Incidence, stage and outcome of malignant melanoma, keratinocyte and other cancers in individuals with vitiligo or alopecia: intraindividual or familial risks?

Abstract

Background: Vitiligo and autoimmune alopecia (AA) are caused by T cell-mediated autoimmunity in genetically predisposed individuals. Studies in vitiligo have reported reduced risks for malignant melanoma (MM), as well as for keratinocyte cancer (KC). Similarly, in AA, reduced risks for KC and MM have been reported. The driving mechanisms (genetic predisposition, immunological or other effects of the disease phenotypes, or environmental factors) remain unclear. Whether or not the immune-related genetic predisposition in vitiligo and AA offers 'inherent' protection against other types of cancer remains unresolved.

Objectives: To investigate the incidence and outcome of MM, squamous cell carcinoma (SCC) and noncutaneous cancers in vitiligo and AA, compared with the general population, and to investigate the corresponding risks in their respective siblings.

Methods: We performed a population-based matched cohort study using data from linkage of Swedish registers. We used Cox proportional hazards regression to calculate hazard ratios (HRs) contrasting patients with vitiligo or AA with the general population, as well as contrasting patients' siblings with siblings of individuals from the general population.

Results: Between 2006 and 2021, we included 15 030 patients with vitiligo and 18 541 with AA, along with, respectively, 17 853 and 21 821 of their siblings. Based on 17 MM events [crude incidence rate per 100 000 person-years (IR) = 16] and 23 SCC events (IR = 22) in vitiligo, along with 20 MM events (IR = 15) and 24 SCC events (IR = 18) in AA, the hazard ratio (HR) for MM was 0.53 [95% confidence interval (CI) 0.32-0.86] in vitiligo and 0.53 (95% CI 0.34-0.83) in AA. Regarding SCC, the HR was 0.81 (95% CI 0.53-1.24) in vitiligo and 0.65 (95% CI 0.43-0.98) in AA. Stage at diagnosis of MM did not differ substantially between patients and the general population. Among siblings, HRs for MM and SCC were not statistically significantly altered (0.82 ≤ HR ≤ 1.10; P > 0.05). In patients and their siblings, HRs for noncutaneous solid or haematological cancers were not reduced.

Conclusions: In vitiligo and in AA the decreased risk of cutaneous cancers extends beyond the cell type targeted by the autoimmune reaction. The general tendency towards somewhat reduced skin cancer risks among patients' siblings suggests a role for factors other than the disease phenotypes per se. Neither the vitiligo and AA phenotypes nor their immune-related genetic predispositions seem to offer any 'inherent' protection against noncutaneous malignancies.