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The Cochrane Database of Systematic... Aug 2023Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first... (Review)
Review
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Oral steroids are the standard treatment. We have updated this review, which was first published in 2002, because several new treatments have since been tried.
OBJECTIVES
To assess the effects of treatments for bullous pemphigoid.
SEARCH METHODS
We updated searches of the following databases to November 2021: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched five trial databases to January 2022, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
RCTs of treatments for immunofluorescence-confirmed bullous pemphigoid.
DATA COLLECTION AND ANALYSIS
At least two review authors, working independently, evaluated the studies against the review's inclusion criteria and extracted data from included studies. Using GRADE methodology, we assessed the certainty of the evidence for each outcome in each comparison. Our primary outcomes were healing of skin lesions and mortality.
MAIN RESULTS
We identified 14 RCTs (1442 participants). The main treatment modalities assessed were oral steroids, topical steroids, and the oral anti-inflammatory antibiotic doxycycline. Most studies reported mortality but adverse events and quality of life were not well reported. We decided to look at the primary outcomes 'disease control' and 'mortality'. Almost all studies investigated different comparisons; two studies were placebo-controlled. The results are therefore based on a single study for each comparison except azathioprine. Most studies involved only small numbers of participants. We assessed the risk of bias for all key outcomes as having 'some concerns' or high risk, due to missing data, inappropriate analysis, or insufficient information. Clobetasol propionate cream versus oral prednisone Compared to oral prednisone, clobetasol propionate cream applied over the whole body probably increases skin healing at day 21 (risk ratio (RR 1.08, 95% confidence interval (CI) 1.03 to 1.13; 1 study, 341 participants; moderate-certainty evidence). Skin healing at 21 days was seen in 99.8% of participants assigned to clobetasol and 92.4% of participants assigned to prednisone. Clobetasol propionate cream applied over the whole body compared to oral prednisone may reduce mortality at one year (RR 0.73, 95% CI 0.53 to 1.01; 1 study, 341 participants; low-certainty evidence). Death occurred in 26.5% (45/170) of participants assigned to clobetasol and 36.3% (62/171) of participants assigned to oral prednisone. This study did not measure quality of life. Clobetasol propionate cream may reduce risk of severe complications by day 21 compared with oral prednisone (RR 0.65, 95% CI 0.50 to 0.86; 1 study, 341 participants; low-certainty evidence). Mild clobetasol propionate cream regimen (10 to 30 g/day) versus standard clobetasol propionate cream regimen (40 g/day) A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen probably does not change skin healing at day 21 (RR 1.00, 95% CI 0.97 to 1.03; 1 study, 312 participants; moderate-certainty evidence). Both groups showed complete healing of lesions at day 21 in 98% participants. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change mortality at one year (RR 1.00, 95% CI 0.75 to 1.32; 1 study, 312 participants; low-certainty evidence), which occurred in 118/312 (37.9%) participants. This study did not measure quality of life. A mild regimen of topical clobetasol propionate applied over the whole body compared to the standard regimen may not change adverse events at one year (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 309 participants; low-certainty evidence). Doxycycline versus prednisolone Compared to prednisolone (0.5 mg/kg/day), doxycycline (200 mg/day) induces less skin healing at six weeks (RR 0.81, 95% CI 0.72 to 0.92; 1 study, 213 participants; high-certainty evidence). Complete skin healing was reported in 73.8% of participants assigned to doxycycline and 91.1% assigned to prednisolone. Doxycycline compared to prednisolone probably decreases mortality at one year (RR 0.25, 95% CI 0.07 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) = 14; 1 study, 234 participants; moderate-certainty evidence). Mortality occurred in 2.4% (3/132) of participants with doxycycline and 9.7% (11/121) with prednisolone. Compared to prednisolone, doxycycline improved quality of life at one year (mean difference 1.8 points lower, which is more favourable on the Dermatology Life Quality Index, 95% CI 1.02 to 2.58 lower; 1 study, 234 participants; high-certainty evidence). Doxycycline compared to prednisolone probably reduces severe or life-threatening treatment-related adverse events at one year (RR 0.59, 95% CI 0.35 to 0.99; 1 study, 234 participants; moderate-certainty evidence). Prednisone plus azathioprine versus prednisone It is unclear whether azathioprine plus prednisone compared to prednisone alone affects skin healing or mortality because there was only very low-certainty evidence from two trials (98 participants). These studies did not measure quality of life. Adverse events were reported in a total of 20/48 (42%) participants assigned to azathioprine plus prednisone and 15/44 (34%) participants assigned to prednisone. Nicotinamide plus tetracycline versus prednisone It is unclear whether nicotinamide plus tetracycline compared to prednisone affects skin healing or mortality because there was only very low-certainty evidence from one trial (18 participants). This study did not measure quality of life. Fewer adverse events were reported in the nicotinamide group. Methylprednisolone plus azathioprine versus methylprednisolone plus dapsone It is unclear whether azathioprine plus methylprednisolone compared to dapsone plus methylprednisolone affects skin healing or mortality because there was only very low-certainty evidence from one trial (54 participants). This study did not measure quality of life. A total of 18 adverse events were reported in the azathioprine group and 13 in the dapsone group.
