Dear Editor, The disease course of nonsegmental vitiligo is relatively unstudied. Clinical and epidemiological differences have been described in early‐ vs. later‐onset vitiligo, but the duration of disease has not been taken into account.1 2 Also, the prevalence of autoimmune comorbidities in patients with vitiligo has been studied mostly in populations of young patients with vitiligo, while autoimmune comorbidity may manifest later in life.1 2 3 The aim of this study was to assess retrospectively factors associated with disease extent and the lifetime prevalence of autoimmune comorbidities in a large cohort of older patients with nonsegmental vitiligo. A postal survey, approved by the institutional review board of the Academic Medical Center (AMC) Amsterdam, was conducted among patients with nonsegmental vitiligo, aged ≥ 50 years, who visited the Netherlands Institute for Pigment Disorders at the AMC between January 1995 and September 2010. These patients were also asked to invite a genetically nonrelated person of the same age group without vitiligo (e.g. a life partner) to fill in a control questionnaire. Questionnaires addressed self‐reported data on general demographics, vitiligo characteristics as previously described4 and clinically experienced autoimmune diseases (Appendix S1; see Supporting Information). Differences between groups were compared using the χ2‐test or Mann–Whitney U‐test. Univariate and multivariate regression models were used to quantify the relationship between time of vitiligo onset, sex and other variables, and extent of vitiligo and occurrence of thyroid disease, calculating odds ratios (ORs) with 95% confidence intervals (CIs). Potential confounders were identified by (borderline) significant outcome (95% CI) in the univariate regression analysis and were included in the adjusted multivariate analysis. Of 2635 eligible patients with vitiligo invited by mail, 1653 (63%) responded. Nonresponse was due to returned invalid address (n = 363), confirmation of death (n = 48) or unknown reasons. Questionnaires were sent to 1505 patients, of whom 1311 responded (87%), resulting in a 50% overall response rate.4 Characteristics of patients and controls are presented in Table 1. The median ages of patients with vitiligo and controls were 61 and 60 years, respectively. Early‐onset vitiligo (≤ 12 years) was present in 102 (7·8%) and later‐onset vitiligo (> 12 years) in 1205 (92·2%) patients. The mean age of vitiligo onset was 37 years and the median duration of vitiligo was 23 years. Extensive vitiligo (> 10% body surface area) was present in 670 patients (51·3%). Characteristics of patients with vitiligo and controls Values are n (%) unless stated otherwise. IQR, interquartile range. aIncludes head–neck, hands, arms, legs, feet, back, thorax. bPsoralen–ultraviolet A and narrowband ultraviolet B combined. cPatients may have more than one autoimmune disease. dOther autoimmune diseases specified as reported by patients: Addison disease, psoriatic arthritis, autoimmune hepatitis, irritable bowel disease, coeliac disease, limited cutaneous systemic sclerosis, morphoea, pernicious anaemia, polymyalgia rheumatica, sarcoidosis, scleroderma, Sjögren syndrome. Characteristics of patients with vitiligo and controls Values are n (%) unless stated otherwise. IQR, interquartile range. aIncludes head–neck, hands, arms, legs, feet, back, thorax. bPsoralen–ultraviolet A and narrowband ultraviolet B combined. cPatients may have more than one autoimmune disease. dOther autoimmune diseases specified as reported by patients: Addison disease, psoriatic arthritis, autoimmune hepatitis, irritable bowel disease, coeliac disease, limited cutaneous systemic sclerosis, morphoea, pernicious anaemia, polymyalgia rheumatica, sarcoidosis, scleroderma, Sjögren syndrome. In a multivariate regression analysis on vitiligo extent (Table 2), early‐onset vitiligo (OR 1·76, 95% CI 1·15–2·70) and female sex (OR 1·66, 95% CI 1·32–2·08) were both associated with extensive vitiligo (> 10% body surface area) at older age, adjusted for a history of phototherapy. Thus, female patients were more likely to have significantly more extensive depigmentation than male patients. Interestingly, evaluating the impact of the duration of vitiligo on disease extent in general, a trend could be seen regarding increasing decades of having vitiligo and an association with higher odds for extensive vitiligo at a later age, adjusting for age and sex. This was assessed in a multivariate analysis