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Frontiers in Immunology 2022Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious...
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious adverse events. Rituximab, omalizumab, and dupilumab should be explored as alternative treatment options to improve outcomes.
OBJECTIVE
To systematically review the rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid.
METHODS
A PubMed, Embase, Web of Science, and Cochrane library search were conducted on March 10, 2022. A total of 75 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.
RESULTS
Use of rituximab (n=122), omalizumab (n=53) and dupilumab (n=36) were reported in 211 patients with BP. Rituximab led to complete remission in 70.5% (n=86/122) and partial remission in 23.8% (n=29/122) of patients within 5.7 months, with a recurrence rate of 20.5% (n=25/122). 9.0% (n=11/122) of patients died and infection (6.6%, n=8/122) was the most common adverse event. Omalizumab led to complete remission in 67.9% (n=36/53) and partial remission in 20.8% (n=11/53) of patients within 6.6 months, with a recurrence rate of 5.7% (n=3/53). 1.9% (n=1/53) of patients died and thrombocytopenia (1.9%, n=1/53) was observed as the most common adverse event. Dupilumab led to complete remission in 66.7% (n=24/36) and partial remission in 19.4% (n=7/36) of patients within 4.5 months of treatment without any reported adverse events, with a recurrence rate of 5.6% (n=2/36).
CONCLUSIONS
Rituximab, omalizumab, and dupilumab have similar clinical benefits for BP patients. However, rituximab resulted in higher recurrence rates, adverse events, and mortality rates.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022316454.
Topics: Antibodies, Monoclonal, Humanized; Humans; Omalizumab; Pemphigoid, Bullous; Rituximab; Treatment Outcome
PubMed: 35769474
DOI: 10.3389/fimmu.2022.928621 -
Acta Dermato-venereologica Aug 2020Bullous pemphigoid is an autoimmune subepithelial disease characterised by pruritus followed by urticarial plaques and finally bullae on the skin and mucosa....
Bullous pemphigoid is an autoimmune subepithelial disease characterised by pruritus followed by urticarial plaques and finally bullae on the skin and mucosa. Drug-associated bullous pemphigoid (DABP) is a term used to describe instances of bullous pemphigoid demonstrating clinical, histological, or immunopathological features identical or similar to those of the idiopathic form of bullous pemphigoid, associated with the systemic ingestion, or topical application of particular drugs. In this study, we conducted a comprehensive search of the literature according to PRISMA guidelines and a total of 170 publications were included in the final qualitative analysis. In conclusion, 89 drugs were implicated in DABP. The strongest evidence for DABP is seen with gliptins, PD-1/PD-L1 inhibitors, loop diuretics, penicillin and derivatives. An appreciation of the medications associated with bullous pemphigoid enables clinicians to identify potential cases of DABP earlier and cease the offending medication.
Topics: Blister; Humans; Pemphigoid, Bullous; Pharmaceutical Preparations; Pruritus; Skin
PubMed: 32176310
DOI: 10.2340/00015555-3457 -
Frontiers in Immunology 2019During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have...
During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have been published on biologicals, which complicates the decision making process on the use of the most appropriate biologic for a given immune-mediated disease. This systematic review is the first of a series of articles assessing the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. To evaluate rituximab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment, or other biologics. The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 26 July 2018 concentrating on immune-mediated disorders. The literature search identified 19,665 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 105 articles were finally included in a narrative synthesis. Rituximab is both safe and effective for the treatment of acquired angioedema with C1-inhibitor deficiency, ANCA-associated vasculitis, autoimmune hemolytic anemia, Behçet's disease, bullous pemphigoid, Castleman's disease, cryoglobulinemia, Goodpasture's disease, IgG4-related disease, immune thrombocytopenia, juvenile idiopathic arthritis, relapsing-remitting multiple sclerosis, myasthenia gravis, nephrotic syndrome, neuromyelitis optica, pemphigus, rheumatoid arthritis, spondyloarthropathy, and systemic sclerosis. Conversely, rituximab failed to show an effect for antiphospholipid syndrome, autoimmune hepatitis, IgA nephropathy, inflammatory myositis, primary-progressive multiple sclerosis, systemic lupus erythematosus, and ulcerative colitis. Finally, mixed results were reported for membranous nephropathy, primary Sjögren's syndrome and Graves' disease, therefore warranting better quality trials with larger patient numbers.
