Granülmatöz Hastalıkları ve D Vitamini
Özet
Granülo_matöz deri hastalıkları, histiyositlerin baskın olduğu granülom oluşumuyla karakterize heterojen bir gruptur. İmmünmodülatör ve antiinflamatuar etkileri olan D vitamini (DV), bu hastalıkların patogenezinde ve seyrinde önemli roller üstlenmektedir. Sarkoidozda granülomlardaki makrofajlarca sentezlenen ekstrarenal 1-alfa hidroksilaz enzimi, düzensiz 1,25(OH)2D3 (kalsitriol) üretimine ve dolayısıyla hiperkalsemi ile hiperkalsiüriye yol açar. Tüberkülozda DV eksikliği önemli bir risk faktörüdür; vitamin katelisidin aracılığıyla otofajiyi indükleyerek mikobakterilere karşı savunmayı destekler. Benzer şekilde kronik bir enfeksiyon olan leprada da DV eksikliği hastalık riskini artırmakta, makrofajların patojen öldürme kapasitesini etkileyen VDR ve katelisidin aktivitesi nedeniyle tedaviye DV takviyesi eklenmesi önerilmektedir. Wegener granülomatozunda (WG) ve derin fungal enfeksiyonlarda (özellikle histoplazmozis), granülom kaynaklı kontrolsüz kalsitriol üretimi nedeniyle "granüloma ilişkili hiperkalsemi" gelişebilir. Granülomatöz polianjiitiste (GPA) düşük DV seviyeleri hastalık aktivitesinden ziyade solunum yolu enfeksiyonu riskini artırırken, granüloma anularede kalsitriolün sitokin etkileşimleri sayesinde sistemik tedavide etkinliği varsayılmaktadır. Candida ile ilişkili protez stomatitinde ise DV düzeylerinin hastalık duyarlılığıyla doğrudan ilişkisi saptanmamıştır.
Granulomatous skin diseases represent a heterogeneous group characterized by the formation of histiocyte-dominated granulomas, where Vitamin D (VD) plays crucial regulatory roles due to its immunomodulatory and anti-inflammatory properties. In sarcoidosis, the extrarenal 1-alpha hydroxylase enzyme synthesized by macrophages within granulomas leads to unregulated 1,25(OH)2D3 (calcitriol) production, causing hypercalcemia and hypercalciuria. VD deficiency serves as a significant risk factor in tuberculosis, as the vitamin enhances mycobacterial defense by inducing autophagy via cathelicidin. Similarly, in leprosy, a chronic infection, low VD levels increase disease susceptibility, and incorporating VD supplementation into multidrug therapy is advised since the VDR-calcitriol interaction modulates macrophage pathogen-killing capacity through cathelicidin expression. Uncontrolled granuloma-derived calcitriol synthesis can also trigger granuloma-associated hypercalcemia in Wegener's granulomatosis and deep fungal infections like histoplasmosis. While low VD concentrations in granulomatosis with polyangiitis correlate with an increased risk of respiratory tract infections rather than overall disease activity, systemic calcitriol shows therapeutic potential in granuloma annulare through its interaction with tissue cytokines. Conversely, VD levels demonstrate no significant correlation with host susceptibility or onset in Candida-associated denture stomatitis.
Referanslar
Rota DD, Emeksiz MC. Granülomatöz deri enfeksiyonları. Turkderm-Turk Arch Dermatol Venereol, 2021; 55: 1-8.
Kulie T, Groff A, Redmer J, et al. Vitamin D: An Evidence-Based Review. The Journal of the American Board of Family MedicinE. 2009;22(6):698-706.
Büyükdere Y, Ayaz A. Tüberküloz ve D vitamini arasındaki ilişkinin değerlendirilmesi: Güncel yaklaşımlar. Sakarya Med J, 2019; 9: 565-73.
Tekin NS. Sarkoidoz. Turk J Dermatol, 2012; 6: 80-6.
Burke RR, Rybicki BA, Rao SD. Calcium and vitamin D in sarcoidosis: how to assess and manage. Semin Respir Crit Care Med, 2010; 31 (4): 474-84.
Gianella F, Hsia CC, Sakhaee K. The role of vitamin D in sarcoidosis. Fac Rev, 2020; 9: 14.
Spiro A, Buttriss JL. Vitamin D: An overview of vitamin D status and intake in Europe. Nutr Bull, 2014; 39: 322-50.
Kiani A, Abedini A, Adcock MI, et al. Association Between Vitamin D Deficiencies in Sarcoidosis with Disease Activity, Course of Disease and Stages of Lung Involvements. J Med Biochem. 2018;37(2):103-9.
Kamphuis SL, Bonte-Mineur F, Laar JA, et al. Calcium and vitamin D in sarcoidosis: is supplementation safe? J Bone Miner Res. 2014;29(11):2498-503.
Dini C, Bianchi A. The potential role of vitamin D for prevention and treatment of tuberculosis and infectious diseases. Ann Ist Super Sanita, 2012; 48 (3): 319-27.
Nouri-Vaskeh M, Sadeghifard S, Saleh P. Vitamin D Deficiency among Patients with Tuberculosis: a Cross-Sectional Study in Iranian-Azari Population. Tanaffos, 2019; 18 (1): 11-7.
Brighenti S, Bergman P, Martineau AR. Vitamin D and tuberculosis: where next? J Intern Med, 2018; 284: 145-62.
Mozart Darus NI, Dumasari Lubis R, Karmila Jusuf N. Analysis of Serum Vitamin D Level in Leprosy Patients. Bali Medical Journal, 2019; 8 (3): 795-9.
Dennison C, B de Oliveira L, A de O Fraga L. Mycobacterium leprae-helminth co-infections and vitamin D deficiency as potential risk factors for leprosy: A case-control study in south-eastern Brazil. Int J Infect Dis, 2021; 105: 261-6.
Bosch X, López-Soto A, Morelló A, et al. Vitamin D metabolite-mediated hypercalcemia in Wegener's granulomatosis . Mayo Clin Proc. 1997;72(5):440-4.
Perez MO, Oliveira RM, Mauricio Levy-Neto M, et al. Serum 25-hydroxyvitamin D levels in patients with Granulomatosis with Polyangiitis: association with respiratory infection. Clinics (Sao Paulo). 2017;72(12):723-8.
Alan S Boyd. Granuloma annulare responsive to oral calcitriol. Int J Dermatol, 2012; 51 (1): 120-2.
Wang IK, Shen TS, Lee KF, et al. Hypercalcemia and elevated serum 1.25-dihydroxyvitamin D in an end-stage renal disease patient with pulmonary cryptococcosis. Ren Fail. 2004;26(3):333-8.
Murray JJ, Heim CR. Hypercalcemia in disseminated histoplasmosis. Aggravation by vitamin D. Am J Med, 1985; 78 (5): 881-4.
Muhvić-Urek M, Saltović E, Braut A, Pavičić DK. Association between Vitamin D and Candida-Associated Denture Stomatitis. Dent J (Basel), 2020; 8 (4): 121.
