Pemphigus Foliaceus Research Articles

Understanding patient perspectives on vaccine decision making in adults with autoimmune bullous diseases: a qualitative study.

Patients with autoimmune bullous diseases are at an increased risk of infection, both from the underlying skin disease and from immunosuppressive treatments. Limited information is available on vaccine beliefs and behaviors in dermatology patients and adults with autoimmune bullous diseases in particular. To understand vaccine decision making, identify perceived risks and benefits of vaccinations, and discuss individual experiences in patients with autoimmune bullous diseases in the United States. A qualitative study was performed utilizing semi-structured interviews, and analysis was conducted on NVivo. Patterns were identified in the coded data, and representative quotations were recorded for each major theme. Interviews were conducted between February 15, 2022 and September 15, 2022. Twenty patients with a diagnosis of bullous pemphigoid, mucous membrane pemphigoid, pemphigus vulgaris, or pemphigus foliaceous were interviewed. Of the 20 participants, 14 (70%) were female, with a mean (SD, range) age of 64.8 (13.2, 34-83) years. Key themes that emerged from qualitative analysis of the interviews included patient concerns regarding their increased susceptibility to infection, potential exacerbation of skin disease following vaccination, and the effect of immunosuppressive medications on humoral response to vaccines. Lack of appointment availability, difficulty accessing vaccines, and cost were commonly identified barriers to vaccination. These findings provide valuable knowledge for dermatologists in regard to providing counseling specific to patient concerns and to improve communication surrounding vaccination in the dermatology setting.

Pemphigus Foliaceous with special reference to Visphota Kushta

Pemphigus is an autoimmune blistering disease which can be fatal if left untreated. In case of secondarily infected skin lesions, life threatening sepsis may develop. There is no specific treatment protocol for the management of pemphigus. The present study is aimed to treat a 57-year-old male patient clinically diagnosed with pemphigus foliaceus admitted in Kayachikitsa department in Govt. Ayurveda College, Thiruvananthapuram. Treatment was aimed at controlling the progression of disease, preventing infection and inducing healing of the affected area. In Ayurveda symptoms are more similar to Kaphapitha kushta especially Visphota kushta. Langhana, Snehapana and repeated Sodhana were the treatment protocols adopted. Ayurvedic approach in this single case of pemphigus is beneficial in correcting the inherent Agnimandya at Koshta and Dhatu level and thus provides significant result. PDAI score was used for assessment. Before treatment PDAI was 96, reduced to 24 after Sodhana and after treatment it was 6. There was no recurrence of symptoms after 2 weeks.

Diagnostic Utility of Direct Immunofluorescence on Paraffin-Embedded Skin Biopsy Samples for the Diagnosis of Autoimmune Vesiculobullous Lesions.

Background Autoimmune vesiculobullous diseases (AIBDs) are a group of diseases characterized by blisters of the skin/mucosa due to the presence of circulating autoantibodies against antigens in the epidermis or the dermo-epidermal junction. Direct immunofluorescence (DIF) for immunoglobulin (Ig)G, IgC3, and IgA on fresh-frozen tissue is the gold standard diagnostic test for AIBDs. However, DIF in the absence of frozen tissue is challenging for the diagnosis of AIBDs. This study aimed to analyze the practical utility of DIF using paraffin-embedded skin biopsy rather than fresh frozen tissue for the diagnosis of AIBDs. Methodology This cross-sectional comparative study included 30 cases of AIBDs. DIF for IgG and IgA was performed on paraffin-embedded tissue (PE-DIF) after proteinase digestion on histopathologically confirmed 15 pemphigus vulgaris (PV), three pemphigus foliaceous (PF), four bullous pemphigoid (BP), three dermatitis herpetiformis (DH), three subcorneal pustular dermatosis (SCPD), and one case each of linear IgA disease and pemphigoid gestationis (PG). PE-DIF staining pattern was compared with the DIF on fresh frozen tissue (FF-DIF). Results All cases of PV and PF showed an intercellular IgG chicken wire staining pattern similar to FF-DIF. However, background staining was more intense in PV cases while less intense in PF cases. Three BP cases showed linear IgG staining in PE-DIF. DH, SCPD, linear IgA disease, and PG cases did not show IgG positivity. Out of three DH cases, two cases showed granular IgA positivity while linear IgA positivity along the basement membrane was seen in a single case of linear IgA disease. Negative IgG staining was observed in SCPD. Immunofluorescence in PE-DIF was rapidly deteriorating than in FF-DIF. Conclusions DIF done on paraffin-embedded tissue can be used as a supplement and salvage technique with histopathology for the diagnosis of AIBDs,particularly when a cryostat facility for frozen tissue is not available and the patient is unable to undergo a second biopsy procedure.