labelling patients with 10–20, 20–30, 30–40 and > 40 years of reported vitiligo duration compared with the reference group having < 10 years of vitiligo (data not shown). Apparently, the extent of vitiligo later in life appears not to be strictly influenced by the start of disease before or after the age of 12 years, as suggested by others,1 2 5 but may reflect the effect of cumulative years of disease duration. Univariate and multivariate logistic regression analyses on risk of extensive vitiligo (> 10% body surface area, BSA) and thyroid disease in patients with vitiligo OR, odds ratio; CI, confidence interval; ref, reference value. Univariate and multivariate logistic regression analyses on risk of extensive vitiligo (> 10% body surface area, BSA) and thyroid disease in patients with vitiligo OR, odds ratio; CI, confidence interval; ref, reference value. Overall, 29% of patients with vitiligo reported having experienced an autoimmune disease during their life, mostly thyroid disease (18·4%); this differs significantly from nonvitiligo controls (13·2% and 5·5%, respectively) (Table 1). Female patients with vitiligo had developed more thyroid disease (27%) than male patients with vitiligo (6%) (P < 0·001). In addition, female patients with vitiligo had developed more autoimmune disease and specifically more thyroid disease (P < 0·001), alopecia areata (P = 0·04) and rheumatoid arthritis (P = 0·032) than female controls without vitiligo, while male patients with vitiligo had developed more autoimmune diabetes mellitus than male controls (P = 0·001) (data not shown) . In a multivariate analysis (Table 2), female sex was associated with a fivefold increased risk of having thyroid disease, adjusted for age, time of vitiligo onset and extent of vitiligo (OR 5·06, 95% CI 3·38–7·58). The covariates age, time of vitiligo onset and extent of vitiligo were associated with thyroid disease in the univariate analysis, but this effect disappeared in the multivariate analysis including sex. This is in contrast to the results of others who described a positive relationship between affected body surface area and associated comorbid thyroid disease.3 6 7 The lifetime prevalence of 29% of comorbid autoimmune disease found in this cohort is comparable with that in an American cross‐sectional study of 2273 adult patients with vitiligo (median age unknown), describing 34·8% of self‐reported comorbid autoimmune disease.6 8 A Belgian vitiligo cohort study described 15·4% of self‐reported comorbid autoimmune disease in 700 patients; however, the mean age of this study population was 31 years.7 The lifetime prevalence of clinical thyroid disease of 18·4% found in the current study is in concordance with a systematic review reporting a median prevalence of autoimmune thyroid disease of 18·6% in adult patients with vitiligo.9 Overall, the reported prevalences of comorbid thyroid disease in patients with vitiligo vary, depending on the age of the patients included.1 2 6 7 10 Studies like this do have limitations. We included patients from one specialized institute and analysed patient‐reported answers on decades of disease history, which has an inherent potential of recall bias. Furthermore, patients with vitiligo and their doctors are possibly more alert for comorbid autoimmune disease, and patients might be screened for this more often. In conclusion, our results suggest that vitiligo leads to progressive lesions throughout life, which may be explained by the cumulative effect of episodes of disease activity, rather than the age of vitiligo onset. Female patients with vitiligo, with a median age of 61 years, had developed more extensive lesions and had a five‐times increased risk for thyroid comorbidity compared with male patients of that age. Although recommendations state to screen all patients with vitiligo annually for autoimmune thyroid disease, our data suggest that especially adult female patients should be regularly screened during their lives. Larger, and if possible, multicentre prospective cohort studies would be needed to corroborate these findings. Funding sources: H.E.T. is supported by a grant from the Dutch Cancer Society (grant UVA2009‐4378). Conflicts of interest: none declared. R.M.L. and J.P.W.vdV. contributed equally. Appendix S1. Netherlands Institute for Pigment Disorders vitiligo questionnaire.
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Teulings et al. (2016) studied this question.
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