The Association Between Vitamin D Level and PFAPA Syndrome: A Systematic Review

Periodic Fever, Aphthous Ulcers, Pharyngitis and Adenitis (PFAPA) Syndrome's etiology is not well understood. The objective of this study is to explore the association between vitamin D level and PFAPA syndrome. A systematic review of all publications addressing the association between vitamin D level and PFAPA syndrome prior to May 2019 was conducted. Data were collected from online medical databases namely, PubMed, Ovid Medline, Embase, Cochrane Library, Google Scholar, and Scopus. The review adhered to the PRISMA statement and was performed in 3 main phases; an initial screening review of abstracts was performed, followed by a detailed review of full articles based on inclusion and exclusion criteria, and lastly a final review to extract data from selected articles. 3 prospective review-based and one case report articles were included with a total of 281 patients, 98 of whom were cases of PFAPA, while 183 were controls. Vitamin D levels were deficient in 27% of PFAPA group as compared with the control. Vitamin D supplementation was given as an initial treatment in 25/98 of the patients. Only 1 patient received it as a second treatment. After vitamin D supplementation, a marked reduction of the number of febrile episodes and modification of the mean duration were recognized. There may be an association between Vitamin D deficiency and a higher frequency of PFAPA episodes. Vitamin D supplementation in children with PFAPA may reduce the frequency of episodes and help manage the condition.