Pediatric granulomatous arthritis: An international registry

Abstract

Objective. 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.Methods. Histologically confirmed granuloma and arthritis were required for inclusion. Probands and relatives were genotyped for CARD15. Deidentified clinical information was collected.Results. 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).Conclusion. 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.

Autoinflammatory diseases in Pediatrics

“…As a counteracting measure, several international studies or registries (Eurofever, Infevers, Blau Registry) have been developed to expand the knowledge regarding their clinical presentation, complications and management, to streamline and quickly recognize them in the medical community, and also to provide information to parents and patients. 57,59 n…”

Síndromes autoinflamatórias hereditárias na faixa etária pediátrica

“…116 The typical rash of PGA is described as brown in color and ichthyosis-like, and is found in 88% of patients. 116,117 Less common findings include fever, camptodactyly, and cranial neuropathy. 114 Figure 3 shows a patient with PGA and ichthyosiform rash.…”

“…116 Non-caseous granulomas may be found in the synovial tissue, skin, and liver. 116,117 Definitive diagnosis can only be established by a finding of NOD2 mutation. 18 Treatment is NSAID-based in patients with mild disease, whereas more severe manifestations require systemic corticosteroid therapy.…”

A Novel Mutation in Helical Domain 2 of NOD2 in Sporadic Blau Syndrome

“…Familial BS and its sporadic variant early-onset sarcoidosis (EOS) consist of a triad of dermatitis, arthritis, and uveitis. Ocular manifestations include anterior uveitis, multifocal choroiditis, and panuveitis appearing around 4 years of age 3 . Treatment with corticosteroids and immunosuppressive is not always effective and long-term prognosis is unknown 3 .…”

“…Ocular manifestations include anterior uveitis, multifocal choroiditis, and panuveitis appearing around 4 years of age 3 . Treatment with corticosteroids and immunosuppressive is not always effective and long-term prognosis is unknown 3 . We report a case of sporadic BS (EOS) with a novel NOD2 mutation.…”