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Experimental Dermatology Jul 2023Autoimmune bullous diseases (AIBDs) are a group of rare blistering dermatoses of the mucous membrane and/or skin. The efficacy, safety and treatment durability of... (Review)
Review
A systematic review on efficacy, safety and treatment durability of intravenous immunoglobulin in autoimmune bullous dermatoses: Special focus on indication and combination therapy.
Autoimmune bullous diseases (AIBDs) are a group of rare blistering dermatoses of the mucous membrane and/or skin. The efficacy, safety and treatment durability of intravenous immunoglobulin (IVIg) as an alternative treatment should be explored to systematically review the available literature regarding treatment outcomes with IVIg in AIBD patients. The predefined search strategy was incorporated into the following database, MEDLINE/PubMed, Embase, Scopus and Web of Science on 18 July 2022. Sixty studies were enrolled using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The use of IVIg alone or combined with rituximab was reported in 500 patients with pemphigus, 82 patients with bullous pemphigoid, 146 patients with mucous membranes pemphigoid and 19 patients with epidermolysis bullosa acquisita. Disease remission with IVIg therapy and RTX + IVIg combination therapy were recorded as 82.8% and 86.7% in pemphigus, 88.0% and 100% in bullous pemphigoid and 91.3% and 75.0% in mucous membrane pemphigoid, respectively. In epidermolysis bullosa acquisita, treatment with IVIg led to 78.6% disease remission; no data were available regarding the treatment with RTX + IVIg in this group of patients. Among all the included patients, 37.5% experienced at least one IVIg-related side effect; the most common ones were headaches, fever/chills and nausea/vomiting. The use of IVIg with or without rituximab had a favourable clinical response in patients with AIBDs. IVIg has no major influence on the normal immune system, which makes its utilization for patients with AIBDs reasonable.
Topics: Humans; Pemphigoid, Bullous; Immunoglobulins, Intravenous; Epidermolysis Bullosa Acquisita; Pemphigus; Rituximab; Autoimmune Diseases; Skin Diseases, Vesiculobullous; Pemphigoid, Benign Mucous Membrane
PubMed: 37150538
DOI: 10.1111/exd.14829 -
Dermatology (Basel, Switzerland) 2023Pemphigus vulgaris is a life-threatening autoimmune bullous disease characterized by flaccid blister formation. As there has been no macroscopic assessment of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pemphigus vulgaris is a life-threatening autoimmune bullous disease characterized by flaccid blister formation. As there has been no macroscopic assessment of epidemiological characteristics, its disease burden in the general population remains unknown.
OBJECTIVES
The aim of this study was to assess the global incidence rate of pemphigus vulgaris in the general population.
METHODS
The search was conducted in databases including Medline, Embase, Web of Science, and the Cochrane Library from inception to May 1, 2022. We included original studies that either reported the incidence of pemphigus vulgaris or provided raw data for calculating. Studies based on a specific population instead of the general population were excluded. Individual studies were summarized using random-effects mode. The pooled incidence rate of pemphigus vulgaris among the general population and subgroups was obtained. Heterogeneity (I2 statistic) was assessed with the χ2 test on Cochrane's Q statistic.
RESULTS
Twenty-nine studies were eligible for final analysis, and the pooled incidence rate of pemphigus vulgaris was 2.83 per million person-years (95% CI, 2.14-3.61). The incidence rate was similar between men and women and remained stable in the past half-century. Southern Asia showed the highest rate among subcontinents that had more than one study conducted as 4.94 per million person-years (95% CI, 2.55-8.10). Economic levels do not seem to have any bearing on incidence.
CONCLUSIONS
Despite the substantial heterogeneity among studies, this meta-analysis revealed the worldwide incidence rate of pemphigus vulgaris for the first time and may assist in assessing global disease burden and promoting health policy.
Topics: Male; Humans; Female; Pemphigus; Incidence; Autoimmune Diseases; Asia, Southern
PubMed: 36944327
DOI: 10.1159/000530121 -
Journal Der Deutschen Dermatologischen... Jan 2023Dupilumab interferes with the signaling pathways of IL-4 and IL-13 and is effective in treating atopic dermatitis. Specific genodermatoses, including Netherton syndrome,... (Review)
Review
Dupilumab interferes with the signaling pathways of IL-4 and IL-13 and is effective in treating atopic dermatitis. Specific genodermatoses, including Netherton syndrome, epidermolysis bullosa pruriginosa, and hyper-IgE syndrome, are Th2 skewed diseases with activation of type 2 inflammation. We performed this systematic review to investigate the therapeutic role of dupilumab in the treatment of genodermatosis. A systematic search was conducted of the PubMed, Embase, Web of Science, and Cochrane databases from inception to December 13, 2021. The review included studies with relevant terms including "dupilumab," "genodermatosis", "Netherton syndrome", "ichthyosis", "epidermolysis bullosa" and "hyper-IgE syndrome". The initial search yielded 2,888 results, of which 28 studies and 37 patients with genodermatosis were enrolled. The assessed genodermatoses included Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with genetic disorders. Most of the reported cases showed significant clinical improvement after the initiation of dupilumab treatment without major adverse events. Decreased immunoglobulin E levels and cytokine normalization have also been documented. In conclusion, Dupilumab may have a potential therapeutic role in certain genodermatoses skewed towards T helper 2 (Th2) immunity, including Netherton syndrome, epidermolysis bullosa pruriginosa, hyper-IgE syndrome, Hailey-Hailey disease, and severe eczema associated with some genetic disorders.
