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Research Letter |

Association Between Vitiligo and Atopic Disorders: A Pilot Study FREE

Jonathan I. Silverberg, MD, PhD, MPH1; Nanette B. Silverberg, MD1
[+] Author Affiliations
1Department of Dermatology, Beth Israel Medical Center and St Luke’s–Roosevelt Hospital Center, New York, New York
JAMA Dermatol. 2013;149(8):963-986. doi:10.1001/jamadermatol.2013.4228.
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Published online

Vitiligo is an autoimmune disorder characterized by melanocyte destruction and loss of pigmentation. Vitiligo has a higher prevalence of autoimmune disorders.1 Little is known about the atopic comorbidities associated with vitiligo. We hypothesized that the proinflammatory state in vitiligo may contribute toward atopic disorders.

We previously reported a high prevalence of skin symptoms in vitiligo, such as itching or burning.1 We hypothesized that a subset of symptomatic patients may actually have a history of eczema and atopy. We conducted a prospective epidemiological study to elucidate these points.

This prospective online-questionnaire based study was approved by the institutional review board at St Luke’s-Roosevelt Hospital Center. The survey validation and distribution were performed as previously described.1 Two distinct questionnaires were created for adults with vitiligo and parents of children and adolescents with vitiligo (eTable [Supplement]). Questionnaire items were developed to determine novel risk and prognostic factors for vitiligo. The a priori aims of the questionnaire included identification of comorbid atopic disease in vitiligo.

Data processing and statistical analysis were performed with SAS statistical software (version 9.2; SAS Institute Inc). Current age and duration of vitiligo were divided into quartiles for statistical analysis owing to wide skewing.

Logistic regression models were constructed to examine associations between clinical parameters and atopic disease, with specific etiologies as dependent variables. The independent variables were self-reported body surface area (BSA), duration of vitiligo and itching or burning of skin. Adjusted odds ratios (aORs) were calculated by including sex, age, and race/ethnicity in multivariate models. Linear interaction terms were tested and only included in final models if significant (P < .05). Correction for multiple dependent tests (k = 38) with the approaches of Benjamini and Hochberg2 yielded a critical P value of .03.

A total of 2848 patients started the survey, of whom 2763 completed it (a 97.0% completion rate). There were 2645 diagnosed as having vitiligo by a physician, including 2273 adults and 371 children and adolescents. The patient characteristics are listed in Table 1.

Table Graphic Jump LocationTable 1.  Characteristics of 2645 Patients1

A total of 1635 patients (61.8%) reported a history of at least 1 atopic disease. The most common etiology was hay fever (48.2%), followed by atopic dermatitis (AD) (24.0%), food allergy (18.2%), and asthma (17.8%). A history of any atopic disease was more common in those older than 40 years (P ≤ .03) and patients who were multiracial or of “other” race/ethnicity (P = .03), but was less common in Indians (P < .001). There was no association between sex and history of atopic disease (P = .44).

Atopic disease was associated with vitiligo involving a BSA of at least 76% (aOR, 1.47 [95% CI, 1.10-1.97]; P = .009) and itching or burning of skin (aOR, 1.64 [95% CI, 1.38-1.96]; P < .001) but not duration of vitiligo (P ≥ .04). Among patients who had an atopic disease involving a BSA of 76% (aOR, 1.57 [95% CI, 1.12-2.18]; P = .008) and itching or burning (aOR, 1.48 [95% CI, 1.20-1.83]; P < .001) were associated with higher odds of multiple disorders compared with those who had only 1 atopic disease.

In a subset analysis, a BSA of least 76% was associated with AD (aOR, 1.71 [95% CI, 1.26-2.31]; P < .001), hay fever (aOR, 1.35 [95% CI, 1.03-1.79]; P = .03), and food allergy (aOR, 1.35 [95% CI, 1.03-1.79]; P = .03) but not asthma (aOR, 1.21 [95% CI, 0.85-1.71]; P = .30) (Table 2). Itching or burning was associated with all 4 atopic diseases (P < .001).

Table Graphic Jump LocationTable 2.  Association Between Atopic Disease and Vitiligo Extent and Symptoms for Any Atopic Disease1

The present study found higher prevalences of atopic disease in vitiligo compared with previously established prevalences in the general adult population (AD, 3%3; asthma, 8%4; hay fever, 24%5; food allergy, 5%6). These results are consistent with those of a previous study of 59 patients with vitiligo that found increased rates of asthma, hay fever, and positive results from skin prick and radiosorbent allergen testing.7 Similarly, a Chinese study of 6516 patients with vitiligo found a higher prevalence of asthma in familial probands.8

History of atopic disease may be helpful to predict which patients with vitiligo will experience progression to extensive disease. There are several possible explanations for the association of vitiligo involving a BSA of at least 76% and itching or burning with atopic diseases. The proinflammatory state of AD may predispose toward melanocyte destruction, while scratching of pruritic AD lesions may koebnerize vitiligo. Alternatively, there may be a common genetic mutation(s) that predisposes to both AD and vitiligo. One such example might be vitamin D receptor polymorphisms that are associated with generalized vitiligo and severe AD.9 Filaggrin mutations are thought to mediate severity for patients with alopecia areata and with AD and should be explored in vitiligo.10 This raises an important question: does atopy predispose toward vitiligo or do the 2 diseases merely coexist?

