Abstract
Objective
The purpose of this study was to investigate the relationship between vitiligo and body mass index (BMI) to assess the possible association between vitiligo and obesity.
Subjects and Methods
This was a case-control study on a total of 400 participants, i.e., 200 patients with vitiligo and 200 healthy volunteers. Medical assessments were performed by dermatologists using the modified Vitiligo European Task Force form. The height and weight of all of the participants were measured and used to calculate the BMI. Data were analyzed using multivariate logistic regression models. Adjustment for age and gender was carried out preliminarily in the case-control analysis, whereas a forward stepwise selection algorithm was used to assess which independent factors were associated with a BMI ≥30 or a BMI ≤18.5.
Results
Comparison of the vitiligo and control groups revealed the absence of a significant association. The multivariate analysis of factors associated with a high BMI (≥30) in vitiligo patients showed a significant association between a high BMI and a sudden onset of vitiligo (p = 0.021; OR = 3.83; 95% CI 1.22–11.99) and the presence of inflammation and pruritus (p = 0.031; OR = 3.26; 95% CI 1.11–9.57). No significant association was observed in the analysis of factors associated with a low BMI (≤18.5) in vitiligo patients.
Conclusion
In this study, vitiligo did not appear to be associated with a high BMI; obesity might not be a risk factor for vitiligo, in contrast to most autoimmune diseases which are significantly associated with obesity.
Keywords: Vitiligo, Obesity, Case-control study, Body mass index
Significance of the Study
• In this study, vitiligo did not appear to be associated with a high body mass index, in contrast to most other autoimmune diseases. This lack of an association could be due to a high expression of p53 and a high concentration of transforming growth factor-β in vitiligo patients. Hence, in these patients, vitiligo could not lead to obesity.
Introduction
Vitiligo is an acquired, depigmenting skin disorder characterized by the appearance of well-delineated, white macules on the skin due to the selective disappearance of functional melanocytes in the epidermis [1]. Vitiligo affects people of all ages and both sexes equally, with a prevalence of approximately 0.5% of the world population [2]. Currently, vitiligo is considered a multifactorial disease with the specific involvement of autoimmunity, and thus vitiligo is regarded mainly as an autoimmune dermatosis [3, 4].
The association between many autoimmune or inflammatory diseases and obesity had been demonstrated [5, 6]. Rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, systemic sclerosis, psoriasis, and autoimmune thyroid diseases are some of the disorders linked to obesity and they can also be associated with vitiligo [5, 6, 7, 8, 9].
In obese people, fat cells produce high levels of leptin, a cytokine-like hormone that mediates the autocrine production of a wide variety of mediators including the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 which contribute to creating a chronic inflammatory state capable of increasing the risk of autoimmune diseases [10, 11, 12, 13].
In vitiligo, a significantly high expression of proinflammatory cytokines has been reported in lesional and perilesional skin. These are thought to be essential regulators of melanocyte dysfunction and death. Contradictory results have been observed at a systemic level [14, 15, 16, 17]. Recently, elevated serum interleukin-17A, transforming growth factor-β1, and interleukin-21 levels have been identified at a systemic level in vitiligo patients [18].
Karadag et al. [19] showed that patients with vitiligo have a higher insulin resistance, a higher LDL/HDL ratio, and a higher systolic blood pressure. A recent report provided information on the reduction of some cardiovascular risk factors in patients with vitiligo. However, the relationship between vitiligo and cardiovascular disease is not yet clear and no association between vitiligo and obesity has ever been documented in a case-control study [20].
The purpose of this study was to investigate the relationship between vitiligo and body mass index (BMI) to assess the possible association between vitiligo and obesity.
Subjects and Methods
A case-control study was performed at our specialized vitiligo outpatient service in Florence, Italy, during a 3-year period (March 2012 to March 2015). A total of 400 Caucasian participants were included in this study, i.e., 200 patients with vitiligo and 200 healthy volunteers. Of the 200 vitiligo patients, 92 were males and 108 females, with ages ranging between 14 and 75 years. In doubtful cases, a histological examination was performed to confirm the diagnosis. This study was conducted according to the principles of the Declaration of Helsinki, and written informed consent was obtained from each patient for retrospective data collection. The medical assessment involved natural and Wood's light examinations consistent with the modified Vitiligo European Task Force form [21]. Based on the Vitiligo European Task Force, a patient's palm corresponding to 1% of body surface area was used to calculate the total vitiligo extension [22]. Exclusion criteria were segmental vitiligo, doubtful diagnosis of vitiligo with no histological evidence, and no written informed consent.
