovary Estrogenic Lesions of the Ovary Juvenile Granulosa Cell Tumor Clinical Manifestations and Diagnosis Treatment and Prognosis Follicular Cyst Androgenic Lesions of the Ovary Bibliography 588 Disorders of Sex Development 588 Disorders of Sex Development Sex Differentiation Diagnostic Approach to the Patient with Atypical or Ambiguous Genitalia 588.1 46,XX DSD Congenital Adrenal Hyperplasia Aromatase Deficiency Glucocorticoid Receptor Gene Mutation Virilizing Maternal Tumors Administration of Androgenic Drugs to Women during Pregnancy Bibliography 588.2 46,XY DSD Defects in Testicular Differentiation Denys-Drash Syndrome WAGR Syndrome Campomelic Syndrome XY Pure Gonadal Dysgenesis (Swyer Syndrome) XY Gonadal Agenesis Syndrome (Embryonic Testicular Regression Syndrome) Defects in Testicular Hormones Leydig Cell Aplasia Lipoid Adrenal Hyperplasia 3β-Hydroxysteroid Dehydrogenase Deficiency Deficiency of 17-Hydroxylase/17,20-Lyase Deficiency of 17-Ketosteroid Reductase Persistent Müllerian Duct Syndrome Defects in Androgen Action Dihydrotestosterone Deficiency Androgen Insensitivity Syndromes Clinical Manifestations Diagnosis Treatment and Prognosis Undetermined Causes Bibliography 588.3 Ovotesticular DSD Diagnosis and Management of Disorders of Sex Development Bibliography 589 Diabetes Mellitus 589 Diabetes Mellitus 589.1 Classification Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Other Specific Types of Secondary Diabetes Impaired Glucose Tolerance 589.2 Type 1 Diabetes Mellitus (Immune Mediated) Epidemiology Genetics Monogenic Type 1 Diabetes Mellitus Genes Altering the Risk of Autoimmune Type 1 Diabetes Mellitus Major Histocompatibility Complex/Human Leukocyte Antigen Encoded Susceptibility to Type 1 Diabetes Mellitus Role of Aspartate at Position 57 in DQB1 Role of Human Leukocyte Antigen Class I Insulin Gene Locus, IDDM2 PTPN22 (Lymphoid Tyrosine Phosphatase) Cytotoxic T Lymphocyte Antigen 4 Interleukin-2 Receptor Interleukin-1 Receptor Interferon-Induced Helicase CYP27B1 Environmental Factors Viral Infections Congenital Rubella Syndrome Enteroviruses Mumps Virus The Hygiene Hypothesis: Possible Protective Role of Infections Diet Psychologic Stress Pathogenesis and Natural History of Type 1 Diabetes Mellitus Initiation of Autoimmunity Preclinical Autoimmunity with Progressive Loss of β-Cell Function Role of Autoantibodies Role of Genetics in Disease Progression Role of Environmental Factors Onset of Clinical Disease Prediction and Prevention Primary Prevention of Type 1 Diabetes Mellitus Secondary Prevention Pathophysiology Clinical Manifestations Diagnosis Diabetic Ketoacidosis Treatment New-Onset Diabetes Without Ketoacidosis Insulin Therapy Insulin Pump Therapy Continuous Glucose Monitoring Systems Amylin-Based Adjunct Therapy Basic and Advanced Diabetes Education Ketoacidosis Hyperglycemia and Dehydration Catabolic Losses Keto Acid Accumulation Diabetic Ketoacidosis Protocol Cerebral Edema Nonketotic Hyperosmolar Coma Nutritional Management Monitoring Real-Time Continuous Glucose Monitoring Glycosylated Hemoglobin Exercise Benefits of Improved Glycemic Control Current Intensive Insulin Replacement Regimens Hypoglycemic Reactions Dawn Phenomenon and Somogyi Phenomenon Behavioral/Psychologic Aspects and Eating Disorders Cognitive Function Coping Styles Nonadherence Anxiety and Depression Fear of Self-Injecting and Self-Testing Eating Disorders Management During Infections Management During Surgery Long-Term Complications: Relation to Glycemic Control Diabetic Neuropathy Prognosis Pancreas and Islet Transplantation and Regeneration 589.3 Type 2 Diabetes Mellitus Natural History Epidemiology Genetics Epigenetics and Fetal Programming Environmental and Lifestyle-Related Risk Factors Clinical Features Treatment Complications Prevention 589.4 Other Specific Types of Diabetes Genetic Defects of β-Cell Function Maturity-Onset Diabetes of Youth MODY2 MODY3 Mitochondrial Gene Defects Maternally Inherited Diabetes and Deafness. Diabetes Mellitus of the Newborn Transient Neonatal Diabetes Mellitus Permanent Neonatal Diabetes Mellitus IPEX Syndrome Abnormalities of the Insulin Gene Genetic Defects of Insulin Action Donohue Syndrome Rabson-Mendenhall Syndrome Lipoatrophic Diabetes Stiff-Person Syndrome Systemic Lupus Erythematosus Cystic Fibrosis–Related Diabetes Autoimmune Diseases Endocrinopathies Drugs Genetic Syndromes Associated with Diabetes Mellitus Bibliography Epidemiology, Etiology, Genetics, Pathology, Classification, and Prevention Genetics Diabetic Ketoacidosis Management of Type 1 Diabetes in Children Long-Term Outcome of Childhood Diabetes: Relation of Control to Development of Complications Type 2 Diabetes and Diseases and Syndromes Associated with Diabetes Diabetes of the Newborn Hypoglycemia and Diabetes Pancreas and Islet Transplantation The Nervous System 590 Neurologic Evaluation 590 Neurologic Evaluation History Neurologic Examination Mental Status Head Cranial Nerves Olfactory Nerve (Cranial Nerve I) Optic Nerve (Cranial Nerve II) Vision Oculomotor (Cranial Nerve III), Trochlear (Cranial Nerve IV), and Abducens Nerves (Cranial Nerve VI) Trigeminal Nerve (Cranial Nerve V) Facial Nerve (Cranial Nerve VII) Vestibulocochlear Nerve (Cranial Nerve VIII) Glossopharyngeal Nerve (Cranial Nerve IX) Vagus Nerve (Cranial Nerve X) Accessory Nerve (Cranial Nerve XI) Hypoglossal Nerve (Cranial Nerve XII) Motor Examination Bulk Tone Strength Involuntary Movements Sensory Examination Reflexes Deep Tendon Reflexes and the Plantar Response Primitive Reflexes Coordination Station and Gait General Examination Special Diagnostic Procedures Lumbar Puncture and Cerebrospinal Fluid Examination Neuroradiologic Procedures Electroencephalography Evoked Potentials Bibliography 591 Congenital Anomalies of the Central Nervous System 591 Congenital Anomalies of the Central Nervous System 591.1 Neural Tube Defects 591.2 Spina Bifida Occulta (Occult Spinal Dysraphism) 591.3 Meningocele 591.4 Myelomeningocele Etiology Prevention Clinical Manifestations Treatment Prognosis Bibliography 591.5 Encephalocele Bibliography 591.6 Anencephaly 591.7 Disorders of Neuronal Migration Lissencephaly Schizencephaly Neuronal Heterotopias Polymicrogyrias Focal Cortical Dysplasias Porencephaly Bibliography 591.8 Agenesis of the Corpus Callosum Holoprosencephaly Bibliography 591.9 Agenesis of the Cranial Nerves and Dysgenesis of the Posterior Fossa Congenital Cranial Dysinnervation Disorders Brainstem and Cerebellar Disorders Bibliography 591.10 Microcephaly Etiology Clinical Manifestations and Diagnosis Treatment Bibliography 591.11 Hydrocephalus Physiology Pathophysiology and Etiology Clinical Manifestations Diagnosis and Differential Diagnosis Megalencephaly Hydranencephaly Treatment Prognosis Bibliography 591.12 Craniosynostosis Development and Etiology Clinical Manifestations and Treatment Bibliography Bibliography 592 Deformational Plagiocephaly 592 Deformational Plagiocephaly Epidemiology and Etiology Incidence Risk Factors Causes Examination and Differentiating between Deformational Plagiocephaly and Craniosynostosis History and Physical Exam Treatment Prevention Treatment Options Outcomes Bibliography 593 Seizures in Childhood 593 Seizures in Childhood Evaluation of the First Seizure 593.1 Febrile Seizures Genetic Factors Evaluation Lumbar Puncture Electroencephalogram Blood Studies Neuroimaging Treatment Bibliography 593.2 Unprovoked Seizures History and Examination Differential Diagnosis Long-Term Approach to the Patient and Additional Testing Bibliography 593.3 Partial Seizures and Related Epilepsy Syndromes Focal Seizures without Impairment of Consciousness Focal Seizures with Impairment of Consciousness Secondary Generalized Seizures Benign Epilepsy Syndromes with Focal Seizures Severe Epilepsy Syndromes with Focal Seizures 593.4 Generalized Seizures and Related Epilepsy Syndromes Absence Seizures Generalized Motor Seizure Benign Generalized Epilepsies Severe Generalized Epilepsies 593.5 Mechanisms of Seizures Bibliography 593.6 Treatment of Seizures and Epilepsy Deciding on Long-Term Therapy Counseling Mechanisms of Action of Antiepileptic Drugs Choice of Drug According to Seizure Type and Epilepsy Syndrome Choice of Drug: Other Considerations Initiating and Monitoring Therapy Titration Monitoring Side Effects Additional Treatments Approach to Epilepsy Surgery Discontinuation of Therapy Sudden Unexpected Death in Epilepsy Bibliography 593.7 Neonatal Seizures Pathophysiology Types of Neonatal Seizures Subtle Seizures Clonic Seizures Tonic Seizures Spasms Myoclonic Seizures Seizures vs Jitteriness Etiology Hypoxic–Ischemic Encephalopathy