This study has several strengths, including being prospective with a validated survey instrument for vitiligo. However, it is limited by the lack of a control group without vitiligo. A large randomized sample of healthy patients with minimization of bias should be used for controls. However, that is a very ambitious undertaking, beyond the scope of this pilot study, and will be the subject of future studies.

Corresponding Author: Jonathan I. Silverberg, MD, PhD, MPH, Department of Dermatology, St Luke’s–Roosevelt Hospital Center and Beth Israel Medical Center, 1090 Amsterdam Ave, Ste 11B, New York, NY 10025 (JonathanISilverberg@gmail.com).

Accepted for Publication: February 22, 2013.

Published Online: June 5, 2013. doi:10.1001/jamadermatol.2013.4228.

Author Contributions: Both authors had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.

Study concept and design: J. I. Silverberg.

Acquisition of data: J. I. Silverberg.

Analysis and interpretation of data: Both authors.

Drafting of the manuscript: J. I. Silverberg.

Critical revision of the manuscript for important intellectual content: Both authors.

Statistical analysis: J. I. Silverberg.

Administrative, technical, and material support: N. B. Silverberg.

Study supervision: N. B. Silverberg.

Conflict of Interest Disclosures: None reported.

Trial Registration: clinicaltrials.gov Identifier: NCT01401374.

Silverberg  JI, Silverberg  NB.  Association between vitiligo extent and distribution and quality-of-life impairment. JAMA Dermatol. 2013;149(2):159-164.
PubMed   |  Link to Article
Benjamini  Y, Hochberg  Y.  Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57:289-300.
Muto  T, Hsieh  SD, Sakurai  Y,  et al.  Prevalence of atopic dermatitis in Japanese adults. Br J Dermatol. 2003;148(1):117-121.
PubMed   |  Link to Article
Centers for Disease Control and Prevention (CDC).  Vital signs: asthma prevalence, disease characteristics, and self-management education: United States, 2001-2009. MMWR Morb Mortal Wkly Rep. 2011;60(17):547-552.
PubMed
Sibbald  B, Rink  E.  Epidemiology of seasonal and perennial rhinitis: clinical presentation and medical history. Thorax. 1991;46(12):895-901.
PubMed   |  Link to Article
Vierk  KA, Koehler  KM, Fein  SB, Street  DA.  Prevalence of self-reported food allergy in American adults and use of food labels. J Allergy Clin Immunol. 2007;119(6):1504-1510.
PubMed   |  Link to Article
Perfetti  L, Cespa  M, Nume  A, Orecchia  G.  Prevalence of atopy in vitiligo: a preliminary report. Dermatologica. 1991;182(4):218-220.
PubMed   |  Link to Article
Zhang  Z, Xu  SX, Zhang  FY,  et al.  The analysis of genetics and associated autoimmune diseases in Chinese vitiligo patients. Arch Dermatol Res. 2009;301(2):167-173.
PubMed   |  Link to Article
Heine  G, Hoefer  N, Franke  A,  et al.  Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults. Br J Dermatol. 2013;168(4):855-858.
PubMed   |  Link to Article
Blyumin  ML, Hu  S, Kirsner  RS.  Filaggrin gene mutations mediate severity of alopecia areata when associated with atopic dermatitis. J Invest Dermatol. 2007;127(11):2494.
Link to Article

Figures

Tables

Table Graphic Jump LocationTable 1.  Characteristics of 2645 Patients1
Table Graphic Jump LocationTable 2.  Association Between Atopic Disease and Vitiligo Extent and Symptoms for Any Atopic Disease1

References

Silverberg  JI, Silverberg  NB.  Association between vitiligo extent and distribution and quality-of-life impairment. JAMA Dermatol. 2013;149(2):159-164.
PubMed   |  Link to Article
Benjamini  Y, Hochberg  Y.  Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57:289-300.
Muto  T, Hsieh  SD, Sakurai  Y,  et al.  Prevalence of atopic dermatitis in Japanese adults. Br J Dermatol. 2003;148(1):117-121.
PubMed   |  Link to Article
Centers for Disease Control and Prevention (CDC).  Vital signs: asthma prevalence, disease characteristics, and self-management education: United States, 2001-2009. MMWR Morb Mortal Wkly Rep. 2011;60(17):547-552.
PubMed
Sibbald  B, Rink  E.  Epidemiology of seasonal and perennial rhinitis: clinical presentation and medical history. Thorax. 1991;46(12):895-901.
PubMed   |  Link to Article
Vierk  KA, Koehler  KM, Fein  SB, Street  DA.  Prevalence of self-reported food allergy in American adults and use of food labels. J Allergy Clin Immunol. 2007;119(6):1504-1510.
PubMed   |  Link to Article
Perfetti  L, Cespa  M, Nume  A, Orecchia  G.  Prevalence of atopy in vitiligo: a preliminary report. Dermatologica. 1991;182(4):218-220.
PubMed   |  Link to Article
Zhang  Z, Xu  SX, Zhang  FY,  et al.  The analysis of genetics and associated autoimmune diseases in Chinese vitiligo patients. Arch Dermatol Res. 2009;301(2):167-173.
PubMed   |  Link to Article
Heine  G, Hoefer  N, Franke  A,  et al.  Association of vitamin D receptor gene polymorphisms with severe atopic dermatitis in adults. Br J Dermatol. 2013;168(4):855-858.
PubMed   |  Link to Article
Blyumin  ML, Hu  S, Kirsner  RS.  Filaggrin gene mutations mediate severity of alopecia areata when associated with atopic dermatitis. J Invest Dermatol. 2007;127(11):2494.
Link to Article

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