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دانلود کتاب Dermatology: 2-Volume Set
دانلود کتاب پوست: ست 2 جلدی
مشخصات کتاب
Dermatology: 2-Volume Set
ویرایش: 5 نویسندگان: Jean L. Bolognia MD, Julie V. Schaffer MD, Lorenzo Cerroni MD سری: ISBN (شابک) : 0702082252, 9780702082252 ناشر: Elsevier سال نشر: 2024 تعداد صفحات: 3205 زبان: English فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود) حجم فایل: 241 مگابایت
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0- Basic Principles of Dermatology 0 Basic Principles of Dermatology INTRODUCTION TO CLINICAL DERMATOLOGY Etiologic Premises Inflammatory versus neoplastic Morphology Palpation and appreciation of textural changes Color Variation in skin color within the human population Configuration and Distribution Configuration Distribution Augmented Examination – Wood’s Lamp and Dermoscopy Temporal Course THE ROLE OF DERMATOPATHOLOGY IN CLINICOPATHOLOGIC CORRELATION The Skin Biopsy Site selection Biopsy techniques Handling of the specimen after biopsy Classification of Inflammatory Skin Diseases by Pattern Analysis Ten major patterns defined Perivascular dermatitis Interface dermatitis Spongiotic dermatitis Psoriasiform dermatitis Vesiculobullous and pustular dermatoses Intraepidermal vesiculation (see Fig. 0.14E) Subepidermal vesiculation (see Fig. 0.14F) Vasculitis/pseudovasculitis Nodular and diffuse dermatitis Folliculitis/perifolliculitis Fibrosing/sclerosing conditions Panniculitis Invisible dermatoses Deposition of Materials within the Skin Histologic Stains Immunohistochemical Testing INTRODUCTION TO THE USE OF DERMOSCOPY (DERMATOSCOPY) INTRODUCTION TO CONFOCAL MICROSCOPY RCM Principals, Technology, and Limitations RCM Applications Cutaneous tumors Inflammatory skin diseases INTRODUCTION TO ARTIFICIAL INTELLIGENCE Training and Testing AI Models Image-Based Tasks Solved with Neural Networks Shortcomings and Limitations of AI Possible Clinical Implementations of AI Future of AI CONCLUSION REFERENCES 1- Anatomy and Pathophysiology 1 Anatomy and Pathophysiology INTRODUCTION THE BASIC STRUCTURE OF SKIN Epidermis Dermis Dermal–Epidermal Interface STRUCTURE AND FUNCTION OF THE SKIN AS IT RELATES TO DISEASE Protecting the DNA Immunologic Protection Infection Autoimmunity Immune surveillance and cancer Maintaining a Barrier Protection against dehydration and infection Protection against toxic chemicals Protection against UV radiation Repairing Injury Delayed wound healing Keloids Xeroderma pigmentosum Circulation: Providing Thermoregulation, Nutrition, Immunoregulation Embolic occlusion of arteries Vasculitis Occlusive vasculopathy Venous insufficiency Lymphatic blockage Communicating with External and Internal Environments Communication via nerves Itch and pain Excessive sweating Loss of sensation Communication via hormones and cytokines Hormones Cytokines Communication via cells Regulating Temperature Effects of excessive heat Effects of excessive cold Interpersonal Communication: Beauty, Attention, and Self-Identity Failures to present an attractive appearance Pigmentation disorders Inappropriate hair distribution Undesirable fat distribution An Important Corollary, with an Eye to the Future Acknowledgment REFERENCES 2- Skin Development and Maintenance 2 Skin Development and Maintenance INTRODUCTION EMBRYONIC ORIGIN OF THE SKIN EPIDERMAL DEVELOPMENT Clinical Relevance DEVELOPMENT OF SPECIALIZED CELLS WITHIN THE EPIDERMIS Clinical Relevance DEVELOPMENT OF THE DERMIS AND SUBCUTIS Clinical Relevance DEVELOPMENT OF THE DERMAL–EPIDERMAL JUNCTION Clinical Relevance DEVELOPMENT OF SKIN APPENDAGES (ADNEXAE) Hair Follicle Development Nail Development Eccrine and Apocrine Sweat Gland Development Clinical Relevance SKIN STEM CELLS Epidermal Stem Cells Hair Follicle Stem Cells Stem Cell Plasticity Stem Cell-Based Therapy for Genetic Skin Disease PRENATAL DIAGNOSIS OF GENODERMATOSES SIGNIFICANCE OF SKIN DEVELOPMENT IN POSTNATAL LIFE REFERENCES 3- Molecular Biology 3 Molecular Biology INTRODUCTION EXPERIMENTAL TECHNIQUES Tissue Processing The Foundations of Molecular Techniques for Analyzing DNA, RNA, and Protein Measuring Cells Within Tissues Measuring the Transcriptome and Proteome Mouse Models of Skin Disease Gene-Based Therapy for Skin Diseases CONCLUSIONS Copyright notice REFERENCES 4- Immunology 4 Immunology INTRODUCTION INNATE IMMUNE RESPONSE Complement Toll-Like Receptors Inflammasomes The Skin Microbiota and Antimicrobial Peptides Cytokines Monocytes and Macrophages Neutrophils Eosinophils Basophils and Mast Cells Innate Lymphoid Cells Natural Killer Cells ADAPTIVE IMMUNE RESPONSE Antigen-Presenting Cells Langerhans cells Other dendritic cells Antigen presentation Antigen-presenting cells: activation and migration Antigen presentation to T cells T Cells T cell development T cell receptor T cell receptor diversity T cell receptor signaling Costimulatory signals Memory cells Conventional T cells T helper cells Cytotoxic T cells Regulatory T cells Unconventional T cells Natural killer T cells γ/δ T cells Dendritic epidermal γ/δ T cells Mucosal associated invariant T cells Lymphocyte recruitment B Cells Immunoglobulins Immunoglobulin M Immunoglobulin G Immunoglobulin A Immunoglobulin E Immunoglobulin D B cell activation Allergic Contact Hypersensitivity Induction of CHS Elicitation of CHS REFERENCES 5- Cutaneous Neurophysiology 5 Cutaneous Neurophysiology INTRODUCTION PRURITUS PATHWAYS Central Pathways to Higher Nervous System Centers Pruritus Receptor Units MEDIATORS OF PRURITUS Histamine Gastrin-Releasing Peptide B-Type Natriuretic Peptide Proteases Opioid Peptides Substance P Neurotrophins Prostanoids and Leukotrienes Mediators That Activate Transient Receptor Potential Receptors Other Peripheral Mediators of Itch Other neurotransmitters Other mediators with potential roles in itch Immune Cells as Itch Mediators and Modulators CHRONIC ITCH Peripheral Sensitization in Chronic Itch Central Sensitization in Chronic Itch Itch Related to Impaired Skin Barrier Function Itch in Older Adults Cholestatic Pruritus TREATMENTS FOR PRURITUS FUTURE DIRECTIONS 6- Pruritus and Dysesthesia 6 Pruritus and Dysesthesia INTRODUCTION EPIDEMIOLOGY EVALUATION OF THE PATIENT History Examination Laboratory Investigation and Radiographic Imaging PRURITUS IN DERMATOLOGIC DISEASE Inflammatory Dermatoses Urticaria Atopic dermatitis Psoriasis Infestations Scabies Pediculosis (lice) Cutaneous T Cell Lymphoma (CTCL) DERMATOSES INDUCED BY PRURITUS-ASSOCIATED SCRATCHING OR RUBBING Prurigo Nodularis Lichen Simplex Chronicus PRURITUS IN SPECIFIC LOCATIONS Scalp Pruritus Anogenital Pruritus Pruritus ani Pruritus vulvae and scroti PRURITUS VARIANTS Aquagenic Pruritus Pruritus in Scars Post-Thermal Burn Pruritus Fiberglass Dermatitis PRURITUS IN SYSTEMIC DISEASE Chronic Kidney Disease-Associated Pruritus (Renal Pruritus) Cholestatic Pruritus Hematologic Pruritus Iron deficiency Polycythemia vera Pruritus and Malignancy Hodgkin lymphoma Non-Hodgkin lymphoma Leukemia Endocrine Pruritus Thyroid disease Diabetes mellitus Pruritus in HIV Infection PRURITUS IN PREGNANCY PHARMACOLOGIC PRURITUS PSYCHOGENIC PRURITUS NEUROPATHIC ETIOLOGIES OF PRURITUS AND DYSESTHESIA Sensory (Mono)Neuropathies with Pruritus and Dysesthesia Notalgia paresthetica Brachioradial pruritus Meralgia paresthetica Cheiralgia paresthetica Digitalgia paresthetica Regional Dysesthesias with Burning or Pain Burning mouth syndrome Burning scalp syndrome Red ear syndrome Dysesthetic anogenital pain syndromes Trigeminal neuralgia and trigeminal trophic syndrome Complex regional pain syndrome (reflex sympathetic dystrophy) Congenital Insensitivity to Pain and Related Conditions TREATMENT General Measures Topical Treatment Systemic Treatment Physical Treatment Modalities Psychological Approaches REFERENCES 7- Psychocutaneous Diseases 7 Psychocutaneous Diseases INTRODUCTION OVERVIEW PRIMARY PSYCHODERMATOLOGIC DISORDERS Delusional Infestation Introduction Epidemiology Clinical features Differential diagnosis Treatment General Features of Obsessive–Compulsive and Related Disorders Body Dysmorphic Disorder Introduction Epidemiology Clinical features Treatment Trichotillomania Introduction Epidemiology Clinical features Diagnosis and pathology Differential diagnosis Treatment Excoriation Disorder Introduction Epidemiology Clinical features Differential diagnosis Treatment Acne Excoriée Clinical features Treatment Dermatitis Artefacta Introduction Epidemiology Clinical features Pathology Differential diagnosis Treatment Other Somatic Symptom and Related Disorders Nonsuicidal Self-Injury Epidemiology and clinical features Treatment Excessive Tanning Behavior SECONDARY PSYCHODERMATOLOGIC DISORDERS Adjustment Disorder REFERENCES 8- Psoriasis 8 Psoriasis INTRODUCTION HISTORY EPIDEMIOLOGY AND GENETICS Genetic Factors HLA studies Genome-wide association studies Functional genomic studies PATHOGENESIS Immunopathogenesis Role of T cells and dendritic cells Cytokines, chemokines, and transcription factors Innate immunity and role of keratinocytes Disease memory Triggering Factors External triggering factors Systemic triggering factors Infections HIV Endocrine factors Psychogenic stress Drugs Alcohol consumption, smoking, and obesity CLINICAL FEATURES Chronic Plaque Psoriasis Guttate Psoriasis Erythrodermic Psoriasis CARD14-associated papulosquamous eruption Pustular Disease Generalized pustular psoriasis Pustulosis of the palms and soles Acrodermatitis continua of Hallopeau Special Locations Scalp psoriasis Flexural psoriasis Oral mucosa Nail psoriasis Psoriatic Arthritis Disorders Related to Psoriasis Inflammatory linear verrucous epidermal nevus (ILVEN) Reactive arthritis Sneddon–Wilkinson disease (subcorneal pustular dermatosis) Associations Between Psoriasis and Other Diseases Associations with skin diseases Infections Cancer Association with internal diseases (including comorbidities) DIFFERENTIAL DIAGNOSIS PATHOLOGY Papulosquamous Lesions Initial lesion Active lesion Stable lesion Pustular Psoriasis TREATMENT Topical Treatments Corticosteroids Vitamin D3 analogues Anthralin Topical retinoids Additional topical treatments Recently approved topical treatments Photo(chemo)therapy and Systemic Medications Photo(chemo)therapy Methotrexate Cyclosporine Systemic retinoids JAK and TYK2 inhibitors Apremilast and other systemic therapies Targeted immunomodulators (“biologic” therapies) Therapeutic Management General considerations Management with topical agents Management with photo(chemo)therapy and classic systemic medications Management with targeted immunomodulators (“biologic” therapies) Combining treatments Beneficial combinations Contraindicated combinations and combinations with restricted use Management of childhood psoriasis Management of psoriasis in patients with comorbidities Treatment of elderly patients REFERENCES e-References 9- Other Papulosquamous Disorders 9 Other Papulosquamous Disorders SMALL PLAQUE PARAPSORIASIS Introduction and History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment LARGE PLAQUE PARAPSORIASIS PITYRIASIS LICHENOIDES Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment PITYRIASIS RUBRA PILARIS History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment PITYRIASIS ROSEA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment PITYRIASIS ROTUNDA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment GRANULAR PARAKERATOSIS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment REFERENCES 10- Erythroderma 10 Erythroderma Introduction Historical Perspective Epidemiology Pathogenesis Clinical Features Cutaneous Manifestations Systemic Manifestations Specific Findings of the Underlying Disease Psoriasis Atopic dermatitis Drug reactions Idiopathic erythroderma Cutaneous T cell lymphoma (Sézary syndrome and erythrodermic mycosis fungoides) Pityriasis rubra pilaris Papuloerythroderma of Ofuji Paraneoplastic erythroderma Bullous dermatoses Ichthyoses Staphylococcal scalded skin syndrome Omenn syndrome Pathology Differential Diagnosis Treatment References 11- Lichen Planus and Lichenoid Dermatoses 11 Lichen Planus and Lichenoid Dermatoses Lichen Planus Introduction History Epidemiology Pathogenesis Target antigens Hepatitis C virus Other viruses Vaccines Bacteria Contact allergens Drugs Autoantigens, including tumor antigens Effector cells The innate immune system, regulatory T cells (Tregs), and Th17 cells Effector T cells\' access to the epidermis Sweating disturbance Clinical Features Actinic LP Acute (exanthematous) LP Annular LP Atrophic LP Bullous LP and LP pemphigoides Hypertrophic LP Inverse LP LP pigmentosus Lichen planopilaris Linear LP Discoid lupus erythematosus/lichen planus overlap syndrome Nail LP Oral LP Ulcerative LP Vulvovaginal LP Lichenoid drug eruption (drug-induced LP) Lichenoid granulomatous dermatitis Immune checkpoint inhibitor-induced lichenoid eruption Pathology Differential Diagnosis Treatment Systemic therapies Phototherapy Lichen Striatus Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Lichen Nitidus Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Erythema Dyschromicum Perstans Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Keratosis Lichenoides Chronica Actinic Lichen Nitidus (Summertime Actinic Lichenoid Eruption) Annular Lichenoid Dermatitis (of Youth) References 12- Atopic Dermatitis 12 Atopic Dermatitis INTRODUCTION HISTORY AND DEFINITIONS EPIDEMIOLOGY PATHOGENESIS Genetic Factors Epidermal Barrier Dysfunction Filaggrin and other structural proteins Stratum corneum lipids Proteases and protease inhibitors Immune Dysregulation Thymic stromal lymphopoietin (TSLP) IL-4 and IL-13 Other cytokines Innate lymphoid cells The Cutaneous Microbiome CLINICAL FEATURES Age-Related Cutaneous Findings Regional Variants of Atopic Dermatitis Associated Cutaneous Features Pruritus Atopic stigmata Pityriasis alba Infectious Complications Impact on Quality of Life Associated Extracutaneous Disorders Ocular manifestations Psychiatric disease and psychosocial burden Cardiovascular complications DIAGNOSTIC CRITERIA AND SEVERITY SCORES PATHOLOGY DIFFERENTIAL DIAGNOSIS TREATMENT General Approach Educational interventions Bathing Moisturizers Topical Anti-Inflammatory Therapy Topical corticosteroids Topical calcineurin inhibitors Crisaborole Topical JAK inhibitors Wet wrap therapy Phototherapy Systemic Anti-Inflammatory Therapy Interleukin-4/-13 receptor inhibitors Interleukin-13 inhibitors Oral JAK inhibitors (see Ch. 128) Conventional immunosuppressive agents (for details see Ch. 130) Adjunctive Therapy Antimicrobials and antiseptics Antihistamines Melatonin Omalizumab Systemic immunotherapy Dietary manipulation and supplements Complementary Therapies Management of Coexisting Disease Food allergies Aeroallergen reactivity Allergic contact dermatitis (ACD) Prevention Probiotics and prebiotics Emollients REFERENCES 13- Other Eczematous Eruptions 13 Other Eczematous Eruptions Seborrheic Dermatitis Introduction History Epidemiology Pathogenesis Malassezia Malassezia and seborrheic dermatitis Active sebaceous glands and seborrheic dermatitis Immune responses to Malassezia in seborrheic dermatitis Clinical Features Infantile seborrheic dermatitis Adult seborrheic dermatitis Pathology Differential Diagnosis Treatment Infantile seborrheic dermatitis Adult seborrheic dermatitis Asteatotic Eczema Introduction History and Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Disseminated Eczema (Autosensitization) Introduction History and Pathogenesis Epidemiology Clinical Features Pathology Differential Diagnosis Treatment Nummular Dermatitis Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Pityriasis Alba Htlv-Associated Infective Dermatitis Introduction and Pathogenesis History and Epidemiology Clinical Features Differential Diagnosis Treatment Regional Eczematous Disorders Stasis Dermatitis Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Dyshidrotic Eczema Introduction Pathogenesis Clinical features Pathology Differential diagnosis Treatment Infectious Eczematous Dermatitis Juvenile Plantar Dermatosis Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Diaper Dermatitis Epidemiology Pathogenesis Clinical features Differential diagnosis Treatment References 14- Allergic Contact Dermatitis 14 Allergic Contact Dermatitis Introduction History Of Patch Testing Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Patch Testing Technique Interpreting the test Treatment And Patient Education Allergens Nickel Methylisothiazolinone (MI) Fragrance Mix Hydroperoxides of Linalool and Limonene Myroxylon pereirae Formaldehyde Quaternium-15 p-Phenylenediamine Benzisothiazolinone Cobalt Chromium Topical Antibiotics Thimerosal Gold Corticosteroids Textile Dermatitis Rubber Chemicals Systemic Contact Dermatitis Airborne Contact Dermatitis References 15- Irritant Contact Dermatitis 15 Irritant Contact Dermatitis Introduction History Epidemiology Pathogenesis Clinical Features Acute Irritant Contact Dermatitis Acute Delayed Irritant Contact Dermatitis Irritant Reaction Irritant Contact Dermatitis Cumulative Irritant Contact Dermatitis Asteatotic Dermatitis Traumatic Irritant Contact Dermatitis Pustular and Acneiform Irritant Contact Dermatitis Non-erythematous Irritant Contact Dermatitis Subjective or Sensory Irritant Contact Dermatitis Airborne Irritant Contact Dermatitis Frictional Irritant Contact Dermatitis Contact Urticaria Pathology Classification Of Irritant Chemicals Acids Alkalis Metal Salts Solvents Alcohols/Glycols Detergents and Cleansers Disinfectants Plastics Food and Plants Water Bodily Fluids Differential Diagnosis Prognosis Treatment References 16- Occupational Dermatoses 16 Occupational Dermatoses Introduction History Epidemiology The Occupational Dermatoses Contact Dermatitis Introduction History Epidemiology Pathogenesis Clinical features Occupational contact dermatitis Allergic contact dermatitis (see Ch. 14) Irritant contact dermatitis (see Ch. 15) Chemical burns Fiberglass dermatitis Phototoxic eruptions (see Ch. 87) Mechanical Pathology Differential diagnosis Treatment Contact Urticaria Introduction History Epidemiology Pathogenesis Clinical features Foods Latex Low-molecular-weight chemicals Protein contact dermatitis Pathology Differential diagnosis Treatment Occupational Skin Cancer Introduction History Epidemiology Pathogenesis Clinical features and diagnosis Pathology and treatment Occupational Acne Introduction History Epidemiology Pathogenesis Clinical features Oil acne and tar acne Acne mechanica Acne cosmetica Chloracne Acne due to halogens Pathology Treatment Vibration White Finger Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Infections References 17- Dermatoses Due to Plants 17 Dermatoses Due to Plants INTRODUCTION Botanical Aspects Poison ivy – just as allergenic despite a name change Binomial nomenclature Plant identification Patch Testing IMMUNOLOGIC CONTACT URTICARIA Epidemiology Pathogenesis (see Ch. 18) Clinical Features Differential Diagnosis and Pathology Treatment TOXIN-MEDIATED (NON-IMMUNOLOGIC) CONTACT URTICARIA History Epidemiology Pathogenesis (see Ch. 18) Clinical Features Pathology (see Ch. 18) Differential Diagnosis (see Ch. 18) Treatment MECHANICAL IRRITANT DERMATITIS Epidemiology Pathogenesis Clinical Features Treatment CHEMICAL IRRITANT DERMATITIS History Epidemiology Pathogenesis, Clinical Features, and Treatment (see Ch. 15) PHYTOPHOTODERMATITIS History Epidemiology Apiaceae Rutaceae Moraceae Other families Pathogenesis Clinical Features Phytophotoallergic Contact Dermatitis Treatment ALLERGIC CONTACT DERMATITIS (see Ch. 14) Epidemiology Anacardiaceae and related families Toxicodendron identification Allergenic Anacardiaceae Cross-reactors from other families Asteraceae and related families Asteraceae identification Allergenic Asteraceae Cross-reactors from other families Pathogenesis Anacardiaceae allergens Asteraceae allergens Clinical Features Anacardiaceae dermatitis Asteraceae dermatitis Photosensitivity and Asteraceae allergy Treatment (Anacardiaceae and Asteraceae Dermatitis) Other Plant Families Causing Allergic Contact Dermatitis Alliaceae Alstroemeriaceae and Liliaceae Myrtaceae Botanical products OCCUPATIONAL PLANT DERMATOSES Bakers Florists and Horticulturalists43–45 Food Handlers Outdoor Workers DERMATOSES ERRONEOUSLY ASCRIBED TO PLANTS Lichen Dermatitis47 Chlorella Photodermatitis Seaweed Dermatitis48 Pseudo-Phytodermatitis From Plant Hitchhikers REFERENCES 18- Urticaria and Angioedema 18 Urticaria and Angioedema INTRODUCTION Definition of Urticaria EPIDEMIOLOGY PATHOGENESIS The Mast Cell Distribution and diversity Degranulating stimuli Proinflammatory mediators Blood Vessels Blood Autoantibodies Leukocytes Nerves Mechanisms of Urticaria Formation Mast cell-dependent urticaria Mast cell-independent urticaria C1 esterase inhibitor (C1 inh) deficiency CLINICAL FEATURES Clinical Diversity Classification Acute Versus Chronic Urticaria Spontaneous Urticaria Associations and comorbidities Inducible Urticarias (syn. Physical Urticarias) Urticaria due to mechanical stimuli Dermographism (literally “skin writing”) (syn. dermatographism, factitious urticaria) Immediate dermographism Rarer forms of dermographism Delayed pressure urticaria Vibratory angioedema Urticaria due to temperature changes Heat exposure Heat contact urticaria Cold exposure Primary cold contact urticaria Secondary cold contact urticaria Reflex cold urticaria Familial cold urticaria Urticaria due to sweating or stress Cholinergic urticaria Exercise-induced anaphylaxis (EIA) Adrenergic urticaria Urticaria due to other exposures Solar urticaria Aquagenic urticaria Contact Urticaria (see Ch. 16) Food contact hypersensitivity syndrome Angioedema Without Wheals Drug reactions Hereditary angioedema (HAE), types I and II (inherited C1 inh deficiency) Hereditary angioedema (HAE) with normal C1 inh activity (nC1-INH-HAE previously type III) Distinctive Syndromes with Urticarial Lesions Hereditary periodic fever syndromes Cryopyrin-associated periodic syndromes (CAPS) Other syndromes Acquired autoinflammatory syndromes Schnitzler syndrome Adult-onset Still disease Episodic angioedema with eosinophilia (Gleich syndrome) Systemic capillary leak syndrome Urticarial vasculitis (see Ch. 24) PATHOLOGY DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS Diagnosis Acute urticaria Chronic urticaria Physical urticarias Urticarial vasculitis Angioedema without wheals TREATMENT Acute, Chronic Spontaneous, and Inducible Urticarias First-line therapies Classic antihistamines Second-generation antihistamines Addition of H2 antagonists to conventional H1 antihistamines Antihistamines in pregnancy Second-line therapies (targeted interventions) Drug therapies Non-drug therapies Third-line therapies C1 Esterase Inhibitor (C1 inh) Deficiency PROGNOSIS REFERENCES REFERENCE 19- Figurate Erythemas 19 Figurate Erythemas Introduction Erythema Annulare Centrifugum Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Erythema Marginatum Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Erythema Migrans Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Erythema Gyratum