Vascular Events Intracranial Infections Brain Malformations Metabolic Disturbances Drug Withdrawal Neonatal Seizure Syndromes Miscellaneous Conditions Diagnosis Prognosis Treatment Lorazepam Diazepam Midazolam Phenobarbital Phenytoin and Fosphenytoin Other Medications Duration of Therapy Bibliography 593.8 Status Epilepticus Etiology Mechanisms Therapy Bibliography 593.9 Reflex Seizures (Stimulus Precipitated Seizures) Bibliography 593.10 Nodding Syndrome Bibliography 594 Conditions That Mimic Seizures 594 Conditions That Mimic Seizures Syncope and Other Generalized Paroxysms Apnea Breath-Holding Spells Compulsive Valsalva Neurally Mediated Syncope Cardiac Syncope Other Causes of Syncope Sporadic and Familial Hemiplegic Migraine Benign Paroxysmal Vertigo of Childhood Cyclic Vomiting Syndrome The “Alice in Wonderland” Syndrome Migraine-Induced Syncope Psychologic Disorders Paroxysmal Extreme Pain Disorder Autonomic Storms (Diencephalic Seizures) Movement Disorders and Other Abnormal Movements and Postures Neonatal Jitteriness and Clonus Hyperekplexia (Stiff Baby Syndrome) and Pathologic Startles Benign Paroxysmal Torticollis of Infancy Sandifer Syndrome Alternating Hemiplegia of Childhood Paroxysmal Dyskinesias and Other Movement Disorders Motor Tics Episodic Ataxias Benign Myoclonus of Early Infancy, Shuddering Attacks, and Chin Trembling Brainstem Dysfunction Psychologic Disorders Oculomotor Abnormalities and Visual Hallucinations Paroxysmal Tonic Upgaze of Childhood Oculomotor Apraxia and Saccadic Intrusions Spasmus Nutans Opsoclonus Myoclonus Syndrome Daydreaming and Behavioral Staring Visual Hallucinations Sleep Disorders Benign Sleep Myoclonus and Neonatal Sleep Myoclonus Nonrapid Eye Movement Partial Arousal Disorders Rapid Eye Movement Sleep Disorders Sleep Transition Disorders Narcolepsy-Cataplexy Syndrome Bibliography 595 Headaches 595 Headaches 595.1 Migraine Epidemiology Classification and Clinical Manifestations Migraine Without Aura Migraine with Aura Diagnosis and Differential Diagnosis Treatment Acute Treatment Emergency Department Treatments for Intractable Headaches Antidopaminergic Drugs: Prochlorperazine and Metoclopramide. Nonsteroidal Antiinflammatory Drugs: Ketorolac. Antiepileptic Drugs: Sodium Valproate. Triptans. Dihydroergotamine. Inpatient Management of Intractable Migraine and Status Migrainosus Dihydroergotamine. Sodium Valproate. Preventive Therapy Biobehavioral Therapy Bibliography 595.2 Secondary Headaches Bibliography 595.3 Tension-Type Headaches Bibliography 596 Neurocutaneous Syndromes 596 Neurocutaneous Syndromes 596.1 Neurofibromatosis Clinical Manifestations and Diagnosis Management Genetic Counseling Bibliography 596.2 Tuberous Sclerosis Clinical Manifestations and Diagnosis Skin Lesions Other Organ Involvement Management Bibliography 596.3 Sturge-Weber Syndrome Etiology Clinical Manifestations Diagnosis Management Bibliography 596.4 Von Hippel-Lindau Disease Bibliography 596.5 Linear Nevus Syndrome Bibliography 596.6 PHACE Syndrome Bibliography 596.7 Incontinentia Pigmenti Clinical Manifestations and Diagnosis Management Bibliography 597 Movement Disorders 597 Movement Disorders 597.1 Ataxias 597.2 Chorea, Athetosis, Tremor 597.3 Dystonia Inherited Primary Dystonias Drug-Induced Dystonias Cerebral Palsy Metabolic Disorders Other Disorders Treatment Bibliography 598 Encephalopathies 598 Encephalopathies 598.1 Cerebral Palsy Epidemiology and Etiology Clinical Manifestations Diagnosis Treatment Bibliography 598.2 Mitochondrial Encephalomyopathies Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Strokelike Episodes Myoclonus Epilepsy and Ragged Red Fibers Neuropathy, Ataxia, and Retinitis Pigmentosa Syndrome Leber Hereditary Optic Neuropathy Kearns-Sayre Syndrome Reversible Infantile Cytochrome C Oxidase Deficiency Myopathy Leigh Disease (Subacute Necrotizing Encephalomyopathy) Reye Syndrome Bibliography 598.3 Other Encephalopathies Hiv Encephalopathy Lead Encephalopathy Burn Encephalopathy Hypertensive Encephalopathy Radiation Encephalopathy Acute Necrotizing Encephalopathy Cystic Leukoencephalopathy Bibliography 598.4 Autoimmune Encephalitis Anti-N-Methyl-D-Aspartate Receptor Encephalitis Limbic Encephalitis Hashimoto Encephalopathy Opsoclonus–Myoclonus and Other Brainstem–Cerebellar Encephalitides Bickerstaff Encephalitis Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids Autoimmune Encephalopathies Associated with Epilepsy and Status Epilepticus Other Suspected Autoimmune Encephalitides Bibliography 599 Neurodegenerative Disorders of Childhood 599 Neurodegenerative Disorders of Childhood 599.1 Sphingolipidoses Gangliosidoses GM1 Gangliosidoses GM2 Gangliosidoses Krabbe Disease (Globoid Cell Leukodystrophy) Metachromatic Leukodystrophy Bibliography 599.2 Neuronal Ceroid Lipofuscinoses Bibliography 599.3 Adrenoleukodystrophy 599.4 Sialidosis Bibliography 599.5 Miscellaneous Disorders Pelizaeus-Merzbacher Disease Alexander Disease Canavan Spongy Degeneration Other Leukodystrophies Menkes Disease Rett Syndrome Subacute Sclerosing Panencephalitis Neurodegeneration with Brain Iron Accumulation Bibliography 600 Demyelinating Disorders of the Central Nervous System 600 Demyelinating Disorders of the Central Nervous System 600.1 Multiple Sclerosis Epidemiology Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Prognosis Bibliography 600.2 Neuromyelitis Optica Epidemiology Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Complications Treatment Prognosis Bibliography 600.3 Acute Disseminated Encephalomyelitis Epidemiology Pathogenesis Clinical Manifestations Neuroimaging Laboratory Findings Differential Diagnosis Treatment Prognosis Bibliography 601 Pediatric Stroke 601 Pediatric Stroke 601.1 Arterial Ischemic Stroke Perinatal Arterial Ischemic Stroke Bibliography 601.2 Cerebral Sinovenous Thrombosis Bibliography 601.3 Hemorrhagic Stroke Bibliography 601.4 Differential Diagnosis of Stroke-Like Events Migraine Seizure Infection Demyelination Hypoglycemia Global Hypoxic–Ischemic Encephalopathy Hypertensive Encephalopathy Inborn Errors of Metabolism Vestibulopathy/Ataxia Channelopathies Alternating Hemiplegia of Childhood 602 Central Nervous System Vasculitis 602 Central Nervous System Vasculitis Epidemiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 603 Central Nervous System Infections 603 Central Nervous System Infections 603.1 Acute Bacterial Meningitis Beyond the Neonatal Period Etiology Epidemiology Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenzae Type B Pathology and Pathophysiology Pathogenesis Clinical Manifestations Diagnosis Lumbar Puncture Differential Diagnosis Treatment Initial Antibiotic Therapy Duration of Antibiotic Therapy Corticosteroids Supportive Care Complications Prognosis Prevention Neisseria meningitidis Haemophilus influenzae Type B Streptococcus pneumoniae Bibliography 603.2 Viral Meningoencephalitis Etiology Epidemiology Pathogenesis and Pathology Clinical Manifestations Diagnosis Differential Diagnosis Laboratory Findings Treatment Prognosis Prevention Bibliography 603.3 Eosinophilic Meningitis Etiology Epidemiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 604 Brain Abscess 604 Brain Abscess Pathology Etiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 605 Idiopathic Intracranial Hypertension/Pseudotumor Cerebri 605 Idiopathic Intracranial Hypertension/Pseudotumor Cerebri Etiology Clinical Manifestations Treatment Bibliography 606 Spinal Cord Disorders 606 Spinal Cord Disorders 606.1 Tethered Cord Clinical Manifestations Diagnostic Evaluation Treatment Outcome Bibliography 606.2 Diastematomyelia Diastematomyelia: Split-Cord Malformation Clinical Manifestations Diagnostic Evaluation Treatment Bibliography 606.3 Syringomyelia Clinical Manifestations Diagnostic Evaluation Treatment Bibliography 606.4 Spinal Cord Tumors Clinical Manifestations Diagnostic Evaluation Treatment Outcome Bibliography 606.5 Spinal Cord Injuries in Children Clinical Manifestations Clearing the Cervical Spine in Children Treatment Prevention Bibliography 606.6 Transverse Myelitis Clinical Manifestations Diagnostic Evaluation Treatment Bibliography 606.7 Spinal Arteriovenous Malformations Diagnostic Evaluation Treatment Neuromuscular Disorders 607 Evaluation and Investigation 607 Evaluation and Investigation Clinical Manifestations Laboratory Findings Serum Enzymes Molecular Genetic Markers Nerve Conduction Velocity Electromyography Imaging of Muscle and Central Nervous System Muscle Biopsy Nerve Biopsy Cardiac Assessment Bibliography 608 Developmental Disorders of Muscle 608 Developmental Disorders of Muscle Myogenic Regulatory Genes and