The control group included 200 healthy volunteers (92 males and 108 females, aged between 17 and 76 years, with no history of dermatological or systemic disease and who were age and sex matched to the vitiligo patients.
The height and weight of all of the participants were measured and used to calculate the BMI (weight in kg divided by height in m squared [kg/m2]). All of the participants were measured for height and weight and the BMI was calculated. BMI was taken as an index of obesity (BMI ≥30 was the obesity marker and BMI ≤18.5 was the underweight marker) and analyzed its possible relationship with the following clinical features of vitiligo: age at onset, vitiligo onset, modality of onset, growth of lesions, disease activity, total disease extension, Koebner's phenomenon, and inflammation/pruritus.
A personal history of cardiovascular disease, cancer, autoimmune disease (discoid lupus erythematosus, alopecia areata, autoimmune thyroiditis and/or gastritis, celiac disease, type 1 diabetes, Addison's disease, and scleroderma) and psoriasis were all evaluated. In addition, corticosteroid therapy, immunosuppressive therapy, and smoking habit were assessed. All of these data were obtained from paper and computerized medical records.
Statistical Analysis
Data were analyzed using multivariate logistic regression models. Adjustment for age (in quintiles) and gender was carried out preliminarily in the case-control analysis, whereas a forward stepwise selection algorithm was then used to assess which independent factors were associated with a BMI ≥30 or a BMI ≤18.5. The effect of selected factors was expressed in terms of OR with 95% CI and p values. p < 0.05 was considered statistically significant.
Results
The general data for the cases and controls are summarized in Appendix 1. The mean (±SD) and median age of the patients was 43.7 ± 16 and 45 years, respectively, and that of the controls was 44.3 ± 16.1 and 48.0 years, respectively. Comparison of the vitiligo and control groups revealed the absence of a significant association (Table 1). A crude analysis of the factors associated with a high BMI (≥30, obese) in vitiligo patients had a highlighted significant association between a high BMI and sudden onset of vitiligo (appearance of all of the patches present at the time of the visit in <1 month) (p = 0.028), the presence of inflammation and pruritus in vitiligo lesions (p = 0.037), and a personal history of cardiovascular disease (p = 0.003) (Table 2). Multivariate analysis revealed a significant association between a high BMI and sudden onset of vitiligo (p = 0.021; OR = 3.83; 95% CI 1.22–11.99) and the presence of inflammation and pruritus in vitiligo lesions (p = 0.031; OR = 3.26; 95% CI 1.11–9.57).
Table 1.
Case-control analysis
| Vitiligo (n = 200) |
Control (n = 200) |
p value | ||||
|---|---|---|---|---|---|---|
| n | % | n | % | |||
| Age, years | 43.7 | 16.1 | 44.4 | 16.2 | ||
| <35 | 65 | 32.5 | 61 | 30.5 | 0.544 | |
| 35–49 | 53 | 26.5 | 63 | 31.5 | ||
| 50+ | 82 | 41.0 | 76 | 38.0 | ||
| Sex | ||||||
| Female | 108 | 54.0 | 108 | 54.0 | 1 | |
| Male | 92 | 46.0 | 92 | 46.0 | ||
| BMI | 23.8 | 3.5 | 23.6 | 4.3 | ||
| ≤18.5 | 29 | 14.5 | 33 | 16.5 | 0.667 | |
| 18.6–29.9 | 153 | 76.5 | 154 | 77.0 | ||
| ≥30.0 | 18 | 9.0 | 13 | 6.5 | ||
| Type of vitiligo onset | ||||||
| Early (age <18 years) | 49 | 24.6 | − | − | − | |
| Late (>18 years) | 150 | 75.4 | − | − | ||
