IFN-γ ELISpot in severe cutaneous adverse reactions to First-line Antituberculosis drugs in an HIV endemic setting

M. Porter; P. Choshi; S. Pedretti; T. Chimbetete; R. Smith; G. Meintjes; E. Phillips; R. Lehloenya; J. Peters

doi:10.1016/j.jid.2022.05.1059

Back

IFN-γ ELISpot in severe cutaneous adverse reactions to First-line Antituberculosis drugs in an HIV endemic setting

Journal article

Peer reviewed

IFN-γ ELISpot in severe cutaneous adverse reactions to First-line Antituberculosis drugs in an HIV endemic setting

M. Porter, P. Choshi, S. Pedretti, T. Chimbetete, R. Smith, G. Meintjes, E. Phillips, R. Lehloenya and J. Peters

Journal of Investigative Dermatology, Vol.142(11), pp.2920-2928.e5

2022

DOI: https://doi.org/10.1016/j.jid.2022.05.1059

Files and links (1)

url

Link to Published Version *Subscription may be requiredView

Abstract

Severe cutaneous adverse reactions related to first-line antituberculosis drugs are associated with high mortality and long-term morbidity. Oral sequential drug challenge, as a form of drug provocation testing, helps to salvage therapy by identifying culprit drugs but is associated with risk and is costly. IFN-γ enzyme-linked immune absorbent spot (ELISpot), an adjunctive in vitro diagnostic tool, may help to guide risk-stratification approaches. To determine the diagnostic accuracy of IFN-γ ELISpot against full-dose sequential drug challenge, we analyzed samples collected prospectively at multiple time points in 32 patients with first-line antituberculosis drug‒associated severe cutaneous adverse reaction (81% HIV infected, 25 with drug reaction with eosinophilia and systemic symptoms, and 7 with Stevens‒Johnson syndrome/toxic epidermal necrolysis). Sensitivity of IFN-γ ELISpot was 33% (4 of 12), 13% (1 of 8), 11% (1 of 9), and 0% (0 of 4) for rifampicin, isoniazid, pyrazinamide, and ethambutol, respectively (positivity threshold ≥50 spot forming units/million cells). Specificity was 100% for all the four drugs. Rifampicin IFN-γ ELISpot sensitivity increased to 58% (7 of 12) if a threshold of 20 spot forming units was used and to 75% (3 of 4) when restricted to samples <12 weeks after acute severe cutaneous adverse reaction event; specificity remained 100% for both. IFN-γ ELISpot offers adequate risk stratification of rifampicin severe cutaneous adverse reaction using acute samples and lowered threshold for positivity. Given the low sensitivity of IFN-γ ELISpot for other first-line antituberculosis drugs, additional optimization is needed to improve risk-stratification potential.

Details

Title: IFN-γ ELISpot in severe cutaneous adverse reactions to First-line Antituberculosis drugs in an HIV endemic setting
Authors/Creators: M. Porter (Author/Creator)
P. Choshi (Author/Creator)
S. Pedretti (Author/Creator)
T. Chimbetete (Author/Creator)
R. Smith (Author/Creator)
G. Meintjes (Author/Creator)
E. Phillips (Author/Creator)
R. Lehloenya (Author/Creator)
J. Peters (Author/Creator)
Publication Details: Journal of Investigative Dermatology, Vol.142(11), pp.2920-2928.e5
Publisher: Elsevier, Inc. on behalf of the Society for Investigative Dermatology.
Identifiers: 991005544909307891
Copyright: © 2022 The Authors.
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Metrics

23 Record Views

14 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.265 Dermatology - Skin Allergies; 1.265.1140 Drug Hypersensitivity
Web Of Science research areas: Dermatology
ESI research areas: Clinical Medicine