Genetic Loci of Inherited Diseases of Muscle Bibliography 608.1 Myotubular Myopathy (Centronuclear Myopathy) Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis Genetics Treatment Prognosis Bibliography 608.2 Congenital Muscle Fiber-Type Disproportion Pathogenesis Clinical Manifestations Laboratory Findings Diagnosis Genetics Treatment Bibliography 608.3 Nemaline Rod Myopathy Clinical Manifestations Laboratory Findings Genetics Treatment and Prognosis Bibliography 608.4 Central Core, Minicore, and Multicore Myopathies Bibliography 608.5 Myofibrillar Myopathies Bibliography 608.6 Brain Malformations and Muscle Development Bibliography 608.7 Amyoplasia 608.8 Muscular Dysgenesis (Proteus Syndrome Myopathy) Bibliography 608.9 Benign Congenital Hypotonia Bibliography 608.10 Arthrogryposis Bibliography 609 Muscular Dystrophies 609 Muscular Dystrophies 609.1 Duchenne and Becker Muscular Dystrophies Clinical Manifestations Laboratory Findings Diagnosis Genetic Etiology and Pathogenesis Treatment Bibliography 609.2 Emery-Dreifuss Muscular Dystrophy Genetics Diagnosis and Investigations Bibliography 609.3 Myotonic Muscular Dystrophy Clinical Manifestations Laboratory Findings Diagnosis Genetics Treatment Other Myotonic Syndromes Bibliography 609.4 Limb-Girdle Muscular Dystrophies Bibliography 609.5 Facioscapulohumeral Muscular Dystrophy Clinical Manifestations Laboratory Findings Diagnosis and Differential Diagnosis Treatment Bibliography 609.6 Congenital Muscular Dystrophies Clinical Manifestations Laboratory Findings Diagnosis Treatment Bibliography 610 Endocrine and Toxic Myopathies 610 Endocrine and Toxic Myopathies Thyroid Myopathies Steroid-Induced Myopathy Bibliography 611 Metabolic Myopathies 611 Metabolic Myopathies 611.1 Periodic Paralyses (Potassium-Related) and Other Muscle Channelopathies Treatment Other Muscle Channelopathies Bibliography 611.2 Malignant Hyperthermia 611.3 Glycogenoses Bibliography 611.4 Mitochondrial Myopathies Investigations Treatment Bibliography 611.5 Lipid Myopathies Bibliography 611.6 Vitamin E Deficiency Myopathy Bibliography 612 Disorders of Neuromuscular Transmission and of Motor Neurons 612 Disorders of Neuromuscular Transmission and of Motor Neurons 612.1 Myasthenia Gravis Autoimmune Myasthenia Gravis Clinical Manifestations Congenital Myasthenic Syndromes Rare Other Causes of Myasthenia Laboratory Findings and Diagnosis Recommendations on the Use of Cholinesterase Inhibitors as a Diagnostic Test for Myasthenia Gravis in Infants and Children Children 2 Yr and Older For Children Younger Than 2 Yr Treatment Complications Prognosis Other Causes of Neuromuscular Blockade Bibliography 612.2 Spinal Muscular Atrophies Etiology Clinical Manifestations Laboratory Findings Diagnosis Genetics Treatment Bibliography 612.3 Other Motor Neuron Diseases 613 Hereditary Motor-Sensory Neuropathies 613 Hereditary Motor-Sensory Neuropathies 613.1 Peroneal Muscular Atrophy (Charcot-Marie-Tooth Disease, Hereditary Motor-Sensory Neuropathy Type IIa) Clinical Manifestations Laboratory Findings and Diagnosis Treatment 613.2 Peroneal Muscular Atrophy (Axonal Type) 613.3 Congenital Hypomyelinating Neuropathy and Dejerine-Sottas Disease (Hereditary Motor-Sensory Neuropathy Type III) 613.4 Roussy-Lévy Syndrome 613.5 Refsum Disease (Hereditary Sensory Neuropathy Type IV) and Infantile Refsum Disease 613.6 Fabry Disease Clinical Manifestations Laboratory Findings Treatment 613.7 Giant Axonal Neuropathy 613.8 Tomaculous (Hypermyelinating) Neuropathy; Hereditary Neuropathy with Liability to Pressure Palsies 613.9 Leukodystrophies Bibliography 614 Toxic Neuropathies 614 Toxic Neuropathies Bibliography 615 Autonomic Neuropathies 615 Autonomic Neuropathies 615.1 Familial Dysautonomia Pathology Clinical Manifestations Laboratory Findings Diagnosis Treatment Prognosis Bibliography 615.2 Other Autonomic Neuropathies Congenital Insensitivity to Pain and Anhidrosis Reflex Sympathetic Dystrophy Bibliography 616 Guillain-Barré Syndrome 616 Guillain-Barré Syndrome Clinical Manifestations Laboratory Findings and Diagnosis Treatment Prognosis Bibliography 617 Bell Palsy 617 Bell Palsy Clinical Manifestations Imaging the Facial Nerve and Its Bony Canal Treatment Prognosis Facial Palsy at Birth Bibliography Disorders of the Eye 618 Growth and Development 618 Growth and Development Bibliography 619 Examination of the Eye 619 Examination of the Eye Visual Acuity Visual Field Assessment Color Vision Testing Pupillary Examination Ocular Motility Binocular Vision External Examination Biomicroscopy (Slit-Lamp Examination) Fundus Examination (Ophthalmoscopy) Refraction Tonometry Bibliography 620 Abnormalities of Refraction and Accommodation 620 Abnormalities of Refraction and Accommodation Hyperopia Myopia Astigmatism Anisometropia Accommodation Bibliography 621 Disorders of Vision 621 Disorders of Vision Amblyopia Diplopia Suppression Amaurosis Nyctalopia Psychogenic Disturbances Dyslexia Bibliography 622 Abnormalities of Pupil and Iris 622 Abnormalities of Pupil and Iris Aniridia Coloboma of the Iris Microcoria Congenital Mydriasis Dyscoria and Corectopia Anisocoria Dilated Fixed Pupil Tonic Pupil Marcus Gunn Pupil Horner Syndrome Paradoxical Pupil Reaction Persistent Pupillary Membrane Heterochromia Other Iris Lesions Leukocoria Bibliography 623 Disorders of Eye Movement and Alignment 623 Disorders of Eye Movement and Alignment Strabismus Diagnosis Clinical Manifestations and Treatment Comitant Strabismus Noncomitant Strabismus 3rd Nerve Palsy 4th Nerve Palsy 6th Nerve Palsy Strabismus Syndromes Monocular Elevation Deficiency Duane Syndrome Möbius Syndrome Brown Syndrome Parinaud Syndrome Congenital Ocular Motor Apraxia Nystagmus Other Abnormal Eye Movements Opsoclonus Ocular Motor Dysmetria Flutter-Like Oscillations Bibliography 624 Abnormalities of the Lids 624 Abnormalities of the Lids Ptosis Epicanthal Folds Lagophthalmos Lid Retractions Ectropion, Entropion, and Epiblepharon Blepharospasm Blepharitis Hordeolum (Stye) Chalazion Coloboma of the Eyelid Tumors of the Lid Bibliography 625 Disorders of the Lacrimal System 625 Disorders of the Lacrimal System The Tear Film Dacryostenosis Alacrima and “Dry Eye” Bibliography 626 Disorders of the Conjunctiva 626 Disorders of the Conjunctiva Conjunctivitis Ophthalmia Neonatorum Epidemiology Clinical Manifestations Diagnosis Treatment Prognosis and Prevention Acute Purulent Conjunctivitis Viral Conjunctivitis Epidemic Keratoconjunctivitis Membranous and Pseudomembranous Conjunctivitis Allergic Conjunctivitis Vernal Conjunctivitis Parinaud Oculoglandular Syndrome Chemical Conjunctivitis Other Conjunctival Disorders Bibliography 627 Abnormalities of the Cornea 627 Abnormalities of the Cornea Megalocornea Microcornea Keratoconus Neonatal Corneal Opacities Sclerocornea Peters Anomaly Corneal Dystrophies Dermoids Dendritic Keratitis Corneal Ulcers Phlyctenules Interstitial Keratitis Corneal Manifestations of Systemic Disease Bibliography 628 Abnormalities of the Lens 628 Abnormalities of the Lens Cataracts Differential Diagnosis Developmental Variants Prematurity Mendelian Inheritance Congenital Infection Syndrome Metabolic Disorders Chromosomal Defects Drugs, Toxic Agents, and Trauma Miscellaneous Disorders Treatment Prognosis Ectopia Lentis Differential Diagnosis Treatment and Prognosis Microspherophakia Anterior Lenticonus Posterior Lenticonus Bibliography 629 Disorders of the Uveal Tract 629 Disorders of the Uveal Tract Uveitis (Iritis, Cyclitis, Chorioretinitis) Treatment Bibliography 630 Disorders of the Retina and Vitreous 630 Disorders of the Retina and Vitreous Retinopathy of Prematurity Pathogenesis Classification Clinical Manifestations and Prognosis Diagnosis Treatment Prevention Persistent Fetal Vasculature Pathogenesis Clinical Manifestations Treatment Retinoblastoma Clinical Manifestations Diagnosis Treatment Retinitis Pigmentosa Stargardt Disease (Fundus Flavimaculatus) Best Vitelliform Degeneration Cherry-Red Spot Phakomas Retinoschisis Retinal Detachment Coats Disease Familial Exudative Vitreoretinopathy Hypertensive Retinopathy Diabetic Retinopathy Treatment Subacute Bacterial Endocarditis Blood Disorders Trauma-Related Retinopathy Myelinated Nerve Fibers Coloboma of the Fundus Bibliography 631 Abnormalities of the Optic Nerve 631 Abnormalities of the Optic Nerve Optic Nerve Aplasia Optic Nerve Hypoplasia Optic Nerve Coloboma Morning Glory Disc Anomaly Tilted Disc Drusen of the Optic Nerve Papilledema Optic Neuritis Leber Optic Neuropathy Optic Atrophy Optic Nerve Glioma Traumatic Optic Neuropathies Bibliography 632 Childhood Glaucoma 632 Childhood Glaucoma Clinical Manifestations