Immunology, Allergy, and Systemic Associations: Timing and Mechanisms
Hypersensitivity and drug reactions
This domain links immunology to clinical medicine. Learn the four Gell-Coombs types: immediate IgE (urticaria, anaphylaxis), antibody-mediated (pemphigus, bullous pemphigoid), immune complex (vasculitis, serum sickness), and delayed T-cell (contact dermatitis, morbilliform drug eruptions). Patch testing is the gold standard for allergic contact dermatitis, read at 48 and 96 hours; a positive reaction is a delayed type IV response.
Drug hypersensitivity is heavily tested. Morbilliform exanthem occurs 4–14 days after a new drug. Urticaria is immediate or accelerated. DRESS develops 2–8 weeks after exposure with fever, facial edema, eosinophilia, and organ involvement; stop the drug and avoid cross-reacting agents. SJS/TEN presents with mucosal erosions, painful skin, and epidermal detachment; SCORTEN predicts mortality. AGEP is pustular and neutrophilic. Trap: Stevens-Johnson syndrome and erythema multiforme major both show target lesions, but EM is usually infection-triggered (Mycoplasma, HSV) with acral targets and less mucosal disease.
Systemic associations: urticarial vasculitis shows lesions lasting more than 24 hours, burning, and residual purpura; biopsy confirms leukocytoclastic vasculitis. Lupus and dermatomyositis require systemic workup. Biologics demand screening for tuberculosis and hepatitis before anti-TNF therapy.
Rule of thumb: timing is the diagnostic clue - immediate (minutes), accelerated (hours to days), or delayed (days to weeks). Worked example: a patient develops fever, facial swelling, and eosinophilia three weeks after starting an anticonvulsant; this is DRESS, requiring immediate drug withdrawal and monitoring of liver and renal function.