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In a metaanalysis a negative association was also found between high bilirubin levels and severity of atherosclerosis (37)

On the contrary, alopecia areata and vitiligo mostly appear simultaneously, indicating that the two diseases could share the exact pathogenetic mechanism ( Genome-wide association studies (GWAS) underscored a clear genetic background shared between vitiligo and other autoimmune diseases ( 2.2 Oncological aspects of vitiligo comorbidities Epidemiological data indicate that vitiligo patients have a diminished overall incidence rate of cancer ( Despite the impaired protection from UV rays due to lack of melanin, patients with vitiligo display lower incidence of non-melanoma skin cancers (squamous and basal cell carcinomas) ( Moreover, significant resistance to UV damage is appreciable at a molecular level, as indicated by the presence of a low UV-regulated transcriptome and an anti-tumoral molecular signature ( 2.3 Neurological comorbidities Given that melanocytes are not only present in the skin but can also be found in the iris (eye), cochlea, mesencephalon, leptomeninges, heart, and adipose tissue ( Neuromelanin is a neuronal pigment composed of both eumelanin and pheomelanin that can be found mainly in brain regions enriched in dopaminergic or noradrenergic neurons, brain components highly exposed to oxidative stress

doi: 10.1111/ajt.13909 67 DivangahiMAabyPKhaderSABarreiroLBBekkeringSChavakisTet al

Apart from its well-known immunomodulatory role, histamine can act as a neurotransmitter in the brain, acting as a critical modulator of other neurotransmitters, and influencing arousal, motivation, and energy balance [180]