Keywords
Hepatitis B Vaccination Military Medicine Primary Prevention Vitiligo
Hepatitis C virus (HCV) infection is now recognized as a major health problem worldwide (1, 2) and after hepatitis B, it is one of the major causes of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Controlling HCV infection is an important public health concern because the majority of infections do not resolve and instead lead to chronic infection (3-5). It is estimated that around 200 million individuals are infected with HCV infection worldwide (6, 7). Even within the same geographic region, there are significant demographical variations in HCV prevalence (4, 5). Pegylated recombinant human α-interferons (PEGIFN) in combination with ribavirin are now the first line treatment for chronic HCV infection (8). Numerous side effects with combination therapy have been reported. The major side effects include influenza-like symptoms, gastrointestinal disturbances, psychiatric symptoms, hematologic abnormalities (leukopenia, neutropenia and thrombocytopenia), thyroid dysfunction and occasionally respiratory and dermatologic symptoms (9). Most of the side effects are mild, reversible and controllable; however, some of them are severe and even life threatening.
Autoimmune disorders are the main contraindication to HCV infection treatment with alpha-interferon (INF-α) (10). Alpha-INF is the main therapeutic agent in patients infected with HCV; however, it can induce the production of autoantibodies and can lead to autoimmune disease (11). Interferons are cytokines that can regulate the functions of immune effectors and are responsible for signals linking innate and adoptive immunity, and potentially co-ordinate the autoimmunity associated with INF-α therapy. Alpha-INF induces numerous target genes in antigen presenting cells (APCs) leading to APCs stimulation, humoral autoimmunity enhancement, isotype switching promotion, and potently autoreactive T cells activation. Moreover, INF-α can synergistically amplify T cell auto-reactivity by directly promoting T cell activation and keeping activated T cells alive (12).
Vitiligo is an idiopathic, acquired form of skin disorder that occurs when melanocytes die or become nonfunctional. Although the etiology of vitiligo is unknown, the role of autoimmunity and genetic factors are currently more suspected. The presence of serum autoantibodies targeting the melanocytes surface antigens (13) and existence of a large number of T cells specific for melanocyte antigens in vitiligenous lesions (14) suggests an autoimmune etiology. HCV is associated with autoimmune disorders, however, no study has shown any association between HCV infection and vitiligo (15, 16).
Vitiligo can occur after ∝-INF therapy in patients with chronic hepatitis C and B (17, 18). The first case of vitiligo in patients with chronic hepatitis B was reported by Alavian et al (18) in 2002; in their report, the lesions appeared after initiation of therapy with ∝-INF and disappeared after the therapy was stopped. The onset and course of INF-α therapy-associated vitiligo is variable and the existence of other autoimmune disorders such as hashimato’s thyroiditis can predispose the patient to this side effect (19). It is interesting to mention that there is a report of vitiligo lesions disappearance after initiation of INF-α and ribavirin therapy due to immune modulation effects (20). Vitiligo at injection site of PEG-α2a-IFN was reported in patients with chronic hepatitis C infection (21). However, despite the worldwide use of interferon therapy for HCV and HBV infection, the occurrence of vitiligo is very rarely reported in the literature, although we have seen a few cases during our practice (19). Finally, it is important to emphasize that the existence of vitiligo is not a contraindication for interferon therapy.
Acknowledgements
References
-
1.
Alavian SM. New globally faces of hepatitis B and C in the world. Gastro Hepat FBB. 2011;4(4):171-4.
-
2.
Ataei B, Shirani K, Alavian SM, Ataie M. Evaluation of Knowledge and Practice of Hairdressers in Women's Beauty Salons in Isfahan About Hepatitis B, Hepatitis C, and AIDS in 2010 and 2011. Hepat Mon. 2013;13(3). ee6215. [PubMed ID: 23658593]. https://doi.org/10.5812/hepatmon.6215.
-
3.
Alavian SM. We Need a New National Approach to Control Hepatitis C: It is Becoming too Late. Hepat Mon. 2008;8(3):165-9.
-
4.
Alter MJ. Epidemiology of hepatitis C virus infection. World J Gastroenterol. 2007;13(17):2436-41. [PubMed ID: 17552026].
-
5.
Alavian SM, Adibi P, Zali MR. Hepatitis C virus in Iran: Epidemiology of an emerging infection. Arch Iran Med. 2005;8:84-90.
