Nivolumab induced inflammation of seborrheic keratoses: a novel cutaneous manifestation in a metastatic melanoma patient

Abstract

Immune checkpoint inhibitors targeting the programmed cell death (PD)-1 receptor have dramatically changed the landscape of metastatic melanoma treatment. Nevertheless, these immuno-modulatory agents have associated side effects, including dermatologic manifestations. To this end, we report a patient with metastatic melanoma that was treated with a PD-1 inhibitor, and subsequently developed inflammation of existing seborrheic keratosis lesions and new verrucous keratoses, a cutaneous side effect that has not been previously reported to our knowledge. The etiology of seborrheic and verrucous keratoses is not well understood, although their physical and histopathologic similarities to chronic viral-derived lesions, such as human papilloma virus, suggest a potential viral association. Chronic viral infections are known to result in T-cell tolerance because of persistent antigen stimulation. PD-1 inhibition is able to reinvigorate exhausted T cells, which are accordingly able to decrease viral load. Thus, the inflammatory reaction, seen in our patient, may be the result of PD-1 inhibition reactivating virally driven T lymphocytes.

Diffuse lichen planus-like keratoses and clinical pseudo-progression associated with avelumab treatment for Merkel cell carcinoma, a case report

“…The pathogenesis of LPLK is unknown, but it has been postulated that they represent an inflammatory response targeting a pre-existing epidermal lesion such as SK, lentigo, or actinic keratosis [12]. Extensive inflamed SKs presenting as an immune-mediated adverse event has also been reported in a patient receiving nivolumab for metastatic melanoma [13].…”

Recent advances in managing and understanding seborrheic keratosis

“…The inflammation of pre-existing seborrheic warts during chemotherapy of malignancies using drugs such as cytarabine, docetaxel, gemcitabine, or PD1 inhibitors like nivolumab has been coined pseudo-Leser–Trélat sign 42, 43 . It can be associated with burning and pruritus.…”

Immune Checkpoint Inhibitor Can Reduce HCV-RNA without Liver Damage

“…Another group also reported the safety with an efficacy signal during treatment of PD-1 inhibitor for cancers with HIV ( 20 ). In a metastatic melanoma patient, nivolumab might induce inflammation of seborrheic keratoses by PD-1 inhibition reactivating virally driven T lymphocytes ( 21 ). Furthermore, CTLs can control viruses non-cytotoxically via interferon-γ production ( 22 ).…”