-
Dermatologic Therapy Mar 2021
Meta-Analysis
Topics: Arthritis, Rheumatoid; Humans; Pemphigus; Skin
PubMed: 33528863
DOI: 10.1111/dth.14845 -
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 -
Frontiers in Immunology 2021The presence of anti-desmocollin (Dsc) antibodies is rarely described in autoimmune blistering diseases patients. Moreover, several clinical phenotypes of pemphigus may...
The presence of anti-desmocollin (Dsc) antibodies is rarely described in autoimmune blistering diseases patients. Moreover, several clinical phenotypes of pemphigus may be associated with these antibodies. In this review we analyze clinicopathological, immunologic and outcome features of anti-Dsc autoimmune blistering diseases patients, to improve their diagnosis and management. We conducted a systematic search of PubMed and Embase (1990-present) for studies reporting cases of autoimmune blistering diseases with anti-Dsc antibodies. We classified the selected patients as patients with exclusively anti-Dsc autoantibodies, and patients with anti-Dsc and other autoantibodies. Of 93 cases with anti-Dsc autoantibodies included, 38 (41%) had exclusively these antibodies. Only 18% of patients presented with the typical clinicopathological phenotype of pemphigus vulgaris or pemphigus foliaceous. Mucosal involvement was seen in approximately half of the patients. Up to 18% of cases were associated with neoplasms. Acantholysis was described in 54% of cases with histopathological information. Treatments and outcomes vary in the different clinical phenotypes. The presence of anti-Dsc antibodies must be suspected mainly in those patients with either atypical pemphigus, in special with clinical pustules, or in cases showing intraepithelial or dermal neutrophilic/eosinophilic infiltrate on histological examination and dual pattern by direct immunofluorescence examination.
Topics: Acantholysis; Animals; Autoantibodies; Autoimmunity; Desmocollins; Desmogleins; Eosinophils; Humans; Neutrophils; Pemphigus; Phenotype; Skin
PubMed: 34567003
DOI: 10.3389/fimmu.2021.740820 -
International Journal of Environmental... May 2023(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic... (Review)
Review
(1) Background: Immunological laboratory testing is known to be complex, and it is usually performed in tertiary referral centers. Many criticalities affect diagnostic immunological testing, such as limited availability, the need for specifically trained laboratory staff, and potential difficulties in collecting blood samples, especially in the most vulnerable patients, i.e., the elderly and children. For this reason, the identification of a new feasible and reliable methodology for autoantibody detection is urgently needed. (2) Methods: We designed a systematic review to investigate the available literature on the utilization of saliva samples for immunological testing. (3) Results: A total of 170 articles were identified. Eighteen studies met the inclusion criteria, accounting for 1059 patients and 671 controls. The saliva collection method was mostly represented by passive drooling (11/18, 61%), and the most frequently described methodology for antibody detection was ELISA (12/18, 67%). The analysis included 392 patients with rheumatoid arthritis, 161 with systemic lupus erythematosus, 131 with type 1 diabetes mellitus, 116 with primary biliary cholangitis, 100 with pemphigus vulgaris, 50 with bullous pemphigoids, 49 with Sjogren syndrome, 39 with celiac disease, 10 with primary antiphospholipid syndromes, 8 with undifferentiated connective tissue disease, 2 with systemic sclerosis, and 1 with autoimmune thyroiditis. The majority of the reviewed studies involved adequate controls, and saliva testing allowed for a clear distinction of patients (10/12 studies, 83%). More than half of the papers showed a correlation between saliva and serum results (10/18, 55%) for autoantibody detection, with varying rates of correlation, sensitivity, and specificity. Interestingly, many papers showed a correlation between saliva antibody results and clinical manifestations. (4) Conclusions: Saliva testing might represent an appealing alternative to serum-based testing for autoantibody detection, considering the correspondence with serum testing results and the correlation with clinical manifestations. Nonetheless, standardization of sample collection processing, maintenance, and detection methodology has yet to be fully addressed.
Topics: Child; Humans; Aged; Saliva; Lupus Erythematosus, Systemic; Sjogren's Syndrome; Autoantibodies; Arthritis, Rheumatoid
PubMed: 37239511
DOI: 10.3390/ijerph20105782 -
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 -
Dermatology (Basel, Switzerland) 2022The common inflammatory scalp diseases, such as psoriasis, seborrheic dermatitis, lichen planopilaris, discoid lupus erythematosus, contact dermatitis, or pemphigus may... (Review)
Review
BACKGROUND
The common inflammatory scalp diseases, such as psoriasis, seborrheic dermatitis, lichen planopilaris, discoid lupus erythematosus, contact dermatitis, or pemphigus may share similar clinical features.
OBJECTIVE
To identify and systematically review the available evidence on the accuracy of trichoscopy in inflammatory scalp disorders.
METHODS
A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 58 articles were included in the analysis.
RESULTS
The following trichoscopy features were found to show the highest specificity for the respective diseases: in psoriasis: diffuse scaling, simple and twisted red loops, red dots and globules, and glomerular vessels; in seborrheic dermatitis: atypical vessels, thin arborizing vessels, and structureless red areas; in discoid lupus erythematosus: follicular plugs and erythema encircling follicles; in lichen planopilaris: milky red areas or fibrotic patches; in contact dermatitis: twisted red loops; in pemphigus foliaceus: white polygonal structures and serpentine vessels; in pemphigus vulgaris: red dots with whitish halo and lace-like vessels; and in dermatomyositis: lake-like vascular structures.