Topics: Animals; Antigens, CD20; B-Lymphocytes; Disease Progression; Humans; Immune System Diseases; Immunotherapy; Lymphocyte Depletion; Rituximab; Treatment Outcome
PubMed: 31555262
DOI: 10.3389/fimmu.2019.01990 -
Biomolecules Mar 2023Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks the signaling of interleukin (IL)-4 and -13. Several other chronic skin conditions... (Review)
Review
Dupilumab was first approved for the treatment of atopic dermatitis (AD) and blocks the signaling of interleukin (IL)-4 and -13. Several other chronic skin conditions share mechanistic overlaps with AD in their pathophysiology, i.e., are linked to type 2 inflammation. Most recently, dupilumab was approved by the U.S. Food and Drug Administration for prurigo nodularis (PN). Given its relatively good safety profile, effective off-label use of dupilumab has been reported for a multitude of dermatologic diseases and several clinical trials for dermatologic skin conditions are currently ongoing. We conducted a systematic review of applications of dupilumab in dermatology other than AD and PN by searching the databases PubMed/Medline, Scopus, Web of Science and Cochrane Library as well as the clinical trial registry ClinicalTrials.gov. We found several reports for effective treatment of bullous autoimmune diseases, eczema, prurigo, alopecia areata, chronic spontaneous urticaria, Netherton syndrome and a variety of other chronic inflammatory skin diseases.
Topics: Humans; Prurigo; Antibodies, Monoclonal, Humanized; Dermatitis, Atopic; Skin
PubMed: 37189381
DOI: 10.3390/biom13040634 -
Cureus Jun 2023Bullous pemphigoid (BP) is an autoimmune blistering disease that mainly affects the elderly. The human leukocyte antigen (HLA) system is believed to be one of the... (Review)
Review
Bullous pemphigoid (BP) is an autoimmune blistering disease that mainly affects the elderly. The human leukocyte antigen (HLA) system is believed to be one of the genetic factors involved in the development of BP. The connection between major histocompatibility complex class II, specifically HLA-DQA1, and BP remains inconclusive. The objective of this review is to find potential associations between BP and HLA-DQA1 alleles, identify the HLA-DQA1 alleles associated with an increased or decreased risk of developing BP, and highlight literature gaps for future research. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to conduct a literature review. Databases used included PubMed/MEDLINE, Google Scholar, Embase, and Cochrane Library. Only studies written in English and conducted after 2000 that investigated the association between HLA-DQA1 and BP in human subjects were included. Odds ratios were calculated from the data provided in the studies, and a meta-analysis was conducted using Review Manager (The Cochrane Collaboration, London, United Kingdom) and MetaXL (EpiGear International Pty Ltd., Queensland, Australia) software. The systematic review found five eligible studies, and all were included in the meta-analysis. Results show an increased odds for BP in the HLA-DQA1*05:05 loci (odds ratio (OR) = 2.25; 95% confidence interval (CI) = 1.80, 2.80) and decreased odds for BP in the HLA-DQA1*02:01 loci (OR = 0.50; 95% CI = 0.36, 0.70). Further research is needed to confirm these findings and explore the potential clinical implications for personalized medicine approaches in BP patients.
PubMed: 37416040
DOI: 10.7759/cureus.39923 -
PloS One 2022To systematically evaluate the prognostic factors for mortality in bullous pemphigoid. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the prognostic factors for mortality in bullous pemphigoid.
METHODS
PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc and Wanfang Database were searched to collect literature on the prognostic factors for mortality in bullous pemphigoid. The quality of studies was assessed by Newcastle-Ottawa Quality Assessment Scale. Two researchers extracted relevant data and scored study quality independently. The hazard ratio (HR) was calculated using the random effects model. Study heterogeneity was assessed using both Cochran's Q test and I2 statistics. The causes of heterogeneity were assessed by subgroup analysis and/ or sensitivity analysis when heterogeneity was significant. When ten or more studies were included as outcome indicators, publication bias was evaluated by funnel plot and Egger's test.