| Speed of vitiligo onset | ||||||
| Sudden | 83 | 42.3 | − | − | − | |
| Gradual | 113 | 57.7 | − | − | ||
| Growth of vitiligo lesions | ||||||
| Absent | 12 | 6.1 | − | − | − | |
| Slow | 145 | 73.6 | − | − | ||
| Rapid | 40 | 20.3 | − | − | ||
| Inflammation/pruritus | ||||||
| No | 147 | 75.4 | − | − | − | |
| Yes | 48 | 24.6 | − | − | ||
| Total vitiligo extension, % | 7.6 | 16.7 | ||||
| <1.0 | 50 | 29.1 | − | − | − | |
| 1.0–4.9 | 71 | 41.3 | − | − | ||
| ≥5.0 | 51 | 29.7 | − | − | ||
| Disease activity | ||||||
| Active | 104 | 53.6 | − | − | − | |
| Borderline | 34 | 17.5 | − | − | ||
| Stable | 56 | 28.9 | − | − | ||
| Koebner's phenomenon | ||||||
| No | 99 | 51.6 | − | − | − | |
| Yes | 93 | 48.4 | − | − | ||
| Personal history of cardiovascular disease | ||||||
| No | 176 | 88.0 | 164 | 82.0 | 0.193 | |
| Yes | 24 | 12.0 | 36 | 18.0 | ||
| Personal history of cancer | ||||||
| No | 191 | 96.0 | 184 | 92.0 | 0.295 | |
| Yes | 8 | 4.0 | 16 | 8.0 | ||
| Personal history of autoimmune disease | ||||||
| No | 165 | 82.5 | 194 | 97.0 | 0.101 | |
| Yes | 35 | 17.5 | 6 | 3.0 | ||
| Personal history of psoriasis | ||||||
| No | 190 | 95.0 | 189 | 94.5 | 0.823 | |
| Yes | 10 | 5.0 | 11 | 5.5 | ||
| Smoker | ||||||
| No | 108 | 60.0 | 142 | 71.0 | 0.224 | |
| Yes | 72 | 40.0 | 58 | 29.0 | ||
| Corticosteroid therapy | ||||||
| No | 198 | 99.0 | 195 | 97.5 | 0.449 | |
| Yes | 2 | 1.0 | 5 | 2.5 | ||
| Immunosuppressive therapy | ||||||
| No | 200 | 100.0 | 197 | 98.5 | 0.248 | |
| Yes | 0 | 0.0 | 3 | 1.5 | ||
Table 2.
Crude analysis of factors associated with a high BMI (≥30) in vitiligo patients
| N | BMI ≥30 |
p value | ||
|---|---|---|---|---|
| n | % | |||
| Age | ||||
| <35 years | 126 | 4 | 3.2 | 0.055 |
| 35–49 years | 116 | 10 | 8.6 | |
| 50+ years | 158 | 17 | 10.8 | |
| Sex | ||||
| Female | 216 | 11 | 5.1 | 0.031 |
| Male | 184 | 20 | 10.9 | |
| Type of vitiligo onset | ||||
| Early (age <18 years) | 49 | 2 | 4.1 | 0.251 |
| Late (age >18 years) | 150 | 16 | 10.7 | |
| Speed of vitiligo onset | ||||
| Sudden | 83 | 12 | 14.5 | 0.028 |
| Gradual | 113 | 6 | 5.3 | |
| Growth of vitiligo lesions | ||||
| Absent | 12 | 0 | 0.0 | 0.746 |
| Slow | 145 | 15 | 10.3 | |
| Rapid | 40 | 3 | 7.5 | |
| Inflammation/pruritus | ||||
| No | 147 | 9 | 6.1 | 0.037 |
| Yes | 48 | 8 | 16.7 | |
| Total vitiligo extension | ||||
| <1.0% | 50 | 4 | 8.0 | 1 |
| 1.0–4.9% | 71 | 6 | 8.5 | |
| ≥5.0% | 51 | 5 | 9.8 | |
| Disease activity | ||||
| Active | 104 | 11 | 10.6 | 0.456 |
| Borderline | 34 | 1 | 2.9 | |
| Stable | 56 | 5 | 8.9 | |
| Koebner's phenomenon | ||||
| No | 99 | 9 | 9.1 | 0.695 |
| Yes | 93 | 7 | 7.5 | |
| Personal history of cardiovascular disease | ||||
| No | 340 | 20 | 5.9 | 0.003 |
| Yes | 60 | 11 | 18.3 | |
| Personal history of cancer | ||||
| No | 375 | 30 | 8.0 | 0.240 |
| Yes | 24 | 0 | 0.0 | |
| Personal history of autoimmune disease | ||||
| No | 359 | 30 | 8.4 | 0.348 |
| Yes | 41 | 1 | 2.4 | |
| Personal history of psoriasis | ||||
| No | 379 | 29 | 7.7 | 0.673 |
| Yes | 21 | 2 | 9.5 | |
| Smoker | ||||
| No | 250 | 16 | 6.4 | 0.210 |
| Yes | 130 | 13 | 10.0 | |
| Corticosteroid therapy | ||||
| No | 393 | 31 | 7.9 | 1 |
| Yes | 7 | 0 | 0.0 | |
| Immunosuppressive therapy | ||||
| No | 397 | 30 | 7.6 | 0.215 |
| Yes | 3 | 1 | 33.3 | |
No significant association was observed in the analysis of factors associated with a low BMI (≤18.5) in vitiligo patients (Table 3).
