Allergy Essentials

Front Cover
Allergy Essentials
Copyright Page
Contributors
Contents
1 Introduction to Mechanisms of Allergic Diseases
	Summary of Important Concepts
	Introduction
	Innate Immunity
		Microbial Pattern Recognition by the Innate Immune System
		Pattern Recognition Receptors
		Cellular Responses of Innate Immunity
		Innate Instruction of Adaptive Immune Responses
		Innate Immunity and Allergy
	Adaptive Immunity
		Adaptive Immune Response in Allergic Disease
		Main Components of the Adaptive Immune System
		Features of the Adaptive Immune Response
		Mechanisms of Diseases Involving Adaptive Immunity
	Immunoglobulin Structure and Function
		B Lymphocytes and the Humoral Immune Response
		Immunoglobulin Structure and Gene Rearrangement
		Immunoglobulin Function
	Immunoglobulins and Human Disease
	Immune Tolerance
		Introduction
		Central and Peripheral Tolerance Mechanisms
		Central Tolerance
		Peripheral Tolerance
		Histamine Receptors in Peripheral Tolerance
		Immune Effector Cells and Molecules
			Treg Cells and Regulatory B cells
			Transforming Growth Factor-β (TGF-β)
			Interleukin-10 (IL-10)
	Cytokines and Chemokines in Allergic Inflammation
		Cytokines in Allergic Inflammation
			Interleukin-4 (IL-4)
			Interleukin-5 (IL-5)
			Interleukin-9 (IL-9)
			Interleukin-13 (IL-13)
			Interleukin-25 (IL-25)
			Interleukin-33 (IL-33)
			Interleukin-35 (IL-35)
			Thymic Stromal Lymphopoietin (TSLP)
		Chemokines in Allergic Diseases
			Asthma
			Atopic Dermatitis
	Biology of Immune Cells
		T Lymphocytes
		B Lymphocytes
		Innate Lymphoid Cells
		Dendritic Cells
		Mast Cells
		Basophils
		Eosinophils
	Contribution of Structural Cells to Allergic Inflammation
		Airway Epithelial Cells
		Airway Smooth Muscle Cells
		Neuronal Control of Airway Function
	Cytokine Networks in Allergic Inflammation
	Microbiome and Immune System
	Food Allergy as a Model for Allergic Diseases
	Resolution of Allergic Inflammation and Major Pathways
	References
2 Precision Medicine
	Precision Medicine: A Brief History and Definition
	Evidence-Based Versus Precision Medicine
	Components of Precision Medicine in Allergic Disorders
		Endotypes/Biomarkers in Allergic Disorders
		Immune Profiling of Allergic Disorders
		Role of -omics
			Genomics
			Transcriptomics
			Epigenomics
			Proteomics
			Metabolomics
			Microbiome
			Exposomics
			Comprehensive Integrative Omics
			Pharmacogenomics and Drug Dosing
	Precision Medicine in the Management of Allergic Disorders
		Nutrition
			Vitamin D
			Fatty Acids
		Respiratory Pathogens and Allergic Disease
	Biologics and Precision Medicine
		Asthma
			Anti-IgE
			Anti–IL-5 or Anti–IL-5 Receptor
			Anti–IL-4/IL-13
			Other
		Atopic Dermatitis
		Chronic Rhinosinusitis With Nasal Polyposis
		Eosinophilic Esophagitis (EoE)
		Food Allergy
	Challenges in Precision Medicine
	Summary
	References
3 Epidemiology of Allergic Diseases
	Summary of Important Concepts
	Introduction
	Epidemiological Definitions of Allergic Diseases: Part of the Challenge
		Asthma
		Allergic Rhinitis
		Atopic Dermatitis/Eczema
		Atopic March, Comorbidity or Multimorbidity of AD, Asthma, and Allergic Rhinitis
		Allergic Sensitization
		Food Allergy
	Estimates of Worldwide Prevalence of Asthma, Rhinitis, Ad, and Food Allergy
		Asthma
		Geographical Variations in the Prevalence of Asthma
			Childhood Asthma
			Adult Asthma
		Allergic Rhinitis
		Atopic Dermatitis
		Food Allergy
	Trends in Prevalence Over Time
		Asthma, Allergic Rhinitis, and Sensitization
		Food Allergy
	Risk Factors for Asthma and Allergic Diseases
		Protective Environments