Repens Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment References 20- Erythema_Multiforme,_Stevens–Johnson_Syndrome,_and_Toxic_Epidermal 20 Erythema Multiforme, Stevens–Johnson Syndrome, and Toxic Epidermal Necrolysis Erythema Multiforme Introduction History Epidemiology Pathogenesis Herpes simplex virus and Mycoplasma pneumoniae Clinical Features Elementary skin lesions (Fig. 20.1) Distribution of skin lesions (topography) Mucosal lesions Systemic symptoms Natural history Pathology Differential Diagnosis Treatment Stevens–Johnson Syndrome And Toxic Epidermal Necrolysis Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment References 21- Drug Reactions 21 Drug Reactions INTRODUCTION EPIDEMIOLOGY PATHOGENESIS Immunologically Mediated Drug Reactions Genetic factors Non-immunologic Mechanisms (see Table 21.4) Overdose Pharmacologic side effects Cumulative toxicity Delayed toxicity Drug–drug interactions Alterations in metabolism Exacerbation of disease Photosensitivity Idiosyncratic With a Possible Immunologic Mechanism (see Table 21.4) DIAGNOSTIC FEATURES CLINICAL FEATURES Urticaria (see Ch. 18 for details) Angioedema (see Ch. 18 for details) Anaphylaxis Exanthematous Drug Eruptions Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) Serum Sickness-Like Eruption Vasculitis (see Ch. 24) Neutrophilic Drug Eruptions Acute generalized exanthematous pustulosis Sweet syndrome (acute febrile neutrophilic dermatosis) (see Ch. 25) Halogenoderma Other Neutrophilic Eruptions Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE) Bullous Eruptions Fixed drug eruption Linear IgA bullous dermatosis Drug-induced bullous pemphigoid Stevens–Johnson syndrome and toxic epidermal necrolysis (see Ch. 20) Photosensitivity (see Ch. 87) Phototoxicity Photoallergy Reactions to Anti-Neoplastic Agents – Chemotherapy, Targeted Therapy, and Immunotherapy Chemotherapy Alopecia Stomatitis Additional reactions Targeted therapy Immunotherapy Drug-Induced Adverse Reactions Involving Hair and Mucosae Hair Mucosal ulcerations Other Drug-Induced Cutaneous Reactions Acneiform eruptions (including folliculitis) Anticoagulant-induced skin necrosis Granulomatous reactions Drug reactions in HIV infection Drug-induced lupus erythematosus (LE) Lymphomatoid drug reaction (see Ch. 121) Pigmentary changes (see Ch. 67) Drug-induced psoriasis Additional uncommon drug reactions Cutaneous Side Effects of Vaccines and Injected Medications Vaccine-induced reactions Localized reactions to injected medications Treatment Acknowledgments REFERENCES 22- Purpura Mechanisms and Differential Diagnosis 22 Purpura: Mechanisms and Differential Diagnosis Introduction The Time Course Of Purpura Hemostasis/Coagulation Overlap Of Coagulation And Inflammatory Vessel Disease Tests For Coagulation Antiplatelet And Anticoagulant Agents Selected Purpura Syndromes Pigmented Purpuric Dermatoses Introduction Pathogenesis Clinical features Pathology Differential diagnosis Treatment Benign Hypergammaglobulinemic Purpura of Waldenström Introduction Pathogenesis Clinical features Pathology Differential diagnosis Treatment Gardner–Diamond Syndrome Introduction Clinical features Pathology Differential diagnosis and treatment Paroxysmal Finger Hematoma Clinical features Differential diagnosis Treatment Onyalai Mondor Disease Introduction Pathogenesis Clinical features Pathology Differential diagnosis Treatment References 23- Cutaneous_Manifestations_of_Microvascular_Occlusion_Syndromes 23 Cutaneous Manifestations of Microvascular Occlusion Syndromes INTRODUCTION DISORDERS OF PLATELET-RELATED THROMBOPATHY Heparin-Induced Thrombocytopenia (HIT) Syndrome Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Philadelphia Chromosome-Negative Myeloproliferative Neoplasms Introduction Pathogenesis Epidemiology Clinical features Pathology Differential diagnosis Treatment Paroxysmal Nocturnal Hemoglobinuria Introduction Pathogenesis Clinical features Pathology Differential diagnosis Treatment Primary Thrombotic Microangiopathy Introduction Pathogenesis Clinical features Pathology Differential diagnosis Treatment Introduction Pathogenesis Epidemiology Clinical features Pathology Differential diagnosis Treatment Introduction/pathogenesis Clinical features/pathology Differential diagnosis Treatment DISORDERS OF CRYOPRECIPITATION OR CRYOAGGLUTINATION DISORDERS OF OCCLUSION BY OPPORTUNISTIC ORGANISMS PROLIFERATING WITHIN VESSELS DISORDERS OF OCCLUSION BY EMBOLI Cholesterol Embolus Introduction Pathogenesis Clinical features Pathology Differential diagnosis Treatment Oxalate Embolus Introduction Clinical features Pathology Differential diagnosis Treatment Other Embolus-Associated Syndromes SYSTEMIC COAGULOPATHIES WITH CUTANEOUS MANIFESTATIONS Protein C and S Disorders, Congenital and Acquired Introduction Pathogenesis/clinical features Neonatal purpura fulminans Warfarin necrosis Warfarin-associated venous limb gangrene Purpura fulminans with sepsis Purpura fulminans postinfection Antiphospholipid Antibody/Lupus Anticoagulant Syndrome Introduction Epidemiology Pathogenesis Clinical features Pathology and laboratory findings Differential diagnosis Treatment DISORDERS OF VASCULAR COAGULOPATHIES WITH CUTANEOUS MANIFESTATIONS Sneddon Syndrome Introduction Pathogenesis Clinical features Pathology Differential diagnosis Treatment Livedoid Vasculopathy Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Hydroxyurea-Associated Vasculopathy Interferon-Induced Vasculopathy/Cutaneous Necrosis Benign and Malignant Atrophic Papulosis Introduction Pathogenesis Clinical features Pathology Differential diagnosis Treatment Levamisole-Adulterated Cocaine-Induced Vasculopathy/Vasculitis Clinical features Pathology and laboratory findings Differential diagnosis Treatment Calciphylaxis DISORDERS OF CELL-RELATED VASCULAR OCCLUSION Red Blood Cell (RBC) Vascular Occlusion: Sickle Cell Disease (SCD) Introduction and pathogenesis Clinical features Treatment Red Blood Cell (RBC) Vascular Occlusion/Ischemia: Thalassemia Red Blood Cell (RBC) Vascular Occlusion/Ischemia: Other Intravascular Cellular Occlusion DISORDERS OF OCCLUSION, MISCELLANEOUS Loxosceles Spider Bites Hematoma-Associated Retiform Purpura SARS-CoV-2 Purpuric Syndromes Pernio/chilblains-like disease (“COVID toes”) Immune complex vasculitis and antiphospholipid antibodies Retiform thrombotic purpura SARS-CoV-2-related systemic coagulopathy Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) REFERENCES 24- Cutaneous Vasculitis 24 Cutaneous Vasculitis INTRODUCTION Terminology Introduction Epidemiology Pathogenesis Clinical features Differential diagnosis Treatment CLASSIFICATION EPIDEMIOLOGY PATHOGENESIS GENERAL CLINICAL FEATURES PATHOLOGY DIFFERENTIAL DIAGNOSIS SMALL VESSEL VASCULITIS IgA Vasculitis (Henoch–Schönlein Purpura) Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Acute Hemorrhagic Edema of Infancy Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Urticarial Vasculitis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Erythema Elevatum Diutinum Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Granuloma Faciale Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment PREDOMINANTLY SMALL AND MEDIUM-SIZED VESSEL VASCULITIDES Cryoglobulinemic Vasculitis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment ANCA-Associated Vasculitides Introduction Epidemiology Pathogenesis Natural history, clinical features, and treatment Granulomatosis With Polyangiitis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Microscopic Polyangiitis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Eosinophilic Granulomatosis With Polyangiitis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment PREDOMINANTLY MEDIUM-SIZED VESSEL VASCULITIS Polyarteritis Nodosa Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment TEMPORAL ARTERITIS (GIANT CELL ARTERITIS) DIAGNOSTIC APPROACH TO A PATIENT WITH SUSPECTED VASCULITIS History and Physical Examination Laboratory Evaluation Treatment REFERENCES eREFERENCES 25- Neutrophilic Dermatoses 25 Neutrophilic Dermatoses Introduction Neutrophil Biology Inflammation Sweet Syndrome History Epidemiology Pathogenesis Clinical Features Associated Diseases Pathology Diagnosis and Differential Diagnosis Treatment Pyoderma Gangrenosum Introduction History Epidemiology Pathogenesis Clinical Features Associated Diseases Pathology Differential Diagnosis Treatment Behçet Disease Introduction History Epidemiology Pathogenesis Clinical Features and Differential Diagnosis Mucocutaneous involvement Systemic involvement Pathology Diagnosis Treatment Bowel-Associated Dermatosis–Arthritis Syndrome Introduction History Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Synovitis, Acne, Pustulosis, Hyperostosis, And Osteitis (Sapho) Syndrome Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Erosive Pustular Dermatosis History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Copyright Notice References 26- Eosinophil-Associated Dermatoses 26 Eosinophil-Associated Dermatoses Eosinophil Biology Granular Contents Tissue Effects And Innate Immunity Eosinophil-Associated Dermatoses Wells Syndrome Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Hypereosinophilic Syndromes Introduction History Epidemiology Clinical Features Pathology Differential Diagnosis Treatment References 27- Pregnancy Dermatoses 27 Pregnancy Dermatoses INTRODUCTION AND BACKGROUND GESTATIONAL PEMPHIGOID Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment POLYMORPHIC ERUPTION OF PREGNANCY Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment INTRAHEPATIC CHOLESTASIS OF PREGNANCY Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ATOPIC ERUPTION OF PREGNANCY Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment APPROACH TO THE PREGNANT WOMAN WITH PRURITUS DERMATOSES INFLUENCED BY PREGNANCY PHYSIOLOGIC CHANGES DURING PREGNANCY AUTOIMMUNE PROGESTERONE DERMATITIS Acknowledgment REFERENCES e-References 28- The Biology of the Basement Membrane 28 The Biology of the Basement Membrane INTRODUCTION ORIGIN OF THE EPIDERMAL BASEMENT MEMBRANE BASAL KERATINOCYTES: HEMIDESMOSOME-ANCHORING FILAMENTS AND INTEGRINS Plectin Bullous Pemphigoid Antigen 1 Bullous Pemphigoid Antigen 2 Integrins Hemidesmosome-associated integrin α6β4 Plasma membrane-associated integrins Tetraspan CD151 THE LAMINA DENSA Laminins Type IV Collagen Nidogen Heparan Sulfate Proteoglycans ANCHORING FIBRILS AND THE SUBLAMINA DENSA REGION Type VII Collagen Microfibrils BASEMENT MEMBRANE REMODELING THE EPIDERMAL BASEMENT MEMBRANE IN BULLOUS DISEASES Autoimmune Subepidermal Blistering Diseases Inherited Subepidermal Blistering Diseases SUMMARY REFERENCES 29- Pemphigus 29 Pemphigus Introduction History Epidemiology Fogo Selvagem Pathogenesis Pathogenic Autoantibodies in Pemphigus Desmogleins as Pemphigus Antigens Desmoglein Compensation Theory as Explanation for Localization of Blisters Humoral and Cellular Autoimmunity in Paraneoplastic Pemphigus Immunologic Mechanism of Pathogenic Autoantibody Production in Pemphigus Clinical Features Pemphigus Vulgaris Pemphigus Vegetans Pemphigus Foliaceus Pemphigus Erythematosus (Senear–Usher Syndrome) Herpetiform Pemphigus Drug-Induced Pemphigus Paraneoplastic Pemphigus IgA Pemphigus Pathology Pemphigus Vulgaris Pemphigus Foliaceus Paraneoplastic Pemphigus IgA Pemphigus Differential Diagnosis Differential Diagnosis of Pemphigus Vulgaris Differential Diagnosis of Pemphigus Foliaceus Differential Diagnosis of Paraneoplastic Pemphigus Differential Diagnosis of IgA Pemphigus Treatment Pemphigus Vulgaris Pemphigus Foliaceus Paraneoplastic Pemphigus IgA Pemphigus References 30- Pemphigoid Group 30 Pemphigoid Group Bullous Pemphigoid Introduction History Epidemiology Pathogenesis Humoral and cellular responses Clinical Features Non-bullous pemphigoid Bullous phase Clinical variants Associated Diseases Drug-induced bullous pemphigoid Diagnosis Light microscopy Direct immunofluorescence (DIF) microscopy Indirect immunofluorescence (IIF) microscopy ELISA Other immunopathological studies Differential Diagnosis Prognosis Monitoring Treatment Mucous Membrane Pemphigoid Introduction History Epidemiology Pathogenesis Clinical Features Mucous membranes Cutaneous lesions Diagnosis and Differential Diagnosis Light microscopy and electron microscopy Direct immunofluorescence (DIF) microscopy Immunoelectron microscopy Indirect immunofluorescence (IIF) microscopy Immunochemical studies, including ELISA Differential diagnosis Prognosis Treatment Epidermolysis Bullosa Acquisita Introduction History Epidemiology Pathogenesis Clinical Features Diagnosis and Differential Diagnosis Light microscopy and electron microscopy Direct immunofluorescence (DIF) microscopy Indirect immunofluorescence (IIF) microscopy Immunoelectron microscopy Other immunochemical studies, including ELISA Differential diagnosis Treatment References 31- Dermatitis Herpetiformis and Linear IgA Bullous Dermatosis 31 Dermatitis Herpetiformis and Linear IgA Bullous Dermatosis Dermatitis Herpetiformis Introduction History Epidemiology Pathogenesis Genetic predisposition Gluten-sensitive enteropathy (GSE) Circulating antibodies Granular IgA deposition Iodide Associated Disorders and Malignancies Clinical Features Pathology IgA Deposits Laboratory evaluation Differential Diagnosis Treatment Patient Support Linear Iga Bullous Dermatosis Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment References 32- Epidermolysis Bullosa 32 Epidermolysis Bullosa INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS EB Simplex Junctional EB Dystrophic EB CLINICAL FEATURES Cutaneous Findings Extracutaneous Findings Cutaneous Malignancies APPROACH TO DIAGNOSIS Differential Diagnosis TREATMENT KINDLER EPIDERMOLYSIS BULLOSA Introduction History Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment REFERENCES 33- Other Vesiculobullous Diseases 33 Other Vesiculobullous Diseases BULLOSIS DIABETICORUM History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment COMA BLISTERS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment FRICTION BLISTERS Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment BULLOUS CUTANEOUS SMALL VESSEL VASCULITIS BULLOUS DRUG ERUPTIONS BULLOUS INSECT BITE REACTIONS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment DELAYED POSTBURN/POSTGRAFT BLISTERS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment EDEMA BLISTERS Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ADDITIONAL VESICULOBULLOUS DISORDERS REFERENCES 34- Vesiculopustular_and_Erosive_Disorders_in_Newborns_and_Infants 34 Vesiculopustular and Erosive Disorders in Newborns and Infants COMMON CAUSES Erythema Toxicum Neonatorum Transient Neonatal Pustular Melanosis Sterile Transient Neonatal Pustulosis Miliaria Neonatal Cephalic Pustulosis Cutaneous Candidiasis Sucking Blisters Exogenous Causes of Erosions UNCOMMON AND RARE CAUSES Acropustulosis of Infancy Eosinophilic Pustular Folliculitis of Infancy Congenital and Neonatal Langerhans Cell Histiocytosis Incontinentia Pigmenti Autosomal Dominant Hyperimmunoglobulin E (Hyper-IgE) Syndrome VERY RARE DISORDERS Neonatal Behçet Disease Vesiculopustular Eruption in Transient Myeloproliferative Disorder of Down Syndrome Congenital Erosive and Vesicular Dermatosis Pyoderma Gangrenosum Restrictive Dermopathy Noma Neonatorum Perinatal Gangrene of the Buttock REFERENCES 35- Structure_and_Function_of_Eccrine,_Apocrine,_and_Sebaceous_Glands 35 Structure and Function of Eccrine, Apocrine, and Sebaceous Glands ECCRINE AND APOCRINE SWEAT GLANDS Introduction ECCRINE SWEAT GLANDS Structure Development Function Pathophysiology Hyper- and Hypohidrosis Drug-Related Eccrine Disorders Disorders of Sweat Retention APOCRINE SWEAT GLANDS Structure Development Function Pathophysiology SEBACEOUS GLANDS Introduction Structure Development Function Pathophysiology REFERENCES 36- Acne Vulgaris 36 Acne Vulgaris INTRODUCTION HISTORY EPIDEMIOLOGY Genetic Factors Dietary Factors PATHOGENESIS OF ACNE Follicular Hyperkeratinization Hormonal Influences on Sebum Production and Composition Inflammation in Acne Cutibacterium acnes colonization and activities CLINICAL FEATURES Acne Variants Post-adolescent acne in women Acne fulminans Acne conglobata and associated conditions Solid facial edema Neonatal cephalic pustulosis (neonatal acne) Infantile acne Mid-childhood acne Preadolescent acne Acne excoriée Acne associated with endocrinologic abnormalities Acne associated with genetic syndromes Acneiform Eruptions Drug-induced acne Occupational acne, acne cosmetica, and pomade acne Chloracne (metabolizing acquired dioxin-induced skin hamartomas [MADISH]) Acne mechanica Tropical acne Radiation acne “Pseudoacne” of the nasal crease Idiopathic aseptic facial granuloma (idiopathic facial aseptic granuloma) Childhood flexural comedones PATHOLOGY DIFFERENTIAL DIAGNOSIS TREATMENT Topical Treatments Topical retinoids Antimicrobial agents Other topical medications Systemic Therapies Antibiotics Hormonal therapy Isotretinoin Surgical Treatment REFERENCES 37- Rosacea and Related Disorders 37 Rosacea and Related Disorders INTRODUCTION HISTORY AND EPIDEMIOLOGY PATHOGENESIS Genetic Factors Dysregulated Cutaneous Immunity Neurogenic Inflammation Vascular Alterations Ultraviolet Radiation (UVR) Epidermal Barrier Dysfunction Microorganisms CLINICAL FEATURES Diagnostic Phenotypes (Table 37.2) Fixed centrofacial erythema in a characteristic pattern that may periodically intensify Phymatous changes Major Phenotypes Papules and pustules Flushing Telangiectasia Ocular manifestations Secondary Signs and Symptoms Burning and stinging Facial edema Dry appearance Other ocular manifestations Other Clinical Rosacea Presentations Ocular rosacea Granulomatous rosacea DIFFERENTIAL DIAGNOSIS PATHOLOGY TREATMENT Transient and Persistent Erythema and Telangiectasia Papules and Pustules Other Forms of Rosacea ROSACEA-LIKE DISORDERS Acknowledgment REFERENCES 38- Folliculitis,_Follicular_Occlusion_Tetrad,_and_Other_Follicular 38 Folliculitis, Follicular Occlusion Tetrad, and Other Follicular Disorders Introduction Superficial Folliculitis Malassezia (Pityrosporum) Folliculitis Eosinophilic Folliculitis Eosinophilic pustular folliculitis Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Immunosuppression-associated eosinophilic pustular folliculitis Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Eosinophilic pustular folliculitis of infancy Introduction Epidemiology and Pathogenesis Clinical features Pathology Differential diagnosis Treatment History and epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Introduction History Epidemiology Pathogenesis Clinical features Staging and outcome measures Pathology Differential diagnosis Treatment Disseminate and Recurrent Infundibulofolliculitis Disorders Of Follicular Keratinization Erythromelanosis Follicularis Faciei Keratosis Pilaris Atrophicans Lichen Spinulosus Phrynoderma Trichostasis Spinulosa Viral-Associated Trichodysplasia Spinulosa Deep Folliculitis Pseudofolliculitis Barbae Acne Keloidalis Follicular Occlusion Tetrad Hidradenitis Suppurativa Acknowledgment References 39- Diseases of the Eccrine and Apocrine Sweat Glands 39 Diseases of the Eccrine and Apocrine Sweat Glands Sweat Glands Eccrine Sweat Glands Apocrine Sweat Glands Hyperhidrosis Primary Hyperhidrosis Secondary Hyperhidrosis Disorders associated with cortical (emotional) hyperhidrosis Hypothalamic (thermoregulatory) hyperhidrosis Medullary (gustatory) hyperhidrosis Physiologic medullary hyperhidrosis Pathologic medullary hyperhidrosis Spinal (cord transection) sweating Autonomic dysreflexia Compensatory hyperhidrosis Non-neural hyperhidrosis Diagnosis of Hyperhidrosis Treatment of Hyperhidrosis Hypohidrosis And Anhidrosis Central and Neuropathic Hypohidrosis Peripheral Anhidrosis Diagnosis of Anhidrosis Treatment of Anhidrosis Abnormalities And Alterations Of Eccrine And Apocrine Sweat Composition Diagnostic Microscopic Changes In Eccrine Sweat Glands Influence Of Sweat On Skin Diseases Additional Disorders Of The Eccrine Sweat Gland Miliaria Epidemiology and pathogenesis Clinical features Pathology Differential diagnosis Treatment Multiple Sweat Gland Abscesses Neutrophilic Eccrine Hidradenitis Epidemiology and pathogenesis Clinical features Pathology Differential diagnosis Treatment Idiopathic Palmoplantar Hidradenitis Granulosis Rubra Nasi Keratolysis Exfoliativa Disorders Of The Apocrine Sweat Gland Fox–Fordyce Disease Epidemiology and pathogenesis Clinical features Pathology Treatment References 40- Autoantibodies_Encountered_in_Patients_with_Autoimmune_Connective 40 Autoantibodies Encountered in Patients with Autoimmune Connective Tissue Diseases INTRODUCTION HISTORICAL PERSPECTIVE THE FLUORESCENT ANTI-NUCLEAR ANTIBODY (FANA) TEST Automated Immunoassays – Solid Phase and Bead-Based Multiplex “Normal” Versus “Abnormal” ANA Titers Immunofluorescence Patterns Clinical Utility of the ANA Assay Clinical Value of aAb in Diagnosis, Prognosis, and Disease Activity Monitoring “Sontheimer’s Corollary” to Greenwald’s Law of Lupus Phototherapy and ANA How Does One Evaluate a Positive ANA Result in a Patient Suspected of Having SLE? AUTOANTIBODIES IN LUPUS ERYTHEMATOSUS Anti-dsDNA Antibodies Anti-SSA/Ro and Anti-SSB/La Antibodies Drug-Induced ANA/SLE Induction of ANA and anti-dsDNA antibodies by tumor necrosis factor inhibitors AUTOANTIBODIES IN IDIOPATHIC INFLAMMATORY DERMATOMYOPATHIES Anti-TIF1-γ (p155), -TIF1-α (p140) Antibodies Anti-MDA5/CADM-140 Antibodies Anti-Jo-1 Antibodies Anti-Mi-2, -SRP, -NXP-2, and –SAE Antibodies AUTOANTIBODIES IN SYSTEMIC SCLEROSIS (SSc SCLERODERMA) AND MORPHEA (LOCALIZED SCLERODERMA) AUTOANTIBODIES IN OTHER RHEUMATIC DISORDERS AFFECTING THE SKIN Acknowledgment REFERENCES 41- Lupus Erythematosus 41 Lupus Erythematosus INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES Cutaneous Lupus – Three Major Forms Classification Discoid lupus erythematosus (DLE) Subacute cutaneous lupus erythematosus (SCLE) Acute cutaneous lupus erythematosus (ACLE) Cutaneous Lupus – Additional Variants (See Fig. 41.2) Lupus erythematosus tumidus Lupus panniculitis Chilblain lupus Discoid lupus erythematosus/lichen planus overlap syndrome Neonatal lupus erythematosus (NLE) Bullous lesions Systemic Lupus Erythematosus Nonspecific Cutaneous Lesions PATHOLOGY Histopathology Antibody Deposits in Lesional Skin Antibody Deposits Within Normal-Appearing Skin DIFFERENTIAL DIAGNOSIS AND EVALUATION TREATMENT Topical Therapy Systemic Therapy Adjunctive Therapy REFERENCES 42- Dermatomyositis 42 Dermatomyositis INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES Cutaneous Disease Systemic Disease Malignancy PATHOLOGY DIFFERENTIAL DIAGNOSIS AND EVALUATION TREATMENT REFERENCES 43- Systemic Sclerosis (Scleroderma) and Related Disorders 43 Systemic Sclerosis (Scleroderma) and Related Disorders Systemic Sclerosis Introduction History Epidemiology Pathogenesis Vascular dysregulation Immune dysregulation Extracellular matrix dysregulation Clinical Features Classification and diagnostic criteria Cutaneous features Extracutaneous features Autoantibodies Pathology Differential Diagnosis Treatment Raynaud phenomenon Cutaneous ulcers Cutaneous sclerosis