Bullous Pemphigoid Research Articles

Eosinophil-rich Linear IgA Bullous Dermatosis: A Case Report of a Rare Entity

Linear IgA bullous dermatosis (LABD) is an uncommon autoimmune bullous disease characterized by a subepidermal neutrophilic infiltrate. It classically presents as widespread tense vesicles in an annular pattern and is defined by the presence of linear deposition of IgA at the dermal-epidermal junction. Eosinophil-rich LABD has been rarely reported in the literature, including in association with COVID-19 booster vaccination, parvovirus B19 infection, hematologic malignancies, and drug-induced LABD. The varied clinical and histopathologic findings often make it difficult to differentiate LABD from other blistering diseases such as bullous pemphigoid and dermatitis herpetiformis. For this reason, immunofluorescence and serologic testing are critical for identifying the underlying diagnosis.

Use of multivariant enzyme-linked immunosorbent assay (ELISA) in the diagnosis of autoimmune bullous disorders in a resource-limited setting: A single-center experience

Background Autoimmune blistering disorders (AIBD) result from the formation of auto-antibodies against adhesion proteins of the skin/mucosa(e). These auto-antibodies can be detected in the bound form in the tissue using direct immunofluorescence (DIF) or blood circulation using enzyme-linked immunosorbent assay (ELISA) or other methods. Objectives The objective of this study was to evaluate the concordance rate between the results of multivariant ELISA and the diagnosis of AIBD made using DIF and histopathology in an appropriate clinical context. Methods This was a retrospective study (December 2020 to April 2023) in which the multivariant ELISA assay (able to detect antibodies against desmoglein 1, desmoglein 3, BP180, BP230, envoplakin, and collagen VII) data were retrieved from the dermatology laboratory. Corresponding clinical and histopathology data were searched from relevant institutional databases. As per routine practice, the final diagnosis was assigned based on the clinical presentation, histopathology features and corresponding DIF report. Results After screening the records of 338 patients during the study period, 253 patients were included. Of them, 194 had AIBD and 59 had non-AIBD. In the autoimmune blistering disorder group, 122 and 72 patients had pemphigus and pemphigoid, respectively. Overall, a good level of agreement was found between multivariant ELISA results and the final diagnosis (Fleiss kappa = 0.631, p-value < 0.001). The pemphigus vulgaris group exhibited good agreement (kappa = 0.796, p < 0.001), while pemphigus foliaceous, bullous pemphigoid and non-autoimmune blistering disorders demonstrated moderate agreement (kappa = 0.641, 0.651, 0.533, respectively; p < 0.001). The mucous membrane pemphigoid group had a fair agreement (kappa = 0.289; p < 0.001). Limitations The limitations for the study were its retrospective design, fewer number of patients in certain groups like paraneoplastic pemphigus and gold-standard single antigen specific ELISA was not done. Conclusion Considering good agreement between the multivariant ELISA and the gold-standard diagnosis (clinical findings plus histopathology plus DIF), multivariant ELISA can be used for the diagnosis of AIBDs in places where facilities for DIF are unavailable. Multivariant ELISA can improve etiological diagnosis for a set of autoimmune blistering disorders whose target antigens are represented in the multivariant panel.

An uncommon cause of dysphagia: esophagitis dissecans superficialis secondary to bullous pemphigoid after vaccination for SARS-CoV-2.

Esophagitis dissecans superficialis (EDS) is an uncommon condition that is infrequently associated with autoimmune dermatoses. We present the case of a 75-year-old patient who developed EDS secondary to bullous pemphigoid after vaccination against SARS-CoV-2, with typical endoscopic and histological findings.