Gut microbiota and relevant abundances of<i> Prevotella copri, Lachnospiraceae, Collinsella, Helicobacter cinaedi, Desulfovibrio</i>, and <i>Escherichia coli</i> among cats with <i>Pemphigus foliaceus</i>

The cat gut-inhabitant conjoint microbiota is a peculiar ecosystem in relationship with several bodily functions and immunity. Gut microbiota dysbiosis could participate within autoimmune disease pathogenesis, whereas its niche, whether causative or influencing role regarding systemic immunity in autoimmune diseases, remains fugitive. The purpose of the present study was to identify gut microbiota alterations and probable mechanisms that participated in the development of Pemphigus foliaceus for a better understanding of future effective therapeutical armamentarium based on gut microbiota. In the present article, the authors investigated gut microbiota alterations to those of eight cats diagnosed with Pemphigus foliaceus. Furthermore, the study thoroughly analyzed pathogenic bacteria species as triggers of autoimmunity. The diagnostic algorithm involved two distinct sides: i) on referral with the first criteria was proof of evidence for possible autoimmunity, and ii) Pemphigus foliaceus diagnosis with relevant analytes. A total of eight cats were enrolled, and gut microbiomes were detected by the use of the MIDOG All-in-One Microbial Test targeting Next-Generation DNA Sequencing. By this methodology, we analyzed the dysbiosis network for bacterial kingdoms and determined the relationship between disease activity related to Pemphigus foliaceus and gut microbiota. The data showed increasing abundances of Collinsella, Lachnospiroceae, and Escherichia coli and decreasing Desulfovibrio piger, Prevotella copri, and Helicobacter cianedi among cats with pemphigus foliaceus. For the first time in Turkey, the gut microbiota of cats with pemphigus foliaceus were detected, the results of which could be cautiously taken into consideration for novel and effective therapeutical approaches.

TARC/CCL17 reflects the severity of pemphigus (pemphigus vulgaris and pemphigus foliaceus) at the initial presentation

AbstractBackgroundPemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering diseases targeting desmoglein 3 (Dsg3) or desmoglein 1 (Dsg1). The current scoring system, pemphigus disease area index (PDAI), has limitations including inter‐ and intra‐evaluator variability, as well as a time‐consuming evaluation process.ObjectivesTo identify objective and quantitative surrogate markers for assessing disease severity in PV and PF.MethodsEleven PV and PF patients were included. PDAI scores and candidate biomarkers [anti‐Dsg3 antibody, anti‐Dsg1 antibody, thymus and activation‐regulated chemokine (TARC)/CCL17, immunoglobulin E (IgE) levels and eosinophil counts] were measured before oral corticosteroid treatment. Pearson's correlation coefficient was used for correlations between PDAI and candidate biomarkers.ResultsSerum TARC/CCL17 levels significantly correlated with PDAI scores in PV and PF (R = 0.72, p = 0.02), while anti‐Dsg3 antibody levels correlated with PDAI scores for PV (R = 0.86, p = 0.012). No significant correlations were observed for anti‐Dsg1 antibody, eosinophil counts or IgE levels.ConclusionsSerum TARC/CCL17 may be a quantitative and unbiased disease biomarker in pemphigus patients, although further studies involving larger patient cohorts are needed.

