Risk of Non-Melanoma Skin Cancer in Connective Tissue Disease and The Impact of Immunosuppressive Therapy

May 2020 | Volume 19 | Issue 5 | Original Article | 519 | Copyright © May 2020

Published online April 3, 2020

Nilanthi D. Gunawardane MD,a Makdine Dontsi MS,b Liisa L. Lyon MSb

aThe Permanente Medical Group Fremont, CA bThe Kaiser Permanente Division of Research in Oakland, CA

The risk of skin cancer in connective tissue disease and the impact of immunosuppressive therapy on this risk has not been well studied. The objective of this study is to investigate the risk of non-melanoma skin cancer in patients with connective tissue disease and to assess the impact of immunosuppressive therapy on this risk. This is a retrospective case control cohort study of 8281 patients with connective tissue disease (systemic lupus erythematosus, Sjogren’s disease and scleroderma) and 8281 age, race, and gender matched controls followed for a 5-year period between 2002-2012, who obtained their care from a large integrated multispecialty group practice in Northern California. The odds ratio for developing squamous cell skin cancer among patients with connective tissue disease was 1.47 (95% CI, 1.14-1.90) (P=0.003) while the odds ratio for developing all non-melanoma skin cancer was 1.26 (95% CI, 1.08-1.49) (P=0.005). Patients on immunosuppressive medication for at least one year had an OR of 1.69 (95% CI, 1.16-2.45) of developing non-melanoma skin cancer (P=0.006) when controlled for age, race, gender, type of connective tissue disease, smoking status, and health care utilization. Our study shows an increased risk of non-melanoma skin cancer among patients with connective tissue disease. We also note that patients on immunosuppressive therapy for at least one year had an increased incidence of non-melanoma skin cancer. Further studies are needed to confirm these findings.

J Drugs Dermatol. 2020;19(5):  doi:10.36849/JDD.2020.4781


Connective tissue diseases (CTD), specifically systemic lupus erythematosus (SLE), scleroderma and Sjogren’s disease have been reported to be associated with an increased overall malignancy risk.1-11 There have been only a few studies, mostly in the European literature, that have studied the association between CTD and skin cancer. In these studies, a higher skin cancer incidence has been reported in patients with CTD including SLE and scleroderma.1-3,5-7,11 The incidence and odds of skin cancer in US patients with CTD has not been well studied. The relationship between CTD and skin cancer is complicated by the use of immunosuppressive medications to treat these diseases. Studies to assess the potential impact of immunosuppressive medications on skin cancer incidence in this patient population have been lacking.

It is important to determine if there is an increased incidence of skin cancer in this patient population as the first step to determine if increased screening would be warranted. CTD are associated with significant morbidity and mortality, hence any increased morbidity and mortality due to skin cancer can be minimized by early diagnosis and treatment.


Study Population and Inclusion/Exclusion Criteria
Kaiser Permanente Northern California (KPNC) is a large, integrated health care delivery system caring for over 3 million members who are broadly representative of the local and statewide population. This study is a retrospective matched cohort study of all patients with a first CTD diagnosed between the years 2002-2012 and matched controls with no CTD. Patients with SLE, scleroderma and Sjogren’s disease were identified through the KPNC electronic database using ICD 9 codes for the years 2002-2012. Controls were randomly selected from the KPNC member population. Each control was matched to a case by year of birth, race and gender. The date of the first diagnosis of CTD was used as the index date for each case and matched control. Cases and controls were required to have had a minimum of one-year membership prior to the index date and a minimum 5-year membership after the index date. In addition, all subjects (cases and controls) were required be at least 18 years of age on the index date with no previous diagnosis of a basal cell or squamous cell skin cancer at time of diagnosis or within one year of the diagnosis. Stem cell and solid organ transplant recipients as well as patients with rheumatoid arthritis, dermatomyositis and inflammatory bowel disease were excluded from cases and controls due to their known increased risk of malignancy. Subjects were also excluded if they lost KPNC coverage for more than 90 days anytime during the 5-year follow-up period. Controls were required to have at least 2 clinic visits in the year prior to the index date as a proxy for healthcare utilization.