Topics: Humans; Pemphigus, Benign Familial; Eczema; Immunoglobulin E
PubMed: 36657040
DOI: 10.1111/ddg.14924 -
JAAD International Dec 2022Systemic glucocorticoids are first-line treatment options for autoimmune blistering diseases; however, their long-term use is associated with significant toxicities. (Review)
Review
BACKGROUND
Systemic glucocorticoids are first-line treatment options for autoimmune blistering diseases; however, their long-term use is associated with significant toxicities.
OBJECTIVE
To evaluate the side effects of steroid-sparing agents and compare them with those of steroids.
METHODS
We searched Cochrane Reviews, Embase, MEDLINE, and Scopus between October 1978 and May 2020 using the keywords "bullous pemphigoid," "pemphigus," "autoimmune blistering diseases," and "side effects." A total of 31 randomized controlled trials and retrospective case series were critically appraised.
RESULTS
This review includes a total of 1685 patients with autoimmune blistering diseases, of whom 781 had bullous pemphigoid and 904 had either pemphigus vulgaris or pemphigus foliaceous.
LIMITATIONS
A major limitation is that because adjuvants are generally used in combination with steroids, only 12 of the studies reviewed included a "steroid-only" arm to allow for a direct comparison of side effects. Additionally, there is inadequate literature and lack of standardized grade reporting of specific side effects of each steroid-sparing agent.
CONCLUSION
In the future, researchers should consider implementing the Common Terminology Criteria for Adverse Events, version 5.0, for reporting of all side effects to allow for consistency and standardization. It would be useful to have an index similar to the Glucocorticoid Toxicity Index to quantify these side effects.
PubMed: 36089938
DOI: 10.1016/j.jdin.2022.07.005 -
Dermatologic Therapy Nov 2022Pemphigus is a group of autoimmune blistering diseases. Given the ulcerative nature of the diseases, the full healing of ulcers and erosions might be challenging. The... (Review)
Review
Pemphigus is a group of autoimmune blistering diseases. Given the ulcerative nature of the diseases, the full healing of ulcers and erosions might be challenging. The aim of this study was to determine various topical wound care options for pemphigus patients, the advantage of each alternative, and to compare their efficacy, safety, and feasibility. In accordance with PRISMA guideline, we performed a systematic search in PubMed/Medline, web of science, and Scopus databases for articles published from inception until February 2, 2022. Out of 703 initially retrieved articles, 11 full texts were included. Our findings were divided into the following categories: silver-containing dressings, paraffin-embedded tulle nets, topical insulin, EPIFIBROIN 0039, platelet gel, and Biobrane®. The most commonly used topical care in pemphigus patients was silver-containing dressings in six studies. All of the included studies reported acceptable outcomes without any severe adverse effects. Due to the few available studies in this field, a definite suggestion cannot be made. We recommend larger randomized controlled studies to identify the best topical care modality in pemphigus patients.
Topics: Humans; Bandages, Hydrocolloid; Silver; Pemphigus; Wound Healing
PubMed: 36070217
DOI: 10.1111/dth.15808 -
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 -
Scientific Reports Jun 2022Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic... (Meta-Analysis)
Meta-Analysis
Autoimmune diseases caused by pathogenic IgG4 subclass autoantibodies (IgG4-AID) include diseases like MuSK myasthenia gravis, pemphigus vulgaris or thrombotic thrombocytopenic purpura. Their etiology is still unknown. Polymorphisms in the human leukocyte antigen (HLA) gene locus, particularly in HLA-DRB1, are known genetic susceptibility factors for autoimmune diseases. We hypothesized a similar role for HLA polymorphisms in IgG4-AID and conducted a systematic review and meta-analysis with case-control studies on IgG4-AID based on MOOSE/ HuGENet guidelines. Genotype (G) and allele (A) frequencies of HLA-DQB1*05 (G: OR 3.8; 95% CI 2.44-5.9; p < 0.00001; A: OR 2.54; 95% CI 1.82-3.55; p < 0.00001) and HLA-DRB1*14 (G: OR 4.31; 95% CI 2.82-6.59; p < 0.00001; A: OR 4.78; 95% CI 3.52-6.49; p < 0.00001) and the HLA-DRB1*14-DQB1*05 haplotype (OR 6.3; 95% CI 3.28-12.09; p < 0.00001/OR 4.98; 95% CI 3.8-6.53; p < 0.00001) were increased while HLA-DRB1*13 (G: OR 0.48; 95% CI 0.34-0.68; p < 0.0001; A: OR 0.46; 95% CI 0.34-0.62; p < 0.00001) was decreased in IgG4-AID patients. In conclusion, the HLA-DQB1*05, HLA-DRB1*14 alleles and the HLA-DQB1*05-DRB1*14 haplotype could be genetic risk factors that predispose for the production of pathogenic IgG4 autoantibodies and the HLA-DRB1*13 allele may protect from IgG4 autoimmunity.
