Hypersensitivity Reactions in Dermatology
Introduction
Hypersensitivity reactions represent immune responses that are exaggerated or inappropriate, causing tissue damage rather than protection. skin, as a major immunological organ constantly exposed to environmental antigens, is frequently affected by hypersensitivity reactions ranging from urticaria to blistering drug eruptions.
The Gell and Coombs classification remains the foundation for understanding these reactions, though considerable overlap exists in clinical practice.
Gell and Coombs Classification
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Type I: IgE-Mediated (Immediate) Hypersensitivity
Mechanism
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Clinical Manifestations
| Manifestation | Timing | Key Features |
|---|
| Urticaria | Minutes | Wheals, pruritus, self-resolving |
| Angioedema | Minutes-hours | Deep swelling, face/lips/tongue |
| Anaphylaxis | Minutes | Systemic: hypotension, bronchospasm |
| Allergic contact urticaria | Minutes | Contact with allergen (latex, foods) |
Examples in Dermatology
| Condition | Trigger | Mechanism |
|---|
| Acute urticaria | Foods, drugs | IgE-mediated mast cell degranulation |
| Latex allergy | Latex proteins | IgE to natural rubber proteins |
| Food allergy | Peanuts, shellfish | IgE to food proteins |
| Drug allergy (some) | β-lactams | IgE to drug/hapten |
Type II: Antibody-Mediated Cytotoxic
Mechanism
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Examples in Dermatology
| Disease | Target Antigen | Effector Mechanism | Result |
|---|
| Pemphigus vulgaris | Desmoglein 3 | Steric hindrance, signaling | Acantholysis |
| Bullous pemphigoid | BP180, BP230 | Complement, eosinophils | Subepidermal blister |
| Epidermolysis bullosa acquisita | Type VII collagen | Complement, neutrophils | Subepidermal blister |
| Pemphigoid gestationis | BP180 | Complement | Subepidermal blister |
Type III: Immune Complex-Mediated
Mechanism
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Examples in Dermatology
| Disease | Antigen Source | Presentation |
|---|
| Leukocytoclastic vasculitis | Drugs, infections | Palpable purpura |
| IgA vasculitis (HSP) | Upper respiratory infections | Purpura, arthritis, nephritis, GI |
| Cryoglobulinemic vasculitis | HCV, B cell malignancy | Purpura, ulcers, neuropathy |
| Serum sickness | Foreign proteins, drugs | Urticaria, fever, arthralgia |
| SLE (partial) | Nuclear antigens | Multiple manifestations |
| Erythema nodosum | Various (strep, sarcoid, drugs) | Tender nodules on shins |
Arthus Reaction
The Arthus reaction is a localized Type III hypersensitivity:
- Occurs at injection site
- IgG + antigen → local immune complexes
- Peaks at 4-10 hours
- Can occur with repeated vaccinations
Type IV: Delayed-Type (T Cell-Mediated) Hypersensitivity
Classical DTH (Type IVa)
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Type IV Subtypes
| Subtype | Mediating Cells | Key Cytokines | Examples |
|---|
| IVa (Th1) | Th1, macrophages | IFN-γ | Tuberculin reaction, contact dermatitis |
| IVb (Th2) | Th2, eosinophils | IL-4, IL-5, IL-13 | Chronic atopic dermatitis, MPE |
| IVc (CTL) | CD8+ CTL | Perforin, granzymes | SJS/TEN, fixed drug eruption |
| IVd (Neutrophilic) | T cells, neutrophils | IL-8, GM-CSF | AGEP |
Contact Dermatitis: DTH Prototype
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Severe Cutaneous Adverse Reactions (SCARs)
Type IV reactions underlie severe drug reactions:
| Reaction | Latency | Histology | Key Features |
|---|
| SJS/TEN | 1-3 weeks | Epidermal necrosis | CD8+ CTL, FasL, granulysin |
| DRESS | 2-8 weeks | Interface, eosinophils | HHV-6 reactivation, multiorgan |
| AGEP | 1-2 days | Subcorneal pustules | IL-8, neutrophils (Type IVd) |
| Fixed drug eruption | Hours (sensitized) | Interface, CD8+ TRM | Site-specific TRM |
Comparative Summary
| Feature | Type I | Type II | Type III | Type IV |
|---|
| Timing | Minutes | Hours-days | Hours-days | 24-72 hours |
| Mediator | IgE | IgG/IgM | Immune complexes | T cells |
| Effector | Mast cells | Complement, ADCC | Complement, neutrophils | Macrophages, CTLs |
| Test | Skin prick, IgE | None specific | None specific | Patch test |
| Dermatology examples | Urticaria | Pemphigus, BP | Vasculitis | Contact dermatitis |
Diagnostic Approaches
Testing by Hypersensitivity Type
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Summary
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Key Clinical Pearls
| Topic | Pearl |
|---|
| Type I timing | Immediate = minutes; IgE and mast cells |
| Type II in derm | Pemphigus and pemphigoid = IgG autoantibodies |
| Type III | Palpable purpura = immune complex vasculitis |
| Type IV latency | Patch test read at 48-96 hours |
| SJS/TEN | Type IVc; CD8+ CTLs with granulysin cause keratinocyte death |
| DRESS | Type IVb; eosinophils, HHV-6 reactivation, long latency |
| AGEP | Type IVd; neutrophils, rapid onset |
Cross-References
How to Cite
Cutisight. "Hypersensitivity Classification." Encyclopedia of Dermatology [Internet]. 2026. Available from: https://cutisight.com/education/volume-03-skin-reactions-and-interactions/04-immunology/03-clinical-immunology/01-hypersensitivity/01-hypersensitivity-classification
This is an open-access resource. Please cite appropriately when using in academic or clinical work.