Department of Paediatric Rheumatology, CeReMAIA, CHU Bicêtre, Assistance Publique - Hôpitaux de Paris, Université Paris-Sud-Saclay, 94270, Le Kremlin Bicêtre, France.
Department of Paediatrics, CHU Jean Minjoz, Besançon, France.
Orphanet J Rare Dis. 2020 Apr 17;15(1):95. doi: 10.1186/s13023-020-1345-5.
Castleman disease (CD) is a rare non-malignant lymphoproliferation of undetermined origin. Two major disease phenotypes can be distinguished: unicentric CD (UCD) and multicentric CD (MCD). Diagnosis confirmation is based on histopathological findings in a lymph node. We attempted to survey all cases of paediatric CD identified to date in France to set up a national registry aiming to improve CD early recognition, treatment and follow-up, within the context of a new national reference center (http://www.castleman.fr).
In 2016, we e-mailed a questionnaire to members of the French paediatric immunohaematology society, the paediatric rheumatology society and the Reference Centre for Castleman Disease to retrospectively collect cases of paediatric CD (first symptoms before age 18 years). Anatomopathological confirmation was mandatory.
We identified 23 patients (12 girls) with a diagnosis of UCD (n = 17) and MCD (n = 6) between 1994 and 2018. The mean age at first symptoms was 11.47 ± 4.23 years for UCD and 8.3 ± 3.4 years for MCD. The mean diagnosis delay was 8.16 ± 10.32 months for UCD and 5.16 ± 5.81 years for MCD. In UCD, the initial symptoms were isolated lymph nodes (n = 10) or lymph node associated with other symptoms (n = 7); fever was present in 3 patients. Five patients with MCD presented fever. No patients had HIV or human herpesvirus 8 infection. Autoinflammatory gene mutations were investigated in five patients. One patient with MCD carried a K695R heterozygous mutation in MEFV, another patient with MCD and Duchenne myopathy carried two variants in TNFRSF1A and one patient with UCD and fever episodes carried two heterozygous mutations, in IL10RA and IL36RN, respectively. Treatment of UCD was mainly surgical resection, steroids, and radiotherapy. Treatment of MCD included tocilizumab, rituximab, anakinra, steroids, chemotherapy, and splenectomy. Overall survival after a mean of 6.1 ± 6.4 years of follow-up, was 100% for both forms.
Paediatric CD still seems underdiagnosed, with a significant diagnosis delay, especially for MCD, but new international criteria will help in the future. Unlike adult CD, which is strongly associated with HIV and human herpesvirus 8 infection, paediatric CD could be favored by primary activation of innate immunity and may affect life expectancy less.
卡斯特曼病（CD）是一种罕见的起源不明的非恶性淋巴组织增生。可以区分两种主要的疾病表型：局灶性 CD（UCD）和多中心 CD（MCD）。诊断的确认基于淋巴结的组织病理学发现。我们试图调查迄今为止在法国发现的所有儿科 CD 病例，以建立一个国家登记处，旨在改善 CD 的早期识别、治疗和随访，这是在新的国家参考中心（http://www.castleman.fr）的背景下进行的。
2016 年，我们通过电子邮件向法国儿科免疫血液学学会、儿科风湿病学会和参考中心的成员发送了一份问卷，以回顾性收集儿科 CD（18 岁前首次出现症状）的病例。必须进行解剖病理学确认。
我们在 1994 年至 2018 年间发现了 23 例 UCD（n=17）和 MCD（n=6）患儿的诊断。UCD 的首次症状平均年龄为 11.47±4.23 岁，MCD 为 8.3±3.4 岁。UCD 的平均诊断延迟为 8.16±10.32 个月，MCD 为 5.16±5.81 年。在 UCD 中，初始症状为孤立性淋巴结（n=10）或淋巴结伴其他症状（n=7）；3 例患者有发热。5 例 MCD 患者发热。无患者感染 HIV 或人类疱疹病毒 8。5 例患者检测了自身炎症基因的突变。1 例 MCD 患者携带 MEFV 中的 K695R 杂合突变，另 1 例 MCD 和杜氏肌营养不良症患者携带 TNFRSF1A 中的两个变体，1 例 UCD 和发热患者携带 IL10RA 和 IL36RN 中的两个杂合突变。UCD 的治疗主要是手术切除、类固醇和放疗。MCD 的治疗包括托珠单抗、利妥昔单抗、阿那白滞素、类固醇、化疗和脾切除术。在平均 6.1±6.4 年的随访后，两种形式的总生存率均为 100%。
儿科 CD 似乎仍未被充分诊断，诊断延迟明显，尤其是 MCD，但新的国际标准将有助于未来的诊断。与强烈与 HIV 和人类疱疹病毒 8 感染相关的成人 CD 不同，儿科 CD 可能由先天免疫的初始激活引起，对预期寿命的影响可能较小。
