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FMF: another autoimmune disease associated with low vitamin D – Nov 2013

P01-025 – Decreased vitamin D levels in children with FMF

Presented at 7th Congress of International Society of Systemic Auto-Inflammatory Diseases (ISSAID), Lausanne, Switerland. 22-26 May 2013
B Makay1*, A Anık2, G Çatlı2, A Abacı2, T Küme3, E Böber2 and E Ünsal1
* Corresponding author: B Makay
1 Pediatric Rheumatology, Dokuz Eylül University Hospital, İzmir, Turkey
2 Pediatric Rheumatology, Dokuz Eylül University Hospital, İzmir, Turkey
3 biochemistry, Dokuz Eylül University Hospital, İzmir, Turkey

Introduction: Several recent studies have reported a link between vitamin D deficiency and certain chronic inflammatory disorders such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Behçet’s disease.These recent findings have led to greater emphasis on treatment of vitamin D deficiency and vitamin D supplementation in rheumatological diseases. To our knowledge, vitamin D levels have not been previously investigated in children with FMF disease.

Objectives: To determine the frequency of vitamin D deficiency in children with familial Mediterranean fever (FMF) and to investigate the factors associated with low vitamin D status.

Methods: Forty-four patients with FMF and 39 age- and sex-matched healthy controls were enrolled in this study. Demographic data, disease duration, time to delay for diagnosis, FMF symptoms, disease severity score, MEFV mutation, dose and duration of colchicine therapy and compliance to treatment were recorded for each patient. Serum 25- hydroxyvitamin D levels were measured by original commercial kit based on Chemiluminescent Microparticle İmmunoassay (CMIA) principle.

Results: The serum 25- hydroxyvitamin D levels were significantly lower in FMF patients than the healthy controls (12.9 ± 3.6 and 16.3 ± 5.5, respectively, p=0.001).
The vitamin D level was similar in patients homozygous for M694V and other genotypes (11.8 ± 3.7 and 13.2 ± 3.6, respectively, p=0.21).
There was a significant negative correlation between the duration and cumulative dose of colchicine use and vitamin D levels (r=-0.410, p=0.006 and r=-443, p=0.004, respectively).
There was no correlation between vitamin D levels and C-reactive protein, white blood cell count, disease duration, disease severity score or age of the patient.

Conclusion: The results of this study suggest that serum 25- hydroxyvitamin D levels are decreased in children with FMF.
Duration of colchicine use and cumulative colchicine dose appear to effect vitamin D levels negatively.


Decreased vitamin D levels in patients with familial mediterranean fever.

Rheumatol Int. 2013 May;33(5):1355-7. doi: 10.1007/s00296-011-2278-z. Epub 2011 Dec 21.
Kisacik B, Kaya SU, Pehlivan Y, Tasliyurt T, Sayarlioglu M, Onat AM.
Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Gaziantep University, 27100 Şahinbey, Gaziantep, Turkey. Bunyamin_k at hotmail.com

Familial mediterranean fever (FMF) is an autosomal recessive disorder caused by mutations in the FMF gene (MEFV). The gene causing FMF, designated MEFV, encodes a protein called pyrin or marenostrin that is expressed mainly in myeloid bone marrow precursors, neutrophils, and monocytes. Since there are several etiological factors, FMF is the most common periodic fever syndrome. However, it is still unknown what triggers or ends these periodical attacks. As a pleiotropic hormone, vitamin D has immunomodulation effects. The aim of this study was to evaluate the vitamin D levels in FMF patients. The study group was comprised of 26 patients diagnosed with FMF (men/women: 12/14), and 34 healthy control (men/women: 17/17). Vitamin D levels in FMF patients and healthy controls were 11.05 ± 7.11, 17.15 ± 6.49, respectively. FMF patients had significantly decreased vitamin D levels compared with healthy controls (P < 0.001). In conclusion, it is thought that vitamin D deficiency in FMF patients may trigger the attacks. Further studies with larger patient populations need to hold to investigate the vitamin D deficiency in patients with FMF and that may assist to clarify the mechanism behind the colchicines resistant cases.

PMID: 22187059


Low plasma vitamin D levels in patients with familial Mediterranean fever.

Rheumatol Int. 2012 Dec;32(12):3845-9. doi: 10.1007/s00296-011-2281-4. Epub 2011 Dec 23.
Erten S, Altunoğlu A, Ceylan GG, Maraş Y, Koca C, Yüksel A.
Department of Internal Medicine, Atatürk Education and Research Hospital, Ankara, Turkey. sukranerten at yahoo.com

Familial Mediterranean fever (FMF) is an autosomal recessive, inherited autoinflammatory disease characterized by recurrent, self-limited attacks of fever and inflammation of serosal surfaces. There is an explosion of the data regarding inflammatory markers in FMF and clinical effects of chronic inflammation on the disease presentation. Vitamin D (vit D) is the common denomination of a group of sterols with a crucial role in phospho-calcium metabolism. There are some data about the importance of vit D in the initiation and propogation of a range of autoimmune diseases. The aim of the present study was to determine whether vit D deficiency is present in patients with FMF compared with healthy individuals. The study group included 99 patients with diagnosis of FMF attended to our outpatient Rheumatology and Nephrology Clinics of Atatürk Education and Research Hospital. The control group comprised 51 age- and sex-matched healthy people selected from hospital staff. Serum baseline 25-hydroxy vit D levels were measured by HPLC method using an Agilent 1100 Liquid Chromatograph. We found significantly lower serum 25-hydroxy vit D levels among FMF patients compared with matched controls and a high prevalence of vit D deficiency. This study demonstrated that vit D deficiency is frequent in patients with FMF than the healthy controls. It is convenient to look for vit D deficiency and to correct vit D nutritional status in FMF patients.

PMID: 22193220


See also VitaminDWiki

See also web

  • Familial_Mediterranean_fever Wikipedia Nov 2013
    Familial Mediterranean fever (FMF), also known as Armenian disease is a hereditary inflammatory disorder
    FMF is an autoinflammatory disease caused by mutations in MEFV, a gene which encodes a 781–amino acid protein denoted pyrin
    FMF affects groups of people originating from around the Mediterranean Sea (hence its name).
    It is prominently present in the Armenians, Sephardi Jews (and, to a much lesser extent, Ashkenazi Jews), Cypriots, Turks, and Arabs.
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