		Air Pollution
	Concluding Remarks
	References
4 Indoor and Outdoor Allergens and Pollutants
	Summary of Important Concepts
	Introduction
	Allergens and Allergenicity
	Indoor and Outdoor Allergen Sources
	Aerobiology of Indoor and Outdoor Allergen Sources
	Allergen Monitoring—Whole Spores, Pollens, and Mites
	Measuring Specific Allergens
	The Chemical Nature of Allergens
	Allergen Nomenclature and Allergen Databases
	Outdoor Allergens
		Outdoor Aeroallergens—Pollen
			Pollen Structure
			Allergenic Pollen
			Pollen Allergens
		Outdoor Allergens—Fungi
		Outdoor Allergens—Stinging and Biting Arthropods
	Indoor Allergens
		Indoor Allergen Sources—Nonmammalian
			Acaridae
			Insecta
		Indoor Allergen Sources—Mammalian
			Cats, Dogs, and Rabbits
			Rodents and Rodent Allergens
	Allergens and Allergenicity
		Allergens and Functionalism
		Allergens as Proteases
		Allergens and Toll-like Receptors (TLRs)
		Allergens and C-type Lectin Receptors (CTLRs)
	Environmental Modifiers of Allergic Sensitization and Disease
		Avoidance Measures for Indoor Allergens
			House-Dust Mites
			Furry Animals
			Cockroaches and Other Allergens
			The Indoor Microbiome
	Environmental Air Pollution, Allergic Sensitization, and Disease
		Sources of Air Pollution
			Biomass
			Environmental Tobacco Smoke (ETS) and Electronic Cigarettes (E-cigs)
			Lipopolysaccharide (LPS)
	Types of Pollutant and Their Effects on Allergens, Allergic Sensitization, and Asthma
		Particulates
		Gaseous Pollutants
			Sulfur Dioxide (SO2)
			Nitrogen Dioxide (NO2)
			Ozone (O3)
	Air Pollution, Climate Change, and Allergens
	Conclusions
	Acknowledgments
	References
5 Principles of Allergy Diagnosis
	Introduction
	Use of IgE Sensitization Tests in Epidemiology
	Pathogenesis and Etiology
	Clinical Features
	Patient Evaluation
		Why Test
			Why Search for IgE Sensitization?
		Whom to Test
			Who Would Benefit From Testing?
		When to Test
			Is There an Age Limit to Perform Skin Tests?
			Does My Patient Need to Be Tested Regularly?
		Where to Test
			The Location: Are Skin Tests Safe to Perform and Can They Be Performed in Office Settings?
		What to Test
			Do All Allergists Test the Same Allergens? Is There a “Standardized” Panel to Be Observed, and If So, How Many Allergens Sh ...
			Can We Test Anything on the Skin?
			My Patient May Be Allergic to Mango Fruit, Is There an Allergen Extract for This Specific Food?
			My Patient Was Referred to the Allergist for a Suspicion of Food Allergy. The Allergist Also Performed Skin Tests to Inhala ...
		How to Test
			What Skin Tests Are Recommended in Allergy Practice?
			Are Both Types of Tests Mandatory?
			What Quantity of Allergen Penetrates the Skin Using These Techniques?
			What Is the Reference to Ensure Reliable Skin Reactivity?
			My Patient Is Under Antihistaminic and Antiasthmatic Treatment. How Long Does He Need to Stop the Treatment Before Skin Tes ...
			Antihistamines
			Imipramines, Phenothiazines, and Tranquilizers
			Corticosteroids
			Other Immunomodulators
		Other Drugs
			Can Skin Tests Be Performed Despite Ongoing Antihistaminic Treatment?
			On Which Area of the Body Are Skin Tests Performed?
			How Much Does It Take to Get the Result of the Skin Tests?
		How to Interpret
			When Is a Skin Test Considered Positive?
			Can Skin Tests Become Positive Later On? My Patient Developed a Reaction a Few Hours After the Allergy Visit and Skin Tests
			How Reliable Is Skin Testing?
			My Patient Has Positive Skin Tests for Cat Dander but No Allergic Symptoms in the Presence of Cats. Does This Mean He Is Al ...
