medigraphic.com
Centro de Investigaciones Regionales Dr. Hideyo Noguchi, Universidad Autónoma de Yucatán

2014, Number 3

<< Back Next >>

Rev Biomed 2014; 25 (3)

Vitiligo: Autoimmune Hypothesis

Zúñiga-Rosales Y, González-Herrera Y, Miyares-Díaz E, Rodríguez-Pelier CV

Language: Spanish
References: 59
Page: 145-155
PDF size: 230.11 Kb.


ABSTRACT

Introduction. Vitiligo is an acquired hypomelanosis characterized by the progressive appearance of patches of depigmented skin, with great aesthetic repercussions, and it significantly impairs the self-esteem of people who suffer from it. The etiopathogenesis of vitiligo is still unclear. Different theories have been proposed, with the autoimmune hypothesis gaining the most current acceptance.
Objective. Analyze the evidence that supports the hypothesis that vitiligo meets the criteria for the key characteristics of human autoimmune diseases.
Method. A literature review of Vitiligo's causes was completed for scientific articles published in the last 15 years, including PubMed, and Dermatology and Immunology, focusing on both previously accepted and novel information.
Development. The major direct, indirect and incidental evidences of autoimmune symptoms in Vitiligo cases were evaluated. Findings that support the autoimmune characteristics of Vitiligo were evaluated, including: the presence of T lymphocytes in the lesions and surrounding skin; plus detection of autoantibodies against melanocytes antigens; organ specific antibodies in the patient´s serum; the frequent association of other autoimmune illnesses with certain MHC II alleles; along with the existence of model animal, and the therapeutic response to topical immunosuppressants.
Conclusions. Although the etiology of Vitiligo is not well defined, there is strong evidence to classify it as an autoimmune disease. Its frequent association with other autoimmune diseases indicates patient evaluations with Vitiligo should include tests that promote early diagnosis.


REFERENCES

  1. Al-Mutairi N, Al-Sebeih KH. Late onset vitiligo and audiological abnormalities: Is there any association?. Indian J Dermatol Venereol Leprol. 2011 Aug; 77(5): 571-6

  2. Nunes DH, Esser LMH. Perfil epidemiologico dos pacientes com vitiligo e sua associacao com doencas da tireoide. An Bras Dermatol. 2011 Mar; 86(2): 241-8.

  3. Garg BJ, Saraswat A, Bhatia A, Katare OP. Topical treatment in vitiligo and the potential uses of new drug delivery systems. Indian J Dermatol Venereol Leprol 2010 May; 76(3): 231-8.

  4. Martis J, Bhat R, Nandakishore B, Shetty JN. A clinical study of vitiligo. Indian J Dermatol Venereol Leprol. 2002; 68(2): 92-3.

  5. Sehgal VN, Srivastava G. Vitiligo: Compendium of clinico-epidemiological features. Indian J Dermatol Venereol Leprol. 2007; 73(3): 149-56.

  6. Shah H, Mehta A, Astik B. Clinical and sociodemographic study of vitiligo. Indian J Dermatol Venereol Leprol. 2008; 74(6): 701.

  7. Jayanth DP, Pai BS, Shenoi SD, Balachandran C. Efficacy of antioxidants as an adjunct to photochemotherapy in vitiligo: A case study of 30 patients. Indian J Dermatol Venereol Leprol. 2002 Jul-Aug; 68(4): 202-5.

  8. Steiner D, Bedin V, Moraes MB, Villas RT, Steiner T. Vitiligo. An Bras Dermatol. 2004 may-jun; 79(3): 335-51.

  9. Korsunskaya IM, Suvorova KN, Dvoryankova EV. Modern aspects of Vitiligo pathogenesis. Dokl Biol Sci. 2003 Jan-Feb; 388(6): 38-40.

  10. Sandoval-Cruz M, García-Carrasco M, Sánchez- Porras R, Mendoza-Pinto C, Jiménez-Hernández M, Munguía-Realpozo P, et al. Immunopathogenesis of vitiligo. Autoimmun Rev. 2011 Oct; 10(2): 762–5.

  11. Alarcón H, Gutiérrez R, Gracida C. Vitiligo. Actualidades en el tratamiento. Rev Cent Dermatol Pascua. 2000; 9(3): 177-88.

  12. Kovacs SO, Vitiligo. J Am Acad Dermatol 1998 May; 38(5): 647-66.

  13. Pawelek J, Korner A, Bergstrom A. New regulation of melanin biosynthesis and autodestruction of melanoma cells. Nature. 1980 Aug; 286: 617-9.

  14. Ongenae K, Van Geel N, Naeyaert JM. Evidence for autoimmune pathogenesis of Vitiligo. Pigment Cell Res. 2003 Apr; 16(2): 90-100.

  15. Naughton GK, Eisinger M, Bystryn J-C. Antibodies to normal human melanocytes in Vitiligo. J Exp Med. 1983; 158: 246-251.

  16. Harning P, Cui J, Bystryn JC. Relation between the incidence and level of pigment cell antibodies and disease activity in Vitiligo. J Invest Dermatol. 1991 Dec; 97(6): 1078-80.

