Comparison between vitiligo patients with and without MS (Table 3) revealed that patients with MS had significantly higher mean age, disease duration, VASI (disease severity), and IR. Table 4 shows that there were nonsignificant differences regarding VASI, serum fasting insulin, and IR between male and female patients. Finally, age, serum TGs, body weight, BMI, WC, and IR showed significant positive correlations with VASI (disease severity) (Table 5).
In the present study, there was no significant difference between patients and controls regarding the number of individuals fulfilling the previously mentioned criteria for diagnosis of MS as well as systolic blood pressure and fasting blood glucose levels. In addition, patients showed significantly lower BMI, WC, and serum TGs compared with the control group, whereas diastolic blood pressure and serum HDL-C were significantly higher than the control group. Diastolic blood pressure was the only characteristic of MS that showed a significant increase in vitiligo patients than in controls.
These results are in agreement with Rodriguez-Martin et al.10, who found that analysis of MS parameters revealed lower significant prevalence of altered WC, TGs, and low HDL-C in vitiligo patients. In addition, no significant differences could be observed in blood glucose levels or BMI. According to these findings, they suggested that patients with vitiligo tended to present lower CVD risk than controls, as vitiligo patients presented a better lipid profile, with higher levels of HDL-C and lower TGs and WC values.
Rodriguez-Martin et al.10 explained that these results were a result of increased levels of superoxide dismutase and glutathione peroxidase in patients with active vitiligo 18,19. This upregulation could be an enzymatic basis that makes vitiligo patients less prone to CVD 10. However, this explanation is doubted, as oxidative stress presents in vitiligo and it is responsible for the cytotoxic effects on melanocytes. Excess reactive oxygen species (ROS) were documented in active vitiligo skin – for example, high H2O2 levels were found throughout the epidermis 20.
We suggested that a relatively short vitiligo history (2–6 years duration) may explain the nonstatistically different values between the studied and control groups as well as absence of lipid abnormalities and metabolic disturbances such as obesity, hypertension, and DM in the studied patients. We found that vitiligo patients with MS had statistically significant higher mean age, disease duration, VASI (disease severity), and IR than patients without MS. In addition, this explanation was suggested by Pietrzak et al.21 but in children with vitiligo (0.5–9 years duration).
Almost similar to our results, Karadag et al.9 reported that no significant differences were present between vitiligo patients and controls regarding BMI, WC, fasting blood glucose, serum TGs, and diastolic blood pressure measurements. Yet, vitiligo patients had significantly lower HDL-C levels than controls, and systolic blood pressure of the patients was significantly higher than controls. These changes could be due to IR and hyperinsulinemia found in vitiligo patients. Hyperinsulinemia may increase the production of very low-density lipoprotein TGs, and IR can raise blood pressure 22.
On the other hand, investigation of lipid disturbances in vitiligo children revealed decreased levels of HDL-C as well as increased TGs concentrations in the studied group of vitiligo girls 6. In another study, HDL-C concentration was significantly lower in the studied vitiligo children in comparison with the healthy control group 7. In addition, in more recent study, it was reported that HDL-C concentration was significantly lower in children with vitiligo compared with healthy controls, whereas no significant differences were observed regarding height, weight, BMI, fasting serum glucose, and serum TGs of children with vitiligo and healthy children 21.
This can be explained as proinflammatory cytokines TNF, IL-1, IL-6 and other inflammatory factors (e.g. C-reactive protein) are involved in evoking IR as well as other metabolic complications and atherosclerosis 8. In addition, higher levels of homocysteine reported in vitiligo patients may be involved in the development of the metabolic disturbances in vitiligo patients and increase CVD risk 23,24. Furthermore, hypovitaminosis D reported in vitiligo patients may increase CVD risk 25.
As oxidative stress plays a vital role in the pathogenesis of both MS and vitiligo, metabolic disturbances in vitiligo seem to be a result of increased production of ROS. Excessive ROS is known to be responsible for lipid peroxidation, protein oxidation, and oxidative DNA damage 26. The processes promoting lipid peroxidation that occur in the epidermis, and perhaps in the adipose tissue as well, may be a plausible explanation for the lipid abnormalities detected 21.
In the present study, serum fasting insulin and IR (homeostatic model assessment of IR) were significantly higher in the patient group compared with the control group. Serum fasting insulin was significantly higher in patients with acrofacial vitiligo. In agreement with this, Karadag et al.9 reported similar results. Additional contributors to IR include abnormalities in insulin secretion and insulin receptor signaling, impaired glucose disposal, and proinflammatory cytokines. The relationship between impaired glucose tolerance and IR is well documented. Reilly et al.27 believe that insulin assays or alternative biomarkers of IR may facilitate CVD risk prediction in individuals with MS. Even without diabetes, IR is a major risk factor for CVD and early mortality.
The association of vitiligo with glucose intolerance, IR, lipid abnormalities, hyperhomocysteinemia also characterizes systemic involvement in the skin disease 6,9,20, and the proinflammatory cytokines TNF, IL-1, and IL-6 and other inflammatory factors involved in vitiligo are known to be involved in evoking IR as well as other metabolic complications and atherosclerosis 8.
There were nonsignificant differences regarding VASI, serum fasting insulin, and IR between male and female patients. Rodriguez-Martin et al.10 also reported that no significant differences could be observed between all studied variables regarding sex in the patient group.
Finally, in the present study, age, serum TGs, body weight, BMI, WC, and IR of the vitiligo patients showed significant positive correlations with VASI (disease severity). This can be expected as proinflammatory cytokines (TNF, IL-1, IL-6), other inflammatory factors, ROS, and lipid peroxidation involved in vitiligo showed increased levels and activity with increased disease severity. These factors also are known to be involved in evoking IR, lipid abnormalities, as well as other metabolic complications and atherosclerosis 8,20,26.
Finally, despite absence of a defined significant association between vitiligo and MS, we expect development of such a relationship with longer duration of the disease and lifetime of the patient as vitiligo and MS have shared etiopathogenic factors – for example, proinflammatory cytokines and oxidative stress. In addition, there is a shared genetic background for both conditions. The angiotensin-converting enzyme gene and catalase gene were reported to be susceptibility genes in vitiligo and MS patients 28–32. In addition, the HLA region, IFIH1, BTNL2, IL2RA, SH2B3, IKZF4, and CASP7 are vitiligo risk loci involved in pathways and are shared with type 1 DM, whereas the ZMIZ1 gene is shared with type 2 DM 33.
Although the present study showed a nonsignificant relationship between vitiligo and MS, further studies are needed to approve or deny our results and to reach a clear conclusion about the pathogenic connection between them that will be of clinical importance.
Conflicts of interest
There are no conflicts of interest.
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Keywords:© 2017 Egyptian Women's Dermatologic Society
homeostatic model assessment of insulin resistance; insulin resistance; metabolic syndrome; vitiligo