Other cutaneous complications Internal organ involvement Eosinophilic Fasciitis History Clinical Features Pathology Treatment Stiff Skin Syndrome History Epidemiology Pathogenesis Clinical Features Pathology Treatment Sclerodermoid Syndromes Induced By Exogenous Substances Nephrogenic Systemic Fibrosis Toxic Oil Syndrome Eosinophilia–Myalgia Syndrome Sclerodermoid Syndromes Induced by Other Chemicals Silicosis Sclerodermoid Syndromes Induced by Drugs References 44- Morphea and Lichen Sclerosus 44 Morphea and Lichen Sclerosus MORPHEA INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS Vascular Changes Control of Fibroblast Function by T Cell-Derived Cytokines Animal Model and Genetics Triggering Events CLINICAL FEATURES Plaque-Type (Circumscribed) Morphea Variants Linear Morphea and Parry–Romberg Syndrome Generalized Morphea Morphea in Childhood LABORATORY FINDINGS PATHOLOGY MORPHEAFORM (AND SCLERODERMOID) INFLAMMATORY SYNDROMES DIFFERENTIAL DIAGNOSIS TREATMENT Phototherapy Systemic Therapies LICHEN SCLEROSUS INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES PATHOLOGY DIFFERENTIAL DIAGNOSIS TREATMENT Genital Lichen Sclerosus Phototherapy Surgery Extragenital Lichen Sclerosus REFERENCES 45- Other Rheumatologic Disorders and Autoinflammatory Diseases 45 Other Rheumatologic Disorders and Autoinflammatory Diseases Systemic-Onset Juvenile Idiopathic Arthritis (Still Disease) Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Adult-Onset Still Disease Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Relapsing Polychondritis Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Sjögren Syndrome Introduction History Epidemiology Pathogenesis Clinical Features Laboratory Findings Pathology Differential Diagnosis Treatment Mixed Connective Tissue Disease Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Extra-Articular Manifestations of Rheumatoid Arthritis Introduction Epidemiology Pathogenesis Clinical Features Rheumatoid nodules Rheumatoid vasculitis Bywaters lesions Felty syndrome Neutrophilic dermatoses Other Pathology Differential Diagnosis Treatment Autoinflammatory Diseases Acknowledgment References 46- Mucinoses 46 Mucinoses INTRODUCTION CLASSIFICATION PRIMARY DEGENERATIVE–INFLAMMATORY MUCINOSES Dermal Mucinoses Scleromyxedema Lichen myxedematosus (localized variants) Self-healing cutaneous mucinosis Scleredema Mucinoses associated with altered thyroid function Localized (pretibial) myxedema Definition Epidemiology and pathogenesis Clinical features Pathology Differential diagnosis Treatment Generalized myxedema Definition Pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Introduction and definition History Epidemiology and pathogenesis Clinical features Pathology Differential diagnosis Treatment Treatment History, epidemiology, and pathogenesis Clinical features Pathology Differential diagnosis Treatment Reticular erythematous mucinosis Papulonodular mucinosis associated with autoimmune connective tissue diseases Cutaneous focal mucinosis Primary Follicular Mucinoses Follicular mucinosis Urticaria-like follicular mucinosis PRIMARY HAMARTOMATOUS–NEOPLASTIC MUCINOSES Mucinous Nevus Superficial (Angio)Myxoma SECONDARY CUTANEOUS MUCINOSES REFERENCES 47- Amyloidosis 47 Amyloidosis INTRODUCTION History Epidemiology Classification Pathogenesis Amyloid Properties PRIMARY LOCALIZED CUTANEOUS AMYLOIDOSIS Clinical Features – Macular, Lichenoid, Biphasic, and Dyschromic Amyloidosis Familial primary cutaneous amyloidosis syndromes IL-31 receptor-associated amyloidosis (PLCA1 and PLCA2) Dyschromic amyloidosis (PLCA3) Sipple syndrome or multiple endocrine neoplasia (MEN) type 2A X-linked reticulate pigmentary disorder (Partington amyloidosis) Other associated disorders Clinical Features – Nodular Amyloidosis Pathology Differential Diagnosis Treatment SECONDARY CUTANEOUS AMYLOIDOSIS SYSTEMIC AMYLOIDOSIS Primary Systemic Amyloidosis AL amyloidosis Clinical features Pathology Differential diagnosis Treatment Secondary Systemic Amyloidosis (AA Amyloidosis) Hemodialysis-Associated Amyloidosis (Aβ2M Amyloidosis) INHERITED AMYLOIDOSES Familial Amyloidosis, Finnish Type (AGel Amyloidosis) Transthyretin Amyloidosis (ATTRwt/ATTRv Amyloidosis) APPENDIX REFERENCES 48- Deposition Diseases 48 Deposition Diseases Introduction Gout Introduction Epidemiology Pathogenesis Clinical Features Acute gouty arthritis Chronic tophaceous gout Pathology Differential Diagnosis Treatment Pseudogout Lipoid Proteinosis History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Colloid Milium Introduction and Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Mucopolysaccharidoses Clinical Features and Pathology Treatment References 49- Porphyria 49 Porphyria INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS Cutaneous Findings Acute Porphyric Attack CLINICAL AND LABORATORY INVESTIGATION THE NON-ACUTE PORPHYRIAS Porphyria Cutanea Tarda (PCT) Erythropoietic Protoporphyria (EPP) X-linked Dominant Protoporphyria (XLDPP) Congenital Erythropoietic Porphyria (CEP) Hepatoerythropoietic Porphyria (HEP) Pseudoporphyria Differential Diagnosis Treatment THE ACUTE PORPHYRIAS Acute Intermittent Porphyria (AIP) Variegate Porphyria (VP) Hereditary Coproporphyria (HCP) δ-Aminolevulinic Acid Dehydratase (ALA-D) Deficiency Porphyria Differential Diagnosis Treatment Cutaneous symptoms Acute porphyric attack APPENDIX REFERENCES 50- Calcifying and Ossifying Disorders of the Skin 50 Calcifying and Ossifying Disorders of the Skin INTRODUCTION CUTANEOUS CALCIFICATION Dystrophic Calcification Autoimmune connective tissue disease Treatment of dystrophic calcification Panniculitis Genetic disorders Infections Neoplasms Other Metastatic Calcification Renal disease Milk–alkali syndrome Hypervitaminosis D Mixed Calcification Calciphylaxis Diagnosis of calciphylaxis Treatment of calciphylaxis including wound care Idiopathic Calcification Idiopathic calcified nodules of the scrotum Subepidermal calcified nodule Tumoral calcinosis Milia-like calcinosis Iatrogenic Calcification CUTANEOUS OSSIFICATION (OSTEOMA CUTIS) “Secondary” Cutaneous Ossification LABORATORY EVALUATION OF PATIENTS WITH CUTANEOUS CALCIFICATION AND OSSIFICATION REFERENCES 51- Nutritional Diseases 51 Nutritional Diseases INTRODUCTION EPIDEMIOLOGY AND PATHOGENESIS CLINICAL FEATURES Protein–Energy Malnutrition Essential Fatty Acid Deficiency Vitamins and Trace Elements Vitamins Vitamin excess Vitamin D Trace elements Zinc Copper Selenium Anorexia Nervosa and Bulimia (Nervosa) Obesity Bariatric Surgery and Gastrointestinal Malabsorption PATHOLOGY DIFFERENTIAL DIAGNOSIS TREATMENT REFERENCES 52- Graft-versus-Host Disease 52 Graft-versus-Host Disease INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES Acute GVHD Chronic GVHD PATHOLOGY DIFFERENTIAL DIAGNOSIS TREATMENT Acute GVHD Chronic GVHD REFERENCES 53- Dermatologic_Manifestations_in_Patients_with_Systemic_Disease 53 Dermatologic Manifestations in Patients with Systemic Disease CUTANEOUS RHEUMATOLOGY CUTANEOUS HEMATOLOGY AND ONCOLOGY CUTANEOUS DISEASES IN PATIENTS WITH ENDOCRINOLOGIC AND/OR METABOLIC DISORDERS CUTANEOUS GASTROENTEROLOGY OTHER SYSTEMIC DISEASES WITH CUTANEOUS MANIFESTATIONS REFERENCES 54- Basic Principles of Genetics 54 Basic Principles of Genetics INTRODUCTION GENETIC DISEASES MENDELIAN PATTERNS OF INHERITANCE Autosomal Dominant Inheritance Autosomal Recessive Inheritance X-Linked Recessive Inheritance X-Linked Dominant Inheritance EXCEPTIONS TO BASIC MENDELIAN PATTERNS OF HERITANCE EPIGENETICS AND IMPRINTING CHROMOSOMAL DISORDERS COMPLEX GENETIC TRAITS IDENTIFICATION OF DISEASE GENES INTERPRETATION OF SEQUENCE VARIANTS NEXT-GENERATION (MASSIVELY PARALLEL) SEQUENCING GENETIC COUNSELING TUMOR GENETICS FOR THE DERMATOLOGIST Somatic Versus Germline Mutations Testing of Cutaneous Tumors for Somatic Mutations Testing for Hereditary Cancer Predisposition Syndromes REFERENCES 55- Genetic Basis of Cutaneous Diseases 55 Genetic Basis of Cutaneous Diseases INTRODUCTION McKUSICK’S MENDELIAN INHERITANCE IN MAN GENOTYPE–PHENOTYPE CORRELATIONS MOLECULAR CLASSIFICATION OF HEREDITARY SKIN DISORDERS Keratin Defects Defects in Intercellular Junctions Desmosomal defects Connexin defects Defects in Keratinocyte–Extracellular Matrix Adhesion Transmembrane Transporter Defects Calcium pump defects ATP-binding cassette transporter defects Nuclear Envelope Defects Defects in Pyrin/NOD Family Members and Related Proteins Defects in DNA Repair Genes, Tumor Suppressor Genes, and Oncogenes Defective DNA repair and protection of genomic integrity Defective tumor suppressor genes Activated oncogenes Defects in WNT/β-Catenin Signaling CONTIGUOUS GENE SYNDROMES CUTANEOUS MOSAICISM REVERTANT MOSAICISM CHROMOSOMAL DISORDERS INSIGHT INTO ACQUIRED SKIN DISORDERS PROVIDED BY THE STUDY OF GENODERMATOSES PRENATAL AND PREIMPLANTATION GENETIC DIAGNOSIS TREATMENT FOR HEREDITARY SKIN DISORDERS Gene Therapy Therapy Targeting Affected Molecular Pathways REFERENCES 56- Biology of Keratinocytes 56 Biology of Keratinocytes INTRODUCTION THE EPIDERMIS: STRUCTURE AND FUNCTION KERATIN INTERMEDIATE FILAMENTS Keratins and Signaling Hair Keratins EPIDERMAL DIFFERENTIATION Regulatory Pathways Involved in Epidermal Development and Differentiation Genes required for establishing and maintaining basal keratinocytes Genes required for differentiation in mature epidermis Roles of Ca2+ in epidermal differentiation Genes required for development of the embryonic epidermis KERATINOCYTE ADHESION Desmosomes What happens when desmosomes do not function properly? Adherens Junctions Tight Junctions KERATINOCYTE–MATRIX INTERACTIONS RELATED DISEASES Keratin Disorders Epidermolysis bullosa simplex Epidermolytic ichthyosis and palmoplantar keratoderma White sponge nevus Gastrointestinal disorders Filaggrin Deficiency Disorders Mouse Models for Structural and Desmosomal Proteins CONCLUSION REFERENCES 57- Ichthyoses, Erythrokeratodermas, and Related Disorders 57 Ichthyoses, Erythrokeratodermas, and Related Disorders INTRODUCTION COMMON ICHTHYOSES ICHTHYOSIS VULGARIS History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment STEROID SULFATASE DEFICIENCY History Epidemiology Pathogenesis Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment KERATINOPATHIC ICHTHYOSES EPIDERMOLYTIC ICHTHYOSIS History Epidemiology Pathogenesis Clinical Features Classic epidermolytic ichthyosis and variants Superficial epidermolytic ichthyosis (SEI) Epidermolytic epidermal nevi (mosaic epidermolytic ichthyosis) Pathology Other diagnostic tests Differential Diagnosis Treatment ICHTHYOSIS WITH CONFETTI ICHTHYOSIS HYSTRIX CURTH–MACKLIN Introduction History Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment AUTOSOMAL RECESSIVE CONGENITAL ICHTHYOSES AUTOSOMAL RECESSIVE CONGENITAL ICHTHYOSIS (ARCI): CLINICAL AND GENETIC SPECTRUM Introduction History Epidemiology Pathogenesis and Clinical Features COLLODION BABY Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment LAMELLAR ICHTHYOSIS Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment CONGENITAL ICHTHYOSIFORM ERYTHRODERMA Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment HARLEQUIN ICHTHYOSIS History Epidemiology Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment SYNDROMIC ICHTHYOSES NETHERTON SYNDROME History Epidemiology Pathogenesis Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment SJÖGREN–LARSSON SYNDROME History Epidemiology Pathogenesis Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment NEUTRAL LIPID STORAGE DISEASE WITH ICHTHYOSIS History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment TRICHOTHIODYSTROPHY WITH ICHTHYOSIS History Epidemiology Pathogenesis Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment ERYTHROKERATODERMAS ERYTHROKERATODERMIA VARIABILIS ET PROGRESSIVA History Epidemiology Pathogenesis Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment KERATITIS–ICHTHYOSIS–DEAFNESS SYNDROME History Epidemiology Pathogenesis Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment X-LINKED DOMINANT ICHTHYOSIFORM DISORDERS CHILD SYNDROME History Epidemiology Pathogenesis Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment CONRADI–HÜNERMANN–HAPPLE SYNDROME History Epidemiology Pathogenesis Clinical Features Pathology Other diagnostic tests Differential Diagnosis Treatment OTHER ICHTHYOSES, PEELING SKIN SYNDROMES, AND RELATED DISORDERS REFERENCES 58- Palmoplantar Keratodermas 58 Palmoplantar Keratodermas INTRODUCTION HEREDITARY KERATODERMAS DIFFUSE PALMOPLANTAR KERATODERMA WITHOUT ASSOCIATED FEATURES (ISOLATED, NON-SYNDROMIC) Diffuse Epidermolytic Palmoplantar Keratoderma (EPPK) History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Management Diffuse Non-epidermolytic Palmoplantar Keratoderma (NEPPK) Epidemiology and pathogenesis Clinical features Differential diagnosis Pathology Management Keratolytic Winter Erythema and CTSB-Related Palmoplantar Keratoderma DIFFUSE PALMOPLANTAR KERATODERMAS WITH ICHTHYOSIS Loricrin Keratoderma Clinical and histologic features Management Keratosis Linearis–Ichthyosis Congenita–Sclerosing Keratoderma (KLICK) DIFFUSE PALMOPLANTAR KERATODERMAS WITH ASSOCIATED FEATURES/SYNDROMIC Vohwinkel Syndrome Mitochondrial Palmoplantar Keratoderma With Hearing Impairment Huriez Syndrome Palmoplantar Keratoderma With Sex Reversal and Squamous Cell Carcinoma Clouston Syndrome Odonto-onycho-dermal Dysplasia Olmsted Syndrome Papillon–Lefèvre and Haim–Munk Syndromes Naxos Disease FOCAL PALMOPLANTAR KERATODERMA WITHOUT ASSOCIATED FEATURES (ISOLATED, NON-SYNDROMIC) Striate/Focal Palmoplantar Keratoderma FOCAL PALMOPLANTAR KERATODERMA WITH ASSOCIATED FEATURES/SYNDROMIC Pachyonychia Congenita History, epidemiology, and pathogenesis Clinical features Pathology Differential diagnosis Treatment Richner–Hanhart Syndrome Howel–Evans Syndrome Carvajal Syndrome PUNCTATE PALMOPLANTAR KERATODERMA WITHOUT ASSOCIATED FEATURES (ISOLATED, NON-SYNDROMIC) Punctate Palmoplantar Keratoderma, Buschke–Fischer–Brauer type Spiny Keratoderma Marginal Papular Keratoderma: Acrokeratoelastoidosis and Focal Acral Hyperkeratosis PUNCTATE PALMOPLANTAR KERATODERMA WITH ASSOCIATED FEATURES/SYNDROMIC Cole Disease Keratoderma Climactericum Keratoderma and Cancer Other Etiologies of Acquired Keratoderma Aquagenic Palmoplantar Keratoderma Circumscribed Palmar or Plantar Hypokeratosis ACQUIRED KERATODERMAS AND RELATED CONDITIONS REFERENCES 59- Darier Disease and Hailey–Hailey Disease 59 Darier Disease and Hailey–Hailey Disease Darier Disease Introduction History Epidemiology Pathogenesis Clinical Features Onset and clinical pattern Symptoms Modifying factors Course of the disease Infectious complications Salivary glands Neuropsychiatric disorders Others Clinical subtypes of darier disease Acral hemorrhagic type Segmental types 1 and 2 Pathology Differential Diagnosis Acrokeratosis verruciformis of Hopf Other conditions Treatment General measures Topical and intralesional therapy Systemic therapy Surgical therapy Hailey–Hailey Disease Introduction History Epidemiology Pathogenesis Clinical Features Onset and clinical pattern Symptoms Modifying factors Course of the disease Complications Infections Malignant transformation Clinical subtypes of Hailey–Hailey disease Segmental type 1 Segmental type 2 Pathology Differential Diagnosis Treatment General measures Topical and intralesional therapy Surgical and physical therapy Systemic therapy Copyright notice References 60- Primary Immunodeficiencies 60 Primary Immunodeficiencies INTRODUCTION ATAXIA–TELANGIECTASIA Introduction Epidemiology Pathogenesis Clinical Features Laboratory Findings Differential Diagnosis Treatment CHRONIC MUCOCUTANEOUS CANDIDIASIS Introduction Epidemiology Pathogenesis Clinical Features Laboratory Findings Differential Diagnosis Treatment CARTILAGE–HAIR HYPOPLASIA SYNDROME CHÉDIAK–HIGASHI SYNDROME Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment COMPLEMENT DISORDERS Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment CHRONIC GRANULOMATOUS DISEASE Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment HYPERIMMUNOGLOBULIN E SYNDROMES Introduction and History Epidemiology Pathogenesis Clinical Features Laboratory Findings and Pathology Differential Diagnosis Treatment IMMUNOGLOBULIN DEFICIENCIES IPEX SYNDROME LEUKOCYTE ADHESION DEFICIENCY Introduction Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment SEVERE COMBINED IMMUNODEFICIENCY AND OMENN SYNDROME Introduction Epidemiology Pathogenesis Clinical Features Laboratory Findings and Pathology Differential Diagnosis Treatment WISKOTT–ALDRICH SYNDROME Introduction Epidemiology Pathogenesis Clinical Features Laboratory Findings and Pathology Differential Diagnosis Treatment REFERENCES 61- Neurofibromatosis and Tuberous Sclerosis Complex 61 Neurofibromatosis and Tuberous Sclerosis Complex INTRODUCTION NEUROFIBROMATOSIS TYPE 1 History Epidemiology Pathogenesis Clinical Features Oculocutaneous manifestations Neurologic manifestations Skeletal manifestations Cardiovascular manifestations Timing of onset of clinical manifestations Pathology Differential Diagnosis Management TUBEROUS SCLEROSIS COMPLEX Introduction History Epidemiology Pathogenesis Clinical Features Oculocutaneous manifestations Neurologic manifestations Cardiovascular manifestations Renal manifestations Other manifestations Pathology Differential Diagnosis Management REFERENCES 62- Mosaicism and Linear Lesions 62 Mosaicism and Linear Lesions Chapter Contents Introduction and History Patterns and Pathogenesis of Cutaneous Mosaicism APPROACH TO MOLECULAR TESTING FOR GENOMIC MOSAICISM FUNCTIONAL MOSAICISM IN X-LINKED GERMLINE DISORDERS Incontinentia Pigmenti Introduction History Genetics Pathogenesis Clinical features Pathology Differential diagnosis Treatment Hypohidrotic Ectodermal Dysplasia With Immune Deficiency Goltz Syndrome (Focal Dermal Hypoplasia) Introduction Genetics Pathogenesis Clinical features Pathology Differential diagnosis Treatment Conradi–Hünermann–Happle Syndrome (X-Linked Dominant Chondrodysplasia Punctata) CHILD Syndrome (Congenital Hemidysplasia With Ichthyosiform Erythroderma [or Nevus] and Limb Defects) Linear Skin Defects With Multiple Congenital Anomalies (Including MIDAS Syndrome) Oral–Facial–Digital Syndrome Type I X-linked Etiologies of Blaschko-Linear Hypo- and Hyperpigmentation X-Linked Hypohidrotic Ectodermal Dysplasia (Female Patients) Menkes Disease (Female Carriers) X-Linked Reticulate Pigmentary Disorder Epidermal Nevi and Related Syndromes Classification and Clinical Features of Epidermal Nevi Genetics of Epidermal Nevi Epidermal Nevus Syndromes Introduction History and terminology Phakomatosis Pigmentokeratotica, Schimmelpenning Syndrome, and Cutaneous Skeletal Hypophosphatemia Syndrome PIK3CA-Related Overgrowth Spectrum (PROS) Proteus Syndrome Superimposed (Type 2) Mosaic PTEN Hamartoma Tumor Syndrome ILVEN (Inflammatory Linear Verrucous Epidermal Nevus) Mosaicism in Other Autosomal Dominant Disorders Linear Darier Disease (Acantholytic Dyskeratotic Epidermal Nevus) Linear Hailey–Hailey Disease (Relapsing Linear Acantholytic Dermatosis) Linear Porokeratosis Porokeratotic Adnexal Ostial Nevus (PAON) Linear Basal Cell Nevus Syndrome Curry-Jones and Happle-Tinschert Syndromes Mosaic Neurofibromatosis Type 1 and Legius Syndrome Linear or Segmental Angiofibromas and Mosaicism in Tuberous Sclerosis Complex Linear or Segmental Benign Tumors Encephalocraniocutaneous Lipomatosis (Haberland Syndrome) Vascular Malformations Venous and Glomuvenous Malformations Capillary Malformations (Port-Wine Birthmarks) Pigmented Lesions With a Mosaic Distribution Pattern Congenital Melanocytic Nevi (CMN) Nevus Spilus McCune–Albright Syndrome Linear Inflammatory Disorders Linear Psoriasis Linear Lichen Planus Lichen Striatus “Blaschkitis” Other Linear Inflammatory Disorders Pigmentary Mosaicism Linear and Block-Like Hypo- and Hyperpigmentation Introduction History Epidemiology Genetics and pathogenesis Clinical features Associated syndromes Pathology Differential diagnosis Evaluation and management Nevus Depigmentosus Chimerism Block-Like Hyper- and Hypopigmentation Due to Chimerism References 63- Other Genodermatoses 63 Other Genodermatoses Introduction DISORDERS FEATURING TUMORIGENESIS MULTIPLE ENDOCRINE NEOPLASIA PTEN HAMARTOMA TUMOR SYNDROME, INCLUDING COWDEN SYNDROME Introduction History Epidemiology Pathogenesis Clinical Features Mucocutaneous manifestations Extracutaneous manifestations Pathology Differential Diagnosis Treatment GARDNER SYNDROME (VARIANT OF FAMILIAL ADENOMATOUS POLYPOSIS) Introduction History Epidemiology Pathogenesis Clinical Features Cutaneous and soft tissue manifestations Other extraintestinal manifestations Gastrointestinal manifestations Pathology Differential Diagnosis Management MUIR–TORRE SYNDROME (VARIANT OF LYNCH SYNDROME) Introduction History Epidemiology Pathogenesis Clinical Features Diagnosis Pathology Differential Diagnosis Treatment ENZYME DEFICIENCY DISEASES ALKAPTONURIA BIOTINIDASE AND HOLOCARBOXYLASE SYNTHETASE DEFICIENCIES FABRY DISEASE FUCOSIDOSIS GAUCHER DISEASE HARTNUP DISEASE MITOCHONDRIAL DISORDERS ACID SPHINGOMYELINASE DEFICIENCY (NIEMANN–PICK DISEASE) PHENYLKETONURIA Acknowledgment PREMATURE AGING SYNDROMES AND POIKILODERMAS HUTCHINSON–GILFORD PROGERIA SYNDROME Introduction History Epidemiology Pathogenesis Clinical Features Pathology and Laboratory Findings Differential Diagnosis Treatment WERNER SYNDROME Introduction History Epidemiology Pathogenesis Clinical Features Pathology and Laboratory Findings Differential Diagnosis Treatment ECTODERMAL DYSPLASIAS HYPOHIDROTIC ECTODERMAL DYSPLASIA Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment HYPOHIDROTIC ECTODERMAL DYSPLASIA WITH IMMUNE DEFICIENCY Pathogenesis Clinical Features Treatment HIDROTIC ECTODERMAL DYSPLASIA Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment WITKOP TOOTH AND NAIL SYNDROME ANKYLOBLEPHARON–ECTODERMAL DEFECTS–CLEFT LIP/PALATE SYNDROME Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ECTODERMAL DYSPLASIA–ECTRODACTYLY–CLEFTING SYNDROME Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Acknowledgments and disclosures REFERENCES 64- Developmental Anomalies 64 Developmental Anomalies INTRODUCTION THE MIDLINE LESION Midline Lesions of the Head, Neck, and Anterior Trunk Midline nasal lesions Midline lesions of the scalp Other developmental anomalies of the scalp Dermoid cysts Cephaloceles Nasal glial heterotopia Heterotopic brain tissue and rudimentary meningoceles Midline anterior neck inclusion cyst Midline cervical cleft Sternal clefts and supraumbilical raphae Midline Lesions of the Spine APLASIA CUTIS CONGENITA OTHER DEVELOPMENTAL ANOMALIES Congenital Lip Pits Accessory Tragi Congenital Cartilaginous Rests of the Neck Branchial Cleft Sinuses and Fistulae Supernumerary Nipples and Other Forms of Accessory Mammary Tissue Absent, Hypoplastic or Anomalous Nipples Skin Dimples Congenital Malformations of the Dermatoglyphics Rudimentary Polydactyly Amniotic Band Sequence and Disorganization Syndrome Other Developmental Anomalies Associated with Cutaneous Diseases REFERENCES 65- Melanocyte Biology 65 Melanocyte Biology INTRODUCTION ORIGIN AND FUNCTION OF THE MELANOCYTE