Splenic tuberculosis in a patient with Crohn's disease on infliximab: case report.
Splenic tuberculosis in a patient with Crohn's disease on infliximab: case report.
复制标题
服用英夫利昔单抗的克罗恩病患者出现脾结核：病例报告。
作者：
M. Cappello;C. Randazzo;G. Rizzuto;C. Bonura;G. Di Vita;M. Galia
致编辑：2001 年首次报道肿瘤坏死因子 α (TNFa) 拮抗剂治疗期间潜在结核病 (TB) 重新激活的风险增加。因此，在开始抗 TNFa 治疗之前，现在常规通过纯化蛋白衍生物试验 (PPD) 和胸部 X 光检查是否存在潜在结核分枝杆菌感染。然而，在抗 TNFa 治疗期间，仍有结核病病例，尤其是肺外结核病例的报告。这可能与 PPD 皮试对于因既往治疗而免疫抑制的患者的敏感性有限有关。这导致了更准确测试的开发。我们报告了一例接受英夫利昔单抗治疗的克罗恩病 (CD) 患者，尽管筛查测试呈阴性，但仍出现发烧和脾局灶性病变，最初被解释为淋巴瘤，导致脾切除。根据切除的标本诊断出脾结核。一名患有回结肠CD的34岁男性，于2008年6月住进消化内科和肝病科。2002年，由于反复腹痛，他接受了后续结肠镜检查，显示回盲瓣狭窄，并接受了一个疗程的口服泼尼松治疗。该患者在2004年至2006年期间没有任何症状。2007年5月，他因腹腔脓肿再次复发。他接受了与静脉注射类固醇相关的全肠外营养，并接受了回盲部切除和回结肠吻合术。术后 6 个月发生早期临床和内镜下吻合口复发，并发肠肌瘘和右髂窝脓肿。患者接受了抗生素和类固醇治疗，脓肿得到了缓解。由于瘘管仍然活跃，2008 年 4 月，他开始在第 0、2、6 周使用英夫利昔单抗（Remicade，先灵葆雅，米兰，意大利）5 mg/kg 进行诱导治疗。PPD 测试、胸部 X 光检查以及丙型肝炎病毒和乙型肝炎病毒标志物筛查结果均为阴性。未观察到输注反应或迟发型超敏反应样反应。第三次英夫利昔单抗输注后，瘘管闭合，患者处于临床缓解状态，并且能够停止使用类固醇。 2008 年 6 月，他在最后一次注射英夫利昔单抗 2 周后出现高烧（高达 39°C）。既往无感染史、无出国旅行史、无传染性接触史。体检发现心动过速和脾肿大。他没有肠道症状，磁共振成像 (MRI) 证实瘘管闭合。实验室检查显示红细胞沉降率（90 毫米/小时）和 C 反应蛋白（7 毫克/分升；正常 <1）升高。超声检查（US）显示脾脏多处低回声局灶性病变。没有腹腔脓肿的证据。胸部 X 光检查以及布鲁氏菌、沙门氏菌、人类免疫缺陷病毒 (HIV) 和巨细胞病毒血清学检测以及血液和尿液培养结果均为阴性。血液和尿液样本中分枝杆菌的聚合酶链反应 (PCR) 呈阴性。腹部 MRI 证实脾脏肿大（14 cm）和多个局灶性病变，在 T1 和 T2 加权图像上为等信号病变（<1 cm），在动态增强图像上为低信号伴周围增强（图 1）。影像结果提示淋巴瘤，但骨髓活检呈阴性。胸部计算机断层扫描 (CT) 显示气管旁、肺门、气管前和隆突下淋巴结（直径 1.5-2.5 厘米），经正电子发射断层扫描 (PET) 扫描证实。 PET 扫描未显示脾脏中放射性同位素的异常摄取。经过哌拉西林-他唑巴坦（4 g/天）、头孢他啶（4 g/天）、甲硝唑（1.5 g/天）和氟康唑（100 mg/天）经验性治疗7天后，发热消失，患者最初出院，但2个月后随访CT显示持续性脾低密度病变和纵隔淋巴结。我们决定进行脾切除术。切除的器官上可见弥漫性干酪样肉芽肿，但 Ziehl-Neelsen 染色呈阴性。然而，脾组织 PCR 显示存在分枝杆菌。 QuantiFeron-TB 是一种体外全血测定，用于检测结核分枝杆菌特异性抗原产生的 IFN-c 产生，结果呈阳性：IFN-c 水平 8.84 IU/ml（正常 <0.35）。患者接受异烟肼（300 毫克/天）、利福平（600 毫克/天）、乙胺丁醇（1200 毫克/天）和吡嗪酰胺（1000 毫克/天）的治疗方案，并补充 B6 维生素。使用英夫利昔单抗治疗的患者发生感染并发症的风险增加。 Keane 等人的一份报告涉及 147,000 名患者在英夫利昔单抗治疗期间发生的 70 例结核病，其中 57% 和 24% 的患者观察到肺外结核和播散性结核；这些比率远高于一般人群中观察到的比率。除了感染程度外，TNF拮抗剂治疗期间发生的结核病临床表现也可能不寻常，并构成诊断困境。本报告中的患者患有回结肠 CD，英夫利昔单抗用于治疗传统疗法难治的瘘管病。 版权所有 VC 2009 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20998 2009 年 7 月 9 日在线发表于 Wiley InterScience (www.interscience.wiley.com)。
To the Editor: An increased risk of reactivation of latent tuberculosis (TB) during therapy with tumor necrosis factor alpha (TNFa)-antagonists was first reported in 2001. Therefore, screening for the presence of latent Mycobacterium tuberculosis infection by purified protein derivative test (PPD) and chest x-ray is now routinely performed before starting treatment with anti-TNFa. Nevertheless, cases of TB, especially extrapulmonary, are still reported during anti-TNFa treatment. This may be related to the limited sensitivity of the PPD skin test in patients who are already immunosuppressed as the result of previous treatment. This has led to the development of more accurate tests. We report a case of a patient with Crohn’s disease (CD) treated with infliximab who, in spite of negative screening tests, developed fever and splenic focal lesions that were initially interpreted as lymphoma leading to splenectomy. Splenic TB was diagnosed on the resected specimen. A 34-year-old man with ileocolonic CD was admitted to the Gastroenterology and Hepatology Unit in June 2008. In 2002, because of recurrent abdominal pain, he underwent a follow-up colonoscopy that showed a stenosis of the ileocecal valve and was treated with a course of oral prednisone. The patient was asymptomatic from 2004 to 2006. In May 2007 he experienced a new relapse complicated by an abdominal abscess. He received total parenteral nutrition associated with intravenous steroids and underwent an ileocecal resection with ileocolonic anastomosis. An early clinical and endoscopic anastomotic relapse, complicated by enteromuscular fistula and