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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. [ABSTRACT FROM AUTHOR]

Depression is related to increased morbidity and mortality from coronary heart disease (CHD), but the underlying mechanisms are unclear. One possibility is that depressive symptoms influence CHD pathogenesis by fostering endothelial dysfunction. To evaluate this possibility, we studied one hundred and two adolescent women with no known or suspected major health problems. Depressive symptoms were assessed using the Beck Depression Inventory (BDI) and endothelial function with a non-invasive beat-to-beat plethysmographic recording of the finger arterial pulse-wave amplitude (PWA) before and after occlusion of the brachial artery. Regression analysis revealed a significant inverse relationship between depressive symptoms and endothelial function. This persisted after controlling for age, ethnicity, health practices and waist circumference. Depression explained 4-6% of the variance in endothelial function above and beyond the effects of covariates. Most patients in our sample had subclinical depressive symptoms, suggesting that even mild affective difficulties are capable of negatively influencing endothelial function in otherwise healthy youngsters. [ABSTRACT FROM AUTHOR]

Pediatric granulomatous arthritis (PGA) has been associated with 12 different substitutions in the NOD2 gene thus far. We report a case of PGA in a 6-year-old girl with the NOD2 E383K gene substitution. Genotype analysis of the patient's family members revealed that her affected paternal aunt, as well as her asymptomatic father and 3 younger siblings, were heterozygous for the E383K substitution. The patient's mother did not have a NOD2 mutation. This is the first report of a pedigree in which 4 asymptomatic members carry the E383K substitution in NOD2, as well as the first observation of an asymptomatic carrier state for any of the NOD2 'Blau mutations.' [ABSTRACT FROM AUTHOR]