  17. Le Poole IC, Das PK, van den Wijngaard RMJGJ et al. Review of the etiopathomechanism of vitiligo: a convergence of the etiopathomechanism of vitiligo: a convergence theory. Exp Dermatol 1993 Aug; 2(4): 145-53.

  18. Rose NR, Bona C. Defining criteria for autoimmune diseases (Witebsky's postulates revisited). Immunol Today. 1993 Sep; 14(9): 426-30.

  19. Abu Tahir M, Pramod K, Ansari SH, Ali J. Current remedies for vitiligo. Autoimmun Rev. 2010 May; 9(7): 516–20.

  20. Kemp EH, Gavalas NG, Gawkrodger DJ, Weetman AP. Autoantibody responses to melanocytes in the depigmenting skin disease vitiligo. Autoimmun Rev. 2007 Jan; 6(3):138–42.

  21. Mittal RR, Popli R, Jassal JS, Kumar D. Immunological study in vitiligo and contact depigmentation. Indian J Dermatol Venereol Leprol. 1994; 60: 92-4.

  22. Ogg GS, Dumbar PR, Romero P, Chen JL, Cerundolo V. High Frequency of Skin-homing Melanocyte-specific Cytotoxic T Lymphocytes in Autoimmune Vitiligo. J Exp Med. 1998 Sep; 188(6): 1203-8.

  23. Garbelli S, Mantovani S, Palermo B, Giachino C. Melanocyte-specific, cytotoxic T cell responses in vitiligo: the effective variant of melanoma immunity?. Pigment Cell Research. 2005 Aug; 18(4): 234 - 42.

  24. Lang KS, Caroli CC, Muhm A, Wernet D, Moris A, Schittek B, et al. HLA-A2 restricted, melanocytespecific CD8(+) T lymphocytes detected in vitiligo patients are related to disease activity and are predominantly directed against MelanA/MART1. J Invest Dermatol. 2001 Jun; 116(6): 891-7.

  25. Mantovani S, Garbelli S, Palermo B, Campanelli R, Brazzelli V, Borroni G, et al. Molecular and functional bases of self-antigen recognition in longterm persistent melanocyte-specific CD8+ T cells in one Vitiligo patient. J Invest Dermatol. 2003; 121 (2): 308-14.

  26. Norris DA, Kissinger RM, Naughton GM, Bystryn GC. Evidence for Immunological Mechanisms in Human Vitiligo: Patients' Sera Induce Damage to Human Melanocytes In Vitro by Complement- Mediated Damage and Antibody-Dependent Cellular Cytotoxicity. J Invest Dermatol. 1988; 90: 783–9.

  27. Van den Wijngaard R, Wankowicz-Kalinska A, Pals S, Weening J, Das P. Autoimmune Melanocyte Destruction in Vitiligo. Lab Invest. 2001 Aug; 81(8):1061-8.

  28. Ruiz-Argüelles A, Brito GJ, Reyes-Izquierdo P, Pérez-Romano B, Sánchez-Sosa S. Apoptosis of melanocytes in vitiligo results from antibody penetration. J Autoimmun. 2007 Dec; 29(4): 281–6.

  29. Doshi B, Mahajan S, Khopkar US, Kharkar V, Agarwal P. Epidermotropic metastatic melanoma with perilesional depigmentation in an Indian male. Indian J Dermatol. 2013 Sep; 58(5): 396-9.

  30. Nigam PK, Patra PK, Khodiar PK, Gual J. A study of blood CD3+, CD4+, and CD8+ T cell levels and CD4+:CD8+ ratio in vitiligo patients. Indian J Dermatol Venereol Leprol 2011; 77(1): 111.

  31. Antelo DP, Filgueira AL, Cunha JMT. Redução dos linfócitos TCD8+ citotóxicos observada com a terapia Puvaem paciente com vitiligo. An Bras Dermatol. 2008; 83(6): 572-4.

  32. Steitz J, Brück J, Lenz J, Büchs S, Tüting T. Peripheral CD8+ T cell tolerance against melanocytic self-antigens in the skin is regulated in two steps by CD4+ T cells and local inflammation: implications for the pathophysiology of vitiligo. J Invest Dermatol 2005 Jan; 124(1): 144–50.

  33. Gattinoni L, Ranganathan A, Surman DR, Palmer DC, Antony PA, Theoret MR, et al. CTLA-4 dysregulation of self/tumorreactiveCD8+ T-cell function is CD4+ T-cell dependent. Blood 2006 Dec; 108(12): 3818–23.

  34. Bellet JS, Prose NS. Vitiligo em crianças: uma revisão de classificação, hipótesis sobre patogênese e tratamento. An Bras Dermatol. 2005; 80(6):631-6.

  35. Terras S, Gambichler T, Moritz RK, Altmeyer P, Lambert J. Immunohistochemical analysis of FOXP3+ regulatory T cells in healthy human skin and autoimmune dermatoses. Int J Dermatol. 2014 Mar; 53 (3): 294-9.

