Practical management of suspected hypersensitivity reactions to anti-tuberculosis drugs
Bermingham, William Hywel Bhogal, Rashmeet Arudi Nagarajan, Sowmya Mutlu, Leman El-Shabrawy, Reham Mohamed Madhan, Ramesh Krishnaswamy, Uma Maheswari Murali, Mandakolathur Ramaswamy Kudagammana, Sanath Thushara Shrestha, Rajeev
Bermingham, William Hywel
Bhogal, Rashmeet
Arudi Nagarajan, Sowmya
Mutlu, Leman
El-Shabrawy, Reham Mohamed
Madhan, Ramesh
Krishnaswamy, Uma Maheswari
Murali, Mandakolathur Ramaswamy
Kudagammana, Sanath Thushara
Shrestha, Rajeev
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Affiliation
University Hospitals Birmingham NHS Foundation Trust; Kanagaroo Care Paediatric Hospital; Zagazig University; JSS AHER; St Johns Medical College; Massachusetts General Hospital; University of Peradeniya; Teaching Hospital Peradeniya; Dhulikhel Hospital Kathmandu University Hospital; Universitas Pelita Harapan; Siloam Academic Hospital Lippo Village; Christian Medical College; University of Birmingham
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Publication date
2022-02-23
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Abstract
Tuberculosis (TB) is the commonest cause of death by a single infectious agent globally and ranks amongst the top ten causes of global mortality. The incidence of TB is highest in Low-Middle Income countries (LMICs). Prompt institution of, and compliance with, therapy are cornerstones for a favourable outcome in TB and to mitigate the risk of multiple drug resistant (MDR)-TB, which is challenging to treat. There is some evidence that adverse drug reactions (ADRs) and hypersensitivity reactions (HSRs) to anti-TB drugs occur in over 60% and 3%-4% of patients respectively. Both ADRs and HSRs represent significant barriers to treatment adherence and are recognised risk factors for MDR-TB. HSRs to anti-TB drugs are usually cutaneous and benign, occur within few weeks after commencement of therapy and are likely to be T-cell mediated. Severe and systemic T-cell mediated HSRs and IgE mediated anaphylaxis to anti-TB drugs are relatively rare, but important to recognise and treat promptly. T-cell-mediated HSRs are more frequent amongst patients with co-existing HIV infection. Some patients develop multiple sensitisation to anti-TB drugs. Whilst skin tests, patch tests and in vitro diagnostics have been used in the investigation of HSRs to anti-TB drugs, their predictive value is not established, they are onerous, require specialist input of an allergist and are resource-dependent. This is compounded by the global, unmet demand for allergy specialists, particularly in low-income countries (LICs)/LMICs and now the challenging circumstances of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. This narrative review provides a critical analysis of the limited published evidence on this topic and proposes a cautious and pragmatic approach to optimise and standardise the management of HSRs to anti-TB drugs. This includes clinical risk stratification and a dual strategy involving sequential re-challenge and rapid drug desensitisation. Furthermore, a concerted international effort is needed to generate real-time data on ADRs, HSRs, safety and clinical outcomes of these interventions.
Citation
Bermingham WH, Bhogal R, Arudi Nagarajan S, Mutlu L, El-Shabrawy RM, Madhan R, Krishnaswamy UM, Murali MR, Kudagammana ST, Shrestha R, Sumantri S, Christopher DJ, Mahesh PA, Dedicoat M, Krishna MT. Practical management of suspected hypersensitivity reactions to anti-tuberculosis drugs. Clin Exp Allergy. 2022 Mar;52(3):375-386. doi: 10.1111/cea.14084. Epub 2022 Jan 20.
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Article