Clinical characteristics of bullous pemphigoid patients of different ages and the possible mechanism

Abstract

Bullous pemphigoid (BP) is an acquired autoimmune bullous disease that often occurs in elderly patients. Some BP patients with early age of disease onset were observed to have difficulty in receiving applicable disease control. It remains challenging for clinicians to choose the appropriate treatment for these patients. This study aimed to analyze the differences between patients of different ages at disease onset and further explore the possible mechanism of these differences between patients of different ages. A total of 215 BP patients seen at the dermatology department of Peking Union Medical College Hospital between January 2009 and September 2020 were included. The patients were allocated to five groups according to the age at disease onset. Clinical data were collected through medical records and telephone follow-up interviews. Analyses of anti-BP180 antibody subclasses, anti-BP230 antibodies, complement fixation, serum cytokine levels, and single nucleotide polymorphisms (SNPs) were conducted. Nearly 52% of patients under 60 were misdiagnosed on their first visit, often presenting with oral mucosal involvement. The anti-BP180 immunoglobulin (Ig) E titers and C3 deposition increased in patients under 60 (p = 0.044 and p = 0.014, respectively), while the anti-BP230 IgG titers decreased (p = 0.043). The hospitalization rate of patients under 50 was significantly higher than that of patients aged 80 and older (p < 0.001). The patients under 60 had a significantly higher serum concentration of interleukin (IL)-13, tumor necrosis factor (TNF)-α, and interferon gamma (IFN-γ) (p < 0.005, respectively). We observed significant differences in the distribution of genotypes or alleles of TNF-α rs1799964, TNF-α rs1800630, and IFN-γ rs2069705. Approximately one-third of the elderly patients suffered from neurological diseases. Elderly patients usually presented with peripheral eosinophilia (p = 0.013). No significant difference was identified in the recurrence rate and complement-activating capacity among the age groups. In conclusion, the early age of BP onset was associated with a more severe clinical presentation, higher titers of anti-BP180 IgE, lower titers of anti-BP230 IgG, and significantly higher serum concentrations of IL-13, TNF-α, and IFN-γ. It may also be associated with the presence of SNPs of cytokines, including TNF-α rs1799964, TNF-α rs1800630, and IFN-γ rs2069705 variants.