Abstract
Pemphigus is a life-threatening and skin-specific inflammatory autoimmune disease, characterized by intraepidermal blistering between the mucous membranes and skin. Chinese herbal medicine (CHM) has been used as an adjunct therapy for treating many diseases, including pemphigus. However, there are still limited studies in effects of CHM treatment in pemphigus, especially in Taiwan. To more comprehensively explore the effect of long-term CHM treatment on the overall mortality of pemphigus patients, we performed a retrospective analysis of 1,037 pemphigus patients identified from the Registry for Catastrophic Illness Patients database in Taiwan. Among them, 229 and 177 patients were defined as CHM users and non-users, respectively. CHM users were young, predominantly female, and had a lesser Charlson comorbidity index (CCI) than non-CHM users. After adjusting for age, sex, prednisolone use, and CCI, CHM users had a lower overall mortality risk than non-CHM users (multivariate model: hazard ratio (HR): 0.422, 95% confidence interval (CI): 0.242–0.735, p = 0.0023). The cumulative incidence of overall survival was significantly higher in CHM users than in non-users (p = 0.0025, log rank test). Association rule mining and network analysis showed that there was one main CHM cluster with Qi–Ju–Di–Huang–Wan (QJDHW), Dan–Shen (DanS; Radix Salviae miltiorrhizae; Salvia miltiorrhiza Bunge), Jia–Wei–Xiao–Yao-–San (JWXYS), Huang–Lian (HL; Rhizoma coptidis; Coptis chinensis Franch.), and Di–Gu–Pi (DGP; Cortex lycii; Lycium barbarum L.), while the second CHM cluster included Jin–Yin–Hua (JYH; Flos lonicerae; Lonicera hypoglauca Miq.) and Lian–Qiao (LQ; Fructus forsythiae; Forsythia suspensa (Thunb.) Vahl). In Taiwan, CHMs used as an adjunctive therapy reduced the overall mortality to approximately 20% among pemphigus patients after a follow-up of more than 6 years. A comprehensive CHM list may be useful in future clinical trials and further scientific investigations to improve the overall survival in these patients.
Highlights
Pemphigus is a life-threatening and skin-specific inflammatory autoimmune disease, characterized by painful erosion of mucous membranes or flaccid blistering of the skin, in addition to mucous membrane lesions (Didona et al, 2019)
Patients with pemphigus (ICD-9-CM-code: 694.4) in Taiwan were selected from the database of Registry for Catastrophic Illness Patients of Taiwan’s National Health Insurance Research Database (NHIRD) (Figure 1)
After excluding patients who received less than 14 cumulative Chinese herbal medicine (CHM) days within the first year after the diagnosis of pemphigus, there were 229 patients classified as CHM users and 177 patients as non-CHM users
Summary
Pemphigus is a life-threatening and skin-specific inflammatory autoimmune disease, characterized by painful erosion of mucous membranes or flaccid blistering of the skin, in addition to mucous membrane lesions (Didona et al, 2019). This intraepidermal blistering is called acantholysis due to the loss of cell-cell adhesion, and is predominantly induced by pathogenic IgG autoantibodies (autoAbs) against epidermal adhesion proteins of keratinocytes (Buonavoglia et al, 2019). Other types with varying degrees of inflammation and IgG autoAb concentrations against adhesion proteins have been reported (Amber et al, 2018; Chernyavsky et al, 2019). Patients with other types have a variety of IgG autoAbs against the plakin family, plakophilin 3, desmocollins 1 and 3, and alpha-2 macroglobulinlike 1 adhesion proteins (Kasperkiewicz et al, 2017; Kim and Kim, 2019)
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