Vitiligo: Genetic Aspects - Research Paper Example

Vitiligo: Genetic Aspects Pigmentary disease of the mucous membranes and the skin that is acquired and progressive, is known as vitiligo. Characteristic features of the disease are patches and macules that are depigmented. The disease occurs due to either selective or complete destruction of melanocytes in the body. According to Kar (2001), vitiligo "does not result in restriction of capacity to work or expectancy of life, but it causes cosmetic disfigurement leading to psychological trauma to the patients." Due to its visibility to others, the condition can lead to several emotional and social sufferement and lead to consequences like depression, anxiety, low self-esteem and even stigmatization (Gawkrodger et al, 2008). Demographics The incidence rate all over the world is 1-2 percent and 30 percent cases occur as familial clusters. In the US, the incidence rate is 1 percent. Though not significant statistically, slight female preponderance has been noticed. The clinical presentation can occur at any age, the most common presentation time being between 10 and 30 years (Groysman and Sami, 2009). The "average age of onset for vitiligo is approximately 20 years" (Groysman and Sami, 2009) and it is the same for both sexes. Pathogenesis The pathogenesis of the disease is a complex one with multiple factors being involved in the etiology. Infact, the main pathogenesis is yet unknown and hence only theories exist to explain the pathogenesis of the disease. The main pathogenic feature is "absence of functional melanocytes in vitiligo skin and a loss of histochemically recognized melanocytes, owing to their destruction" (Groysman and Sami, 2009)). The process of destruction is a slow one and thus decrease in melanocytes is a progressive course (Groysman and Sami, 2009). Some theorists believe that the destruction of melanocytes in vitiligo occurs due to autoimmunity. According to this autoimmune theory, changes in either cellular immunity, or humoral immunity or both can result in the destruction of melanocytes. The fact that vitiligo occurs in coincidence with several other autoimmune disorders like Graves disease, hashimoto's thyroiditis, Addison disease, pernicious anemia, autoimmunepolyglandular disease and diabetes mellitus proves the autoimmune etiology of this disease (Groysman and Sami, 2009). Another evidence for autoimmune basis of the disease is the presence of circulating antibodies against melanocytes in the blood of vitiligo patients. Also, some research in mice injected with sera from vitiligo patients has shown that when healthy skin is grafted into them, it is rejected. This shows that humoral immunity plays a major role in the pathogenesis of vitiligo (Groysman and Sami, 2009). According to the theory of "intrinsic defect of melanocytes", melanocytes in patients with vitiligo have some intrinsic problems because of which the cells die. The abnormalities include "incompetent synthesis and processing of melanocytes" and "abnormal, rough endoplasmic reticulum". Other defects include dysregulation of homing-receptor and "early apoptosis of melanocytes" (Groysman and Sami, 2009). Some studies have shown that oxidant stress also contributes to vitiligo. Free radicals are toxic to melanocytes and their accumulation destroys them. In some patients defective homeostasis of tetrahydrobiopterin leads to accumulation of hydrogen peroxide which is toxic to melanocytes. To support this theory, there is some evidence of low levels of catalase and high levels of superoxide dismutase in vitiligo patients (Groysman and Sami, 2009). In some patients, vitiligo is noted after nerve injury and this has led to the neural theory. Clinical aspects that support this theory are the dermatomal pattern of occurrence of segmental vitiligo and increased adrenergic activity features like vasoconstriction and sweating. Infact, there are reports of rise in vanilmandelic acid and other neurometabolites, biochemical evidence of adrenergic activity (Groysman and Sami, 2009). Thus, it can be said that vitiligo occurs due to melanocyte loss secondary to various causes like immunologic problems, defects at molecular level and neural problems (Groysman and Sami, 2009). Genetic aspects In vitiligo, there is "incomplete penetrance, multiple susceptibility loci, and genetic heterogeneity." These genetic attributes affect melanin biosynthesis, immune regulation and response to stress. there is evidence of association of human leukocyte antigens or HLA, but the evidence is inconsistent (Groysman and Sami, 2009). Clinical presentation More often than not, vitiligo appears as an amelanotic patch which is surrounded by skin that is healthy. The color of macules are milkwhite. These lesions are easily seen under wood lamp examination. Each lesion appears well demarcated and take shapes like round, oval or linear. the borders are usually convex. the size of the lesions gradually increase in centrifugal direction. The size and rate of increase in size varies from one individual to other and is unpredictable. The lesions may be confined to a single area or may be general and the most common areas of presentation are neck, face and scalp. Even mucus membranes like lips can be involved. Body hair in the area of involvement may appear depigmented. Presence of leukotrichia indicates resistance to medication therapy. In some patients, an intermediate zone between loss of pigmentation and normal skin, appearing brown can occur. Thus 3 colors of skin are seen in the patient. This is known as trichrome vitiligo. In some other patients, inflammation of the margin of the lesions may occur giving a red, itchy and raised border. This is known as marginal inflammatory vitiligo. In quadrichrome vitiligo, in some sites, repigmentation of perifollicular region may occur, giving a dark brown