Ga-Young Ban1, Yoon-Jeong Jeong2, So-Hee Lee3, Seung-Soo Shin2, Yoo-Seob Shin3, Hae-Sim Park3, Seung-Hyun Kim4, Young-Min Ye5. 1. Department of Pulmonary, Allergy and Critical Care Medicine, Kangdong Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 05355, Republic of Korea. 2. Department of Pulmonology and Critical Care Medicine, Ajou University School of Medicine, Suwon, 16499, Republic of Korea. 3. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea. 4. Translational Research Laboratory for Inflammatory Disease, Clinical Trial Center, Ajou University Medical Center, Suwon, 16499, Republic of Korea. Electronic address: kimsh@ajou.ac.kr. 5. Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea. Electronic address: ye9007@ajou.ac.kr.
Abstract
BACKGROUND: Delayed drug hypersensitivity to first-line anti-tuberculosis medication is a major challenge in tuberculosis treatment. OBJECTIVE: This study was performed to investigate the efficacy/tolerability of desensitization therapy in treatment of first-line anti-tuberculosis medication hypersensitivity and the usefulness of immunologic evaluation therein. METHODS: This study was conducted as a prospective, observational cohort study. Subjects who experienced hypersensitivity reactions, including maculopapular exanthema (MPE) and drug reaction with eosinophilia and systemic symptoms (DRESS), to first-line anti-tuberculosis medications (isoniazid [INH], ethambutol [EMB], rifampin [RFP], and pyrazinamide [PZA]) were enrolled. Patch, intradermal, lymphocyte transformation, and oral provocation tests were performed to determine culprit drugs, which were desensitized with rapid and graded challenge protocols. Breakthrough reactions (BTRs) during or after desensitization were assessed. RESULTS: In total, 31 desensitization treatments (INH, 8; EMB, 8; RFP, 11; PZA, 4) to 12 patients (8 with MPE and 4 with DRESS) were performed. The overall success rate of desensitization was 80.7%. All the study subjects except one completed the full course of anti-tuberculosis treatment. The overall BTR free rate was 64.5%. Sixteen (80%) treatments for MPE and four (36.4%) for DRESS were BTR free (P = 0.023). Drugs that were positive on any two of three immunologic studies showed significantly high BTR rates (P = 0.014), although this was not correlated with desensitization failure rate. CONCLUSION: Rapid desensitization therapy to multiple anti-tuberculosis medications for delayed drug hypersensitivity was safe and successful. Combination of multiple immunologic evaluations may predict BTR although it needs validation in larger studies.
BACKGROUND: Delayed drug hypersensitivity to first-line anti-tuberculosis medication is a major challenge in tuberculosis treatment. OBJECTIVE: This study was performed to investigate the efficacy/tolerability of desensitization therapy in treatment of first-line anti-tuberculosis medication hypersensitivity and the usefulness of immunologic evaluation therein. METHODS: This study was conducted as a prospective, observational cohort study. Subjects who experienced hypersensitivity reactions, including maculopapular exanthema (MPE) and drug reaction with eosinophilia and systemic symptoms (DRESS), to first-line anti-tuberculosis medications (isoniazid [INH], ethambutol [EMB], rifampin [RFP], and pyrazinamide [PZA]) were enrolled. Patch, intradermal, lymphocyte transformation, and oral provocation tests were performed to determine culprit drugs, which were desensitized with rapid and graded challenge protocols. Breakthrough reactions (BTRs) during or after desensitization were assessed. RESULTS: In total, 31 desensitization treatments (INH, 8; EMB, 8; RFP, 11; PZA, 4) to 12 patients (8 with MPE and 4 with DRESS) were performed. The overall success rate of desensitization was 80.7%. All the study subjects except one completed the full course of anti-tuberculosis treatment. The overall BTR free rate was 64.5%. Sixteen (80%) treatments for MPE and four (36.4%) for DRESS were BTR free (P = 0.023). Drugs that were positive on any two of three immunologic studies showed significantly high BTR rates (P = 0.014), although this was not correlated with desensitization failure rate. CONCLUSION: Rapid desensitization therapy to multiple anti-tuberculosis medications for delayed drug hypersensitivity was safe and successful. Combination of multiple immunologic evaluations may predict BTR although it needs validation in larger studies.
Authors: Bernard Yu-Hor Thong; Michaela Lucas; Hye-Ryun Kang; Yoon-Seok Chang; Philip Hei Li; Min Moon Tang; James Yun; Jie Shen Fok; Byung-Keun Kim; Mizuho Nagao; Iris Rengganis; Yi-Giien Tsai; Wen-Hung Chung; Masao Yamaguchi; Ticha Rerkpattanapipat; Wasu Kamchaisatian; Ting Fan Leung; Ho Joo Yoon; Luo Zhang; Amir Hamzah Abdul Latiff; Takao Fujisawa; Francis Thien; Mariana C Castells; Pascal Demoly; Jiu-Yao Wang; Ruby Pawankar Journal: Asia Pac Allergy Date: 2020-01-30