Gender Differences in Alopecia Areata
April 2014 | Volume 13 | Issue 4 | Original Article | 409 | Copyright © April 2014
Michael Lundin BS,a Simran Chawa BS,a Amit Sachdev MD,b Dhaval Bhanusali MD,c Kristina Seiffert-Sinha MD,d Animesh A. Sinha MD PhDd
aDivision of Dermatology, Michigan State University, East Lansing, MI bDepartment of Neurology, Thomas Jefferson University, Philadelphia, PA cDepartment of Dermatology, St. Luke’s-Roosevelt Hospital, New York, NY dDepartment of Dermatology, University at Buffalo, Buffalo, NY
Alopecia areata (AA) is a common, non-scarring, autoimmune hair-loss disorder with a complex genetic and environmental etiology. A higher incidence rate of AA in the female population is well described. It is unclear why females are more likely to be diagnosed with AA and what, if any, differences in disease phenotype exist between males and females. The identification of gender specific characteristics of disease may help clinical management and patient education in cases of AA. Accordingly, we recruited 481 North-American Caucasian AA patients (336 female, 145 male) to assess age of onset, autoimmune and atopic co-morbidity, nail involvement, family history of AA and autoimmune disease, and disease subtype. There was a female predominance (female to male ratio 2.3:1) in this AA study population. We found that male AA patients are more likely to be diagnosed in childhood (age <10 years, P= 0.067) and have a family history of AA (P= 0.004). On the other hand, female AA patients are more likely to be diagnosed in adolescence (age 10-20 years, P= 0.083), have co-morbid nail involvement (P= 0.0257), and have concomitant autoimmune disease (P= 0.014), particularly thyroid disease (P= 0.058). The clinical implications of disease heterogeneity between males and females remains to be determined. J Drugs Dermatol.
Alopecia areata (AA) is a multifactorial, non-scarring, hair-loss disorder of autoimmune origin.1 Although the exact etiology of AA remains unclear, both genetic and environmental components likely contribute to development and progression of AA.2 Genetic susceptibility to AA is suggested by associations with AIRE,3 HLA-DR/DQ,4 IL-15, MX1, TRAF1/C5, and Notch4,6,7 as well as by the over-representation of concomitant autoimmune conditions such as systemic lupus, rheumatoid arthritis, pemphigus, Type I Diabetes, and thyroid disease in AA patients.5,8,9
In a number of autoimmune diseases, a higher incidence rate in females versus males is established, eg, SLE, Sjögren’s syndrome, rheumatoid arthritis, primary biliary cirrhosis, and multiple sclerosis.10,11,12 In AA, however, a female predisposition in the European and North-American Caucasian populations is controversial, with female to male ratios ranging from 1:1.9 to 2.6:1 (Table 1).
The etiology of the observed female bias towards autoimmune disease development in general is not known. Proposed mechanisms include: 1)Differences in immune cell androgen and estrogen receptor activation between males and females, particularly during pregnancy; 2)X chromosome mediation of innate immune response and immune tolerance; and 3)Maternal microchimerism of fetal immune cell lines, among others.11,13,14 It is unclear how the multifactoral etiology of the female bias towards autoimmune disease development interacts with the multifactorial etiology of AA to predispose susceptible individuals to disease and affect clinical presentation.
Clinically, female patients with AI diseases such as SLE, rheumatoid arthritis, pemphigus, type I diabetes, and Hashimoto’s disease have been reported to present and progress differently than their male counterparts.12 The average age of onset of AA has been shown to vary by gender and ethnicity.15-17 However, it is unclear whether a difference in age of disease onset exists between males and females in the Caucasian AA population. Descriptions of gender variance in alopecia areata disease including autoimmune and atopic co-morbidity, nail involvement, family history of AA and autoimmune disease, and disease subtype, has been limited.15-25 Further study of gender specific characteristics of disease may be of great value in diagnosis, predicting clinical course, and selecting at-risk patients for basic research into the inherited and environmental mediators of disease.
In order to investigate the potential differences between males and females diagnosed with AA, we recruited 481 clinician-confirmed North-American-Caucasian AA patients from our clinics and from AA patient conferences. Patients were classified on the basis of seven clinical parameters, and in each case, male vs female patients were compared. Our analysis revealed the existence of significant disease heterogeneity between males and females with AA in defined patient subgroups.
MATERIALS AND METHODS
This study was approved by the Institutional Review Boards (IRB) of Michigan State University (IRB No. 05-1026) and Weill Medical College of Cornell University (IRB No. 0998-398). We recruited 481 North-American Caucasian patients from AA