			My Patient Is Sensitized to Many Respiratory Allergens. Can He Benefit From Allergen Immunotherapy?
			My Patient Has Undergone Allergen Immunotherapy for 3 Years to House-Dust Mites but Still Has Positive Skin Tests to These  ...
			My Patient Has Suffered From an Anaphylactic Shock a Few Days Ago. The Allergist Prescribed an Emergency Kit, but Did Not P ...
	Referral
	Conclusions
	References
6 Allergen-Specific Immunotherapy
	Summary of Important Concepts
	Introduction
	Historical Perspective
	Indications for Specific Allergen Immunotherapy
	Clinical Efficacy with Specific Allergens
		Grass, Tree, and Weed Pollens
		House-Dust Mites
		Domestic Pets
		Fungi
		Cockroach
		Multiple Allergen Mixtures
	Specificity of Allergen Immunotherapy
	Evidence of Disease Modification
		Persistence of Clinical Improvement After Cessation of Immunotherapy
	Pharmacoeconomics of Sit
	Immunologic Response to Inhalant Sit
	Overview of the Immune Response to Immunotherapy
	Indications for Sit
		Injection Schedules
		Adverse Reactions to SIT
		SIT in Pregnancy
		Adherence to SIT
	Sublingual Immunotherapy
		Mechanisms of SLIT
		Side Effects of SLIT
		Efficacy of SLIT
		SLIT for Asthma
		Durability of Treatment
		Effects of SLIT on the Natural History of Allergic Disease
		Safety and Cost-Effectiveness of SLIT
	Modified Allergen Extracts and Adjuvants (Box 6.6)
		Recombinant Allergen Vaccines
		Unmodified Allergens
		Modified Allergens
	The Future of Slit
	Conclusions
	References
	Suggested Reading
7 Asthma
	Summary of Important Concepts
	Introduction and Overview
		Background
		Diagnosis
		Airway Inflammation and Remodeling
		Treatment
		Prevalence and Impact of Asthma
	Historical Perspective
	Epidemiology
		Incidence
		Prevalence
		Changing Trends
	Pathogenesis and Etiology
		Inflammatory Changes
		Structural Changes and Airway Remodeling
		Immunologic Factors
		Genetics and Epigenetics
	Clinical Features and Phenotypes of Asthma
		Phenotypes of Adult Asthma
		Phenotypes in Children
	Evaluation and Diagnosis
		Diagnosis in Adults
			Risk Factors
			History and Examination
			Lung Function
			Bronchial Hyperreactivity (BHR or Bronchial Hyperresponsiveness)
			Determination of the Allergic Status
			Assessment of Airway Inflammation
			Imaging
		Asthma Diagnosis in Specific Settings
			Occupational Asthma
			Asthma in the Elderly
			Asthma in the Athlete
			Conditions That May Mimic Asthma
		Diagnosis in Children
			History and Examination
			Radiographic Studies
			Pulmonary Function Tests
			Laboratory Evaluation
		Monitoring Asthma
			Severity
			Symptom Control
			Exacerbations
			Asthma-Related Quality of Life
			Lung Function
			Rescue Medication Use
			Adherence With Regular Medication and Inhaler Technique
			Personal Asthma Action Plan
	Asthma Management
		Long-Term Management in Adults
			Control of Environmental Factors
			Comorbidity
		Pharmacologic Treatment in Adults
			Quick-Relief Medications
				Short-Acting β2-Agonists.
				Anticholinergics.
			Long-Term Control Medications
				Corticosteroids.
				Leukotriene Modifiers.
				Long-Acting β2-Agonists.
				Biologics.
				Methylxanthines.
				Cromolyn Sodium and Nedocromil Sodium.
		Step Care Approach to Asthma Management
			Intermittent Asthma
				Step 1 Care.
			Persistent Asthma (see Fig. 7.10)
				Step 2 Care: Mild Persistent Asthma.
				Step 3 Care: Moderate Persistent Asthma.
				Steps 4 and 5 Care: Severe Persistent Asthma.
				Step 5 Care in Severe Persistent Asthma.
				Bronchial Thermoplasty.
				Step-up and Step-down Considerations.
					Immunotherapy
					Vaccination.
					Food Allergy and Anaphylaxis.
