Notes on Hypersensitivity Reactions

Definitions of Hypersensitivity, Allergy, and Atopy

  • Allergy: The term "allergy" was first used in 1906 by Clemens von Pirquet, derived from the Greek words "allos" (meaning "other" or "different") and "ergon" (meaning "work" or "reaction"). A sudden, abnormal, or excessive reaction to an exogenous stimulus related to the immune system.

  • Atopy: Introduced by Arthur F. Coca and Robert A. Cooke in the early 20th century, it refers to a predisposition to develop asthma, rhinoconjunctivitis, or dermatitis due to sensitization to allergens. It comes from the Greek word "topos" meaning "place", and "atopos" meaning "out of place" or "strange".

  • Hypersensitivity: First used by Gell and Hinde in 1951 to describe the tuberculin reaction. In 1963, Gell and Coombs defined hypersensitivity as an unwanted, uncomfortable, or harmful response resulting from an excessive adaptive immune reaction, including allergies from external irritants and autoimmune reactions from internal factors.

Types of Hypersensitivity Reactions

  • Hypersensitivity reactions are categorized based on the type of antigen that triggers them:

    • Type I: Immediate hypersensitivity (e.g., anaphylaxis, asthma)

    • Mediated by IgE antibodies binding to allergens, causing mast cell degranulation and release of inflammatory mediators.

    • Type II: Cytotoxic hypersensitivity

    • Mediated by IgG or IgM binding to cell-bound antigens, leading to cell damage (e.g., autoimmune hemolytic anemia).

    • Type III: Immune complex hypersensitivity

    • Involves the formation of immune complexes (antigen-antibody) that cause tissue damage (e.g., serum sickness).

    • Type IV: Delayed-type hypersensitivity

    • Mediated by T lymphocytes and macrophages, leading to localized inflammation (e.g., contact dermatitis).

Coombs and Gell Classification of Hypersensitivity Reactions

  • Type I (IgE-mediated)

    • Mechanism: Allergen binds IgE to mast cells.

    • Reaction Timing: Immediate.

    • Clinical Examples: Anaphylaxis, urticaria, angioedema.

  • Type II (Cytotoxic)

    • Mechanism: IgG/IgM binds to an allergen on target cells, activating complement.

    • Clinical Examples: Neutropenia, thrombocytopenia, hemolytic anemia.

  • Type III (Immune complex)

    • Mechanism: Tissue deposition of IgG antibodies.

    • Clinical Examples: Serum sickness, vasculitis.

  • Type IV (Delayed)

    • Mechanism: T-lymphocytes and macrophages cause cellular damage.

    • Clinical Examples: Contact dermatitis.

Clinical Manifestations of Allergic Reactions

  • Common clinical manifestations associated with Type I hypersensitivity include:

    • Allergic rhinitis

    • Asthma

    • Urticaria (hives)

    • Angioedema

    • Atopic dermatitis

    • Anaphylaxis

The Allergic March

  • The Allergic March refers to the progression of allergic diseases over a person's lifespan:

    • Atopic dermatitis usually occurs in infancy.

    • Food allergies tend to develop in childhood.

    • Allergic rhinitis and asthma often appear during early school years.

    • Around 50% of children with atopic dermatitis may also develop asthma.

Diagnosis of Allergic Conditions

  • Skin Prick Test: Involves introducing a drop of allergen to the skin, and monitoring the reaction for erythema and wheal formation, which indicates sensitivity.

  • Specific IgE Testing: Blood tests that measure levels of IgE antibodies against specific allergens, helping in identifying the causes of allergic reactions.

  • Anamnestic and Clinical Examination: Gathering a detailed history (anamnese) of symptoms and previous allergic reactions.

Treatment of Allergic Reactions

  • Treatment options depend on the severity and nature of the allergic reaction:

    • Antihistamines

    • Glucocorticoids

    • Adrenaline (for anaphylaxis)

    • Immunotherapy (desensitization)

    • Biological treatments targeting specific cytokines (e.g., anti-IgE, anti-IL4, anti-IL-5).

Sources and Further Reading

  • The information compiled from various sources, including:

    • Abbas M., et al. Type I Hypersensitivity Reaction. StatPearls.

    • Helbert M. Immunology for Medical Students. Elsevier, 2017.

    • Jutel M., et al. Nomenclature of allergic diseases and hypersensitivity reactions. Allergy, 2023.