Vitiligo y vitamina D
Resumen
El vitiligo es la despigmentación cutánea adquirida más común. Se caracteriza por máculas acrómicas que afectan la autoimagen de los pacientes e impactan negativamente su calidad de vida. En cuanto a las teorías sobre la etiopatogénesis del vitiligo, está la autoinmunidad. Se ha demostrado que hay un déficit de vitamina D en numerosas enfermedades autoinmunitarias.
La vitamina D es una hormona esencial con efectos pleiotrópicos y funciones especialmente antiapoptóticas y modificadoras de la proliferación y diferenciación de los melanocitos. Hipotéticamente, puede desempeñar un papel coadyuvante en la repigmentación de las lesiones vitiliginosas. La actividad inmunorreguladora de la vitamina D podría ser utilizada en el tratamiento del vitiligo.
A continuación, se hace una revisión de tema sobre el vitiligo, su relación con las concentraciones de la vitamina D y las influencias que podría tener en la fisiopatología; además, se analiza su posible uso como herramienta terapéutica para el vitiligo. El comportamiento de los niveles de vitamina D en rangos de deficiencia e insuficiencia entre pacientes con vitiligo y controles sanos son controversiales; algunos muestran niveles más bajos en el grupo de vitiligo y otros no muestran diferencias entre los grupos. A pesar de lo anterior, los estudios recientes sugieren una relación entre la insuficiencia de vitamina D en pacientes con vitiligo y un riesgo mayor de padecer otras enfermedades autoinmunitarias y que el uso de dosis altas de vitamina D en pacientes con vitiligo podría mejorar la repigmentación. La información revisada permite concluir que la relación entre el vitiligo y los niveles de vitamina D requiere de más estudios que aclaren su papel en la inmunopatogénesis y en la probabilidad de recomendar su uso terapéutico.
Referencias bibliográficas
Grimes PE. Vitiligo: pathogenesis, clinical features, and diagnosis. En: Tsao H (editor). UpToDate; 2016. Recuperado de: http://www.uptodate.com/contents/vitiligo-pathogenesis-clinical-features-and-diagnosis?source5search_result&search5grimes1vitiligo&selectedTitle54%7E88.
Iannella G, Greco A, Didona D, Didona B, Granata G, Manno A, et al. Vitiligo: Pathogenesis, clinical variants and treatment approaches. Autoimmun Rev. 2016;15(4):335-43. doi: 10.1016/j.autrev.2015.12.006.
https://doi.org/10.1016/j.autrev.2015.12.006
Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: a comprehensive overview. Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011;65(3):473-91. doi: 10.1016/j.jaad.2010.11.061.
https://doi.org/10.1016/j.jaad.2010.11.061
Birlea SA, Costin GE, Norris DA. New insights on therapy with vitamin D analogs targeting the intracellular pathways that control repigmentation in human vitiligo. Med Res Rev. 2009;29(3):514-46. doi: 10.1002/med.20146.
https://doi.org/10.1002/med.20146
Taieb A, Alomar A, Böhm M, Dell'Anna ML, De Pase A, Eleftheriadou V, et al. Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Br J Dermatol. 2013;168(1):5-19. doi: 10.1111/j.1365-2133.2012.11197.x.
https://doi.org/10.1111/j.1365-2133.2012.11197.x
Yazdani Abyaneh M, Griffith RD, Falto-Aizpurua L, Nouri K. Narrowband ultraviolet B phototherapy in combination with other therapies for vitiligo: mechanisms and efficacies. J Eur Acad Dermatol Venereol. 2014;28(12):1610-22. doi: 10.1111/jdv.12619.
https://doi.org/10.1111/jdv.12619
Xu H, Elmets CA. UVB immunosuppression: vitamin D or not vitamin D? That is the question. J Invest Dermatol. 2012;132(12):2676-8. doi: 10.1038/jid.2012.327.
