Gender-Based Variability in Disease Presentation in Pemphigus Vulgaris
October 2014 | Volume 13 | Issue 10 | Original Article | 1225 | Copyright © October 2014
Sahar Y. Naseer MS,a Liza Gill BS,b Jay Shah MD,b and Animesh A. Sinha MD PhDa
aDepartment of Dermatology, University at Buffalo, State University of New York, Buffalo, NY
bDivision of Dermatology, Michigan State University, Grand Rapids, MI
Pemphigus vulgaris is a chronic autoimmune blistering disorder of the skin. As with many autoimmune diseases, a female predominance in pemphigus vulgaris is well established. The genetic and physiological basis for this gender bias is not well understood. Moreover, it is unclear whether the affect of gender extends beyond disease susceptibility to influence disease presentation. To address this issue, we performed a comprehensive analysis of 72 male and 125 female pemphigus vulgaris patients across a set of defined demographic (HLA type, ethnicity) and clinical (age at disease onset, anti-desmoglein antibody levels, site of lesions, and history of autoimmune disease) factors. We find that male patients are more likely to present with disease onset before age 40 than females. Additionally, we find that males have increased cutaneous involvement and display greater co-expression of anti-Dsg1 and anti-Dsg3 antibodies, while females tend to have mucosal predominance and stronger personal and family histories of autoimmunity. We do not find any differences in the distribution of HLA type or ethnicity between male and female pemphigus vulgaris patients. Our findings establish that gender does influence disease presentation in pemphigus vulgaris, supporting a role for genetic and hormonal factors in immune dysregulation and perpetuation of the autoimmune phenotype. J Drugs Dermatol
Pemphigus vulgaris is a classic organ-specific autoimmune disease. The disease presents with flaccid blisters in the mucous membranes and skin, most often in the 5th decade of life. Although the precise pathologic mechanism of keratinocyte separation and blister formation remains unknown, there is likely a complex interplay between anti-desmosomal autoantibodies, as well as other self-antigens and immunoregulatory cells.1 Epidemiologically, the incidence of pemphigus vulgaris is enriched in certain ethnic groups including Ashkenazi Jews and select Asian populations.1 Studies have also shown that similar to many other autoimmune diseases, pemphigus vulgaris is more prevalent in females versus males, reporting male: female ratios ranging from 1: 1.3 to 1: 1.72-8 (Table 1).
The mechanistic basis of the increased incidence of pemphigus vulgaris in females is not well understood but may involve hormonal influences, genetic variations, and/or epigenetic regulation of gene expression. Moreover, although gender appears to be a component of underlying genetic susceptibility for the development of pemphigus vulgaris, it remains unclear whether gender can also influence phenotypic expression of the disease. Such a precedent has been established in other autoimmune diseases, including alopecia areata9 and rheumatoid arthritis,10 wherein gender has been shown to correlate with distinct epidemiologic and clinical features. For example, in rheumatoid arthritis, male patients have been found to have significantly later onset of disease and higher antibody titers than female patients. However, a similar analysis in pemphigus vulgaris has not been reported in the literature.
In order to assess the association between gender and clinical heterogeneity in pemphigus vulgaris, we performed a retrospective analysis of 72 male and 125 female pemphigus vulgaris patients across a range of demographic (HLA type, ethnicity) and clinical (age at disease onset, anti-desmoglein antibody levels, site of lesions, and history of autoimmune disease) factors.
We find that male patients are more likely to present with pemphigus vulgaris before 40 years of age and have increased cutaneous involvement compared to females, whereas females most commonly present between the ages of 40-49 years and report higher personal and family histories of autoimmune disease than males. These findings help advance our understanding of variations in disease presentation based on gender differences.
Recruitment of Study Subjects
One hundred and ninety-seven patients were enrolled in this study from dermatology outpatient clinics and annual meetings of the International Pemphigus and Pemphigoid Foundation (IPPF). The study was reviewed and approved by the institutional review boards at each of the three participating institutions: Weill-Cornell Medical College (IRB 0998-398), Michigan State University (IRB 05-1034), and the University at Buffalo (IRB 456887).