Phys · general-medicine
Drug Allergy and Desensitisation
Also known as drug hypersensitivity · drug allergy · penicillin allergy · beta-lactam allergy · drug desensitisation · rapid drug desensitisation · drug provocation testing · aspirin-exacerbated respiratory disease · AERD · Samter triad · DRESS · drug reaction with eosinophilia and systemic symptoms · Stevens-Johnson syndrome · SJS · toxic epidermal necrolysis · TEN · SCORTEN
Consultant-physician-depth guide to drug allergy and desensitisation for FRACP DWE and DCE — the allergy-versus-intolerance distinction, the immediate IgE-mediated versus delayed T-cell mediated classification, beta-lactam allergy with penicillin skin testing and side-chain-based cross-reactivity and the modern delabeling strategy, non-beta-lactam allergies (sulfonamide, NSAID hypersensitivity and aspirin-exacerbated respiratory disease, local anaesthetics, radiocontrast media), the severe cutaneous adverse reactions DRESS and Stevens-Johnson syndrome or toxic epidermal necrolysis with the RegiSCAR and SCORTEN scores, and the principle and indications of drug desensitisation with the Brigham 12-step protocol and drug provocation testing as the diagnostic gold standard.
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Red flags
- A patient with a penicillin allergy label presenting with an infection for which a beta-lactam is first-line (endocarditis, meningitis, syphilis in pregnancy) — do not default to vancomycin; risk-stratify and consider delabeling, a non-cross-reactive cephalosporin, or desensitisation if the drug is essential
- A maculopapular rash that progresses to blistering, skin detachment or mucosal erosion within days of a new drug — Stevens-Johnson syndrome or toxic epidermal necrolysis until proven otherwise; stop the culprit drug immediately, calculate SCORTEN, and involve a burns unit for detachment over 10 per cent of body surface area
- Fever, facial oedema, lymphadenopathy, eosinophilia and hepatitis 2 to 8 weeks after starting a new anticonvulsant, sulfonamide or allopurinol — DRESS; stop the culprit drug and start systemic glucocorticoids for organ involvement
- An adult with asthma and nasal polyps who develops bronchospasm within 30 to 120 minutes of taking aspirin or a non-selective NSAID — aspirin-exacerbated respiratory disease (Samter triad); the leukotriene excess from COX-1 inhibition is the mechanism
- Urticaria, angioedema, bronchospasm or hypotension within minutes to one hour of a drug dose — IgE-mediated anaphylaxis; give intramuscular adrenaline 0.5 mg immediately and observe for a biphasic reaction
Drug Allergy and Desensitisation
Meet the patient
A 32-year-old primigravida at 24 weeks gestation presents with secondary syphilis — a diffuse rash and positive serology. She carries a penicillin allergy label from a childhood rash of uncertain nature. Benzathine penicillin is the only recommended treatment to prevent congenital syphilis. The registrar reaches for vancomycin. [1]
The question is not whether you can find an alternative antibiotic. It is whether the label is real, whether you can delabel her safely, and whether desensitisation is justified when the disease is worse than the procedure. Three steps — structured history, risk stratification, and a clear management pathway — resolve the dilemma. [1]
References7ShowHide
- [1]Khan DA, Banerji A, Blumenthal KG, et al. Drug allergy: A 2022 practice parameter update J Allergy Clin Immunol, 2022.PMID 36122788
- [2]Kardaun SH, Sekula P, Valeyrie-Allanore L, et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study Br J Dermatol, 2013.PMID 23855313
- [3]Bastuji-Garin S, Fouchard N, Bertocchi M, et al. SCORTEN: a severity-of-illness score for toxic epidermal necrolysis J Invest Dermatol, 2000.PMID 10951229
- [4]Zagursky RJ, Pichichero ME Cross-reactivity in β-Lactam Allergy J Allergy Clin Immunol Pract, 2018.PMID 29017833
- [5]Castells MC, Tennant NM, Sloane DE, et al. Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases J Allergy Clin Immunol, 2008.PMID 18502492
- [6]Castells MC Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century J Investig Allergol Clin Immunol, 2014.PMID 24834769
- [7]Demoly P, Adkinson NF, Brockow K, et al. International Consensus on drug allergy Allergy, 2014.PMID 24697291