Pathogenesis of vitiligo: Immunomodulating therapies favored course of action

Edmonton, Alberta - Although several different theories exist with regard to the pathogenesis of vitiligo, an immune basis appears to be the most favored mechanism, with cytokines and other chemical mediators playing a center role in disease development and progression. As a result, immunomodulating therapies such as tacrolimus (Protopic, Astellas) are employed.

Recent study

According to a recent study, the key to the therapeutic efficacy of tacrolimus appears to be due to its unique immunosuppressive actions of the T lymphocyte T-helper (Th) 2 cytokine, interleukin (IL)-10.

"Interleukin-10 is an immunomodulatory cytokine which appears to be stimulated by tacrolimus during the treatment of vitiligo, which may at least in part account for its efficacy of repigmentation of lesions seen in vitiligo patients," says Marlene T. Dytoc, M.D., clinical associate professor of the division of dermatology and cutaneous sciences, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

In a three-month, 20-patient study, Dr. Dytoc monitored the clinical changes in vitiligo lesions treated twice daily with 0.1 percent tacrolimus ointment and quantified the levels of IL-10 cytokine in non-vitiliginous skin and vitiliginous skin, both before and after therapy.

Biopsy specimens of the vitiliginous and nonvitiliginous skin were taken both before and after therapy and subsequently analyzed for expression of IL-10 using ELISA (Enzyme-linked immunosorbent assay.) Vitiligo lesions were graded on the basis of diameter and presence of follicular repigmentation using digital photographs, and margins of lesions were verified using Wood’s lamp. Patients were evaluated at baseline, week two and at months one, two and three.

Of the 20 patients enrolled in the study, 17 completed the study and returned for follow-up at all time points.

Results

Results showed that after three months of treatment with topical tacrolimus, all patients who completed the study showed an improvement in lesion size, with follicular repigmentation seen in all cases and data showing a statistically significant mean ± SEM decrease in vitiligo lesion size of 41.0 ± 5.2 percent.

Data also showed that there was a statistically significant difference between IL-10 expression in vitiligo lesions following the three-month treatment, compared with untreated vitiligo lesions and normal skin.

"These results prove that topical tacrolimus is effective in treating vitiligo lesions. Topical tacrolimus was found to increase IL-10 expression in vitiligo lesions. It is possible that the increase of this key immunomodulatory cytokine inhibits the destruction of the melanocytes triggered by unchecked Th1 pathways in vitiligo and may be the reason why repigmentation was seen in the study patients.

"We believe that the Th1-mediated process results in macrophage- and cytotoxic T lymphocyte-mediated destruction of melanocytes seen as depigmentation in vitiligo. In order to prove this theory; however, direct evidence would be needed from further studies," Dr. Dytoc says.

Therapeutic modalities

Several different therapeutic approaches are currently available for the treatment of vitiligo, including topical and intralesional corticosteroids, topical calcineurin inhibitors, phototherapy (PUVA and narrow-band UVB) and transplantation of autologous pigment cells. Calcineurin inhibitors represent an effective alternative treatment to topical corticosteroid therapy and are viewed as a major advance in topical therapy, as they can achieve repigmentation without causing skin atrophy or immunosuppression (as is commonly seen with corticosteroid therapy). Experts agree that there is no cure for vitiligo, but these therapeutic modalities have been shown to achieve repigmentation - though the results may not be permanent or long lasting.

"How easily vitiligo lesions repigment depends heavily on a number of factors, including lesion location as well as duration and severity of disease. Patients who have vitiligo for longer periods of time classically have lesions that are more difficult to repigment, and lesions located around the distal extremities are classically more recalcitrant to therapies.

"Moreover, these locations are much more subject to koebnerization resulting from trauma," Dr. Dytoc says.

According to Dr. Dytoc, tacrolimus could be used for localized lesions, but for more generalized vitiligo, phototherapy may be a wiser therapeutic choice. Moreover, tacrolimus could be combined with phototherapy (such as narrow-band UVB), with the hope of achieving an enhanced therapeutic response. Therapy could be done two to three times a week, and patients would be re-assessed after a month.

"We should not give up on an effective treatment for a chronic condition such as vitiligo, as new and exciting therapeutic options are always evolving. I believe we should base our choice of therapy not only on the characteristics of the patient, but also in terms of the scientific evidence or mechanism underlying the efficacy of the treatment," Dr. Dytoc explains. DT

Disclosures: The study was supported by research funding from Astellas Canada, Inc.