A Retrospective Study on 464 Bullous Pemphigoid Patients in Northeast China
Bullous pemphigoid (BP) is a chronic autoimmune blistering disease characterized by the presence of autoantibodies targeting two hemidesmosomal proteins, BP180 and BP230. These autoantibodies interfere with the adhesion of basal epidermal keratinocytes, leading to the formation of blisters. The global incidence of BP ranges from 2.5 to 75 cases per million per year. Genetic, environmental, and stochastic factors contribute to the susceptibility to BP. This retrospective study aimed to evaluate the clinical characteristics of BP in Northeast China by analyzing data from 464 BP patients treated at Shenyang Seventh People’s Hospital between January 2015 and January 2020. All patients met the diagnostic criteria for BP, and the study was approved by the Institutional Review Board of Shenyang Seventh People’s Hospital (No. 2015-WQ-01).
Epidemiological and Clinical Characteristics
The study included patients aged 14 to 97 years, with an average age of 73.14 ± 2.32 years. The male-to-female (M/F) ratio was 1.32:1, indicating a higher prevalence among males. BP accounted for 0.73% (464/63,969) of dermatology inpatients, with a stable annual incidence. The average hospital stay was 24.93 ± 6.21 days. Among the patients, 15.73% (73/464) had mucous membrane involvement, and 7.54% (35/464) experienced fever. The temperature of febrile patients fluctuated between 37.5°C and 38.5°C. Fever and elevated blood eosinophils were correlated with the severity of BP.
Auxiliary Examinations and Laboratory Findings
All patients underwent histopathological examinations, which revealed subcutaneous blisters and eosinophilic granulocyte infiltration. Routine laboratory tests after hospitalization showed elevated leukocytes in 21.1% (98/464) of patients, eosinophils >5% in 19.2% (89/464) of patients, hemoglobin <110 g/L in 23.5% (109/464) of patients, hypoalbuminemia in 17.0% (79/464) of patients, and blood electrolyte disorders in 13.8% (64/464) of patients. Direct immunofluorescence (DIF) examination showed a higher BP positive rate compared to indirect immunofluorescence (IIF), although the difference was not statistically significant. The levels of anti-BP180 and anti-BP230 antibodies were positively correlated with the severity of BP.
Comorbidities and Associated Conditions
A total of 278 patients had one or more systemic diseases, and 34 patients had other skin diseases such as eczema, psoriasis, and lichen planus. Neurological system diseases were the most common comorbidities, affecting 21.8% (101/464) of patients, followed by circulatory system diseases (15.3%, 71/464), respiratory system diseases (11.4%, 53/464), motor system diseases (7.1%, 33/464), immune system diseases (6.5%, 30/464), urinary system diseases (3.7%, 17/464), digestive system diseases (2.6%, 12/464), blood system diseases (1.5%, 7/464), and genital system diseases (1.1%, 5/464).
Treatment and Outcomes
Diamino diphenyl sulfone was ineffective in four patients. Two patients treated with oral cyclosporine experienced fading of most rashes within 4 to 5 days, but blisters continued to appear until glucocorticoids were added. Intravenous immune globulin (IVIG) was effective in 58 patients, and plasmapheresis was effective in 11 patients. Topical treatments included glucocorticoid cream, antibiotic ointment, and He-NE laser. Blood-cooling detoxification decoction, a traditional Chinese medicine (TCM), was used to treat patients with acute paroxysm, rapid blister multiplication, fever, thirst, dry stool, dark urine, and red tongue. The effectiveness and safety of TCM in early treatment were investigated in a randomized study involving 28 patients receiving combined Western and Chinese medicine and 20 patients receiving Western medicine alone. The time from treatment initiation to blister disappearance and dry erosive surface formation was significantly shorter in the TCM group compared to the control group.
Disease Severity and Misdiagnosis
The severity of BP was classified based on body surface area (BSA) involvement: mild (skin lesions 30% of BSA). In this study, 17.9% (83/464) of patients had mild BP, 58.0% (269/464) had moderate BP, and 24.1% (112/464) had severe BP. The misdiagnosis rate was 5.17% (24/464), as BP can present as eczematoid erythema in the early stages, leading to diagnostic challenges. Multiple biopsies were often required for a definitive diagnosis.
Fever and Drug-Induced BP
Fever is uncommon in BP, but this study found that 7.5% (35/464) of patients had fever, which was associated with increased blood eosinophils, flushing, rashes, and severe pruritus. Some patients had a history of drug use, including quinolones, antibiotics, nonsteroidal drugs, and angiotensin-converting enzyme inhibitors, before the onset of BP. Although no direct correlation between drugs and BP was established, these patients were prone to be diagnosed with drug-induced BP.
Treatment Strategies and Glucocorticoid Use
Glucocorticoids remain the most effective treatment for BP, especially in recurrent cases. Many experts recommend a lower dose of corticosteroids for BP compared to pemphigus, but this study suggested that a larger dose may be required for impact therapy in severe cases. Minocycline, nicotinamide, and Tripterygium wilfordii were effective in mild patients with frequent recurrences 2 to 3 years later. Immunosuppressors such as cyclosporine were not the preferred treatment option. IVIG effectively neutralized various pathogenic factors and enhanced the body’s anti-infection and immune-modulating functions. Plasmapheresis was used to remove disease-related autoantibodies and reduce glucocorticoid doses but was reserved for severe cases due to its high cost.
Traditional Chinese Medicine and Disease Onset
TCM practitioners believe that disease onset is correlated with specific months. In this study, June and December were the most common months for BP onset. TCM was widely applied in dermatologic therapy and showed good efficacy in early BP treatment without adverse events. Antipyretic-alexipharmic drugs were effective in treating fiery syndromes such as rapidly increased blisters, red tongue, and yellow moss.
Severe Cases and Topical Treatments
Severe BP patients often suffered from extensive surface erosion, leading to hypoproteinemia and skin infections. Topical treatments in this study included He-NE laser, antibiotic ointment, hormone cream, and nursing care. The death causes in BP patients were mostly related to systemic illnesses and glucocorticoid-induced side effects, often requiring multidisciplinary treatment.
Mortality and Genetic Factors
The 1-year mortality rate in this study was 4.1%, which is lower than the global combined BP mortality rate of 6% to 40%. This lower mortality rate was not attributed to the diagnostic criteria. Genetic factors, such as major histocompatibility complex (MHC) class II alleles, play a significant role in BP susceptibility. HLA-DRB110:01 is associated with susceptibility to BP, while DRB107:01 allele is associated with protection against BP. Differences in alleles lead to diverse pathogenesis, affecting BP severity, clinical manifestations, and 1-year combined mortality.
Conclusion
This retrospective study provides comprehensive insights into the clinical characteristics, treatment outcomes, and associated factors of BP in Northeast China. The findings highlight the importance of early diagnosis, appropriate treatment strategies, and the potential role of TCM in managing BP. Further research is needed to explore the underlying mechanisms and genetic factors contributing to BP susceptibility and severity.
doi.org/10.1097/CM9.0000000000001744
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