FORMATION AND FUNCTION OF THE MELANOSOME REGULATION OF MELANIN BIOSYNTHESIS Ultraviolet Radiation (UVR) REFERENCES E-References 66- Vitiligo and Other Disorders of Hypopigmentation 66 Vitiligo and Other Disorders of Hypopigmentation INTRODUCTION Diagnosis of Leukodermas VITILIGO Epidemiology Pathogenesis Genetics Pathogenic pathway Clinical Features Characteristics of vitiligo lesions Clinical classification of vitiligo Clinical variants Disease course Ocular involvement Associated disorders Childhood vitiligo Pathology Differential Diagnosis Treatment Topical corticosteroids Topical calcineurin inhibitors (TCIs) Topical Janus kinase (JAK) inhibitors Photo(chemo)therapy Narrowband UVB Psoralen plus UVA (PUVA) Excimer laser and lamp Oral corticosteroid mini-pulse therapy Other systemic immunomodulators Antioxidants Afamelanotide Surgical therapies Combination therapies Maintenance therapies Micropigmentation Depigmentation Psychological support HEREDITARY HYPOMELANOSIS Oculocutaneous Albinism Epidemiology Pathogenesis Clinical features Ocular manifestations OCA1 OCA1A OCA1B OCA2 OCA3 OCA4 OCA5–8 Ocular albinism type 1 (OA1) Pathology Differential diagnosis Treatment Piebaldism Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Waardenburg Syndrome Epidemiology Pathogenesis Clinical features Waardenburg syndrome type 1 (WS1) Waardenburg syndrome type 2 (WS2) Klein–Waardenburg syndrome (WS3) Shah–Waardenburg syndrome (WS4) Tietz syndrome Pathology Diagnosis Treatment Disorders of Melanosome Biogenesis Hermansky–Pudlak syndrome Pathogenesis Clinical features Laboratory findings and pathology Differential diagnosis Treatment Cross syndrome Chédiak–Higashi syndrome Tricho-hepato-enteric syndrome (phenotypic diarrhea of infancy) Disorders of Melanosome Transport and/or Transfer Epidemiology Pathogenesis Clinical features Treatment Tuberous Sclerosis Complex Clinical features Pathogenesis Diagnosis “Pigmentary Mosaicism”: Blaschko-Linear Hypopigmentation, Segmental Pigmentation Disorder, and Nevus Depigmentosus Clinical features Pathology Pathogenesis (see Ch. 62) Diagnosis Epidemiology Pathogenesis Clinical features Pathology Treatment NUTRITIONAL HYPOMELANOSIS HYPOMELANOSIS SECONDARY TO CUTANEOUS INFLAMMATION Pityriasis Alba Sarcoidosis Hypopigmented Mycosis Fungoides Systemic Sclerosis (Scleroderma) and Lichen Sclerosus Lupus Erythematosus INFECTIOUS AND PARASITIC HYPOMELANOSIS Tinea (Pityriasis) Versicolor Hansen Disease (Leprosy) Treponematoses Onchocerciasis Post-Kala-Azar Dermal Leishmaniasis Herpes Zoster HALO NEVUS AND MELANOMA-ASSOCIATED LEUKODERMA Halo Nevus Melanoma-Associated Leukoderma CHEMICAL AND PHARMACOLOGIC HYPOMELANOSIS HYPOMELANOSIS FROM PHYSICAL AGENTS MISCELLANEOUS Idiopathic Guttate Hypomelanosis Vagabond’s Leukomelanoderma Progressive Macular Hypomelanosis Hair Hypomelanosis Leukodermas Without Hypomelanosis Woronoff’s ring Nevus anemicus Cutaneous edema and anemia Angiospastic macules (Bier spots) REFERENCES 67- Disorders of Hyperpigmentation 67 Disorders of Hyperpigmentation DIFFUSE AND CIRCUMSCRIBED HYPERPIGMENTATION Introduction POSTINFLAMMATORY HYPERPIGMENTATION Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ERYTHEMA DYSCHROMICUM PERSTANS Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment LICHEN PLANUS PIGMENTOSUS MELASMA Introduction and Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ADDITIONAL FORMS OF CIRCUMSCRIBED HYPERPIGMENTATION Segmental Pigmentation Disorder Familial Progressive Hyperpigmentation GIST-Cutaneous Hyperpigmentation Disease Primary (Localized) Cutaneous Amyloidosis Mastocytosis Tinea (Pityriasis) Versicolor Atrophoderma of Pasini and Pierini PIGMENTED LESIONS Lentigines Café-au-Lait Macules DRUG-INDUCED HYPERPIGMENTATION OR DISCOLORATION ADDITIONAL FORMS OF DIFFUSE HYPERPIGMENTATION PIGMENTARY DEMARCATION LINES Introduction Differential Diagnosis Treatment LINEAR POSTINFLAMMATORY HYPERPIGMENTATION Clinical Features Differential Diagnosis FLAGELLATE PIGMENTATION FROM BLEOMYCIN Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment SHIITAKE DERMATITIS (FLAGELLATE MUSHROOM DERMATITIS) Introduction History and Epidemiology Pathogenesis Clinical Features Pathology Treatment HYPERPIGMENTATION ALONG THE LINES OF BLASCHKO Linear and Whorled Nevoid Hypermelanosis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Incontinentia Pigmenti RETICULATED HYPERPIGMENTATION PRURIGO PIGMENTOSA DYSKERATOSIS CONGENITA Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment NAEGELI–FRANCESCHETTI–JADASSOHN SYNDROME Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment DERMATOPATHIA PIGMENTOSA RETICULARIS Introduction and Pathogenesis Clinical Features Pathology Differential Diagnosis X-LINKED RETICULATE PIGMENTARY DISORDER Introduction and Pathogenesis Epidemiology Clinical Features Pathology Differential Diagnosis Treatment DOWLING–DEGOS DISEASE Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment RETICULATE ACROPIGMENTATION OF KITAMURA Introduction and Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment DYSCHROMATOSES DYSCHROMATOSIS SYMMETRICA HEREDITARIA Introduction Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment DYSCHROMATOSIS UNIVERSALIS HEREDITARIA Introduction and Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ACQUIRED BRACHIAL CUTANEOUS DYSCHROMATOSIS REFERENCES 68- Biology of Hair and Nails 68 Biology of Hair and Nails PRINCIPLES OF ADNEXAL MORPHOGENESIS BIOLOGY OF HAIR Hair Follicle Morphogenesis Hair follicle patterning Postnatal hair follicle development The Mature Hair Follicle: Cycling and Anatomy Anagen Catagen Telogen Exogen Structure of the hair fiber Hair Keratins Desmosomes in the Hair Follicle Hair Follicle Stem Cells The Hair Follicle and the Immune System BIOLOGY OF NAILS Nail Unit Anatomy Nail Embryology Nail Matrix Matrix anatomy Matrix function Nail Stem Cells Nail Unit Melanocytes The Nail Immune System Nail Keratins Other Nail Plate Components Nail Growth REFERENCES 69- Alopecias 69 Alopecias INTRODUCTION NON-CICATRICIAL (NON-SCARRING) ALOPECIAS Androgenetic Alopecia Introduction Pathogenesis Genetic factors Hormonal factors Clinical features Diagnosis Differential diagnosis Treatment Telogen Effluvium Introduction Pathogenesis Clinical features and diagnosis Treatment Anagen Effluvium Alopecia Areata Introduction Pathogenesis Clinical features Comorbidities and associated disorders Differential diagnosis Treatment Topical and intralesional Systemic Trichotillomania Pathogenesis Clinical features Treatment Pressure Alopecia (Pressure-Induced Alopecia) Temporal Triangular Alopecia Traction Alopecia Lipedematous Scalp and Lipedematous Alopecia Psoriatic Alopecia Syphilitic Alopecia Non-Cicatricial Alopecia in Systemic Lupus Erythematosus Congenital Atrichia with Papular Lesions CICATRICIAL (SCARRING) ALOPECIAS Introduction Lichen Planopilaris Classic Lichen Planopilaris Pathophysiology Clinical features and diagnosis Treatment Frontal Fibrosing Alopecia Pathogenesis Clinical features Treatment Graham Little–Piccardi–Lasseur Syndrome Fibrosing Alopecia in a Pattern Distribution Classic Pseudopelade (Pseudopelade of Brocq) Central Centrifugal Cicatricial Alopecia Pathophysiology Clinical features Differential diagnosis Treatment Discoid Lupus Erythematosus Introduction Clinical features Diagnosis Treatment Follicular mucinosis Keratosis Follicularis Spinulosa Decalvans Folliculitis Decalvans Pathophysiology Clinical features Treatment Acne Keloidalis Pathophysiology Clinical features Treatment Dissecting Cellulitis Clinical features and diagnosis Treatment Acne Necrotica Erosive Pustular Dermatosis of the Scalp Nonspecific (End-Stage) Cicatricial Alopecia HAIR SHAFT ABNORMALITIES Hair Shaft Abnormalities Associated With Increased Hair Fragility “Bubble hair” Monilethrix Pili torti Trichorrhexis invaginata Trichorrhexis nodosa Trichothiodystrophy Hair Abnormalities Not Associated With Increased Hair Fragility Acquired progressive kinking of the hair Loose anagen hair syndrome Pili annulati Pili bifurcati Pili multigemini Uncombable hair (spun-glass hair) Woolly hair ALOPECIA OF SITES OTHER THAN THE SCALP Acknowledgment REFERENCES 70- Hypertrichosis and Hirsutism 70 Hypertrichosis and Hirsutism HYPERTRICHOSIS Introduction Clinical Features Generalized hypertrichosis Congenital generalized hypertrichosis Prepubertal hypertrichosis Acquired generalized hypertrichosis Acquired hypertrichosis lanuginosa Localized hypertrichosis Congenital localized hypertrichosis Congenital melanocytic nevi and plexiform neurofibromas Becker melanosis (nevus) Other hamartomas and infantile tumors Nevoid hypertrichosis Spinal dysraphism and the hair collar sign Localized hypertrichosis in hereditary and acquired systemic diseases Acquired localized hypertrichosis Treatment HIRSUTISM Introduction Epidemiology Classification Clinical Features Idiopathic (constitutional) hirsutism Ovarian hirsutism Non-tumoral ovarian hirsutism Polycystic ovary syndrome (PCOS) Ovarian hyperthecosis Tumoral ovarian hirsutism Adrenal hirsutism Non-tumoral adrenal hirsutism – adrenal hyperplasias Tumoral adrenal hirsutism Other endocrinopathies associated with hirsutism Hypercortisolism (Cushing syndrome) Hyperprolactinemia Acromegaly Thyroid disorders Insulin-resistance disorders Drug-induced hirsutism Diagnosis Treatment Systemic therapy Topical therapy Direct hair removal methods REFERENCES 71- Nail Disorders 71 Nail Disorders ANATOMY NAIL SIGNS Nail Signs Due to Abnormal Nail Matrix Function Beau’s lines Onychomadesis (nail shedding) Pitting Onychorrhexis Trachyonychia (twenty-nail dystrophy, sandpapered nails) True leukonychia Koilonychia (spoon nails) Nail Signs Due to Nail Bed Disorders Onycholysis Subungual hyperkeratosis Apparent leukonychia Splinter hemorrhages Nail Signs Due to Deposition of Pigment Longitudinal melanonychia Green nail syndrome CONGENITAL AND HEREDITARY NAIL DISEASES Congenital Malalignment of the Great Toenails Congenital Hypertrophy of the Lateral Fold of the Hallux Racquet Thumbs (Brachyonychia) Nail–Patella Syndrome (Onycho-Osteodysplasia Fong Disease) Epidermolysis Bullosa Ectodermal Dysplasias Pachyonychia Congenita Darier Disease (Follicular Dyskeratosis) THE NAIL IN DERMATOLOGIC DISEASES Psoriasis Treatment Acrodermatitis Continua of Hallopeau (Hallopeau’s Acrodermatitis, Dermatitis Repens) Treatment Parakeratosis Pustulosa Treatment Lichen Planus Treatment Trachyonychia (Twenty-Nail Dystrophy, Sandpapered Nails) Alopecia Areata Eczema (Dermatitis) THE NAIL IN SYSTEMIC DISEASES Clubbing (Watch-Glass Nails, Hippocratic Fingers, Drumstick Fingers) Yellow Nail Syndrome Treatment Apparent Leukonychia Autoimmune Connective Tissue Disorders HIV Infection Drug-Induced Nail Abnormalities INFECTIONS Acute Paronychia Treatment Warts Treatment Onychomycosis (Tinea Unguium) ENVIRONMENTAL NAIL DISORDERS Brittle Nails (Fragility, Onychoschizia) Treatment Chronic Paronychia Treatment Idiopathic Onycholysis Treatment TRAUMATIC NAIL ABNORMALITIES Onychotillomania Treatment Subungual Hematoma Treatment Traumatic Toenail Abnormalities Onychogryphosis Pincer Nails (Trumpet Nails) Treatment Ingrown Toenails (Onychocryptosis) Treatment NAIL TUMORS Benign Tumors and Proliferations Pyogenic granuloma (botryomycoma) Fibromas/fibrokeratomas Subungual exostosis Myxoid cyst (mucous cyst, digital mucous cyst) Treatment Glomus tumor Onychomatricoma Onychopapilloma Melanocytic nevi of the nail matrix Treatment Malignant Tumors Bowen disease (squamous cell carcinoma in situ) Keratoacanthoma Squamous cell carcinoma Verrucous carcinoma (carcinoma cuniculatum, epithelioma cuniculatum) Melanoma REFERENCES 72- Oral Diseases 72 Oral Diseases Introduction COMMON BENIGN CONDITIONS OF THE ORAL CAVITY Fordyce Granules Introduction Epidemiology Clinical features Pathology Treatment Geographic Tongue Introduction Epidemiology Clinical features Pathology Treatment Fissured Tongue Introduction Epidemiology Clinical features Pathology Treatment Hairy Tongue Introduction Epidemiology Clinical features Pathology Treatment Central Papillary Atrophy Introduction Epidemiology Clinical features Pathology Treatment SYNDROMES OF THE HEAD AND NECK Basal Cell Nevus Syndrome Gardner Syndrome Multiple Endocrine Neoplasia Syndrome Type 2B PERIODONTAL AND DENTAL DISEASE Necrotizing Ulcerative Gingivitis Introduction Epidemiology Clinical features Pathology Treatment Desquamative Gingivitis Introduction Epidemiology Clinical features Pathology Treatment Sequelae of Dental Caries Introduction Clinical features Treatment PHYSICAL AND CHEMICAL INJURIES Fibroma Introduction Epidemiology Clinical features Pathology Treatment Contact Stomatitis Introduction Epidemiology Clinical features Pathology Treatment Morsicatio Mucosae Oris Introduction Epidemiology Clinical features Pathology Treatment Traumatic Ulcer Introduction Epidemiology Clinical features Pathology Treatment Drug-Related Gingival Hyperplasia Introduction Epidemiology Clinical features Pathology Treatment ALLERGIC AND IMMUNOLOGIC DISEASES Recurrent Aphthous Stomatitis Introduction Epidemiology Clinical features Pathology Treatment Behçet Disease Autoimmune Bullous Diseases CHEILITIS Introduction Eczematous cheilitis Actinic Cheilitis (see below) Angular Cheilitis Drug-Induced Cheilitis Exfoliative Cheilitis Plasma Cell Cheilitis Cheilitis Glandularis Orofacial Granulomatosis (OFG) Introduction Epidemiology Clinical features Pathology Treatment Granulomatosis with Polyangiitis (Formerly Wegener Granulomatosis) Introduction Epidemiology Clinical features Pathology Treatment EPITHELIAL PATHOLOGY Oral Leukoplakia and Proliferative Verrucous Leukoplakia Introduction Epidemiology Clinical features Pathology Differential diagnosis Treatment Erythroplakia Introduction Epidemiology Clinical features Pathology Treatment Nicotinic Stomatitis Introduction Epidemiology Clinical features Pathology Treatment Actinic Cheilitis Introduction Epidemiology Clinical features Pathology Treatment Oral Squamous Cell Carcinoma Introduction Epidemiology Clinical features Pathology Treatment Verrucous Carcinoma Introduction Epidemiology Clinical features Pathology Treatment SALIVARY GLAND DISEASES Mucocele Introduction Epidemiology Clinical features Pathology (see Ch. 110) Treatment Necrotizing Sialometaplasia Introduction Epidemiology Clinical features Pathology Treatment Sjögren Syndrome Introduction Epidemiology Clinical features Pathology Treatment (see Table 40.5) Salivary Gland Tumors Introduction Epidemiology Clinical features Pathology Treatment ORAL MANIFESTATIONS OF HEMATOLOGIC/ONCOLOGIC DISEASE Oral Mucositis Introduction Epidemiology Clinical features Treatment Leukemia Introduction Clinical features Treatment Lymphoma Introduction Clinical features Pathology Treatment Melanoma Introduction Clinical features Pathology Treatment ORAL MANIFESTATIONS OF SYSTEMIC DISEASE Amyloidosis Introduction Clinical features Pernicious Anemia Introduction Epidemiology Clinical features Treatment Crohn Disease Introduction/epidemiology Clinical features Pathology Treatment Pyostomatitis Vegetans Introduction Epidemiology Clinical features Pathology Treatment Oral Manifestations of HIV Infection REFERENCES 73- Anogenital (Non-venereal) Diseases 73 Anogenital (Non-venereal) Diseases INTRODUCTION LICHEN SCLEROSUS LICHEN PLANUS ZOON BALANITIS/VULVITIS EPITHELIAL DISORDERS OF THE ANOGENITAL REGION Dermatitis Introduction Pathogenesis Clinical features Differential diagnosis Treatment Contact Dermatitis Psoriasis Clinical features Differential diagnosis Treatment RED SCROTUM SYNDROME/RED VULVA SYNDROME PREMALIGNANT AND MALIGNANT LESIONS Squamous Intraepithelial Neoplasia (Vulvar, Penile, Anal) Introduction Epidemiology Pathogenesis Pathology Clinical features Differential diagnosis Treatment Prevention Pseudoepitheliomatous Keratotic and Micaceous Balanitis Invasive Squamous Cell Carcinomas Epidemiology Pathogenesis Clinical features Differential diagnosis Treatment Anogenital Melanoma Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Basal Cell Carcinoma Genital Lymphoma Extramammary Paget Disease Introduction Epidemiology Etiology and classification Clinical features Pathology Differential diagnosis Evaluation Treatment DYSESTHETIC GENITAL PAIN SYNDROMES General Principles of Management Localized Vulvodynia (Vestibulodynia) Introduction Clinical features Differential diagnosis Treatment Generalized Vulvodynia/Scrotodynia (Dysesthetic Vulvodynia/Scrotodynia) Introduction Clinical features Differential diagnosis Treatment Anal Pain BENIGN LESIONS Epidermoid Cysts Vestibular Papillomatosis THE ANOGENITAL REGION AND SYSTEMIC DISEASE INFECTIONS Perianal Streptococcal Disease Recurrent Toxin-Mediated Perineal Erythema Kawasaki Disease Fournier Gangrene Erythrasma Dermatophytosis Genital Candidiasis Introduction Epidemiology Etiology Clinical features Differential diagnosis Treatment Recurrent Candidiasis Schistosomiasis EROSIVE GENITAL DISEASE Acquired Autoimmune Bullous Diseases Acquired Inflammatory Bullous Diseases Erythema multiforme and Stevens–Johnson syndrome Fixed drug eruption Inherited Bullous Disease Hailey–Hailey disease REFERENCES 74- Bacterial Diseases 74 Bacterial Diseases THE CUTANEOUS MICROBIOTA GRAM-POSITIVE BACTERIA STAPHYLOCOCCAL AND STREPTOCOCCAL SKIN INFECTIONS Impetigo Introduction Epidemiology Pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Bacterial Folliculitis Introduction Epidemiology and pathogenesis Clinical features Diagnosis and differential diagnosis Treatment Abscesses, Furuncles, and Carbuncles Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Methicillin-Resistant Staphylococcus aureus Infection Introduction Clinical features Pathogenesis Diagnosis and treatment Blistering Distal Dactylitis Ecthyma Staphylococcal Scalded Skin Syndrome Introduction Epidemiology Pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Toxic Shock Syndrome Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Scarlet Fever Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Streptococcal Toxic Shock Syndrome Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Erysipelas Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Streptococcal Intertrigo Perianal and Vulvovaginal (Perineal) Streptococcal Infection Cellulitis Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Pyomyositis Botryomycosis Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Necrotizing Fasciitis Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Bacteremia/Septicemia CLOSTRIDIAL SKIN INFECTIONS CORYNEBACTERIAL SKIN INFECTIONS Erythrasma Pitted Keratolysis Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Trichomycosis Axillaris, Pubis, and Capitis Cutaneous Diphtheria OTHER GRAM-POSITIVE SKIN INFECTIONS Cutaneous Anthrax Introduction and epidemiology History Pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Bacillus cereus Infection Erysipeloid Listeriosis GRAM-NEGATIVE BACTERIA NEISSERIA MENINGITIDIS Acute and Chronic Meningococcemia Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment PSEUDOMONAS AERUGINOSA Green Nail Syndrome Pseudomonal Pyoderma and Blastomycosis-Like Pyoderma Otitis Externa and Necrotizing (Malignant) Otitis Externa Pseudomonal Folliculitis Pseudomonas Hot-Foot Syndrome Ecthyma Gangrenosum BARTONELLA Bartonellosis Introduction History Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Cat Scratch Disease Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Bacillary Angiomatosis Introduction History Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment OTHER GRAM-NEGATIVE SKIN INFECTIONS Brucellosis Glanders Melioidosis Cutaneous Malacoplakia (Malakoplakia) Tularemia Haemophilus influenzae Cellulitis Rhinoscleroma Salmonellosis Rat-Bite Fever Plague Vibrio vulnificus Infection EHRLICHIOSIS AND ANAPLASMOSIS SPIROCHETES BORRELIA BURGDORFERI Lyme Disease Borrelial Lymphocytoma Acrodermatitis Chronica Atrophicans NON-VENEREAL (ENDEMIC) TREPONEMATOSES Yaws Pinta Bejel LEPTOSPIROSIS BACTERIA PREVIOUSLY CLASSIFIED AS FUNGI ACTINOMYCOSIS Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment NOCARDIOSIS REFERENCES 75- Mycobacterial Infections 75 Mycobacterial Infections HANSEN DISEASE (LEPROSY) Introduction History Epidemiology Pathogenesis Clinical Features Pathology and Laboratory Evaluation Differential Diagnosis Treatment CUTANEOUS TUBERCULOSIS Introduction History Epidemiology Pathogenesis Clinical Features and Pathology Cutaneous tuberculosis Tuberculids BCG inoculation Diagnosis Treatment NON-TUBERCULOUS MYCOBACTERIOSES Introduction Mycobacterium ulcerans Introduction and history Epidemiology Pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Mycobacterium marinum Introduction and history Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Mycobacterium kansasii Introduction and history Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Mycobacterium fortuitum, Mycobacterium chelonae, and Mycobacterium abscessus Introduction and history Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Mycobacterium avium Complex (MAC) Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Mycobacterium haemophilum Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment Mycobacterium scrofulaceum Introduction Epidemiology and pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment REFERENCES 76- Rickettsial Diseases 76 Rickettsial Diseases INTRODUCTION SPOTTED FEVER AND TYPHUS GROUP RICKETTSIAL INFECTIONS History Epidemiology Pathogenesis Clinical Features Clinical course and systemic features Shared cutaneous features Features of specific diseases Pathology Diagnosis and Differential Diagnosis Treatment SCRUB TYPHUS HUMAN EHRLICHIOSES HUMAN GRANULOCYTIC ANAPLASMOSIS Q FEVER REFERENCES 77- Fungal Diseases 77 Fungal Diseases SUPERFICIAL MYCOSES Introduction Non-inflammatory Superficial Mycoses History Epidemiology Pathogenesis Clinical features Piedra Tinea nigra Tinea (pityriasis) versicolor Malassezia (Pityrosporum) folliculitis Pathology and fungal culture Differential diagnosis Treatment Dermatophytoses Introduction History Epidemiology Pathogenesis Clinical features Tinea corporis Tinea cruris Tinea manuum Tinea barbae Tinea faciei Tinea capitis Tinea pedis Tinea unguium (dermatophytic onychomycosis) Pathology Differential diagnosis Treatment Invasive dermatophytosis Mucocutaneous Candida Infections Chronic mucocutaneous candidiasis Erosive Papulonodular Dermatosis: Granuloma Gluteale Infantum/Adultorum and Perianal Pseudoverrucous Papules/Nodules (see C ... SUBCUTANEOUS MYCOSES Chromoblastomycosis Introduction History Epidemiology and pathogenesis Clinical features Pathology Differential diagnosis Treatment Mycetoma Introduction History and epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Sporotrichosis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Lobomycosis SYSTEMIC MYCOSES True Pathogens Introduction Histoplasmosis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Blastomycosis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Coccidioidomycosis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Paracoccidioidomycosis Introduction and epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Opportunistic