Clinical and immunological predictors of post-rituximab paradoxical pemphigus flare: A prospective cohort study.

Background Paradoxical flare of pemphigus following rituximab infusion has been reported previously, however, its incidence or risk factors have not been studied in detail. Objectives To evaluate the clinical and immunological predictors associated with post-rituximab paradoxical pemphigus flare. Materials and Methods This was a prospective cohort study including adult patients with pemphigus vulgaris or foliaceus who were treated with rituximab. Patients were administered 1000 mg of intravenous rituximab on days 0 and 14 (Rheumatoid arthritis (RA) protocol), with or without oral prednisolone and/or conventional immunosuppressive agents. Baseline clinical and immunological predictors of post-rituximab pemphigus flares were assessed. Results Fifty patients (mean age 40.44 ± 12.36 years) with a mean pemphigus disease area index (PDAI) score of 27.8 ± 15.48 were administered rituximab. Post-rituximab flare occurred in 10 (20%) patients after a mean of 14.1 ± 4.33 days after the first rituximab infusion. The mean baseline PDAI score (36.4 ± 11.7 vs. 25.6 ± 15.7, P = 0.02) and serum anti-Dsg1 levels (1216.8 ± 850.1 vs. 592 ± 562.12 RU/mL, P = 0.03) were statistically significantly higher in patients experiencing a flare. Using ROC-curve analysis, a PDAI score of 328 (OR 8.3, 95% CI 1.5-44.7) was 80% sensitive and 67.5% specific in predicting post-rituximab flare, while serum anti-Dsg1 level of 31137.78 RU/ml had a sensitivity of 60% and specificity of 85%. There was no significant difference in terms of affected body surface area, type of pemphigus, starting prednisolone dose, oral immunosuppressive adjuvant, serum anti-Dsg3, serum anti-AchRM3, and peripheral CD19+ B cell population. Limitations Our study is limited by a relatively small sample size. Immunological factors were not evaluated at the time of pemphigus flare. Though these unexpected pemphigus flares are likely to be associated with rituximab infusion, the possibility of spontaneous disease exacerbation cannot be entirely excluded. Conclusions Patients with more severe pemphigus or high serum anti-Dsg1 are at risk of post-rituximab paradoxical flare, and may benefit from rituximab administration under close monitoring.

Evaluation of the Status of Patients with Autoimmune Bullous Diseases (Pemphigus and Bullous Pemphigoids) in Dermatology Clinics of Mashhad University of Medical Sciences During the COVID-19 Pandemic Using Telemedicine.

Background: The COVID-19 pandemic impacted the growth of telemedicine. The challenge was in the way of dermatologists, who needed a comprehensive examination of the lesions. Here, we tried a tele-management of patients with autoimmune bullous diseases. Methods: This cross-sectional study was conducted on confirmed bullous disorder cases. Demographic data and the status of COVID-19 infection were assessed in the patients. Some of the cases were provided online, and some with office visits. Drug and treatment plan changes were compared between these two groups. All statistical analysis was conducted using SPSS version 20. Result: Totally, 100 patients, including 46 males (46.0%) and 54 females (54.0%), 48.15 ± 11.11 years old, were studied. Among them, 73 were pemphigus vulgaris (73.0%), 11 were bullous pemphigoid (11.0%), 10 were pemphigus foliaceus (10.0%), and the other 6 (6.0%) were categorized as other autoimmune bullous diseases. During the pandemic, 38 cases (38.0%) had COVID-19 infection. 72 patients had office and 28 had online visits. Treatment plans after visits during the pandemic (p = 0.588) and drug dose change (p = 0.297) showed no significant difference between office and online visits. Conclusion: Our patients tended to plan office visits more than online; however, we found no differences regarding the plan or treatment changes. Online visit has good efficacy, but further investigation in case of provision of a suitable platform and getting the attention of the patients is needed.