		Asthma Management in Infants and Children
		Nonpharmacologic Management in Children
			Environmental Control
			Psychosocial Factors
		Asthma Education
			Pharmacologic Therapy in Children
				Inhaled Corticosteroids.
				Long-Acting Bronchodilators (LABAs).
				Leukotriene Modifiers.
				Cromolyn Sodium and Nedocromil Sodium.
				Theophylline.
				Immunomodifiers.
				Immunotherapy.
	Acute Asthma and Referral for Hospital Care
		Introduction
		Evaluation
		Treatment
			Adults: Home Management of Asthma Exacerbation
			Adults: Hospital and Emergency Department Care
				Oxygen.
				Inhaled, Short-Acting β2-Agonists.
				Inhaled Anticholinergic Agents.
				Systemic Corticosteroids.
				Magnesium Sulfate.
				Heliox.
				Other Therapies.
		Care After Hospitalization and ED Visits
		Managing Exacerbations in Children
		Home Management
		Office or Emergency Department Management in Children
		Hospital Management in Children
		Posthospital Care
	Conclusions
	Asthma Diagnosis and Monitoring
		Asthma Treatment
			Better Use of Current Treatments
			New Treatments
		Prevention
	References
8 Allergic Rhinitis and Conjunctivitis
	Summary of Important Concepts
	Introduction
	Historic Perspective
	Epidemiology
		Incidence and Prevalence
		Quality of Life and Economic Impact
		Associated Diseases
	Pathogenesis and Etiology
		Clinical Features
		Patient Evaluation, Diagnosis, and Differential Diagnosis
			Physical Examination
			Fiberoptic Rhinoscopy
		Laboratory Testing
			Testing for Specific Immunoglobulin E
			Blood Eosinophils and Total Serum Immunoglobulin E
			Radiographic Imaging
			Other Tests
		Differential Diagnosis of Allergic Rhinitis
			Work-Related Rhinitis
			Chronic Rhinosinusitis With and Without Nasal Polyps
			Non-Allergic Rhinitis
				Idiopathic Non-Allergic Rhinitis (Vasomotor Rhinitis).
				Non-Allergic Rhinitis with Eosinophilia.
				Atrophic Rhinitis.
				Rhinitis Associated With Drugs.
				Hormonal Rhinitis.
				Rhinitis Related to Systemic Disease.
			Nasal and Pharyngeal Structural Abnormalities
		Differential Diagnosis of Allergic Conjunctivitis
			Other Allergy-Associated Forms of Conjunctivitis
			Infectious Conjunctivitis
			Dry Eye Syndrome
			Blepharitis
			Toxic Conjunctivitis
			Ocular Rosacea
			Keratitis
			Angle Closure Glaucoma
	Treatment
		Allergen Avoidance
		Pharmacotherapy
			Antihistamines
			Decongestants
			Intranasal Corticosteroids
			Systemic Corticosteroids
			Leukotriene Inhibitors
			Cromolyn Sodium
			Anticholinergics
			Medications for Ocular Symptoms
			Combinations of Medications
		Allergen Immunotherapy
		Surgery
		Overall Approach to Treatment
			Allergic Rhinitis
			Non-Allergic Rhinitis
		Treatment Considerations in Select Populations
			Pregnancy
			Elderly
	Indications for Referral
	CONCLUDING REMARKS
	References
9 Drug Allergy
	Summary of Important Concepts
	Introduction
	Historical Perspective
	Epidemiology
	Pathogenesis and Etiology
	Clinical Features (Phenotypes)
	Urticaria And Angioedema (Immediate Type)
	Maculopapular Exanthem (Delayed Type)
	Fixed Drug Eruptions (Delayed Type)
	Exfoliative Dermatitis (Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis) (Delayed Type)
	Systemic Drug Reactions—Severe Drug Hypersensitivity Syndromes (DHS/DRESS) (Delayed Type)
	Isolated Drug-Induced Organ Damage (Delayed Type)
	Pediatric Aspects in Drug Allergy
	Patient Evaluation, Diagnosis, and Differential Diagnosis
	Drug Classes of Special Interest
		Nonsteroidal Antiinflammatory Drugs (NSAIDs)
		Angiotensin-Converting Enzyme Inhibitor (ACE-I)
		Beta-Lactams
		Fluoroquinolones
		Antiepileptic Drugs
		Radio Contrast Media (RCM)
		Biologicals
		Checkpoint Inhibitors
	Treatment
	Referral
	Conclusions
	References
10 Urticaria
	Summary of Important Concepts
	Introduction and Historical Perspective
	Definitions and Classifications
		Urticaria
	Epidemiology
	Natural History and Prognosis
	Disease Associations
		Autoimmunity
			Infections
		Allergen-Triggered Urticaria
		Nonsteroidal Antiinflammatory Drugs (NSAIDs)
			Malignancy
	Pathogenesis and Etiology
		Skin Histopathologic Features
		Pathogenesis
			Autoimmune Hypothesis
			Skin Mast Cells
			Blood Basophils
	Diagnostic Approach
		History
		Physical Examination
		Laboratory Assessments
			Inducible Urticarias
				Cold-Induced Urticarias.