Pathogens Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Phaeohyphomycosis Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Pneumocystis REFERENCES 78- Cutaneous Manifestations of HIV Infection 78 Cutaneous Manifestations of HIV Infection INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS HIV-RELATED INFECTIOUS SKIN CONDITIONS Viral Infections Primary HIV exanthem (acute retroviral syndrome) Herpes simplex virus (HSV) infection Varicella and herpes zoster Molluscum contagiosum Human papillomavirus (HPV) infections Oral hairy leukoplakia due to Epstein–Barr virus (EBV) infection Cytomegalovirus (CMV) infections Bacterial Infections Staphylococcus aureus infections Bacillary angiomatosis Mycobacterial infections Syphilis Fungal and Related Infections Candidiasis Dermatophytoses Systemic fungal infections Pneumocystis jirovecii infections Other fungal and related infections Parasitic Infections Leishmaniasis Strongyloidiasis Acanthamebiasis Ectoparasitic Infestations and Insect Bites Scabies Demodicosis Insect bite reactions NON-INFECTIOUS HIV-RELATED DERMATOSES Papulosquamous and Eczematous Disorders Seborrheic dermatitis Psoriasis Reactive arthritis Other eczematous and papulosquamous dermatoses Non-Infectious Pruritic Papular Disorders Pruritic papular eruption Eosinophilic folliculitis Hair and Nail Disorders Vasculitis Photosensitivity Reactions UV light hypersensitivity Porphyria cutanea tarda (PCT) Chronic actinic dermatitis Metabolic Changes HIV/ART-associated lipodystrophy and weight gain Malnutrition Miscellaneous Dermatoses HIV-RELATED CUTANEOUS NEOPLASMS Kaposi Sarcoma (KS) Keratinocyte Carcinomas and Melanoma Lymphomas Other Cutaneous Neoplasms DIFFERENTIAL DIAGNOSIS AND DIAGNOSIS Differential Diagnosis of HIV-Associated Skin Conditions Diagnosis of HIV-associated skin conditions Laboratory Diagnosis of HIV Infection ANTIRETROVIRAL THERAPY (ART) Antiretroviral Medications for Treatment and Prevention Immune Reconstitution Inflammatory Syndrome (IRIS) Drug–Drug Interactions Drug Eruptions CONCLUSIONS REFERENCES 79- Human Papillomaviruses 79 Human Papillomaviruses INTRODUCTION History EPIDEMIOLOGY PATHOGENESIS Papillomavirus Evolution Virology Papillomavirus Life Cycle Host Immune Response Oncogenic Potential of HPV CLINICAL FEATURES Cutaneous Infections Mucosal Infections PATHOLOGY Common and Deep Palmoplantar Warts Flat Warts Epidermodysplasia Verruciformis Anogenital Warts Giant Condylomata of Buschke–Löwenstein Squamous Intraepithelial Neoplasias DIFFERENTIAL DIAGNOSIS Common, Flat, and Palmoplantar Warts Anogenital Lesions Oral Warts THERAPY General Considerations Local Destructive Therapy Topical and Intralesional Cytotoxic Therapy Topical Immunomodifiers Systemic Immunomodifiers Immunotherapy Antiviral Agents Retinoids Anti-PD-1/PD-L1 Antibodies Special Considerations, Including Intraepithelial Neoplasias and Pregnancy HPV VACCINES REFERENCES 80- Human Herpesviruses 80 Human Herpesviruses HERPES SIMPLEX VIRUSES (HSV-1 AND HSV-2) Introduction History Epidemiology Pathogenesis Clinical Features Other Clinical Presentations of HSV Infection Diagnosis and Pathology Differential Diagnosis Treatment and Prevention VARICELLA–ZOSTER VIRUS (VZV HHV-3) Introduction History Epidemiology Pathogenesis Clinical Features Varicella Herpes zoster Diagnosis and Pathology Differential Diagnosis Treatment and Prevention Varicella Herpes zoster EPSTEIN–BARR VIRUS (HHV-4) Introduction and History Epidemiology Pathogenesis Clinical Features Diagnosis and Pathology Differential Diagnosis Treatment CYTOMEGALOVIRUS (HHV-5) Introduction History Epidemiology Pathogenesis Clinical Features Diagnosis and Pathology Differential Diagnosis Treatment and Prevention HUMAN HERPESVIRUS TYPE 6 (HHV-6) Introduction History Epidemiology Pathogenesis Clinical Features Diagnosis and Pathology Differential Diagnosis Treatment HUMAN HERPESVIRUS TYPE 7 (HHV-7) HUMAN HERPESVIRUS TYPE 8 (HHV-8) Introduction History Epidemiology Pathogenesis Clinical Features Diagnosis and Pathology Treatment CONCLUSION REFERENCES 81- Other Viral Diseases 81 Other Viral Diseases INTRODUCTION ENTEROVIRUS INFECTIONS Introduction Epidemiology Pathogenesis Clinical Features and Differential Diagnosis Pathology Treatment MEASLES Introduction and History Epidemiology Pathogenesis Clinical Features and Differential Diagnosis Pathology Treatment RUBELLA Introduction and History Epidemiology Pathogenesis Clinical Features and Differential Diagnosis Pathology Treatment ERYTHEMA INFECTIOSUM Introduction and History Epidemiology Pathogenesis Clinical Features and Differential Diagnosis Pathology Treatment ROSEOLA INFANTUM UNILATERAL LATEROTHORACIC EXANTHEM Introduction and History Epidemiology Pathogenesis Clinical Features and Differential Diagnosis Pathology Treatment GIANOTTI–CROSTI SYNDROME Introduction and History Epidemiology Pathogenesis Clinical Features and Differential Diagnosis Pathology Treatment POXVIRUS INFECTIONS VIRAL HEMORRHAGIC FEVERS, INCLUDING DENGUE WEST NILE VIRUS INFECTION ZIKA VIRUS INFECTION CHIKUNGUNYA FEVER BARMAH FOREST AND ROSS RIVER VIRUS INFECTIONS CUTANEOUS MANIFESTATIONS OF HEPATITIS A, B, AND C INFECTION POLYOMAVIRUS INFECTIONS RABIES CUTANEOUS MANIFESTATIONS OF SARS-CoV-2 INFECTION KAWASAKI DISEASE Introduction and History Epidemiology Pathogenesis Clinical Features and Differential Diagnosis Pathology Treatment REFERENCES 82- Sexually Transmitted Infections 82 Sexually Transmitted Infections INTRODUCTION SYPHILIS History Epidemiology Biology of T. pallidum Pathogenesis of Untreated Syphilis Primary stage Secondary stage Latency Tertiary stage Syphilis and HIV Clinical Features Primary syphilis Secondary syphilis Latent syphilis Tertiary (late) syphilis “Benign” late syphilis Cardiovascular syphilis Neurosyphilis Neurosyphilis in HIV-infected individuals Laboratory diagnosis of neurosyphilis Congenital syphilis Early congenital syphilis Late congenital syphilis and stigmata Laboratory diagnosis of congenital syphilis Laboratory Diagnosis of Syphilis Identification of T. pallidum Microscopic examination Polymerase chain reaction-based assays Serologic tests for syphilis Non-treponemal tests Treponemal tests Pathology Differential Diagnosis Treatment GONORRHEA History Epidemiology Transmission Biology of N. gonorrhoeae Pathogenesis Clinical Features Gonococcal infection in men Gonococcal infection in women Extragenital gonorrhea Pharyngeal gonorrhea Rectal gonorrhea Gonococcal ophthalmia (including ophthalmia neonatorum) Disseminated gonococcal infection Arthritis–dermatosis syndrome (gonococcemia) Laboratory Diagnosis Staining methods Culture techniques Non-culture techniques for gonococcal diagnosis Nucleic acid amplification techniques (NAATs) Pathology Differential Diagnosis Treatment CHANCROID History Epidemiology Transmission Chancroid and HIV Biology of the Organism Pathogenesis Clinical Features Pathology Diagnosis Differential Diagnosis Treatment LYMPHOGRANULOMA VENEREUM History Epidemiology Pathogenesis Clinical Features Pathology Diagnosis Differential Diagnosis Treatment DONOVANOSIS (GRANULOMA INGUINALE) History Epidemiology Pathogenesis Clinical Features Pathology Diagnosis Differential Diagnosis Treatment REFERENCES 83- Protozoa and Worms 83 Protozoa and Worms PROTOZOA LEISHMANIASIS Introduction Epidemiology Pathogenesis Clinical Features Cutaneous leishmaniasis Mucocutaneous/mucosal leishmaniasis Visceral leishmaniasis (kala-azar) Leishmaniasis and HIV Pathology Diagnosis Differential Diagnosis Treatment CUTANEOUS DISEASES CAUSED BY AMEBAS Amebiasis Due to Entamoeba histolytica Introduction Epidemiology Pathogenesis Clinical features Pathology and diagnosis Differential diagnosis Treatment Balamuthia mandrillaris Infection Introduction Epidemiology Pathogenesis Clinical features Pathology and diagnosis Treatment TRYPANOSOMIASIS Chagas Disease Epidemiology Pathogenesis Clinical features Pathology Diagnosis and differential diagnosis Treatment African Trypanosomiasis Epidemiology Pathogenesis Clinical features Pathology and diagnosis Differential diagnosis Treatment TOXOPLASMOSIS WORMS (HELMINTHS) CUTANEOUS LARVA MIGRANS Epidemiology and Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment GNATHOSTOMIASIS Introduction Epidemiology Pathogenesis Clinical Features Pathology Diagnosis and Differential Diagnosis Treatment ONCHOCERCIASIS Introduction Epidemiology Pathogenesis Clinical Features Pathology Diagnosis Differential Diagnosis Treatment FILARIASIS Introduction Epidemiology Pathogenesis Clinical Features Diagnosis Differential Diagnosis Treatment SCHISTOSOMIASIS AND SWIMMER’S ITCH Introduction Epidemiology Pathogenesis Clinical Features Pathology Diagnosis Differential Diagnosis Treatment CYSTICERCOSIS AND ECHINOCOCCOSIS Introduction Epidemiology Pathogenesis Clinical Features Diagnosis Treatment REFERENCES 84- Infestations 84 Infestations Scabies Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Permethrin Spinosad Lindane Crotamiton Sulfur ointment Benzyl benzoate Ivermectin Head Lice Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Pyrethrins Permethrin Malathion Ivermectin Dimethicone Spinosad Abametapir Benzyl alcohol Lindane Carbaryl Crab Lice Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Body Lice Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Tungiasis Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Cutaneous Myiasis Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Preventative Measures References 85- Bites and Stings 85 Bites and Stings Insects Insect Bites and Stings (Class Insecta) Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Fire Ants Introduction Pathogenesis Clinical features Treatment Bedbugs Introduction Pathogenesis Clinical features Treatment Triatomine (Reduviid) Bug Introduction Clinical features Blister Beetles Introduction Clinical features Pathology Treatment Rove Beetles Introduction Clinical features Pathology Treatment Carpet Beetles Introduction Clinical features Treatment Fleas Introduction Clinical features Treatment Lepidopterism Introduction Pathogenesis Clinical features Arachnids Tick Bites (Class Arachnida: Subclass Acarina) Introduction Clinical features Treatment Environmental measures Repellents Tick removal Antibiotic prophylaxis after tick bites Amblyomma Ticks Introduction Clinical features Dermacentor Ticks Introduction Pathogenesis Clinical features Rhipicephalus Ticks Introduction Clinical features Ixodes Ticks Introduction Clinical features Mites (Class Arachnida: Subclass Acarina) Introduction Clinical features Differential diagnosis Treatment Chiggers Introduction Clinical features Treatment Cheyletiella Introduction Clinical features Treatment Spider Bites (Class Arachnida: Order Araneae) Widow Spiders (Latrodectus) Introduction Pathogenesis Clinical features Treatment Loxosceles Spiders Introduction Pathogenesis Clinical features Pathology Treatment Funnel Web Spiders Introduction Pathogenesis Clinical features Tarantulas (Family Theraphosidae) Introduction Clinical features Pathology Scorpions (Class Arachnida: Order Scorpiones) Introduction Clinical features Treatment Centipedes (Class Chilopoda) And Millipedes (Class Diplopoda) Introduction Clinical features Treatment Snake Bites Introduction Clinical features Treatment Dog And Cat Bites Introduction Clinical features Treatment Leeches Introduction Pathogenesis Clinical features Treatment Leech therapy Marine Injuries Introduction Pathogenesis Clinical features Pathology Treatment References 86- Ultraviolet Radiation 86 Ultraviolet Radiation INTRODUCTION SPECTRUM OF UV LIGHT AND ABSORPTION SPECTRA SHORT-TERM EFFECTS OF ULTRAVIOLET LIGHT: SUNBURN AND TANNING EFFECTS ON THE CUTANEOUS IMMUNE SYSTEM LONG-TERM EFFECTS OF ULTRAVIOLET LIGHT: PHOTOAGING AND PHOTOCARCINOGENESIS Photoaging UV-Induced Tumor Formation UV INDUCTION OF DNA DAMAGE REPAIR OF UV-INDUCED DNA DAMAGE UV-INDUCED MUTATIONS MECHANISMS OF UV-BASED PHOTOTHERAPY PHOTOPROTECTION BY UV FILTERS AND OTHER MODALITIES REFERENCES 87- Photodermatologic Disorders 87 Photodermatologic Disorders Introduction Abnormal Cutaneous RESPONSES To Light Immunologically-Mediated Photodermatoses Polymorphous light eruption Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Actinic prurigo Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Hydroa vacciniforme Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Chronic actinic dermatitis Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Solar urticaria Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Photosensitivity Due to Hereditary Defects in DNA Repair Xeroderma pigmentosum Introduction and history Epidemiology Pathogenesis Clinical features Treatment Cockayne syndrome Introduction and history Epidemiology Pathogenesis Clinical features Treatment UV-sensitive syndrome Trichothiodystrophy Introduction and history Epidemiology Pathogenesis Clinical features Treatment Photosensitivity Due to Chromosomal Instability Bloom syndrome Introduction and history Epidemiology Pathogenesis Clinical features Treatment Rothmund–Thomson syndrome Introduction and history Epidemiology Pathogenesis Clinical features Differential diagnosis Treatment Chemical- and Drug-Induced Photosensitivity Exogenous photosensitivity Introduction and history Epidemiology Pathogenesis Clinical features Phototoxicity Photoallergy Pathology Differential diagnosis Treatment Endogenous photosensitivity Introduction and history Epidemiology Clinical features Pathology Differential diagnosis Treatment Photoaggravated Dermatoses Grover Disease Normal Cutaneous Effects Of Uvr And Visible Light Exposure Acute and Subacute Effects Acute inflammatory erythema (sunburn) Pigment darkening and delayed tanning Epidermal hyperplasia Immunologic changes Vitamin D3 synthesis Other changes Chronic Effects Photoaging in fair-skinned patients Photoaging in patients with dark skin phototypes Photocarcinogenesis References 88- Environmental and Sports-Related Skin Diseases 88 Environmental and Sports-Related Skin Diseases Injury Due To Heat Exposure Heat-Related Illnesses and Thermal Burns Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Erythema Ab Igne Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Burns and Cutaneous Radiation Injury Associated With Magnetic Resonance Imaging (MRI) and Fluoroscopy Introduction Pathogenesis Clinical features Differential diagnosis Treatment Airbag Burns Introduction Pathogenesis Clinical features Differential diagnosis Treatment Injury Due To Cold Exposure Frostbite Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Pernio Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Injury Due To Water Exposure Immersion Foot Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Injury Due To Electricity Electrical Burns Introduction Pathogenesis Clinical features Pathology Treatment Chemical Burns and Exposures Injury Due To Chemical Exposure Chemical Hair Discoloration Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Arsenical, Elemental and Heavy Metal Dermatoses Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Illness due to Aquatic Toxin Ingestion Introduction Epidemiology Pathogenesis Clinical features Treatment Frictional And Traumatic Injury To The Skin Corns and Calluses Introduction Epidemiology Pathogenesis Clinical features Differential diagnosis Treatment Black Heel and Palm Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Senile Gluteal Dermatosis Environmental Dermatoses Of The External Ear Sports-Related Dermatoses Introduction History Epidemiology Pathogenesis Clinical features Pathology Treatment Amputee-Related Dermatoses Treatment Musical Instrument-Related Dermatoses Introduction History Epidemiology Pathogenesis and clinical features Pathology Differential diagnosis Treatment Appendix References 89- Signs of Substance Use Disorder 89 Signs of Substance Use Disorder INTRODUCTION Alcohol Stimulants Hallucinogens Opioids (Includes Opiates) Gamma-Hydroxybutyrate Benzodiazepines Cannabis Anabolic Steroids PATHOPHYSIOLOGY OF SUBSTANCE USE DISORDERS EPIDEMIOLOGY CLINICAL FEATURES Scars, Ulcerations, and Skin Necrosis Bacterial Infections Fungal Infections Granulomas Mucous Membrane Lesions Burns Formication Additional Cutaneous Findings Drug-Induced Reactions Vascular Lesions Systemic Complications TREATMENT REFERENCES 90- Skin Signs of Abuse 90 Skin Signs of Abuse Child Abuse Introduction History Epidemiology Clinical Features Physical abuse Physical neglect Emotional deprivation Sexual abuse Human trafficking Differential Diagnosis Evaluation and Management Elder Abuse Introduction Risk Factors for Elder Abuse Clinical Features and Assessment Management References 91- Histiocytoses 91 Histiocytoses OVERVIEW “L” GROUP: LANGERHANS-RELATED HISTIOCYTOSES Langerhans Cell Histiocytosis Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Indeterminate Cell Histiocytosis Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Erdheim–Chester Disease Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment “C” GROUP: CUTANEOUS AND MUCOCUTANEOUS HISTIOCYTOSES Benign Cephalic Histiocytosis Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Generalized Eruptive Histiocytoma Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Juvenile Xanthogranuloma Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Progressive Nodular Histiocytosis Introduction, epidemiology, and pathogenesis Clinical features Pathology Differential diagnosis Treatment Xanthoma Disseminatum Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Progressive Mucinous Histiocytosis Introduction and pathogenesis Epidemiology Clinical features Pathology Differential diagnosis Treatment Necrobiotic Xanthogranuloma Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Multicentric Reticulohistiocytosis Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment “R” GROUP: ROSAI–DORFMAN DISEASE “M” GROUP: MALIGNANT HISTIOCYTOSES Miscellaneous ALK+ histiocytosis Acknowledgment REFERENCES 92- Xanthomas 92 Xanthomas INTRODUCTION EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES Eruptive Xanthomas Tuberous/Tuberoeruptive Xanthomas Tendinous Xanthomas Plane Xanthomas and Xanthelasma Verruciform Xanthomas PATHOLOGY DIFFERENTIAL DIAGNOSIS TREATMENT Acknowledgment REFERENCES 93- Non-infectious Granulomas 93 Non-infectious Granulomas INTRODUCTION SARCOIDOSIS History Epidemiology Pathogenesis Immune mechanisms Triggers Genetics Clinical Features Pathology Diagnosis and Differential Diagnosis Treatment GRANULOMA ANNULARE History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment NECROBIOSIS LIPOIDICA History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment CUTANEOUS CROHN DISEASE History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment FOREIGN BODY GRANULOMAS (see Ch. 94) OROFACIAL GRANULOMATOSIS (OFG see Ch. 72) REACTIVE GRANULOMATOUS DERMATITIS – INCLUDES INTERSTITIAL GRANULOMATOUS DERMATITIS, PALISADED NEUTROPHILIC AND GRANULOMATOU ... Introduction History Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Acknowledgment REFERENCES 94- Foreign Body Reactions 94 Foreign Body Reactions GENERAL CONSIDERATIONS Definition Routes of Entry Accidental Surgical procedures Iatrogenic Tattooing Topical application Self-inflicted Pathogenesis Clinical Features Pathology Diagnosis FOREIGN BODY REACTIONS TO INORGANIC AND METALLIC COMPOUNDS Tattoo Clinical features Pathology Diagnosis and differential diagnosis Treatment Paraffin Clinical features Pathology Treatment Silicone Clinical features Pathology Treatment Silica Clinical features Pathology Differential diagnosis Treatment Talc Clinical features Pathology Treatment Zirconium Beryllium Aluminum Zinc Treatment REACTIONS TO ORGANIC AND BIOLOGIC PRODUCTS Starch Pathology Cactus Spines Pathology Cnidaria (Coelenterata) – Jellyfish, Corals Clinical features Pathology Treatment Keratin Pseudofolliculitis barbae Treatment Pilonidal sinus INJECTABLE SOFT TISSUE FILLERS Hyaluronic Acid Bovine Collagen MISCELLANEOUS Intralesional Corticosteroids Sutures Polyamide “Hair” Implants Mesotherapy Gouty tophi REFERENCES 95- Biology of the Extracellular Matrix 95 Biology of the Extracellular Matrix INTRODUCTION STRUCTURE AND FUNCTION OF THE EXTRACELLULAR MATRIX Collagens Collagen triple helix Biosynthesis of collagens The collagen family Collagens of the skin Elastic Fibers Elastin Microfibrils The Extrafibrillar Matrix Glycosaminoglycans and proteoglycans Laminins and Other Glycoproteins Functions of the Extracellular Matrix Structural role of the extracellular matrix Regulation of cellular functions Ehlers–Danlos syndrome Collagens and tenascin-X Post-translational modification of collagen Proteoglycan processing Cutis laxa Marfan syndrome Loeys–Dietz syndrome Other fibrillin-associated syndromes Pseudoxanthoma elasticum Epidermolysis bullosa Other hereditary matrix diseases with skin symptoms Extracellular matrix components as autoantigens Skin aging and other acquired ECM abnormalities DISEASES RELATED TO ECM DEFECTS Animal Models Potential for Biologically Valid Molecular Therapies REFERENCES 96- Perforating Diseases 96 Perforating Diseases INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES Reactive Perforating Collagenosis Elastosis Perforans Serpiginosa Acquired Perforating Dermatosis and Kyrle Disease Perforating Calcific Elastosis PATHOLOGY DIFFERENTIAL DIAGNOSIS TREATMENT REFERENCES 97- Heritable Disorders of Connective Tissue 97 Heritable Disorders of Connective Tissue INTRODUCTION EHLERS–DANLOS SYNDROME History Epidemiology Pathogenesis Clinical Features Major subtypes Less common subtypes Pathology and Laboratory Findings Differential Diagnosis Treatment PSEUDOXANTHOMA ELASTICUM History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment CUTIS LAXA History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment REFERENCES 98- Dermal Hypertrophies 98 Dermal Hypertrophies HYPERTROPHIC SCARS AND KELOIDS Introduction Epidemiology Etiology Pathogenesis Clinical Features Scar assessment Pathology Differential Diagnosis Treatment DUPUYTREN DISEASE History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment CUTIS VERTICIS GYRATA Clinical Features Pathology Differential Diagnosis Treatment HYALINE FIBROMATOSIS SYNDROME (JUVENILE HYALINE FIBROMATOSIS AND INFANTILE SYSTEMIC HYALINOSIS) Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ELASTIC TISSUE-RELATED DISORDERS REFERENCES 99- Atrophies of Connective Tissue 99 Atrophies of Connective Tissue Mid-Dermal Elastolysis Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Anetoderma Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential diagnosis Treatment Striae Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Atrophoderma Of Pasini And Pierini Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Follicular Atrophoderma Clinical features Atrophoderma Vermiculatum Bazex–Dupré–Christol Syndrome Conradi–Hünermann–Happle Syndrome (X-Linked Dominant Chondrodysplasia Punctata, CDPX2) Atrophia Maculosa Varioliformis Cutis Piezogenic Pedal Papules (Piezogenic Papules) Other Atrophies of the Connective Tissue References 100- Panniculitis 100 Panniculitis INTRODUCTION ERYTHEMA NODOSUM Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment SUBACUTE NODULAR MIGRATORY PANNICULITIS History and Clinical Features Pathology Treatment MORPHEA/SCLERODERMA PANNICULITIS Clinical Features Pathology Differential Diagnosis ALPHA-1 ANTITRYPSIN DEFICIENCY PANNICULITIS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ERYTHEMA INDURATUM Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment PANCREATIC PANNICULITIS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment SCLEREMA NEONATORUM, SUBCUTANEOUS FAT NECROSIS OF THE NEWBORN, AND POST-STEROID PANNICULITIS Sclerema Neonatorum History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Subcutaneous Fat Necrosis of the Newborn Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Post-Steroid Panniculitis History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment LUPUS ERYTHEMATOSUS PANNICULITIS (LUPUS PANNICULITIS) History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment PANNICULITIS OF DERMATOMYOSITIS Introduction Clinical Features Pathology Differential Diagnosis Treatment TRAUMATIC PANNICULITIS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment LIPODERMATOSCLEROSIS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment INFECTION-INDUCED PANNICULITIS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment CYTOPHAGIC HISTIOCYTIC PANNICULITIS MALIGNANT SUBCUTANEOUS INFILTRATES UNUSUAL OR NEWLY DESCRIBED FORMS OF PANNICULITIS REFERENCES 101- Lipodystrophies 101 Lipodystrophies Introduction Pathogenesis Congenital Generalized Lipodystrophy (Berardinelli–Seip Congenital Lipodystrophy, Berardinelli–Seip Syndrome) Familial Partial Lipodystrophy Acquired Generalized Lipodystrophy (Lawrence Syndrome) Acquired Partial Lipodystrophy Syndrome (Barraquer–Simons Syndrome) Localized Lipoatrophy Clinical Features Congenital Generalized Lipodystrophy (CGL) Familial Partial Lipodystrophy Proteasome-Associated Autoinflammatory Syndromes Recurrent lipoatrophic panniculitis of children Acquired Generalized Lipodystrophy (Lawrence Syndrome) Acquired Partial Lipodystrophy (Barraquer–Simons Syndrome) Localized Lipoatrophy Lipohypertrophy Pathology Differential Diagnosis Treatment Acquired Lipodystrophy Due To Other Causes Medications HIV/ART-associated lipodystrophy Immune Checkpoint Inhibitor-Associated Lipodystrophy POEMS Syndrome Allogeneic Hematopoietic Stem Cell Transplantation-Associated Lipodystrophy References 102- Vascular Biology 102 Vascular Biology STRUCTURE AND FUNCTION OF CUTANEOUS BLOOD VESSELS VASCULAR DEVELOPMENT Regulation of Skin Angiogenesis Angiogenesis and Wound Healing Regulation of Leukocyte–Endothelial Cell Interactions STRUCTURE AND FUNCTION OF THE CUTANEOUS LYMPHATIC VASCULAR SYSTEM ANGIOGENESIS- AND LYMPHANGIOGENESIS-RELATED DISEASES ANTIANGIOGENIC THERAPIES REFERENCES 103- Infantile Hemangiomas 103 Infantile Hemangiomas INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS Role of Hypoxia Signaling Pathways Genetic Factors Factors Influencing Natural History CLINICAL FEATURES Presentation Natural History Complications Ulceration Disfigurement and interference with function related to IH size and/or location Extracutaneous involvement RADIOLOGIC FEATURES PATHOLOGY DIFFERENTIAL DIAGNOSIS TREATMENT Active Non-Intervention Management of Ulceration Wound care Specific therapy Pain control Local Therapies Topical β-blockers Intralesional corticosteroids Systemic Therapies Systemic β-blockers Systemic corticosteroids Other systemic therapies Surgical Therapy RAPIDLY INVOLUTING AND NON-INVOLUTING CONGENITAL HEMANGIOMAS REFERENCES 104- Vascular Malformations 104 Vascular Malformations INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES Capillary Malformations Nevus simplex Port-wine birthmark (PWB) and variants Sturge–Weber syndrome Capillary malformations associated with overgrowth, including the PIK3CA-related overgrowth spectrum (PROS) Diffuse capillary malformation with overgrowth Klippel–Trenaunay syndrome CLOVES syndrome Megalencephaly–capillary malformation CLAPO syndrome Proteus syndrome Cutis marmorata telangiectatica congenita Telangiectasias Hereditary hemorrhagic telangiectasia Ataxia–telangiectasia Angiokeratomas Venous Malformations Cephalic venous malformation Trunk and limb venous malformation Sinusoidal hemangioma Fibro-adipose vascular anomaly (FAVA) Verrucous venulocapillary malformation (verrucous VM, verrucous “hemangioma”) Syndromes associated with venous malformations Familial cutaneous and mucosal venous malformation (VMCM) Blue rubber bleb nevus syndrome (BRBNS Bean syndrome) Maffucci syndrome Glomuvenous malformation (GVM) Cerebral cavernous malformation and hyperkeratotic cutaneous capillary–venous malformation Lymphatic Malformations Primary lymphedema Macrocystic lymphatic malformation (“cystic hygroma”) Microcystic lymphatic malformation (“lymphangioma circumscriptum”) Combined microcystic and macrocystic lymphatic malformation Generalized lymphatic anomaly (GLA) Kaposiform lymphangiomatosis (KLA) Gorham–Stout disease Central conducting lymphatic anomalies (CCLAs channel-type LMs) Arteriovenous Malformations Syndromes associated with arteriovenous malformations Cobb syndrome Bonnet–Dechaume–Blanc syndrome (BDBS Wyburn–Mason syndrome) Parkes Weber syndrome Capillary malformation–arteriovenous malformation (CM-AVM) syndrome PTEN hamartoma tumor syndrome (PHTS) PATHOLOGY Capillary Malformations Venous Malformations Lymphatic Malformations Arteriovenous Malformations DIFFERENTIAL DIAGNOSIS TREATMENT Capillary Malformations Venous Malformations Lymphatic Malformations Arteriovenous Malformations Combined Malformations and the PIK3CA-Related Overgrowth Spectrum (PROS) Acknowledgment Appendix REFERENCES 105- UlcersAriela Hafner and Eli Sprecher 105 Ulcers Ariela Hafner and Eli Sprecher INTRODUCTION VENOUS ULCERS Pathogenesis Clinical Features Laboratory Evaluation Pathology Differential Diagnosis Treatment Moisture and occlusion Debridement Wound dressings Management of wound infection Adjuncts to wound care Compression Manual lymph drainage Topical negative pressure wound therapy Skin substitutes Topical and oral medications LYMPHEDEMA ARTERIAL ULCERS Pathogenesis Clinical Manifestations Laboratory Evaluation Differential Diagnosis Treatment DIABETIC (AND NEUROPATHIC) ULCERS Pathogenesis Clinical Features Laboratory Evaluation Treatment Prevention ULCERS DUE TO PHYSICAL FACTORS Pathogenesis Clinical Features Pathology Treatment OTHER CAUSES OF SKIN ULCERATION Diffuse Dermal Angiomatosis Hematologic Disorders Tropical Ulcers Additional Causes REFERENCES 106- Other Vascular Disorders 106 Other Vascular Disorders INTRODUCTION LIVEDO RETICULARIS AND LIVEDO RACEMOSA Introduction History Pathogenesis Clinical Features Livedo reticularis Congenital livedo reticularis Cutis marmorata telangiectatica congenita Acquired livedo reticularis Cutis marmorata/physiologic livedo reticularis Livedo reticularis due to intraluminal pathology Livedo racemosa Livedo racemosa due to vessel wall pathology Livedo racemosa due to intraluminal pathology Other causes of livedo reticularis and livedo racemosa Differential Diagnosis Pathology Treatment FLUSHING Introduction Pathogenesis Clinical Features Differential Diagnosis Treatment ERYTHROMELALGIA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment TELANGIECTASIAS Introduction Spider Telangiectasia Generalized Essential Telangiectasia Cutaneous Collagenous Vasculopathy Unilateral Nevoid Telangiectasia Angioma Serpiginosum Hereditary Hemorrhagic Telangiectasia Ataxia–Telangiectasia VENOUS LAKES NEVUS ANEMICUS ANGIOSPASTIC MACULES (BIER SPOTS) REFERENCES 107- Principles of Cutaneous Tumor Biology 107 Principles of Cutaneous Tumor Biology INTRODUCTION THE GENOME PERSPECTIVE The DNA Sequencing Revolution Types of Somatic Mutations The Darwinian Model of Gradual Cancer Evolution Single Catastrophic Events in Genome Evolution Gradual Cancer Evolution Versus Punctuated Evolution and Catastrophic Events THE CELL PERSPECTIVE Functional Capabilities Acquired by Cancer Cells Sustaining Proliferative Signaling Deregulating Cellular Metabolism Mutations in p53 and Rb Tumor Suppressor Pathways Deregulate Cell Cycle Control Resisting Cell Death Genome Instability and Mutation THE TISSUE PERSPECTIVE Architectures in Cancer Ecosystems Phenotypic Plasticity and Epigenetic Reprogramming Avoiding Immune Destruction Cancer-Promoting Inflammation Inducing or Accessing Vasculature Activating Invasion and Metastasis PATHOGENESIS OF KERATINOCYTE CARCINOMAS Molecular Pathogenesis of Basal Cell Carcinoma (BCC) Molecular Pathogenesis of Cutaneous Squamous Cell Carcinoma (cSCC) CURRENT DEVELOPMENTS AND FUTURE PERSPECTIVES Mapping the Evolution of Cancer Ecosystems in Space and Time The Microbiome and Cancer Future Perspectives for Clinical Translation REFERENCES 108- Actinic_Keratosis,_Basal_Cell_Carcinoma,_and_Squamous_Cell_Carcinoma 108 Actinic Keratosis, Basal Cell Carcinoma, and Squamous Cell Carcinoma INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS RISK FACTORS (Table 108.2) Environmental Exposures Ultraviolet radiation (UVR) Indoor tanning usage Therapeutic UVR exposure Ionizing radiation Occupational risk factors Chemical exposures Human Papillomavirus Infection Immunosuppression Organ transplantation Immunosuppressive drugs HIV infection Other Risk Factors, Including BRAF Inhibitors Genetic Risk Factors Genetic predisposition Genetic syndromes associated with an increased risk of BCCs and/or cSCCs Xeroderma pigmentosum Oculocutaneous albinism Epidermodysplasia verruciformis Dystrophic epidermolysis bullosa Basal cell nevus syndrome (BCNS) Bazex–Dupré–Christol syndrome and Rombo syndrome Bloom syndrome Rothmund–Thomson syndrome (RTS) Keratitis–ichthyosis–deafness (KID) syndrome Risk of Additional Cancers Field cancerization ACTINIC KERATOSIS AND SQUAMOUS CELL CARCINOMA Clinical Features Actinic keratosis Cutaneous squamous cell carcinoma in situ Invasive cutaneous squamous cell carcinoma Keratoacanthoma Verrucous carcinoma Lymphoepithelioma-like carcinoma of the skin In vivo Imaging Methods Dermoscopy Reflectance confocal microscopy Pathology Actinic keratosis Squamous cell carcinoma in situ Invasive cutaneous squamous cell carcinoma Keratoacanthoma Verrucous carcinoma Histopathologic simulators of SCC Atypical squamous proliferation BASAL CELL CARCINOMA Clinical Features Nodular basal cell carcinoma Superficial basal cell carcinoma Morpheaform basal cell carcinoma Fibroepithelial basal cell carcinoma (fibroepithelioma of Pinkus) In vivo Imaging Methods Dermoscopy Reflectance confocal microscopy (RCM) Pathology Additional histopathologic subtypes of BCC Basosquamous carcinoma Micronodular basal cell carcinoma Histopathologic simulators of BCC TREATMENT Evaluation and Risk Assessment Surgical and Destructive Procedures Standard excision Cutaneous squamous cell carcinoma Basal cell carcinoma Curettage alone Curettage with electrodesiccation Mohs micrographic surgery Radiation therapy Cryosurgery Photodynamic therapy Laser Non-Surgical Treatments Topical therapies Combination therapy Chemowraps Intralesional treatment Systemic Therapy Treatment of advanced cutaneous SCC Immunotherapy with immune checkpoint inhibitors Treatment of advanced BCC Hedgehog signaling pathway inhibition Immunotherapy with immune checkpoint inhibitors Prophylaxis Reduction of immunosuppression Prevention Acknowledgment REFERENCES 109- Benign Epidermal Tumors and Proliferations 109 Benign Epidermal Tumors and Proliferations SOLAR LENTIGO Epidemiology Pathogenesis Clinical Features Associated Diseases and Special Forms Pathology Differential Diagnosis Treatment SEBORRHEIC KERATOSIS Introduction History Epidemiology Pathogenesis Clinical Features Seborrheic Keratosis and Malignancy Pathology Differential Diagnosis Treatment LICHENOID KERATOSIS History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment DERMATOSIS PAPULOSA NIGRA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment STUCCO KERATOSIS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment POROKERATOSIS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment FLEGEL DISEASE Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ACROKERATOSIS VERRUCIFORMIS Clinical Features and Pathogenesis Pathology Differential Diagnosis Treatment CUTANEOUS HORN Clinical Features Pathology Treatment CLEAR CELL ACANTHOMA Introduction Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment INVERTED FOLLICULAR KERATOSIS History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis WARTY DYSKERATOMA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ACANTHOLYTIC (DYSKERATOTIC) ACANTHOMA EPIDERMOLYTIC ACANTHOMA Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment LARGE CELL ACANTHOMA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment EPIDERMAL NEVUS (SEE Ch. 62) Introduction Epidemiology Pathogenesis – see Ch. 62 and Table 62.6 Clinical Features Pathology Differential Diagnosis Treatment INFLAMMATORY LINEAR VERRUCOUS EPIDERMAL NEVUS Introduction History Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment NEVUS COMEDONICUS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ACANTHOSIS NIGRICANS NEVOID HYPERKERATOSIS OF THE NIPPLE AND AREOLA CONFLUENT AND RETICULATED PAPILLOMATOSIS History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment TERRA FIRMA-FORME DERMATOSIS CLEAR CELL PAPULOSIS Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment Acknowledgment REFERENCES 110- Cysts 110 Cysts INTRODUCTION CYSTS WITH A LINING OF STRATIFIED SQUAMOUS EPITHELIUM Epidermoid Cyst Pathology Treatment Dilated Pore of Winer Pathology Differential diagnosis Treatment Milium Pathology Treatment Tricholemmal Cyst Pathology Differential diagnosis Treatment Verrucous Cyst Pathology Treatment Proliferating Tricholemmal Cyst Pathology Treatment Proliferating Epidermoid Cyst Pathology Treatment Vellus Hair Cysts Pathology Treatment Steatocystoma Pathology Treatment Follicular Hybrid Cyst Pigmented Follicular Cyst Dermoid Cyst Pathology Treatment Ear Pit Pathology Treatment Pilonidal Cyst Pathology Treatment CYSTS LINED WITH NON-STRATIFIED SQUAMOUS EPITHELIUM Hidrocystoma Pathology Treatment Bronchogenic Cyst Pathology Treatment Thyroglossal Duct Cyst Pathology Treatment Branchial Cleft Cyst Pathology Treatment Cutaneous Ciliated Cyst and Ciliated Cyst of the Vulva Pathology Differential diagnosis Treatment Median Raphe Cyst Pathology Treatment Omphalomesenteric Duct Cyst Pathology Differential diagnosis Treatment Urachal Cyst Pathology Treatment CYSTS WITHOUT AN EPITHELIAL LINING Mucocele Pathology Treatment Digital Mucous Cyst (Pseudocyst) Pathology Treatment Ganglion Pathology Treatment Pseudocyst of the Auricle Pathology Treatment Cutaneous Metaplastic Synovial Cyst (Pseudocyst) Pathology Treatment REFERENCES 111- Adnexal Neoplasms 111 Adnexal Neoplasms NEOPLASMS AND PROLIFERATIONS WITH FOLLICULAR DIFFERENTIATION Follicular and Folliculosebaceous-Apocrine Hamartomas Hair follicle nevus Introduction Clinical features Pathology Treatment Trichofolliculoma Introduction Clinical features Pathology Treatment Fibrofolliculoma, perifollicular fibroma, and trichodiscoma Introduction Clinical features Pathology Treatment Nevus sebaceus Introduction Clinical features Pathology Treatment Mixed tumor (chondroid syringoma) Introduction Clinical features Pathology Treatment Neoplasms and Proliferations with Follicular Germinative Differentiation Trichoepithelioma/trichoblastoma Introduction Clinical features Pathology Treatment Desmoplastic trichoepithelioma (desmoplastic trichoblastoma) Introduction Clinical features Pathology Treatment Neoplasms and Proliferations with Matrical Differentiation Pilomatricoma (pilomatrixoma, trichomatrioma, calcifying epithelioma) Introduction Clinical features Pathology Treatment Pilomatrical carcinoma Introduction Clinical features Pathology Treatment Neoplasms and Proliferations with Follicular Sheath (Tricholemmal) Differentiation Tricholemmoma (trichilemmoma) Introduction Clinical features Pathology Treatment Tricholemmal (trichilemmal) carcinoma Treatment Neoplasms and Proliferations with Superficial Follicular (Infundibular and Isthmic) Differentiation Tumor of follicular infundibulum (infundibuloma isthmicoma) Introduction Clinical features Pathology Treatment Trichoadenoma (trichoadenoma of Nikolowski) Introduction Clinical features Pathology Treatment Proliferating pilar tumor (proliferating follicular-cystic neoplasm) Introduction Clinical features Pathology Treatment Sebaceous gland hyperplasia Introduction Clinical features Pathology Treatment Sebaceous adenoma, sebaceoma, and sebaceous epithelioma Introduction Clinical features Pathology Treatment Sebaceous carcinoma Introduction Clinical features Pathology Treatment NEOPLASMS AND PROLIFERATIONS WITH SEBACEOUS DIFFERENTIATION NEOPLASMS AND PROLIFERATIONS WITH APOCRINE (OR ECCRINE) DIFFERENTIATION Benign Neoplasms and Proliferations with Apocrine (or Eccrine) Ductal and Tubular Differentiation Syringoma Introduction Clinical features Pathology Treatment Poroma Introduction Clinical features Pathology Treatment Hidradenoma Introduction Clinical features Pathology Treatment Benign Neoplasms with Apocrine Differentiation Apocrine adenoma Introduction Clinical features Pathology Treatment Undifferentiated Neoplasms of Apocrine Lineage Spiradenoma Definition Clinical features Pathology Treatment Cylindroma Introduction Clinical features Pathology Treatment Carcinomas of apocrine lineage Introduction Clinical features Pathology Treatment Eccrine nevus (hamartoma) Treatment Syringoma, poroma, hidradenoma, adnexal adenocarcinoma Syringofibroadenoma Papillary adenoma and adenocarcinoma Introduction Clinical features Pathology Treatment NEOPLASMS AND PROLIFERATIONS WITH ECCRINE DIFFERENTIATION REFERENCES 112- Benign Melanocytic Neoplasms and Melanotic Lesions 112 Benign Melanocytic Neoplasms and Melanotic Lesions INTRODUCTION CIRCUMSCRIBED MELANOTIC LESIONS EPHELIDES Epidemiology and Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment CAFÉ-AU-LAIT MACULES Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment BECKER MELANOSIS (NEVUS) Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment SOLAR LENTIGINES LENTIGO SIMPLEX AND MUCOSAL MELANOTIC MACULES Epidemiology Pathogenesis Clinical Features Associated syndromes Pathology Differential Diagnosis Treatment DERMAL MELANOCYTOSIS Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment NEVUS OF OTA, NEVUS OF ITO, AND RELATED CONDITIONS Nevus of Ota Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Nevus of Ito and Related Conditions MELANOCYTIC NEVI BLUE NEVUS AND ITS VARIANTS Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment PIGMENTED EPITHELIOID MELANOCYTOMA Epidemiology and Pathogenesis Clinical Features and Pathology COMMON ACQUIRED MELANOCYTIC NEVI Epidemiology Pathogenesis Clinical Features Melanocytic nevi associated with epidermolysis bullosa Melanocytic nevi associated with lichen sclerosus Pathology Differential Diagnosis Treatment GENITAL NEVUS AND NEVI OF SPECIAL SITES Clinical Features Pathology Differential Diagnosis ACRAL NEVUS Epidemiology and Pathogenesis Clinical Features Pathology SPITZ NEVUS AND ATYPICAL SPITZ TUMOR Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment PIGMENTED SPINDLE CELL NEVUS Epidemiology and Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment WNT-ACTIVATED DEEP PENETRATING/PLEXIFORM NEVUS Epidemiology and Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment BAP1-INACTIVATED MELANOCYTIC NEVUS Epidemiology and Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment ATYPICAL (DYSPLASTIC) MELANOCYTIC NEVUS History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment CONGENITAL MELANOCYTIC NEVUS Introduction Epidemiology Pathogenesis Clinical Features Neurocutaneous melanosis (melanocytosis) Melanoma arising in congenital nevi Abnormalities associated with congenital nevi Pathology Differential Diagnosis Treatment NEVUS SPILUS Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment HALO NEVUS Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment COMBINED NEVUS Introduction and Epidemiology Clinical Features Pathology Differential Diagnosis and Treatment RECURRENT MELANOCYTIC NEVUS Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment REFERENCES 113- Melanoma 113 Melanoma INTRODUCTION MOLECULAR PATHOGENESIS HOST IMMUNE RESPONSE TO MELANOMA EPIDEMIOLOGY RISK FACTORS FOR CUTANEOUS MELANOMA Genetic Risk Factors BAP1 tumor syndrome Genetic screening in familial melanoma Phenotypic Risk Factors Reflecting Gene/Environment Interactions Common melanocytic nevi Atypical melanocytic nevi Environmental Risk Factors Ultraviolet radiation Sun protection TYPES OF PRIMARY MELANOMAS Superficial Spreading Melanoma Nodular Melanoma Lentigo Maligna Melanoma Acral Lentiginous Melanoma OTHER MELANOMA VARIANTS Amelanotic Melanomas Melanoma with Features of a Spitz Nevus (Spitzoid Melanoma and Spitz Melanoma) Desmoplastic Melanoma Clear Cell Sarcoma (“Melanoma of Soft Parts”) Melanoma Arising in a Blue Nevus (Blue Nevus-Like Melanoma) Primary Dermal Melanoma Ocular Melanoma Mucosal Melanoma MELANOMA AND PREGNANCY MELANOMA IN THE PEDIATRIC AND ADOLESCENT POPULATION DIAGNOSIS Differential Diagnosis Dermoscopy Photography Non-Invasive Diagnostic Imaging PATHOLOGY Microstaging Immunohistopathology Molecular Analysis Gene Expression Profiling (GEP) Gene expression profiling for diagnosis Gene expression profiling for prognosis STAGING PROGNOSIS EVALUATION OF A PATIENT WITH SUSPECTED MELANOMA Medical History Skin Investigation and Clinical Diagnosis Laboratory Investigations and Imaging MANAGEMENT Management of the Primary Melanoma (Stage I and II) Mohs micrographic surgery (MMS) Topical imiquimod Adjuvant Therapy Considerations for Stage II Melanoma Local Recurrences Management of Regional Metastatic Melanoma (Stage III) Sentinel lymph node biopsy (SLNB) and completion lymph node dissection Skin satellite and in-transit metastases Clinically detectable regional lymph node metastases Adjuvant therapy Management of Distant Metastases (Stage IV) Surgery Radiation therapy Systemic therapy Molecularly targeted therapy Immunotherapy Immune checkpoint blockade Cancer vaccines Chemotherapy MELANOMA SURVEILLANCE REFERENCES 114- Vascular Neoplasms and Neoplastic-Like Proliferations 114 Vascular Neoplasms and Neoplastic-Like Proliferations INTRODUCTION BENIGN VASCULAR NEOPLASMS AND REACTIVE HYPERPLASIAS Intravascular Papillary Endothelial Hyperplasia (PEH) Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Reactive Angioendotheliomatosis Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Angiokeratomas Introduction Clinical features Solitary or multiple angiokeratomas Genital Angiokeratomas Angiokeratoma corporis diffusum Angiokeratoma of Mibelli Angiokeratoma circumscriptum Pathology Differential diagnosis Treatment Targetoid Hemosiderotic Lymphatic Malformation (Hobnail “Hemangioma”) Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Verrucous Venulocapillary Malformation (Verrucous “Hemangioma”) Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis and treatment Pyogenic