https://doi.org/10.1038/jid.2012.327
Silverberg JI, Silverberg AI, Malka E, Silverberg NB. A pilot study assessing the role of 25 hydroxy vitamin D levels in patients with vitiligo vulgaris. J Am Acad Dermatol. 2010;62(6):937-41. doi: 10.1016/j.jaad.2009.11.024.
https://doi.org/10.1016/j.jaad.2009.11.024
Silva de Castro CC, do Nascimento LM, Olandoski M, Mira MT. A pattern of association between clinical form of vitiligo and disease-related variables in a Brazilian population. J Dermatol Sci. 2012;65(1):63-7. doi: 10.1016/j.jdermsci.2011.09.011.
https://doi.org/10.1016/j.jdermsci.2011.09.011
Mchepange UO, Gao XH, Liu YY, Liu YB, Ma L, Zhang L, et al. Vitiligo in North-Eastern China: An association between mucosal and acrofacial lesions. Acta Derm Venereol. 2010;90(2):136-40.
https://doi.org/10.2340/00015555-0799
Ohguchi R, Kato H, Furuhashi T, Nakamura M, Nishida E, Watanabe S, et al. Risk factors and treatment responses in patients with vitiligo in Japan--A retrospective large-scale study. Kaohsiung J Med Sci. 2015;31(5):260-4. doi: 10.1016/j.kjms.2015.02.003.
https://doi.org/10.1016/j.kjms.2015.02.003
Casas MY, Torres PA. Enfermedad ocular y auditiva asociada al vitiligo. Rev Asoc Colomb Dermatol. 2017;24(1):29-37.
https://doi.org/10.29176/2590843X.319
Kawakami T, Hashimoto T. Disease severity indexes and treatment evaluation criteria in vitiligo. Dermatol Res Pract. 2011;2011:750342. doi: 10.1155/2011/750342.
https://doi.org/10.1155/2011/750342
van Geel N, Lommerts J, Bekkenk M, Wolkerstorfer A, Prinsen CAC, Eleftheriadou V, et al. Development and validation of the Vitiligo Extent Score (VES): an International Collaborative Initiative. J Invest Dermatol. 2016;136(5):978-84. doi: 10.1016/j.jid.2015.12.040.
https://doi.org/10.1016/j.jid.2015.12.040
Kohli I, Veenstra J, Hamzavi I. Vitiligo assessment methods - Vitiligo Area Scoring Index and Vitiligo European Task Force assessment. Br J Dermatol. 2015;172(2):318-9. doi: 10.1111/bjd.13531.
https://doi.org/10.1111/bjd.13531
van Geel N, Lommerts JE, Bekkenk MW, Prinsen CA, Eleftheriadou V, Taieb A, et al. Development and validation of a patient-reported outcome measure in vitiligo: The Self Assessment Vitiligo Extent Score (SA-VES). J Am Acad Dermatol. 2017;76(3):464-71. doi: 10.1016/j.jaad.2016.09.034.
https://doi.org/10.1016/j.jaad.2016.09.034
Lotti T, Buggiani G, Troiano M, Assad GB, Delescluse J, De Giorgi V, et al. Targeted and combination treatments for vitiligo comparative evaluation of different current modalities in 458 subjects. Dermatol Ther. 2008;21 Suppl 1:S20-6. doi: 10.1111/j.1529-8019.2008.00198.x.
https://doi.org/10.1111/j.1529-8019.2008.00198.x
Khurrum H, AlGhamdi KM. The relationship between the serum level of vitamin D and vitiligo: A controlled study on 300 subjects. J Cutan Med Surg. 2016;20(2):139-45. doi: 10.1177/1203475415610071.
https://doi.org/10.1177/1203475415610071
Saleh HMA, Abdel Fattah NSA, Hamza H-TMM. Evaluation of serum 25-hydroxyvitamin D levels in vitiligo patients with and without autoimmune diseases: Serum 25-hydroxyvitamin D levels in vitiligo. Photodermatol Photoimmunol Photomed. 2013;29(1):34-40. doi: 10.1111/phpp.12016.