The Prevalence of Clinically Undiagnosed Depression in Patients With Autoimmune Bullous Diseases Seen at Inkosi Albert Luthuli Central Hospital, Durban, South Africa.

Background Chronic autoimmune bullous diseases have been associated with major depression in previous studies. This has been attributed to inflammatory cytokines, chronic pain, and the chronicity and debilitating nature of the disease. As no similar studies have been conducted in our setting, we aimed to determine the prevalence and severity of clinically undiagnosed depression in patients with autoimmune bullous diseases. Methodology We performed a cross-sectional study among outpatients managed in a bullous disease clinic at Inkosi Albert Luthuli Central Hospital, a quaternary provincial hospital in Durban, South Africa. Results A total of 44 participants were recruited and included in this study. The majority of the participants were females (29, 65.9%). The most common autoimmune bullous diseases were pemphigus vulgaris (19, 43.2%), bullous pemphigoid (18, 40.9%), and pemphigus foliaceus (5, 11.4%). The overall prevalence of at least mild and at least moderate depression in patients with autoimmune bullous diseases in our clinic was 52.3% and 20.5%, respectively. Pemphigus vulgaris showed the highest median Patient Health Questionnaire-9 score compared to other bullous dermatoses. Statistically significant differences were observed between females and males for the duration with the bullous disease (p = 0.014) and between intraepidermal and subepidermal disease for both the mean age (p = 0.038) and age at onset (p = 0.015). Conclusions Clinically undiagnoseddepression is common in patients with autoimmune bullous disease. Its frequency and severity may differ depending on the underlying autoimmune bullous disease and possibly other factors. Dermatologists should always be alert to this fact and prompt psychiatric consultation as required to comprehensively manage these patients.

Direct immunofluorescence (DIF) versus immunohistochemical (IHC) staining of complements and immunoglobulins (Ig) in pemphigus group.

Pemphigus is a group of bullous disorders of the skin characterized by the formation of autoantibodies present in the intercellular junction of the epidermis. Diagnosis is made by clinical, histopathological examination, and DIF. As DIF needs frozen sections, fluorescent tagged antibodies, UV light microscope for examination, and trained personnel, its non-availability makes a definitive diagnosis challenging. To evaluate the utility of IHC staining of complements and Ig in cases of Pemphigus. Twenty-six diagnosed cases of Pemphigus were stained by Peroxidase immunohistochemical method using monoclonal antibody to IgG, IgA, IgM, IgG4, C3, C4 d with DAB as chromogen. Pemphigus cases include twenty of pemphigus vulgaris (PV), four cases of pemphigus foliaceous (PF), and two of pemphigus vegetans (Pveg). Positivity was defined as the deposition of Ig and complements as distinct, continuous brown staining of keratinocytes at intercellular junctions. On IHC total of 20 PV 17 showed positivity (85%) for IgG, 11 (55%) C4d, 19 (95%) C3d, and 16 (80%) IgG4 deposits at the intercellular junction of the epidermis. All cases of PF showed a deposit of IgG, with three (75%) cases for IgG4, C3d, and C4d. Both cases of Pveg showed positivity for IgG and C4d while one case was negative for IgG4 and C3d. The overall IgG, C3, IgG4, and C4d expression for pemphigus was seen in 88%, 88%, 76.9%, and 61.5% of cases. The relation between these markers, combination of IgG and C3, was best related to each other ( P value = 0.80). The sensitivities for IgG, IgG4, and C3 were 77.8%%, 73%, and 73% resp. We conclude that IHC is a useful tool in the diagnosis of PV with the highest sensitivity of IgG and C3d. The combination of IgG and C3d could replace the DIF in almost all of our cases, so IHC on FFPE sections be used as an alternative method to DIF.

Microarray Gene Expression Analysis of Lesional Skin in Canine Pemphigus Foliaceus.

