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Clinical Features of Childhood Behçet 's Disease Like Trisomy 8: A Summary of 19 Cases
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摘要:
目的 结合文献报道, 对多中心诊治的白塞病样8号染色体三体(Behçet's disease like trisomy 8, T8-BD)患儿的临床特征进行总结, 以提升临床医生对该病的认识与处理能力。 方法 回顾性收集2016年1月至2022年6月吉林大学第一医院、复旦大学附属儿科医院、中国医学科学院北京协和医院住院治疗及中英文文献库中检索的T8-BD患儿的临床资料, 对其一般资料、症状与体征、辅助检查结果、治疗及预后情况进行归纳、总结。 结果 共纳入吉林大学第一医院、复旦大学附属儿科医院、中国医学科学院北京协和医院住院治疗的T8-BD患儿6例、10篇文献中的T8-BD患儿13例。19例T8-BD患儿中, 男童4例(21.1%), 女童15例(78.9%); 中位起病年龄为8岁(范围: 0~16岁); 主要临床表现为口腔溃疡(94.7%), 外阴溃疡(57.9%), 发热(57.9%, 其中4例有周期热样表现); 合并恶性血液病14例(73.7%), 消化道病变9例(47.4%), 皮肤病变7例(36.8%), 脑脊液压力升高1例(5.3%)。发育异常7例(36.8%), 其中发育迟缓5例, 褶纹深3例, 关节畸形3例, 特殊面容1例, 智力障碍1例, 胼胝体发育不全1例。辅助检查示血细胞减少11例(57.9%); C反应蛋白升高11例(57.9%), 红细胞沉降率升高9例(47.4%)。治疗方面, 糖皮质激素治疗11例(57.9%), 传统免疫抑制剂治疗9例(47.4%), 生物制剂治疗6例(31.6%), 造血干细胞移植6例(31.6%), 化学药物治疗3例(15.8%)。预后方面, 死亡4例(21.1%), 均为合并恶性血液病者。 结论 T8-BD患儿以女童多见, 常见的临床症状为口腔溃疡、外阴溃疡、发热, 可合并消化道病变、皮肤病变、恶性血液病、发育异常, 但亦有部分患儿起病时伴有其他不典型表现, 临床医生应注意识别。整体来看, T8-BD患儿预后尚可, 但合并恶性血液病者对免疫抑制治疗反应差, 死亡风险增高。 Abstract:Objective The clinical characteristics of children with Behçet's disease like trisomy 8 (T8-BD) diagnosed and treated in multi-centers were summarized, so as to improve the understanding and treatment ability of clinicians. Methods Clinical data of children with T8-BD who were hospitalized in the First Hospital of Jilin University, Children's Hospital of Fudan University and Peking Union Medical College Hospital from January 2016 to June 2022 were retrospectively collected, and then based on the literature, to summarize their general data, symptoms and signs, auxiliary examination results, and treatment and prognosis. Results A total of 6 children with T8-BD hospitalized in the First Hospital of Jilin University, Children's Hospital of Fudan University and Peking Union Medical College Hospital and 13 children with T8-BD recorded in 10 literature reports were included. Among the 19 children with T8-BD, there were 4 males (21.1%) and 15 females (78.9%). The median age of onset was 8 years (range: 0-16 years). The main clinical manifestations were oral ulcer (94.7%), vulvar ulcer (57.9%) and fever (57.9%, including 4 cases with periodic fever-like manifestations). There were 14 cases (73.7%) of malignant hematologic diseases, 9 cases (47.4%) of digestive tract lesions, 7 cases (36.8%) of skin lesions, and 1 case (5.3%) of cerebrospinal fluid pressure elevation. There were 7 cases (36.8%) of abnormal development, including 5 cases of developmental delay, 3 cases of deep folds, 3 cases of joint deformity, 1 case of special facial appearance, 1 case of intellectual impairment, and 1 case of agenesis of corpus callosum. Auxiliary examination showed hemocytopenia in 11 cases (57.9%); C-reactive protein increase in 11 cases (57.9%), and erythrocyte sedimentation rate increase in 9 cases (47.4%). In terms of treatment, 11 cases (57.9%) were treated with glucocorticoid, 9 cases (47.4%) with traditional immunosuppressant, 6 cases (31.6%) with biological agents, 6 cases (31.6%) with