Discussion

This case highlights two important observations: first, that dupilumab therapy was temporally associated with the onset of vitiligo in a patient with no prior personal or family history of the condition, and second, that topical ruxolitinib was associated with more pronounced repigmentation than tacrolimus in this patient, an observation that warrants further controlled study given important limitations discussed below.

The association between dupilumab therapy and new-onset vitiligo is increasingly recognized in the literature, though this relationship remains largely inferred from temporal proximity rather than confirmed through mechanistic or laboratory evidence [3-6]. Several case reports have documented vitiligo development within months of treatment initiation, and some have described rapid enlargement of pre-existing vitiligo lesions following dupilumab initiation, suggesting the drug may exacerbate existing subclinical disease [4]. A literature survey conducted by Mehta et al. reported an average latency of 3.11 months from dupilumab initiation to vitiligo onset, which aligns with the timeline observed in our patient [7]. The incidence of dupilumab-induced vitiligo appears to be low but may be underreported due to limited clinician awareness of this adverse effect. In this case, no autoimmune serologic workup, including thyroid function testing or autoantibody panels, was performed, and the patient reported no family history of vitiligo or other autoimmune disease. Because this evaluation was not pursued, alternative or contributing causes, such as subclinical autoimmune thyroid disease or an independent, coincidentally timed autoimmune process, cannot be excluded. The temporal relationship observed here is consistent with prior reports but should be interpreted as a plausible association rather than established causation.

The development of vitiligo during dupilumab therapy has been proposed to involve complex immunological mechanisms related to the drug's effects on cytokine balance. One hypothesis suggests that inhibition of Th2 cytokines (IL-4 and IL-13) by dupilumab may shift the immune balance toward Th1 and Th17 responses, which are implicated in mediating melanocyte destruction in vitiligo [3]. This shift could theoretically unmask latent autoimmune processes or trigger de novo autoimmunity against melanocytes, though this mechanism has not been directly confirmed in our patient. IL-13 also plays a role in maintaining skin barrier function and regulating local inflammatory responses [8], and blockade of IL-4 signaling may alter the cutaneous microenvironment in ways that could indirectly affect melanocyte survival through changes in keratinocyte-melanocyte interactions or local immune surveillance [9]. These mechanisms remain hypothetical in the context of this case and are drawn from the broader literature rather than from patient-specific mechanistic data.

This case also provided an opportunity to observe two topical vitiligo treatments applied concurrently, as tacrolimus 0.1% ointment was applied to the left hand while ruxolitinib cream was applied to the right hand, with both hands treated alongside systemic nemolizumab. Over the eight-week observation period, repigmentation appeared more pronounced on the ruxolitinib-treated hand. However, this observation carries several important limitations. Baseline disease severity differed between the two hands, with more extensive depigmentation present on the right hand prior to treatment initiation, which may itself influence the apparent degree of visible improvement independent of treatment effect. Additionally, this comparison is based on a single patient, relied on visual assessment rather than objective or quantitative outcome measures, and involved simultaneous discontinuation of dupilumab, initiation of nemolizumab, and introduction of both topical therapies. As a result, this case cannot isolate which intervention, or combination of interventions, was primarily responsible for the observed clinical improvement, and the finding should not be interpreted as evidence that ruxolitinib is more effective than tacrolimus. It is reported descriptively as an observed clinical outcome that may help generate hypotheses for future controlled comparison. Prior literature has proposed that the JAK-STAT pathway plays a role in vitiligo pathogenesis, with JAK inhibitors showing promise in modulating interferon-gamma signaling and other inflammatory cascades involved in vitiligo progression [10], which may offer biologic plausibility for the pattern observed here, though it does not substitute for a controlled comparison.