Canine pemphigus foliaceus (PF) is considered the most common autoimmune skin disease in dogs; the mechanism of PF disease development is currently poorly understood. Therefore, this study aimed to characterize the molecular mechanisms and altered biological pathways in the skin lesions of canine PF patients. Using an RNA microarray on formalin-fixed, paraffin-embedded samples, we analyzed the transcriptome of canine PF lesional skin (n = 7) compared to healthy skin (n = 5). Of the 800 genes analyzed, 420 differentially expressed genes (DEGs) (p < 0.05) were found. Of those, 338 genes were significantly upregulated, including pro-inflammatory and Th17-related genes. Cell type profiling found enhancement of several cell types, such as neutrophils, T-cells, and macrophages, in PF skin compared to healthy skin. Enrichment analyses of the upregulated DEGs resulted in 78 statistically significant process networks (FDR < 0.05), including the Janus kinase signal transducer and activator of transcription (JAK-STAT) and mitogen-activated protein kinase (MAPK) signaling. In conclusion, canine PF lesional immune signature resembles previously published changes in human pemphigus skin lesions. Further studies with canine PF lesional skin using next-generation sequencing (e.g., RNA sequencing, spatial transcriptomics, etc.) and the development of canine keratinocyte/skin explant PF models are needed to elucidate the pathogenesis of this debilitating disease.

Paraneoplastic pemphigus and reported, identified underlying diseases

Introduction: Pemphigus is a rare group of autoimmune diseases that promote development of various skin eruptions, the most commonly it presents with blisters. The several types of pemphigus are: pemphigus vulgaris, pemphigus foliaceus, intraepidermal neutrophillic IgA dermatosis and especially rare type- paraneoplastic pemphigus, which is main topic of this publication. Paraneoplastic pemphigus is a disease which affects patients with developing carcinogenesis process. Usually it is a malignant process, but there are also some cases which describe paraneoplastic pemphigus associated with benign tumors. Because of its occurence our current level of knowledge about different aspects of paraneoplastic pemphigus is not final and as comprehensive as researchers and patients wish. Aim of study: The main purpose of this publication is presentation a review of literature about paraneoplastic pemphigus- its epidemiology, physiopathology, pathomorfology, clinical features, and description of different types of benign or malignant processes which concomitence with paraneoplastic pemphigus. State of knowledge: Paraneoplastic pemphigus is a rare autoimmune disease, which aspects are not widely described, but there are some reports about epidemiology, pathophysiology, histopathology, treatment and associated confirmed malignancies. The challenge for future is to formulate clear, formal, treatment protocols for paraneoplastic pemphigus. Conclusion: Paraneoplastic pemphigus is a very fascinating disease for researchers because there are still very limited reports and statistics about this very rare disorder. Nonetheless year by year our level of knowledge about pathogenesis, clinical features, associated malignant and benign processes is growing and it can affect more personalized, effective treatment methods and protocoles.

Rituximab in the Management of Autoimmune Bullous Diseases: A Treatment-Resistant Case Series from a Single Central European Referral Center.

Background and Objectives: Rituximab (RTX) has been the predominant treatment for autoimmune bullous diseases (AIBDs). The objective of this research was to assess the advantages and safety characteristics of RTX treatment in individuals with AIBD. This assessment focused on clinical remission and a reduction in glucocorticosteroid usage, its effect on the titers of autoantibodies targeting desmoglein-1 (DSG-1) and desmoglein-3 (DSG-3), and adverse occurrences during a 12-month follow-up period in a dermatology department within a Central European university context. Materials and Methods: Our case series involved eleven patients, including eight patients with pemphigus vulgaris, two with pemphigus foliaceus, and one with epidermolysis bullosa acquisita. They received a 1 g dose of rituximab, repeated over a two-week interval. Results: The reduction in a prednisone-equivalent dosage after 2, 6, and 12 months following the second RTX infusion was 65.05%, 73.99%, and 76.93%, in that order. The titers of antibodies against DSG-1 exhibited reductions of 43.29%, 75.86%, and 54.02% at 2, 6, and 12 months, respectively. By contrast, the antibody concentrations targeting DSG-3 displayed a decrease of 27.88%, 14.48%, and 5.09% at the corresponding time points. Over the course of the 12-month monitoring period, 18.18% of patients experienced disease relapse, while the remaining individuals achieved either complete or partial remission with minimal or no therapy. Adverse effects were noted in 36.36% of the patient population; they were mild, and no serious adverse effects were reported. Conclusions: RTX represents an efficacious and well-tolerated therapeutic option for the management of AIBD and merits consideration in cases of refractory AIBD. However, further research is imperative to delineate the most optimal dosage, dosing frequency, and total quantity of maintenance infusions required. Additionally, there is a compelling need for studies that explore the impact of RTX on individuals with AIBD who do not exhibit a significant reduction in anti-desmoglein autoantibody levels.

