A case of mogamulizumab-induced vitiligo in a patient with mycosis fungoides

Vitiligo is an acquired disorder of pigmentation characterized by the development of asymptomatic, well-defined, depigmented macules and/or patches on the skin. The pathogenesis involves an interplay of genetic, environmental triggers, autoimmunity and oxidative stress mechanisms, thus leading to chemokine-driven melanocyte destruction by autoreactive cytotoxic CD8+ T lymphocytes.¹

Drug-induced vitiligo has been associated with biologic medications, including monoclonal antibodies, TNF-⍺ inhibitors, and interleukin inhibitors. Vitiligo-like depigmentation has also been reported in patients on immune checkpoint inhibitors.² Mogamulizumab is an anti-CC chemokine receptor-4 (CCR4) monoclonal antibody used to treat recalcitrant mycosis fungoides (MF) and Sézary syndrome (SS). The most common dermatologic adverse event is the ‘mogamulizumab-associated’ rash characterized by papules/plaques, folliculotropic MF-like plaques and cutaneous granulomatous drug eruption.^{3, 4} Alopecia areata universalis⁵ and a few cases of vitiligo have been reported.^{6, 7} In this case report, we add to the existing literature by presenting another case of mogamulizumab-induced vitiligo.

An 83-year-old African American male with a history of hypertension and stage IV-A2 MF with leukaemic disease and lymph node involvement presented to the dermatology clinic for follow-up visit and complaint of skin discoloration. The patient's initial peripheral blood smear revealed 60% atypical lymphocytes with cerebriform morphology. Flow cytometry findings revealed CD4:CD8 ratio of 48:1, and CD4+ population was divided into: 89% CD7− and 91% CD26−. His skin disease was initially controlled on topical corticosteroids; however, he began to have progression of his MF as evidenced by erythroderma, persistent skin erosions, new lymphadenopathy, and multiple hospitalizations for superinfection. Repeat biopsies were consistent with MF and negative for infection. Due to progression and lack of adequate disease control on topical corticosteroids and pulse dexamethasone, mogamulizumab was recommended and subsequently initiated. Approximately 6 months following the initial dose of mogamulizumab, the patient developed depigmented macules and patches on his bilateral upper extremities that slowly progressed in a symmetrical, generalized distribution consistent with non-segmental vitiligo (Figures 1a,b; 2a,b; and 3). The patient's vitiligo was not affecting him psychosocially, and he was not interested in pursuing treatment.

In this report, we present the case of a patient who developed vitiligo 6 months following the initiation of mogamulizumab. In Algarni et al.'s report of three cases, patients presented with well-demarcated hypopigmented patches ranging from acrofacial to scalp, truncal and upper extremity distribution from 6 to 8 months after initial treatment with mogamulizumab.⁶ Serrano et al. discussed two cases of vitiligo with an onset of 4 and 7 months after treatment with mogamulizumab, respectively.⁷ As an anti-CCR4 antibody, mogamulizumab works by depleting CCR4 on regulatory T-cells, which are overexpressed in patients with cutaneous T-cell malignancies.^{8, 9}

Vitiligo has been associated with MF/CTCL. In Herrmann et al., vitiliginous macules and patches were localized to CTCL-affected areas in patients with CD8+/CD4− malignant phenotypes.¹⁰ This suggests the role of malignant T-cell clones in the cytotoxic destruction of melanocytes seen in the pathophysiology of CTCL-induced vitiligo.¹⁰

Similarly, Suzuki et al. hypothesized that mogamulizumab triggers autoantibodies binding keratinocytes and melanocytes, which may play an important role in the pathogenesis of mogamulizumab-induced skin-related adverse events, including vitiligo.⁹ While eliminating CCR4-expressing T-regs, mogamulizumab may trigger melanocyte destruction via autoimmune mechanisms.^{8, 9}

Worldwide, the prevalence of vitiligo is approximately 0.5%−2% with an estimated prevalence up to 1.11% in the United States.¹ Due to the rarity of MF/SS, it is challenging to estimate the prevalence of vitiligo in this patient population. Although mogamulizumab-induced vitiligo is a clinical diagnosis, a biopsy may be performed to distinguish it from CTCL-associated vitiligo and other disorders of depigmentation. Due to the paucity of reported cases, further research is needed to further characterize the pathophysiology of mogamulizumab-induced vitiligo.

All authors contributed to the preparation of this manuscript, which involved the following tasks: (i) conception and design, (ii) drafting and revision of the manuscript and (iii) approval of the final manuscript version to be published.

The authors declare no conflict of interest.

The patient in this manuscript has given written informed consent for participation in the study and the use of their deidentified, anonymized, aggregated data and their case details (including photographs) for publication. Ethical Approval: Not applicable