Resolution of Bullous Pemphigoid Following Lung Cancer Resection: A Case of Paraneoplastic Pemphigoid

Resolution of Bullous Pemphigoid Following Lung Cancer Resection: A Case of Paraneoplastic Pemphigoid

COVID-19 infection is associated with an elevated risk for autoimmune blistering diseases while COVID-19 vaccination decreases the risk: A large-scale population-based cohort study of 112 million individuals

Numerous diseases associated with COVID-19 infection and vaccination have been reported, including conditions such as the autoimmune blistering diseases (AIBD) pemphigus and pemphigoid. However, robust evidence supporting these associations is lacking. To investigate the risk of developing AIBD following COVID-19 infection and vaccination. Population-based retrospective cohort study utilizing data from over 112 million patients. The risk of AIBD within three months was compared among three cohorts: COVID-19 infection, COVID-19 vaccination, and controls, along with seven sensitivity analyses. COVID-19 infection was associated with an increased risk of AIBD (HR 1.508, 95% CI 1.260-1.805), with the risk being more pronounced for pemphigus (HR 2.432, 1.618-3.657) compared to bullous pemphigoid (HR 1.376, 1.019-1.857). Conversely, COVID-19 vaccination was associated with an almost halved risk of AIBD (HR 0.514, 0.394-0.672), with the risk reduction most significant for pemphigus (HR 0.477, 0.241-0.946). Comparisons between COVID-19 infection and vaccination revealed a more than threefold increased risk of AIBD in the infection cohort (HR 3.130, 2.411-4.063), particularly for pemphigus (HR 5.508, 2.973-10.205). Retrospective design and potential underreporting of COVID-19 cases and vaccinations. COVID-19 infection significantly increases the risk of AIBD while vaccination appears to reduce this risk.

Bullous pemphigoid induced by adalimumab in a patient with psoriasis.

Bullous pemphigoid induced by adalimumab in a patient with psoriasis.

Newly Diagnosed Bullous Pemphigoid in a Patient Receiving Sitagliptin

Newly Diagnosed Bullous Pemphigoid in a Patient Receiving Sitagliptin

Skin Biopsy Detection of Phosphorylated α-Synuclein in Patients of Bullous Pemphigoid with or without Parkinson's Disease.

High positivity rate of skin phosphorylated α-synuclein (P-SYN) was observed in Parkinson's disease (PD). Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases associated with PD. Our aim was to investigate whether BP patients might be a targeted risk population for the screening of skin P-SYN. Skin P-SYN expression was evaluated by immunohistochemistry in BP patients with/without PD. Twenty-two BP patients with PD, 24 BP patients without PD, and seven healthy donors were enrolled. Colocalization of P-SYN and PGP9.5 was found in all BP patients, but only one healthy control, whereas BP patients with PD showed higher expression than BP patients without PD (mean ± standard deviation, 10.7 ± 6.7 vs. 7.3 ± 3.2; P = 0.027). Positive expression was mainly observed in basement membrane zone and dermis. These results indicated BP patients might be a targeted risk population for the screening of skin P-SYN, which was helpful for the detection of PD early. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control study.

Bullous pemphigoid (BP) is an autoimmune skin disease that affects mainly older people. Numerous drugs have been previously associated with BP based on case series and small hospital-based studies. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of potential increased risk of BP following certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different types of culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved well-being. To determine the association between drugs/vaccines commonly prescribed to older people and BP risk. We conducted a population-based nested case-control study between 1998-2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched BP cases with up to 5 controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, we considered prescriptions may be prescribed for undiagnosed symptoms of BP which resemble skin infection (protopathic bias) in a sensitivity analysis. Antibiotics were the therapeutic group associated with the highest risk of BP (OR: 4.60; 95%CI 4.40-4.80). However, after adjusting for protopathic bias, the OR reduced to 2.08 (95%CI 1.99-2.17). After adjusting for protopathic bias, of all antibiotic classes and subclasses, penicillins and penicillinase-resistant penicillins had the strongest associations with BP risk (OR: 3.44; 95%CI 3.29-3.60; sensitivity analysis OR; 1.74; 1.66-1.84 and OR: 7.56; 95%CI 7.15-8.00; sensitivity analysis OR: 2.64; 95%CI 2.45-2.85, respectively). Other drugs strongly associated with increased risk were gliptins (OR: 2.77; 95% CI 2.37-3.23), and second-generation antipsychotics (OR: 2.58; 95%CI 2.20-3.03). Healthcare professionals need to be aware of BP risk in older people particularly when prescribing penicillinase-resistant penicillins, gliptins, and second-generation antipsychotic drugs to recognise and manage BP early. Due to the low prevalence of disease, we do not suggest avoidance of drugs/vaccines to prevent BP. Further research should consider recency, dosage, and duration of antibiotic treatments.