Table 3.
Analysis of factors associated with a low BMI (≤18.5) in vitiligo patients
| N | BMI <20 |
p value | ||
|---|---|---|---|---|
| n | % | |||
| Age | ||||
| <35 years | 126 | 29 | 23.0 | <0.001 |
| 35–49 years | 116 | 23 | 19.8 | |
| 50+ years | 158 | 10 | 6.3 | |
| Sex | ||||
| Female | 216 | 49 | 22.7 | <0.001 |
| Male | 184 | 13 | 7.1 | |
| Type of vitiligo onset | ||||
| Early (age <18 years) | 49 | 12 | 24.5 | 0.023 |
| Late (age >18 years) | 150 | 17 | 11.3 | |
| Speed of vitiligo onset | ||||
| Sudden | 83 | 11 | 13.3 | 0.602 |
| Gradual | 113 | 18 | 15.9 | |
| Growth of vitiligo lesions | ||||
| Absent | 12 | 2 | 16.7 | 0.639 |
| Slow | 145 | 23 | 15.9 | |
| Rapid | 40 | 4 | 10.0 | |
| Inflammation/pruritus | ||||
| No | 147 | 25 | 17.0 | 0.143 |
| Yes | 48 | 4 | 8.3 | |
| Total vitiligo extension | ||||
| <1.0% | 50 | 8 | 16.0 | 0.254 |
| 1.0–4.9% | 71 | 13 | 18.3 | |
| ≥5.0% | 51 | 4 | 7.8 | |
| Disease activity | ||||
| Active | 104 | 16 | 15.4 | 0.843 |
| Borderline | 34 | 4 | 11.8 | |
| Stable | 56 | 9 | 16.1 | |
| Koebner phenomenon | ||||
| No | 99 | 13 | 13.1 | 0.556 |
| Yes | 93 | 15 | 16.1 | |
| Personal history of cardiovascular disease | ||||
| No | 340 | 59 | 17.4 | 0.015 |
| Yes | 60 | 3 | 5.0 | |
| Personal history of cancer | ||||
| No | 375 | 59 | 15.7 | 1 |
| Yes | 24 | 3 | 12.5 | |
| Personal history of autoimmune disease | ||||
| No | 359 | 54 | 15.0 | 0.454 |
| Yes | 41 | 8 | 19.5 | |
| Personal history of psoriasis | ||||
| No | 379 | 59 | 15.6 | 1 |
| Yes | 21 | 3 | 14.3 | |
| Smoker | ||||
| No | 250 | 40 | 16.0 | 0.969 |
| Yes | 130 | 21 | 16.2 | |
| Corticosteroid therapy | ||||
| No | 393 | 60 | 15.3 | 0.297 |
| Yes | 7 | 2 | 28.6 | |
| Immunosuppressive therapy | ||||
| No | 397 | 62 | 15.6 | 1 |
| Yes | 3 | 0 | 0.0 | |
Discussion
In this study, the high BMI was significantly associated with the sudden onset of vitiligo, inflammation, and pruritus. Obesity is a proinflammatory condition in which hypertrophic adipocytes and adipose tissue-resident cells contribute to increase circulating levels of proinflammatory cytokines [23]. Leptin plays a pivotal role that can reduce the function and expansion of regulatory T cells and thereby amplifies inflammatory processes through the recruitment of CD8+ Th1 lymphocytes, mast cells, and macrophages and stimulates the release of proinflammatory cytokines and interleukin-2 [6]. Therefore, this chronic low-grade systemic inflammation can explain the association between a high BMI and the presence of inflammation/pruritus in vitiligo macules and possibly also the sudden onset of the disease.
