Assessing skin cancer risk in systemic sclerosis patients with organ transplantation: A cohort study

Systemic sclerosis (SSc) is an autoimmune condition characterized by fibrosis of the skin and organs. Cancer is a well-known association of SSc, with a higher incidence in men, and with particular evidence of elevated lung, breast, and melanoma incidence. In addition, non-melanoma skin cancer (NMSC) has been reported to have increased incidence, with one study showing higher incidence in women compared to men. The impact of solid organ or hematopoietic transplantations - known to confer increased risk of NMSC - on skin cancer risk have not been specifically characterized in the SSc population. We sought to explore skin cancer incidence in SSc patients with a history of kidney, bone marrow (BM), or lung transplantation. The Research Patient Data Registry of Mass General Brigham was queried from 1979 to 2024 for SSc and lung, kidney, or BM transplantation in clinical documentation. For the unexposed cohort, patients with SSc and no transplantation (2:1 controls per case) were matched by age, sex, and race. For each exposed patient, up to one matched unexposed patient was included in the analysis. Among 178 exposed and 374 unexposed extracted, 48 SSc patients with transplant and 45 SSc patients without transplant were included after chart review. NMSC risk was calculated with either basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). We observed an increased association of skin cancer with transplantation (relative risk (RR) 5.31, 95% p=0.0047), specifically with NMSC (RR 4.69, p=0.0097), compared to non-transplantation. In addition, when examining only skin cancers that emerged after transplantation, there was an increased risk compared to controls (RR 3.75, p=0.0306), specifically with SCC (RR=4.69, p=0.0384). Subsequent subgroup analysis of transplanted patients by sex showed that females had an increased risk of skin cancer (RR 3.7, p=0.0298) and NMSC (RR 3.33, p=0.0468), while males did not. Cutaneous malignancy amongst SSc patients remains understudied, and characterizing the contribution of transplantation to observed increased risks is necessary. Our results suggest that patients with SSc undergoing transplantation -- specifically females -- may have an increased risk of developing both NMSC and skin cancers compared to those without transplantation. Limitations include our study's retrospective nature and limited generalizability due use of one health system.