Immune checkpoint inhibitor-associated bullous pemphigoid: Aretrospective and real-world study based on the United States Food and Drug Administration adverse event reporting system.

This study aimed to describe bullous pemphigoid (BP) associated with immune checkpoint inhibitors (ICIs) reported in the United States Food and Drug Administration adverse event reporting system (FAERS). We obtained reports of ICI-associated BP from the first quarter of 2011 to the first quarter of 2024 in the FAERS database. The reporting odds ratio (ROR) method of the disproportionality analysis was performed to assess the potential risk for ICI-associated BP. We also described the clinical characteristics of ICI-associated BP and evaluated the time to onset (TTO) of BP developed after treatment with ICIs. Eight hundred and six cases of ICI-associated BP were gathered, in which 56.58% of the patients were aged 65 years or older. The majority of patients were male, accounting for 68.49% of all cases. The prevalent potential cancer type was skin cancer (31.64%). The results of the disproportionality analysis showed that males (ROR = 2.10 [1.78-2.49]), patients aged 65 or older (ROR = 2.13 [1.79-2.55]), and patients with skin cancer (ROR = 2.08 [1.80-2.43]) were more likely to develop ICI-associated BP. In comparison to cytotoxic T-lymphocyte-associated antigen 4 inhibitor and programmed cell death ligand 1 inhibitor, programmed cell death 1 inhibitor-associated BP has a higher risk of development (ROR = 24.45 [22.52-26.56]). ICI-associated BP had a median TTO of 204 days (interquartile range 57-426 days). ICI-associated BP is a rare but important immune-related adverse event. Our study provided helpful information to help medical professionals further understand ICI-associated BP.

Evaluation of Sarcopenia by Psoas Muscle Measurements in Bullous Pemphigoid: A Single-Institution Survey in Japan

Evaluation of Sarcopenia by Psoas Muscle Measurements in Bullous Pemphigoid: A Single-Institution Survey in Japan

A case of rapidly progressive hair loss due to azathioprine, and the prevalence of NUDT15 variants among Japanese patients with autoimmune blistering diseases: A single-center retrospective observational study.

Autoimmune blistering diseases (AIBDs), classified into pemphigus and pemphigoid, consist of relatively rare skin disorders caused by autoantibodies that target desmosomal and hemidesmosomal proteins, respectively. Although systemic corticosteroids are used as a first-line treatment for AIBDs, azathioprine is frequently co-administered as a steroid-sparing agent. Azathioprine is metabolized into thioguanine nucleotides (TGNs) which are its major active metabolites. The enzyme nudix hydrolase 15 (NUDT15) plays a key role in regulating TGNs. Serious side effects of azathioprine, including leukopenia and alopecia, are known to be particularly problematic in individuals with NUDT15 variants. The single-nucleotide polymorphism c.415C >T (p.Arg139Cys) is one of the most frequent NUDT15 variants associated with severe thiopurine toxicity. Recently, we treated a case of pemphigus vulgaris in a patient with NUDT15 variants in which the patient developed rapidly progressive diffuse hair loss and myelosuppression while receiving azathioprine. Previous reports on NUDT15 polymorphisms mainly focused on patients with inflammatory bowel disease or hematological malignancies, and the prevalence of NUDT15 polymorphisms remains unknown in AIBDs. This highlights the urgent need for research on NUDT15 polymorphisms in AIBDs to achieve a better understanding of the genetic factors influencing adverse reactions to azathioprine. To clarify the prevalence of NUDT15 variants in Japanese patients with AIBDs, we retrospectively reviewed the medical records of 78 patients with AIBDs (26 with bullous pemphigoid, 26 with pemphigus vulgaris, 17 with pemphigus foliaceus, and nine with other AIBDs) who had come to Hokkaido University Hospital between 2018 and 2023. The frequencies of NUDT15 variants of Arg/Arg, Arg/Cys, and Cys/Cys in these patients were approximately 72%, 23%, and 5%, respectively. Our findings indicate a prevalence of NUDT15 variants in AIBD patients that is similar to the prevalences of previous studies on patients with other diseases. These results emphasize the importance of screening for NUDT15 variants prior to initiating azathioprine treatment in Japanese patients with AIBDs.

