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

BackgroundThe 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.ObjectiveTo 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 designWe 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.ResultsPFAPA 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).ConclusionsDeficient 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.