Oral Upadacitinib Combined with Phototherapy for Progressive Vitiligo in 7-Year-Old Children: A Two-Case Report

Abstract

We report two 7-year-old children with progressive vitiligo despite prior topical therapy and phototherapy; one patient had also received low-dose systemic corticosteroid therapy. Oral upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, was initiated at 15 mg once daily in both patients in combination with phototherapy. The boy underwent 308-nm excimer laser therapy every 3 days, whereas the girl received narrowband ultraviolet B phototherapy at the same interval. Before treatment, baseline screening was performed to exclude contraindications, and no clinically significant abnormalities were identified. After 4 weeks, both patients showed rapid repigmentation and a reduction in lesion extent. The boy with facial vitiligo achieved near-complete repigmentation (Vitiligo Area Scoring Index [VASI] reduced from 0.4 to nearly 0), while the girl with non-segmental vitiligo involving the trunk and extremities showed progressive repigmentation (VASI reduced from 2.7 to approximately 1.0 by week 8). Follow-up laboratory tests during upadacitinib treatment, including complete blood counts, liver and renal function tests, and lipid profiles, remained within normal limits, and no clinically significant adverse events were observed during 18–20 weeks of treatment. Oral upadacitinib combined with phototherapy was associated with rapid disease stabilization and repigmentation in these two children, although larger and longer-term studies remain necessary.

Introduction

Vitiligo is an acquired depigmenting disorder primarily associated with autoimmune dysregulation. Its worldwide prevalence is estimated at approximately 0.5%–2%.¹ In a population-based survey of 5209 US children aged 4–11 years, the clinician-adjudicated point prevalence of vitiligo was estimated at 0.84%.² In pediatric patients, particularly those with extensive involvement or lesions affecting exposed areas, the disease may impose a substantial psychosocial burden and significantly impair quality of life.³ Current treatment options for vitiligo include systemic corticosteroids, topical corticosteroids and calcineurin inhibitors, phototherapy, and surgical interventions; however, each has limitations, particularly in young children and in patients with active or extensive disease.^4,5 Systemic corticosteroids are constrained by adverse effects such as weight gain, insomnia, growth impairment, and immunosuppression, whereas prolonged topical corticosteroid use may cause cutaneous atrophy and calcineurin inhibitors may cause application-site reactions. Narrowband ultraviolet B (NB-UVB) and 308-nm excimer phototherapy require repeated treatment sessions and dose titration and may induce erythema; moreover, NB-UVB requires adequate cooperation for whole-body irradiation, whereas excimer treatment may be impractical for extensive disease. Surgical interventions are generally reserved for localized, stable disease after failure of medical treatment.^5,6 Consequently, safe and effective systemic treatment options for young children with progressive vitiligo remain limited.

Interferon-γ (IFN-γ)-driven immune responses play a central role in the pathogenesis of vitiligo and are largely mediated through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Accordingly, targeting the JAK pathway has emerged as a promising therapeutic strategy.⁷ Upadacitinib, a selective JAK1 inhibitor, has demonstrated efficacy in a Phase 2 trial involving adults with extensive non-segmental vitiligo;⁸ however, data in children younger than 12 years remain scarce. Therefore, we report two cases of progressive pediatric vitiligo treated with upadacitinib in combination with phototherapy to describe the clinical responses and short-term safety observations in children younger than 12 years.

Case Reports

Before initiating upadacitinib, both patients underwent baseline screening, including complete blood counts, liver and renal function tests, lipid profiles, cardiac enzyme testing, T-SPOT.TB testing, chest radiography, hepatitis B serology and HBV DNA testing, anti-HCV and HIV testing, and herpesvirus serology. No clinically significant abnormalities were identified. During upadacitinib treatment, complete blood counts, liver and renal function tests, and lipid profiles were monitored every 8 weeks and remained within normal limits.

