Study of vitamin D status and vitamin D receptor polymorphisms in a cohort of Italian patients with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is the most common chronic arthritis of children and adolescents. Autoimmune mechanisms are suspected to have a central role in its development. Vitamin D is an immuno-modulator in a variety of conditions, including autoimmune diseases. Low levels of vitamin D have commonly been found in JIA patients, but the influence of this hormone insufficiency in JIA pathogenesis is still unclear. Vitamin D receptor (VDR) mediates a great majority of vitamin D biological activities; specific polymorphisms of the VDR gene have been associated with different biologic responses to vitamin D. In this study, we analysed clinical characteristics of a cohort of 103 Italian JIA patients. The distribution of VDR polymorphisms in affected patients versus healthy controls was evaluated, as well as if and how these polymorphic variants associate with different disease presentations (active disease vs non-active disease), different JIA subtypes, serum levels of 25-hydroxy-vitamin D and parathyroid hormone (PTH), and lumbar spine Z-score values (osteopenia vs normal bone mineral density). A great majority of our JIA patients (84.5%) showed a suboptimal vitamin D status, in many cases (84.1%) not solved by vitamin D supplementation. Vitamin D status resulted to be independent of VDR genotypes. ApaI genotypes showed a highly significant different distribution between JIA patients and unaffected controls, with both the TT genotype and the T allele significantly more frequent in patient group.

Determinants of vitamin D levels in children, adolescents, and young adults with juvenile idiopathic arthritis.

OBJECTIVE: Deficiency of 25-hydroxyvitamin D [25(OH)D] is reported to be common in patients with rheumatoid arthritis (RA); data in patients with juvenile idiopathic arthritis (JIA) are inconsistent. We assessed serum 25(OH)D in children, adolescents and young adults with JIA, in order to identify the risk factors for vitamin D deficiency in patients with JIA. METHODS: We evaluated 152 patients with JIA: 115 female, 37 male, mean age 16.2 ± 7.4 yrs; evaluated by onset type, 96 had oligoarticular, 35 polyarticular, 7 systemic, and 14 enthesitis-related arthritis (ERA). Patients were compared with a control group matched for sex and age. All patients and controls underwent laboratory tests of plasma 25(OH)D, parathyroid hormone (PTH), calcium, phosphorus, and bone alkaline phosphatase levels, and dual-energy x-ray absorptiometry examination. RESULTS: Patients with JIA showed significantly reduced 25(OH)D levels compared to controls (p < 0.001), even divided into subtypes (oligoarticular, p < 0.05; polyarticular, p < 0.005; systemic, p < 0.001; ERA, p < 0.005). Patients with active disease and/or frequent relapses had significantly reduced 25(OH)D levels compared to patients with no active disease and no frequent flares (p < 0.005, respectively). Nevertheless, JIA patients had significantly higher PTH levels compared to controls (p < 0.0001). JIA patients with 25(OH)D deficiency showed a significantly lower bone mineral apparent density than those with normal 25(OH)D levels (p < 0.001). CONCLUSION: JIA patients have reduced 25(OH)D and higher PTH values. This may explain at least in part why JIA patients, despite more effective current drugs, do not achieve bone-normal condition over time. JIA patients with more severe disease could require higher supplementation of vitamin D to maintain normal 25(OH)D serum levels. Longterm studies are needed to investigate the relationship between serum 25(OH)D levels and disease activity in JIA.

Vitamin D levels and effects of vitamin D replacement in children with periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome.

BACKGROUND: The periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease characterized by regularly recurrent fever episodes due to seemingly unprovoked inflammation. OBJECTIVE: To assess serum 25-hydroxyvitamin D [25(OH)D] concentrations in children with PFAPA syndrome and evaluate longitudinally the effect of wintertime vitamin D supplementation on the disease course. STUDY DESIGN: We have evaluated 25 Italian patients (19 males, 6 females, aged 2.4-5.3 years), fulfilling the Euro-Fever PFAPA criteria. For each patient, we recorded demographic and anthropometric data, clinical manifestations, serum calcium, phosphate, and 25(OH)D. After 400 IU vitamin D supplementation during wintertime, clinical and auxological characteristics, calcium, phosphate, and 25(OH)D levels were re-evaluated. Data were compared with a sex- and age-matched control group. RESULTS: PFAPA patients showed reduced 25(OH)D levels than controls (p<0.0001). Regarding the effect of seasons on vitamin D, winter 25(OH)D levels were significantly reduced than summer ones (p<0.005). Moreover, these levels were significantly lower than in healthy controls (p<0.005), and correlated with both fever episodes (p<0.005) and C-reactive protein values (p<0.005). After vitamin D supplementation, PFAPA patients showed a significantly decreased number of febrile episodes and modification of their characteristics (mean duration of fever episodes, p<0.05; number of febrile episodes per year p<0.005). CONCLUSIONS: Deficient and insufficient vitamin D serum levels were found in most children with PFAPA syndrome, and hypovitaminosis D might be a significant risk factor for PFAPA flares. However, vitamin D supplementation seems to significantly reduce the typical PFAPA episodes and their duration, supporting the role of vitamin D as an immune-regulatory factor in this syndrome.