RESULTS
Out of a total of 1,546 articles retrieved, 15 studies involving 2,435 patients were included. The meta-analysis showed that the mortality of patients with bullous pemphigoid increased with positive bullous pemphigoid 180 antibody (HR = 1.85, 95%CI: 1.25~2.75, P = 0.002); concomitant dementia (HR = 2.26, 95%CI: 1.43~3.59, P<0.001); stroke (HR = 2.09, 95% CI: 1.23-3.55, P = 0.007); heart disease (HR = 1.96, 95% CI: 1.41-2.73, P<0.001) and diabetes mellitus (HR = 2.39, 95% CI: 1.55-3.69, P<0.001). Sex, positive indirect immunofluorescence and hypertension were not associated with prognosis.
CONCLUSION
Positive bullous pemphigoid 180 antibody, dementia, stroke, heart disease and diabetes mellitus were the prognostic factors for mortality in bullous pemphigoid.
Topics: Dementia; Heart Diseases; Humans; Pemphigoid, Bullous; Prognosis; Stroke
PubMed: 35427358
DOI: 10.1371/journal.pone.0264705 -
Medicina (Kaunas, Lithuania) Apr 2023Bullous pemphigoid (BP), the most common subepidermal autoimmune skin blistering disease (AIBD) has an estimated annual incidence of 2.4 to 42.8 new cases per million... (Review)
Review
Bullous pemphigoid (BP), the most common subepidermal autoimmune skin blistering disease (AIBD) has an estimated annual incidence of 2.4 to 42.8 new cases per million in different populations, designating it an orphan disease. Characterized by disruption of the skin barrier combined with therapy-induced immunosuppression, BP could pose a risk for skin and soft tissue infections (SSTI). Necrotizing fasciitis (NF) is a rare necrotizing skin and soft tissue infection, with a prevalence of 0.40 cases per 100,000 to 15.5 cases per 100,000 population, often associated with immunosuppression. Low incidences of NF and BP classify them both as rare diseases, possibly contributing to the false inability of making a significant correlation between the two. Here, we present a systematic review of the existing literature related to the ways these two diseases correlate. This systematic review was conducted according to the PRISMA guidelines. The literature review was conducted using PubMed (MEDLINE), Google Scholar, and SCOPUS databases. The primary outcome was prevalence of NF in BP patients, while the secondary outcome was prevalence and mortality of SSTI in BP patients. Due to the scarcity of data, case reports were also included. A total of 13 studies were included, six case reports of BP complicated by NF with six retrospective studies and one randomized multicenter trial of SSTIs in BP patients. Loss of skin integrity, immunosuppressive therapy, and comorbidities commonly related to BP patients are risk factors for necrotizing fasciitis. Evidence of their significant correlation is emerging, and further studies are deemed necessary for the development of BP-specific diagnostic and treatment protocols.
Topics: Humans; Fasciitis, Necrotizing; Pemphigoid, Bullous; Retrospective Studies; Skin; Soft Tissue Infections; Risk Factors; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 37109703
DOI: 10.3390/medicina59040745 -
JAMA Dermatology Aug 2020The association between the use of medications and the development of bullous pemphigoid (BP) is unclear. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The association between the use of medications and the development of bullous pemphigoid (BP) is unclear.
OBJECTIVE
To assess the associations between previous exposure to certain medications and BP.
DATA SOURCES
For this systematic review and meta-analysis, PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched for relevant studies from inception to February 20, 2020.
STUDY SELECTION
Case-control or cohort studies and randomized clinical trials that examined the odds or risk of BP in patients with previous medication use were included. No geographic or language limitations were imposed.
DATA EXTRACTION AND SYNTHESIS
The Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included observational studies; Cochrane Collaboration's tool was used for randomized clinical trials. Aggregate data were used to conduct a random-effects model meta-analysis if the included studies were sufficiently homogenous. Subgroup analyses were performed for use of various medications of the same category.
MAIN OUTCOMES AND MEASURES
Odds ratio (OR), hazard ratio, and risk ratio of bullous pemphigoid in association with medication use.