Diagnosis and Treatment Bibliography 633 Orbital Abnormalities 633 Orbital Abnormalities Hypertelorism and Hypotelorism Exophthalmos and Enophthalmos Orbital Inflammation Tumors of the Orbit Bibliography 634 Orbital Infections 634 Orbital Infections Dacryoadenitis Dacryocystitis Preseptal Cellulitis Orbital Cellulitis Bibliography 635 Injuries to the Eye 635 Injuries to the Eye Ecchymosis and Swelling of the Eyelids Lacerations of the Eyelids Superficial Abrasions of the Cornea Foreign Body Involving the Ocular Surface Hyphema Open Globe Optic Nerve Trauma Chemical Injuries Orbital Fractures Penetrating Wounds of the Orbit Child Abuse Fireworks-Related Injuries Sports-Related Ocular Injuries and Their Prevention Handheld Laser Retinal Injury Bibliography The Ear 636 General Considerations and Evaluation 636 General Considerations and Evaluation Clinical Manifestations Facial Paralysis Physical Examination Bibliography 637 Hearing Loss 637 Hearing Loss Incidence and Prevalence Types of Hearing Loss Etiology Infectious Causes Genetic Causes Physical Causes Effects of Hearing Impairment Hearing Screening Identification of Hearing Impairment Clinical Audiologic Evaluation Audiometry Speech-Recognition Threshold Play Audiometry Visual Reinforcement Audiometry Behavioral Observation Audiometry Acoustic Immittance Testing Tympanometry Tympanometry in Otitis Media with Effusion Acoustic Reflex Test Auditory Brainstem Response Otoacoustic Emissions Acoustic Reflectometry Treatment Genetic Counseling Bibliography 638 Congenital Malformations 638 Congenital Malformations Pinna Malformations Congenital Stenosis or Atresia of the External Auditory Canal Congenital Middle-Ear Malformations Congenital Inner Ear Malformations Congenital Cholesteatoma Bibliography 639 External Otitis (Otitis Externa) 639 External Otitis (Otitis Externa) Etiology Clinical Manifestations Diagnosis Treatment Prevention Other Diseases of the External Ear Furunculosis Acute Cellulitis Perichondritis and Chondritis Dermatoses Herpes Simplex Virus Bullous Myringitis Exostoses and Osteomas Bibliography 640 Otitis Media 640 Otitis Media Epidemiology Age Gender Race Genetic Background Socioeconomic Status Breast Milk Compared to Formula Feeding Exposure to Tobacco Smoke Exposure to Other Children Season Congenital Anomalies Vaccination Status Other Factors Etiology Acute Otitis Media Otitis Media with Effusion Pathogenesis Anatomic Factors Host Factors Viral Pathogens Allergy Clinical Manifestations Examination of the Tympanic Membrane Otoscopy Clearing the External Auditory Canal Tympanic Membrane Findings Diagnosis Conjunctivitis-Associated Otitis Media Asymptomatic Purulent Otitis Media Tympanometry Prevention Immunoprophylaxis Treatment Management of Acute Otitis Media Bacterial Resistance First-Line Antimicrobial Treatment Duration of Treatment Follow-Up Unsatisfactory Response to First-Line Treatment Second-Line Treatment Antimicrobial Prophylaxis Myringotomy and Tympanocentesis Early Recurrence After Treatment Myringotomy and Insertion of Tympanostomy Tubes Tube Otorrhea Management of Otitis Media with Effusion Variables Influencing Otitis Media with Effusion Management Decisions Medical Treatment Myringotomy and Insertion of Tympanostomy Tubes Adenoidectomy Complications of Acute Otitis Media Intratemporal Complications Infectious Dermatitis Tympanic Membrane Perforation Chronic Suppurative Otitis Media Acute Mastoiditis Facial Paralysis Cholesteatoma Labyrinthitis Intracranial Complications Physical Sequelae Possible Developmental Sequelae Bibliography 641 The Inner Ear and Diseases of the Bony Labyrinth 641 The Inner Ear and Diseases of the Bony Labyrinth Viruses Toxoplasmosis Bacterial Meningitis Syphilis Other Diseases of the Inner Ear Bibliography 642 Traumatic Injuries of the Ear and Temporal Bone 642 Traumatic Injuries of the Ear and Temporal Bone Auricle and External Auditory Canal Tympanic Membrane and Middle Ear Temporal Bone Fractures Acoustic Trauma Bibliography 643 Tumors of the Ear and Temporal Bone 643 Tumors of the Ear and Temporal Bone Bibliography The Skin 644 Morphology of the Skin 644 Morphology of the Skin Epidermis Dermis Subcutaneous Tissue Appendageal Structures Hair Follicles Sebaceous Glands Apocrine Glands Eccrine Sweat Glands Nails Bibliography 645 Evaluation of the Patient 645 Evaluation of the Patient History and Physical Examination Biopsy of Skin Wood Lamp Potassium Hydroxide Preparation Tzanck Smear Immunofluorescence Studies 645.1 Cutaneous Manifestations of Systemic Diseases Connective Tissue Diseases Lupus Erythematosus Systemic Lupus Erythematosus Neonatal Lupus Erythematosus Discoid Lupus Erythematosus Juvenile Dermatomyositis Systemic Sclerosis Vasculitides Henoch-Schönlein Purpura (Immunoglobulin A Vasculitis) Kawasaki Disease Behçet Disease Gastrointestinal Diseases Inflammatory Bowel Disease Cutaneous Manifestations of Malignancy Sweet Syndrome Necrolytic Migratory Erythema (Glucagonoma Syndrome) Cutaneous Reactions in the Setting of Immunosuppression Medication Reactions Graft-Versus-Host Disease Bibliography 645.2 Multisystem Medication Reactions Drug Rash with Eosinophilia and Systemic Symptoms (DRESS Syndrome) Serum Sickness–Like Reaction Acute Generalized Exanthematous Pustulosis Bibliography 646 Principles of Therapy 646 Principles of Therapy Wet Dressings Bath Oils, Colloids, Soaps Lubricants Shampoos Shake Lotions Powders Pastes Keratolytic Agents Tar Compounds Antifungal Agents Topical Antibiotics Topical Corticosteroids Topical Nonsteroidal Antiinflammatory Agents Sunscreens Laser Therapy Bibliography 647 Diseases of the Neonate 647 Diseases of the Neonate Sebaceous Hyperplasia Milia Sucking Blisters Cutis Marmorata Harlequin Color Change Nevus Simplex (Salmon Patch) Dermal Melanocytosis (Mongolian Spots) Erythema Toxicum Transient Neonatal Pustular Melanosis Infantile Acropustulosis Eosinophilic Pustular Folliculitis Bibliography 648 Cutaneous Defects 648 Cutaneous Defects Skin Dimples Redundant Skin Amniotic Constriction Bands Preauricular Sinuses and Pits Accessory Tragi Branchial Cleft and Thyroglossal Cysts and Sinuses Supernumerary Nipples Aplasia Cutis Congenita (Congenital Absence of Skin) Focal Facial Dermal Dysplasias Focal Dermal Hypoplasia (Goltz Syndrome) Dyskeratosis Congenita (Zinsser-Engman-Cole Syndrome) Cutis Verticis Gyrata Bibliography 649 Ectodermal Dysplasias 649 Ectodermal Dysplasias Hypohidrotic Ectodermal Dysplasia Hidrotic Ectodermal Dysplasia (Clouston Syndrome) Bibliography 650 Vascular Disorders 650 Vascular Disorders Vascular Malformations Capillary Malformation (Port-Wine Stain) Angiokeratoma Circumscriptum Venous Malformation Cutis Marmorata Telangiectatica Congenita Blue Rubber Bleb Nevus Syndrome Klippel-Trenaunay and Parkes-Weber Syndromes Arteriovenous Malformation Lymphatic Malformations Phakomatosis Pigmentovascularis Nevus Anemicus Vascular Tumors Infantile Hemangioma Multifocal Infantile Hemangioma Kaposiform Hemangioendothelioma Kasabach-Merritt Phenomenon Pyogenic Granuloma (Lobular Capillary Hemangioma) Angiokeratoma of Mibelli Spider Angioma Maffucci Syndrome Hereditary Hemorrhagic Telangiectasia (Osler-Weber-Rendu Disease) Ataxia-Telangiectasia Angiokeratoma Corporis Diffusum (Fabry Disease) Bibliography 651 Cutaneous Nevi 651 Cutaneous Nevi Acquired Melanocytic Nevus Epidemiology Clinical Manifestations Prognosis and Treatment Atypical Melanocytic Nevus Congenital Melanocytic Nevus Melanoma Halo Nevus Spitz Nevus (Spindle and Epithelioid Cell Nevus) Zosteriform Lentiginous Nevus (Agminated Lentigines) Nevus Spilus (Speckled Lentiginous Nevus) Nevus of Ota and Nevus of Ito Blue Nevi Nevus Depigmentosus (Achromic Nevus) Epidermal Nevi Nevus Sebaceus (Jadassohn) Becker Nevus (Becker Melanosis) Nevus Comedonicus Connective Tissue Nevus Smooth Muscle Hamartoma Bibliography 652 Hyperpigmented Lesions 652 Hyperpigmented Lesions Disorders of Pigment Ephelides (Freckles) Lentigines Café-Au-Lait Spots Neurofibromatosis Type 1 (von Recklinghausen Disease) Incontinentia Pigmenti (Bloch-Sulzberger Disease) Postinflammatory Pigmentary Changes Bibliography 653 Hypopigmented Lesions 653 Hypopigmented Lesions Albinism Oculocutaneous Albinism with Melanosomal Abnormalities Melanoblast Migration Abnormalities Piebaldism Waardenburg Syndrome Tuberous Sclerosis Complex (TSC1, TSC2 Genes) Hypomelanosis of Ito Vitiligo Epidemiology and Etiology Clinical Manifestations Treatment Bibliography 654 Vesiculobullous Disorders 654 Vesiculobullous Disorders 654.1 Erythema Multiforme Etiology Clinical Manifestations Pathogenesis Pathology Differential Diagnosis Treatment Bibliography 