Management Of Bullous Pemphigoid Research Articles

Burden of Disease of Bullous Pemphigoid: A Targeted Literature Review.

Bullous pemphigoid (BP) is a rare, chronic, autoimmune, blistering disease characterized by heterogenous lesions including the formation of fluid-filled blisters on frequently flexed areas of the skin and involvement of the mucosa in 10%-25% of patients. BP mainly affects older patients and is associated with increased morbidity and mortality. The aim of the targeted literature review was to assess the clinical, humanistic and economic burden associated with BP. Targeted searches were conducted in Embase and MEDLINE for studies published in English up to November 2022 that reported burden of illness of BP. A total of 42 publications on the clinical (n=37), humanistic (n=6) and economic burden (n=8) of BP were identified. BP was associated with a high mortality rate (27%-72%), and an increased risk of death compared to matched controls. The majority of patients had at least one comorbidity, including hypertension, diabetes mellitus, stroke, and neurological disorders, and showed severe symptoms such as itching and pain. BP was associated with a negative impact on BP- and pruritus-related quality of life and mental health, with 31% and 38% of patients with BP experiencing depression and anxiety in the "Borderline/Abnormal" range, respectively. BP was further associated with high economic burden, reflected by increased healthcare resource utilization, such as longer hospital stays (7.3 days in patients with BP vs. 4.7 days in those without BP), and direct disease-related costs. This review provides a detailed assessment of the evidence base for BP, characterizing key aspects of the disease burden including clinical, humanistic and economic burden. The results emphasize that this rare disease is associated with a substantial burden to patients and have implications for clinical practice in the management of BP.

A Literature Review and Clinical Consensus Guidelines on the Management of Bullous Pemphigoid

Abstract Bullous pemphigoid (BP) is the most common autoimmune blistering disease primarily characterized by tense blisters and occasionally with urticarial plaques, affecting the skin and mucous membranes. These are caused by autoantibodies against BP180 and BP230 which target antigens on the basement membrane zone. The diagnosis relies on the integration of clinical, histopathological, immunopathological, and serological findings. The management depends on the clinical extent and severity. We present in this article a literature review and the clinical consensus guidelines of the Immunodermatology Subspecialty Core Group of the Philippine Dermatological Society in the management of BP.

Pathogenesis and practical guide into the management of Bullous pemphigoid, Pemphigus Vulgaris and Linear IgA disease

Autoimmune blistering diseases are common dermatologic emergencies, with extensive morbidity and mortality. Vesiculobullous diseases are characterized by skin separation at a variety of levels on histopathology, and they have intersecting clinical and histological features which can cause diagnosis uncertainty. For proper treatment decision, an accurate diagnosis is pivotal and can be established by clinical, histopathology and immunofluorescence tools.

Analysis of the clinical characteristics of pembrolizumab-induced bullous pemphigoid.