However, vitiligo did not seem to be associated with a high BMI, in contrast to most autoimmune diseases which are significantly associated with obesity [6]. Increasing evidence suggests that the p53 tumor suppressor protein which also has important regulatory functions in cell growth/differentiation and metabolism is overexpressed in both lesional and nonlesional epidermis of patients with vitiligo [24, 25, 26]. A recent in vivo study showed that p53 exerts a suppressive effect on white adipocyte differentiation in both mouse and human cells, suggesting that this protein has a potential protective effect against diet-induced obesity [27]. The same study highlighted how p53 is implicated in proper brown adipose tissue differentiation which seemingly is protective against obesity [27]. Thus, it is conceivable that in vitiligo patients p53 is overexpressed in adipose tissue as well as in the skin, explaining our results at least in part.
An additional explanation of our results may be that in vitiligo there is a high systemic concentration of transforming growth factor-β, which is known to be a potent inhibitor of white adipose tissue differentiation [18, 28, 29].
Thus, it is conceivable that the high expression of p53 and the high concentration of transforming growth factor-β can contribute to the absence of obesity in our patients, as opposed to other autoimmune diseases.
A possible limitation of this study was noninvestigation of p53 and transforming growth factor-β, which could have affected the findings.
Conclusion
In this study, in contrast with most autoimmune diseases which are significantly associated with obesity, vitiligo did not appear to be related to a high BMI. Therefore, neither a high BMI nor obesity represents a feature of vitiligo in these patients and this seems to be an unusual autoimmune disease.
Appendix 1
General characteristics of the case and control groups.
| Characteristic | Vitiligo (n = 200) | Control (n = 200) |
|---|---|---|
| Gender | ||
| Female | 108 | 108 |
| Male | 92 | 92 |
| Age range | 14–75 | 17–76 |
| Type of onset of vitiligo | ||
| Early (age <18 years) | 49 (24.6%) | |
| Late (age >18 years) | 150 (75.4%) | |
| Speed of vitiligo onset | ||
| Sudden | 83 (42.3%) | |
| Gradual | 113 (57.7%) | |
| Growth of vitiligo lesions | ||
| Absent | 12 (6.1%) | |
| Slow | 145 (73.6%) | |
| Rapid | 40 (20.3%) | |
| Inflammation/pruritus | ||
| No | 147 (75.4%) | |
| Yes | 48 (24.6%) | |
| Disease activity | ||
| Active | 104 (53.6%) | |
| Borderline | 34 (17.5%) | |
| Stable | 56 (28.9%) | |
| Total vitiligo extension | ||
| <1% | 50 (29.1%) | |
| 1–4.9% | 71 (41.3%) | |
| ≥5% | 51 (29.7%) | |
| Koebner's phenomenon | ||
| No | 99 (51.6%) | |
| Yes | 93 (48.4%) | |
| Personal history of cardiovascular disease | ||
| No | 176 (88.0%) | 164 (82.0%) |
| Yes | 24 (12.0%) | 36 (18.0%) |
| Personal history of autoimmune disease | ||
| No | 165 (82.5%) | 194 (97.0%) |
| Yes | 35 (17.5%) | 6 (3.0%) |
| Personal history of cancer | ||
| No | 191 (96.0%) | 184 (92.0%) |
| Si | 8 (4.0%) | 16 (8.0%) |
| Personal history of psoriasis | ||
| No | 190 (95.0%) | 189 (94.5%) |
| Yes | 10 (5.0%) | 11 (5.5%) |
| Corticosteroid therapy | ||
| No | 198 (99.0%) | 195 (97.5%) |
| Yes | 2 (1.0%) | 5 (2.5%) |
| Immunosuppressive therapy | ||
| No | 200 (100.0%) | 197 (98.5%) |
| Yes | 0 (0.0%) | 3 (1.5%) |
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