A 7-year-old boy presented in July 2025 with a 3-year history of depigmented lesions around the mouth. The lesions were initially localized and slowly progressive; however, rapid expansion and further depigmentation were noted during the week before presentation, consistent with active disease. Physical examination revealed annular, milk-white depigmented patches distributed periorally with well-defined borders. Wood’s lamp examination showed bright blue-white fluorescence. The baseline Vitiligo Disease Activity (VIDA) score was 4, and the Vitiligo Area Scoring Index (VASI) was approximately 0.4. The guardian reported that previous treatment with topical tacrolimus and phototherapy had yielded no appreciable clinical improvement. After obtaining informed consent from the guardian, oral upadacitinib 15 mg once daily (0.625 mg/kg) was initiated in combination with 308-nm excimer laser therapy administered every 3 days (starting dose 100 mJ/cm², gradually increased according to erythema response). After 4 weeks of treatment, near-complete repigmentation was achieved, with the VASI decreasing to nearly 0. At week 8, upadacitinib was reduced to 15 mg twice weekly and excimer laser treatment to once weekly for maintenance. The maintenance regimen was continued through week 20, when upadacitinib and excimer laser therapy were discontinued. Topical tacrolimus 0.03% was then used for 3 months, followed by 5 months without treatment; no new depigmented lesions developed (Figure 1).

Figure 1.

Treatment response of facial vitiligo under clinical examination (A–C) and Wood’s lamp (D–F) before treatment (A and D) and after week 4 (B and E) and week 20 (C and F), showing marked and sustained repigmentation of lesions.

A 7-year-old girl presented in June 2025 with a 3-year history of depigmented lesions initially confined to the neck and right hand. The lesions gradually enlarged, and during the preceding 6 months, new depigmented patches developed on the trunk and extremities, indicating active disease. Physical examination revealed multiple irregular, partly coalescent depigmented patches on the neck and chest, with additional scattered lesions on the extremities and in the axillae, consistent with active non-segmental vitiligo. The baseline VIDA score was 4, and the VASI was approximately 2.7. Despite prior treatment with oral prednisone 5 mg/day, NB-UVB phototherapy, and topical therapies, new lesions continued to develop and existing lesions enlarged. After contraindications had been excluded and informed consent had been obtained, prednisone and topical therapies were discontinued, and oral upadacitinib 15 mg once daily (0.6 mg/kg) was initiated while NB-UVB phototherapy was continued every 3 days. After 4 weeks, perifollicular and island-like repigmentation was observed within the lesions, with a reduction in VASI to approximately 2.0. By week 8, lesions on the anterior neck had nearly resolved, while varying degrees of repigmentation were observed at other sites (VASI approximately 1.0; Figure 2). Upadacitinib was administered at 15 mg once daily for 18 weeks. Thereafter, travel-related difficulties precluded further follow-up at our center, and the subsequent clinical course could not be assessed.

Figure 2.

Treatment response of trunk vitiligo under Wood’s lamp before treatment (A) and after week 4 (B) and week 8 (C), showing progressive reduction and partial repigmentation of lesions.

Discussion

In the present report, two pediatric patients with progressive vitiligo achieved rapid disease stabilization and marked repigmentation following treatment with oral upadacitinib in combination with phototherapy. IFN-γ/JAK–STAT signaling contributes to vitiligo by inducing CXCL9/CXCL10-mediated recruitment of cytotoxic CD8⁺ T cells, while lesional tissue-resident memory T cells may sustain this inflammatory response and contribute to disease persistence and recurrence.^9,10

Upadacitinib, a selective JAK1 inhibitor, targets IFN-γ-mediated JAK–STAT signaling, providing a mechanistic rationale for its use in vitiligo.¹¹ In a phase 2 trial involving adults with extensive non-segmental vitiligo, the 11-mg and 22-mg upadacitinib groups achieved significantly greater improvements in Facial Vitiligo Area Scoring Index (F-VASI) at week 24 than the placebo group, with continued numerical improvement through week 52.⁸ However, because this trial enrolled only adults, high-quality clinical evidence in pediatric patients, particularly young children, remains scarce. Current evidence regarding the safety of upadacitinib in children is derived primarily from studies of other indications. Two open-label Phase 1 trials enrolled children as young as 2 years with severe atopic dermatitis or polyarticular-course juvenile idiopathic arthritis. The safety profile of upadacitinib was generally consistent with that previously observed in adults and adolescents, with no new safety signals identified.^12,13