Topics: Autoantibodies; Autoimmunity; Gene Frequency; HLA-DRB1 Chains; Humans; Immunoglobulin G; Pemphigus
PubMed: 35654912
DOI: 10.1038/s41598-022-13042-2 -
Journal of Cellular Physiology Jul 2022Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by cell-cell detachment (or acantholysis) and blister formation. While the... (Review)
Review
Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterized by cell-cell detachment (or acantholysis) and blister formation. While the signaling mechanisms that associate with skin/mucosal blistering are being elucidated, specific treatment strategies targeting PV-specific pathomechanisms, particularly kinase signaling, have yet to be established. Hence, the aim of this review was to systematically evaluate molecules in the class of kinases that are essential for acantholysis and blister formation and are therefore candidates for targeted therapy. English articles from PubMed and Scopus databases were searched, and included in vitro, in vivo, and human studies that investigated the role of kinases in PV. We selected studies, extracted data and assessed risk of bias in duplicates and the results were reported according to the methodology outlined by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The risk of bias assessment was performed on in vivo studies utilizing SYRCLE's risk of bias tool. Thirty-five studies were included that satisfied the pathogenicity criterion of kinases in PV, the vast majority being experimental models that used PV sera (n = 13) and PV-IgG (n = 22). Inhibition of kinase activity (p38MAPK, PKC, TK, c-Src, EGFR, ERK, mTOR, BTK, and CDK2) was achieved mostly by pharmacological means. Overall, we found substantial evidence that kinase inhibition reduced PV-associated phosphorylation events and keratinocyte disassociation, prevented acantholysis, and blocked blister formation. However, the scarce adherence to standardized reporting systems and the experimental protocols/models used did limit the internal and external validity of these studies. In summary, this systematic review highlighted the pathogenic intracellular events mediated by kinases in PV acantholysis and presented kinase signaling as a promising avenue for translational research. In particular, the molecules identified and discussed in this study represent potential candidates for the development of mechanism-based interventions in PV.
Topics: Acantholysis; Autoantibodies; Blister; Humans; Immunoglobulin G; Keratinocytes; Pemphigus; Phosphorylation
PubMed: 35616233
DOI: 10.1002/jcp.30784 -
Journal of the European Academy of... Sep 2022
Meta-Analysis
Topics: Humans; Occupational Exposure; Pemphigus; Pesticides
PubMed: 35607897
DOI: 10.1111/jdv.18258 -
International Journal of Laboratory... Aug 2022An indolent T-lymphoblastic proliferation (iT-LBP) is a rare benign disorder characterized by an abnormal expansion of immature T-cells, which morphologically can mimic... (Review)
Review
An indolent T-lymphoblastic proliferation (iT-LBP) is a rare benign disorder characterized by an abnormal expansion of immature T-cells, which morphologically can mimic malignancy. Since the first case was described in 1999, dozens more have been reported in the literature. However, the epidemiologic, clinical, pathologic, and biologic features of this disease have not been well described. Here, we retrospectively reviewed all known cases reported in the literature to better understand this entity. A PubMed search up to January 2022 highlighted 25 papers describing cases/case series of iT-LBP, one of which was a case presentation in a slide workshop. Except for 9 of the cases in one of the papers, where it was evident that the number of CD3+/TdT+ cells were too few to conform with a diagnosis of iT-LBP, all papers and all the cases reported were included in the study amounting to a total of 45 cases. Clinicopathologic characteristics were analyzed using descriptive statistics and frequencies. Our analysis highlighted the previously known association with Castleman disease and Castleman-like features and underlined its association with dendritic cell proliferations in general, as well as uncovering high frequency of concurrence with hepatocellular carcinoma and autoimmune diseases, most notably myasthenia gravis, paraneoplastic pemphigus and paraneoplastic autoimmune multiorgan syndrome. Furthermore, the co-expression of CD4 and CD8 and high prevalence of extranodal disease and recurrences were other less well described features that were revealed.
Topics: Carcinoma, Hepatocellular; Cell Proliferation; Humans; Liver Neoplasms; Lymphoproliferative Disorders; Retrospective Studies
PubMed: 35577551
DOI: 10.1111/ijlh.13873