Pembrolizumab, a programmed cell death protein 1 checkpoint inhibitor, is a novel drug used to treat a variety of advanced malignancies. However, it can also result in many immune-related adverse events, with cutaneous toxicities being the most frequent. Regarding pembrolizumab-induced skin adverse reactions, bullous pemphigoid (BP) has the worst effects on quality of life. Recently, there have been more and more reports of BP incidents resulting from pembrolizumab therapy in patients with cancer. This study aimed to define the clinical characteristics, diagnosis and management of pembrolizumab-induced BP and identify potential differences between classical BP and pembrolizumab-induced BP. Case reports, case series, and case analyses of pembrolizumab-induced BP up to 10 December 2022 were collected for retrospective analysis. Our study included 47 patients (33 males and 14 females) from 40 studies. The median age was 72 years (range 42-86 years). The median time to cutaneous toxicity was 4 months (range 0.7-28 months), and the median time to bullae formation was 7.35 months (range 0.7-32 months). The most common clinical features were tense bullae and blisters (85.11%), pruritus (72.34%), and erythema (63.83%) on the limbs and trunk. In 20 of the 22 cases tested, the serum anti-BP180 autoantibodies were positive. However, in 10 cases (91.90%, 10/11) the circulating autoantibodies of anti-BP230 were negative. 40 patients had skin biopsies and the skin biopsy revealed subepidermal bullae or blister eosinophil infiltration in 75.00% of patients with pembrolizumab-induced BP, 10.00% of patients with lymphocyte infiltration and 20.00% of patients with neutrophil infiltration. There were 20 patients (50%) with eosinophilic infiltration around the superficial dermis vessels, 8 patients (20.00%) with lymphocyte infiltration around the superficial dermis vessels, and 4 patients (10.00%) with neutrophil infiltration around the superficial dermis vessels. Direct immunofluorescence detected linear immunoglobulin G (IgG) IgG and/or complement C3 along the dermo-epidermal junction in 36 patients (94.74%) with BP. IgG positivity was detected by indirect immunofluorescence in 81.82% of patients with BP. All patients were in complete remission (95.65%,44/46) or partial remission (4.35%, 2/46) of BP, whereas 9/46 patients had a relapse or refractory. The majority of patients achieved BP remission after discontinuation of pembrolizumab with a combination of topically and systemically administered steroid treatments, or other medications. The median duration of BP remission was 2 months (range 0.3-15 months). A thorough diagnosis of pembrolizumab-induced BP should be made using clinical signs, biochemical markers, histopathological and immunopathological tests. Pembrolizumab-induced BP had similar clinical characteristics to classic BP. Temporary or permanent discontinuation of pembrolizumab therapy may be required in patients with perbolizumab-induced BP depending on the severity of BP and the response to medication. Pembrolizumab-induced BP may be effectively treated using topical and systemic steroid treatments in combination with other medications (e.g., doxycycline, niacinamide, dapsone, rituximab, intravenous immunoglobulins, dupilumab, cyclophosphamide, methotrexate, mycophenolate mofetil, and infliximab). Clinicians should provide better management to patients with BP receiving pembrolizumab to prevent progression and ensure continuous cancer treatment.

Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life. The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included. Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations. The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice.

A Review of the Immunologic Pathways Involved in Bullous Pemphigoid and Novel Therapeutic Targets.

Bullous pemphigoid (BP) is a rare, chronic antibody-mediated autoimmune blistering disease primarily affecting the elderly, with an age of onset over 60. Current treatment options are limited and involve the use of corticosteroids and immunosuppressants, but their long-term use is associated with significant morbidity and mortality. In Japan, human intravenous immunoglobin is approved for the treatment of corticosteroid-refractory BP. However, no treatment option is approved by the Food and Drug Administration for the management of BP. Therefore, developing effective therapies free of debilitating side effects is imperative. In this review, we summarize the main immunologic pathways involved in the pathogenesis of BP, with an emphasis on the role of eosinophils, immunoglobulins, cytokines such as the interleukin (IL)-4 and IL-5, and complements. We further discuss the latest advances with novel therapeutic targets tested for the management of BP. Ongoing efforts are needed to run well-designed controlled trials and test the efficacy and safety of investigational drugs while providing much-needed access to these medications for refractory patients who will not otherwise be able to afford them as off-label prescriptions.

Bullous pemphigoid: An immune disorder related to aging (Review).

Bullous pemphigoid (BP) is the most frequent subepidermal autoimmune blistering disease and is caused by autoantibodies directed against two principal antigens of the hemidesmosome, BP antigen 180 and BP antigen 230. The pathogenesis of BP is dependent upon the interaction between genetic predisposition, physiological skin alterations due to aging and specific triggers. Several triggers have already been reported to induce this disease and include drugs, thermal or electrical burns, surgical procedures, trauma, UV radiation, radiotherapy, chemicals and infections. Data from the current literature support the hypothesis that alterations of the skin barrier associated with aging increase individual susceptibility to these aforementioned triggers. Consequently, this has been reported to lead to the attack of autoantibodies, demonstrating the predilection of BP for the elderly population. The identification of triggering factors and comorbidities may aid in understanding the pathogenesis of BP and improve clinical management by encouraging their prompt recognition and removal. Moreover, the present review has indicated that current management of BP should be aimed at counteracting the detrimental effects of aging on the skin by restoring skin barrier integrity and maintaining cutaneous homeostasis, for example with systematic applications of topical emollients and photoprotection. This strategy could prove even more beneficial in the elderly, in which frequent comorbidities associated with age often narrow available immunosuppressive treatment options. Furthermore, the safety of treatment regimens may significantly affect outcome and prognosis.