https://doi.org/10.1111/phpp.12016
Dell'Anna ML, Mastrofrancesco A, Sala R, Venturini M, Ottaviani M, Vidolin AP, et al. Antioxidants and narrow band-UVB in the treatment of vitiligo: A double-blind placebo controlled trial. Clin Exp Dermatol. 2007;32(6):631-6.
https://doi.org/10.1111/j.1365-2230.2007.02514.x
Takci Z, Tekin Ö, Ertuğru DT, Karadağ AS, Akin KO. A case-control study: evaluation of vitamin D metabolism in patients with vitiligo. Turk J Med Sci. 2015;45(4):837-41.
https://doi.org/10.3906/sag-1405-17
Kechichian E, Ezzedine K. Vitamin D and the skin: An update for dermatologists. Am J Clin Dermatol. 2018;19(2):223-35. doi: 10.1007/s40257-017-0323-8.
https://doi.org/10.1007/s40257-017-0323-8
Lips P. Worldwide status of vitamin D nutrition. J Steroid Biochem Mol Biol. 2010;121(1-2):297-300. doi: 10.1016/j.jsbmb.2010.02.021.
https://doi.org/10.1016/j.jsbmb.2010.02.021
Mostafa WZ, Hegazy RA. Vitamin D and the skin: Focus on a complex relationship: A review. J Adv Res. 2015;6(6):793-804. doi: 10.1016/j.jare.2014.01.011.
https://doi.org/10.1016/j.jare.2014.01.011
Harinarayan CV, Holick MF, Prasad UV, Vani PS, Himabindu G. Vitamin D status and sun exposure in India. Dermatoendocrinol. 2013;5(1):130-41. doi: 10.4161/derm.23873.
https://doi.org/10.4161/derm.23873
Pludowski P, Grant WB, Bhattoa HP, Bayer M, Povoroznyuk V, Rudenka E, et al. Vitamin D status in Central Europe. Int J Endocrinol. 2014;2014:589587. doi: 10.1155/2014/589587.
https://doi.org/10.1155/2014/589587
Vanchinathan V, Lim HW. A dermatologist's perspective on vitamin D. Mayo Clin Proc. 2012;87(4):372-80. doi: 10.1016/j.mayocp.2011.12.010.
https://doi.org/10.1016/j.mayocp.2011.12.010
Wadwa B, Relhan V, Goel K, Kochhar A, Garg V. Vitamin D and skin diseases: A review. Indian J Dermatol Venereol Leprol. 2015;81(4):344-55. doi: 10.4103/0378-6323.159928.
https://doi.org/10.4103/0378-6323.159928
Birlea SA, Costin GE, Norris DA. Cellular and molecular mechanisms involved in the action of vitamin D analogs targeting vitiligo depigmentation. Curr Drug Targets. 2008;9(4):345-59.
https://doi.org/10.2174/138945008783954970
Huang CL, Nordlund JJ, Boissy R. Vitiligo: a manifestation of apoptosis? Am J Clin Dermatol. 2002;3(5):301-8.
https://doi.org/10.2165/00128071-200203050-00001
Ben-Shoshan M. Vitamin D deficiency/insufficiency and challenges in developing global vitamin D fortification and supplementation policy in adults. Int J Vitam Nutr Res. 2012;82(4):237-59. doi: 10.1024/0300-9831/a000117.
https://doi.org/10.1024/0300-9831/a000117
Kulling PM, Olson KC, Olson TL, Feith DJ, Loughran TP Jr. Vitamin D in hematological disorders and malignancies. Eur J Haematol. 2017 Mar;98(3):187-197. doi: 10.1111/ejh.12818. Epub 2016 Nov 21.
https://doi.org/10.1111/ejh.12818
UV exposure guidance: a balanced approach between health risks and health benefits of UV and vitamin D. Prog Biophys Mol Biol. 2006;92(1):1-184.
Díaz ME, Llinas A. Niveles de vitamina D y prevalencia de déficit de vitamina D" en mujeres postmenopáusicas mayores de 50 años en Bogotá [Internet]. Universidad del Rosario - Universidad CES; 2014 [cited 2017 Feb 26]. Recuperado de: http://repository.urosario.edu.co/bitstream/handle/10336/9037/80871284-2014.pdf?sequence=5&isAllowed=y.
