Significant repigmentation in pediatric vitiligo treated with oral upadacitinib

Dear Editor,

Vitiligo is an acquired pigmentary disorder characterised by melanocyte destruction, primarily mediated by autoimmune mechanisms. It affects approximately 1% of the global population, with childhood onset reported in up to 25% of patients.¹Paediatric vitiligo is associated with psychosocial distress and reduced quality of life for both children and their caregivers.²

However, treatment options remain limited, especially for progressive forms. Systemic therapies such as corticosteroids and immunosuppressants have been used cautiously due to their safety concerns in children. Emerging evidence supports Janus kinase (JAK) inhibitors in adult vitiligo by interrupting interferon gamma interferon (IFN)-γ-mediated melanocyte destruction.³ Therefore, JAK inhibitors represent a rational and targeted therapeutic alternative. Despite the growing use of JAK inhibitors in dermatology, paediatric data are scarce. We present a case series demonstrating the potential of upadacitinib in children with active vitiligo.

This institutional review board-approved case series enrolled children aged over 6 years with rapidly progressive vitiligo (Vitiligo Disease Activity Score, VIDA ≥4) and no recent immunosuppressive therapy. All participants had completed age-appropriate routine immunizations or other significant comorbidities. Exclusion criteria comprised prior exposure to JAK inhibitors, immunosuppressants, and the presence of active infections (hepatitis B, hepatitis C, or tuberculosis), malignancy, or pregnancy. Patients had no personal or family history of autoimmune diseases such as alopecia areata, psoriasis, or thyroid disorders. Patients received oral upadacitinib (15mg) once daily for 24 weeks. Due to the extended-release tablet formulation, dosage modification was not possible. Topical tacrolimus 0.1% was allowed as an adjunct therapy, while all other interventions, including phototherapy, were prohibited. Clinical response was evaluated using the Vitiligo Area Scoring Index (VASI) at baseline and every four weeks. Safety monitoring included complete blood counts, hepatic/renal function tests and infection screening.

The clinical characteristics of patients are shown in Table 1. The series included three girls and one boy with a mean age of 6.5 years and disease duration ranging from 0.25 to 10 months. One patient had segmental vitiligo, and the rest presented with generalised distribution. Disease stabilisation occurred within 2–3 weeks in all patients. At 24 weeks, the mean VASI improvement was 60.2% [Table 1]. Facial lesions showed the highest response (mean improvement 92.1%), with two patients reaching VASI90 [Figures 1a-c, 2a-c, 3 and Table 1]. Regional responses varied: trunk (69.3%), genital areas (60.0%), neck (30.4%), and limbs (27.0%) [Table 1]. The reduced response in certain regions may be related to frictional stress or earlier melanocyte loss.

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Figure 1:

(Patient 1) a) Baseline facial lesions, b) Perilesional repigmentation 8-weeks post treatment, c) Significant improvement at 24-weeks of treatment.

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Figure 2:

(Patient 4) a) Baseline hypopigmented patches on the forehead and around the eyes, b) Repigmentation after 8 weeks of treatment, c) Significant repigmentation at 24- weeks.

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Figure 3:

The changes in VASI scores of patients before and after treatment decreased to varying degrees.

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Treatment was well tolerated. One patient developed a mild upper respiratory tract infection, and another experienced a transient elevation in alkaline phosphatase, which normalised without intervention. No severe adverse events occurred, and no patient discontinued treatment.

Upadacitinib inhibits JAK1-mediated IFN-γ signalling, thereby disrupting the recruitment of CD8⁺ cytotoxic T-cells that play a central role in melanocyte apoptosis.³ A phase 2 study assessed upadacitinib in adults with extensive non-segmental vitiligo, which demonstrated significant repigmentation of vitiligo lesions over a 52-week period, with no new safety data identified beyond the known safety profile of upadacitinib.⁴ There have been a few reports about upadacitinib in young children with refractory vitiligo, with encouraging outcomes.⁵ Its safety in paediatric populations has been demonstrated in a phase 1 study for atopic dermatitis, where it was found to be generally well tolerated even in children as young as two years.⁶

In our series, though not weight-adjusted, a 15mg dose was safe and effective, likely owing to the extended-release formulation and stable pharmacokinetics. The substantial facial response aligns with previous reports in both adults and adolescents.^4,5 The neck’s relatively poor response, especially in one case, may be explained by early-onset disease, deeper melanocyte depletion, or mechanical irritation, suggesting that anatomical site and disease chronicity affect outcomes.⁷

Notably, all patients tolerated the treatment without serious adverse events. These findings align with safety data from studies of upadacitinib in paediatric atopic dermatitis, which suggest acceptable short-term tolerability in children as young as two years old.⁵

Additionally, this report adds to the limited data on systemic JAK inhibitor in paediatric segmental vitiligo which is otherwise a treatment-resistant form. These preliminary observations may be valuable for future trial design, including decisions around dosing, safety endpoints, and target lesion selection.

This study is limited by its small sample size, short follow-up duration, and a lack of control group. The off-label use of upadacitinib in this age group also warrants cautious interpretation of safety data. Furthermore, the absence of standardised quality-of-life assessments and immunological biomarkers restricts mechanistic insights.

Oral upadacitinib may represent a promising therapeutic option for progressive vitiligo in children. It can rapidly stabilise disease activity and induce significant repigmentation, particularly in facial areas, with good short-term tolerability. Further randomised controlled trials are needed to confirm efficacy, refine dosing, and establish long-term safety in paediatric populations.