Types of Hypersensitivity Reactions
Hypersensitivity reactions are classified into four main types (I-IV), each with distinct immunological mechanisms and clinical manifestations, as established by the Gell and Coombs classification system. 1
Type I: Immediate/IgE-Mediated Hypersensitivity
- Mechanism: Mediated by IgE antibodies binding to mast cells and basophils
- Onset: Rapid (minutes to hours after exposure)
- Clinical manifestations:
- Anaphylaxis
- Urticaria (hives)
- Angioedema
- Bronchospasm
- Allergic rhinitis
- Allergic asthma
Type II: Cytotoxic/IgG or IgM-Mediated Hypersensitivity
- Mechanism: IgG/IgM antibodies target cell surface antigens, leading to cell destruction
- Subtypes:
- Type IIa: Traditional cytotoxic reactions
- Type IIb: Antibody-mediated cell stimulating (e.g., Graves' disease, autoimmune chronic urticaria) 2
- Clinical manifestations:
- Hemolytic anemia
- Thrombocytopenia
- Blood transfusion reactions
- Autoimmune disorders
Type III: Immune Complex-Mediated Hypersensitivity
- Mechanism: Formation and deposition of IgG/IgM immune complexes in tissues
- Clinical manifestations:
- Serum sickness
- Vasculitis
- Joint pain
- Systemic lupus erythematosus
- Some drug reactions
Type IV: Delayed-Type/T-Cell Mediated Hypersensitivity
- Mechanism: T-lymphocyte mediated reactions
- Onset: Delayed (hours to days after exposure)
- Subtypes 1, 2, 3:
Type IVa: CD4+ Th1 lymphocyte-mediated with macrophage activation
- Examples: Granuloma formation, Type 1 diabetes mellitus, contact dermatitis
- Key cytokines: IFN-γ, IL-1, IL-2
Type IVb: CD4+ Th2 lymphocyte-mediated with eosinophilic involvement
- Examples: Persistent asthma, allergic rhinitis, maculopapular exanthema with eosinophilia
- Key cytokines: IL-4, IL-5, IL-13
Type IVc: Cytotoxic CD8+ T-lymphocyte mediated
- Examples: Stevens-Johnson syndrome, toxic epidermal necrolysis
- Key mediators: Perforin, granzyme B, Fas ligand
Type IVd: T-lymphocyte-driven neutrophilic inflammation
- Examples: Acute generalized exanthematous pustulosis (AGEP), pustular psoriasis
- Key cytokines: IL-8, GM-CSF
Important Clinical Considerations
Many hypersensitivity disorders involve multiple types of reactions occurring simultaneously 4
Understanding the specific type of hypersensitivity is crucial for:
- Accurate diagnosis
- Appropriate treatment selection
- Prevention strategies
- Risk assessment for rechallenge 1
When evaluating suspected hypersensitivity reactions:
- Timing of symptom onset after exposure helps distinguish between immediate (Type I) and delayed (Type IV) reactions
- Laboratory tests may include:
- Histamine levels (elevated 5-60 minutes after Type I reactions)
- Tryptase levels (optimally measured 15 min to 3 hours after reaction onset)
- Serial tryptase measurements are more useful than single measurements 5
Risk factors for severe reactions (particularly anaphylaxis) include:
- Age-related factors
- Chronic respiratory or cardiovascular diseases
- Mastocytosis or clonal mast cell disorders
- Severe atopic disease
- Concurrent medications (e.g., β-blockers, ACE inhibitors) 5
The World Allergy Organization defines:
- Hypersensitivity: Objectively reproducible symptoms/signs from exposure to a defined stimulus at doses tolerated by normal persons
- Allergy: Hypersensitivity initiated by specific immunological mechanisms
- Anaphylaxis: Severe, life-threatening, generalized/systemic hypersensitivity 5
Understanding these classifications helps guide appropriate management strategies and informs decisions about potential rechallenge or alternative treatments in patients with hypersensitivity reaction history.