Van der Meer IM, Middelkoop BJC, Boeke AJP, Lips P. Prevalence of vitamin D deficiency among Turkish, Moroccan, Indian and sub-Sahara African populations in Europe and their countries of origin: an overview. Osteoporos Int. 2011;22(4):1009-21. doi: 10.1007/s00198-010-1279-1.
https://doi.org/10.1007/s00198-010-1279-1
Reichrath J, Zouboulis CC, Vogt T, Holick MF. Targeting the vitamin D endocrine system (VDES) for the management of inflammatory and malignant skin diseases: An historical view and outlook. Rev Endocr Metab Disord. 2016;17(3):405-17.
https://doi.org/10.1007/s11154-016-9353-4
Piotrowska A, Wierzbicka J, Żmijewski MA. Vitamin D in the skin physiology and pathology. Acta Biochim Pol. 2016;63(1):17-29. doi: 10.18388/abp.2015_1104.
https://doi.org/10.18388/abp.2015_1104
Upala S, Sanguankeo A. Low 25-hydroxyvitamin D levels are associated with vitiligo: A systematic review and meta-analysis. Photodermatol Photoimmunol Photomed. 2016;32(4):181-90. doi: 10.1111/phpp.12241.
https://doi.org/10.1111/phpp.12241
Xu X, Fu WW, Wu WY. Serum 25-hydroxyvitamin D deficiency in Chinese patients with vitiligo: A case-control study. PLoS One. 2012;7(12):e52778. doi: 10.1371/journal.pone.0052778.
https://doi.org/10.1371/journal.pone.0052778
Doss R, El-Rifaie AA, Gohary Y, Rashed L. Vitamin D receptor expression in vitiligo. Indian J Dermatol. 2015;60(6):544-8. doi: 10.4103/0019-5154.169123.
https://doi.org/10.4103/0019-5154.169123
Aksu Cerman A, Sarikaya Solak S, Kivanc Altunay I. Vitamin D deficiency in alopecia areata. Br J Dermatol. 2014;170(6):1299-304. doi: 10.1111/bjd.12980.
https://doi.org/10.1111/bjd.12980
Karagüzel G, Sakarya NP, Bahadır S, Yaman S, Ökten A. Vitamin D status and the effects of oral vitamin D treatment in children with vitiligo: A prospective study. Clin Nutr ESPEN. 2016;15:28-31. doi: 10.1016/j.clnesp.2016.05.006.
https://doi.org/10.1016/j.clnesp.2016.05.006
Sehrawat M, Arora TC, Chauhan A, Kar HK, Poonia A, Jairath V. Correlation of vitamin D levels with pigmentation in vitiligo patients treated with NBUVB therapy. ISRN Dermatol. 2014;2014:493213. doi: 10.1155/2014/493213.
https://doi.org/10.1155/2014/493213
Finamor DC, Sinigaglia-Coimbra R, Neves LC, Gutiérrez M, Silva JJ, Torres LD, et al. A pilot study assessing the effect of prolonged administration of high daily doses of vitamin D on the clinical course of vitiligo and psoriasis. Dermatoendocrinol. 2013;5(1):222-34. doi: 10.4161/derm.24808.
https://doi.org/10.4161/derm.24808
Lehmann B, Querings K, Reichrath J. Vitamin D and skin: new aspects for dermatology. Exp Dermatol. 2004 Dec;13(s4):11-5.
https://doi.org/10.1111/j.1600-0625.2004.00257.x
Albenali LH, Danby S, Moustafa M, Brown K, Chittock J, Shackley F, et al. Vitamin D and antimicrobial peptide levels in patients with atopic dermatitis and atopic dermatitis complicated by eczema herpeticum: A pilot study. J Allergy Clin Immunol. 2016 Dec;138(6):1715-1719.e4.
