Serum vitamin D level in Egyptian children with Familial Mediterranean fever
Introduction
FMF (MIM 249100) which is an autosomal recessive periodic fever syndrome is most common among hereditary recurrent inflammatory disorders [1]. The disease affects populations of Mediterranean descent; Arabs, Armenians, Turks, non-Ashkenazi,other Jews, Druzes, Lebanese, Italians, and Greeks. Patients have also been described in Japan [2].
The disease is characterized by recurrent flares of systemic inflammation presenting as fever associated with a number of clinical manifestations and a dramatic rise in acute phase reactants. Rash, serositis (peritonitis, pleuritis), lymphadenopathy and arthritis are the main associated clinical manifestations [3]. Disease flares are usually separated by symptom-free intervals of variable duration [4]. Mediterranean fever gene (MEFV); responsible for FMF is located on the short arm of chromosome 16 and encodes pyrin; a protein that has a role in suppression of inflammation. Mutations in MEFV gene cause uncontrolled innate immune response through overproduction of interleukin-1β and tumor necrosis factor-α [5]. Inflammation is the main pathology in FMF attacks and some patients experience it even in attack-free periods. This chronic inflammation may cause complications such as splenomegaly, anemia, decrease bone mineral density, growth retardation and amyloidosis [6].
Vitamin D is a fat-soluble vitamin with a fundamental role in calcium metabolism. Exposure of the skin to the UVR of the sun is a major source of Vitamin D in the body. After hydroxylation in the liver and kidney, the active metabolite (1,25dihydroxy vitamin D) can enter the cell, bind to the vitamin D-receptor and mediates calcium absorption from the gut [7]. It also modulates adaptive immunity to minimize inflammation and autoimmunity [8] .Moreover it helps proliferation of inhibitory T-cells and shift towards T-helper 2 response, which produces suppressive IL-10 and IFN-γ [9]. Thus, a compromised vitamin D status was linked to the pathogenesis of many inflammatory diseases [10], such as SLE [11], JIA [12], and Behcet’s disease [13] .Few researches have studied serum vitamin D level in children with FMF compared with healthy controls [14], [15], [16].
Vitamin D deficiency is a worldwide problem especially in the Middle East, with a Prevalence of Vitamin D deficiency ranging between 30 and 90% when the cut-off used is 20 ng/mL [17], [18]. The aim of the present study was to measure plasma vitamin D levels in Egyptian children with FMF compared to healthy controls and study its effect; if any; on disease severity, subclinical inflammation.
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Patients and methods
This cross sectional study enrolled 92 children, 52 patients diagnosed as FMF according to criteria defined by Yalcınkaya et al. [19]. All patients were following up at the Pediatric Rheumatology Clinic, Specialized Children Hospital of Cairo University during the period from October 2014 to October 2015. Forty apparently healthy children, age-, gender and body mass index (BMI) matched, coming for regular follow-up at the outpatient clinic were also included.
None of our patients had chronic
Results
The study included 52 Egyptian children with FMF, and 40 apparently healthy controls. Twenty-eight patients were males and 24 were females (male to Female ratio 1.16:1). The mean age at diagnosis was 6.4 ± 3.2 years. The mean disease duration was 4.3 ± 2.8 years (range 0.3-12.0 years). Parents of (32.7%) of patients were consanguineous. The demographic and the presenting FMF manifestations of the study group were summarized in Table 1.
The most frequent clinical manifestations of FMF attacks were
Discussion
This study was able to detect a significant decrease in the serum level of vitamin D in children with FMF compared to the control group.
No significant correlation was detected between vitamin D level and acute phase reactants. This was in concordance with the results of Anik et al. [14] showing insignificant correlation between serum vitamin D level and acute phase reactants. Our patients displayed a much higher titer of CRP (12 ± 8.3 versus 4.7 ± 8.7) either due to low colchicine dose tolerated by
Conflict of interest
The authors declare that they have no conflict of interest.
Contribution
Prof. Dr. Hala M Lotfy: supervision of data collection, revision of the statistical analysis of the results, writing and revising the manuscript, and corresponding for publication.
Dr. Huda Marzouk: idea, data collection, revision of the statistical analysis of the result, writing and revising the results, revising the manuscript.
Dr. Yomna Farag: data collection, revision of the statistical analysis of the results, writing and revising the manuscript.
Dr. Ahmed Salah: revision of results and
Ethical approval
The Cairo University Clinical Research Ethics Committee approved this study, and informed consents were obtained from parents of all participants.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Acknowledgments
Special thanks to all pediatric rheumatology clinic members, who helped us in our work, and to our dear patients, who participated in conducting the study.
References (30)
- et al.
Guidelines for the management and treatment of periodic fever syndromes familial Mediterranean fever
Rev. Bras. Reumatol. Engl. Ed.
(2016) Vitamin D physiology
Prog. Biophys. Mol. Biol.
(2006)- et al.
Vitamin D3 metabolite calcidiol primes human dendritic cells to promote the development of immunomodulatory IL-10-producing T cells
Vaccine
(2014) - et al.
Vitamin D in rheumatoid arthritis
Autoimmun. Rev.
(2007) - et al.
Microtubules mediate cellular 25-hydroxyvitamin D3 trafficking and the genomic response to 1,25-dihydroxyvitamin D3 in normal human monocytes
J. Biol. Chem.
(1995) - et al.
Colchicine is a safe drug in children with familial Mediterranean fever
J. Pediatr.
(2012) - et al.
Vitamin D status in patients with behcet's disease
Clinics (Sao Paulo)
(2011) - et al.
Subclinical vitamin D deficiency is increased in adolescent girls who wear concealing clothing
J. Nutr.
(2005) - et al.
A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin
Nat. Rev. Rheumatol.
(2014) - et al.
Familial Mediterranean fever is no longer a rare disease in Japan
Arthritis Res. Ther.
(2016)
Criteria for the diagnosis of familial Mediterranean fever
Arthritis Rheum.
Mutations/polymorphisms in a monogenetic autoinflammatory disease may be susceptibility markers for certain rheumatic diseases: lessons from the bedside for the benchside
Clin. Exp. Rheumatol.
Chronic inflammation in FMF: markers, risk factors, outcomes and therapy
Nat. Rev. Rheumatol.
The role of vitamin D in gastrointestinal inflammation
Expert Rev. Gastroenterol. Hepatol.
Vitamin D and calcium insufficiency-related chronic diseases: molecular and cellular pathophysiology
Eur. J. Clin. Nutr.
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