appearance, the fourth color (Groysman and Sami, 2009). Associated problems In about 30 percent of the cases, abnormalities of the choroid have been reported. In 5 percent of the patients, iritis can occur. Other ocular problems associated with vitiligo are uveitis, and exophthalmos. In many patients, other autoimmune problems can occur, the most common ones being those related o thyroid gland. Since melanocytes are present in the auditory system too, defects in the modulation of auditory stimuli, auditory disturbances, hypoacusis and hearing abnormalities can occur. Due to "T-cell–mediated reaction to antigenic melanoma cells and cross-reactivity to healthy melanocytes" (Groysman and Sami, 2009), depigmentation can be seen in malignant melanoma too (Groysman and Sami, 2009). Laboratory investigations The diagnosis of vitiligo is mainly established through clinical presentation. Wood lamp examination is useful for inspection of lesions. However, biopsy may be essential to differentiate it from other causes of hypopigmentation. The biopsy of involved skin will reveal "complete absence of melanocytes in association with a total loss of epidermal pigmentation. Superficial perivascular and perifollicular lymphocytic infiltrates may be observed at the margin of vitiliginous lesions, consistent with a cell-mediated process destroying melanocytes. Degenerative changes have been documented in keratinocytes and melanocytes in both the border lesions and adjacent skin" (Groysman and Sami, 2009)). Since vitiligo can be associated with other autoimmune causes, evaluation for those conditions may be done as the clinical presentation demands. The most important test to screen for thyroid disease is thyroitropin test, which is a cost effective one (Groysman and Sami, 2009). Treatment There is no definite treatment for vitiligo which delivers good results in all patients. Response to different therapies is different in different patients and hence therapy must be individualized. In medical therapy, melanocytes arise from pilisebaceous glands, melanocytes that have not been affected in the disease process or from border lesions. Systemic phototherapy is the most commonly employed treatment and repigmentation occurs in 70 percent of the patients with early disease. The most widely used phototherapy is "narrow-band UV-B phototherapy" (Groysman and Sami, 2009). For this, "narrow-band fluorescent tubes (Philips TL-01/100W) with an emission spectrum of 310-315 nm and a maximum wavelength of 311 nm are used" (Groysman and Sami, 2009). The frequency of therapy is twice to thrice weekly. the adverse effects are not dangerous and hence the treatment can be administered even during pregnancy and lactation. Infact, even children can receive this treatment safely. The main adverse effects of this treatment are xerosis and pruritus. There are reports that co-administration of oral vitamin E can result in decrease in the incidence of side effects (Groysman and Sami, 2009). For small specific lesions, "UV-B narrow-band microphototherapy" (Groysman and Sami, 2009) is an useful strategy. Infact this is the choice of therapy for those with generalised vitiligo. In psoralen photochemotherapy, psoralens are used adjunct to UV-A light therapy. They are given either topically or orally. This therapy is mainly effective only in certain regions like trunk, face and proximal parts of hands and legs. It is not useful for lesions in feet and hands. In laser therapy using excimer laser, only stable vitiligo patches are targeted. The treatment is not only safe, but also efficacious. It is also well tolerated with minimal side effects. The treatment is very expensive. Some studies have shown superior results with "combination treatment with 0.1% tacrolimus ointment plus the 308-nm excimer laser." Steroids, both in the form of systemic and local have been used. Systemic steroids are effective, but associated with many side effects. Intralesional steroids have many side effects including pain and cutaneous atrophy. other medical therapies include topical tracrolimus administration, topical Vitamin D analog use and khellin 4 percent ointment. in some patients, when repigmentation is not possible, permanent depigmentation using monobenzylether of hydroquinone may be tried. However, this treatment is associated with side effects like burning, pruritus and allergic contact dermatitis. Surgical remedies include repigmentation using "Noncultured epidermal suspensions", "Thin dermoepidermal grafts", "Suction epidermal grafting", "Punch minigrafting" and "Cultured epidermis with melanocytes or cultured melanocyte suspensions" (Groysman and Sami, 2009). Prognosis In many patients, regardless of the treatment instituted, repigmentation is very slow and may never be complete, especially in areas like feet, finger tips, bony prominences, lips, wrists and genitalia. In some others, the whole body skin may become white with some interspersed regions of dark skin and such patients need to opt for complete depigmentation. Indicators of poor prognosis are early ag of onset, presence of associated autoimmune disorders, increased stress, acrofacial vitiligo, generalised vitiligo, segmental vitiligo and presence of leukotrichia (Babu, 2009). References Babu, H. (2009). Normal Course and Prognosis of Vitiligo. Retrieved on 9th November, 2010 from http://www.suite101.com/content/normal-course-and-prognosis-of-vitiligo-a130721 Groysman, V., and Sami, N. (2009). Vitiligo. Emedicine from WebMD. Retrieved on 9th November, 2010 from http://emedicine.medscape.com/article/1068962-overview Gawkrodger, D.J., Ormerod, A.D., Shaw, L., et al. (2008). Guideline for the Diagnosis and Management of Vitiligo. The British Journal of Dermatology, 159,(5),1051-1076. Kar, P.K. (2001). Vitiligo: A study of 120 cases. Indian J Dermatol Venereol Leprol., 67, 302-4. Read More