Behçet Hastalığı ve D Vitamini
Özet
Behçet hastalığı (BH); oral aftlar, genital ülserler ve oküler tutulumla karakterize, kökeni bilinmeyen kronik sistemik bir vaskülittir. Genetik ve çevresel faktörlerin rol oynadığı bu hastalıkta, bağışıklık sistemini düzenleyici (immünmodülatör) etkisiyle bilinen D vitamininin payı son yıllarda sıkça araştırılmaktadır. D vitamini, vitamin D reseptörleri (VDR) aracılığıyla T ve B lenfositler, makrofajlar ile dendritik hücreler üzerinde baskılayıcı bir etki göstererek inflamasyonu modüle eder. Yapılan çalışmaların büyük çoğunluğu, Behçet hastalarında serum D vitamini düzeylerinin sağlıklı kontrollere kıyasla istatistiksel olarak anlamlı derecede düşük olduğunu ortaya koymaktadır. Aktif hastalık dönemlerinde D vitamini seviyelerinin daha da gerilediği, eritrosit sedimentasyon hızı (ESR) ve C-reaktif protein (CRP) gibi inflamasyon belirteçleri ile negatif bir korelasyon gösterdiği belirlenmiştir. Ayrıca, mukokutanöz tutulumların tedavisinde ilk tercih olan kolşisin kullanımı ile yaş, alkol ve sigara tüketiminin de düşük D vitamini düzeylerini öngördüren bağımsız faktörler olduğu saptanmıştır. Bazı genetik çalışmalarda ise VDR gen polimorfizmlerinin (FokI, BsmI, Apal) Türk ve Mısır popülasyonlarında hastalık patogenezi ve klinik bulgularla ilişkili olabileceği öne sürülmüştür. Sonuç olarak, sınırlı ve heterojen verilere rağmen D vitamininin günlük pratikte Behçet hastalarına profilaktik veya destekleyici bir tedavi seçeneği olarak sunulması önerilmektedir.
Behçet's disease (BD) is a chronic systemic vasculitis of unknown origin, characterized by oral aphthae, genital ulcers, and ocular involvement. In this disease, where genetic and environmental factors play a role, the impact of vitamin D, known for its immunomodulatory effects on the immune system, has been frequently investigated in recent years. Vitamin D modulates inflammation through vitamin D receptors (VDR) by exerting a suppressive effect on T and B lymphocytes, macrophages, and dendritic cells. The vast majority of studies demonstrate that serum vitamin D levels in patients with BD are statistically significantly lower compared to healthy controls. It has been determined that vitamin D levels decline further during active disease periods and show a negative correlation with inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Furthermore, the use of colchicine, which is the primary choice in treating mucocutaneous involvements, along with age, alcohol, and smoking consumption, have been identified as independent factors predicting low vitamin D levels. Some genetic studies have suggested that VDR gene polymorphisms (FokI, BsmI, Apal) might be associated with disease pathogenesis and clinical findings in Turkish and Egyptian populations. Consequently, despite limited and heterogeneous data, it is recommended to offer vitamin D as a prophylactic or supportive treatment option for BD patients in daily practice.
Referanslar
Avci A, Avci D, Erden F, et al. Can we use the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume values for the diagnosis of anterior uveitis in patients with Behcet’s disease? Ther Clin Risk Manag. 2017;13:881-6. doi:10.2147/TCRM.S135260
Dalvi SR, Yildirim R, Yazici Y. Behcet ’ s Syndrome. 2012;72(17):2223-41.
