Background: Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion. Herein, we assessed clinical, serological and histopathological findings of a single-center, large cohort of CD patients diagnosed and followed-up over forty years.

Methods: From January 1980 to December 2020, 1547 CD patients (1170 females; age range: 8-81 years; F:M ratio = 3.1:1) were diagnosed in an Italian tertiary referral center. Comorbidities and complications were recorded at diagnosis and during follow-up.

Results: CD diagnoses quadrupled after 2000. The most frequent phenotype was the non-classical CD (63.3%), and the most prevalent histotype was Marsh 3C (44.7%). Gastrointestinal manifestations, detectable in 51% of patients, were diarrhea (24.3%), bloating (28%) and aphthous stomatitis (19.7%). The most common CD-associated disorder was osteopenia (59.9%), predominant in females (64.3%); extraintestinal manifestations included anemia (35.8% iron-deficiency; 87% folic acid malabsorption), cryptogenic hypertransaminasemia (27.9%), and recurrent miscarriages (11.5%). Thyroiditis (26.9%), type 1 diabetes mellitus (2.9%), and dermatitis herpetiformis (1.4%) were the most common CD-related autoimmune disorders. Six patients had inflammatory bowel disease. Complications and mortality rate occurred in 1.8% and 1.9%, respectively.

Conclusions: This single-center, large cohort analysis confirmed that CD presentation changed over the years, with an increase of non-classical and subclinical clinical phenotypes.

Keywords: celiac disease; clinical features; natural history; osteoporosis; refractory celiac disease.

背景： 肠胃病（CD）是一种由麸质摄入引发的自身免疫性疾病。本文评估了一个中心在四十年间诊断并随访的大规模CD患者队列的临床、血清学和组织病理学结果。

方法： 从1980年1月至2020年12月，在一个意大利三级转诊中心诊断了1547名CD患者（女性1170人；年龄范围：8-81岁；女男比例 = 3.1:1）。在确诊和随访期间记录了合并症和并发症。

结果： 2000年后CD的确诊数量翻了四倍。最常见的表型是非典型CD（63.3%），最普遍的组织类型是Marsh 3C（44.7%）。胃肠道表现可以在51%的患者中检测到，包括腹泻（24.3%）、腹胀（28%）和口疮性口炎（19.7%）。最常见的CD相关疾病是骨质减少症（59.9%），在女性中尤为普遍（64.3%）；肠外表现包括贫血（35.8% 铁缺乏；87% 叶酸吸收不良）、不明原因的转氨酶升高（27.9%）和反复流产（11.5%）。甲状腺炎（26.9%）、1型糖尿病（2.9%）和疱疹样皮炎（1.4%）是最常见的与CD相关的自身免疫疾病。六名患者患有炎症性肠病。并发症和死亡率分别为1.8%和1.9%。

结论： 这项单中心、大规模队列分析证实，CD的临床表现随时间发生了变化，非典型和无症状表型的比例增加。

关键词： 肠胃病；临床特征；自然史；骨质疏松症；难治性肠胃病。