Male genital vitiligo: Topical tofacitinib and 308 nm excimer light combination treatment – Retrospective analysis of efficacy and safety

INTRODUCTION

Vitiligo alters the quality of life, self-esteem, and body image. Pure mucosal vitiligo accounts for 2–3% of total vitiligo cases. Due to paucity of melanocytes, reservoir mucosal vitiligo is difficult to treat. Male genital vitiligo is not uncommon and often has tremendous impact on quality of life and represents a specific therapeutic challenge, as regimentation remains difficult to achieve in most cases.¹ This leads to psychosocial and sexual comorbidities. As a result loss of libido, erectile dysfunction, and mental depression due to lack of performance are reported.² The extent of psycho social comorbidities supports the use of multidisciplinary treatment strategies and education to address the vitiligo-associated burden of disease. Melanocytes in the bulb and infundibulum of hair follicle are destroyed in vitiligo, but the lower and middle portions of the follicles as well as the outer sheath are spared.³ As mucosal lining of genitalia is devoid of these reservoir melanocytes, repigmentation over genitalia is very difficult.⁴

Mucosal lining of lips has shown promising results to 308 nm excimer light with or without topical calcineurin inhibitor.^5,6 Although there are limitations to the medical line of treatment for genital vitiligo, calcineurin inhibitor – pimecrolimus and topical Janus Kinase inhibitors (JAK inhibitors) are found effective with or without phototherapy. Topical JAK inhibitors have shown encouraging repigmentation rate on the face, although specific efficacy in genital area remains to be assessed. There are few reports of successful use of topical tofacitinib with narrow band ultra-violet B (NB-UVB) phototherapy in localized vitiligo.⁷ Herewith, author wishes to share our experience of 308 excimer lamp therapy with topical tofacitinib ointment for the treatment of male genital vitiligo.

MATERIAL AND METHODS

Total 15 male patients having genital vitiligo who were treated with tofacitinib ointment with 308 nm excimer lamps were analyzed retrospectively. The average age of patient was 23.4 years and the average duration of illness was 2.3 years. Patients having lesions elsewhere on the body but having genital lesions were excluded from the study. All of them have received topical pimecrolimus, mild-to-moderate potent topical steroid, and/or decapeptide lotion with non-satisfactory results in the past. Ethics committee approval was not sought for, as it was a retrospective analysis. After informed written consent and counseling about the nature of treatment, each patient was asked to apply 2% tofacitinib ointment twice a day after thorough cleaning of the lesion with soap and water. 308 nm excimer lamp treatment was performed on a biweekly basis using proper eye protection. The initial dose of 50 mj/cm² was given covering the surrounding normal area. The dose was gradually increased by 20 mj/cm² every week up to 350–400 mj/cm² twice a week. The treatment was continued till complete repigmentation of the lesions. After the complete repigmentation was achieved, excimer sessions were reduced to once a week and later once in 10 days and then stopped, while topical tofacitinib was continued for further 12 weeks and then discontinued. Patients were followed for 6 months post completion. Clinical photographs were taken before and after complete repigmentation of the lesion. The results were assessed subjectively as well as objectively.

RESULTS

All patients tolerated the treatment well. Post treatment erythema was observed in all individuals which settle down within 30–45 min. Burns due to 308 nm excimer lamps were not observed. Out of 15 patients, four patients start repigmenting after eight sessions with energy of 130 mj/cm² while remaining patients start showing improvement at weeks 12–14 with energy of around 180–200 mj/cm². Complete repigmentation took place after 16–20 weeks of treatment with 30–35 sessions of 308 nm excimer lamps in majority of the patients (11 out of 15) while remaining individuals needed another 8–10 sessions. There was no recurrence post 6 months of completion of treatment [Figures 1-3].

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Figure 1:

(a) Before treatment case 1. (b) After treatment case 1.

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Figure 2:

(a) Before treatment case 6. (b) After treatment case 6.

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Figure 3:

(a) Before treatment case 8. (b) After treatment case 8.

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DISCUSSION

The pathogenesis of vitiligo is complex. Neural dysregulation, autoimmunity, and oxidative destruction of melanocytes are the proposed theory put forward in the pathogenesis of vitiligo.⁸ It is the combination of these mechanisms with genetic and environmental factors which lead to the destruction of melanocytes. Such predisposed melanocytes produce shock protein 70 and other varieties of inflammatory chemokines such as C-X-C motif chemokine 10 (CXCL10). Naïve T-cells get polarized into Type1 T helper cells (TH1) due to release of CXCL10. These TH1 cells in turn release chemoattractant, interferon-gamma which further upregulates CXCL-10 and CXCR 3 production. This upregulation of CXCL10 and CXCR3 production mediates cytotoxic T lymphocytes and natural killer cell activity, leading to melanocyte destruction.⁹ This entire pathway of melanocyte destruction is mediated by JAK/STAT signaling cascade. This relationship between the JAK/STAT pathway and vitiligo pathogenesis helps make useful therapeutic options. Topical tofacitinib might be a safe and effective therapy for vitiligo especially in those patients with localized disease.¹⁰ Topical JAK inhibitors lack the efficacy for lesions over photo protected or covered areas of the body largely due to inconsistent environmental ultraviolet (UV) exposure. Furthermore, it is practically impossible to expose genital skin for environmental UV radiation. Excimer lamp shows superior and faster treatment for vitiligo compared with NB-UVB therapy. Excimer light delivers high intensity radiation to the vitiliginous area thereby halting the disease progression and induction of repigmentation.¹¹

Deshpande in a short case series of lip vitiligo used excimer light therapy and found to be very effective with long remission period. However, it is not effective in all patients with vitiligo, wherein the combination with topical agents like calcineurin inhibitors was more effective.¹²

In this case series, topical tofacitinib 2% along with 308nm excimer light therapy has synergistically shown remarkable efficacy in producing repigmentation of male genital vitiligo lesions, thereby providing excellent treatment modality in the armamentarium for genital vitiligo. Similar results would be expected in female genital vitiligo.

CONCLUSION

Male genital vitiligo is relatively frequent and often induces marked impairment in quality of life in particular sexual life. Prompt recognition of activity remains mandatory to halt disease progression. Topical tofacitinib 2% with 308 excimer light should be a bright ray of hope in the management of relatively difficult to treat disease.