Acute Cytomegalovirus Infection Is a Risk Factor in Refractory and Complicated Inflammatory Bowel Disease

Acute Cytomegalovirus Infection Is a Risk Factor in Refractory and Complicated Inflammatory Bowel Disease
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DOI:
10.1007/s10620-008-0639-6
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发表时间:
2009-11-01
影响因子:
3.1
通讯作者:
Nassar, Mahmoud I.
Nassar, Mahmoud I.
中科院分区:
医学3区
文献类型:
--
作者:
Maher, Maha M.;Nassar, Mahmoud I.

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巨细胞病毒(CMV)感染在炎症性肠病(IBD)患者中的作用存在争议。虽然巨细胞病毒与难治性疾病有明确的联系,但这种联系的强度和性质一直是争论的主题。本研究的目的是评估急性巨细胞病毒感染在严重难治性和复杂性炎症性肠病患者中的患病率和预后。本研究纳入72例活动期IBD患者(溃疡性结肠炎[UC]和克罗恩病[CD])。对所有患者进行彻底的病史记录和体格检查,特别强调巨细胞病毒病的症状和体征。对IBD的程度、活动性及标本的采集进行结肠镜检查。CMV感染的发生率通过血清学、抗CMV IgM和IgG抗体以及结肠活检常规苏木精-伊红(H&E)和单抗免疫组织化学(IHC)来评估。对所有患者进行全血细胞计数和肝功能检查。72例活动性炎症性肠病患者中,23例(31.9%)对静脉注射激素耐药。23例(34.8%)激素耐药患者中有8例(UC患者6例,CD患者2例)检出CMV,其余31例接受激素治疗的患者中仅1例(3.2%)检出CMV,18例未使用激素的IBD患者未检出CMV。在9例CMV阳性的IBD患者中,6例(66.6%)为女性,6例有发热;与CMV阴性组相比,5例患者有颈部淋巴结病变,2例有脾肿大(P分别为0.01和0.03)。巨细胞病毒阳性患者与巨细胞病毒阴性患者相比,主要表现为白细胞减少和血小板减少(分别为2.1+/-0.3比5.9+/-3.4和98+/-34比165+/-101)。在9例巨细胞病毒阳性的IBD患者中,有5例发现了泛结肠炎,而在63例巨细胞病毒阴性的患者中,只有2例发现了泛结肠炎(P=0.005)。IBD患者急性巨细胞病毒感染并不罕见,常常被低估。在积极的免疫抑制治疗之前,应排除难治性或并发IBD患者中CMV感染的可能性。临床上对CMV感染与IBD相关的高度怀疑指标应针对女性IBD患者,表现为发热、淋巴病变、脾肿大、白细胞减少和轻度肝炎。CMV IHC明显比常规H&E染色更敏感,在进行其他内科或外科治疗之前,应考虑将其作为IBD患者严重恶化或类固醇难治性疾病的常规评估的一部分。
The role of cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is controversial. Although CMV has been specifically associated with refractory disease, the strength and nature of this association have been a subject of debate. The aim of this study was to evaluate the prevalence and outcome of acute cytomegalovirus infection in patients with severe refractory and complicated inflammatory bowel disease. Seventy-two patients with active IBD (both ulcerative colitis [UC] and Crohn's diseases [CD]) were included in this study. Thorough history taking and physical examination of all patients was made with special emphasis on symptoms and signs of CMV disease. Colonoscopic assessment was made for the extent and activity of IBD and collection of specimen. Prevalence of CMV infection was estimated by serology; anti-CMV IgM and IgG antibodies, and pathologic studies of colonic biopsies used conventional haematoxylin and eosin (H & E) and immunohistochemistry (IHC) with monoclonal antibodies. Complete blood count and liver function tests were done for all patients. Among 72 patients with active inflammatory bowel disease, 23 (31.9%) were resistant to intravenous steroids. CMV was detected in eight (six with UC and two with CD) of the 23 (34.8%) steroid-resistant patients and in only one (3.2%) patient in the remaining 31 patients under steroid treatment and was not detected in 18 IBD patients not using steroids. Among nine CMV-positive IBD patients, six (66.6%) were female and six had fever; cervical lymphadenopathy was found in five patients and splenomegaly in two, compared to no patients in the CMV-negative group (P = 0.01 and 0.03, respectively). Leucopenia and thrombocytopenia were predominantly seen in the CMV-positive versus CMV-negative patients (2.1 +/- 0.3 vs. 5.9 +/- 3.4 and 98 +/- 34 vs. 165 +/- 101, respectively). Pancolitis was found in five of nine CMV-positive IBD patients whereas in only two patients out of 63 in the CMV-negative group (P = 0.005). Acute CMV infection in patients with IBD is not rare and is often underestimated. CMV infection in patients with refractory or complicated IBD should be ruled out before aggressive immunosuppressive therapy. High clinical index of suspicion for the association of CMV infection with IBD should be directed towards female IBD patients presenting with fever, lymphadenopathy, splenomegaly, leucopenia, and mild hepatitis. CMV IHC is significantly more sensitive than routine H & E stain and should be considered as part of the routine evaluation of IBD patients with severe exacerbation or steroid-refractory disease before proceeding with other medical or surgical therapy that may not be necessary once the CMV is treated.