Scleroderma Induced by Pembrolizumab: A Case Series

Barbosa, Naiara S.; Wetter, David A.; Wieland, C; Shenoy, Niraj; Markovic, Svetomir N.; Thanarajasingam, Uma

doi:10.1016/j.mayocp.2017.03.016

Cited by 95 publications

(67 citation statements)

References 21 publications

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“…Recently, sclerodermoid reactions were identified in two patients receiving pembrolizumab therapy . Cases of scleroderma‐like changes have been reported in association with chemotherapeutic agents such as bleomycin, aldesleukin, uracil‐tegafur, taxanes, gemcitabine, capecitabine, doxorubicin, and cyclophosphamide .…”

Section: Discussionmentioning

confidence: 99%

Scleroderma‐like skin changes induced by checkpoint inhibitor therapy

et al. 2018

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Checkpoint inhibitors have emerged as beneficial therapies in many different types of malignancy. The most common toxicities of checkpoint inhibitors are immune-related adverse events (irAEs). As clinical experience with these agents increases, more irAEs have been described. We report a case of scleroderma-like skin changes induced by checkpoint inhibitor therapy. A 61-year-old man was treated with nivolumab for oligometastatic renal cell carcinoma. He initially tolerated the therapy well, but after 16 treatments he began experiencing skin thickening and edema of the abdominal wall, which progressed down the trunk and legs. A punch biopsy revealed epidermal attenuation overlying thickened dermal collagen with entrapment and displacement of the eccrine coils and loss of periadnexal adipose tissue. Focally increased plasma cells were present near the junction of the dermis and subcutaneous adipose tissue. Loss of CD34 staining was seen throughout the dermis. These findings were consistent with a diagnosis of scleroderma. After discontinuation of nivolumab and initiation of steroid therapy, the patient's symptoms significantly improved. This case is among the first reports of scleroderma-like changes induced by a checkpoint inhibitor.

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Section: Discussionmentioning

confidence: 99%

Scleroderma‐like skin changes induced by checkpoint inhibitor therapy

et al. 2018

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“…Significant inflammatory or immune-mediated reactions included infusion-related reactions (3.0%), hypothyroidism (6.9%) and pneumonitis (3.6%) 4. Furthermore, newer reports described notable toxicities, such as type 1 diabetes mellitus,5 pancytopenia,6 colitis,7 keratoacanthomas,8 scleroderma,9 myasthenia gravis10 and uveitis 11. In terms of cardiotoxicity, two case reports are available in the published literature.…”

Section: Discussionmentioning

confidence: 99%

New drugs and new toxicities: pembrolizumab-induced myocarditis

et al. 2018

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Pembrolizumab is an immune checkpoint inhibitor that significantly improves clinical outcomes in numerous solid organ malignancies. Despite successful therapeutic responses, this new drug comes with a constellation of adverse reactions. Herein, we chronicle the case of a patient with metastatic non-small-cell lung cancer treated with pembrolizumab. After two cycles, he developed new-onset dyspnoea on exertion. Electrocardiogram showed idioventricular rhythm with diffuse ST-segment elevations. Echocardiography revealed severe biventricular cardiac dysfunction. Based on diagnostic workup and exclusion of probable aetiologies, the patient was diagnosed with pembrolizumab-induced myocarditis. The treatment was initiated with corticosteroids and guideline-conform heart failure therapy. He demonstrated a marked clinical response with resolution of congestive heart failure symptoms. This article summarises the clinical evidence regarding the epidemiology, pathophysiology, clinical features, diagnostic modalities and management of patients with pembrolizumab-associated myocarditis. In addition, it highlights that programmed death receptor-1 inhibition can cause a spectrum of autoimmune adverse events requiring clinical monitoring and periodic screenings.

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“…Of patients treated with pembrolizumab, 30‐40% experience dermatologic irAEs . Six cases of sclerodermoid changes in the setting of anti‐PD‐1 therapy have been reported, including morphea, systemic sclerosis, and eosinophilic fasciitis . The timing for these skin changes varies, with onset from after 5 to 36 cycles of therapy.…”

Section: Discussionmentioning

confidence: 99%