  36. Parsad D.A New Era of Vitiligo Research and Treatment. J Cutan Aesthet Surg. 2013 Apr-Jun; 6(2): 63–4.

  37. Rezaei N, Gavalas NG, Weetman AP, Kemp EH. Autoimmunity as an aetiological factor in vitiligo. J Eur Acad Dermatol Venereol. 2007 Sep; 21(7): 865–76.

  38. Escobar RC, Falabella FR. Vitiligo, la faceta inmunológica. Dermatol Venez. 1998; 36(4): 123-31

  39. Silva de Castro C. Prevalência de psoríase em estudo de 261 pacientes com vitiligo. An Bras Dermatol. 2005; 80(5): 489-92.

  40. Conceição NF, Cajueiro MMC. Vitiligo na criança e doença da tireóide. An Bras Dermatol. 2009; 84(2): 200-2.

  41. Holthausen DN, Hademann LM. P e r f i l epidemiológico dos pacientes com vitiligo e sua associação com doenças da tireoide. An Bras Dermatol. 2011; 86(2): 241-8.

  42. Ingordo V, Gentile C, Iannazzone S, Cusano F, Naldi L. Vitiligo and autoimmunity: an epidemiological study in a representative sample of young Italian males. J Eur Acad Dermatol Venereol. 2011 Jan; 25(1): 105-9.

  43. Uncu S, Yayl S, Bahad S, Ãkten A, Alpay K. Relevance of autoimmune thyroiditis in children and adolescents with vitiligo. Int J Dermatol 2011 Feb; 50 (2): 175-9.

  44. Gey A, Diallo A, Seneschal J, Léauté-Labrèze C, Boralevi F, Jouary T, et al. Autoimmune thyroid disease in vitiligo: multivariate analysis indicates intricate pathomechanisms. Br J Dermatol. 2013 Apr; 168(4): 756-61.

  45. Daneshpazhooh M, Mostofizadeh MG, Behjati J, Akhyani M, Reza MR. Anti-thyroid peroxidase antibody and vitiligo: a controlled study. BMC Dermatol. 2006 Mar; 6: 3

  46. Behl PN, Agarwal A, Srivastava G. Etiopathogenesis of vitiligo: Are we dealing with an environmental disorder?. Indian J Dermatol Venereol Leprol. 1999; 65: 161-7

  47. Jabbour SA. Cutaneous Manifestations of Endocrine Disorders. A Guide for Dermatologists. Am J Clin Dermatol. 2003; 4(5): 315-31.

  48. Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA, et al. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their relatives. Pigment Cell Res. 2003 Jun; 16(3): 208–14.

  49. Birlea S, Birlea M, Cimponeriu D, Apostol P, Cosgarea R, Gavrila L, et al. Autoimmune Diseases and Vitamin D Receptor Apa-I Polymorphism are Associated with Vitiligo in a Small Inbred Romanian Community. Acta Derm Venereol. 2006; 86: 209–14.

  50. Akay BN, Bozkir M, Anadolu Y, Gullu S. Epidemiology of vitiligo, associated autoimmune diseases and audiological abnormalities: Ankara study of 80 patients in Turkey. J Eur Acad Dermatol Venereol. 2010; 24: 1144–50.

  51. Dittmar M, Kahaly GJ. Polyglandular autoinmune syndromes: immunogenetics and long term follow-up. J. Clin Endocrinol Metab 2003; 88: 2983-92.

  52. Sheth VM, Guo Y, Qureshi AA. Comorbidities associated with vitiligo: a ten-year retrospective study. Dermatology. 2013 Oct; 227(4): 311-5

  53. Spritz RA. The genetics of generalized vitiligo and associated autoimmune diseases. Pigment Cell Res. 2007 Aug; 20(4): 271-8.

  54. Misri R, Khopkar U, Shankarkumar U, Ghosh K. Comparative case control study of clinical features and human leukocyte antigen susceptibility between familial and non familial vitiligo. Indian J Dermatol Venereol Leprol. 2009; 75: 583-7.

  55. Grimes PE, Soriano T, Dytoc MT. Topical tacrolimus for repigmentation of vitiligo. J Am Acad Dermatol. 2002; 47: 789-91.

  56. Aghaei S, Ardekani GS. Topical immunotherapy with diphenylcyclopropenone in vitiligo: A preliminary experience. Indian J Dermatol Venereol Leprol. 2008; 74: 628-31.

  57. Tjioe M, Vissers WH, Gerritsen MJ. Topical macrolide immunomodulators: a role in the treatment of vitiligo?. Am J Clin Dermatol. 2006; 7(1): 7-12.

  58. Tamler C, Duque-Estrada B, Oliveira PA, Avelleira JCR. Pomada de tacrolimo 0,1% no tratamento de vitiligo: série de casos. An Bras Dermatol. 2011; 86(1): 167-9.

  59. Lo YH, Cheng GS, Huang CC, Chang WY, Wu CS. Efficacy and safety of topical tacrolimus for the treatment of face and neck vitiligo. J Dermatol. 2010 Feb; 37(2): 125-9.




2020     |     www.medigraphic.com