654.2 Stevens-Johnson Syndrome Etiology Clinical Manifestations Pathogenesis Differential Diagnosis Treatment Bibliography 654.3 Toxic Epidermal Necrolysis Epidemiology and Etiology Clinical Manifestations Treatment Bibliography 654.4 Mechanobullous Disorders Epidermolysis Bullosa Epidermolysis Bullosa Simplex Junctional Epidermolysis Bullosa Dystrophic Epidermolysis Bullosa Kindler Syndrome Bibliography 654.5 Pemphigus Pemphigus Vulgaris Etiology/Pathogenesis Clinical Manifestations Pathology Differential Diagnosis Treatment Pemphigus Foliaceus Etiology/Pathogenesis Clinical Manifestations Pathology Differential Diagnosis Bullous Pemphigoid Etiology/Pathogenesis Clinical Manifestations Pathology Diagnosis and Differential Diagnoses Treatment Bibliography 654.6 Dermatitis Herpetiformis Etiology/Pathogenesis Clinical Manifestations Pathology Differential Diagnosis Treatment Bibliography 654.7 Linear Immunoglobulin A Dermatosis (Chronic Bullous Dermatosis of Childhood) Etiology/Pathogenesis Clinical Manifestations Pathology Differential Diagnosis Treatment Bibliography 655 Eczematous Disorders 655 Eczematous Disorders 655.1 Contact Dermatitis Irritant Contact Dermatitis Diaper Dermatitis Allergic Contact Dermatitis Bibliography 655.2 Nummular Eczema Bibliography 655.3 Pityriasis Alba Bibliography 655.4 Lichen Simplex Chronicus 655.5 Acute Palmoplantar Eczema (Dyshidrotic Eczema, Dyshidrosis, Pompholyx) 655.6 Seborrheic Dermatitis Etiology Clinical Manifestations Differential Diagnosis Treatment Bibliography 656 Photosensitivity 656 Photosensitivity Acute SUNBURN Reaction Photosensitive Reactions Porphyrias Colloid Milium Hydroa Vacciniforme Solar Urticaria Polymorphous Light Eruption Actinic Prurigo Cockayne Syndrome Xeroderma Pigmentosum Rothmund-Thomson Syndrome Bloom Syndrome Hartnup Disease Bibliography 657 Diseases of the Epidermis 657 Diseases of the Epidermis 657.1 Psoriasis Etiology/Pathogenesis Clinical Manifestations Differential Diagnosis Pathology Treatment Prognosis Bibliography 657.2 Pityriasis Lichenoides Etiology/Pathogenesis Clinical Manifestations Pathology Differential Diagnosis Treatment Bibliography 657.3 Keratosis Pilaris 657.4 Lichen Spinulosus 657.5 Pityriasis Rosea Etiology/Pathogenesis Clinical Manifestations Differential Diagnosis Treatment Bibliography 657.6 Pityriasis Rubra Pilaris Etiology/Pathogenesis Clinical Manifestations Differential Diagnosis Histology Treatment Bibliography 657.7 Darier Disease (Keratosis Follicularis) Etiology/Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Bibliography 657.8 Lichen Nitidus Etiology/Pathogenesis Clinical Manifestations Differential Diagnosis Histology Treatment Bibliography 657.9 Lichen Striatus Etiology/Pathogenesis Clinical Manifestations Differential Diagnosis Treatment Bibliography 657.10 Lichen Planus Etiology/Pathogenesis Clinical Manifestations Histology Treatment Bibliography 657.11 Porokeratosis Etiology/Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Bibliography 657.12 Gianotti-Crosti Syndrome (Papular Acrodermatitis) Etiology/Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Bibliography 657.13 Acanthosis Nigricans Etiology/Pathogenesis Clinical Manifestations Histology Treatment Bibliography 658 Disorders of Keratinization 658 Disorders of Keratinization Disorders of Cornification Collodion Baby Common Ichthyoses Ichthyosis Vulgaris Etiology/Pathogenesis Clinical Manifestations Treatment X-Linked Ichthyosis Etiology/Pathogenesis Clinical Manifestations Treatment Autosomal Recessive Congenital Ichthyoses (ARCI) Harlequin Ichthyosis Etiology/Pathogenesis Clinical Manifestations Treatment Lamellar Ichthyosis and Congenital Ichthyosiform Erythroderma (Nonbullous Congenital Ichthyosiform Erythroderma) Etiology/Pathogenesis Clinical Manifestations Treatment Keratinopathic Ichthyoses Epidermolytic Ichthyosis (Bullous Congenital Ichthyosiform Erythroderma; Epidermolytic Hyperkeratosis) Etiology/Pathogenesis Clinical Manifestations Histopathology Treatment Other Nonsyndromic Ichthyoses Erythrokeratoderma Variabilis Etiology/Pathogenesis Clinical Manifestations Treatment Symmetric Progressive Erythrokeratoderma Etiology/Pathogenesis Clinical Manifestations Treatment Syndromic Ichthyoses Sjögren-Larsson Syndrome Etiology/Pathogenesis Clinical Manifestations Treatment Netherton Syndrome Etiology/Pathogenesis Clinical Manifestations Treatment Refsum Syndrome Etiology/Pathogenesis Clinical Manifestations Treatment Chondrodysplasia Punctata Etiology/Pathogenesis Clinical Manifestations Other Syndromes with Ichthyosis Palmoplantar Keratodermas Diffuse Hyperkeratosis of Palms and Soles (Unna-Thost, Vorner) Mal De Meleda (SLURP-1 Gene) Vohwinkel Palmoplantar Keratoderma (Mutilating Keratoderma) Papillon-Lefèvre Syndrome (Cathepsin C Gene) Other Syndromes Treatment Bibliography 659 Diseases of the Dermis 659 Diseases of the Dermis Keloid Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Striae Cutis Distensae (Stretch Marks) Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Treatment Corticosteroid-Induced Atrophy Etiology and Pathogenesis Clinical Manifestations Histology Treatment Granuloma Annulare Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Histology Treatment Necrobiosis Lipoidica Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Lichen Sclerosus Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Histology Treatment Morphea Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Histology Treatment Scleredema (Scleredema Adultorum, Scleredema of Buschke) Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Histology Treatment Lipoid Proteinosis (Urbach-Wiethe Disease, Hyalinosis Cutis Et Mucosae) Etiology and Pathogenesis Clinical Manifestations Histology Treatment Macular Atrophy (Anetoderma) Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Cutis Laxa (Dermatomegaly, Generalized Elastolysis) Etiology and Pathogenesis Clinical Manifestations Histology Treatment Ehlers-Danlos Syndrome Classification Classic (COL5A1, COL5A2, COL1A1 Genes; Previously EDS Type I—Gravis, EDS Type II—MITIS) Hypermobile (COL3A1 Gene; Previously EDS Type III) Vascular (COL3A1 Gene; Previously EDS Type IV—Arterial Ecchymotic) Kyphoscoliosis (Lysyl Hydroxylase [PLOD Gene] Deficiency; Previously EDS Type VI) Arthrochalasia (COLA1A Gene, Type A; COL1A2 Gene, Type B; Previously EDS Types VIIA and B—Arthrochalasis Multiplex Congenita) Dermatosparaxis (Type 1 Collagen N-Peptidase; Previously EDS Type VIIC) Differential Diagnosis Pseudoxanthoma Elasticum Etiology and Pathogenesis Clinical Manifestations Pathology Treatment Elastosis Perforans Serpiginosa Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Reactive Perforating Collagenosis Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Xanthomas Fabry Disease Mucopolysaccharidoses Mastocytosis Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Prognosis Treatment Bibliography 660 Diseases of Subcutaneous Tissue 660 Diseases of Subcutaneous Tissue Corticosteroid-Induced Atrophy 660.1 Panniculitis and Erythema Nodosum Erythema Nodosum Etiology and Pathogenesis Clinical Manifestations Histology Treatment Post-Steroid Panniculitis Etiology and Pathogenesis Clinical Manifestations Histology Treatment Lupus Erythematosus Profundus (Lupus Erythematosus Panniculitis) Etiology and Pathogenesis Clinical Manifestations Histology Treatment α1-Antitrypsin Deficiency Etiology and Pathogenesis Clinical Manifestations Histology Treatment Pancreatic Panniculitis Etiology and Pathogenesis Clinical Manifestations Histology Treatment Subcutaneous Fat Necrosis Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Sclerema Neonatorum Etiology and Pathogenesis Clinical Manifestations Histology Treatment Cold Panniculitis Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Chilblains (Pernio) Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Factitial Panniculitis Etiology and Pathogenesis Clinical Manifestations Histology Treatment Bibliography 660.2 Lipodystrophy Partial Lipodystrophy Generalized Lipodystrophy Bibliography 661 Disorders of the Sweat Glands 661 Disorders of the Sweat Glands Anhidrosis Hyperhidrosis Etiology and Pathogenesis Clinical Manifestations Treatment Miliaria Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Bromhidrosis Hidradenitis Suppurativa Etiology and Pathogenesis Clinical Manifestations Histology Differential Diagnosis Treatment Fox-Fordyce Disease Etiology and Pathogenesis Clinical Manifestations Histology Treatment Bibliography 662 Disorders of Hair 662 Disorders of Hair Hypertrichosis Hypotrichosis and Alopecia Traumatic Alopecia (Traction Alopecia, Hair Pulling, Trichotillomania) Traction