ABSTRACT Segmental vitiligo (SV) is a distinct subtype of vitiligo characterized by an early onset, unilateral distribution, and rapid stabilization. Although traditionally considered neurogenic in origin, recent evidence suggests an immune‐mediated pathomechanism. However, the molecular mechanisms underlying SV remain poorly characterized, and therapeutic options are limited. Topical calcineurin inhibitors (TCI) are widely used in immune‐mediated dermatoses, but clinical data supporting their use in SV are scarce. We conducted a retrospective observational study of paediatric patients with SV treated with TCI, recording demographics, disease duration and 3‐month clinical response. In parallel, selected public transcriptomic datasets were re‐analysed to examine enrichment of TCR/Ca2 + −calcineurin/NFAT‐related pathways as supportive mechanistic context. Five of eight patients (62.5%) achieved significant repigmentation (VNS ≥ 4) after 12 weeks, with shorter disease duration correlating with better outcomes ( p = 0.0002451). Early intervention determined good clinical response even in cases with leukotrichia, and no adverse effects were observed. Transcriptomic re‐analysis provided supportive, descriptive signals consistent with activation of T‐cell signalling and Ca2 + −calcineurin/NFAT pathways in SV blood, while proxy datasets from non‐segmental vitiligo skin did not show similar enrichment. Overall, in this small retrospective paediatric case series, early use of topical calcineurin inhibitors was associated with favourable clinical outcomes in SV and demonstrated a good safety profile. Larger, prospective studies are warranted to confirm these preliminary findings and refine therapeutic strategies.
Paganelli et al. (2026) studied this question.