Allergy & Hypersensitivity for USMLE Step 3

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Allergy for the USMLE Step 3 Exam

Allergy Overview

Allergies involve an immune overreaction to typically harmless substances (allergens) that leads to clinical symptoms, often IgE-mediated.
Initial sensitization to an allergen triggers IgE antibody production, which binds to mast cells and basophils. Upon re-exposure, cross-linking of IgE causes degranulation and release of histamine and other mediators.

Environmental: Pollens, animal dander, dust mites, and molds.
Food: Common allergens include peanuts, shellfish, tree nuts, milk, and eggs.
Medications: Commonly antibiotics (penicillin), NSAIDs, and vaccines.
Insect Stings: Hymenoptera (e.g., bees, wasps).
Occupational: Latex and certain workplace chemicals.

Mechanisms of Hypersensitivity

Mechanism: IgE antibodies generated on initial allergen exposure sensitize mast cells and basophils. Re-exposure leads to cross-linking and release of histamine, prostaglandins, and leukotrienes.
Examples: Allergic rhinitis, asthma, anaphylaxis, and urticaria.

Mechanism: IgG or IgM antibodies bind to cell-bound antigens, leading to complement activation and cell destruction.
Examples: Hemolytic anemia, Goodpasture syndrome.

Mechanism: Antigen-antibody complexes deposit in tissues, causing inflammation via complement activation.
Examples: Serum sickness, systemic lupus erythematosus (SLE).

Mechanism: T-cell mediated response occurring 24-72 hours post-exposure, with cytokine release and macrophage activation.
Examples: Contact dermatitis, tuberculosis skin test reaction.

Clinical Presentations

Symptoms: Sneezing, nasal congestion, itchy eyes, and rhinorrhea; seasonal or perennial.
Diagnosis: Based on history, supported by skin or IgE testing.
Treatment: Intranasal corticosteroids, antihistamines, and allergen avoidance.

Symptoms: Cough, wheezing, dyspnea, and chest tightness, often allergen-triggered.
Diagnosis: Pulmonary function tests showing reversible obstruction; IgE testing may help identify triggers.
Treatment: Inhaled corticosteroids, bronchodilators, leukotriene modifiers, and avoidance of known allergens.

Symptoms: Pruritic, erythematous rash on flexural surfaces.
Diagnosis: Clinical features and consideration of allergy testing for environmental or food triggers.
Treatment: Emollients, topical corticosteroids, and avoidance of irritants.

Symptoms: Urticaria, angioedema, gastrointestinal symptoms, and in severe cases, anaphylaxis.
Diagnosis: Skin prick or serum IgE testing, with oral food challenges if necessary.
Treatment: Avoidance of allergens and carrying an epinephrine autoinjector.

Symptoms: Varies from mild rash to severe anaphylaxis.
Diagnosis: Based on history and, for certain drugs like penicillin, skin testing.
Treatment: Avoidance of the drug, substitution, and desensitization when necessary.

Symptoms: Rapid onset of multisystem involvement including urticaria, bronchospasm, hypotension, and shock.
Diagnosis: Clinical, based on acute presentation following exposure.
Treatment: Immediate intramuscular epinephrine, followed by antihistamines and corticosteroids. Patients should carry an epinephrine autoinjector.

Diagnostic Tests

Procedure: Small allergen amounts introduced into the skin; a positive response is a wheal-and-flare reaction.
Indications: Allergic rhinitis, asthma, and food allergies.

Procedure: Gradual exposure to the suspect allergen under medical supervision, especially when other tests are inconclusive.

Treatment Overview

Avoidance: First-line management, particularly for food and environmental allergens.
Pharmacologic Therapy:

Antihistamines: Effective for allergic rhinitis and urticaria.
Corticosteroids: Intranasal for rhinitis, inhaled for asthma, topical for dermatitis.
Bronchodilators: Short-acting beta agonists for acute asthma symptoms.

Subcutaneous and Sublingual Immunotherapy: Indicated for allergic rhinitis and asthma, promoting tolerance to specific allergens.

Key Points

Allergies are often IgE-mediated hypersensitivity reactions that can range from mild (e.g., rhinitis) to severe (e.g., anaphylaxis).
Common allergens include environmental triggers, foods, medications, and insect stings.
Diagnosis relies on history, physical examination, and confirmatory testing (e.g., skin prick, serum IgE).
Management includes allergen avoidance, pharmacologic therapy (antihistamines, corticosteroids), and immunotherapy.
Anaphylaxis requires prompt epinephrine administration; patients at risk should carry an epinephrine autoinjector.