Alopecia Hair Pulling Trichotillomania Etiology and Pathogenesis. Clinical Manifestations. Differential Diagnosis. Histology. Treatment. Alopecia Areata Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Histology Treatment Acquired Diffuse Hair Loss Telogen Effluvium Toxic Alopecia (Anagen Effluvium) Congenital Diffuse Hair Loss Structural Defects of Hair Trichorrhexis Nodosa Acquired Trichorrhexis Nodosa Pili Torti Menkes Kinky Hair Syndrome (Trichopoliodystrophy) Monilethrix Trichothiodystrophy Trichorrhexis Invaginata (Bamboo Hair) Pili Annulati Woolly Hair Disease Uncombable Hair Syndrome (Spun-Glass Hair) Bibliography 663 Disorders of the Nails 663 Disorders of the Nails Abnormalities in Nail Shape or Size Changes in Nail Color Nail Separation Nail Changes Associated with Skin Disease Trachyonychia (20-Nail Dystrophy) Nail Infection Paronychial Inflammation Paronychial Tumors Bibliography 664 Disorders of the Mucous Membranes 664 Disorders of the Mucous Membranes Angular Cheilitis Aphthous Stomatitis (Canker Sores) Fordyce Spots Epstein Pearls (Gingival Cysts of the Newborn) Mucocele Fissured Tongue Geographic Tongue (Benign Migratory Glossitis) Black Hairy Tongue Oral Hairy Leukoplakia Acute Necrotizing Ulcerative Gingivitis (Vincent Stomatitis, Fusospirochetal Gingivitis, Trench Mouth) Noma Cowden Syndrome (Multiple Hamartoma Syndrome) Bibliography 665 Cutaneous Bacterial Infections 665 Cutaneous Bacterial Infections 665.1 Impetigo Etiology/Pathogenesis Clinical Manifestations Nonbullous Impetigo Bullous Impetigo Differential Diagnosis Complications Treatment Bibliography 665.2 Subcutaneous Tissue Infections Cellulitis Etiology Clinical Manifestations Diagnosis Treatment Necrotizing Fasciitis Etiology Clinical Manifestations Diagnosis Treatment Prognosis Bibliography 665.3 Staphylococcal Scalded Skin Syndrome (Ritter Disease) Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Histology Treatment Bibliography 665.4 Ecthyma Bibliography 665.5 Other Cutaneous Bacterial Infections Blastomycosis-Like Pyoderma (Pyoderma Vegetans) Blistering Distal Dactylitis Perianal Infectious Dermatitis Erysipelas Folliculitis Furuncles and Abscesses Etiology Clinical Manifestations Treatment Pitted Keratolysis Erythrasma Erysipeloid Tuberculosis of the Skin Bibliography 666 Cutaneous Fungal Infections 666 Cutaneous Fungal Infections Tinea Versicolor Etiology Clinical Manifestations Differential Diagnosis Treatment Dermatophytoses Etiology Epidemiology Tinea Capitis Clinical Manifestations Differential Diagnosis Treatment Tinea Corporis Clinical Manifestations Differential Diagnosis Treatment Tinea Cruris Clinical Manifestations Differential Diagnosis Treatment Tinea Pedis Clinical Manifestations Differential Diagnosis Treatment Tinea Unguium Clinical Manifestations Differential Diagnosis Tinea Nigra Palmaris Candidal Infections (Candidosis, Candidiasis, and Moniliasis) Oral Candidosis (Thrush) Vaginal Candidosis Congenital Cutaneous Candidosis Candidal Diaper Dermatitis Intertriginous Candidosis Perianal Candidosis Candidal Paronychia and Onychia Candidal Granuloma Bibliography 667 Cutaneous Viral Infections 667 Cutaneous Viral Infections Wart (Verruca) Etiology Clinical Manifestations Histology Differential Diagnosis Treatment Molluscum Contagiosum Etiology Clinical Manifestations Differential Diagnosis Histology Treatment Bibliography 668 Arthropod Bites and Infestations 668 Arthropod Bites and Infestations 668.1 Arthropod Bites Clinical Manifestations Treatment Bibliography 668.2 Scabies Etiology and Pathogenesis Clinical Manifestations Differential Diagnosis Treatment Norwegian Scabies Canine Scabies Other Types of Scabies Bibliography 668.3 Pediculosis Bibliography 668.4 Seabather’s Eruption 669 Acne 669 Acne Acne Vulgaris Pathogenesis Clinical Manifestations Treatment Diet Climate Cleansing Topical Therapy Retinoids. Benzoyl Peroxide. Topical Antibiotics. Azelaic Acid. Systemic Therapy Surgical Therapy Drug-Induced Acne Halogen Acne Chloracne Neonatal Acne Infantile Acne Tropical Acne Acne Conglobata Acne Fulminans (Acute Febrile Ulcerative Acne) Bibliography 670 Tumors of the Skin 670 Tumors of the Skin Epidermal Inclusion Cyst (Epidermoid Cyst) Milium Fibrofolliculomas Pilar Cyst (Trichilemmal Cyst) Pilomatricoma Trichoepithelioma Eruptive Vellus Hair Cysts Steatocystoma Multiplex Syringoma Infantile Digital Fibroma Dermatofibroma (Histiocytoma) Juvenile Xanthogranuloma Lipoma Basal Cell Carcinoma Nevoid Basal Cell Carcinoma Syndrome (Basal Cell Nevus Syndrome, Gorlin Syndrome) Mucosal Neuroma Syndrome (Multiple Endocrine Neoplasia Type IIB) Bibliography 671 Nutritional Dermatoses 671 Nutritional Dermatoses Acrodermatitis Enteropathica Essential Fatty Acid Deficiency Kwashiorkor Cystic Fibrosis Pellagra Scurvy (Vitamin C or Ascorbic Acid Deficiency) Vitamin a Deficiency Bibliography Bone and Joint Disorders 672 Growth and Development 672 Growth and Development In Utero Positioning Growth and Development Centers of Ossification Anatomic Locations: Descriptive Terms Important Growth and Developmental Milestones Growth Patterns in Upper and Lower Extremities Gait/Functional Maturation Bibliography 673 Evaluation of the Child 673 Evaluation of the Child History Physical Examination Inspection Palpation Range of Motion Gait Assessment Limping Back Pain Neurologic Evaluation Radiographic Assessment Plain Radiographs Nuclear Medicine Imaging Ultrasonography Magnetic Resonance Imaging Magnetic Resonance Angiography Computed Tomography Laboratory Studies Bibliography 674 The Foot and Toes 674 The Foot and Toes 674.1 Metatarsus Adductus Clinical Manifestations Radiographic Evaluation Treatment Bibliography 674.2 Calcaneovalgus Feet Clinical Manifestations Radiographic Evaluation Treatment Bibliography 674.3 Talipes Equinovarus (Clubfoot) Clinical Manifestations Radiographic Evaluation Treatment Bibliography 674.4 Congenital Vertical Talus Clinical Manifestations Radiographic Evaluation Treatment Bibliography 674.5 Hypermobile Pes Planus (Flexible Flatfeet) Clinical Manifestations Radiographic Evaluation Treatment Bibliography 674.6 Tarsal Coalition Clinical Manifestations Radiographic Evaluation Treatment Bibliography 674.7 Cavus Feet Treatment Bibliography 674.8 Osteochondroses/Apophysitis Bibliography 674.9 Puncture Wounds of the Foot Bibliography 674.10 Toe Deformities Juvenile Hallux Valgus (Bunion) Clinical Manifestations Radiographic Evaluation Treatment Curly Toes Overlapping Fifth Toe Polydactyly Syndactyly Hammer Toe Mallet Toe Claw Toe Annular Bands Macrodactyly Subungual Exostosis Ingrown Toenail Bibliography 674.11 Painful Foot 674.12 Shoes Bibliography 675 Torsional and Angular Deformities 675 Torsional and Angular Deformities 675.1 Normal Limb Development Bibliography 675.2 Evaluation Foot Progression Angle Femoral Anteversion Tibial Rotation Foot Shape and Position Bibliography 675.3 Torsional Deformities Internal Femoral Torsion Internal Tibial Torsion External Femoral Torsion External Tibial Torsion Metatarsus Adductus Bibliography 675.4 Coronal Plane Deformities Genu Varum Tibia Vara Genu Valgum (Knock-Knees) Bibliography 675.5 Congenital Angular Deformities of the Tibia and Fibula Posteromedial Tibial Bowing Anteromedial Tibial Bowing (Postaxial Hemimelia) Anterolateral Tibial Bowing Tibial Longitudinal Deficiency Bibliography 676 Leg-Length Discrepancy 676 Leg-Length Discrepancy Diagnosis and Clinical Findings Radiographic Evaluation Treatment Bibliography 677 The Knee 677 The Knee Normal Development of the Knee Anatomy and Range of Motion 677.1 Discoid Lateral Meniscus Clinical Manifestations and Diagnosis Treatment Bibliography 677.2 Popliteal Cysts (Baker Cysts) Clinical Manifestations and Diagnosis Treatment Bibliography 677.3 Osteochondritis Dissecans Clinical Manifestations and Diagnosis Treatment Bibliography 677.4 Osgood-Schlatter Disease and Sinding-Larsen-Johansson Syndrome Clinical Manifestations and Diagnosis Treatment Bibliography 677.5 Patellofemoral Pain Syndrome Clinical Manifestations and Diagnosis Treatment Bibliography 677.6 Patellofemoral Instability Clinical Manifestations and Diagnosis Treatment Bibliography 677.7 Anterior Cruciate Ligament Rupture Clinical Manifestations and Diagnosis Treatment Bibliography 678 The Hip 678 The Hip Growth and Development Vascular Supply 678.1 Developmental Dysplasia of the Hip Classification Etiology and Risk Factors Epidemiology Pathoanatomy Clinical Findings The Neonate The Infant The Walking Child Diagnostic Testing Ultrasonography Radiography Treatment Newborns and Infants Younger Than 6 Months Children 6 Months to 2 Years of Age Children