Rosé Carlos D, Wouters Carine H, Meiorin Silvia, Doyle Trudy M, Davey Michael P, Rosenbaum James T, Martin Tammy M
duPont Children's Hospital, Wilmington, Delaware 19899, USA.
Arthritis Rheum. 2006 Oct;54(10):3337-44. doi: 10.1002/art.22122.
Blau syndrome and its sporadic counterpart, early-onset sarcoidosis, share an identical phenotype featuring the classic triad of arthritis, dermatitis, and uveitis and are associated with mutations of CARD15 in 50-90% of cases. We chose the term "pediatric granulomatous arthritis" to refer to both. An international registry was established in the spring of 2005 to define the phenotype spectrum and establish the mutation frequency and variants.
Histologically confirmed granuloma and arthritis were required for inclusion. Probands and relatives were genotyped for CARD15. Deidentified clinical information was collected.
One year after the inception of the registry, 61 individuals from 22 pedigrees had been entered. Seven pedigrees with 19 individuals (8 affected, 11 unaffected) had clinical disease that was atypical, and none of the individuals in those pedigrees showed mutations. There were 9 classic simplex pediatric granulomatous arthritis pedigrees including 19 individuals (9 affected, 10 unaffected) and 6 classic multiplex pedigrees with 22 individuals (17 affected, 5 unaffected). Cutaneous presentation was the most common. Arthritis was polyarticular in 96% of patients. Isolated eye disease was never the presenting symptom, but significant/severe visual impairment was observed in 41% of patients. Eye disease was bilateral in 21 of 22 patients and was complicated by glaucoma in 6 of 22 patients and by cataracts in 50% of patients. Skin biopsy was the best diagnostic approach (because of accuracy and low invasiveness).
In this series, the first combining familial and sporadic pedigrees and, to our knowledge, the largest, we further defined the phenotype and showed that all affected classic (and no nonclassic) pedigrees carry a mutation and that there is no asymptomatic carriage. If these data are confirmed, mutation analysis rather than tissue sampling may prove to be the most efficient diagnostic procedure.
布劳综合征及其散发型对应疾病——早发型结节病，具有相同的表型，其特征为关节炎、皮炎和葡萄膜炎的经典三联征，且在50%至90%的病例中与CARD15基因突变相关。我们选用“小儿肉芽肿性关节炎”这一术语来指代这两种疾病。2005年春季建立了一个国际登记处，以确定表型谱，并确定突变频率和变异情况。
纳入组织学确诊的肉芽肿和关节炎患者。对先证者及其亲属进行CARD15基因分型。收集去识别化的临床信息。
登记处设立一年后，已录入来自22个家系的61人。7个家系中的19人（8例患病，11例未患病）患有非典型临床疾病，这些家系中无一例显示出突变。有9个经典的单纯型小儿肉芽肿性关节炎家系，包括19人（9例患病，10例未患病），以及6个经典的复合型家系，有22人（17例患病，5例未患病）。皮肤表现最为常见。96%的患者关节炎为多关节型。孤立性眼病从未作为首发症状出现，但41%的患者出现了明显/严重的视力损害。22例患者中有21例眼病为双侧性，22例患者中有6例并发青光眼，50%的患者并发白内障。皮肤活检是最佳诊断方法（因其准确性和低侵入性）。
在本系列研究中，首次将家族性和散发性家系结合起来，据我们所知也是规模最大的研究，我们进一步明确了表型，并表明所有受影响的经典（而非非经典）家系都携带突变，且不存在无症状携带情况。如果这些数据得到证实，突变分析而非组织取样可能被证明是最有效的诊断程序。
