Background Darier disease is a genodermatosis which manifests as hyperkeratotic papules and superficial erosions mainly in seborrheic skin areas. This retrospective registry-based cohort study aimed to estimate the association between Darier disease and skin cancer.

Results Patients diagnosed with Darier disease were identified from the patient registry of Sahlgrenska University Hospital (Gothenburg, Sweden) in 2016-2020. The local cohort included 13 patients. Verification of Darier disease diagnosis in the National Patient Registry showed positive predictive value of more than 90%. National Patient Registry was searched for Darier disease in 2001-2020, Swedish Cancer Registry for cancers and Prescribed Drug Register for medications. The national cohort included 770 patients and tenfold matched control cohort. Patients with Darier disease had an increased relative risk of keratinocyte carcinoma (basal cell carcinoma and cutaneous squamous cell carcinoma combined) (hazard ratio [HR], 1.6, 95% confidence interval [CI], 1.0-2.5, P = 0.036). The risk increase was significant for basal cell carcinoma (HR, 1.8, 95% CI, 1.1-2.9, P = 0.012), whereas there was a trend for cutaneous squamous cell carcinoma, (HR, 1.9, 95% CI, 0.9-4.1, P = 0.086) and cutaneous melanoma (HR, 2.4, 95% CI, 0.9-6.2, P = 0.083). Standardized incidence ratio for keratinocyte cancers was 2.9 (95% CI, 2.4-3.3. The results were consistent in two subgroup analyses adjusting for use of retinoid and/or immunosuppressive drugs.

Conclusion Patients with Darier disease have an increased risk of skin cancer, particularly keratinocyte carcinoma. This risk was consistent even when known risk modifiers for keratinocyte carcinoma were excluded in sensitivity analyses. The results support previously proposed molecular links between Darier disease and skin cancer, but further investigations are needed. Additional studies are also required to develop clinical management recommendations for Darier disease. In the meantime, dermatologists should be aware of the cancer risk in these patients and remain vigilant, as detecting cancer can be challenging in hyperkeratotic and/or eroded skin.