O02: Doxycycline in the management of bullous pemphigoid: real‐world data from a specialist centre

O02: Doxycycline in the management of bullous pemphigoid: real‐world data from a specialist centre

Treatment concerns for bullous pemphigoid in the COVID-19 pandemic era.

Bullous pemphigoid (BP) is the most common autoimmune blistering disease with subepidermal involvement, typically affecting the elderly. It has spontaneous remissions and exacerbations with significant morbidity. A novel coronavirus called severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is responsible for the new universal coronavirus disease 2019 (COVID‐19) pandemic. The pandemic made concerns, especially about immunosuppressive therapy. In this article, we reviewed the management of BP in the COVID‐19 pandemic era. The data about the best management of autoimmune bullous diseases like BP, during the outbreak of COVID‐19, are evolving and updated every day.

Use of Immunosuppressants/Immunomodulators in Autoimmune/Inflammatory Dermatologic Diseases during COVID-19 Pandemic-General Recommendation Based on Available Evidence.

Use of Immunosuppressants/Immunomodulators in Autoimmune/Inflammatory Dermatologic Diseases during COVID-19 Pandemic-General Recommendation Based on Available Evidence.

Japanese guidelines for the management of pemphigoid (including epidermolysis bullosa acquisita).

The pemphigoid group is a category of autoimmune subepidermal blistering diseases in which autoantibodies deposit linearly at the epidermal basement membrane zone (BMZ). The main subtypes of pemphigoid mediated by immunoglobulin G autoantibodies are bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis bullosa acquisita (EBA). To establish the first guidelines approved by the Japanese Dermatological Association for the management of pemphigoid diseases, the Committee for Guidelines for the Management of Pemphigoid Diseases (Including EBA) was founded as part of the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labor and Welfare Research Project on Overcoming Intractable Diseases. These guidelines aim to provide current information for the management of BP, MMP and EBA in Japan. Based on evidence, the guidelines summarize the clinical and immunological manifestations, pathophysiologies, diagnostic criteria, disease severity determination criteria, treatment algorithms and treatment recommendations. Because of the rarity of these diseases, there are few clinical studies with a high degree of evidence, so several parts of these guidelines were established based on the opinions of the Committee. To further optimize these guidelines, periodic revision in line with the new evidence is necessary.

National audit on the management of bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune, subepidermal, blistering condition that typically affects elderly people. To undertake a national clinical audit based on standards derived from the British Association of Dermatologists (BAD) clinical guidelines on the management of BP. In 2018, BAD members were invited to submit data for five consecutive adults with BP per centre, who had been under hospital supervision for at least 12months, in a national audit over an 11-week period. In total, 123 responders from 120 hospitals provided data for 524 cases. Diagnosis was made either clinically (10.7%; 56 of 524) or through histology with direct immunofluorescence (41.6%; 218 of 524), indirect immunofluorescence (10.3%; 54 of 524) or both (37.4%; 196 of 524). Most patients had very mild baseline disease (63.9%; 225 of 352) with 21.9% (77 of 352) considered mild, 9.8% (31 of 352) moderate and 5.4% (19 of 352) severe. Documentation of diabetes, glycated haemoglobin (HbA1c), blood pressure and hypertension was available for 54.1% (283 of 523), 51% (267 of 524), 44.2% (231 of 522) and 61.5% (321 of 522) of cases, respectively. Oral corticosteroids were commenced in 85.5% (448 of 524) of patients, with 38.4% (172 of 448) of these having documented risk of osteoporosis; data regarding prescription of bone-protection therapies were available for 99.7% (447 of 448) of cases, with 75.6% (338 of 447) of these having a bone-protection prescription. Patient satisfaction was documented in 59.3% (310 of 523) of cases. Systemic treatment was commenced in 95.9% (502 of 524) of cases during the 12-month assessment period, with baseline blood test and follow-up data available for 96.6% (485 of 502) and 95.6% (480 of 502), respectively. Documentation of baseline blood tests was available for 87.4% (424 of 485) of cases, with follow-up tests recorded in 69.8% (335 of 480). Overall, compliance with elements of documentation was moderate or low, whereas standards pertaining to direct care were high.