-
6.
Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005;5(9):558-67. [PubMed ID: 16122679].
-
7.
Alberti A, Benvegnu L. Management of hepatitis C. J Hepatol. 2003;38 Suppl 1:S104-18. [PubMed ID: 12591189].
-
8.
Ebrahimi Daryani N, Alavian SM, Somi MH, Torabi-Nami M. Hepatitis C and Why the Treatment is Needed Now? The Summary Report From the Cross-Border Symposium of the 5th Tehran Hepatitis Congress May 2013. Hepat Mon. 2013;13(11). ee16082. https://doi.org/10.5812/hepatmon.16082.
-
9.
Maddrey WC. Safety of combination interferon alfa-2b/ribavirin therapy in chronic hepatitis C-relapsed and treatment-naive patients. Semin Liver Dis. 1999;19 Suppl 1:67-75. [PubMed ID: 10349694].
-
10.
Namazee N, Sali S, Asadi S, Shafiei M, Behnava B, Alavian SM. Real response to therapy in chronic hepatitis C virus patients: a study from iran. Hepat Mon. 2012;12(9). ee6151. [PubMed ID: 23087759]. https://doi.org/10.5812/hepatmon.6151.
-
11.
Prummel MF, Laurberg P. Interferon-alpha and autoimmune thyroid disease. Thyroid. 2003;13(6):547-51. [PubMed ID: 12930598]. https://doi.org/10.1089/105072503322238809.
-
12.
Conrad B. Potential mechanisms of interferon-alpha induced autoimmunity. Autoimmunity. 2003;36(8):519-23. [PubMed ID: 14984029].
-
13.
Gilhar A, Zelickson B, Ulman Y, Etzioni A. In vivo destruction of melanocytes by the IgG fraction of serum from patients with vitiligo. J Invest Dermatol. 1995;105(5):683-6. [PubMed ID: 7594644].
-
14.
van den Wijngaard R, Wankowicz-Kalinska A, Le Poole C, Tigges B, Westerhof W, Das P. Local immune response in skin of generalized vitiligo patients. Destruction of melanocytes is associated with the prominent presence of CLA+ T cells at the perilesional site. Lab Invest. 2000;80(8):1299-309. [PubMed ID: 10950121].
-
15.
Akbayir N, Gokdemir G, Mansur T, Sokmen M, Gunduz S, Alkim C, et al. Is there any relationship between hepatitis C virus and vitiligo? J Clin Gastroenterol. 2004;38(9):815-7. [PubMed ID: 15365412].
-
16.
Arican O, Sasmaz S, Kokoglu OF. Role of hepatitis B and C viruses in the etiopathogenesis of vitiligo. J Dermatol. 2004;31(6):506-7. [PubMed ID: 15235196].
-
17.
Alavian SM, Shokohi A. [Vitiligo is a complication of interferon therapy in chronic hepatitis B]. Iran J Dermatol. 2002;5(3):45-9.
-
18.
Oiso N, Sato M, Kawada A. Vitiligo after combination therapy of pegylated interferon-alpha-2a, ribavirin and vitamin D in a patient with chronic hepatitis C. J Dermatol. 2013;40(9):772-3. [PubMed ID: 23855823]. https://doi.org/10.1111/1346-8138.12234.
-
19.
Hamadah I, Binamer Y, Sanai FM, Abdo AA, Alajlan A. Interferon-induced vitiligo in hepatitis C patients: a case series. Int J Dermatol. 2010;49(7):829-33. [PubMed ID: 20618507]. https://doi.org/10.1111/j.1365-4632.2009.04443.x.
-
20.
Taffaro M, Pyrsopoulos N, Cedron H, Cacayorin E, Weppler D, Moon J, et al. Vitiligo improvement in a hepatitis C patient after treatment with PEG-interferon alpha-2a and ribavirin: a case report. Dig Dis Sci. 2007;52(12):3435-7. [PubMed ID: 17431776]. https://doi.org/10.1007/s10620-006-9721-0.
-
21.
Arya V, Bansal M, Girard L, Arya S, Valluri A. Vitiligo at Injection Site of PEG-IFN-alpha 2a in Two Patients with Chronic Hepatitis C: Case Report and Literature Review. Case Rep Dermatol. 2010;2(2):156-64. [PubMed ID: 21076689]. https://doi.org/10.1159/000320207.
reply