具有消化道症状的成人自身炎症性疾病临床特点

Clinical characteristics of adult autoinflammatory diseases with gastrointestinal symptoms

目的分析具有消化道症状的成人自身炎症性疾病(autoinflammatory disease,AUIDs)患者的临床特点,寻找提示AUIDs的临床线索。方法2015年4月至2018年4月北京协和医院风湿免疫科成人AUIDs中心诊治的具有消化道症状的拟诊成人(≥16岁)AUIDs患者共39例,收集其临床资料,并进行全基因组二代测序。分析最终确诊为AUIDs患者的临床表现和基因型特点,并比较基因阳性组和基因阴性组临床表现的差异。结果39例患者中26例(66.7%)检测到与AUIDs相符的基因变异,并最终确诊为AUIDs(基因阳性组),包括家族性地中海热11例(42.3%),冷炎素相关周期性综合征、肿瘤坏死因子受体相关周期性综合征、NLRP12相关自身炎症性疾病各4例(各15.4%),要氏综合征3例(11.5%)。基因阴性组共13例(33.3%),包括未分化AUIDs、周期性发热-阿弗它口炎-咽炎-颈淋巴结炎(PFAPA)综合征等。基因阳性组成人AUIDs的消化道症状为发作性,常伴发热(100%)、咽痛(57.7%)、关节痛/炎(53.8%)、肌痛(50%)、皮疹(46.2%)等。每次发作多持续数天或数周,间隔数周或数月再发,发作间期一切如常。AUIDs的消化道症状主要表现为腹痛(84.6%)、恶心呕吐(34.6%)、腹胀(30.8%)及腹泻(11.5%)。影像学、内镜及病理多为非特异性炎症。与基因阴性组相比,基因阳性组平均病程更长[(11.6±11.2)年比(5.5±4.8)年],腹痛(84.6%比38.5%)更常见,伴胸痛/胸腔积液(26.9%比0%)、肌痛(50.0%比7.7%)和咽痛(57.7%比23.1%)亦更多见(P<0.05)。结论成人AUIDs常有消化道症状,对病程长、反复腹痛发作、伴不明原因胸痛/胸腔积液、肌痛等患者,应警惕AUIDs,建议转诊至专病门诊,进行基因检测并提供适宜的诊治方案。

Objective To analyze the clinical features of adult autoinflammatory diseases(AUIDs)patients with gastrointestinal(GI)symptoms.Methods We analyzed 39 adult patients(≥16 years of age)with GI symptoms who were suspected of AUIDs during the period from April 2015 to April 2018,at the adult AUIDs Center,Department of Rheumatology,Peking Union Medical College Hospital.The clinical data was collected and gene tests were examined.The clinical characteristics and genotypes of AUIDs with GI symptoms were evaluated.The clinical features were compared between gene positive and gene negative groups.Results Twenty six out of 39(66.7%)patients were eventually diagnosed as AUIDs(gene positive group),including 11 cases with familial Mediterranean fever(42.3%),4 cases with cryopyrin-associated periodic syndromes,tumor necrosis factor receptor-associated periodic syndrome,or NLRP12 autoinflammatory disease(15.4%separately),3 cases with YAO syndrome(11.5%).There were 13 patients(33.3%)with negative gene testing results(gene negative group),including undifferentiated AUIDs,periodic fever,aphthous stomatitis,pharyngitis,and cervical adenopathy(PFAPA)syndrome and so on.In the gene positive group,adult AUIDs patients usually presented with recurrent GI symptoms with fever(100%),pharyngitis(57.7%),arthralgia/arthritis(53.8%),myalgia(50%)and rash(46.2%).Every attack lasted for several days or weeks,and the interval between attacks was several weeks or months.Patients were healthy during interval courses.The manifestations of adult AUIDs mainly included abdominal pain(84.6%),nausea and vomiting(34.6%),abdominal distension(30.8%),and diarrhea(11.5%).Nonspecific inflammation could be found from image,endoscopy and GI biopsy.Compared with the gene negative group,the average disease course was longer[(11.6±11.2)years vs.(5.5±4.8)years],the arracks of abdominal pain(84.6%vs.38.5%),chest pain/pleural effusion(26.9%vs.0%),myalgia(50.0%vs.7.7%)and pharyngitis(57.7%vs.23.1%)were more frequent in the gene positive group(P<0.05).Conclusions GI symptoms is quite common in AUIDs.AUIDs should be considered in patients with long disease course,recurrent abdominal pain,chest pain/pleural effusion,and myalgia.Gene tests are recommended for these patients.