AUTHORS' CONCLUSIONS
Clobetasol propionate cream applied over the whole body is probably similarly effective as, and may cause less mortality than, oral prednisone for treating bullous pemphigoid. Lower-dose clobetasol propionate cream applied over the whole body is probably similarly effective as standard-dose clobetasol propionate cream and has similar mortality. Doxycycline is less effective but causes less mortality than prednisolone for treating bullous pemphigoid. Other treatments need further investigation.
Topics: Humans; Azathioprine; Prednisone; Clobetasol; Pemphigoid, Bullous; Doxycycline; Methylprednisolone; Dapsone; Niacinamide
PubMed: 37572360
DOI: 10.1002/14651858.CD002292.pub4 -
Frontiers in Immunology 2023Pemphigus foliaceus (PF) differs from pemphigus vulgaris (PV) in that it affects only the skin and mucous membranes are not involved. Pemphigus is commonly treated with...
BACKGROUND
Pemphigus foliaceus (PF) differs from pemphigus vulgaris (PV) in that it affects only the skin and mucous membranes are not involved. Pemphigus is commonly treated with systemic corticosteroids and immunosuppressive agents (ISAs). More recently, biologics have been used. The current literature on biologic therapy often combines treatment of PF with PV, hence it is often difficult for clinicians to isolate the treatment of PF from PV. The purpose of this review was to provide information regarding the use of current biological therapy, specifically in PF.
MATERIALS AND METHODS
A search of PubMed, Embase, and other databases was conducted using keywords pemphigus foliaceus (PF), rituximab (RTX), intravenous immunoglobulin (IVIg), and biologics. Forty-one studies were included in this review, which produced 105 patients with PF, treated with RTX, IVIg, or a combination of both. Eighty-five patients were treated with RTX, eight patients with IVIg, and 12 received both RTX and IVIg.
RESULTS
Most patients in this review had PF that was nonresponsive to conventional immunosuppressive therapies (CIST), and had significant side effects from their use. RTX treatment resulted in complete remission (CR) in 63.2%, a relapse rate of 39.5%, an infection rate of 19.7%, and a mortality rate of 3.9%. Relapse was greater in the lymphoma (LP) protocol than the rheumatoid arthritis (RA) protocol (p<0.0001). IVIg led to CR in 62.5% of patients, with no relapses or infections. Patients receiving both biologics experienced better outcomes when RTX was first administered, then followed by IVIg. Follow-up durations for patients receiving RTX, IVIg, and both were 22.1, 24.8, and 35.7 months, respectively.
DISCUSSION
In pemphigus foliaceus patients nonresponsive to conventional immunosuppressive therapy or in those with significant side effects from CIST, RTX and IVIg appear to be useful agents. Profile of clinical response, as well as relapse, infection, and mortality rates in PF patients treated with RTX were similar to those observed in PV patients. The data suggests that protocols specific for PF may produce better outcomes, less adverse effects, and improved quality of life.