				Mechanically Induced Urticaria.
				Other Inducible Urticarias.
		Diseases Resembling Urticaria
			Differential Diagnosis
		Systemic Diseases
	Treatment of Urticaria
		General Principles
		First-Line Treatments
		Second-Line (Targeted) Treatments
			Leukotriene Pathway Inhibitors
			Oral Corticosteroids
			Other Second-Line Therapies
		Third-Line (Immunosuppresive) Drugs
		Special Considerations
			Urticaria and Angioedema in Children
			Urticaria in Pregnancy
	References
11 Atopic Dermatitis and Allergic Contact Dermatitis
	Atopic Dermatitis
		Summary of Important Concepts in Atopic Dermatitis
	Introduction
	Historical Perspective
	Epidemiology
	Pathogenesis And Etiology
		Genetics
		Atopic Diathesis
		Natural History
		Role of the Abnormal Epidermal Barrier
	Clinical Features (Phenotype)
	Complicating Features
		Ocular Problems
		Hand Dermatitis
		Infections
	Patient Evaluation, Diagnosis, and Differential Diagnosis
		Psychosocial Implications
		Role of Allergens
		Foods
		Aeroallergens
		Microbial Agents
		Autoantigens
		Immunology
		Immunopathologic Features
		Cytokine Expression
		Role of IgE in Cutaneous Inflammation
		Skin-directed Th2-like Cell Response
	Treatment
		Conventional Therapy
		Irritants
		Allergens
		Psychosocial Factors
		Patient Education
		Hydration
		Moisturizers and Occlusives
		Corticosteroids
		Topical Calcineurin Inhibitors
		Topical Phosphodiesterase 4 Inhibitor
		Tar Preparations
		Antiinfective Therapy
		Antipruritic Agents
		Biologic Therapy
	Recalcitrant Disease
		Hospitalization
		Wet Dressings
		Systemic Immunosuppressive Agents
		Phototherapy and Photochemotherapy
		Allergen Immunotherapy
	Experimental and Unproven Therapies
		Omalizumab
		Probiotics
		Emerging Therapies and Investigational Agents
	Conclusions Regarding Ad
	Allergic Contact Dermatitis
		Summary of Important Concepts in Allergic Contact Dermatitis
	Introduction
	Epidemiology
	Pathogenesis and Etiology
	Clinical Features
		Hands
		Dermatitis With Scattered Generalized Distribution
		Face
		Eyelids
	Patient Evaluation, Diagnosis, and Differential Diagnosis
	Treatment
	Referral
	Conclusions Regarding ACD
	What’s New in ACD
	References
12 Food Allergy and Gastrointestinal Syndromes
	Summary of Important Concepts
	Introduction
	Epidemiology
		Children
		Adults
		Prevalence of Food Allergy
		Natural History of Food Allergy
		Food Allergy in Adults
		Food Allergy as a Marker of Atopic Predisposition
		Pathogenesis and Etiology
		Normal Immune Response to the Ingested Food Antigens
		Food Allergens
		Cross-Reactivity
		Pathophysiologic Mechanisms of Food Allergy
		IgE-Mediated Food Allergy
		Augmentation Factors
	Clinical Features
		Gastrointestinal Food Allergy
			Gastrointestinal IgE-Mediated Food Allergy
			Non–IgE-Mediated Gastrointestinal Food Allergy
		Cutaneous Food Allergy
			Cutaneous IgE-Mediated Food Allergy
			Mixed IgE- and Non–IgE-Mediated Cutaneous Food Allergy
			Non–IgE-Mediated Cutaneous Food Allergy
		Respiratory Food Allergy
			Non–IgE-Mediated Respiratory Food Allergy
		Food-Induced Generalized Anaphylaxis
		Food-Dependent, Exercise-Induced Anaphylaxis
		Delayed Anaphylaxis Caused by Mammalian Meat
		Other Food-Induced Hypersensitivity Reactions