abscess in the right iliac fossa, occurred 6 months after the operation. The patient was treated with antibiotics and steroids, obtaining resolution of the abscess. Since the fistula remained active, in April 2008 he started induction therapy with infliximab (Remicade, Schering-Plough, Milan, Italy) 5 mg/kg at weeks 0, 2, 6. Screening with the PPD test, chest x-ray, and hepatitis virus C and B markers was negative. No infusion reaction or delayed hypersensitivity-like reaction was observed. After the third infliximab infusion the fistula closed and the patient was in clinical remission and was able to stop steroids. In June 2008 he presented to our clinic with high fever (up to 39 C) that had developed 2 weeks after the last infliximab infusion. There was no history of prior infection, foreign travel, or infectious contacts. A physical examination revealed tachycardia and splenomegaly. He had no intestinal symptoms and magnetic resonance imaging (MRI) confirmed fistula closure. Laboratory tests showed an elevated erythrocyte sedimentation rate (90 mm/h) and C-Reactive Protein (7 mg/dL; normal <1). Ultrasonography (US) revealed multiple hypoechoic splenic focal lesions. There was no evidence of abdominal abscess. Chest x-ray as well as serologic tests for Brucella, Salmonella, human immunodeficiency virus (HIV), and cytomegalovirus and blood and urine cultures were negative. Polymerase chain reaction (PCR) for mycobacteria on blood and urine samples was negative. Abdominal MRI confirmed an enlarged spleen (14 cm) and multiple focal lesions that were isointense lesions (<1 cm) on T1and T2-weighted images and, on dynamic contrastenhanced images, hypointense with peripheral enhancement (Fig. 1). Image findings suggested lymphoma but a bone marrow biopsy was negative. A chest computed tomography (CT) revealed paratracheal, hilar, pretracheal, and subcarinal lymphnodes (diameter 1.5–2.5 cm), confirmed on positron emission tomography (PET) scan. The PET scan did not show abnormal uptake of the radioisotope in the spleen. Fever disappeared after a 7-day course of empiric treatment with piperacilline-tazobactam (4 g/day), ceftazidime (4 g/day), metronidazole (1.5 g/day), and fluconazole (100 mg/day) and the patient was initially discharged, but follow-up CT 2 months later showed persistent splenic hypodense lesions and mediastinal lymphnodes. We decided to perform a splenectomy. On the resected organ diffuse caseating granulomas were shown but Ziehl–Neelsen staining was negative. PCR on splenic tissue revealed, however, the presence of mycobacteria. The QuantiFeron-TB, an in vitro whole-blood assay for the detection of IFN-c production in response to M. tuberculosis-specific antigens, was positive: IFN-c level 8.84 IU/ml (normal <0.35). The patient was placed on a regimen of isoniazid (300 mg/day), rifampicin (600 mg/day), ethambutol (1200 mg/day), and pyrazinamide (1000 mg/day) associated with B6 vitamin supplementation. Patients treated with infliximab are at increased risk for infectious complications. In a report by Keane et al involving 70 cases of TB occurring during infliximab therapy in 147,000 patients, extrapulmonary and disseminated TB was observed in 57% and 24% of patients; these rates are considerably higher than those observed in the general population. Apart from the extent of infection, the clinical presentation of TB occurring during treatment with TNF antagonists can be unusual and constitute a diagnostic dilemma. The patient in this report had ileocolic CD and infliximab was used for fistulizing disease refractory to conventional CopyrightVC 2009 Crohn’s & Colitis Foundation of America, Inc. DOI 10.1002/ibd.20998 Published online 9 July 2009 in Wiley InterScience (www.interscience.wiley.com).