RESULTS
This meta-analysis included 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with a total of 285 884 participants. The meta-analysis of case-control studies showed a significant association of BP with previous use of aldosterone antagonists (pooled OR, 1.75; 95% CI, 1.28-2.40), dipeptidyl peptidase 4 inhibitors (pooled OR, 1.92; 95% CI, 1.55-2.38), anticholinergics (pooled OR, 3.12; 95% CI, 1.54-6.33), and dopaminergic medications (pooled OR, 2.03; 95% CI, 1.34-3.05). One cohort study found an increased risk of BP among patients receiving dipeptidyl peptidase 4 inhibitors (hazard ratio, 2.38; 95% CI, 1.16-4.88; P = .02). One trial found a higher occurrence of BP in patients with diabetes receiving linagliptin (0.2% in diabetes group vs 0% in the placebo group).
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis suggest that aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications are associated with BP. These medications should be judiciously prescribed, particularly in high-risk patients who are elderly and have disabling neurologic disorders.
Topics: Antihypertensive Agents; Cholinergic Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Diuretics; Dopamine Agents; Humans; Hypoglycemic Agents; Mineralocorticoid Receptor Antagonists; Odds Ratio; Pemphigoid, Bullous; Psychotropic Drugs; Risk Factors
PubMed: 32584924
DOI: 10.1001/jamadermatol.2020.1587 -
Indian Journal of Dermatology,... 2018Increased risk of venous thromboembolism is observed in several autoimmune inflammatory disorders. However, data on bullous pemphigoid, one of the most common autoimmune... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Increased risk of venous thromboembolism is observed in several autoimmune inflammatory disorders. However, data on bullous pemphigoid, one of the most common autoimmune blistering disorders, is limited. This systematic review and meta-analysis was conducted to summarize all available evidence.
METHODS
Two investigators independently searched published studies indexed in MEDLINE and EMBASE from inception to July 2016 using the terms for bullous pemphigoid and venous thromboembolism. The inclusion criteria were as follows: (1) cohort or case-control study evaluated the association between bullous pemphigoid and risk of venous thromboembolism, (2) effect estimates were provided as odds ratios, relative risk, hazard ratio, standardized incidence ratio with 95% confidence intervals, and (3) subjects without bullous pemphigoid were used as comparators for cohort studies, while subjects without venous thromboembolism were used as comparators for case-control studies. Point estimates and 95% confidence intervals were extracted from each study and were pooled together using the random-effect model, generic inverse variance method of DerSimonian and Laird. Cochran's Q test and the I2 statistic were used to evaluate the statistical heterogeneity.
RESULTS
Two retrospective cohort studies, one prospective cohort study, and one case-control study met the eligibility criteria and were included in the meta-analysis. The pooled odds ratio was 2.69 (95% confidence interval, 1.79-4.05). Statistical heterogeneity was high with I2 of 77%.
LIMITATION
Limited accuracy of diagnosis of primary studies and high between-study heterogeneity.
CONCLUSION
This meta-analysis demonstrated that patients with bullous pemphigoid have a significantly increased risk of venous thromboembolism.
Topics: Case-Control Studies; Humans; Pemphigoid, Bullous; Prospective Studies; Retrospective Studies; Risk Factors; Venous Thromboembolism
PubMed: 29185440
DOI: 10.4103/ijdvl.IJDVL_827_16 -
Frontiers in Immunology 2023Bullous pemphigoid is the most common autoimmune blistering disease in industrialized countries and particularly affects the elderly. In this patient population,...
Bullous pemphigoid is the most common autoimmune blistering disease in industrialized countries and particularly affects the elderly. In this patient population, comorbid diseases are frequent and may complicate management and treatment of bullous pemphigoid. A better understanding why distinct diseases are more frequent in bullous pemphigoid patients may lead to new pathophysiological insights and - as a consequence - result in better patient care. The association of bullous pemphigoid with neurological and psychiatric diseases is well known and confirmed by several case-control studies. Association with further diseases such as malignancy and metabolic diseases are still discussed controversially. In recent years new relationships between bullous pemphigoid and autoimmune as well as inflammatory skin diseases have been reported. This review provides a systematic overview on studies addressing comorbidity in bullous pemphigoid patients. Increasing the awareness of both, common and rare comorbid diseases, may enable clinicians to optimize patient support and individualized treatment of bullous pemphigoid.
Topics: Humans; Aged; Pemphigoid, Bullous; Autoimmune Diseases; Blister; Comorbidity; Case-Control Studies
PubMed: 37457698
DOI: 10.3389/fimmu.2023.1196999