Shining a Light on Vitiligo and Associated Comorbidities: What Is the Evidence?

Often dismissed as a cosmetic concern, vitiligo is anything but given its pathophysiology and tremendous impact on quality of life (QoL). Simply put- vitiligo is a medical disease,¹ exhibiting an estimated worldwide prevalence of 0.5 to 2%; irrespective of racial predilection and equally affecting adults and children of both genders.^2,5

The pathophysiology of vitiligo is a complex interplay of genetics, reactive oxidative stress (ROS), and innate and adaptive immunity, culminating in injury and selective destruction of melanocytes.^3,18 While oxidative damage steers vitiligo onset by triggering redox homeostasis imbalance and amplified expression of proinflammatory cytokines and antigen presentation, signaling 

of IFN-γ through the Janus-kinase signal transducer and activator of transcription (JAK-STAT) pathway with subsequent 

transcription of IFN-γ-induced chemokines, namely CXCL9 and CXCL10, are pivotal in driving depigmentation, and mediate targeted melanocyte destruction by autoreactive cytotoxic CD8+ T lymphocytes.^2,4,5,24 Furthermore, increased prevalence of autoantibodies against melanocytes amongst individuals and recurrent presence of concomitant autoimmune comorbidities in 10 to 15% of vitiligo patients compared to 1 to 2% of the general population are some of the most apparent correlations between vitiligo and autoimmunity.^3,18,19

Over the decades, advances in knowledge and growing attention to vitiligo have improved understanding of the disease’s implications, including the possibility of concurrent autoimmune and systemic diagnoses (Figures 2A and 2B) with plausible parallel pathogenetic pathways, many of which lead to increased morbidity. A recent prospective cross-sectional survey found that those with vitiligo were ^2.6 times more likely to have at least one autoinflammatory/autoimmune comorbidity when compared to non-vitiligo groups.²⁵ Physicians must be aware of, identify, and treat additional complications in vitiligo patients to improve patient QoL. Herein, we review evidence and insight for the most frequent comorbidities associated with vitiligo. 

Autoimmune Thyroid Disease (AITD) including Hashimoto thyroiditis and Grave’s disease, have strong links with vitiligo. A recent meta-analysis demonstrated the AITD prevalence in vitiligo patients is 14.3%, while positivity to thyroid-specific antibodies (ie, anti-thyroglobulin (Tg), anti-thyroid peroxidase (anti-TPO), and anti-thyrotropin receptor (TSHR)) is appreciated in 20.8% individuals.⁶ Moreover, the presence of anti-thyroid hormone antibodies were detected in 77 of the 79 vitiligo patients analyzed, suggesting a probable pathogenetic role.^6,7

More notably, there exists a 2.5-fold higher risk for development of AITD in older, non-segmental vitiligo (NSV) patients, and another study disclosed the risk of AITD also increases with vitiligo duration and distribution, with the risk doubling every five years and with greater than 10% body surface area involvement.²  

The reported association of vitiligo with AITD additionally suggests the presence of shared heritable susceptibility genes. Among 27 genes mapping Autoimmune Susceptibility 1 (AIS1) locus on chromosome 1, mutations of FOXD3 exhibit the greatest connections for concurrent occurrence of vitiligo and AITD in both adult and pediatric patients.^{6,7, 8}

Vitiligo and alopecia areata (AA) are autoimmune diseases that occur more commonly together than by chance, with a reported 3 to 8% prevalence of vitiligo in AA patients, and share striking similarities in pathogenesis that may better explain