IFN-$γ$ ELISpot in severe cutaneous adverse reactions to first-line anti-tuberculosis drugs in an HIV endemic setting. Porter, M., Choshi, P., Pedretti, S., Chimbetete, T., Smith, R., Meintjes, G. A, Phillips, E., Lehloenya, R., & Peter, J. Journal of Investigative Dermatology, Elsevier BV, jun, 2022. ![IFN-$γ$ ELISpot in severe cutaneous adverse reactions to first-line anti-tuberculosis drugs in an HIV endemic setting [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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 \textless12 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.
@article{Porter2022,
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-$\gamma$ 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-$\gamma$ 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-$\gamma$ 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-$\gamma$ 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 {\textless}12 weeks after acute severe cutaneous adverse reaction event; specificity remained 100{\%} for both. IFN-$\gamma$ 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-$\gamma$ ELISpot for other first-line antituberculosis drugs, additional optimization is needed to improve risk-stratification potential.},
author = {Porter, Mireille and Choshi, Phuti and Pedretti, Sarah and Chimbetete, Tafadzwa and Smith, Rhodine and Meintjes, Graeme A and Phillips, Elizabeth and Lehloenya, Rannakoe and Peter, Jonny},
doi = {10.1016/j.jid.2022.05.1059},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Porter et al. - 2022 - IFN-$\gamma$ ELISpot in severe cutaneous adverse reactions to first-line anti-tuberculosis drugs in an HIV endemic setti.pdf:pdf},
issn = {0022202X},
journal = {Journal of Investigative Dermatology},
keywords = {ART,DRESS,ELISpot,FLTB,RegiSCAR,Registry of Severe Cutaneous Adverse Reactions,SCAR,SDC,SFU,SJS/TEN,Stevens‒Johnson syndrome/toxic epidermal necrolysi,TB,antiretroviral therapy,drug reaction with eosinophilia and systemic sympt,enzyme-linked immune absorbent spot,first-line antituberculosis,fund{\_}ack,original,sequential drug challenge,severe cutaneous adverse reaction,spot-forming unit,tuberculosis},
mendeley-tags = {fund{\_}ack,original},
month = {jun},
pages = {10.1016/j.jid.2022.05.1059},
pmid = {35659939},
publisher = {Elsevier BV},
title = {{IFN-$\gamma$ ELISpot in severe cutaneous adverse reactions to first-line anti-tuberculosis drugs in an HIV endemic setting}},
url = {http://www.jidonline.org/article/S0022202X22015007/fulltext http://www.jidonline.org/article/S0022202X22015007/abstract https://www.jidonline.org/article/S0022-202X(22)01500-7/abstract},
year = {2022}
}
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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 \\textless12 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. 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