Arthritis and Rheumatism

Publication date: 2009-06
Volume: 60 Pages: 1797 - 1803
ISSN: 0004-3591, 1529-0131 PMID: 19479837
DOI: 10.1002/art.24533
Publisher: John Wiley & Sons

Author:

Rosé, C
Arostegui, JI ; Martin, TM ; Espada, G ; Scalzi, L ; Modesto, C ; Arnal, MC ; Merino, R ; Garcia Consuegra, J ; Carballo, MA ; Wouters, Carine

Keywords:

Science & Technology, Life Sciences & Biomedicine, Rheumatology, EARLY-ONSET SARCOIDOSIS, BLAU-SYNDROME, CARD15 MUTATIONS, CHILDHOOD, UVEITIS, NOD2, RASH, Adolescent, Adult, Arthritis, Child, Child, Preschool, Cohort Studies, Dermatitis, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Mutation, Nod2 Signaling Adaptor Protein, Pedigree, Phenotype, Prevalence, Registries, Spain, Uveitis, Young Adult

Abstract:

OBJECTIVE: To study the phenotype characteristics of the largest to date cohort of patients with pediatric granulomatous arthritis (PGA) and documented mutations in the NOD2 gene. METHODS: We analyzed merged data from 2 prospective cohorts of PGA patients, the International PGA Registry and a Spanish cohort. A systematic review of the medical records of interest was performed to identify phenotype characteristics. RESULTS: Forty-five patients with PGA (23 sporadic cases and 22 from familial pedigrees) and documented NOD2 mutations were identified and formed the basis of the study. Of these 45 patients, 18 had the R334W-encoding mutation, 18 had R334Q, 4 had E383K, 3 had R587C, 1 had C495Y, and 1 had W490L. The majority of patients manifested the typical triad of dermatitis, uveitis, and arthritis. In contrast, in 13 patients, the following "atypical" manifestations were noted: fever, sialadenitis, lymphadenopathy, erythema nodosum, leukocytoclastic vasculitis, transient neuropathy, granulomatous glomerular and interstitial nephritis, interstitial lung disease, arterial hypertension, hypertrophic cardiomyopathy, pericarditis, pulmonary embolism, hepatic granulomatous infiltration, splenic involvement, and chronic renal failure. In addition, 4 individuals who were asymptomatic carriers of a disease-causing mutation were documented. CONCLUSION: NOD2-associated PGA can be a multisystem disorder with significant visceral involvement. Treating physicians should be aware of the systemic nature of this condition, since some of these manifestations may entail long-term morbidity.