Granuloma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Cherry Angioma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Tufted Angioma Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Glomeruloid Hemangioma Introduction and history Clinical features Pathogenesis Pathology Differential diagnosis Treatment Microvenular Hemangioma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Epithelioid Hemangioma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Multifocal Lymphangioendotheliomatosis with Thrombocytopenia Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Sinusoidal Hemangioma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Spindle Cell Hemangioma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment BORDERLINE AND LOW-GRADE MALIGNANT VASCULAR NEOPLASMS Kaposiform Hemangioendothelioma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Papillary Intralymphatic Angioendothelioma (PILA) Introduction and history Epidemiology Clinical features Pathology Differential diagnosis Treatment Retiform Hemangioendothelioma (RHE) and Composite Hemangioendothelioma (CHE) Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Pseudomyogenic Hemangioendothelioma Introduction and epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Kaposi Sarcoma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment MALIGNANT VASCULAR NEOPLASMS Epithelioid Hemangioendothelioma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Angiosarcoma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment PERIVASCULAR NEOPLASMS AND NEOPLASTIC-LIKE PROLIFERATIONS Glomus Tumors and Glomuvenous Malformations Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Infantile Hemangiopericytoma Introduction and history Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment REFERENCES 115- Neural_and_Neuroendocrine_Neoplasms_Other_than_Neurofibromatosis 115 Neural and Neuroendocrine Neoplasms (Other than Neurofibromatosis) CLASSIFICATION, TERMINOLOGY, AND HISTOGENESIS NEUROMAS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment SCHWANNOMA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment NEUROFIBROMA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment NERVE SHEATH MYXOMA AND CELLULAR NEUROTHEKEOMA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment GRANULAR CELL TUMOR Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment PERINEURIOMA Introduction MALIGNANT PERIPHERAL NERVE SHEATH TUMOR MERKEL CELL CARCINOMA Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment HETEROTOPIC NEURAL TISSUE OF THE SKIN Nasal Glial Heterotopia History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Heterotopic Meningeal Tissue History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment PRIMITIVE NEUROECTODERMAL TUMORS Introduction History Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment REFERENCES 116- Fibroblastic,_Myofibroblastic,_and_“Fibrohistiocytic”_Proliferations 116 Fibroblastic, Myofibroblastic, and “Fibrohistiocytic” Proliferations and Neoplasms of the Skin Skin Tags Clinical Features Epidemiology Pathology Treatment Cutaneous Angiofibroma Clinical Features Pathology Dermatofibroma Clinical Features Pathology Treatment Variants of Dermatofibroma Acral Fibrokeratoma Clinical Features Pathology Acral Fibromyxoma Clinical Features Pathology Treatment Sclerotic Fibroma Of The Skin Clinical Features Pathology Pleomorphic Fibroma Of The Skin Clinical Features Pathology Multinucleate Cell Angiohistiocytoma Clinical Features Pathology Treatment Dermatomyofibroma Clinical Features Pathology Treatment Tenosynovial Giant Cell Tumor (Localized Type) Clinical Features Pathology Treatment Fibroma Of Tendon Sheath Clinical Features Pathology Treatment Nodular Fasciitis Clinical Features Pathology Treatment Connective Tissue Nevus Clinical Features Pathology Differential Diagnosis Inclusion Body Fibromatosis Clinical Features Pathology Treatment Infantile Myofibromatosis Clinical Features Pathology Treatment Myopericytoma Clinical Features Pathology Treatment Calcifying Aponeurotic Fibroma Clinical Features Pathology Treatment Fibrous Hamartoma Of Infancy Clinical Features Pathology Treatment Fibromatoses Clinical Features Pathology Treatment Plexiform Fibrohistiocytic Tumor Clinical Features Pathology Treatment Atypical Fibroxanthoma Clinical Features Pathology Treatment Dermatofibrosarcoma Protuberans Clinical Features Pathology Treatment Giant Cell Fibroblastoma Clinical Features Pathology Treatment Fibrosarcoma Clinical Features Pathology Treatment Epithelioid Sarcoma Clinical Features Pathology Treatment References E-References 117- Smooth Muscle, Adipose, and Cartilage Neoplasms 117 Smooth Muscle, Adipose, and Cartilage Neoplasms INTRODUCTION TUMORS OF SMOOTH MUSCLE Leiomyoma Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Leiomyosarcoma Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Smooth Muscle Hamartoma Introduction History Epidemiology Clinical features Pathology Differential diagnosis Treatment TUMORS OF FAT Lipoma Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Angiolipoma Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Spindle Cell/Pleomorphic Lipoma Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Hibernoma Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Nevus Lipomatosus Superficialis Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Lipoblastoma/Lipoblastomatosis Introduction History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Atypical Lipomatous Tumor/Liposarcoma Introduction Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment TUMORS OF CARTILAGE Extraskeletal Chondroma Introduction Epidemiology Clinical features Pathology Differential diagnosis Treatment Acknowledgment REFERENCES 118- Mastocytosis 118 Mastocytosis INTRODUCTION HISTORY EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES Signs and Symptoms Cutaneous Lesions Systemic Manifestations Classification of Mastocytosis PATHOLOGY Direct Studies Indirect Studies DIFFERENTIAL DIAGNOSIS TREATMENT REFERENCES 119- B Cell Lymphomas of the Skin 119 B Cell Lymphomas of the Skin INTRODUCTION HISTORY EPIDEMIOLOGY ETIOLOGY AND PATHOGENESIS CLINICAL FEATURES Primary Cutaneous Follicle Center Lymphoma Primary Cutaneous Marginal Zone B Cell Lymphoproliferative Disorder Primary Cutaneous Diffuse Large B Cell Lymphoma, Leg Type Intravascular Diffuse Large B Cell Lymphoma Precursor B Lymphoblastic Lymphoma/Leukemia Other Cutaneous B Cell Lymphomas PATHOLOGY Primary Cutaneous Follicle Center Lymphoma Primary Cutaneous Marginal Zone B Cell Lymphoproliferative Disorder Primary Cutaneous Diffuse Large B Cell Lymphoma, Leg Type Intravascular Diffuse Large B Cell Lymphoma Precursor B Lymphoblastic Lymphoma/Leukemia Other Cutaneous B Cell Lymphomas DIFFERENTIAL DIAGNOSIS TREATMENT PLASMA CELL DYSCRASIAS, INCLUDING MULTIPLE MYELOMA Histopathology Differential Diagnosis CUTANEOUS AND SYSTEMIC PLASMACYTOSIS References 120- Cutaneous T Cell Lymphoma 120 Cutaneous T Cell Lymphoma INTRODUCTION HISTORY The CTCL Concept The Concept of Primary Cutaneous Lymphomas EORTC, WHO, and WHO-EORTC Classification Schemes PRACTICAL GUIDELINES FOR DIAGNOSIS, CLASSIFICATION AND STAGING OF CTCL Diagnosis Immunophenotyping T Cell Receptor Gene Rearrangement Analysis Classification Practical Guidelines Staging MYCOSIS FUNGOIDES Definition Epidemiology Pathogenesis Genetic factors Environmental factors Immunologic factors Clinical Features Pathology Immunophenotype Differential Diagnosis Staging Systems and Staging Procedures Treatment Skin-directed therapies Topical corticosteroids Topical chemotherapy Radiotherapy Phototherapy Systemic therapies (other than chemotherapy) Interferons Retinoids Denileukin diftitox Histone deacetylase inhibitors Mogamulizumab Systemic chemotherapy Prognosis VARIANTS OF MYCOSIS FUNGOIDES Folliculotropic MF Definition Epidemiology Clinical features Pathology Differential diagnosis Treatment Pagetoid Reticulosis Definition Epidemiology Clinical features Pathology Immunophenotype Differential diagnosis Treatment Granulomatous Slack Skin Definition Epidemiology Clinical features Pathology Treatment SÉZARY SYNDROME Definition Epidemiology Clinical Features Pathology Pathogenesis Differential Diagnosis Treatment ADULT T CELL LEUKEMIA/LYMPHOMA Definition Epidemiology Clinical Features Pathology Differential Diagnosis Treatment PRIMARY CUTANEOUS CD30-POSITIVE LYMPHOPROLIFERATIVE DISORDERS Primary Cutaneous Anaplastic Large Cell Lymphoma Definition Epidemiology Clinical features Pathology Immunophenotype Genetic features Treatment Lymphomatoid Papulosis Definition Pathogenesis Epidemiology Clinical features Pathology Differential diagnosis Treatment SUBCUTANEOUS PANNICULITIS-LIKE T CELL LYMPHOMA Definition Epidemiology Clinical Features Pathology Immunophenotype Genetic Features Treatment EXTRANODAL NK/T CELL LYMPHOMA, NASAL TYPE Hydroa Vacciniforme-Like Lymphoproliferative Disorder PRIMARY CUTANEOUS AGGRESSIVE EPIDERMOTROPIC CD8-POSITIVE CYTOTOXIC T CELL LYMPHOMA PRIMARY CUTANEOUS ACRAL CD8-POSITIVE T CELL LYMPHOPROLIFERATIVE DISORDER PRIMARY CUTANEOUS GAMMA/DELTA T CELL LYMPHOMA PRIMARY CUTANEOUS CD4-POSITIVE SMALL/MEDIUM T CELL LYMPHOPROLIFERATIVE DISORDER PRIMARY CUTANEOUS PERIPHERAL T CELL LYMPHOMA, NOS REFERENCES 121- Other Lymphoproliferative and Myeloproliferative Diseases 121 Other Lymphoproliferative and Myeloproliferative Diseases BENIGN LYMPHOCYTIC INFILTRATES Lymphocytic Infiltrate of Jessner History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Cutaneous Lymphoid Hyperplasia (Pseudolymphoma of the Skin) History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment CUTANEOUS EXTRAMEDULLARY HEMATOPOIESIS Epidemiology Pathogenesis Clinical Features Pathology Differential Diagnosis Treatment MALIGNANT HEMATOPOIETIC INFILTRATES Leukemia Cutis Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Cutaneous Hodgkin Lymphoma History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Blastic Plasmacytoid Dendritic Cell Neoplasm History and epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Angioimmunoblastic T Cell Lymphoma History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment Lymphomatoid Granulomatosis History Epidemiology Pathogenesis Clinical features Pathology Differential diagnosis Treatment References 122- Cutaneous Metastases 122 Cutaneous Metastases INTRODUCTION EPIDEMIOLOGY PATHOGENESIS CLINICAL FEATURES PATHOLOGY TREATMENT AND PROGNOSIS REFERENCES 123- Public Health and Dermatology 123 Public Health and Dermatology INTRODUCTION THE PUBLIC HEALTH IMPORTANCE OF DERMATOLOGY ROLE OF EPIDEMIOLOGY IN DERMATOLOGY OBSERVATIONAL STUDIES Descriptive Studies Using Epidemiology to Identify the Cause of Disease Case–control study Cohort study Cross-sectional study ASSESSING THE EFFICACY OF A PREVENTIVE OR THERAPEUTIC INTERVENTION Clinical Trials Systematic Reviews GENETIC EPIDEMIOLOGY HEALTH SERVICES RESEARCH HEALTH POLICY IMPLICATIONS OF RESEARCH Quality-of-Life Measures IMPORTANT CONCEPTS WHEN DESIGNING AND REVIEWING A STUDY Research Question and Design Methods Results Conclusions Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and the Consolidated Standards for Reporting ... OPPORTUNITIES FOR RESEARCH IN DERMATO-EPIDEMIOLOGY Acknowledgment REFERENCES 124- 1 Skin Barrier 124-1 Skin Barrier 125- Glucocorticoids 125 Glucocorticoids INTRODUCTION PHARMACOLOGY AND MECHANISM OF ACTION Structure and Metabolism Absorption and Distribution The Hypothalamic–Pituitary–Adrenal (HPA) Axis Molecular Mechanisms CLINICAL INDICATIONS, DOSAGES, HPA-AXIS SUPPRESSION, TAPERING, AND CONTRAINDICATIONS Oral Therapy Intramuscular Therapy Intravenous and Pulse Therapy Topical Therapy Intralesional Therapy HPA Axis Suppression Tapering Systemic Glucocorticoids Contraindications MAJOR SIDE EFFECTS Osteoporosis Osteonecrosis Growth Suppression Myopathy Cataracts Metabolic Effects Cardiovascular Effects Gastrointestinal Effects Infection Obstetric and Gynecologic Effects Nervous System Effects Cutaneous Effects INTERACTIONS AND DOSE ALTERATIONS Acknowledgment REFERENCES 126- Retinoids 126 Retinoids Introduction Mechanism Of Action Vitamin A Metabolism Retinoid Receptors Retinoids in the Skin Synthetic Retinoids First-generation retinoids Tretinoin (all-trans-retinoic acid) Isotretinoin (13-cis-retinoic acid) Alitretinoin (9-cis-retinoic acid) Second-generation retinoids Acitretin Third-generation retinoids Adapalene Tazarotene Bexarotene Fourth-generation retinoids Trifarotene Retinoic acid metabolism blocking agents Indications (Table 126.3) Topical Retinoids Acne Psoriasis Photoaging Other indications Systemic Retinoids Psoriasis Acne Cutaneous T cell lymphoma Chronic hand eczema Other “off-label” clinical uses Ichthyosis Darier disease Pityriasis rubra pilaris Rosacea Premalignant and malignant skin lesions Lupus erythematosus Dosage Contraindications Topical Retinoids Systemic Retinoids Major Side Effects Topical Retinoids Systemic Retinoids Teratogenicity Skin and mucous membrane adverse effects Common laboratory abnormalities Dyslipidemia Liver effects Other systemic adverse effects Ophthalmologic effects Bone effects Muscle effects Central nervous system and psychiatric effects Hypothyroidism Hematologic effects Gastrointestinal effects Renal effects Summary Interactions Use In Pregnancy And Lactation References 127- Antimicrobial Drugs 127 Antimicrobial Drugs ANTIBACTERIAL AGENTS INTRODUCTION TOPICAL ANTIBACTERIAL AGENTS Introduction Topical Antibacterial Agents Used to Treat Acne Vulgaris and Rosacea Mechanisms of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Topical Antibacterial Agents Used to Treat Superficial Infections Mechanisms of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Other Topical Antibacterial Agents SYSTEMIC ANTIBACTERIAL AGENTS Penicillins Mechanism of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Cephalosporins Mechanism of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Sulfonamides and Co-trimoxazole Mechanism of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Macrolides Mechanism of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Tetracyclines Mechanism of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Clindamycin Mechanism of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Quinolones Mechanism of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Metronidazole Mechanism of action Indications Dosages Contraindications Major side effects Interactions Pregnancy and lactation Other Antibacterial Agents Used in Gram-Positive Skin Infections Dapsone ANTIFUNGAL AND ANTIVIRAL AGENTS ANTIFUNGAL AGENTS Mechanisms of Action Indications Topical antifungal agents Systemic antifungal agents Dosages Topical antifungal agents Systemic antifungal agents Contraindications Major Side Effects Interactions Pregnancy and Lactation Topical antifungal agents Systemic antifungal agents ANTIVIRAL AGENTS Mechanisms of Action Indications Topical antiviral agents Systemic antiviral agents Dosages Contraindications Major Side Effects Interactions Pregnancy and Lactation Topical antiviral agents Systemic antiviral agents Other Antiviral Agents REFERENCES 128- Systemic Immunomodulators 128 Systemic Immunomodulators INTERFERONS GRANULOCYTE–MACROPHAGE AND GRANULOCYTE COLONY-STIMULATING FACTORS (GM-CSF AND G-CSF) TARGETED IMMUNE MODULATORS Introduction Tumor Necrosis Factor Inhibitors Mechanism of action Contraindications Major side effects (Table 128.5) Infections Risk of malignancy Autoimmunity Demyelinating diseases Congestive heart failure Cutaneous reactions Vaccination Use in pregnancy Etanercept Indications Dosages Specific side effects Interactions Infliximab Indications Dosages Specific side effects Interactions Adalimumab Indications Dosages Side effects Interactions Golimumab Certolizumab pegol Interleukin-12/23 and Interleukin-23 Inhibitors Mechanism of action Contraindications Side effects (see Table 128.5) Interactions Use in pregnancy Ustekinumab Indications Dosages Specific side effects Guselkumab Tildrakizumab Risankizumab Interleukin-17 Inhibitors Contraindications Major side effects Interactions Use in pregnancy Ixekizumab Mechanism of action Indications Dosages Secukinumab Mechanism of action Indications Dosages Brodalumab Mechanism of action Indications Dosages Additional contraindications and major side effects Spesolimab-sbzo Contraindications Major side effects Interactions Use in pregnancy Interleukin-4/13 Receptor and Interleukin-13 Inhibitors Mechanisms of action Contraindications Major side effects Interactions Use in pregnancy Dupilumab Indications Dosages Specific side effects Tralokinumab Interleukin-1 Inhibitors Contraindications Major side effects Interactions Anakinra Mechanism of action Indications Dosages Additional contraindications Additional major side effects Use in pregnancy Canakinumab Mechanism of action Indications Dosages Use in pregnancy Rilonacept Mechanism of action Indications Dosages Use in pregnancy Rituximab Mechanism of action Indications Dosages Contraindications Major side effects (see Table 128.5) Interactions Use in pregnancy Omalizumab Mechanism of action Indications Dosages Contraindications Major side effects (see Table 128.5) Interactions Use in pregnancy Janus Kinase (JAK) Inhibitors Mechanism of action Contraindications Major side effects Interactions Use in pregnancy Abrocitinib Baricitinib Deucravacitinib Ritlecitinib Ruxolitinib Tofacitinib Upadacitinib Targeted Immune Modulators Under Investigation and Other Targeted Therapies INTRAVENOUS IMMUNE GLOBULIN (IVIg) Mechanism of Action Indications Dosages Contraindications Major Side Effects Interactions Use in Pregnancy REFERENCES 129- Other Topical Medications 129 Other Topical Medications INTRODUCTION GENERAL PRINCIPLES OF TOPICAL THERAPY Quantity of Application Formulations and Vehicles Topical Therapy During Pregnancy and Lactation Topical Therapy in Neonates Combination and Rotational Topical Therapy ANTIPRURITIC AGENTS KERATOLYTICS AND HUMECTANTS SKIN-LIGHTENING AGENTS Hydroquinone Introduction, dosages, and indications Mechanism of action Side effects Use in pregnancy Monobenzyl Ether of Hydroquinone Mequinol AGENTS THAT AFFECT HAIR GROWTH Minoxidil Introduction, dosages, and indications Mechanism of action Side effects Use in pregnancy Bimatoprost Introduction, dosages, and indications Mechanism of action Side effects Use in pregnancy Eflornithine IMMUNOMODULATORY AGENTS Imiquimod Introduction, dosages, and indications Mechanism of action Side effects Use in pregnancy Topical Calcineurin Inhibitors (TCIs) Introduction, dosages, and indications Mechanism of action Contraindications Major side effects Use in pregnancy Topical Janus Kinase (JAK) Inhibitors Introduction, dosages, and indications Mechanism of action Major side effects Use in pregnancy Topical Phosphodiesterase-4 Inhibitors Aryl Hydrocarbon Receptor Agonists CHEMOTHERAPEUTIC AGENTS 5-Fluorouracil Mechanism of action Indications and dosages Side effects Contraindications and use in pregnancy Mechlorethamine Hydrochloride Introduction, dosages, and indications Mechanism of action Side effects Use in pregnancy Carmustine Introduction, dosages, and indications Mechanism of action Side effects Use in pregnancy Mechanism of action Topical agents and their indications Side effects Use in pregnancy VITAMIN D ANALOGUES MISCELLANEOUS AGENTS Topical Sirolimus (Rapamycin) Introduction, dosages, and indications Mechanism of action Side effects Use in pregnancy Diclofenac Sodium Ingenol Mebutate Tar Introduction and indications Dosages Mechanism of action Side effects Use in pregnancy Anthralin Introduction, dosages, and indications Mechanism of action Side effects Use in pregnancy Podophyllin and Podophyllotoxin Introduction, dosages, and indications Mechanism of action Side effects Use in pregnancy Cantharidin Introduction, dosages, and indications Mechanism of action Side effects Sulfur Introduction Mechanism of action Side effects Contraindications Use in pregnancy Azelaic Acid Introduction and indications Mechanism of action Dosages Side effects Use in pregnancy Topical Immunotherapy The Old and the New REFERENCES 130- Other Systemic Drugs 130 Other Systemic Drugs INTRODUCTION ANTIMALARIALS Mechanism of Action Dosages Major Side Effects Indications Contraindications Use in Pregnancy and Lactation Drug Interactions APREMILAST Mechanism of Action Dosages Major Side Effects Indications Contraindications Use in Pregnancy and Lactation Drug Interactions AZATHIOPRINE Mechanism of Action Dosages Major Side Effects Indications Contraindications Use in Pregnancy and Lactation Drug Interactions BLEOMYCIN CLOFAZIMINE COLCHICINE CYCLOPHOSPHAMIDE Mechanism of Action Dosages Major Side Effects Indications Contraindications Use in Pregnancy and Lactation Drug Interactions CYCLOSPORINE Mechanism of Action Dosages Major Side Effects Indications Contraindications Use in Pregnancy and Lactation Drug Interactions DAPSONE Mechanism of Action Dosages Major Side Effects Indications Contraindications Use in Pregnancy and Lactation Drug Interactions HYDROXYUREA LEUKOTRIENE (LT) INHIBITORS METHOTREXATE Mechanism of Action Dosages Major Side Effects Drug Indications Contraindications Use in Pregnancy and Lactation Drug Interactions MYCOPHENOLATE MOFETIL AND MYCOPHENOLATE SODIUM Mechanism of Action Dosages Major Side Effects Indications Contraindications Use in Pregnancy and Lactation Drug Interactions SATURATED SOLUTION OF POTASSIUM IODIDE (SSKI) SIROLIMUS (RAPAMYCIN) AND TACROLIMUS THALIDOMIDE AND LENALIDOMIDE Mechanism of Action Dosages Major Side Effects Indications Contraindications Use in Pregnancy and Lactation Drug Interactions REFERENCES 131- Drug Interactions 131 Drug Interactions Introduction Putting Interactions Into Perspective Assessment Of Risk In The Clinical Outcome Of Drug Interactions Levels Of Evidence Absorption P-glycoprotein (PGP) Distribution Drug Biotransformation Cytochrome P450 Enzymes The Confusing World Of Drug Interactions Metabolism Cytochrome induction Cytochrome inhibition How To Minimize The Risk Of Drug–Drug Interactions Allylamine Antifungals Azole Antifungals Azathioprine Colchicine Cyclosporine/Everolimus/Sirolimus/Tacrolimus Grapefruit Juice Herbal Remedies HMG-CoA Reductase Inhibitors Kinase Inhibitors Macrolide Antibiotics Quinolone Antibiotics Pimozide Pharmacogenetics – Role of Polymorphisms Cytochrome P450 enzymes Other drug-metabolizing enzymes Drug–Cytokine Interactions Drug–Virus Interactions Human herpes virus (HHV) 6/7 Human immunodeficiency virus (HIV) Hepatitis C virus Conclusion References 132- Sunscreens and Photoprotection 132 Sunscreens and Photoprotection INTRODUCTION AND HISTORY Sun Exposure Sunscreens SUNSCREEN REGULATION Sun Protection Factor (SPF) Testing for UVA Protection Evolution of FDA Sunscreen Standards MECHANISMS OF SUNSCREEN ACTION ACTIVE INGREDIENTS IN SUNSCREENS Organic (Soluble) Filters Para-aminobenzoic acid and derivatives Cinnamates Salicylates Benzophenones Other organic filters Inorganic (Insoluble) Filters Other Photoprotective Agents SUNSCREEN BENEFITS Sunburn Photoaging Photoimmunologic Suppression Actinic Keratoses and Keratinocyte Skin Cancer Cutaneous Melanoma