Introduction
Dupilumab, a fully human monoclonal antibody, functions as an interleukin-4 receptor alpha (IL-4Rα) antagonist by blocking the signaling pathways of IL-4 and IL-13, two key cytokines driving type 2 inflammatory responses in atopic dermatitis (AD). It is approved for the treatment of moderate-to-severe AD and has demonstrated significant therapeutic efficacy. Nevertheless, dupilumab does not fully eliminate type-2 immune activity; its therapeutic effect relies on partial suppression of type-2 inflammation, which may disturb the homeostatic balance between type 1 and type 2 immunity.
Rare paradoxical autoimmune adverse events such as vitiligo may emerge following dupilumab administration, necessitating heightened vigilance among both clinicians and patients. This report details a case of dupilumab-induced vitiligo, outlining its clinical presentation, diagnostic process, and treatment response. Furthermore, we discuss the potential pathophysiological mechanisms underlying this paradoxical immune-mediated adverse event, together with a comparative summary of previously published similar cases.
Case Presentation
A 72-year-old male with a 2-year-history of atopic dermatitis (AD) presented to our clinic with faint erythematous plaques accompanied by slight desquamation, predominantly involving the scalp, neck, and dorsal aspects of both hands (Figure 1A–C). He had undergone prior treatment with topical corticosteroids and systemic antihistamines, resulting in no significant clinical improvement. His other comorbidities included type 2 diabetes mellitus and hypertension.
During the initial clinical assessment, the Eczema Area and Severity Index (EASI) score was 20, the Pruritus-Numeric Rating Scale (PNRS) score was 8, and the Dermatology Life Quality Index (DLQI) score was 12. Therefore, dupilumab therapy was initiated at a loading dose of 600 mg, followed by maintenance doses of 300 mg every 2 weeks. At the 10-week follow-up appointment, complete resolution of AD cutaneous lesions was noted (EASI: 0; PNRS: 0; DLQI: 0).
Hypopigmented macules were observed diffusely on the scalp, preauricular region, postauricular region, lateral cervical region, posterolateral cervical region, and dorsal aspects of both hands (Figure 1D–F). Suspicious for dupilumab-induced vitiligo, a Wood’s lamp examination indicated bright white fluorescence in the achromatic macules (Figure 1G–I). The patient declined dermatopathological testing.
The diagnosis of vitiligo was supported by characteristic clinical features and Wood’s lamp examination, despite the absence of histopathological confirmation.Figure 1Clinical photographs of the patient at different time-points, including baseline, 10-week follow-up after dupilumab treatment, and Wood’s lamp examination findings. (A) Baseline lateral view of the patient’s scalp and neck before dupilumab therapy, showing faint erythematous plaques with slight desquamation. (B) Baseline dorsal view of the right hand with eczematous lesions.
(C) Baseline dorsal view of the left hand with eczematous lesions. (D) Ten-week post-treatment pre-auricular region with diffuse hypopigmented macules. (E) Ten-week post-treatment postauricular and lateral-cervical regions with diffuse hypopigmented macules.
(F) Ten-week post-treatment dorsal aspects of bilateral hands showing scattered hypopigmented macules. (G) Wood’s lamp view: bright-white fluorescence of depigmented macules in pre-auricular and cervical areas. (H) Wood’s lamp view: bright-white fluorescence of depigmented macules on the scalp.
(I) Wood’s lamp view: bright-white fluorescence of achromatic macules over the dorsal aspects of both hands. Baseline lesions predominantly involved the scalp, neck, and dorsal aspects of both hands. After 10-weeks of dupilumab treatment, diffuse hypopigmented macules appeared on the scalp, preauricular region, postauricular region, lateral cervical region, posterolateral cervical region, and dorsal aspects of both hands.
Wood’s lamp examination demonstrated bright–white fluorescence within these achromatic macules.Clinical and Woods lamp images of a 72-year-old male with atopic dermatitis and hypopigmented macules.
A diagnosis of vitiligo was made. Treatment with topical corticosteroids, topical calcineurin inhibitors and narrow-band ultraviolet B (nbUVB) phototherapy was started. The patient elected to discontinue dupilumab due to complete remission of atopic dermatitis rather than progression of adverse events.
At 24-week follow-up visit, AD has attained complete remission, whereas vitiligo has remained stable without notable improvement.