Topics: Humans; Pemphigus; Immunoglobulins, Intravenous; Quality of Life; Immunosuppressive Agents; Rituximab; Recurrence; Biological Products
PubMed: 37901249
DOI: 10.3389/fimmu.2023.1267668 -
International Journal of Dermatology Jun 2024Pemphigus is a group of autoimmune mucocutaneous bullous disorders characterized by acantholysis resulting from autoantibodies targeting epithelial cell surface... (Review)
Review
Pemphigus is a group of autoimmune mucocutaneous bullous disorders characterized by acantholysis resulting from autoantibodies targeting epithelial cell surface antigens. Studies reflect the presence of nail manifestations in some patients and suggest a potential correlation with clinical severity. This study examines the overall prevalence and characterizes the diverse manifestations of nail changes in pemphigus. We searched Cochrane, MEDLINE, EMBASE, and LILACS from 1990 to June 26, 2023 for studies reporting different nail changes in pemphigus patients. Data were collected and pooled to obtain proportions of the prevalence of nail changes in patients with pemphigus and subgroup analysis for pemphigus foliaceous and pemphigus vulgaris. The risk of bias was assessed with the Joanna Briggs Institute Checklist. Of 321 studies screened, 14 studies with 1,208 patients were included. Paronychia (n = 185) and Beau's lines (n = 104) were the most common nail changes identified. The pooled prevalence of nail disease in pemphigus patients was 0.389 (number of studies; [95% CI]: n = 9; [0.160-0.680], with high heterogeneity between studies (I = 95.0%, P < 0.001). Subgroup analysis revealed the highest prevalence in pemphigus foliaceous at 0.342 (n = 3; [0.109-0.688]) and pemphigus vulgaris at 0.396 (n = 5; [0.114-0.769]). Nail changes exhibited varied temporal relationships with disease onset and flares, preceding, concurrent, or following these events. Correlation with disease severity was noted, although discrepancies between studies were reported. Nail changes in pemphigus, particularly pemphigus vulgaris and pemphigus foliaceous, may be underrecognized. Observations regarding temporal associations and potential correlations with disease severity highlight the diagnostic and prognostic implications of nail changes in pemphigus. The limitations of this study include study heterogeneity and possible bias. Further research to establish the correlation of the presence and severity of nail changes on the overall disease course would be helpful.
PubMed: 38887088
DOI: 10.1111/ijd.17257 -
Cureus Sep 2023Artificial intelligence (AI) has been cited as being helpful in the diagnosis of diseases, the prediction of prognoses, and the development of patient-specific... (Review)
Review
Artificial intelligence (AI) has been cited as being helpful in the diagnosis of diseases, the prediction of prognoses, and the development of patient-specific therapeutic strategies. AI can help dentists, in particular, when they need to make important judgments quickly. It can eliminate human mistakes in making decisions, resulting in superior and consistent medical treatment while lowering the workload on dentists. The existing studies relevant to the study and application of AI in the diagnosis of various forms of mouth ulcers are reviewed in this work. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed in the preparation of the review. There were no rule violations, with the significant exception of the use of a better search method that led to more accurate findings. Using search terms mainly such as AI, oral health, oral ulcers, oral herpes simplex, oral lichen planus, pemphigus vulgaris, recurrent aphthous ulcer (RAU), oral cancer, premalignant and malignant disorders, etc., a comprehensive search was carried out in the reliable sources of literature, namely PubMed, Scopus, Embase, Web of Science, Ovid, Global Health, and PsycINFO. For all papers, exhaustive searches were done using inclusion criteria as well as exclusion criteria between June 28, 2018, and June 28, 2023. An AI framework for the automatic categorization of oral ulcers from oral clinical photographs was developed by the authors, and it performed satisfactorily. The newly designed AI model works better than the current convolutional neural network image categorization techniques and shows a fair level of precision in the classification of oral ulcers. However, despite being useful for identifying oral ulcers, the suggested technique needs a broader set of data for validation and training purposes before being used in clinical settings. Automated OCSCC identification using a deep learning-based technique is a quick, harmless, affordable, and practical approach to evaluating the effectiveness of cancer treatment. The categorization and identification of RAU lesions through the use of non-intrusive oral pictures using the previously developed ResNet50 and YOLOV algorithms demonstrated better accuracy as well as adequate potential for the future, which could be helpful in clinical practice. Moreover, the most reliable projections for the likelihood of the presence or absence of RAU were made by the optimized neural network. The authors also discovered variables associated with RAU that might be used as input information to build artificial neural networks that anticipate RAU.
