Scleroderma‐like skin changes induced by checkpoint inhibitor therapy

Abstract

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.

Intriguing Relationships Between Cancer and Systemic Sclerosis: Role of the Immune System and Other Contributors

“…More recently, anticancer immunotherapy using immune checkpoint inhibitors has been shown to trigger autoimmunity, and a few cases of scleroderma have been reported in the literature (55–57, 140). In this context, the complexity of the interplay between anti-cancer pre-existing autoimmunity, genuine paraneoplastic syndromes and the effects of immune system stimulation by biologics is striking, and strengthens the relationships between SSc and malignancy.…”

Dermatological adverse events of immune checkpoint inhibitors

“…Scleroderma is an even rarer event that has been reported following PD-1 blockade. These cases involved typical skin tightness of the hands and feet and dermal sclerosis on histology [37,38] . The underlying mechanism for this is unknown, it is reported that TGFβ cascade is activated within the skin after treatment with anti-PD-1, which results in fibrosis [37] .…”

“…Alopecia areata (AA) is an autoimmune disease that results in unpredictable, patchy hair loss. AA is reported in 1-2% cancer patients receiving immune checkpoint inhibitor therapy [38,39] . AA caused by checkpoint inhibitor therapy shares several features with the classical AA.…”

Clinical characteristics of rheumatic syndromes associated with checkpoint inhibitors therapy

“…Some patients experienced systemic sclerosis [7] or scleroderma-like reaction [63–65], all presenting with skin thickening but only one with associated recent Raynaud phenomenon. None tested positive for specific autoantibodies.…”