Pemphigoid Gestationis - literature review

Introduction and Objective: Pemphigoid gestationis (PG) is a rare, self-limiting autoimmune disorder, typically appearing in the second or third trimester of pregnancy. It can lead to postpartum exacerbations, and studies suggest an increased risk of preterm birth and the development of Graves' disease in the mother. The aim of this article is to gather the latest information on pemphigoid gestationis. Review Methods: A review of studies available in the PubMed database was conducted using the keywords "pemphigoid gestationis" and "dermatoses of pregnancy" in order to find publications from the last 8 years. Brief Description of the State of Knowledge: Pemphigoid gestationis (PG) is characterized by the production of IgG1 antibodies against bullous pemphigoid antigen 180 (BP180). The primary symptom of PG is intense itching, which often occurs before skin lesions develop. Diagnosis is typically confirmed through direct immunofluorescence (DIF) of perilesional skin. Treatment focuses on relieving itching and preventing new blister formation, usually starting with topical corticosteroids for mild cases, while systemic corticosteroids are reserved for more severe presentations. Recent research indicates that biologic therapies may also offer effective management options for PG. Summary: The authors highlight the need for further research due to the limited sample sizes in existing studies, as well as the potential complications during pregnancy and long-term health effects.

Environmental triggers of pemphigus vulgaris and bullous pemphigoid: a case control study.

Previous case-control studies have suggested that environmental factors including exposure to pesticides and organic materials, diet and medications have an important role in the pathogenesis of pemphigus vulgaris. These studies lacked geographical population controls and had less than three controls per case. To identify environmental and occupational risk factors associated with the development of pemphigus vulgaris (PV) and bullous pemphigoid (BP). Cases were patients with PV (n = 25) and BP (n = 29) recruited from 2009 to 2017. Controls for PV (n = 72) and BP (n = 84) were recruited from the general population via electoral commission matching, matched for age, sex, residential location, and ethnicity. Data about demographics, environmental exposures and occupational exposures, was collected using a structured questionnaire. Conditional logistic regression analysis was undertaken using SPSS software to identify significant variables. Significant factors associated with PV included the daily consumption of leeks (odds ratio (OR) 3.6; p = 0.025), mustard oil (OR = 4.4; p = 0.049), tomatoes (OR = 4.735; p = 0.032), multivitamins (OR 3.6; p = 0.009), alcohol (0.039), and calcium supplements (OR = 44, p < 0.001). Other associated factors included the number of lifetime sunburns (p = 0.019), high levels of mental stress (p < 0.001), and the use of lime household cleaning products (p < 0.001), Significant factors associated with BP included the daily consumption of green or herbal tea (OR = 3.7; p = 0.004), fish oil (OR = 5.7; p < 0.001), calcium supplements (OR = 6.1; p < 0.001), multivitamins (OR = 2.6; p = 0.043), and glucosamine (OR = 3.0; p = 0.046). The use of lime household cleaning products (p < 0.001) and high levels of mental stress (p = 0.007) were also associated with BP. Dietary factors containing thiol groups such as leeks, tomatoes, and mustard oil may be potential triggers for PV. High levels of mental stress, the use of supplementary medications such as calcium and multivitamins, and chemical cleaning products containing lime may be associated with an increased risk of developing both PV and BP. Lifestyle changes should be part of routine management for these patients.