https://doi.org/10.1016/j.jaci.2016.05.039
Hata TR, Audish D, Kotol P, Coda A, Kabigting F, Miller J, et al. A randomized controlled double-blind investigation of the effects of vitamin D dietary supplementation in subjects with atopic dermatitis. J Eur Acad Dermatol Venereol. 2014 Jun;28(6):781-9.
https://doi.org/10.1111/jdv.12176
Peroni DG, Piacentini GL, Cametti E, Chinellato I, Boner AL. Correlation between serum 25-hydroxyvitamin D levels and severity of atopic dermatitis in children: Atopic dermatitis and vitamin D. Br J Dermatol. 2011 May;164(5):1078-82.
https://doi.org/10.1111/j.1365-2133.2010.10147.x
Javanbakht MH, Keshavarz SA, Djalali M, Siassi F, Eshraghian MR, Firooz A, et al. Randomized controlled trial using vitamins E and D supplementation in atopic dermatitis. J Dermatol Treat. 2011 Jun;22(3):144-50.
https://doi.org/10.3109/09546630903578566
Kılıç S, Sılan F, Hız M, Işık S, Ögretmen Z, Özdemir ö. Vitamin D Receptor Gene BSMI, FOKI, APAI, and TAQI Polymorphisms and the Risk of Atopic Dermatitis. J Investig Allergol Clin Immunol. 2016 Apr 1;26(2):106-10.
https://doi.org/10.18176/jiaci.0020
Heine G, Hoefer N, Franke A, Nöthling U, Schumann RR, Hamann L, et al. Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults: VDR SNPs in atopic dermatitis. Br J Dermatol. 2013 Apr;168(4):855-8.
https://doi.org/10.1111/bjd.12077
Camargo CA, Ganmaa D, Sidbury R, Erdenedelger K, Radnaakhand N, Khandsuren B. Randomized trial of vitamin D supplementation for winter-related atopic dermatitis in children. J Allergy Clin Immunol. 2014 Oct;134(4):831-835.e1.
https://doi.org/10.1016/j.jaci.2014.08.002
Schlager JG, Rosumeck S, Werner RN, Jacobs A, Schmitt J, Schlager C, et al. Topical treatments for scalp psoriasis: summary of a Cochrane Systematic Review. Br J Dermatol. 2017 Mar;176(3):604-14.
https://doi.org/10.1111/bjd.14811
Soleymani T, Hung T, Soung J. The role of vitamin D in psoriasis: a review. Int J Dermatol. 2015 Apr;54(4):383-92.
https://doi.org/10.1111/ijd.12790
Bergler-Czop B, Brzezińska-Wcisło L. Serum vitamin D level - the effect on the clinical course of psoriasis. Adv Dermatol Allergol. 2016;6:445-9.
https://doi.org/10.5114/ada.2016.63883
Giuggioli D, Colaci M, Cassone G, Fallahi P, Lumetti F, Spinella A, et al. Serum 25-OH vitamin D levels in systemic sclerosis: analysis of 140 patients and review of the literature. Clin Rheumatol. 2017 Mar;36(3):583-90.
https://doi.org/10.1007/s10067-016-3535-z
Malloy PJ, Feldman D. The role of vitamin D receptor mutations in the development of alopecia. Mol Cell Endocrinol. 2011 Dec;347(1-2):90-6.
https://doi.org/10.1016/j.mce.2011.05.045
Ghafoor R, Anwar MI. Vitamin D Deficiency in Alopecia Areata. J Coll Physicians Surg--Pak JCPSP. 2017 Apr;27(4):200-2.
