Drug Provocation Testing as the Cornerstone for Diagnosing Antituberculosis Drug Hypersensitivity
DOI:
https://doi.org/10.59141/jiss.v7i6.2372Keywords:
anti-tuberculosis therapy, drug provocation test, delayed hypersensitivityAbstract
Drug hypersensitivity reactions (DHRs) remain an important challenge in everyday clinical practice, especially in conditions that require prolonged multidrug treatment such as tuberculosis. Hypersensitivity to anti-tuberculosis therapy (ATT) can disrupt ongoing treatment, reduce adherence, and ultimately compromise therapeutic outcomes. For this reason, an accurate and structured diagnostic approach is crucial to identify drug-related hypersensitivity and non-immunologic adverse reactions is therefore crucial to support safe clinical decision making. A 52-year-old male patient with pulmonary tuberculosis developed recurrent hypersensitivity manifestations during the continuation phase of ATT. The patient experienced two episodes of generalized pruritus, soft tissue swelling, and dyspnea, both of which required hospitalization. Similar symptoms recurred after ATT was substituted with levofloxacin. He was subsequently referred for allergy evaluation and underwent drug provocation testing (DPT) performed as a graded drug challenge with performed sequentially with isoniazid, rifampicin, ethambutol, and pyrazinamide under close clinical supervision. No immediate reactions were observed during in-hospital monitoring. No immediate hypersensitivity reactions were observed during in-hospital monitoring; however, delayed cutaneous symptoms developed after discharge following exposure to each tested agent, supporting the diagnosis of delayed-type hypersensitivity reactions. This case underscores the clinical challenges associated with delayed hypersensitivity reactions to multiple first-line anti-tuberculosis drugs. Drug provocation testing, when applied in a controlled and risk-stratified setting, provides valuable diagnostic clarification and assists in selecting alternative therapeutic strategies. A systematic diagnostic strategy is key to guiding individualized and safe treatment decisions in tuberculosis patients with suspected drug hypersensitivity.
References
Abbas, A. K., Lichtman, A. H., & Pillai, S. (2025). Cellular and molecular immunology (11th ed.). Elsevier.
Barbaud, A., Garvey, L. H., Torres, M., Laguna, J. J., Arcolaci, A., Bonadonna, P., et al. (2024). EAACI/ENDA position paper on drug provocation testing. Allergy: European Journal of Allergy and Clinical Immunology, 79(3), 565–579. https://doi.org/10.1111/all.15996
Bavbek, S., & PhDv, L. B.-R. (2025). Drug hypersensitivity reactions in children in clinical practice: A WAO Statement. World, 1939, 4551.
Bavbek, S., Pagani, M., Alvarez‐Cuesta, E., Castells, M., Dursun, A. B., Hamadi, S., Madrigal‐Burgaleta, R., Sanchez‐Sanchez, S., & Vultaggio, A. (2022). Hypersensitivity reactions to biologicals: An EAACI position paper. Allergy, 77(1), 39–54.
Blanca, M., Romano, A., Torres, M. J., Férnandez, J., Mayorga, C., Rodriguez, J., et al. (2009). Update on the evaluation of hypersensitivity reactions to betalactams. Allergy: European Journal of Allergy and Clinical Immunology, 64(2), 183–193. https://doi.org/10.1111/j.1398-9995.2008.01924.x
Borrás Cuartero, J., Torres Górriz, M. C., Stein Coronado, C. I., Germán Sánchez, A., Pesántez Méndez, C. G., Latorre Ibáñez, M. D., & Enrique, E. (2024). The increasing role of the allergist in the management of infusion reactions at the Oncology Infusion Center. Frontiers in Allergy, 5, 1479469.
Buhari, G. K., Erkekol, F. O., Kalkan, I. K., Ates, H., Solak, G. T. V., Akkale, O., & Aksu, K. (2024). Hypersensitivity reactions with first-line antituberculosis drugs and outcomes of rapid desensitizations. World Allergy Organization Journal, 17(1), 100862.
Cernadas, J. R., Brockow, K., Romano, A., Aberer, W., Torres, M. J., Bircher, A., et al. (2010). General considerations on rapid desensitization for drug hypersensitivity – A consensus statement. Allergy: European Journal of Allergy and Clinical Immunology, 65(11), 1357–1366. https://doi.org/10.1111/j.1398-9995.2010.02441.x
Collado-Chagoya, R., Hernández-Romero, J., Eliosa-Alvarado, G. A., Cruz-Pantoja, R. A., Campos-Gutiérrez, R. I., & Velasco-Medina, A. A. (2018). Tolerance induction to antituberculosis drugs in a patient with Stevens–Johnson syndrome/toxic epidermal necrolysis overlap. Allergy & Rhinology, 9. https://doi.org/10.1177/2152656718783618
Dartois, V. A., & Rubin, E. J. (2022). Anti-tuberculosis treatment strategies and drug development: Challenges and priorities. Nature Reviews Microbiology, 20(11), 685–701.
Demoly, P., Adkinson, N. F., Brockow, K., Castells, M., Chiriac, A. M., Greenberger, P. A., et al. (2014). International consensus on drug allergy. Allergy: European Journal of Allergy and Clinical Immunology, 69(4), 420–437. https://doi.org/10.1111/all.12350
Khan, D. A., Banerji, A., Blumenthal, K. G., Phillips, E. J., Solensky, R., White, A. A., et al. (2022). Drug allergy: A 2022 practice parameter update. Journal of Allergy and Clinical Immunology, 150(6), 1333–1393. https://doi.org/10.1016/j.jaci.2022.08.028
Lehloenya, R. J., & Dheda, K. (2012). Cutaneous adverse drug reactions to anti-tuberculosis drugs: State of the art and into the future. Expert Review of Anti-Infective Therapy, 10(4), 475–486. https://doi.org/10.1586/eri.12.13
Pallardy, M., Bechara, R., Whritenour, J., Mitchell-Ryan, S., Herzyk, D., Lebrec, H., Merk, H., Gourley, I., Komocsar, W. J., & Piccotti, J. R. (2024). Drug hypersensitivity reactions: Review of the state of the science for prediction and diagnosis. Toxicological Sciences, 200(1), 11–30.
Pichler, W. J. (2022). The important role of non‐covalent drug‐protein interactions in drug hypersensitivity reactions. Allergy, 77(2), 404–415.
Sharma, A., Sharma, V., Sharma, S., Sharma, S., Sharma, M., & Sivanesan, I. (2025). Advanced nanosystems and emerging therapies: Innovations in tuberculosis treatment and drug resistance. Pharmaceutics, 17(11), 1459.
Shin, H. J., Chang, J. S., Kim, M. S., Koh, B. G., Park, H. Y., Kim, T. O., et al. (2021). Hypersensitivity reactions to multiple antituberculosis drugs. PLoS ONE, 16(2), e0246291. https://doi.org/10.1371/journal.pone.0246291
Singha, B., Murmu, S., Nair, T., Rawat, R. S., Sharma, A. K., & Soni, V. (2024). Metabolic rewiring of Mycobacterium tuberculosis upon drug treatment and antibiotics resistance. Metabolites, 14(1), 63.
World Health Organization. (2025). WHO operational handbook on tuberculosis. Module 4: Treatment and care. WHO. https://www.who.int/publications/i/item/9789240044210
Zade, D. (2024). Hepatotoxicity associated with anti-tuberculosis medications: Analyzing mechanisms, risk factors, and strategies for prevention and management. Journal of Drug Delivery and Biotherapeutics, 1(03), 1–12.
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