Subject(s)
Glucocorticoids/therapeutic use , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Immunoglobulins, Intravenous/administration & dosage , Skin Diseases/drug therapy , Acute Disease/therapy , Adult , Biopsy , Dose-Response Relationship, Drug , Drug Therapy, Combination/methods , Fatal Outcome , Female , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Graft vs Host Disease/pathology , Humans , Male , Middle Aged , Severity of Illness Index , Skin/pathology , Skin Diseases/diagnosis , Skin Diseases/etiology , Skin Diseases/pathology , Transplantation, Homologous/adverse effects , Treatment OutcomeABSTRACT
Programmed cell death 1 (PD-1) blockade has rapidly emerged as an effective therapy for a wide variety of metastatic malignancies. It has been associated with multiple immune-related adverse effects, including cutaneous eruptions. We describe two patients with clinical and histological findings that were consistent with subacute cutaneous lupus erythematosus (SCLE) after receiving PD-1 inhibitor therapy for metastatic lung cancer. We successfully treated our first patient with systemic and topical steroids, photoprotection and hydroxychloroquine. However, he subsequently developed dermatomyositis after continuing PD-1 inhibitor therapy. Our second patient presented with a protracted course of a cutaneous eruption in spite of discontinuation of anti-PD-1 therapy and treatment with systemic corticosteroids and infliximab. This patient's SCLE resolved after the addition of topical steroids and photoprotection and discontinuation of anti-tumour necrosis factor therapy. She and her oncology team decided to pursue non-PD-1 inhibitor treatment for lung cancer owing to a lack of tumour response. We add SCLE and dermatomyositis to the growing list of autoimmune complications of PD-1 blockade. Our cases raise a number of questions, particularly in relation to the viability of continuing anti-PD-1 therapy after developing SCLE and the role of immunosuppressive therapy in patients with PD-1 inhibitor-associated connective tissue disease. What's already known about this topic? Programmed cell death 1 (PD-1) blockade, which is rapidly emerging as a therapy for a wide variety of metastatic malignancies, has been associated with multiple immune-related adverse effects. These include systemic autoimmune diseases such as colitis and thyroiditis in addition to numerous cutaneous adverse events. Cutaneous side-effects of PD-1 inhibitors most commonly reported in clinical trials include lichenoid reactions, eczematous dermatitis and vitiligo. What does this study add? We report two cases of PD-1 inhibitor-associated subacute cutaneous lupus erythematosus (SCLE), with one patient progressing to dermatomyositis with continued PD-1 inhibitor treatment. In addition to being a novel cutaneous adverse event, we also demonstrate the possibility of development of multiple autoimmune diseases in one patient, which is different from classic drug-related SCLE. We discuss the treatment challenges for patients with autoimmune skin disease receiving PD-1 inhibitor therapy.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Agents, Immunological/adverse effects , Dermatomyositis/immunology , Lupus Erythematosus, Cutaneous/immunology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Biopsy , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/immunology , Dermatomyositis/chemically induced , Dermatomyositis/diagnosis , Dermatomyositis/pathology , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Lupus Erythematosus, Cutaneous/chemically induced , Lupus Erythematosus, Cutaneous/diagnosis , Lupus Erythematosus, Cutaneous/pathology , Male , Middle Aged , Nivolumab/adverse effects , Programmed Cell Death 1 Receptor/immunology , Skin/drug effects , Skin/immunology , Skin/pathology , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/immunologyABSTRACT
BACKGROUND: The incidence of cutaneous squamous cell carcinoma (cSCC) is markedly increased in renal transplant recipients compared with that of the nontransplant population. AIM: To investigate whether there is a relationship between transplant rejection and cSCC. METHODS: The Duke Enterprise Data Unified Content Explorer historical database was used to identify patients who had undergone a renal transplant at Duke University Hospital during a 20-year period. Data on patient demographics, transplant dates, first rejection episodes, first cSCC development, medication, laboratory results and survival were recorded. RESULTS: In total, 1684 patients were identified, of whom 126 (7.5%) experienced an episode of rejection and 46 (4.0%) developed a cSCC after transplant. The incidence of cSCC was significantly greater in the rejection group, with 8.7% of patients developing cSCC compared with 2.2% in the no-rejection group (P < 0.001). Median lag time to cSCC was shorter in the rejection group (2.5 years; age 0.4-9.0 years) than the no-rejection group (4.2 years; range 1.3-20.4 years) (P < 0.03). CONCLUSIONS: Transplant rejection is associated with both a higher incidence and an accelerated time course for development of cSCC following renal transplantation. Close dermatological surveillance should be considered following an episode of rejection in this patient population.