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First-line anti-tuberculosis drug challenge reactions in DRESS in an HIV endemic setting
Journal article   Open access   Peer reviewed

First-line anti-tuberculosis drug challenge reactions in DRESS in an HIV endemic setting

M. Porter, R. Smith, N. Teixeira, B. Thwala, P. Choshi, Elizabeth Phillips, G. Meintjes, S. Dlamini, J. Peter and R.J. Lehloenya
The journal of allergy and clinical immunology. In practice, Vol.12(10), pp.2798-2808.E12
2024
DOI: https://doi.org/10.1016/j.jaip.2024.05.045
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Abstract

Background In high HIV prevalence settings, first line anti-tuberculosis drug (FLTD)-associated DRESS poses therapeutic challenges. Sequential and additive drug challenge (SADC) of FLTDs best identifies offending drug(s), avoids unnecessary exclusions, and optimises re-initiation of non-offending drugs. However, SADC-associated reaction complexities limit its utility. Objective We aimed to describe characteristics of FLTD-associated DRESS patients, their treatment-limiting SADC reactions and related outcomes. Methods Patients hospitalized with FLTD-associated DRESS from 2013–2023 in a South African tertiary hospital and enrolled (retrospectively or prospectively) in an existing registry were eligible. Results SADC was undertaken in 41 patients. Overall, 47 classifiable reactions occurred, 34/47(72%) in 29/41(71%) patients, were treatment-limiting and 12/41(29%) reinitiated FLTDs uneventfully. Fifteen single and eight multiple drug-reactors were identified. Rifampicin, in 13/23(57%) reactors was the commonest individual offender. Ethambutol was most frequently involved in multiple drug-reactors. Median(IQR) time to a detectable reaction was 24(12-120) hours, 6/34(18%) being immediate (<6hours). Itch (65%), eosinophilia (56%), fever (41%), atypical lymphocytosis (41%), rash (38%), transaminitis (32%) and facial oedema (18%), singly or in combination were commonest features. Three reactions, one epidermal necrolysis and two liver derangements, were CTCAE grade 4 (life-threatening) events. No predictors of multiple drug-reactivity were identified, but multiple reactors were hospitalised significantly longer, 125(100-134) versus 60(45-80) days. Conclusions SADC optimises FLTD reinitiation. However, timing, clinical presentation and severity of SADC-associated reactions following FLTD-associated DRESS is markedly heterogenous. Additionally, multiple drug-reactors are a complex group requiring longer hospitalisation, and without routine biomarkers to differentiate true multiple drug hypersensitivity from non-specific flare-ups and guide long-term drug avoidance strategies.

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