Discussion
Dupilumab is a fully human monoclonal antibody that acts as an interleukin-4 receptor alpha (IL-4Rα) antagonist, exerting its effects by blocking the signaling pathways of IL-4 and IL-13. Dupilumab is approved for treating moderate-to-severe AD. Among its adverse events, injection-site reactions are most frequently reported, followed by ophthalmic issues (dry eye, conjunctivitis, blepharitis, keratitis, eye pruritus), alopecia areata, herpes virus infections, paradoxical head and neck erythema (“dupilumab red face”), psoriatic lesion onset, cutaneous T-cell lymphoma progression, and arthritis.1
To date, there have been relatively few reports of vitiligo induced by dupilumab treatment. Vitiligo during dupilumab therapy is linked to imbalanced T helper (Th)2/Th1/Th17 pathways, although exact molecular drivers remain incompletely clarified. Some scholars speculate that dupilumab-mediated blockade of IL-4 signaling induces Th1/Th17 polarization, upregulates vitiligo-related cytokines (such as IL-17 and IFN-γ), and recruits self-reactive CD8⁺ T cells to target melanocytes.2,3 Importantly, dupilumab achieves down-regulation instead of complete abrogation of type 2 inflammation.
It partially blocks IL-4/IL-13 signaling but cannot fully abolish type-2 immune pathways; this partial suppression creates an immune milieu that amplifies type-1 immune responses and promotes autoimmune injury to melanocytes. Our clinical case further supports the concept that modulation of type 2 inflammation may unmask or enhance type 1 immune responses, contributing to autoimmune pigmentary disorders.
The clinical characteristics of previously published cases and our present patient are summarized in Table 1. Mehta S et al found that among patients who developed vitiligo, the average duration from dupilumab initiation to vitiligo onset was 3.11 months, with a range of 1–6 months.4 Our patient developed vitiligo at 10-week follow-up, which falls within this reported time window. While the risk is comparatively low, physicians ought to notify patients about the likelihood of vitiligo occurring, with explicit counselling to closely monitor cutaneous pigmentation alterations in the initial six months following dupilumab initiation.
Ren H et al reported that either topical immunosuppressants or nbUVB phototherapy achieved satisfactory repigmentation or stabilization of vitiligo, even among patients who continued dupilumab therapy.5 In our case, vitiligo remained stable without obvious repigmentation after combined topical and nbUVB treatment, and dupilumab was discontinued owing to complete AD remission. Table 1Summary of Published Case Reports and Case Series of Vitiligo Induced by DupilumabReferenceAge Year OldTime from Dupilumab Initiation to vitiligo onsetVitiligo treatmentDupilumab continuationVitiligo outcomeMehta et al424–77 1–6 months (mean 3.11 months)Topical immunosuppressants, phototherapyContinued / discontinuedStable / partial repigmentationRen et al551–68 2–5 monthsTopical steroids, calcineurin inhibitors, nbUVBContinued in most patientsStable or partial repigmentationPresent case7210 weeksTopical corticosteroids, topical calcineurin inhibitors, nbUVB phototherapyDiscontinuedStable, no obvious repigmentation
Collectively, this case and existing literature emphasize that clinicians should remain alert to paradoxical pigment-altering adverse events under dupilumab. Additional basic and clinical investigations are required to decode the precise immune crosstalk between type 2 and type 1 responses leading to vitiligo.
Conclusion
This case report highlights the occurrence of vitiligo following dupilumab treatment for atopic dermatitis. While dupilumab is highly effective in managing AD, its potential to induce vitiligo, though rare, warrants clinical attention. We hypothesize that dupilumab-mediated down-regulation rather than complete inhibition of type 2 inflammation may augment type 1-driven inflammatory responses, thereby triggering autoimmune-mediated melanocyte injury and vitiligo.
Dupilumab blocks IL-4 and IL-13 signaling to dampen type 2 immune activity but does not fully abolish type 2-related immune pathways; this immune shift may promote Th1-polarized responses with elevated IFN-γ and self-reactive CD8⁺ T-cell recruitment targeting melanocytes.2,3 Despite the vitiligo showing no significant improvement with topical treatments in this patient, the AD achieved complete remission. Therefore, dermatologists should be aware of pigmentary changes as a potential paradoxical immune-mediated adverse event during dupilumab therapy, particularly within the initial six months of treatment. Further studies are needed to elucidate the underlying mechanism of dupilumab-induced vitiligo.