Serum interleukin-10 level is increased and correlated positively with disease severity in patients with dipeptidyl peptidase-4 inhibitor-related bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune subepidermal blistering disease with a linear deposit of autoantibodies at the epidermal basement membrane zone. It was reported that diabetes patients who took a dipeptidyl peptidase-4 inhibitor (DPP4i), an oral antidiabetic drug, had an increased incidence of BP. However, data on DPP4i-related BP are limited. In our study, we measured serum levels of various cytokines using LEGENDplex and assessed correlations of these serum levels with clinical severity and laboratory data. Serum samples obtained from BP patients who visited our hospital from June 2016 to February 2023 were collected in this study. Patients' background, characteristics, and clinical data were retrospectively collected from their charts. Serum samples from 27 patients with DPP4i-unrelated BP, 17 patients with DPP4i-related BP, and 13 healthy controls were analyzed. Patients with DPP4i-related BP had lower score of Bullous Pemphigoid Disease Area Index (BPDAI)-erythema/urticaria, lower number of circulating eosinophils, and lower titer of anti-BP180 antibody than patients with DPP4i-unrelated BP. The serum interleukin (IL)-6 level was significantly higher in patients with DPP4i-related BP than in healthy controls (P = 0.0037). The serum IL-10 level was significantly higher in patients with DPP4i-related BP than in patients with DPP4i-unrelated BP and in healthy controls (P = 0.0006, P = 0.0448), and was positively correlated with the BPDAI-blister/erosions score (r = 0.757, P = 0.001), BPDAI-erythema/urticaria score (r = 0.616, P = 0.013), and BPDAI-total score (r = 0.833, P < 0.001) in patients with DPP4i-related BP. In conclusion, patients with DPP4i-related BP had increased serum levels of IL-6 and IL-10 compared with healthy controls and positive correlations between the serum IL-10 level and BPDAI scores reflecting clinical severity, indicating that the serum IL-10 level is a potential objective biomarker of disease severity in patients with DPP4i-related BP.

Pathophysiology of Bullous Pemphigoid: Role of Type2 Inflammation and Emerging Treatment Strategies (Narrative Review).

Bullous pemphigoid (BP) is an autoimmune blistering disease that most often affects elderly individuals and has a significant negative impact on quality of life. The disease is characterized primarily by autoantibodies to hemidesmosomal proteins BP180 and/or BP230, and an inflammatory reaction with notable features of type2 inflammation, including elevated serum IgE, increased numbers of eosinophils in lesions and peripheral blood, and elevated expression of type2 cytokines and chemokines in skin lesions. In this review, we present what is known about BP pathophysiology, including the role of type2 inflammation, and discuss how findings from studies of biologics targeting type2 immune mediators have helped to clarify the biological mechanisms driving BP pathophysiology. Future studies of these targeted therapies and others in development will help to further elucidate the mechanisms underlying BP pathophysiology and potentially provide better treatment options for patients.

Real-World Evaluation of the Effectiveness and Safety of Dupilumab in Bullous Pemphigoid: An Ambispective Multicenter Case Series.