Serum interleukin-6 concentration in patients with pemphigus.

Pemphigus is a rare blistering autoimmune disease that damages the integumentary system and lowers the quality of life of patients. Interleukin-6 (IL-6) has been linked to the immunopathogenesis of pemphigus, according to recent research. Thus, the investigation purpose was to assess the function of IL-6 in the development and intensity of pemphigus disease. Between January 2022 and August 2022, a case-series study involving 26 patients with pemphigus vulgaris (PV), four patients with pemphigus foliaceus (PF), and 20 healthy volunteers was carried out at the Ho Chi Minh City Hospital of Dermato-Venereology. Patients with PV and PF had significantly higher serum IL-6 concentrations than healthy volunteers (p<0.001). Patients with a positive Nikolsky sign had significantly higher serum IL-6 concentrations than those with a negative sign (p<0.001). The serum IL-6 concentration and the pemphigus disease area index were found to significantly correlate (r=0.8, p<0.001). According to our findings, IL-6 might be a significant factor in pemphigus development and severity. Thus, novel treatments that specifically target IL-6 could be a good option for managing pemphigus, particularly in its more severe forms.

A Global View of Pemphigus: Geographical Variations.

Pemphigus, an autoimmune intraepidermal bullous disease group with roughly eight distinct forms, includes pemphigus vulgaris (PV) and pemphigus foliaceus (PF) as its predominant global forms. Despite the increased utilization of global health records and reporting systems, epidemiological data remain limited and poorly categorized. Therefore, this study aimed to conduct a review to track, identify, and characterize cases of PV and PF published and categorized worldwide. A research question was formulated; studies were selected based on the inclusion criteria; and data from these publications were systematically collected, summarized, and presented using narrative descriptions. The search strategy yielded 3,212 articles, of which 95 underwent critical analysis and data extraction. Studies from 52 countries contributed to the dataset, covering various pemphigus variants. Notably, only two countries, Iran (18.87%) and South Korea (11.43%), accounted for approximately a third of the reported PV cases, while Brazil contributed 40.25% of the foliaceus variants cases documented in the literature. These findings offer valuable insights into the global distribution of pemphigus and inform future research and healthcare efforts.

Overview of Clinical Trials With Efgartigimod in Autoimmune Blistering Diseases: Pemphigus Vulgaris and Pemphigus Foliaceus (ADDRESS and ADDRESS+) and Bullous Pemphigoid (BALLAD and BALLAD+)