Evidence regarding JAK inhibitors for pediatric vitiligo remains largely limited to case reports and small case series. Wang et al reported four children with progressive vitiligo who received upadacitinib; after 24 weeks, the mean improvement in VASI was 60.2%, with the greatest repigmentation observed in facial lesions.¹⁴ Biswal et al treated 13 children and adolescents aged 6–16 years with progressive non-segmental vitiligo using oral tofacitinib combined with brief daily sun exposure; two achieved near-complete repigmentation and six achieved 70%–80% repigmentation.¹⁵ Other case reports have likewise described varying degrees of repigmentation in children with vitiligo and concomitant atopic dermatitis or alopecia areata treated with upadacitinib, together with control of the underlying inflammatory disease.^16,17 An ongoing global Phase 3 study (NCT06118411) is evaluating upadacitinib in adults and adolescents aged ≥12 years with non-segmental vitiligo.¹⁸

Both children in our series received concomitant phototherapy, which may have contributed to the observed clinical responses. Liu et al retrospectively evaluated 10 patients with vitiligo treated with tofacitinib; five achieved repigmentation, predominantly at sites exposed to sunlight or low-dose narrowband UVB (NB-UVB) phototherapy.¹⁹ A subsequent meta-analysis similarly found that concomitant phototherapy was associated with higher rates of repigmentation among patients receiving JAK inhibitors.²⁰ Studies of lesional vitiligo skin have shown that NB-UVB-associated repigmentation is accompanied by activation and proliferation of follicular melanocyte-lineage cells, acquisition of phenotypic features consistent with putative migration, progressive differentiation, and restoration of the epidermal melanocyte population. Upregulation of GLI1 and activation of β-catenin-related signaling may contribute to these processes.^21,22 In addition, NB-UVB treatment has been associated with reductions in the proportions of circulating CD4⁺ and CD8⁺ central memory T cells and in serum CXCL9 and CXCL10 levels, suggesting an immunomodulatory effect.²³ Collectively, these findings provide a biological rationale for the contribution of phototherapy to repigmentation through both melanocyte regeneration and immune modulation. These mechanistic findings are directly relevant to the NB-UVB regimen used in the girl; their extrapolation to the 308-nm excimer laser therapy used in the boy should be made with caution.

Several limitations should be acknowledged. First, this report included only two patients, and the absence of a control group limits the strength and generalizability of the findings. Second, the concomitant use of phototherapy makes it difficult to determine the independent therapeutic effect of upadacitinib. Third, the duration of follow-up was limited and unequal between the two patients. The girl was lost to follow-up after 18 weeks, which limited assessment of the long-term durability of repigmentation and recurrence risk. Finally, as the use of upadacitinib in pediatric vitiligo remains investigational, its long-term safety—particularly with respect to growth, development, and immune function—requires further validation in larger, long-term studies.

Conclusion

In conclusion, oral upadacitinib combined with phototherapy was associated with substantial repigmentation in two pediatric patients with progressive vitiligo, with no clinically significant adverse events observed during 18–20 weeks of treatment. Larger prospective studies are needed to further evaluate the efficacy and long-term safety of this treatment approach.

Funding Statement

No funding was received for this study.

Ethics Statement

Institutional approval was required for publication of the case details and was obtained from the Ethics Committee of Guangzhou Dermatology Hospital (Approval No. gzsp2026669). Written informed consent for publication of the patients’ clinical details and images was obtained from the legal guardians of both pediatric patients.

Disclosure

All authors declare no competing interests.