LIMITATIONS
Different nomenclature and variability in parameters, which were analyzed in different studies.
CONCLUSION
This systemic analysis indicates that trichoscopy may be used with high accuracy in the differential diagnosis of inflammatory scalp diseases.
Topics: Dermatitis, Contact; Dermatitis, Seborrheic; Dermoscopy; Humans; Lichen Planus; Lupus Erythematosus, Discoid; Pemphigus; Psoriasis; Scalp; Scalp Dermatoses
PubMed: 34265772
DOI: 10.1159/000517516 -
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 -
Cutis Jan 2022Autoimmune bullous dermatoses (ABDs), such as pemphigus and bullous pemphigoid (BP), cause cutaneous lesions that are painful and disfiguring. These conditions affect a... (Review)
Review
Autoimmune bullous dermatoses (ABDs), such as pemphigus and bullous pemphigoid (BP), cause cutaneous lesions that are painful and disfiguring. These conditions affect a patient's ability to perform everyday tasks, and individual lesions can take years to heal. Multiple small studies have examined how these conditions affect a patient's lifestyle. We systematically reviewed the trials that have evaluated the mental health of patients with bullous dermatoses. Of the 13 studies assessed, 2 domains of interest were primarily evaluated: quality of life (QOL) and psychological state. Quality of life predominantly was analyzed using the Dermatology Life Quality Index (DLQI). To evaluate psychological state, the General Health Questionnaire (GHQ) primarily was utilized. This review informs providers and summarizes the various ways that ABDs affect mental health.
Topics: Autoimmune Diseases; Humans; Pemphigoid, Bullous; Pemphigus; Quality of Life; Skin Diseases, Vesiculobullous
PubMed: 35180062
DOI: 10.12788/cutis.0439 -
Experimental Dermatology Feb 2022Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterised by cell-cell detachment or acantholysis. The mechanisms which follow antibody... (Review)
Review
Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterised by cell-cell detachment or acantholysis. The mechanisms which follow antibody (Ab) binding and culminate in acantholytic changes and skin/mucosal blistering have not been fully clarified. Current treatment strategies are not specific to PV pathophysiology and although life-saving, harbour considerable side effects. We aimed to systematically assess the molecules amenable to targeted treatments that follow Ab binding and are associated with PV acantholysis. The resulting scoping review was conducted under PRISMA-ScR guidelines with clear inclusion and exclusion criteria and focused specifically on kinases, caspases, proteases, hydrolytic enzymes and other molecules of interest postulated to take part in the pathophysiology of PV. The review process resulted in the identification of 882 articles, of which 56 were eligible for qualitative synthesis. From the included articles, the majority (n = 42) used PV-IgG as the pathogenic agent, mainly via in vitro (n = 16) and in vivo (n = 10) models. Twenty-five molecules were found to play a pathogenic role in PV, including uPA, ADAM10, EGFR, Src, PKC, cdk2, ERK, PLC, calmodulin, NOS, p38MAPK and caspase-3. Selective inhibition of these molecules resulted in varying degrees of reduction in acantholysis and blistering. The pathogenic molecules identified in this review represent potential candidates for clinical translation.
Topics: Acantholysis; Autoantibodies; Blister; Humans; Pemphigus; Signal Transduction; p38 Mitogen-Activated Protein Kinases
PubMed: 34435386
DOI: 10.1111/exd.14453 -
Biology Feb 2022Pemphigus vulgaris (PV) is an IgG-mediated autoimmune disease characterised by epithelial cell-cell detachment (acantholysis) resulting in mucocutaneous blistering. The... (Review)
Review
BACKGROUND
Pemphigus vulgaris (PV) is an IgG-mediated autoimmune disease characterised by epithelial cell-cell detachment (acantholysis) resulting in mucocutaneous blistering. The exact pathogenesis of blister formation is unknown and this has hampered the development of non-steroidal, mechanism-based treatments for this autoimmune disease. This systematic review aims to investigate the role of caspases in the pathogenesis of PV to inform the choice of more targeted therapeutic agents.
METHODS
A systematic search of MEDLINE/PubMed and Scopus databases was conducted to identify eligible studies. Multiple phases of inclusion and exclusion of the primary articles were conducted in pairs, and studies were recorded and analysed according to the latest version of the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Risk of bias assessment was conducted for extracted in vivo animal intervention studies using SYRCLE's risk of bias tool.
RESULTS
Eight articles from a total of 2338 in vitro, in vivo, and human studies met the inclusion criteria, with a high degree of inter-rater reliability. By and large, the results show that caspase activation was pathogenic in experimental PV because pan-caspase inhibitors could block or reduce PV acantholysis and blistering in vitro and in vivo, respectively. The pathogenic pathways identified involved caspase-1 and caspase-3. One study failed to show any improvement in the PV model with a caspase inhibitor. The majority of animal studies had high or unclear risk of bias.
CONCLUSION
There are consistent data pointing towards a pathogenic role of caspase activation in PV acantholysis. However, high-quality evidence to confirm that caspase inhibition can prevent PV-induced blistering in vivo is limited. Therefore, further research is required to test the preclinical efficacy of caspase inhibitors in PV.
PubMed: 35205180
DOI: 10.3390/biology11020314