Wu PW, Rhew EY, Dyer AR, Dunlop DD, Langman CB, Price H, et al. 25-hydroxyvitamin D and cardiovascular risk factors in women with systemic lupus erythematosus. Arthritis Rheum. 2009 Oct 15;61(10):1387-95.
https://doi.org/10.1002/art.24785
Amital H, Szekanecz Z, Szucs G, Danko K, Nagy E, Csepany T, et al. Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis. 2010 Jun 1;69(6):1155-7.
https://doi.org/10.1136/ard.2009.120329
Mok C, Birmingham D, Ho L, Hebert L, Song H, Rovin B. Vitamin D deficiency as marker for disease activity and damage in systemic lupus erythematosus: a comparison with anti-dsDNA and anti-C1q. Lupus. 2012 Jan;21(1):36-42.
https://doi.org/10.1177/0961203311422094
Gruber-Wackernagel A, Obermayer-Pietsch B, Byrne SN, Wolf P. Patients with polymorphic light eruption have decreased serum levels of 25-hydroxyvitamin-D 3 that increase upon 311 nm UVB photohardening. Photochem Photobiol Sci. 2012;11(12):1831-6.
https://doi.org/10.1039/C2PP25188D
Muehleisen B, Bikle DD, Aguilera C, Burton DW, Sen GL, Deftos LJ, et al. PTH/PTHrP and Vitamin D Control Antimicrobial Peptide Expression and Susceptibility to Bacterial Skin Infection. Sci Transl Med. 2012 May 23;4(135):135ra66-135ra66.
https://doi.org/10.1126/scitranslmed.3003759
Martineau AR, Newton SM, Wilkinson KA, Kampmann B, Hall BM, Nawroly N, et al. Neutrophil-mediated innate immune resistance to mycobacteria. J Clin Invest. 2007 Jul 2;117(7):1988-94.
https://doi.org/10.1172/JCI31097
Carless MA, Kraska T, Lintell N, Neale RE, Green AC, Griffiths LR. Polymorphisms of the VDR gene are associated with presence of solar keratoses on the skin. Br J Dermatol. 2008 Oct;159(4):804-10.
https://doi.org/10.1111/j.1365-2133.2008.08745.x
Bijlsma MF, Spek CA, Zivkovic D, van de Water S, Rezaee F, Peppelenbosch MP. Repression of Smoothened by Patched-Dependent (Pro-)Vitamin D3 Secretion. Scott M, editor. PLoS Biol. 2006 Jul 18;4(8):e232.
https://doi.org/10.1371/journal.pbio.0040232
For the Osteoporotic Fractures in Men (MrOS) Study Group, Tang JY, Parimi N, Wu A, John Boscardin W, Shikany JM, et al. Inverse association between serum 25(OH) vitamin D levels and non-melanoma skin cancer in elderly men. Cancer Causes Control. 2010 Mar;21(3):387-91.
https://doi.org/10.1007/s10552-009-9470-4
Rasheed H, Hegazy RA, Gawdat HI, Mehaney DA, Kamel MM, Fawzy MM, et al. Serum Vitamin D and Vitamin D Receptor Gene Polymorphism in Mycosis Fungoides Patients: A Case Control Study. Zmijewski M, editor. PLOS ONE. 2016 Jun 23;11(6):e0158014.
https://doi.org/10.1371/journal.pone.0158014
Orlow I, Roy P, Reiner AS, Yoo S, Patel H, Paine S, et al. Vitamin D receptor polymorphisms in patients with cutaneous melanoma. Int J Cancer. 2012 Jan 15;130(2):405-18.
https://doi.org/10.1002/ijc.26023
Newton-Bishop JA, Beswick S, Randerson-Moor J, Chang Y-M, Affleck P, Elliott F, et al. Serum 25-Hydroxyvitamin D3 Levels Are Associated with Breslow Thickness at Presentation and Survival From Melanoma. J Clin Oncol. 2009 Nov 10;27(32):5439-44.
https://doi.org/10.1200/JCO.2009.22.1135
Field S, Davies J, Bishop DT, Newton-Bishop JA. Vitamin D and melanoma. Dermatoendocrinol. 2013 Jan;5(1):121-9.
https://doi.org/10.4161/derm.25244
Wrzosek M, Łukaszkiewicz J, Wrzosek M, Jakubczyk A, Matsumoto H, Piątkiewicz P, et al. Vitamin D and the central nervous system. Pharmacol Rep. 2013;65(2):271-8.
