TB drug hypersensitivity — DTM&H MCQ

Correct answer: B — Pyrazinamide

The correct answer is B, pyrazinamide. Among the first line anti-tuberculous drugs (rifampicin, isoniazid, pyrazinamide, ethambutol), pyrazinamide is the most frequent cause of cutaneous hypersensitivity reactions, including maculopapular rash, drug fever, and eosinophilia, typically arising within the first few weeks of treatment as part of a delayed (non-immediate) hypersensitivity response. This pattern reflects a T cell mediated reaction rather than direct organ toxicity, distinguishing it from pyrazinamide's dose-related hepatotoxicity and hyperuricaemia. UK TB management guidance recognises this and advises stopping all RHZE drugs until the reaction settles, then sequential reintroduction with pyrazinamide reintroduced last (or omitted) because it carries the highest risk of provoking recurrence. The timing (two weeks in), systemic features (fever, eosinophilia) and rash pattern described in the stem are classic for pyrazinamide hypersensitivity rather than the other agents. Why the other options are wrong: D. Rifampicin: more classically associated with flu-like syndrome, hepatitis, orange discolouration of secretions, and rare immediate (IgE-mediated) reactions such as anaphylaxis or thrombocytopenia, but is a less frequent cause of isolated maculopapular rash with eosinophilia than pyrazinamide. E. Isoniazid: principally causes peripheral neuropathy (from pyridoxine depletion) and hepatotoxicity; hypersensitivity skin reactions occur but are less common than with pyrazinamide. C. Ethambutol: its hallmark adverse effect is dose-dependent optic neuropathy with reduced visual acuity and colour vision loss, not hypersensitivity rash, and it is generally the safest drug to reintroduce first after a reaction. A. Streptomycin: not part of standard RHZE oral regimens in UK practice (only used in specific circumstances by injection); its main toxicities are ototoxicity and nephrotoxicity rather than cutaneous hypersensitivity. Key point: Pyrazinamide is the first-line TB drug most likely to cause hypersensitivity rash, fever, and eosinophilia, and is therefore reintroduced last (or omitted) after a drug reaction settles.

Reference: British National Formulary (BNF), Tuberculosis treatment summary and Pyrazinamide monograph, NICE; joint Tuberculosis Committee of the British Thoracic Society guidance on management of drug hypersensitivity in TB treatment (sequential drug reintroduction, pyrazinamide reintroduced last). https://bnf.nice.org.uk/drugs/pyrazinamide/