Photosensitivity Disorders (see Ch. 87) SUNSCREEN SAFETY Environmental Effects Sunscreen and Vitamin D Status PHOTOPROTECTIVE CLOTHING PHOTOPROTECTION STRATEGIES AND SUNSCREEN RECOMMENDATIONS Special Populations REFERENCES 133- Complementary and Alternative Medicine 133 Complementary and Alternative Medicine Introduction Natural Products – Medical Applications Aloe Vera Capsaicin Chamomile Colloidal Oatmeal Escharotics Feverfew Green and Black Tea Honey Horse Chestnut Seed Extract Indigo Naturalis Licorice Root Marigold Menthol Prebiotics, Probiotics, and Postbiotics Tea Tree Oil Turmeric Vitex (Chasteberry) Cannabinoids Diet-Based Therapies Traditional Chinese Medicine Treatment of Dermatologic Diseases Atopic dermatitis Psoriasis Moxibustion, Cupping and Other Treatment Modalities Homeopathy Aromatherapy Mind–Body Medicine Ayurveda Conclusion References 134- Ultraviolet Therapy 134 Ultraviolet Therapy INTRODUCTION PHOTOTHERAPY WITH UVB Historical Aspects Principles and Mechanisms Action Spectrum and Radiation Sources Treatment Protocols Phototherapy for Psoriasis Phototherapy for Cutaneous T Cell Lymphoma, in Particular Mycosis Fungoides Phototherapy for Vitiligo Phototherapy for Atopic Dermatitis Broadband UVB (BB-UVB) phototherapy UVA/UVB phototherapy Narrowband UVB (NB-UVB) phototherapy Phototherapy for Photodermatoses Phototherapy for Pityriasis Lichenoides Phototherapy for Seborrheic Dermatitis Phototherapy for Pruritus Side Effects of Phototherapy With UVB PHOTOTHERAPY WITH THE 308 NM EXCIMER LASER OR LAMP PHOTOTHERAPY WITH UVA1 Side Effects of Phototherapy with UVA1 PHOTOCHEMOTHERAPY WITH PSORALENS (PUVA) Historical Aspects Psoralens Psoralen photochemistry Action Spectrum and Light Sources Photobiologic Effects of PUVA Treatment Protocols Oral PUVA Bath PUVA Topical PUVA Initial Treatment (Clearing) Phase Maintenance Phase PUVA for Psoriasis Combination Treatments Topical combination Methotrexate, cyclosporine, systemic immunomodulators (“biologics”) Retinoids PUVA for Cutaneous T Cell Lymphoma, in Particular Mycosis Fungoides PUVA for Vitiligo Treatment protocols and results PUVA for Atopic Dermatitis (See Ch. 12) PUVA for Lichen Planus (See Ch. 11) PUVA for Graft-Versus-Host Disease (see Ch. 52) PUVA for Urticaria Pigmentosa (See Ch. 118) PUVA for Miscellaneous Dermatoses PUVA for Photodermatoses Side Effects and Long-Term Hazards of PUVA Ophthalmologic effects Laboratory data Potential long-term risks of PUVA UVB and PUVA in HIV-Infected Patients EXTRACORPOREAL PHOTOCHEMOTHERAPY (PHOTOPHERESIS) Treatment Protocols Mechanism of Action Side Effects Other Indications REFERENCES 135- Photodynamic Therapy 135 Photodynamic Therapy INTRODUCTION HISTORY AND DEVELOPMENT PDT – PHOTOCHEMISTRY, PHOTOBIOLOGY, AND MECHANISM OF ACTION PDT Photochemistry Photobiologic Mechanisms of Action PDT Selectivity Advantages and Limitations of PDT COMPONENTS OF PDT Photosensitizers Light Sources Artificial light sources (conventional PDT) Natural outdoor light (daylight PDT D-PDT) Light delivery PDT Dosimetry DERMATOLOGIC APPLICATIONS Oncologic Actinic keratoses Basal cell carcinomas (BCCs) Squamous cell carcinomas (SCCs) PDT photochemoprevention of AKs and keratinocyte carcinomas Extramammary Paget disease Other neoplasms Non-Oncologic PDT Applications Acneiform disorders Photoaging Cutaneous infections Vascular anomalies ADVERSE EFFECTS AND COMPLICATIONS OF PDT Photosensitivity Pain Inflammation Photosensitizer Allergy Rare, Unusual or Controversial Reactions PRACTICE AND TECHNIQUES FUTURE DIRECTIONS REFERENCES 136- Lasers_and_Other_Energy_Based_Technologies_–_Principles_and_Skin 136 Lasers and Other Energy-Based Technologies – Principles and Skin Interactions INTRODUCTION LASERS SKIN OPTICS THERMAL INTERACTIONS SELECTIVE PHOTOTHERMOLYSIS PHOTOMECHANICAL EFFECTS COOLING FOR SKIN PROTECTION APPLICATIONS OF LASER PRINCIPLES Ablative (Vaporizing) Skin Resurfacing Interactions During Treatment of Vascular Lesions Interactions During Treatment of Pigmented Lesions and Tattoos Interactions During Hair Removal Non-Ablative Skin Rejuvenation Fractional Photothermolysis Laser-Induced Optical Breakdown (Plasma Formation) Interactions During Laser Targeting of Lipids and Sebaceous Glands Laser-Based Diagnostics PRINCIPLES OF LASER SAFETY NON-LASER ENERGY SOURCES Flashlamps (Intense Pulsed Light) Photobiomodulation (PBM, also called Low Level Light Therapy LLLT) Radiofrequency High-Intensity Focused Electromagnetic (HIFEM) Nano-Pulse Stimulation (NPS) Ultrasound Cryolipolysis FUTURE DIRECTIONS REFERENCES 137- Lasers and Other Energy-Based Therapies 137 Lasers and Other Energy-Based Therapies Introduction Types Of Lasers And Intense Pulsed Light Pulsed Dye Laser KTP Laser (Frequency-Doubled Nd:YAG Laser) Nd:YAG Laser Intense Pulsed Light Ablative Lasers: Carbon Dioxide And Er:Yag Fractionated Lasers Non-Ablative Fractional Photothermolysis Ablative Fractional Photothermolysis Fractionated Laser Assisted Drug Delivery Treatment Of Chronic Photodamage Treatment Of Vascular Lesions Port-Wine Birthmarks (PWBs) Infantile Hemangiomas Telangiectasias Poikiloderma of Civatte Telangiectasias and Venulectasias of the Leg (“Spider” Leg Veins) Pyogenic Granulomas Venous Lakes and Cherry Angiomas Verrucae Pain Considerations Treatment Of Melanin-Containing Lesions Ephelides and Lentigines Benign Melanocytic Nevi Café-au-Lait Macules and Nevus Spilus Nevus of Ota and Nevus of Ito Melasma Becker Melanosis (Nevus) Postinflammatory Hyperpigmentation and Drug-Induced Discoloration Hair Removal Treatment Of Scars Treatment Of Striae Distensae Treatment Of Cellulite Treatment Of Tattoos Treatment Of Psoriasis And Vitiligo Pre- And Postoperative Considerations, Side Effects, And Complications Preoperative Considerations Anesthesia and Eye Protection Post-therapy Considerations, Side Effects, and Complications Radiofrequency And Ultrasound Skin Tightening Radiofrequency Microneedling Devices Microwaves Home-Based Lasers Emerging Technologies Conclusions References 138- Cryosurgery 138 Cryosurgery Historical Background Principles Of Cryosurgery And Cryobiology Cryoimmunology Instruments And Techniques Preoperative Considerations Cryoanesthesia Treatment Benign Lesions Premalignant Lesions, Including Actinic Keratoses Cutaneous Malignancies Palliative Treatment Expected Postoperative Events And Care Complications Future Trends (Imaging Technology For Monitoring Cryosurgical Outcome) References 139- Radiotherapy 139 Radiotherapy BASICS OF RADIOTHERAPY Indications Mechanism of Action Treatment Machines Terminology Radiotherapy Doses Radiation Modalities Low-energy photons (superficial and orthovoltage) Superficial radiotherapy Orthovoltage radiotherapy Electron beam therapy Brachytherapy Radioisotope brachytherapy Electronic brachytherapy Advantages of Radiotherapy Disadvantages of Radiotherapy RADIOTHERAPY OF BENIGN SKIN DISORDERS Background Keloids Cutaneous Lymphoid Hyperplasia (Cutaneous Pseudolymphoma) RADIOTHERAPY OF IN SITU CUTANEOUS MALIGNANCIES Squamous Cell Carcinoma In Situ (Bowen Disease) Lentigo Maligna RADIOTHERAPY OF INVASIVE CARCINOMAS, SARCOMAS, AND LYMPHOMAS Basal Cell Carcinoma Definitive radiotherapy Adjuvant (postoperative) radiotherapy Squamous Cell Carcinoma Definitive radiotherapy Adjuvant (postoperative) radiotherapy Keratoacanthomas Special clinical situations SCC of the lip Lymph node metastases of SCC Perineural invasion of SCC and BCC Immunosuppressed hosts Dose fractionation schedules and fields Merkel Cell Carcinoma Angiosarcoma Kaposi Sarcoma Cutaneous Lymphomas Total skin electron beam therapy Adnexal Carcinomas PALLIATION Locally Advanced Tumors Metastases REACTIONS AND COMPLICATIONS Acute Reactions (Acute Radiodermatitis) Late Reactions Younger Patients Cutaneous Diseases Induced by Radiation Therapy FUTURE TRENDS REFERENCES 140- Electrosurgery 140 Electrosurgery Introduction And Background Definition Electrocautery Historical Aspects Electrosurgical Devices and Outputs Terminology: Monopolar, Bipolar, Monoterminal, and Biterminal Indications/Contraindications Preoperative History And Considerations Description Of Techniques Electrodesiccation and Electrofulguration Electrocoagulation Electrosection (Cutting) Variations/Unusual Situations Cardiac Implantable Electronic Devices Postoperative Care Complications Fire Thermoelectric Burns Microorganism Transmission Surgical Smoke Electroepilation Electrolysis vs Thermolysis Side Effects Iontophoresis Future Trends References 141- Biology of Wound Healing 141 Biology of Wound Healing INTRODUCTION Regeneration Versus Repair Effect of Immune Response on Wound Healing MECHANISMS OF TISSUE REPAIR AND REGENERATION ARE EVOLUTIONARILY CONSERVED Amphibians Zebrafish Mammals Clinical Implications IMPACT OF WOUND DEPTH ON WOUND HEALING Primary Versus Second Intention Healing SKIN REPAIR – CELLULAR AND MOLECULAR ASPECTS The Phases of Wound Healing Cellular Components Keratinocytes Endothelial cells Leukocytes and platelets Platelets and polymorphonuclear leukocytes Blood monocytes and tissue macrophages T cells Mast cells Fibroblasts Stem cells Growth Factors and Their Receptors Extracellular Matrix Integrins Proteases (Proteinases) IMPAIRED WOUND HEALING – RISK FACTORS Wound Healing and Aging THERAPEUTIC OPTIONS FOR CHRONIC WOUNDS Wound Dressings Growth Factors Cell- and Tissue-Based Therapies FUTURE DIRECTIONS Stem Cells Molecular Modeling of Growth Factors Biomaterials and Tissue Engineering Wound Metabolism Advances in Systemic Drug Development REFERENCES 142- Surgical Anatomy of the Head and Neck 142 Surgical Anatomy of the Head and Neck TOPOGRAPHIC ANATOMY OF THE HEAD AND NECK SKIN TENSION LINES COSMETIC SUBUNITS FREE MARGINS THE SUPERFICIAL MUSCULOAPONEUROTIC SYSTEM MUSCLES OF FACIAL EXPRESSION VASCULAR ANATOMY THE FACIAL NERVE Temporal Branch Zygomatic and Buccal Branches Marginal Mandibular Branch Cervical Branch SENSORY INNERVATION OF THE HEAD AND NECK LYMPHATIC DRAINAGE OF THE HEAD AND NECK REFERENCES 143- Anesthesia 143 Anesthesia INTRODUCTION DISCUSSION Physiology and Structure Pharmacology Additions to Local Anesthetics Epinephrine Sodium bicarbonate Hyaluronidase Anesthetic Mixtures Side Effects Vasovagal reactions Allergic reactions Local side effects Overdosage Topical Anesthetics Skin Mucous membranes Cryoanesthesia Anesthetic Injection Techniques Local infiltration Field block anesthesia Tumescent anesthesia Nerve Block Techniques Facial nerve blocks Digital nerve blocks Penile nerve block Hand nerve block Foot nerve block Higher Levels of Anesthesia REFERENCES 144- Wound Closure Materials and Instruments 144 Wound Closure Materials and Instruments Introduction Discussion Sutures Types of Suture Material Absorbable sutures Surgical gut Polyglycolic acid Polyglactin 910 Polydioxanone Polyglyconate Poliglecaprone 25 Glycomer 631 and polyglytone 6211 Non-absorbable sutures Silk Nylon Polypropylene Polyester Polybutester Suture Selection Complications Needles Instruments Curettes Scalpels Needle holders Scissors Forceps Hemostats Skin hooks Special Instruments Antiseptics and Sterilization References 145- Dressings 145 Dressings INTRODUCTION MOIST HEALING ENVIRONMENT HISTORY OF WOUND DRESSINGS FUNCTIONS OF A WOUND DRESSING TRADITIONAL WOUND DRESSINGS FIRST AND SECOND INTENTION HEALING ROLE OF DEBRIDEMENT WOUND CLEANSERS TOPICAL ANTIMICROBIALS AND DRESSINGS THAT CONTAIN ANTIMICROBIAL AGENTS MOISTURE-RETENTIVE DRESSINGS Films Advantages/disadvantages Foams Advantages/disadvantages Hydrogels Advantages/disadvantages Alginates Advantages/disadvantages Gelling Fibers (Hydrofibers) Hydrocolloids Advantages/disadvantages Superabsorbent Dressings Contact Layers Composite Dressings ADVANCED WOUND THERAPIES Topical Growth Factors Tissue-Engineered Skin Equivalents or Skin Substitutes Epidermal Grafts Dermal Replacements Xenogeneic Allogeneic Composite Grafts Negative Pressure Wound Therapy (NPWT) Oxygen Therapy COMPRESSION THERAPY Types of Compression Compression stockings Compression bandages Short stretch (inelastic) versus long stretch (elastic) bandages Compression devices FUTURE DIRECTIONS REFERENCES 146- Biopsy Techniques and Basic Excisions 146 Biopsy Techniques and Basic Excisions INTRODUCTION KEY CONCEPTS Site Selection Biopsy Technique Selection Specimen Handling Patient Preparation Site Preparation and Anesthesia Hemostasis Wound Closure INDICATIONS/CONTRAINDICATIONS PREOPERATIVE HISTORY AND CONSIDERATIONS TECHNIQUES Curettage Snip or Scissors Biopsy Shave Biopsy and Saucerization Biopsy Punch Biopsy Incisional Biopsy Excisional Biopsy (Excision in toto) Cutaneous Cone (Dog-Ear) Repair VARIATIONS/UNUSUAL SITUATIONS POSTOPERATIVE CARE COMPLICATIONS FUTURE TRENDS REFERENCES 147- Flaps 147 Flaps INTRODUCTION BACKGROUND Fundamentals of Flap Design and Suturing Technique Flap Movement Characteristics Burow’s triangle displacement flaps Defect reconfiguration flaps Tissue reorientation flaps Tissue importation flaps DESCRIPTION OF TECHNIQUE Burow’s Triangle Displacement Flaps Single tangent advancement flaps (STAFs) and rotation flaps Double tangent advancement flaps (DTAFs) Site-Specific Variations of Burow’s Triangle Displacement Flaps Helical advancement flaps Dorsal nasal flap Other Site-Specific Flaps Alar rotation flap (ARF) and spiral rotation flap (SRF) Cheiloplasty of the lip Defect Reconfiguration (Pedicled V-to-Y) Flaps Pedicled V-to-Y flap variation: the pincer flap Tissue Reorientation Flaps Rhombic transposition flap Bilobed transposition flap Trilobed flap and rhombic flap with Z-plasty Nasolabial transposition flap Tissue Importation Flaps Forehead flaps Nasolabial interpolation flap Retroauricular flap Spear’s flap Tunneled flaps Combination Flaps POSTOPERATIVE CARE COMPLICATIONS REFERENCES 148- Grafts 148 Grafts Introduction And Background Wound Healing Considerations Full-Thickness Skin Grafts Indications/Contraindications Preoperative History and Donor Site Considerations Description of Technique Securing the Graft Postoperative Care Variations/Unusual Situations Purse-string suture Burow’s grafts Deep nasal defects Postoperative Complications Future Directions Split-Thickness Skin Grafts Indications/Contraindications Preoperative History and Donor Site Considerations Description of Grafting Techniques Securing the Graft Donor Site Care Variations/Unusual Situations Postoperative Care Complications Future Directions Composite Grafts Indications/Contraindications Preoperative History and Considerations Donor Site Considerations for Composite Grafts Description of Technique Donor Site Closure48 Variations/Unusual Situations Postoperative Care Complications Free Cartilage Grafts Indications/Contraindications Nasal Ala Nasal Sidewall and Tip Ear Preoperative History and Donor Site Considerations Description of Technique Nasal ala Nasal sidewall and tip Ear Eyelid Postoperative Care Complications Future Trends Conclusions References 149- Nail Surgery 149 Nail Surgery INTRODUCTION SURGICAL ANATOMY OF THE NAIL UNIT Basic Anatomy Innervation Vascular Supply PREOPERATIVE EVALUATION AND PATIENT PREPARATION ANESTHESIA OF THE NAIL UNIT INSTRUMENTS FOR NAIL SURGERY NAIL PLATE AVULSION BIOPSY TECHNIQUES Nail Bed Biopsy Nail Matrix Biopsy Lateral Longitudinal Biopsy Proximal Nail Fold Biopsy SURGICAL PROCEDURES FOR DISORDERS OF THE NAIL UNIT Acute Paronychia Chronic Paronychia Ingrown Toenail Tumors and Cysts Fibrokeratoma Subungual exostosis Glomus tumor Onychomatricoma Digital myxoid cyst (pseudocyst) Squamous cell carcinoma Melanoma Hemostasis POSTOPERATIVE CARE COMPLICATIONS OF NAIL SURGERY REFERENCES Further reading 150- Mohs Micrographic Surgery 150 Mohs Micrographic Surgery Introduction History Training In Mohs Micrographic Surgery Appropriate Use Criteria And Cost-Effective Care Indications Basal Cell Carcinoma Squamous Cell Carcinoma Cutaneous Melanoma Melanoma in situ (lentigo maligna) of the head and neck region Invasive melanoma Staged excisions (“slow Mohs”) for melanoma Uncommon or Rare Cutaneous Neoplasms Atypical fibroxanthoma/pleomorphic dermal sarcoma Dermatofibrosarcoma protuberans Merkel cell carcinoma Microcystic adnexal carcinoma Sebaceous carcinoma Other adnexal carcinomas Miscellaneous tumors Contraindications Preoperative History And Considerations Technique Variations/Refinements Challenges And Pitfalls Reconstruction Postoperative Care Complications Future Trends References E-REFERENCES 151- Surgical Complications and Optimizing Outcomes 151 Surgical Complications and Optimizing Outcomes INTRODUCTION DISCUSSION Preoperative Assessment Potential for bleeding Laboratory evaluation Medications and dietary supplements Wound healing Prophylactic antibiotics Implantable electronic medical devices Cardiac defibrillators and pacemakers Deep brain stimulators Cochlear implants Nerve stimulators Allergies Informed consent Intraoperative Considerations Contamination Bleeding and hemostasis Tissue injury Tension Necrosis Nerve deficits Unsatisfactory scarring Postoperative Considerations Bleeding/hematoma/ecchymosis Infection Necrosis Dehiscence Wound appearance CONCLUSIONS REFERENCES 152- Evaluation of Beauty and the Aging Face 152 Evaluation of Beauty and the Aging Face INTRODUCTION EVALUATION OF BEAUTY ANATOMIC BASIS FOR THE AGING APPEARANCE PHOTOAGING PIGMENTARY SYSTEM VOLUME CHANGES – THE LOSS OF SUBCUTANEOUS FAT CHANGES IN FACIAL MUSCULATURE CHANGES IN UNDERLYING CARTILAGE AND BONE INHERENT LOSS OF ELASTICITY SEX AND GENDER DIFFERENCES ETHNIC DIFFERENCES COMBINATION THERAPIES REFERENCES 153- osmetics and Cosmeceuticals 153 Cosmetics and Cosmeceuticals Introduction Discussion Skin Care Products Cleansers Moisturizers Astringents Colored Facial Cosmetics Facial foundations Formulation Application and cutaneous effects Powders Facial blushes Eye shadows Mascaras Lipsticks Facial cosmetics for camouflaging Hair Care Products Hair shampoos Hair conditioners Safety issues Nail Care Products Nail polish Nail sculptures (artificial nails) Hydroxy Acid Cosmeceuticals Alpha-hydroxy acids Beta-hydroxy acid Additional Cosmeceuticals Future Directions References 154- Chemical and Mechanical Skin Resurfacing 154 Chemical and Mechanical Skin Resurfacing Introduction and History Preoperative History and Considerations Indications Contraindications and Patient Selection Preoperative and Intraoperative Preparations Chemical Resurfacing Procedures Superficial Chemical Peeling Medium-Depth Chemical Peeling TCA CROSS Deep Chemical Peeling Mechanical Resurfacing Procedures Microdermabrasion Manual Dermasanding Motorized Dermabrasion Subcision Microneedling Postoperative Care Complications Conclusions and Future Trends References 155- Phlebology and Treatment of Leg Veins 155 Phlebology and Treatment of Leg Veins Introduction Venous Anatomy, Physiology, And Pathophysiology Physical Examination Of The Phlebology Patient Laboratory Evaluation Of The Superficial Venous System Compression In Sclerotherapy And Venous Disease Sclerosing Solutions Techniques For Treating Telangiectasias And Reticular Veins Injection Technique Treatment Protocol Lasers and Intense Pulsed Light Sources for Treatment of Telangiectasias Larger Varicose Veins Foamed Detergent Solutions Polidocanol 1% injectable foam (Varithena®) Spontaneous foaming with room air Duplex Ultrasonography Postsclerotherapy Compression Complications Postsclerotherapy Pigmentation Telangiectatic Matting Ulceration Systemic Allergic Reaction Arterial Injection Miscellaneous Complications Ambulatory Phlebectomy Preoperative Considerations Anesthesia and Intraoperative Materials for Ambulatory Phlebectomy Ambulatory Phlebectomy Technique Postoperative Considerations for Ambulatory Phlebectomy Complications of Ambulatory Phlebectomy Targeting The Saphenofemoral Junction (Sfj) Endovenous Laser Ablation (EVLA) Endovenous Radiofrequency Closure (Ablation) Combination with Ambulatory Phlebectomy Comparative Clinical Trials Other Endovenous Procedures for the Treatment of Saphenofemoral Junction Incompetence Conclusions References 156- Body Contouring Liposuction and Non-invasive Modalities 156 Body Contouring: Liposuction and Non-invasive Modalities INTRODUCTION AND BACKGROUND CONSULTATION LIPOSUCTION Indications and Contraindications The Preoperative Visit Description of Techniques Tumescent anesthesia Liposuction surgical technique LIPOSUCTION INSTRUMENTATION Liposuction Devices Ultrasound-assisted Power-assisted Laser-assisted Radiofrequency-assisted Water-assisted Manual liposuction versus device-assisted LIPOSUCTION VARIATIONS NON-COSMETIC LIPOSUCTION POSTOPERATIVE CARE COMPLICATIONS OF LIPOSUCTION NON-INVASIVE BODY CONTOURING Injection Lipolysis Low Level Light Therapy (LLLT) High-Intensity Focused Ultrasound Non-thermal Focused Ultrasound Cryolipolysis Radiofrequency CELLULITE External Devices Subdermal Devices Subcision Vacuum-assisted subcision Fat Transfer and Fillers Collagenase CONCLUSION References 157- Hair Restoration 157 Hair Restoration Introduction Historical Perspective Male And Female Pattern Hair Loss (Androgenetic Alopecia) Pathogenesis Clinical Features Treatment (Other Than Transplant Surgery) Medical therapies Low-level light therapy Platelet-rich plasma Hair Transplantation Candidate Selection Key Concepts Staff Training for Manual Hair Transplantation Donor Region Elliptical donor harvesting (follicular unit transplantation [FUT]) Follicular grafts Follicular unit excision (FUE) Hairline Design and Recipient Site Creation Anesthesia and Recipient Site Creation Graft Placement and Postoperative Course Complications Corrective Hair Transplant Surgery Adding follicular unit grafts Surgical removal of grafts Laser-assisted removal of large grafts Hypertrophic or broad scars in the donor region Hair Transplantation in Scarring Alopecias Hair Transplantation in African-Americans Future Trends Acknowledgment References 158- Injectable Soft Tissue Augmentation 158 Injectable Soft Tissue Augmentation HISTORICAL PERSPECTIVE GENERAL INJECTION PROTOCOLS Nose, Glabella, and Forehead Nasolabial Fold, Cheek Temple Lips Chin, Jawline Consultation and Evaluation Preparation Injection Techniques Needles and Cannulas INJECTABLE SOFT TISSUE FILLER MATERIALS Hyaluronic Acid Derivatives Poly-L-Lactic Acid Calcium Hydroxylapatite Lipotransfer Silicone Polymethylmethacrylate (PMMA) Microspheres PLATELET-RICH PLASMA COMPLICATIONS CONCLUSION Copyright notice REFERENCES 159- Botulinum Toxin 159 Botulinum Toxin Introduction Properties Of Botulinum Toxins Formulations Clinical Differences Topical BoNT-A A Note About Dosing Cosmetic Use Of Botulinum Toxin Type A Glabellar Frown Lines Crow\'s Feet Horizontal Forehead Lines Brow Lift and Shaping Hypertrophic Orbicularis Oculi Midface Injections Vertical Lip Rhytides (Perioral Lines) Facial Asymmetry: Functional Muscle Imbalance Mouth Frown Melomental Folds (Marionette Lines) Mental Crease Peau d’Orange (Apple Dumpling) Chin Masseteric Hypertrophy Platysmal Bands Adjunctive Use Medical Uses Of Botulinum Toxin Type A Hyperhidrosis Raynaud Phenomenon Migraine Depression Complications Safety Future Trends Summary References
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