Psoriasis caused by pembrolizumab treatment in advanced melanoma: A positive prognostic side effect?

Abstract

Dear Editor, Melanoma is the malignant tumor whose incidence increases with greater speed, in order to reduce mortality, primary prevention, early diagnosis, and correct therapies are essential. Immune system and checkpoint blockers (ICI) (monoclonal antibodies targeted to the antigen-4 associated with cytotoxic T lymphocytes [CTLA4], programmed cell death protein 1 [PD-1] or ligand of programmed death 1 [PD-L1]), have been increasingly used for their differential impact on the long-term survival of patients with metastatic melanoma. The usefulness of ICI therapy has been limited by immune-related adverse reactions, which affect systems of multiple organs. As reported by Chan et al. skin manifestations are among the most frequent, as eczema, lichenoid reaction, or vitiligolike depigmentation. The presence of at least one of these manifestations is associated with a better prognostic outcome. Recently, a few reports described psoriasis onset or exacerbation during these treatments. We report a case of 72 years old woman who came to our observation sent by oncologist. The patient suffered from a large metastasis of the thigh confirmed by histological examination in the absence of identifiable primary tumor. After the genetic examination excluded the presence of BRAF mutations, oncologist had started immunotherapy treatment with pembrolizumab. After 1 month together with an important and significant response of the melanoma, the appearance of erythemato-squamous patches occurred mainly at the limbs and trunk. Clinical and biopsy examination confirms the diagnosis of psoriasis (Figure 1(A),(B)). The personal and family history was negative for psoriasis. The psoriatic patches were associated with pruritus sometimes so intense to think the patient to stop immunotherapy. We treated the psoriasis lesions first with topical and systemic cortison treatment, then, in according to oncologist, we switched to acitretin therapy (25 mg/ daily) associated with a low dose of systemic corticosteroids (10 mg/daily of methylprednisolone). The psoriasis response was good and the patient was able to continue immunotherapy. Interestingly, together with this side effect, we noted a significant response of melanoma to immunotherapy along 6-months treatment, as depicted in the clinical evaluation and imaging (Figure 1 (C)–(F)). Checkpoint inhibitors are associated with a disease-free survival higher than that of conventional chemotherapy but also with a different spectrum of side effects, essentially of the immune-related type and frequently cutaneous. If these are not adequately recognized and treated, they can lead to discontinuation of therapy. Recent literature describes well-managed cases with acitretin, apremilast, and methotrexate. Psoriasis is a rare side effect, but it was still important to recognize and treat promptly in order not to stop immunotherapy. Furthermore, we want to report this peculiar case because the development of psoriasis was associated with a good melanoma response, therefore it could be considered as a positive prognostic response factor, as reported for vitiligo, and eczematous or lichenoid reaction. The efficacious proliferation and hyperactivation of T lymphocytes, caused by anti PD-1, determine a destruction of cancer cells, but on the other hand, they can play an important role in the pathogenesis of most immune-related skin reaction and pathogenesis. Therefore, the appearance of these manifestation could be indicative of a particularly effective T response also against cancer cells. Further studies will better define the pathogenic mechanisms, most of them still unknown yet, and the prognostic role of psoriasis in immunotherapy.