Aziz Imran, Key Tim, Goodwin John G, Sanders David S
*Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals †Department of Histocompatability & Immunogenetics, NHS Blood & Transplant Centre, Sheffield, UK.
J Clin Gastroenterol. 2015 Jul;49(6):477-82. doi: 10.1097/MCG.0000000000000184.
Duodenal intraepithelial lymphocytosis (D-IEL) is an early marker for celiac disease (CD). However, the majority of cases are due to non-CD-related conditions.
To identify the predictors of CD when presented with D-IEL.
A total of 215 adult patients with D-IEL had undergone prospective and systematic evaluation for CD and other recognized associations.The gold-standard diagnosis of CD was based upon the presence of HLA-DQ2 and/or DQ8, persistence or progression of D-IEL following a gluten challenge, followed by symptomatic improvement on a gluten-free diet.Binary logistic regression models, adjusting for age and sex, were subsequently performed to compare presenting variables between CD and non-CD cases, and to determine their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
CD was diagnosed in 48 cases (22%) and non-CD in 167 cases (78%). There was no statistical difference in baseline demographics, clinical symptoms (ie, diarrhea, weight loss, abdominal pain), anemia, or hematinics between the CD and non-CD group.Patients with CD, in comparison with non-CD, were significantly more likely to have a positive family history of CD (21% vs. 3.6%, OR 6.73; PPV 62.5%, NPV 81%, specificity 96.4%), positive HLA-DQ status (100% vs. 49.1%; PPV 36.4%, NPV 100%, specificity 50.9%), and presence of endomysial antibody (EMA) (48% vs. 0%; PPV 100%, NPV 87%, specificity 100%); all P≤0.001.A normal tissue transglutaminase antibody (TTG) level was seen in 29.2% CD and 83.2% non-CD cases (OR 0.084, P<0.001; PPV 9.2%). There was no difference in the prevalence of TTG levels 1 to 2×upper limit of normal (ULN) between the groups (29.2% CD vs. 14.4% non-CD; PPV 33% to 38%). However, TTG levels between 3 and 20×ULN were significantly more prevalent in the CD group (33.3% vs. 2.4%, PPV 66.6% to 89%), whereas a TTG>20×ULN was exclusive to CD (8.3%, P<0.001, PPV 100%).
In the setting of D-IEL, only the presence of a positive EMA or TTG>20×ULN at the outset can be used to make an immediate diagnosis of CD. Gastrointestinal symptoms, family history, anemia, or other celiac serology results do not reliably distinguish CD from non-CD without further investigations.
十二指肠上皮内淋巴细胞增多症(D-IEL)是乳糜泻(CD)的早期标志物。然而,大多数病例是由非CD相关疾病引起的。
确定出现D-IEL时CD的预测因素。
共有215例成年D-IEL患者接受了针对CD和其他公认关联的前瞻性系统评估。CD的金标准诊断基于HLA-DQ2和/或DQ8的存在、麸质激发后D-IEL的持续或进展,随后无麸质饮食症状改善。随后进行二元逻辑回归模型,对年龄和性别进行校正,以比较CD和非CD病例之间的表现变量,并确定其敏感性、特异性、阳性预测值(PPV)和阴性预测值(NPV)。
48例(22%)诊断为CD,167例(78%)诊断为非CD。CD组和非CD组在基线人口统计学、临床症状(即腹泻、体重减轻、腹痛)、贫血或血液学指标方面无统计学差异。与非CD患者相比,CD患者有CD家族史阳性的可能性显著更高(21%对3.6%,OR 6.73;PPV 62.5%,NPV 81%,特异性96.4%)、HLA-DQ状态阳性(100%对49.1%;PPV 36.4%,NPV 100%,特异性50.9%)以及存在肌内膜抗体(EMA)(48%对0%;PPV 100%,NPV 87%,特异性100%);所有P≤0.001。29.2%的CD病例和83.2%的非CD病例组织转谷氨酰胺酶抗体(TTG)水平正常(OR 0.084,P<0.001;PPV 9.2%)。两组之间TTG水平为正常上限(ULN)的1至2倍的患病率无差异(29.2%的CD对14.4%的非CD;PPV 33%至38%)。然而,TTG水平在3至20倍ULN之间在CD组中显著更常见(33.3%对2.4%,PPV 66.6%至89%),而TTG>20倍ULN仅见于CD(8.3%,P<0.001,PPV 100%)。
在D-IEL的情况下,只有一开始存在EMA阳性或TTG>20倍ULN才能用于立即诊断CD。胃肠道症状、家族史、贫血或其他乳糜泻血清学结果在没有进一步检查的情况下不能可靠地区分CD和非CD。