Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Lung Infection and Immunity Unit, Division of Pulmonology, University of Cape Town, Cape Town, South Africa.
Br J Dermatol. 2016 Jul;175(1):150-6. doi: 10.1111/bjd.14492. Epub 2016 May 26.
The incidence of cutaneous adverse drug reactions (CADRs) to first-line antituberculosis drugs (FLTDs) is higher in HIV-tuberculosis coinfection. However, the utility of patch testing to identify the offending drug in this patient subgroup has been poorly studied.
To identify drugs causing adverse drug reactions in patients with HIV-tuberculosis coinfection.
Fourteen consecutive patients underwent diagnostic work-up (patch testing followed by a skin prick test and an oral rechallenge) to pinpoint the offending drug after developing FLTD-associated CADR, which included drug rash with eosinophilia and systemic symptoms (n = 12), Stevens-Johnson syndrome (SJS, n = 1) and toxic epidermal necrolysis/SJS overlap (n = 1). A positive reaction to any of the three diagnostic modalities eliminated that drug from the regimen. Once patients were clinically stable postreaction, sequential and additive rechallenge with FLTDs was initiated.
Eleven of the 14 participants with FLTD-associated CADR were HIV infected (median CD4 count 149 cells mm(-3) ). In this subgroup, patch testing resulted in generalized systemic reactions in 10 of 11 patients (91%). These included rash in 10 of 13 reactions (77%), eosinophilia in eight (62%), transaminitis in seven (54%) and fever in five (38%). Isoniazid caused six of 13 (46%) generalized systemic reactions, rifampicin four (31%), ethambutol two (15%) and pyrazinamide one reaction. Using the Common Terminology Criteria for Adverse Events, five of 13 reactions were mild, six were moderate and two were severe. There were no life-threatening or fatal reactions.
In HIV-infected persons with tuberculosis-associated CADR, although patch-testing reactions to FLTD are common and tend to be associated with systemic features, they are not life threatening or fatal. These data inform clinical practice in HIV-endemic settings.
在人类免疫缺陷病毒（HIV）合并结核病（TB）患者中，一线抗结核药物（FLTD）引起的皮肤不良反应（CADR）发生率更高。然而，在该患者亚组中，斑贴试验用于识别致病药物的效用尚未得到充分研究。
确定导致 HIV-TB 合并感染患者发生药物不良反应的药物。
14 例连续患者在发生与 FLTD 相关的 CADR 后（包括药物疹伴嗜酸性粒细胞增多和全身症状[12 例]、史蒂文斯-约翰逊综合征[SJS，1 例]和中毒性表皮坏死松解症/SJS 重叠[1 例]）进行了诊断性检查（斑贴试验后进行皮肤划痕试验和口服再激发试验），以确定致病药物。任何三种诊断方法中的阳性反应均排除了该药物的方案。一旦患者在反应后临床稳定，就开始对 FLTD 进行序贯和累加再激发试验。
14 例与 FLTD 相关的 CADR 患者中有 11 例（中位 CD4 计数为 149 个细胞/mm3）为 HIV 感染。在该亚组中，斑贴试验导致 11 例患者中的 10 例（91%）出现全身性系统反应。这些反应包括皮疹（10/13，77%）、嗜酸性粒细胞增多（8/13，62%）、氨基转移酶升高（7/13，54%）和发热（5/13，38%）。异烟肼引起 6 次（46%）全身性系统反应，利福平引起 4 次（31%），乙胺丁醇引起 2 次（15%），吡嗪酰胺引起 1 次。根据不良事件常用术语标准，13 次反应中有 5 次为轻度，6 次为中度，2 次为重度。无危及生命或致命性反应。
在患有结核病相关 CADR 的 HIV 感染者中，尽管 FLTD 斑贴试验反应很常见，且往往与全身特征相关，但不会危及生命或致命。这些数据为 HIV 流行地区的临床实践提供了信息。