Adeeb F, Khan MU, Li X, et al. High Vitamin D Levels May Downregulate Inflammation in Patients with Behçet’s Disease. Int J Inflam. 2017;2017. doi:10.1155/2017/8608716
Ertaş R, Özyurt K, Avci A, et al. Case Report: Behçet’s disease accompanied with vitiligo. F1000Research. 2017;6:2-7. doi:10.12688/f1000research.11025.1
Mohammad A, Mandl T, Sturfelt G, Segelmark M. Incidence, prevalence and clinical characteristics of Behcet’s disease in southern Sweden. Rheumatology (Oxford). 2013;52(2):304-10. doi:10.1093/rheumatology/kes249
Çölgeçen E, Özyurt K, Ferahbaş A, et al. The prevalence of Behçet’s disease in a city in Central Anatolia in Turkey. Int J Dermatol. 2015;54(3):286-9. doi:10.1111/ijd.12173
Atil A, Deniz A, Levent CS, et al. Effect of anterior uveitis in Behçet’s disease on neutrophil to lymphocyte ratio. Int Eye Sci. 2016;16(4):607-9. doi:10.3980/j.issn.1672-5123.2016.4.04
Avcı A, Avcı D, Atasoy M, et al. Clinical Characteristics of Patients with Behçet’s Disease Followed at Outpatient Clinic of Chronic Dermatological Diseases. Turkish J Dermatology / Türk Dermatoloji Derg. 2017;11(2):66-9. doi:10.4274/tdd.3117
Henry HL. Regulation of vitamin D metabolism. Best Pract Res Clin Endocrinol Metab. 2011;25(4):531-41. doi:10.1016/j.beem.2011.05.003
Haussler MR, Whitfield GK, Kaneko I, et al. Molecular mechanisms of vitamin D action. Calcif Tissue Int. 2013;92(2):77-98. doi:10.1007/s00223-012-9619-0
Shirvani SS, Nouri M, Sakhinia E, et al. The expression and methylation status of vitamin D receptor gene in Behcet’s disease. Immunity, Inflamm Dis. 2019;7(4):308-17. doi:10.1002/iid3.275
Pelajo CF, Lopez-Benitez JM, Miller LC. Vitamin D and Autoimmune Rheumatologic Disorders. Autoimmun Rev. 2010;9(7):507-10. doi:10.1016/j.autrev.2010.02.011
Cantorna MT, Yu S, Bruce D. The paradoxical effects of vitamin D on type 1 mediated immunity. Mol Aspects Med. 2008;29(6):369-75. doi:10.1016/j.mam.2008.04.004
Zella JB, McCary LC, DeLuca HF. Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus. Arch Biochem Biophys. 2003;417(1):77-80. doi:10.1016/s0003-9861(03)00338-2
Umar M, Sastry KS, Al Ali F, et al. Vitamin D and the Pathophysiology of Inflammatory Skin Diseases. Skin Pharmacol Physiol. 2018;31(2):74-86. doi:10.1159/000485132
Mahon BD, Wittke A, Weaver V, Cantorna MT. The targets of vitamin D depend on the differentiation and activation status of CD4 positive T cells. J Cell Biochem. 2003;89(5):922-32. doi:10.1002/jcb.10580
Aslan N, Demirci K, Güler T, et al. The effect of Vitamin D on clinical manifestations and activity of Behçet’s disease. Postep Dermatologii i Alergol. 2017;34(1):15-20. doi:10.5114/pdia.2016.57222
Sadeghi K, Wessner B, Laggner U, et al. Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns. Eur J Immunol. 2006;36(2):361-70. doi:10.1002/eji.200425995
Piotrowska A, Wierzbicka J, Zmijewski MA. Vitamin D in the skin physiology and pathology. Acta Biochim Pol. 2016;63(1):17-29. doi:10.18388/abp.2015_1104
Alpsoy E. Behçet disease: An update in ethiopathogenesis. Turk Dermatoloji Derg. 2013;7(1):41-5.
Direskeneli H, Saruhan-Direskeneli G. The role of heat shock proteins in Behçet’s disease. Clin Exp Rheumatol. 2003;21(4 Suppl 30):S44-8.
Raziuddin S, al-Dalaan A, Bahabri S, et al. Divergent cytokine production profile in Behçet’s disease. Altered Th1/Th2 cell cytokine pattern. J Rheumatol. 1998;25(2):329-33.
Karatay S, Yildirim K, Karakuzu A, et al. Vitamin D status in patients with Behcet’s disease. Clinics. 2011;66(5):721-3. doi:10.1590/S1807-59322011000500002
Faezi ST, Ansari N, Paragomi P, et al. Vitamin D deficiency in patients with Behcet’s disease. J Diabetes Metab Disord. 2014;13(1):1-5. doi:10.1186/2251-6581-13-18
Khabbazi A, Rashtchizadeh N, Ghorbanihaghjo A, et al. The status of serum vitamin D in patients with active Behcet’s disease compared with controls. Int J Rheum Dis. 2014;17(4):430-4. doi:10.1111/1756-185X.12153
Can M, Gunes M, Haliloglu OA, et al. Effect of vitamin D deficiency and replacement on endothelial functions in Behçet’s disease. Clin Exp Rheumatol. 2012;30(3 Suppl 72):S57—61. http://europepmc.org/abstract/MED/23020973.
