克罗恩病诊断延迟对早期病程的影响

Effects of diagnostic delay on early disease course of Crohn′s disease

目的探讨诊断延迟对CD早期病程的影响，并分析与早期病程发展有关的危险因素。方法选取2014年12月至2017年7月武汉大学人民医院初次确诊的56例CD患者。收集患者初次确诊时的临床表现、既往病史、影像学检查、内镜检查和病理检查结果，随访患者疾病确诊后CD相关手术、CD相关再住院和积极的免疫调节剂使用情况。依据从症状首发至疾病确诊的时间，将患者分为延迟组（诊断延迟时间〉2年）与非延迟组（诊断延迟时间≤2年），比较两组患者初次确诊时的临床特征及早期预后情况，并分析影响CD患者早期预后的危险因素。采用Kaplan-Meier曲线分析患者预后结果，并对影响CD患者早期预后的因素进行log-rank分析和Cox回归分析。结果延迟组影像学显示肠道损伤的比例高于非延迟组，差异有统计学意义（χ^2＝4.49，P＝0.03）。延迟组在随访期间发生CD相关再住院比例高于非延迟组，差异有统计学意义（χ^2＝7.34，P＝0.01）。9例患者在随访期间接受了手术治疗，1年和3年累积手术发生率分别为10.7%和22.7%，延迟组和非延迟组1年手术累积发生率分别为38.6%和9.6%。Cox单因素和多因素分析均显示，确诊时影像学显示肠道损伤为手术发生的危险因素[风险比（HR）均＝2.313，P均〈0.01]。21例患者在随访期间发生CD相关再住院，1年和31个月累积住院率分别为27.8%和56.3%，延迟组和非延迟组1年CD相关累积再住院率分别为43.7%和21.6%，差异有统计学意义（χ^2＝5.88，P＝0.02）；Cox单因素分析显示，伴随全身症状、影像学显示肠道损伤、诊断延迟均是发生CD相关再住院的危险因素（HR＝2.972、2.313、1.403，P均〈0.05），Cox多因素分析显示，伴随全身症状、影像学显示肠道损伤病变是发生CD相关再住院的独立危险因素（HR＝3.891、2.541，P均〈0.01）。结论诊断延迟患者出现肠道损伤病变比例增高，早期预后结局较差。初次确诊时影像学显示肠道损伤是随访期发生CD相关手术、CD相关再住院的独立危险因素。

Objective To explore the effects of diagnostic delay on early disease course of Crohn′s disease （CD）, and to analyze the risk factors related with the progress of early disease course.MethodsFrom December 2014 to July 2017, a total of 56 patients in Renmin Hospital of Wuhan University initially diagnosed as CD were selected. The clinical manifestation, previous history, imaging examination, endoscopic examination and pathological results of the patients were collected after initial diagnosis of CD. CD-related surgery, CD-related rehospitalization and use of immunomodulators were followed. According to time interval between initial symptom onset and initial diagnosis, the patients were divided into diagnostic delay group （diagnostic delay time〉two years, 14 cases） and non-diagnostic delay group （diagnostic delay time≤two years, 42 cases）. The clinical characteristics at initial diagnosis and early prognosis were compared between the two groups. The risk factors affecting early prognosis of CD patients were analyzed. Kaplan-Meier was used for prognosis analysis. Log-rank test and Cox proportional hazards model were performed to analyze factors affecting early prognosis.ResultsThe results of imaging examination indicated that the proportion of intestinal injury of diagnostic delay group was significantly higher than that of non-diagnostic delay group （χ^2=4.49, P=0.03）. During follow-up, the proportion of CD-related rehospitalization of diagnostic delay group was higher than that of non-diagnostic delay group, and the difference was statistically significant （χ^2=7.34, P=0.01）. During follow-up, the nine patients received surgery. The one-year and three-year cumulative incidence of surgery was 10.7% and 22.7%, respectively; one-year cumulative incidence of surgery in diagnostic delay group and non-diagnostic delay group was 38.6% and 9.6%, respectively. The results of Cox univariable and multivariable analyses both indicated that intestinal injury in imaging examination at diagnosis was the risk factor of surgery （both hazard ratio （HR）=2.313, both P〈0.01）. A total of 21 patients had CD-related rehospitalization during follow-up. And one-year and 31-month cumulative incidence of hospitalization was 27.8% and 56.3%, respectively; one-year cumulative incidence of CD-related rehospitalization in diagnostic delay group and non-diagnostic delay group was 43.7% and 21.6%, respectively; and the difference was statistically significant （χ2=5.88, P=0.02）. The results of Cox univariable analysis indicated that having systematic manifestation, intestinal injury in imaging examination and diagnostic delay were the risk factors of CD-related rehospitalization （HR=2.972, 2.313 and 1.403, all P〈0.05）. The results of multivariable analysis indicated that having systematic manifestation and intestinal injury in imaging examination were independent risk factors of CD-related rehospitalization （HR=3.891 and 2.541, P〈0.01, respectively）.Conclusions The proportion of intestinal injury of patients with diagnostic delay is high and the early prognosis is poor. Intestinal injury in imaging examination at initial diagnosis is independently risk factor of CD-related surgery and rehospitalization during follow-up.