Older Than 2 Years Complications Bibliography 678.2 Transient Monoarticular Synovitis (Toxic Synovitis) Etiology Clinical Manifestations Diagnosis Treatment Bibliography 678.3 Legg-Calvé-Perthes Disease Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Classification Natural History and Prognosis Treatment Bibliography 678.4 Slipped Capital Femoral Epiphysis Classification Etiology and Pathogenesis Epidemiology Clinical Manifestations Diagnostic Studies Treatment Complications Bibliography 679 The Spine 679 The Spine Normal Spinal Curvatures 679.1 Idiopathic Scoliosis Definition Etiology Epidemiology Classification of Idiopathic Scoliosis Clinical Presentation of Idiopathic Scoliosis Physical Examination of Idiopathic Scoliosis Radiographic Evaluation of Idiopathic Scoliosis Natural History of Idiopathic Scoliosis Treatment of Idiopathic Scoliosis Bibliography 679.2 Congenital Scoliosis Definition Etiology Associated Conditions Classification of Congenital Scoliosis Natural History of Congenital Scoliosis Treatment of Congenital Scoliosis Thoracic Insufficiency Syndrome Bibliography 679.3 Neuromuscular Scoliosis, Genetic Syndromes, and Compensatory Scoliosis Neuromuscular Scoliosis Syndromes and Genetic Disorders Compensatory Scoliosis Bibliography 679.4 Kyphosis (Round-Back) Flexible Kyphosis (Postural Kyphosis) Structural Kyphosis Scheuermann Disease Physical Exam and Clinical Manifestations Radiographic Evaluation Natural History Treatment Congenital Kyphosis Bibliography 679.5 Back Pain in Children Clinical Evaluation Medical Decision Making Radiographic and Laboratory Evaluation Bibliography 679.6 Spondylolysis and Spondylolisthesis Clinical Manifestations Physical Exam Radiographic Evaluation Treatment Bibliography 679.7 Spine Infection Clinical Manifestations Radiographic Evaluation Treatment Bibliography 679.8 Intervertebral Disc Herniation/Slipped Vertebral Apophysis Etiology Clinical Manifestations Radiographic Evaluation Treatment Bibliography 679.9 Tumors 680 The Neck 680 The Neck 680.1 Torticollis Congenital Muscular Torticollis Other Causes of Torticollis Bibliography 680.2 Klippel-Feil Syndrome Etiology and Classification Clinical Presentation Physical Examination Radiographic Investigation Treatment Bibliography 680.3 Cervical Anomalies and Instabilities Os Odontoideum Down Syndrome 22q11.2 Deletion Syndrome Bibliography 681 The Upper Limb 681 The Upper Limb Shoulder Brachial Plexus Birth Palsy Treatment Sprengel’s Deformity Treatment Elbow Panner Disease Treatment Radial Longitudinal Deficiency Treatment Nursemaid Elbow Treatment Wrist Madelung Deformity Treatment Ganglion Treatment Hand Camptodactyly Treatment Clinodactyly Treatment Polydactyly Treatment Thumb Hypoplasia Treatment Syndactyly Treatment Fingertip Injuries Trigger Thumb and Fingers Treatment Bibliography 682 Arthrogryposis 682 Arthrogryposis Etiology Neurologic Abnormalities Muscular Abnormalities Limited Intrauterine Spacing Connective Tissue Abnormalities Maternal Diseases Intrauterine Vascular Compromise Classification Management of Orthopedic Problems of Arthrogryposis Foot Problems Knee Problems Hip Problems Ambulation Upper-Extremity Problems Surgery of the Upper Extremity Shoulder Elbow Wrist Scoliosis Surgical Staging Bibliography 683 Common Fractures 683 Common Fractures 683.1 Unique Characteristics of Pediatric Fractures Fracture Remodeling Overgrowth Progressive Deformity Rapid Healing Bibliography 683.2 Pediatric Fracture Patterns Plastic Deformation Buckle or Torus Fracture Greenstick Fracture Complete Fractures Epiphyseal Fractures Child Abuse Bibliography 683.3 Upper Extremity Fractures Phalangeal Fractures Forearm Fractures Distal Humeral Fractures Proximal Humerus Fractures Clavicular Fractures Bibliography 683.4 Fractures of Lower Extremity Hip Fracture Toddler Fracture Proximal Tibia Fractures Tibia and Fibula Shaft Fractures Femoral Shaft Fractures Triplane and Tillaux Fractures Metatarsal Fractures Toe Phalangeal Fractures Bibliography 683.5 Operative Treatment Surgical Techniques Bibliography 683.6 Complications of Fractures in Children 684 Osteomyelitis 684 Osteomyelitis Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Radiographic Evaluation Plain Radiographs Computed Tomography and Magnetic Resonance Imaging Radionuclide Studies Differential Diagnosis Treatment Antibiotic Therapy Surgical Therapy Physical Therapy Prognosis Bibliography 685 Septic Arthritis 685 Septic Arthritis Etiology Epidemiology Pathogenesis Clinical Manifestations Diagnosis Radiographic Evaluation Plain Radiographs Ultrasonography Magnetic Resonance Imaging and Computed Tomography Radionuclide Imaging Differential Diagnosis Treatment Antibiotic Therapy Surgical Therapy Prognosis Bibliography 686 Epidemiology and Prevention of Injuries 686 Epidemiology and Prevention of Injuries Preparticipation Sports Examination History and Physical Examination Bibliography 687 Management of Musculoskeletal Injury 687 Management of Musculoskeletal Injury Mechanism of Injury Acute Injuries Overuse Injuries Initial Evaluation of the Injured Extremity Transition From Immediate Management to Return to Play Phase 1 Phase 2 Phase 3 Phase 4 Relative Rest and Return-to-Play Guidelines Differential Diagnoses of Musculoskeletal Pain Bibliography 687.1 Growth Plate Injuries Bibliography 687.2 Shoulder Injuries Clavicle Fractures Acromioclavicular Separation Anterior Dislocation Rotator Cuff Injury Bibliography 687.3 Elbow Injuries Acute Injuries Chronic Injuries Bibliography 687.4 Low Back Injuries Spondylolysis, Spondylolisthesis, and Facet Syndrome Spondylolysis Spondylolisthesis and Facet Syndrome Lumbar Disk Herniation, Strain, and Contusion Sacroiliitis Other Causes Bibliography 687.5 Hip and Pelvis Injuries Bibliography 687.6 Knee Injuries Initial Treatment of Acute Knee Injuries Chronic Injuries Patellofemoral Stress Syndrome Osgood-Schlatter Disease Other Chronic Injuries Bibliography 687.7 Lower Leg Pain: Shin Splints, Stress Fractures, and Chronic Compartment Syndrome Bibliography 687.8 Ankle Injuries Examination and Injury Grading Scale Radiographs Initial Treatment of Ankle Sprains Rehabilitation Bibliography 687.9 Foot Injuries Bibliography 688 Sports-Related Traumatic Brain Injury (Concussion) 688 Sports-Related Traumatic Brain Injury (Concussion) Epidemiology Pathophysiology Assessment of the Injured Player Management and Treatment Initial Phase Returning to Sport Prevention Bibliography 689 Cervical Spinal Injuries 689 Cervical Spinal Injuries Soft-Tissue Injury Spear Tackler’s Spine Cervical Fractures Stingers (Burners) Transient Quadriparesis Congenital Spinal Stenosis Spinal Cord Injury Bibliography 690 Heat Injuries 690 Heat Injuries Bibliography 691 Female Athletes: 691 Female Athletes: Bibliography 692 Performance-Enhancing Aids 692 Performance-Enhancing Aids Bibliography 693 Specific Sports and Associated Injuries 693 Specific Sports and Associated Injuries Gymnastics Swimming Baseball Dance Wrestling Football Ice Hockey Basketball and Volleyball Running Soccer Tennis Skiing and Snowboarding Cheerleading Skateboarding Bibliography 694 General Considerations 694 General Considerations Clinical Manifestations Growth Non–Growth-Related Manifestations Family and Reproductive History Radiographic Features Diagnosis Molecular Genetics Pathophysiology Treatment Bibliography 695 Disorders Involving Cartilage Matrix Proteins 695 Disorders Involving Cartilage Matrix Proteins Spondyloepiphyseal Dysplasias Lethal Spondyloepiphyseal Dysplasias Spondyloepiphyseal Dysplasia Congenita Kniest Dysplasia Late-Onset Spondyloepiphyseal Dysplasia Aggrecan-Related Spondyloepiphyseal Dysplasias Stickler Syndrome/Dysplasia (Hereditary Osteoarthroophthalmopathy) Schmid Metaphyseal Dysplasia Pseudoachondroplasia and Multiple Epiphyseal Dysplasia Bibliography 696 Disorders Involving Transmembrane Receptors 696 Disorders Involving Transmembrane Receptors Achondroplasia Group Thanatophoric Dysplasia Achondroplasia Diagnosis Clinical Manifestations Genetics Hypochondroplasia Jansen Metaphyseal Dysplasia Bibliography 697 Disorders Involving Ion Transporters 697 Disorders Involving Ion Transporters Diastrophic Dysplasia Achondrogenesis Type 1B and Atelosteogenesis Type II Bibliography 698 Disorders Involving Transcription Factors 698 Disorders Involving Transcription Factors Campomelic Dysplasia Cleidocranial Dysplasia Nail-Patella Syndrome Bibliography 699 Disorders Involving Defective Bone Resorption 699 Disorders Involving Defective Bone Resorption Osteopetrosis Clinical Manifestations Treatment Pyknodysostosis Bibliography 700 Disorders for Which Defects Are Poorly