Veysel Sucu, Müberra Vardar, Ralfi Singer, Mustafa Durmuşcan OD. Behçet Hastalığında Plazma Vitamin D3 düzeylerinin Hastalık Aktivitesi ve İnflamasyon Belirteçleri ile ilişkisi. Türk Klin Biyokim Derg. 2019;17(1):1-9.
Hamzaoui K, Dhifallah I Ben, Karray E, et al. Vitamin D modulates peripheral immunity in patients with Behçet’s disease. Clin Exp Rheumatol. 2010;28(4 SUPPL. 60).
Ganeb SS, Sabry HH, El-Assal MM, et al. Vitamin D levels in patients with behçet’s disease: Significance and impact on disease measures. Egypt Rheumatol. 2013;35(3):151-7. doi:10.1016/j.ejr.2013.01.006
Alnahas Z, Menyawi M El, Fawzy M, et al. 173. 25-Hydroxyvitamin D3 Deficiency and Vitamin D Receptor Polymorphisms in Egyptian Behçet’S Disease Patients: a Pilot Study. Rheumatology. 2019;58(Supplement_2):20-7. doi:10.1093/rheumatology/kez060
Kandi B, Cicek D, Ilhan N. Vitamin levels in Behçet’s disease. J Dermatolog Treat. 2007;18(2):69-75. doi:10.1080/09546630601156355
Kechida M, Harzallah O, Hellara I, et al. Vitamin D status of Behcet’s patients. Analysis of correlation with activity and severity of the disease as well as with the quality of life of patients. Int Arch Med. 2015:1-7. doi:10.3823/1850
Do JE, Kwon SY, Park S, Lee ES. Effects of vitamin D on expression of Toll-like receptors of monocytes from patients with Behçet’s disease. Rheumatology. 2008;47(6):840-8. doi:10.1093/rheumatology/ken109
Ertaş R, Avcı A. Treatment of Systemic Involvement of Behçet’s Disease. Behcet’s Dis - A Compil Recent Res Rev Stud. SM Group 2017:1-13.
Ertaş ŞK, Yıldırım A. Musculoskeletal System Involvement in Behçet’s Disease. Behcet’s Dis - A Compil Recent Res Rev Stud. SM Group 2017:1-10.
Anık A, Catlı G, Makay B, et al. Decreased vitamin D levels in children with familial Mediterranean fever. Int J Rheum Dis. 2014;17(3):321-6. doi:10.1111/1756-185X.12253
Erten S, Altunoğlu A, Ceylan GG, et al. Low plasma vitamin D levels in patients with familial Mediterranean fever. Rheumatol Int. 2012;32(12):3845-3849. doi:10.1007/s00296-011-2281-4
Ganeb SS, Sabry HH, El-Assal MM, et al. Vitamin D levels in patients with behçet’s disease: Significance and impact on disease measures. Egypt Rheumatol. 2013;35(3):151-7. doi:10.1016/j.ejr.2013.01.006
Erten G, Kalkan M, Bilgiç Gazioǧlu S, et al. TaqI, FokI, and ApaI Polymorphisms in the Vitamin D Receptor in Behçet’s Disease in Turkish Population. Dis Markers. 2016;2016. doi:10.1155/2016/7475080
Al-Nahas Z, Fawzy M, El Menyawi M, et al. 25-hydroxyvitamin D3 deficiency and vitamin D receptor polymorphisms in Egyptian patients with Behçet’s disease: a pilot study. Int J Clin Rheumtol. 2017;12:20-7.
Pitukweerakul S, Sinyagovskiy P, Prachuapthunyachart S. The association between vitamin D level and Behcet’s disease: a meta-analysis. Int J Rheum Dis. 2017;20(12):2217-8. doi:10.1111/1756-185X.13108
Çifci N. D vitamini düzeylerinin deri hastalıkları üzerine etkisinin retrospektif değerlendirilmesi. Kocaeli Tıp Derg. 2018;7(3):47-54.
Kul A, Erdal A. Bone Mineral Density and Vitamin D Values in Behçet’s Disease. Turkish J Osteoporos. 2018;24(3):78-83. doi:10.4274/tod.galenos.2018.16362
Dal NE, Cerci P, Olmez U, Keskin G. The role of vitamin D receptor gene polymorphisms in the pathogenesis of Behçet’s disease: A case-control study in Turkish population. Ann Hum Genet. 2019;83(3):177-86. doi:10.1111/ahg.12301