Bullous pemphigoid affects elderly individuals with multiple comorbidities, making conventional treatments unsuitable. Evaluate the effectiveness and safety of dupilumab in the treatment of bullous pemphigoid. A multicenter ambispective cohort study was conducted in 34 hospitals. Patients with bullous pemphigoid treated with Dupilumab were included. Most of patients (97.1%) received an initial 600 mg dose followed by 300 mg every two weeks. The primary outcome was the proportion of patients achieving complete remission within 4 weeks, defined as Investigator Global Assessment score of 0 or 1. Complete remission at weeks 16, 24, and 52, adverse events, reductions in peak pruritus numerical rating scale, and systemic glucocorticoid use were also assessed. The study included 103 patients with a median age of 77.3 years, 58.0% male. Complete remission was achieved by 53.4% within 4 weeks and 95.7% by week 52. Peak pruritus scale reduced by 70.0% by week 4 and was completely controlled by week 24. Thirteen patients presented adverse events, most of which were mild. Systemic glucocorticoid use reduced by 82.1% by week 52. Shorter disease duration and exclusive cutaneous involvement predicted better response at 16 weeks. No differences in response rates to dupilumab were observed between drug-associated bullous pemphigoid and idiopathic cases. No significant difference in response rates was observed between patients treated with dupilumab in monotherapy and those receiving dupilumab with concomitant treatments. Dupilumab is effective, rapid, and safe in managing bullous pemphigoid, reducing the need for corticosteroids and other treatments. Early initiation and exclusive skin involvement predict better outcomes.

Factors Influencing the Clinical Course of Bullous Pemphigoid among Geriatric Patients: A Pilot Study

Background and Objectives: Bullous pemphigoid (BP) is the most common autoimmune blistering disease affecting mainly elderly patients. Still, little is known about the pathogenesis of pruritus in BP or the factors that affect the clinical course of the disease. This study aimed to evaluate the factors influencing the clinical course of BP among older patients. Materials and Methods: A retrospective analysis of medical records of 55 patients with BP hospitalized in the dermatology department in 2015–2021 was conducted. The study focused on preliminary diagnosis, medical history, clinical examination (characteristics and location of cutaneous changes), laboratory investigation, and direct and indirect immunofluorescence. Results: Analysis of laboratory results in combination with the clinical course of BP showed that red blood cell count, hemoglobin, and hematocrit values were negatively associated with a risk of erosions and erythema, while MCHC values were positively correlated with a risk of associated pruritus. A correlation was found between neurological diseases and an increased risk of erosions. Conclusions: We have shown that age and neurological conditions, including stroke, affect the clinical course of BP. Further studies on a larger group of patients should be conducted to investigate the different factors affecting the clinical aspect of BP and to understand the relationship between them.

Systemic Implications of Bullous Pemphigoid: Bridging Dermatology and Internal Medicine.

Background: Bullous pemphigoid is an autoimmune bullous disease that frequently affects a large skin surface area, but it can also present in localized areas. It has been hypothesized that bullous pemphigoid affects the systemic functioning of different organs because inflammatory cells and cytokines circulate throughout numerous organs. Results: Recent clinical and experimental studies have revealed an association between bullous pemphigoid and systemic organ disorders. To avoid the emergence of systemic organ diseases, the significance of systemic treatment in cases of severe bullous pemphigoid should be emphasized. Conclusions: Here, we discuss the specific molecular processes underlying typical systemic organ inflammatory diseases associated with bullous pemphigoids.

Utility of Immunofluorescence in Immune-Mediated Vesiculobullous Lesions of Skin

Bullous lesions may be due to various causes, including bullous pemphigoid, pemphigus vulgaris, linear IgA disease, connective tissue disorders, and other rare vesico-bullous skin diseases. Though histopathology can help narrow down possible diagnoses, direct immunofluorescence is required for a definite diagnosis based on positivity patterns of different immunoglobulins. In this study, 47 cases of clinically suspected immune mediated vesiculo-bullous diseases (IMVBD) were confirmed with histopathology. Females were more commonly affected and the age range was from 10 to 93 years. Among these cases, 23 were diagnosed as pemphigus vulgaris, l6 as bullous pemphigoid, 3 each as pemphigus foliaceus and linear IgA disease. DIF, including testing for c1q, was instrumental for the diagnosis of the disease in order for the patient to get appropriate treatment.