Department of Infectious Diseases, Hospital Universitari Vall d'Hebron, PROSICS Barcelona, Universitat Autònoma de Barcelona, Spain.
Department of Dermatology, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
PLoS Negl Trop Dis. 2019 Aug 30;13(8):e0007708. doi: 10.1371/journal.pntd.0007708. eCollection 2019 Aug.
Tumor necrosis factor alpha (TNF-α) blockers are recognized as a risk factor for reactivation of granulomatous infections. Leishmaniasis has been associated with the use of these drugs, although few cases have been reported.
We performed a retrospective observational study including patients with confirmed leishmaniasis acquired in the Mediterranean basin that were under TNF-α blockers therapy at the moment of the diagnosis. Patients diagnosed in our hospital from 2008 to 2018 were included. Moreover, a systematic review of the literature was performed and cases fulfilling the inclusion criteria were also included.
Forty-nine patients were analyzed including nine cases from our series. Twenty-seven (55.1%) cases were male and median age was 55 years. Twenty-five (51%) patients were under infliximab treatment, 20 (40.8%) were receiving adalimumab, 2 (4.1%) etanercept, one (2%) golimumab and one (2%) a non-specified TNF-α blocker. Regarding clinical presentation, 28 (57.1%) presented as cutaneous leishmaniasis (CL), 16 (32.6%) as visceral leishmaniasis (VL) and 5 (10.2%) as mucocutaneous leishmaniasis (MCL). All VL and MCL patients were treated with systemic therapies. Among CL patients, 13 (46.4%) were treated with a systemic drug (11 received L-AmB, one intramuscular antimonials and one miltefosine) while 14 (50%) patients were given local treatment (13 received intralesional pentavalent antimonials, and one excisional surgery). TNF-α blockers were interrupted in 32 patients (65.3%). After treatment 5 patients (10.2%) relapsed. Four patients with a CL (3 initially treated with local therapy maintaining TNF-α blockers and one treated with miltefosine) and one patient with VL treated with L-AmB maintaining TNF-α blockers.
This data supports the assumption that the blockage of TNF-α modifies clinical expression of leishmaniasis in endemic population modulating the expression of the disease leading to atypical presentations. According to the cases reported, the best treatment strategy would be a systemic drug and the discontinuation of the TNF-α blockers therapy until clinical resolution.
肿瘤坏死因子-α（TNF-α）阻滞剂已被确认为引发肉芽肿性感染复发的一个风险因素。利什曼病与这些药物的使用有关，尽管报告的病例很少。
我们进行了一项回顾性观察性研究，纳入了在地中海盆地获得确诊的利什曼病患者，这些患者在诊断时正在接受 TNF-α 阻滞剂治疗。研究纳入了 2008 年至 2018 年在我院确诊的患者。此外，还进行了文献系统回顾，纳入符合纳入标准的病例。
共分析了 49 例患者，包括我们系列中的 9 例。27 例（55.1%）为男性，中位年龄为 55 岁。25 例（51%）接受英夫利昔单抗治疗，20 例（40.8%）接受阿达木单抗治疗，2 例（4.1%）接受依那西普治疗，1 例（2%）接受戈利木单抗治疗，1 例（2%）接受非特定 TNF-α 阻滞剂治疗。在临床表现方面，28 例（57.1%）为皮肤利什曼病（CL），16 例（32.6%）为内脏利什曼病（VL），5 例（10.2%）为黏膜皮肤利什曼病（MCL）。所有 VL 和 MCL 患者均接受全身治疗。在 CL 患者中，13 例（46.4%）接受全身药物治疗（11 例接受两性霉素 B，1 例接受肌内注射锑剂，1 例接受米替福新），14 例（50%）接受局部治疗（13 例接受局部注射五价锑剂，1 例接受手术切除）。32 例（65.3%）患者中断了 TNF-α 阻滞剂治疗。治疗后 5 例（10.2%）患者复发。4 例 CL 患者（3 例最初接受局部治疗且维持 TNF-α 阻滞剂治疗，1 例接受米替福新治疗）和 1 例 VL 患者（接受两性霉素 B 治疗且维持 TNF-α 阻滞剂治疗）。
这些数据支持这样一种假设，即 TNF-α 的阻断会改变流行地区利什曼病的临床表现，从而改变疾病的表现，导致非典型表现。根据报告的病例，最佳治疗策略是使用全身药物，并在临床缓解前停止 TNF-α 阻滞剂治疗。