Understood or Unknown 700 Disorders for Which Defects Are Poorly Understood or Unknown Ellis–Van Creveld Syndrome Asphyxiating Thoracic Dystrophy (see also Chapter 417.3) Short-Rib Polydactyly Syndromes Cartilage-Hair Hypoplasia Metatropic Dysplasia Spondylometaphyseal Dysplasia, Kozlowski Type Disorders Involving Filamins Juvenile Osteochondroses Caffey Disease (Infantile Cortical Hyperostosis) Fibrodysplasia Ossificans Progressive Bibliography 701 Osteogenesis Imperfecta 701 Osteogenesis Imperfecta Etiology Epidemiology Pathology Pathogenesis Clinical Manifestations Osteogenesis Imperfecta Type I (Mild) Osteogenesis Imperfecta Type II (Perinatal Lethal) Osteogenesis Imperfecta Type III (Progressive Deforming) Osteogenesis Imperfecta Type IV (Moderately Severe) Osteogenesis Imperfecta Type V (Hyperplastic Callus) and Type VI Hyperosteoidosis (Mineralization Defect) Osteogenesis Imperfecta Types VII, VIII, and IX (Autosomal Recessive) Osteogenesis Imperfecta Types X and XI (Autosomal Recessive) High Bone Mass Osteogenesis Imperfecta (Cleavage of the Procollagen C-Propeptide) Other Genes for Osteogenesis Imperfecta Laboratory Findings Complications Treatment Prognosis Genetic Counseling Bibliography 702 Marfan Syndrome 702 Marfan Syndrome Epidemiology Pathogenesis Clinical Manifestations Skeletal System Cardiovascular System Ocular System Other Systems Diagnosis Differential Diagnosis Aortic Aneurysm Syndromes Ectopia Lentis Syndromes Syndromes with Systemic Manifestations of Marfan Syndrome Laboratory Findings Management Current Therapies Activity Restrictions Aortic Surgery Pregnancy Endocarditis Prophylaxis Current Pharmacologic Approaches Emerging Therapeutic Strategies Angiotensin II Receptor Type 1 Blockers Prognosis Genetic Counseling Bibliography 703 Bone Structure, Growth, and Hormonal Regulation 703 Bone Structure, Growth, and Hormonal Regulation Bibliography 704 Primary Chondrodystrophy (Metaphyseal Dysplasia) 704 Primary Chondrodystrophy (Metaphyseal Dysplasia) Bibliography 705 Hypophosphatasia 705 Hypophosphatasia Bibliography 706 Hyperphosphatasia 706 Hyperphosphatasia Bibliography 707 Osteoporosis 707 Osteoporosis Bibliography Rehabilitation Medicine 708 Principles of Rehabilitation Medicine 708 Principles of Rehabilitation Medicine Epidemiology Approach Scope of Practice Prevention of Muscle Weakness Other Assist Devices Bibliography 709 Evaluation of the Child for Rehabilitative Services 709 Evaluation of the Child for Rehabilitative Services Child Characteristics Family Characteristics The Physical Environment The Previously Healthy Child 710 Severe Traumatic Brain Injury 710 Severe Traumatic Brain Injury Etiology Pathophysiology Acute Rehabilitation Outcomes Associated with Severe Traumatic Brain Injury Pediatric Traumatic Brain Injury and Plasticity Bibliography 711 Spinal Cord Injury and Autonomic Crisis Management 711 Spinal Cord Injury and Autonomic Crisis Management Evaluation Clinical Manifestations Prognosis Bibliography 712 Spasticity 712 Spasticity Oral Medications GABAergic Medications α2-Adrenergic Agents Peripherally Acting Calcium Blockers Surgical Management Bibliography 713 Birth Brachial Plexus Palsy 713 Birth Brachial Plexus Palsy Physical Examination Laboratory Examination Treatment Bibliography 714 Traumatic and Sports-Related Injuries of the Lower Extremity 714 Traumatic and Sports-Related Injuries of the Lower Extremity 715 Meningomyelocele (Spina Bifida) 715 Meningomyelocele (Spina Bifida) Etiology Prevention Prenatal Screening Clinical Implications Adolescence and Transition Into Adulthood Bibliography 716 Ambulation Assistance 716 Ambulation Assistance Orthoses Prostheses Assistive Devices Wheelchairs Bibliography 717 Health and Wellness for Children with Disabilities 717 Health and Wellness for Children with Disabilities Health Promotion Definitions and Background for Disability Anticipatory Guidance, Counseling, and Preventive Care Physical Activity and Exercise Nutrition and Obesity Emotional Health and Leisure Activities Dental Care Role of Healthcare Providers Bibliography Environmental Health Hazards 718 Biologic Effects of Radiation on Children 718 Biologic Effects of Radiation on Children Basic Principles Biologic Effects of Radiation Decreasing Unnecessary Diagnostic Radiation in Children While Still Obtaining Diagnostic Images Reducing Radiation from the CT Examination Radiation Therapy—Acute and Late Effects Whole-Body Irradiation Uncontrolled Large- or Small-Scale Exposure to Radiation Clinical Manifestations Treatment Localized Irradiation Clinical Manifestations Treatment Internal Contamination Epidemiology Clinical Manifestations Treatment External Contamination Bibliography 719 Chemical Pollutants 719 Chemical Pollutants Synthetic Chemicals and Human Health Children’s Unique Susceptibility to Synthetic Chemicals Safety Testing of Synthetic Chemicals Synthetic Chemicals and Disease in Children Chemical Pollutants of Major Concern Air Pollutants Oil Spill Hazards Lead Mercury Asbestos Second-Hand Tobacco Smoke Pesticides Polychlorinated Biphenyls, DDT, Dioxins, Brominated Flame Retardants, and Other Halogenated Hydrocarbons Endocrine Disruptors Environmental Carcinogens Routes of Exposure Transplacental. Water. Air. Food. Work Clothes. Schools. Child Labor. The Physician’s Role Bibliography 720 Heavy Metal Intoxication 720 Heavy Metal Intoxication Arsenic Epidemiology Pharmacokinetics Pathophysiology Clinical Manifestations Laboratory Findings Mercury Epidemiology Pharmacokinetics Pathophysiology Clinical Manifestations Laboratory Findings Treatment of Arsenic and Mercury Intoxication Bibliography 721 Lead Poisoning 721 Lead Poisoning Public Health History Sources of Exposure Metabolism Clinical Effects Clinical Symptoms Gastrointestinal Tract and Central Nervous System Diagnosis Screening Treatment Bibliography 722 Nonbacterial Food Poisoning 722 Nonbacterial Food Poisoning 722.1 Mushroom Poisoning Gastrointestinal: Delayed Onset Amanita Poisoning Treatment Monomethylhydrazine Intoxication Treatment Renal: Delayed Onset Orellanine Poisoning Treatment Autonomic Nervous System: Rapid Onset Muscarine Poisoning Treatment Coprine Ingestion Central Nervous System: Rapid Onset Isoxazole Intoxication Indole Intoxication Gastrointestinal: Rapid Onset Bibliography 722.2 Solanine Poisoning Bibliography 722.3 Seafood Poisoning Ciguatera Fish Poisoning Treatment Scombroid (Pseudoallergic) Fish Poisoning Treatment Paralytic Shellfish Poisoning Treatment Neurotoxic Shellfish Poisoning Treatment Diarrhetic Shellfish Poisoning Amnesic Shellfish Poisoning Azaspiracid Poisoning Bibliography Ciguatera Fish Poisoning Scombroid Fish Poisoning Shellfish Poisoning Fish Poisoning 722.4 Melamine Poisoning Bibliography 723 Biologic and Chemical Terrorism 723 Biologic and Chemical Terrorism Etiology Epidemiology and Pediatric-Specific Concerns Clinical Manifestations Sudden-Onset Neuromuscular Syndrome: Nerve Agents Delayed-Onset Neuromuscular Syndrome: Botulism Sudden-Onset Respiratory Syndrome: Chlorine, Phosgene, and Cyanide Delayed-Onset Respiratory Syndrome: Anthrax, Plague, Tularemia, and Ricin Sudden-Onset Dermatologic Syndrome: Mustard and Lewisite Delayed-Onset Dermatologic Syndrome: Smallpox Diagnosis Prevention Treatment Bibliography 724 Animal and Human Bites 724 Animal and Human Bites Epidemiology Clinical Manifestations Diagnosis Complications Treatment Prevention Bibliography 724.1 Rat Bite Fever Etiology Clinical Course Diagnosis Treatment Bibliography 724.2 Monkeypox Etiology Clinical Course Treatment Bibliography 725 Envenomations 725 Envenomations General Approach to the Envenomated Child General Management Antivenom Administration General Wound Care Snake Bites Venoms and Effects Management Disposition Spider Bites Neurotoxic Spiders Venoms and Effects Management Disposition Necrotizing Spiders Venoms and Effects Management Disposition Scorpion Stings Venoms and Effects Management Disposition Hymenoptera Stings Venoms and Effects Management Disposition Marine Envenomation Venoms and Effects Management Disposition Bibliography Laboratory Testing in Infants and Children 726 Laboratory Testing in Infants and Children Accuracy and Precision of Laboratory Tests Sensitivity, Accuracy, and Analytic Testing Predictive Value of Laboratory Tests Neonatal Screening Tests Testing in Refining a Differential Diagnosis Serologic Testing Laboratory Screening Acknowledgments Bibliography Reference Intervals for Laboratory Tests and Procedures Reference Intervals for Laboratory Tests and Procedures Bibliography (for Table 727-5)
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