hematopoietic stem cell transplantation and 3 cases (15.8%) with chemical agents. In terms of prognosis, 4 cases (21.1%) died, all of which were complicated with hematologic malignancies. Conclusions The common clinical symptoms of T8-BD are oral ulcers, vulvar ulcers and fever, which can be combined with digestive tract lesions, skin lesions, hematologic malignancies and developmental abnormalities. However, some children are accompanied by other atypical manifestations at the onset of the disease, to which clinicians should pay attention to identify. Overall, the prognosis of children with T8-BD is reasonable, but patients with hematologic malignancies have poor response to immunosuppressive therapy and increased risk of death. -
Key words:
- Behçet's disease /
- trisomy 8 /
- pediatrics /
- myelodysplastic syndrome
作者贡献：赵婉雯、刘海梅、张天誉负责收集临床资料、初步分析资料，完成初稿撰写；杨思睿、孙利、宋红梅负责审阅、分析临床资料，稿件审校、修订。利益冲突：所有作者均声明不存在利益冲突 -
表 1 19例T8-BD患儿临床特征
指标 1* 2* 3* 4* 5* 6* 7[5] 8[6] 9[7] 10[8] 11[8] 12[8] 13[9] 14[10] 15[11] 16[12] 17[13] 18[13] 19[14] 一般情况 性别 女 女 女 男 男 女 女 女 女 男 男 女 女 女 女 女 女 女 女 起病年龄(岁) 14 7 12 11 15 8 10 4 4 6 6 0 11 16 5 14 5 14 4 诊断BD时年龄(岁) 15 13 13 13 15 13 14 4 6 6 6 1.5 18 16 11 14 13 14 - 诊断T8时年龄(岁) 15 13 14 13 15 13 14 4 7 6 6 1.5 18 16 11 14 11 14 - 合并恶性血液病 N N AML AA MDS、AA MDS MDS MDS AML MDS MDS MDS MDS MDS MDS AML N N N 诊断恶性血液病时年龄(岁) - - 14 7 14 13 14 4 7 6 6 3 18 15 11 15 - - - 症状及体征 口腔溃疡 Y Y Y Y Y N Y Y Y Y Y Y Y Y Y Y Y Y Y 外阴溃疡 Y Y Y Y Y N Y N N N N N Y Y Y Y N Y N 皮肤病变 银屑病 脱屑样皮损 N N N N N 结节性红斑 N N N 下肢溃疡 N 具体不详 N N 结节性红斑 N 结节性红斑 发热 N Y N N Y Y N Y N Y Y Y Y N Y Y N N Y 周期热 N Y N N Y N N Y N N N N N N Y N N N N 眼部病变 N N N N N N - N N - - - - N N N N N Y 消化道病变及位置 - - 溃疡，回盲部 - - 炎症，左半结肠 - 溃疡、横结肠、升结肠 溃疡，回盲部和乙状结肠之间 溃疡，上消化道 溃疡，食管 溃疡，上消化道 溃疡，盲肠 - - 溃疡，回盲部 - - N 关节炎/ 关节痛 N N N N N N - - - - - - Y N Y - - - Y 血管病变 N N 门静脉血栓 N N N - N - - - - - N N 门静脉、脾静脉血栓 N - - 神经系统 N N Y N N N - N - - - - - - N N - - - 肾脏病变 N N N N N N - - - - - - - - N - N - - 发育异常 特殊面容 N N N - - - - - - - - - - - - - Y - - 发育迟缓 N N N - - - - - - Y Y Y - - - - Y Y - 智力障碍 N N N - - - - - - - - - - - - - N Y - 关节畸形 Y N N - - - - - - - - - - - - - Y Y - 褶纹深 Y N N - - - - - - - - - - - Y - Y - - 胼胝体发育不全 N N N - - - - - - - - - - - - - Y - - 辅助检查 血细胞减少 N N N Y Y Y Y Y Y Y Y Y N Y N N N N Y 炎症指标 CRP↑ESR↑ CRP↑ESR↑ CRP↑ESR↑ CRP↑ESR↑ CRP↑ESR↑ CRP↑ESR↑ - CRP↑ - - - - CRP↑ - CRP↑ESR↑ CRP↑ESR↑ - CRP↑ ESR↑ 免疫球蛋白 IgM↑ 正常 正常 正常 IgG↑IgA↑ 正常 - 正常 - - - - 正常 - IgE↑ - 正常 - - 补体 C4↑ C3↑ 正常 - - - - - - - - - - - 正常 - - - - 抗核抗体 阴性 均质型、核点型 颗粒型、胞浆颗粒型 阴性 阴性 阴性 - 阴性 - - - 阴性 阴性 - 阴性 阴性 - - 阴性 治疗及预后 免疫抑制剂 TNFi TNFi GC、TNFi、MTX GC GC、CsA、沙利度胺 GC、CsA 沙利度胺、Tac - Tac、MTX、CsA GC GC、TNFi GC TNFi、MTX GC、CsA - GC、TNFi、MTX GC - GC、CsA、AZA 血液病治疗 无 无 化学药物治疗 - - - - HSCT HSCT、化学药物治疗 HSCT HSCT HSCT HSCT 司坦唑醇、雄激素 - 化学药物治疗 无 无 无 是否死亡 否 否 是 否 否 否 否 否 是 否 是 否 否 否 否 是 否 否 否 T8、BD：同图 1；AML：急性髓系白血病；AA：再生障碍性贫血；MDS：骨髓异常增生综合征；CRP：C反应蛋白，ESR：红细胞沉降率；TNFi：肿瘤坏死因子拮抗剂；GC：糖皮质激素；MTX：甲氨蝶呤；Tac：他克莫司；CsA：环孢素A；AZA：硫唑嘌呤；HSCT：造血干细胞移植；*本文报道病例；“-”：未提及；“↑”表示“升高”；Y表示“有”；N表示“无” 
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