PubMed: 37842407
DOI: 10.7759/cureus.45187 -
Cureus Apr 2024Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion, affecting the skin and mucous membranes. Both... (Review)
Review
Pemphigus vulgaris (PV) is a chronic autoimmune blistering disorder characterized by the loss of intraepithelial adhesion, affecting the skin and mucous membranes. Both males and females are affected, although it predominantly affects females in their fifth and sixth decades of life. Approximately 1.4 to 3.7% of PV cases occur in the pediatric population (≤18 years of age), and may be classified into childhood/pediatric PV, which affects individuals under 12 years old, and juvenile/adolescent PV, affecting those between 12 and 18 years old. Due to its rare occurrence in children and adolescents, there is often a delay in diagnosis and treatment in this age group. A systematic literature search was conducted on MEDLINE/PubMed, Web of Science, EMBASE, SCOPUS, and Cochrane Library databases to evaluate the efficacy of rituximab (RTX) in childhood and juvenile PV patients. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was employed to assess the risk of bias in case reports and series, while the Cochrane ROBINS-I tool was utilized for evaluating observational studies or non-randomized intervention studies. A total of 18 studies encompassing 46 juvenile or childhood PV patients in the pediatric and adolescent age groups were included for qualitative synthesis. The studies included nine case reports, two case series, five retrospective studies, one prospective study, and one open-label pilot study. Almost all cases of childhood and juvenile PV achieved either complete or partial remission after undergoing RTX treatment during the final follow-up periods. Furthermore, most cases reported no relapse, and only minor adverse events were noted in the RTX treatment group. Despite its potential benefits, the utilization of RTX in pediatric patients raises concerns due to the scarcity of evidence and the absence of controlled studies specific to this age group. Further exploration is necessary to establish a standardized treatment regimen for RTX in pediatric PV, which involves identifying the optimal dosage, frequency, treatment cycle duration, and maintenance therapy duration.
PubMed: 38752055
DOI: 10.7759/cureus.58288 -
American Journal of Reproductive... Jan 2024Pemphigus vulgaris may worsen during pregnancy, leading to both maternal and fetal complications. The relationship between pemphigus vulgaris and pregnancy remains...
PROBLEM
Pemphigus vulgaris may worsen during pregnancy, leading to both maternal and fetal complications. The relationship between pemphigus vulgaris and pregnancy remains unclear, and the outcomes and treatments of pemphigus vulgaris during pregnancy have not been extensively discussed.
METHOD OF STUDY
This article systematically reviews the literature, focusing on the relationship between pemphigus vulgaris and pregnancy. We conducted comprehensive searches in PubMed, Embase, Cochrane Library, and Web of Science databases, identifying 42 studies reporting the disease course, pregnancy outcomes, and management of both pregnancy and pemphigus vulgaris.
RESULTS
A total of 57 cases were included in the analysis, categorized into three distinct forms: pemphigus vulgaris onset before pregnancy (n = 33), onset during pregnancy (n = 20), and onset during the postpartum period (n = 4). Fifty four cases reported treatment strategies, among them, 44 cases (81.5%) initially received systemic corticosteroid therapy during pregnancy. Out of these cases, 7 (15.9%) did not achieve successful remission and required alternative treatment approaches. In terms of pregnancy outcomes, 23 out of 62 neonates (37.1%) exhibited skin lesions or tested positive for anti-dsg IgG in their serum, while 16 neonates (25.8%) experienced other complications.
CONCLUSIONS
These findings highlight the importance of effectively managing pemphigus vulgaris during pregnancy to ensure optimal outcomes.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pemphigus
PubMed: 38282607
DOI: 10.1111/aji.13813 -
International Journal of Oral and... Nov 2023The aim of this study was to critically evaluate the diagnostic yields of direct immunofluorescence (DIF) analysis on perilesional and normal-appearing mucosa biopsy... (Review)
Review
The aim of this study was to critically evaluate the diagnostic yields of direct immunofluorescence (DIF) analysis on perilesional and normal-appearing mucosa biopsy samples, to determine the optimal biopsy site for patients presenting with oral pemphigus vulgaris (PV) or mucous membrane pemphigoid (MMP). Electronic databases and article bibliographies were searched in December 2022. The primary outcome was the rate of DIF positivity. Of 374 records identified after the elimination of duplicates, 21 studies with 1027 samples were ultimately included. Meta-analysis revealed a pooled DIF positivity rate of 99.6% (95% confidence interval (CI) 97.4-100.0%, I = 0%) for PV and 92.6% (95% CI 87.9-96.5%, I = 44%) for MMP for biopsies from perilesional sites, and of 95.4% (95% CI 88.6-99.5%, I = 0%) for PV and 94.1% (95% CI 86.5-99.2%, I = 42%) for MMP for biopsies from normal-appearing sites. For MMP, there was no significant difference in the rate of DIF positivity between the two biopsy sites (odds ratio 1.91, 95% CI 0.91-4.01, I = 0%). The results suggest that the perilesional mucosa remains the optimal biopsy site for DIF diagnosis of oral PV, while the normal-appearing mucosa biopsy is optimal for oral MMP.
