Use of Oral Tofacitinib in the Treatment of Pediatric Vitiligo: A Case Series

Abstract

Dear Editor, Vitiligo causes depigmentation by progressive autoimmune melanocyte destruction. Paediatric patients account for 26% of cases, and peak onset is between 4 and 8 years. Available treatment modalities include corticosteroids, calcineurin inhibitors and narrow-band ultraviolet B (NB-UVB) phototherapy.[1] Recently, Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors have been effective in treating vitiligo. However, its use in children is limited. Recent findings indicate JAK-STAT pathway involvement in vitiligo pathogenesis, driven by CD8+ T cells producing IFN-γ via the JAK1/2 pathway. This leads to the expression of CXCL9 and CXCL10 in keratinocytes, further damaging the melanocytes. Tofacitinib, a JAK 1/3 inhibitor, effectively blocks these pathways, showing promise in vitiligo treatment. Originally approved for rheumatoid arthritis, tofacitinib is now used in various dermatological conditions. Few case reports have been published showing repigmentation with oral tofacitinib and sun exposure.[2] We enrolled 13 patients of progressive vitiligo with inclusion criteria being, failure to topical treatment >3 months, oral steroids and cyclosporine >6 weeks, no significant improvement in vitiligo extent score (VES), progressive, non-segmental resistance to treatment cases and excluded patients with a history of any recent live vaccination, active infection or malignancy. Relevant baseline investigations like complete blood count, liver function test, renal function test, lipid profile, Mantoux test, TB QuantiFERON Gold, chest X-ray and Triple H. Patients were started with oral tofacitinib 5 mg twice daily along with sun exposure for 5 to 10 minutes at 8 am. There was gradual dose tapering in 3 to 6 months. Follow-up was done for another 6 months. The response evaluation was assessed by VES at baseline and 6 months. The dermoscopy finding at baseline showed a decreased pigment network and no perilesional pigmentation, and after 6 months of therapy, there was a significant increase in the perilesional and perifollicular pigmentation along with background erythema. The details of all the patients enrolled with their efficacy and safety profiles are depicted in Table 1. The literature regarding the use of tofacitinib in paediatric vitiligo is limited. There is a single case report in paediatric age, where segmental vitiligo was treated successfully with a combination of topical 2% tofacitinib and phototherapy for 3 months.[3] Phan et al. explained the synergistic action of JAK inhibitors with phototherapy.[4] JAK inhibitors suppress the CD8+ T cells and IFN-γ.[5] Joshipura et al. reported rapid improvement in facial vitiligo when treated with a combination of systemic tofacitinib and low-dose NB-UVB phototherapy. Additionally, they reported a comparatively better response over photo-exposed areas.[5] Common systemic side effects include upper respiratory tract infections, nasopharyngitis, transient cytopenias and dearranged lipid profiles. Cutaneous side effects like acne, acneiform eruptions, eczema herpeticum and herpes zoster have been reported recently with JAK inhibitors. In our case series, at the end of 6 months out of 13 patients, TWO Patients showed near complete pigmentation, six patients showed 70–80% repigmentation, one patient was lost to follow-up, and four patients were unresponsive to therapy. Sun-exposed areas responded better than covered areas. Overall the VES score showed significant improvement. After 6 months of treatment with tofacitinib 5 mg twice daily, the dose was tapered to 5 mg once daily for 3 months and then it was stopped. Patients were followed up for 6 months for any side effects or reappearance of lesions. One patient showed the reappearance of vitiligo lesions in the follow-up period and one patient reported grade 2 acne post-3 months of tofacitinib indicating the role of JAK signalling in the expression of acne. We did not encounter any other major side effects. Although serious side effects including lymphoproliferative disorders are uncommon, they need to be addressed and the patient needs to be counselled regarding the same.[5] Our case series suggests tofacitinib monotherapy is a safe and effective treatment modality for paediatric vitiligo. In cases where the immune response in vitiligo patients is significantly suppressed, the need for standard UV radiation therapy two or three times a week may be reduced. Lower UV fluences can still stimulate repigmentation. Larger prospective studies with longer follow-ups are required to confirm the efficacy, long-term safety and durability of treatment response.Table 1: Case descriptionFigure 1: Case 1 images. (a) A single depigmented patch over vulva (Baseline). (b) Complete repigmentation of the patch after 6 months of tofacitinib 5 mg BIDFigure 2: Case 8 images. (a) Depigmented patches over bilateral legs and knee (Baseline). (b) Complete repigmentation of the patches after 6 months of tofacitinib 5 mg BIDFigure 3: Case 4 images. (a) Multiple ill-defined depigmented patches over face and chest (Baseline). (b) Near complete repigmentation of the patches after 6 months of tofacitinib 5 mg BIDDeclaration of patient consent Informed consent was taken from the patient for using the clinical data and publication of photographs after ensuring anonymity. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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