Bullous dermatoses secondary to anti-PD-L1 agents: a case report and review of the literature

Immune checkpoint inhibitors are used to treat numerous malignancies but may be associated with severe adverse events. Bullous dermatoses, chiefly bullous pemphigoid (BP), are potentially progressive adverse events that cause blistering skin lesions and may involve a significant body surface area. Herein, we report an 87-year-old man with urothelial cell carcinoma undergoing atezolizumab treatment who presented with an acute-onset blistering eruption. Biopsy revealed a subepidermal bulla, direct immunofluorescence revealed linear IgG and C3 deposits at the dermal-epidermal junction, and serum studies revealed elevated levels of antibodies to BP180 and BP230. Anti-PD-L1-induced BP was diagnosed, immunotherapy was withheld, and he was treated with oral doxycycline with niacinamide and clobetasol ointment. He restarted atezolizumab and has successfully received four cycles (every 3 weeks) while continuing this BP treatment regimen. A literature review revealed eight other cases of anti-PD-L1-induced bullous disorders. The incidence of bullous dermatoses with anti-PD-1/anti-PD-L1 agents combined is 1%, whereas the reported incidence for anti-PD-L1 agents alone ranges from 1.3-5%, raising concerns for a higher overall risk. In addition to our case, only one other case reported successful resumption of immunotherapy. Early control and management of immunotherapy-induced BP may reduce complications and prevent treatment discontinuation.

Management of bullous pemphigoid: the European Dermatology Forum consensus in collaboration with the European Academy of Dermatology and Venereology.

Bullous pemphigoid is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or generalized bullous lesions. In up to 20% of affected patients, bullae may be completely absent, and only excoriations, prurigo-like lesions, eczematous lesions, urticated lesions and/or infiltrated plaques are observed. The disease is significantly associated with neurological disorders. The morbidity of bullous pemphigoid and its impact on quality of life are significant. So far, a limited number of national treatment guidelines have been proposed, but no common European consensus has emerged. Our consensus for the treatment of bullous pemphigoid has been developed under the guidance of the European Dermatology Forum in collaboration with the European Academy of Dermatology and Venereology. It summarizes evidence-based and expert-based recommendations.

Bullous Pemphigoid: Clinical Practice Guidelines

Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease in which autoantibodies are directed against components of the basement membrane. Most of these antibodies belong to the immunoglobulin G class and bind principally to 2 hemidesmosomal proteins: the 180-kD antigen (BP180) and the 230-kD antigen (BP230). It is the most common blistering disease in the adult population in developed countries, with an estimated incidence in Spain of 0.2 to 3 cases per 100,000 inhabitants per year. The disease primarily affects older people, although it can also occur in young people and even in children. In recent years, advances in clinical practice have led to a better understanding and improved management of this disorder. These advances include new diagnostic techniques, such as enzyme-linked immunosorbent assay for BP180 and new drugs for the treatment of BP, with diverse therapeutic targets. There is, however, still no international consensus on guidelines for the management of BP. This article is an updated review of the scientific literature on the treatment of BP. It focuses primarily on evidence-based recommendations and is written from a practical standpoint based on experience in the routine management of this disease.

Penfigoide ampolloso: guía de manejo práctico

Bullous pemphigoid (BP) is an autoimmune subepidermal bullous disease in which autoantibodies are directed against components of the basement membrane. Most of these antibodies belong to the immunoglobulin G class and bind principally to 2 hemidesmosomal proteins: the 180-kD antigen (BP180) and the 230-kD antigen (BP230). It is the most common blistering disease in the adult population in developed countries, with an estimated incidence in Spain of 0.2 to 3 cases per 100,000 inhabitants per year. The disease primarily affects older people, although it can also occur in young people and even in children. In recent years, advances in clinical practice have led to a better understanding and improved management of this disorder. These advances include new diagnostic techniques, such as enzyme-linked immunosorbent assay for BP180 and new drugs for the treatment of BP, with diverse therapeutic targets. There is, however, still no international consensus on guidelines for the management of BP. This article is an updated review of the scientific literature on the treatment of BP. It focuses primarily on evidence-based recommendations and is written from a practical standpoint based on experience in the routine management of this disease.

Evidence-Based Management of Bullous Pemphigoid

Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease typically affecting the elderly. Although different therapeutic regimens have been proposed, a review of the evidence is needed to aid clinicians in their decision making and management. Systemic therapies such as corticosteroids and adjuvants are effective in BP but are plagued with adverse effects, and potent topical steroids are an alternative treatment. This article reviews the evidence supporting different therapeutic options in the management of BP.