Introduction &amp; Objectives: Efgartigimod is an engineered Fc fragment that inhibits the activity of the neonatal Fc receptor (FcRn), thereby reducing levels of circulating IgG including pathogenic IgG autoantibodies. Pemphigus vulgaris (PV), pemphigus foliaceus (PF), and bullous pemphigoid (BP) are autoimmune blistering diseases. Pemphigus is mediated by IgG autoantibodies targeting desmoglein (Dsg)-3 in PV, and Dsg-1 in mucocutaneous PV (in addition to Dsg-3), while PF is attributed to IgG autoantibodies against Dsg-1 only. Dsg-3 and Dsg-1 are desmosomal proteins mediating keratinocyte cell-cell adhesion. BP is mediated by IgG autoantibodies against BP180 (type XVII collagen) and BP230 structural proteins of the dermal-epidermal junction. Materials &amp; Methods: ADDRESS is a multicenter, randomized, double-blind, placebo-controlled trial evaluating efficacy and safety of efgartigimod in patients with PV or PF (NCT04598451). Participants are undergoing randomization (2:1) to receive subcutaneous efgartigimod co-formulated with PH20 or placebo/PH20 on top of oral prednisone (or equivalent). Primary endpoint is the proportion of patients with PV or PF who achieve complete remission on minimal therapy (CRmin) within 30 weeks. BALLAD is a global, multicenter, phase 2/3, randomized, double-blind, placebo-controlled trial evaluating efficacy and safety of subcutaneously administered efgartigimod in patients with BP (NCT05267600). Part A will be a proof-of-concept study and recruit 40 participants, while the Part B confirmatory study will recruit 120 participants. Parts A and B will be identical in schedule, structure, assessments, and conduct. Primary endpoint is the proportion of participants in complete remission off oral corticosteroid therapy for ≥8 weeks at week 36. Results &amp; Conclusions: As of February 28, 2023, 222 participants have been enrolled into ADDRESS and enrolment of BALLAD has started. It is anticipated that the recruitment of the ADDRESS full study and BALLAD part A will be completed, and a further update will be given at the time of presentation.

Genetic Association and Differential RNA Expression of Histone (De)Acetylation-Related Genes in Pemphigus Foliaceus-A Possible Epigenetic Effect in the Autoimmune Response.

Pemphigus foliaceus (PF) is an autoimmune skin blistering disease characterized by antidesmoglein-1 IgG production, with an endemic form (EPF) in Brazil. Genetic and epigenetic factors have been associated with EPF, but its etiology is still not fully understood. To evaluate the genetic association of histone (de)acetylation-related genes with EPF susceptibility, we evaluated 785 polymorphisms from 144 genes, for 227 EPF patients and 194 controls. Carriers of HDAC4_rs4852054*A were more susceptible (OR = 1.79, p = 0.0038), whereas those with GSE1_rs13339618*A (OR = 0.57, p = 0.0011) and homozygotes for PHF21A_rs4756055*A (OR = 0.39, p = 0.0006) were less susceptible to EPF. These variants were not associated with sporadic PF (SPF) in German samples of 75 SPF patients and 150 controls, possibly reflecting differences in SPF and EPF pathophysiology. We further evaluated the expression of histone (de)acetylation-related genes in CD4+ T lymphocytes, using RNAseq. In these cells, we found a higher expression of KAT2B, PHF20, and ZEB2 and lower expression of KAT14 and JAD1 in patients with active EPF without treatment compared to controls from endemic regions. The encoded proteins cause epigenetic modifications related to immune cell differentiation and cell death, possibly affecting the immune response in patients with PF.

Claudin-4 Upregulation in Acantholytic and Autoimmune-Mediated Bullous Disorders.

Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier by forming a circumferential network in the granular layer that serves as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different blistering disorders. We collected 35 cases, including two Hailey-Hailey disease, one Darier disease, three Grover disease, one acantholytic acanthoma, two warty dyskeratoma, 11 pemphigus vulgaris (PV) including six mucosal PV, and two pemphigus foliaceus. For comparison, we included five cases of normal skin, five eczema, and three bullous pemphigoid cases. Claudin-4 demonstrated weak-to-moderate expression in keratinocytes located in the stratum granulosum, keratinocytes surrounding hair follicles, and adnexal glands. Further, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes surrounding and within the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six cases of mucosal PV) and all three bullous pemphigoids. This finding suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in blistering disorders, independent of the specific underlying disease mechanism.

