Eruptive halo nevi and new-onset vitiligo post-COVID-19 infection

To the Editor: Halo nevi are benign, melanocytic nevi characterized by surrounding depigmentation and are commonly associated with vitiligo. We read the interesting report by Schmidt et al1Schmidt A.F. Rubin A. Milgraum D. Wassef C. Vitiligo following COVID-19: a case report and review of pathophysiology.JAAD Case Rep. 2022; 22: 47-49https://doi.org/10.1016/j.jdcr.2022.01.030Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar describing new-onset of vitiligo post COVID-19 infection and present a patient who developed both eruptive halo nevi and vitiligo after a confirmed COVID-19 infection. It is recognized that COVID-19 infection is able to trigger new-onset autoimmune disease, and like the authors, we propose this presentation is secondary to COVID-19 immunopathogenesis. A 37-year-old female presented for evaluation of a sudden eruption of asymptomatic depigmented patches on her body, both solitary and surrounding preexisting melanocytic nevi, 4 weeks after testing positive for SARS-CoV-2. Uveal melanoma was excluded on ophthalmological assessment. On examination, there were depigmented, scalloped patches ranging in size from 1 to 4 cm, both solitary and around most nevi, located on the chest and back (Fig 1). Wood’s light examination demonstrated bright white fluorescence. Total body examination using dermoscopy (DermLite DL4) did not demonstrate nevi suspicious for melanoma. The etiology of halo nevi and vitiligo remains to be fully elucidated. A cytotoxic, autoimmune mechanism is likely implicated in both diseases, as evidenced by a pronounced infiltration of Granzyme B secreting CD8+ (cluster of differentiation 8+) lymphocytes in lesional skin in halo nevi and vitiligo when compared to healthy controls (P < .01).2Yang Y. Li S. Zhu G. et al.A similar local immune and oxidative stress phenotype in vitiligo and halo nevus.J Dermatol Sci. 2017; 87: 50-59https://doi.org/10.1016/j.jdermsci.2017.03.008Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Additionally, one study showed that 64% of halo nevi (n = 15) exhibited 40% to 80% Programmed cell death-1 (PD-1) staining, which may reflect the presence of T-regulatory (T-reg) cells.3Botella-Estrada R. Kutzner H. Study of the immunophenotype of the inflammatory cells in melanomas with regression and halo nevi.Am J Dermatopathol. 2015; 37: 376-380https://doi.org/10.1097/DAD.0000000000000205Crossref PubMed Scopus (18) Google Scholar T-reg cells are an immunosuppressive subpopulation of T-cells that play a key role in self-tolerance, and their dysfunction is implicated in autoimmunity. The pathogenic role of T-reg cells in halo nevi remains unclear, but their role in halo nevi development may reflect a possible feedback mechanism secondary to CD8+-mediated inflammation. Research examining the immunopathogenesis of COVID-19 describes a shift toward type 1 adaptive immunity, with an increase in CD8+ cell cytotoxicity and a disruption of tolerogenic homeostasis.4Tan Y. Tang F. SARS-CoV-2-mediated immune system activation and potential application in immunotherapy.Med Res Rev. 2021; 41: 1167-1194Crossref PubMed Scopus (29) Google Scholar Schmidt et al1Schmidt A.F. Rubin A. Milgraum D. Wassef C. Vitiligo following COVID-19: a case report and review of pathophysiology.JAAD Case Rep. 2022; 22: 47-49https://doi.org/10.1016/j.jdcr.2022.01.030Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar described new-onset vitiligo post-SARS-CoV-2 infection, postulating a hyperstimulated CD8+ response and increased oxidative stress as catalysts. Furthermore, COVID-19 has been shown to increase multiple pro-inflammatory cytokines, including IFN-γ (interferon gamma).4Tan Y. Tang F. SARS-CoV-2-mediated immune system activation and potential application in immunotherapy.Med Res Rev. 2021; 41: 1167-1194Crossref PubMed Scopus (29) Google Scholar IFN-γ is a robust potentiator of CD8+ cell function, and its role has been implicated in depigmentation in both halo nevi and vitiligo.2Yang Y. Li S. Zhu G. et al.A similar local immune and oxidative stress phenotype in vitiligo and halo nevus.J Dermatol Sci. 2017; 87: 50-59https://doi.org/10.1016/j.jdermsci.2017.03.008Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Interestingly, IFN-γ can be produced by autoreactive CD8+ cells and acts through autocrine signaling to promote local cytotoxic activity.2Yang Y. Li S. Zhu G. et al.A similar local immune and oxidative stress phenotype in vitiligo and halo nevus.J Dermatol Sci. 2017; 87: 50-59https://doi.org/10.1016/j.jdermsci.2017.03.008Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar Additionally, SARS-CoV-2 can lead to a systemic overexpression of PD-1, the blockade of which has been shown to counter post-COVID-19 autoimmune sequalae.5Loretelli C. Abdelsalam A. D'Addio F. et al.PD-1 blockade counteracts post–COVID-19 immune abnormalities and stimulates the anti–SARS-CoV-2 immune response.JCI Insight. 2021; 6e146701https://doi.org/10.1172/jci.insight.146701Crossref PubMed Scopus (35) Google Scholar The exact role of the PD-1/PDL-1 axis in halo nevi and vitiligo etiopathogenesis remains unclear. We hypothesize that in genetically susceptible individuals, COVID-19 disrupts immune tolerance, resulting in increased inflammation potentiated by increased IFN-γ signaling and consequent cytotoxic destruction of melanocytes. None disclosed.

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