	Patient Evaluation, Diagnosis, and Differential Diagnosis
		Unproven Tests for Food Allergy
	Food Allergy Treatment
		Practical Management
		Food Allergen Avoidance Strategies
			General Approach to Avoidance
			Labeling of Manufactured Products
			Cross-Contact
		Manner of Exposure
			Restaurants, Food Establishments, Travel
			Avoidance for Schools and Camp
			Nutritional Issues
	Emergency Management
		Recognition of Reactions
		Treatment With Epinephrine and Antihistamines
		Emergency Plans and Special Considerations for School
		Prevention of Food Allergy
		Future Therapeutic Strategies
		Extensively Heated Milk and Egg Protein
		Sublingual Immunotherapy
		Epicutaneous Immunotherapy
	Conclusions
	References
13 Anaphylaxis
	Summary of Important Concepts
	Introduction
	Historical Perspective
	Epidemiology
	Pathophysiology
		Triggering
		Biochemical Mediators and Effects
		Mechanisms of Anaphylactic Shock
	Clinical Features (Phenotypes)
	Patient Evaluation, Diagnosis, and Differential Diagnosis
		Laboratory Testing
	Treatment
		Epinephrine (Adrenaline)
		Intravenous Fluid (Volume) Resuscitation
		Other Measures
		Monitoring
	Ongoing Management and Referral
	Conclusions
	References
14 Occupational Allergy
	Summary of Important Concepts
	Introduction and Definitions
		Occupational Asthma
		Occupational Rhinitis
	Epidemiology
	Pathogenesis and Etiology
		Agents Causing Occupational Asthma and Rhinitis
		Pathophysiology
			Immunologic, IgE-Mediated
			Immunologic, Non-IgE-Mediated
		Risk Factors
			Environmental Risk Factors
				Level of Exposure.
				Smoking and Exposure to Other Pollutants.
			Individual Risk Factors
				Atopy.
				Rhinitis.
				Nonspecific Bronchial Hyperresponsiveness.
				Genetic Susceptibility.
	Clinical Features
	Patient Evaluation, Diagnosis, and Differential Diagnosis
		Patient Evaluation and Diagnosis
			History
			Assessment of Airway Hyperresponsiveness
			Immunological Testing
			Serial Measurements of Functional Parameters
				Specific Inhalation Challenge Tests.
			Serial Measures of Airway Inflammation
				Sputum Cell Counts.
				Exhaled Nitric Oxide.
				Combination of Different Tests.
		Differential Diagnosis
	Outcomes and Treatment
	Prevention
	SocioEconomic Impact and Medicolegal Aspects
	Work-Related Anaphylaxis
	Conclusions
	References
15 Insect Allergy
	Summary of Important Concepts
	Stinging Insect Allergy
	Historical Perspective
	Epidemiology
	Etiology
		Apids
		Vespids
		Formicids
	Insect Venoms
	Clinical Features and Classification of Reactions
	Patient Evaluation and Diagnosis
		Clinical History
		Skin Tests
		In Vitro Tests
		Sting Challenge Test
	Treatment of Acute Reactions
	Prevention of Acute Reactions
		Epinephrine Kits
	Predictors of Risk for Sting Anaphylaxis
		Natural History
		Markers of Risk for Sting Anaphylaxis
	Venom Immunotherapy
		Indications
		Safety
		Effectiveness
		Venom Species and Dose
		Treatment Schedules
		Maintenance
		Discontinuation
		Fire Ant Immunotherapy
	Biting Insect Allergy
		Triatoma (Kissing Bug, Cone-nose Bug)
		Culicoidae (Mosquito)
		Tabanidae (Horsefly, Deerfly)
		Allergic Reactions to Other Biting Insects
	Inhalant Insect Allergy
	Conclusions
	References
Appendix A. Internet Resources
Index