Abstract
The isotopic response (IR) describes the rare finding of a new skin disorder occurring at the site of a previously healed, unrelated skin disease. This phenomenon is postulated to occur because of the formation of a localized immunocompromised zone secondary to damage to cutaneous lymphatic circulation and, in the setting of viral infection, immune hypersensitization to exogenous proteins. IR which occurs following varicella-zoster virus (VZV) reactivation most commonly manifests as granulomatous dermatitis (GD). Of the reported cases, few have occurred in the setting of treatment with immune checkpoint inhibitors, such as nivolumab and ipilimumab. These agents stimulate T-cell mediated hypersensitivity reactions that may contribute to host sensitization to viral proteins, granuloma formation, and subsequent GD. Here, we present a patient with metastatic melanoma, treated with nivolumab and ipilimumab, who had a reactivation of latent VZV which was treated acutely with antiviral therapy. The initial zoster eruption subsided within a few weeks, although extreme postherpetic neuralgia (PHN) resulted. Months later, scaly red-pink papules coalescing into plaques erupted within the same dermatomal distribution of the previous zoster rash. Given concern for recurrent zoster, treatment with valacyclovir was reinitiated, but did not result in improvement in the new eruption. Punch biopsy was performed, revealing a prominent infiltrate of epithelioid histiocytes in the superficial reticular dermis with poorly formed granulomas and areas of palisaded granuloma formation. No sebaceous gland necrosis or viral cytopathic effect was present. Adjuvant treatment with high-potency topical steroids and oral gabapentin diminished the rash, but minimally improved PHN. This case highlights the importance of keeping post-herpetic IR in the differential diagnosis of a dermatomal rash, particularly in a patient not responding to antiviral therapy or with an otherwise atypical presentation.
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