Management of Bullous Pemphigoid with Topical Steroids in the Clinical Practice of a Single Center: Outcome at 6 and 12 Months

Background: The efficacy of topical steroids in bullous pemphigoid (BP) was assessed by prospective therapeutic trials. Systemic corticosteroids and immunosuppressant agents are indicated in situations of failure or relapses. Objectives: To report our experience in the management of BP outside therapeutic trials focusing on the outcome of the patients at 6 and 12 months, compliance and follow-up difficulties. Methods: Monocenter retrospective study with collection of clinical, therapeutic and follow-up data after 6 and 12 months. Results: Ninety-six patients, mean age 84 years, 65 females, 54% had neurological impairment. The initial dose of clobetasol propionate was 30 g/day, followed by a progressive decrease. In the first 6 months, 14% were lost to follow-up and 17.7% died; 62% were controlled with topical steroids alone, and 25% had adjunctive systemic treatment. Difficulties of compliance were mentioned in 34.4%, without significant difference between controlled and noncontrolled patients. After 12 months, 23% were lost to follow-up and 27.1% died. The mean duration of the treatment was 11.7 ± 8.4 months. After the stop, 18.9% of patients relapsed within 3 months. Conclusion: We emphasize the frequent recourse to systemic treatments in the first few months, the difficulties of compliance and of follow-up in our day-to-day experience.

Blistering skin disorders: an evidence-based update. Conference report

Evidence-based update meetings are held annually by the Centre of Evidence Based Dermatology, University of Nottingham. Past topics have included important themes such as eczema, psoriasis, hair disorders and skin cancers. This year, the seventh Evidence Based Update meeting focused on blistering disorders and took place in Loughborough University on 5 June 2008. The latest data on incidence and mortality, therapeutic trials and management of bullous pemphigoid, pemphigus and epidermolysis bullosa (EB) were presented by an international panel of renowned speakers. The highlights of the meeting included an informal atmosphere, an international perspective, a practical question and answer session and hearing first-hand a patient and carer's perspective of living with EB.

Prediction of Survival for Patients With Bullous Pemphigoid

To identify the prognostic factors of bullous pemphigoid (BP). Prospective study of patients with BP included in a randomized, controlled trial. Twenty dermatology departments in France. Patients One hundred seventy patients with BP initially treated with a 40-g/d dosage of clobetasol propionate cream (testing sample) and 171 patients initially treated with oral corticosteroids at a dosage of 0.5 or of 1.0 mg/kg per day, depending on the extent of BP (validation samples). The end point was overall survival during the first year after BP diagnosis. From the testing sample, associations of clinical and biological variables with overall survival were assessed using univariate and multivariate analyses. Selected predictors were included in a prognostic model. To verify that these predictors were not dependent on the treatment used, the model was then validated independently on the 2 series of BP patients treated with oral corticosteroids. Median age of the BP patients included in the testing sample was 83 years. The 1-year Kaplan-Meier survival rate was 74%. From univariate analysis, the main deleterious predictors were demographic factors (ie, older age and female sex), associated medical conditions (ie, cardiac insufficiency, history of stroke, and dementia), and low Karnofsky score, which is a measure of the patient's general condition. No factors directly related to BP, in particular extent of cutaneous lesions, were shown to be related to the patients' prognosis. From multivariate analysis, only older age (P = .02) and low Karnofsky score (P<.001) appeared independently predictive of death. From the Cox model including these 2 predictors, the predicted 1-year survival rates were 90% (95% confidence interval [CI], 85%-96%) for patients 83 years or younger with Karnofsky score greater than 40, 79% (95% CI, 69%-90%) for patients older than 83 years with Karnofsky score greater than 40, 65% (95% CI, 50%-86%) for patients 83 years or younger with Karnofsky score of 40 or less, and 38% (95% CI, 26%-57%) for patients older than 83 years with Karnofsky score of 40 or less. Kaplan-Meier survival distributions of patients from the validation samples appeared clearly separated according to these 4 categories and were in close agreement with corresponding predicted 1-year survival rates obtained from the testing sample. The prognosis of patients with BP is influenced by age and Karnofsky score. These predictors are easy to use and should facilitate the management of BP.