Intestinal spirochetosis: an unusual cause of IBD flare-up during anti-TNF therapy
Intestinal spirochetosis: an unusual cause of IBD flare-up during anti-TNF therapy
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肠螺旋体病：抗 TNF 治疗期间 IBD 发作的一个不寻常原因
DOI：
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发表时间：
2016
影响因子：
2.8
通讯作者：
H. Pinheiro
中科院分区：
文献类型：
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作者：
J. Chebli;Nathalia Chebli de Abreu;L. Chebli;M. Reboredo;H. Pinheiro
编辑先生：英夫利昔单抗和硫唑嘌呤的联合治疗已被证明在诱导和维持治疗中重度炎症性肠病(IBD)至少一年内比单独使用任何一种药物更有效[1]。然而，人们一直担心与抗肿瘤坏死因子治疗同时使用免疫调节剂会增加感染的风险。IBD患者在维持抗肿瘤坏死因子治疗期间出现的疾病症状可能是由于继发性反应丧失、纤维狭窄、梗阻、重叠感染，尤其是艰难梭菌或巨细胞病毒引起的，或者是与IBD无关的问题[2]。据我们所知，在抗肿瘤坏死因子治疗期间，肠道螺旋体病(IS)导致IBD发作的报道从未见过。一位35岁女性患者在我们的胃肠病门诊就诊，有6周的腹痛和水样腹泻病史。她在15个月前被诊断出患有严重的类固醇难治性克罗恩回肠结肠炎，并通过英夫利昔单抗和硫唑嘌呤的联合治疗成功地进行了治疗。经过10个月的综合治疗，患者仍处于临床缓解期。在过去的6周里，患者再次生病，出现肠道症状，以间歇性右下腹痛为特征，并伴有每天2-5次疏松、多水、急迫的大便。没有呕吐、恶心、发烧、皮疹、体重减轻或最近接触抗生素。常规肠道病原体(沙门氏菌、志贺氏菌、弯曲杆菌)和卵子/寄生虫的粪便培养均为阴性，艰难梭菌毒素的三次粪便培养均为阴性。其他实验室测试并不引人注目，包括炎症标志物(CRP和粪便钙保护素)和阴性的HIV1/2抗体测试。CT肠造影示远端回肠轻度增厚，其他肠段未见活动性病变。结肠镜检查显示所有节段的结肠粘膜正常，末端回肠看起来也正常。随机的结肠活检在苏木精-伊红染色中发现上皮内淋巴细胞局灶性增加，密布的螺旋体广泛附着于上皮表面，银染证实，尤其是在盲肠。没有发现病毒包涵体。诊断为IS合并免疫抑制治疗，患者接受甲硝唑(500 mg，q.i.d)治疗。用英夫利昔单抗和硫唑嘌呤联合治疗10天)。经抗生素治疗后症状完全消失，并持续12个月以上。患者在甲硝唑疗程结束后6个月进行了结肠镜随访，未发现异常。随机的结肠活组织检查没有发现螺旋体的证据。这是一例在生物维持治疗联合免疫抑制药物治疗的情况下，由肠道螺旋体重叠感染引起的克罗恩病发作。IS是一种大肠上皮细胞被螺旋体定植和/或感染的情况[3]。螺旋体病主要发生在与男性发生性行为的男性和艾滋病毒感染患者[4]。最常见的症状是慢性水样腹泻或*Julio Maria Fonseca Chebli Chebli@lobbo.com
Dear Editor: Combination therapy with infliximab and azathioprine has proven to be more effective for induction and maintenance treatment of moderate-to-severe inflammatory bowel diseases (IBDs) over at least 1 year than either agent alone [1]. However, there has been concern about a higher risk of infection associated with concomitant use of immunomodulator with anti-TNF therapy. Disease flares during maintenance antiTNF therapy on IBD patients may be due to secondary loss of response, fibrostenosis, obstruction, superinfection, especially caused by Clostridium difficile or cytomegalovirus, or a problem that is not IBD-related [2]. To the best of our knowledge, intestinal spirochetosis (IS) causing IBD flare-up during anti-TNF therapy has never been reported. A 35-year-old woman presented to our gastroenterology outpatient clinic with a 6-week history of abdominal pain associated with watery diarrhea. She had been diagnosed with severe steroid refractory Crohn’s ileocolitis 15 months prior and had been managed successfully with combination therapy with infliximab and azathioprine. The patient remained in clinical remission on combined therapy for 10 months subsequently. In the last 6 weeks, the patient became ill again, with a flare in bowel symptoms featured by intermittent episodes of right lower-quadrant abdominal pain accompanied by two to five episodes a day of loose, watery, urgent stools. There was no vomiting, nausea, fever, skin rash, weight loss, or recent antibiotic exposure. Stool cultures for conventional enteric pathogens (Salmonella, Shigella, Campylobacter) and ova/ parasites were negative, as well as three stool tests for C. difficile toxin. Additional laboratory tests were unremarkable, including inflammatory markers (CRP and fecal calprotectin) and a negative HIV1/2 antibody test. A CT enterography only showed mild thickening of the distal terminal ileum, with no active disease in other areas of the bowel. A colonoscopy was performed and showed normal colonic mucosa throughout all segments and a normal-appearing terminal ileum. Random colon biopsies demonstrated focal increase in intra-epithelial lymphocytes and extensive end attachment of densely packed spirochetes to the epithelial surface in hematoxylin and eosin stain, confirmed by silver stain, particularly in cecum. No viral inclusions were identified. IS complicating immunosuppressant therapy was diagnosed, and the patient was treated with metronidazole (500 mg q.i.d. for 10 days) and kept on combined therapy with infliximab and azathioprine. Complete resolution of the symptomswas observed and sustained for more than 12 months after antibiotic treatment. The patient underwent the follow-up colonoscopy 6 months after the course of metronidazole, which revealed no abnormality. Random colonic biopsies showed no evidence of spirochetes. This is a case of Crohn’s disease flare caused by intestinal spirochetes superinfection in the setting of biologic maintenance therapy combined with immunosuppressant drug. IS is a condition in which colorectal epithelial cells are colonized and/or infected by spirochetes [3]. Spirochetosis occurs mainly in men who have sex with men and HIV-infected patients [4]. The most common symptoms are chronic watery diarrhea or * Julio Maria Fonseca Chebli chebli@globo.com
影响因子：
29.4
作者：
Hazlewood, Glen S.;Rezaie, Ali;Kaplan, Gilaad G.
通讯作者：
Kaplan, Gilaad G.