Clinico-etiological and histopathological correlation in erythroderma: In a tertiary care hospital of Eastern Odisha

Background: Erythroderma, or “exfoliative dermatitis,” is a generalized inflammatory disorder of the skin manifesting with erythema and scaling affecting more than 90% of the skin surface. Primary erythroderma develops in normal skin, and etiological factors include drug reaction, lymphomas, and hematological malignancies, which may be idiopathic. Aims and Objectives: The present study is to evaluate the clinico-etiological and histopathological correlations in erythroderma. Materials and Methods: This prospective observational study was done in the Department of Dermatology, S.C.B. Medical College, Cuttack, from 2021 to 2022. Erythema and scaling involving more than 90% of the body surface area were calculated by Wallace’s rule of nine. A detailed demographic profile and history were recorded with a thorough clinical examination for each patient, involving type of scales, sizes of scales, color of scales, associated lichenification or fissuring, pedal edema, examination of the scalp for scales, hair loss, examination of the nails and mucosa, and associated arthritis. Results: The most common disease was psoriasis (16), Idiopathic (7), followed by atopic and drug-induced dermatitis 6 patients each. Seborrheic dermatitis showed 3 cases, followed by contact dermatitis, Reiter’s disease, Pemphigus foliaceus, Ichthyosis (congenital), Dermatomyositis, and malignancy-induced 2 cases each, whereas contact dermatitis and Dermatophyte infection were found to be one patient each. Conclusion: Though some of the etiology remains unknown, repeated investigations and continued follow-up are necessary to determine long-term complications. The role of alternative medicines and the injudicious use of steroids by quacks or untrained practitioners should be discouraged, and proper awareness should be given to patients with erythroderma.

A case of myasthenia gravis following alopecia areata

AbstractWe present a case of myasthenia gravis that occurred after alopecia areata and evaluate the literature on the comorbidity of alopecia and myasthenia gravis. A 41‐year‐old male noticed hair loss on his scalp 4 months ago, and his hair loss progressed with drooping of both upper eyelids and diplopia. Physical and laboratory examination identified the comorbidity of myasthenia gravis and alopecia areata. Prednisolone 10 mg/day and tacrolimus 3 mg/day were administered for 7 days following hospitalization, which served to improve diplopia and ptosis. Following methylprednisolone therapy, hair loss in alopecia areata improved without the enlargement of bald areas. Based on the literature review, a total of 29 cases with alopecia and myasthenia gravis including our case have been reported. Among them, seven cases of myasthenia gravis developed after alopecia. The average time for the onset of myasthenia gravis after alopecia was 16.6 months. Four cases showed other autoimmune disease comorbidity, such as vitiligo, lichen planus, cutaneous lupus erythematosus, and pemphigus foliaceus, suggesting the involvement of Th1‐significant immunological states in these patients.

Differences among Indian and European pemphigus patients based on demographics, clinical parameters and propensity for relapse: results of a prospective bicontinental cohort study.

Limited studies have explored pemphigus variations among different ethnic groups residing in their respective geographical locations. This bicontinental study aimed to compare clinical and immunological parameters in Indian and European pemphigus patients in complete remission, off therapy, or on minimal therapy. 105 patients (India, n= 75; Bulgaria, n=15; Greece, n=15) with pemphigus vulgaris (PV) or pemphigus foliaceous (PF) in complete remission on minimal therapy (n=64) or complete remission off therapy (n=41) were recruited. Demographic, clinical, and immunological parameters were compared. Indian patients were significantly younger, the maximal disease severity during the preceding active disease phase was significantly lower, and treatment duration until complete remission was significantly shorter, compared to European patients. European patients had significantly higher anti-Dsg3 serum levels and higher IgG positivity rate based on direct immunofluorescence microscopy at baseline. Furthermore, European patients revealed higher CD19, CD19+ CD27+ cell counts, compared with patients from India. Of note, none of the European patients (n=30) relapsed within the study period, in contrast to 29/75 (38.6%) Indian patients. Treatment strategies differed significantly between the two cohorts, with more frequent utilization of rituximab to achieve remission in the Indian cohort, while prednisolone was more widely used for maintaining remission in the European cohort. The observed heterogeneity of pemphigus among patients of different ethnicities in terms of demographics, clinical parameters, and propensity for relapse may be due to genetic background or different treatment strategies.