Development of Halo Nevi in a Lung Cancer Patient: A Novel Immune-Related Cutaneous Event from Atezolizumab.

Immunotherapy-induced vitiligo is an immune-related adverse event (irAE) observed in metastatic melanoma patients treated with immune checkpoint inhibitors that target the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death-1 (PD-1) pathways. To date, the development of leukoderma, poliosis, and halo nevi during immunotherapy has largely been reported in metastatic melanoma patients. We report a case of immunotherapy-induced leukoderma presenting as halo nevi in a patient with non-small cell lung cancer (NSCLC) treated with atezolizumab, a programmed cell death ligand (PD-L1) antibody. Immunotherapy-induced vitiligo in metastatic melanoma patients may be associated with improved survival, but it remains to be determined whether its occurrence in non-melanoma cancers has the same prognostic significance.

J Drugs Dermatol. 2017;16(10):1047-1049.

Vulvar vitiligo-like depigmentation and multiple halos of hypomelanosis at the trunk following treatment with imiquimod 5% cream for vulvar condylomata: casual or related events?

A 25-year-old Caucasian female with multiple genital warts involving the vulvar area was treated with imiquimod 5% cream. During follow-up the patient developed areas of hypopigmentation at the site of application of imiquimod cream and areas of hypomelanosis around multiple preexisting nevi of the trunk. At 18 months follow-up genital depigmentation persisted and halo nevi of the trunk were still present. Different mechanisms of imiquimod-induced depigmentation have been reported. Halo nevi are considered expression of an autoimmune response. In the case presented here, it might be conceivable that both vitiligo-like depigmentation at the site of application and halo of hypomelanosis around melanocytic nevi have been induced by the same immunologic mechanism elicited by topical application of imiquimod.

Vulvar vitiligo-like depigmentation and multiple halos of hypomelanosis at the trunk following treatment with imiquimod 5% cream for vulvar condylomata: casual or related events?

A 25-year-old Caucasian female with multiple genital warts involving the vulvar area was treated with imiquimod 5% cream. During follow-up the patient developed areas of hypopigmentation at the site of application of imiquimod cream and areas of hypomelanosis around multiple preexisting nevi of the trunk. At 18 months follow-up genital depigmentation persisted and halo nevi of the trunk were still present. Different mechanisms of imiquimod-induced depigmentation have been reported. Halo nevi are considered expression of an autoimmune response. In the case presented here, it might be conceivable that both vitiligo-like depigmentation at the site of application and halo of hypomelanosis around melanocytic nevi have been induced by the same immunologic mechanism elicited by topical application of imiquimod.

Multiple halo naevi associated with tocilizumab.

Tocilizumab, a humanized monoclonal antibody directed against the interleukin (IL)-6 receptor, is approved for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis (JIA). We describe a case of multiple halo naevi occurring in a patient with a history of JIA treated with tocilizumab. IL-6 is a key cytokine in the setting of cancer through its effects on angiogenesis and inhibition of adaptive anti-tumour immunity. IL-6 also plays a role in melanocyte function, and increased levels have been noted in vitiligo skin, where it is a paracrine inhibitor of melanocytes. Tocilizumab may therefore lead to the development of halo naevi secondary to subsequent activation of adaptive immunity. Alternatively, as tocilizumab results in increased serum IL-6 levels, the epidermal cytokine profile is altered. Increased levels of IL-6 may therefore have a direct inhibitory effect on melanocytes, where access by tocilizumab may be limited due to differential size difference.

Deterioration of vitiligo and new onset of halo naevi observed in two patients receiving adalimumab.

Two patients with a long-standing history of recalcitrant ankylosing spondylitis were commenced on adalimumab as monotherapy. Case 1 developed marked rapid deterioration in his previously stable vitiligo within 3 months of commencing treatment. This was attributed to anti-tumor necrosis factor (TNF) therapy, and a marked improvement was noted following withdrawal of adalimumab. Case 2 developed multiple new halo naevi over the trunk and limbs. They did not show dysplastic features and have remained unchanged despite continuation of treatment. Possible mechanisms and implications of the paradoxical occurrence of immune-mediated skin lesions seen in patients receiving anti-TNF therapies are discussed.