Incidence, stage and outcome of 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 melanoma (MM), some also for keratinocyte skin cancer (KC). In AA, reduced risks for KC (and also MM) have been reported. The driving mechanisms (genetic predisposition, immunological or other effects of the disease phenotypes, or environmental) remains unclear. Whether 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 skin cancer (SCC) and non-cutaneous cancers in vitiligo and alopecia, vs. that in the general population, and to investigate the corresponding risks in their 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 (HR) contrasting patients with vitiligo or AA and the general population, and contrasting their siblings.

Results: Between 2006 to 2021, we included 15,030 patients with vitiligo, 18,541 with alopecia, and 17,853 and 21,821 of their siblings. Based on 17 MM events (crude incidence per 100,000, IR: 16), 23 SCC events (IR: 22) in vitiligo, and, 20 MM (IR: 15) and 24 SCC (IR: 18) in AA, the HR for MM was 0.53 (95%CI 0.32-0.86) in vitiligo and 0.53 (95%CI 0.34-0.83) in AA. Regarding SCC, HRs were 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 didn't 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). In patients and their siblings, HRs for non-cutaneous solid or hematological cancers were not reduced.

Conclusion: 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 their siblings suggests a role for other factors 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 non-cutaneous malignancies.