PubMed: 37268547
DOI: 10.1016/j.ijom.2023.05.005 -
Clinical and Experimental Medicine Aug 2023Pemphigus vulgaris is a potential life-threatening autoimmune bullous disorder. The significant role of autoreactive B cells in the pathogenesis of PV has been explained... (Review)
Review
Pemphigus vulgaris is a potential life-threatening autoimmune bullous disorder. The significant role of autoreactive B cells in the pathogenesis of PV has been explained extensively by producing autoantibodies. Recently, attention has been directed toward the role of T cells in the pathogenesis of PV; in other words, the underlying etiology of PV depends on the interaction between T cells and B cells resulting in antibody secretion. Herein, we systematically review the current literature on the emerging role of T cells in PV. To perform this systematic review, an extensive search through EMBASE, PubMed, Scopus, and ISI databases was performed from 1976 through 2021. Articles investigating the function of T cell subgroups in the pathogenesis or treatment of pemphigus vulgaris were included and reviewed. It is evidenced that T cells play a pivotal role in PV pathogenesis. Th1 and Th2 dichotomy including Th1 suppression and Th2 elevation may induce antibody production against desmoglein in keratinocytes. Furthermore, increased level of Th17 and decreased level of regulatory T cells have been detected in PV patients. However, further studies on the exact role of γδ-T cells in PV are required in order to clarify the pathogenesis of PV. T cells and their subtypes can be involved in the pathogenesis of PV. Thus, they can be considered as tentative targets of novel therapies for PV.
Topics: Humans; Pemphigus; Autoantibodies; Autoimmune Diseases; T-Lymphocytes, Regulatory; T-Lymphocyte Subsets
PubMed: 35925475
DOI: 10.1007/s10238-022-00855-8 -
Journal of the European Academy of... Nov 2023
Topics: Humans; Causality; COVID-19; Pemphigus; Vaccination; Case Reports as Topic
PubMed: 37328927
DOI: 10.1111/jdv.19271 -
Vaccines Apr 2024Cases of autoimmune bullous dermatosis (AIBD) have been reported following COVID-19 vaccination. (Review)
Review
BACKGROUND
Cases of autoimmune bullous dermatosis (AIBD) have been reported following COVID-19 vaccination.
OBJECTIVE
We aimed to provide an overview of clinical characteristics, treatments, and outcomes of AIBDs following COVID-19 vaccination.
METHODS
We conducted a systematic review and searched the Embase, Cochrane Library, and Medline databases from their inception to 27 March 2024. We included all studies reporting ≥ 1 patient who developed new-onset AIBD or experienced flare of AIBD following at least one dose of any COVID-19 vaccine.
RESULTS
We included 98 studies with 229 patients in the new-onset group and 216 in the flare group. Among the new-onset cases, bullous pemphigoid (BP) was the most frequently reported subtype. Notably, mRNA vaccines were commonly associated with the development of AIBD. Regarding the flare group, pemphigus was the most frequently reported subtype, with the mRNA vaccines being the predominant vaccine type. The onset of AIBD ranged from 1 to 123 days post-vaccination, with most patients displaying favorable outcomes and showing improvement or resolution from 1 week to 8 months after treatment initiation.
CONCLUSIONS
Both new-onset AIBD and exacerbation of pre-existing AIBD may occur following COVID-19 vaccination. Healthcare practitioners should be alert, and post-vaccination monitoring may be essential.
PubMed: 38793716
DOI: 10.3390/vaccines12050465