Checkpoint Inhibitor-Associated Scleroderma and Scleroderma Mimics

Abstract

Immune checkpoint inhibitors (ICI) are the standard of care for various malignancies and have been associated with a wide spectrum of complications that are phenotypically akin to primary autoimmune diseases. While the literature on these toxicities is growing, there is a paucity of data regarding ICI-associated scleroderma which can carry significant morbidity and limit the ability to continue effective ICI therapy. Our review aimed to analyze the current literature on ICI-associated systemic scleroderma (ICI-SSc) and key scleroderma mimics. Cases of ICI-SSc had notable differences from primary SSc, such as fewer vascular features and less seropositivity (such as scleroderma-specific antibodies and antinuclear antibodies). We found that patients with a diagnosis of SSc prior to the start of ICI can also experience flares of pre-existing disease after ICI treatment used for their cancer. Regarding scleroderma mimics, several cases of ICI-eosinophilic fasciitis have also been described with variable clinical presentations and courses. We found no cases of scleroderma mimics: ICI-scleromyxedema or ICI-scleroedema. There is a critical need for multi-institutional efforts to collaborate on developing a patient database and conducting robust, prospective research on ICI-scleroderma. This will ultimately facilitate more effective clinical evaluations and management for ICI-scleroderma.

Keywords: autoimmune disease; drug toxicities; fasciitis; immune checkpoint inhibitor; morphea; systemic sclerosis.

Figure 1

Physical exam findings associated with systemic sclerosis. Pertinent findings associated with systemic sclerosis include notable skin tightening with sclerodactyly (a) and consequent limitations in “prayer sign” (b) that is demonstrated here by a patient who received diagnosis of systemic sclerosis after start of checkpoint inhibitor therapy.

Figure 2

Similarities and differences between ICI-SSc and primary SSc. This Venn diagram highlights key differences and similarities between immune-checkpoint-inhibitor-associated systemic sclerosis (ICI-SSc) and primary systemic sclerosis (SSc). Abbreviations—ANA: antinuclear antibody; Anti-Scl-70: antibody to the scleroderma 70 kD extractable immunoreactive fragment from topoisomerase antigen; RNA: ribonucleic acid; ILD: interstitial lung disease.