Assessing ST18 gene polymorphisms (rs17315309, rs2304365) in Iraqi patients with Pemphigus vulgaris.

Pemphigus vulgaris (PV) is a potentially fatal autoimmune disease characterized by blistering of the skin, mucous membranes, and oral cavity. Genetics are implicated in its etiology, with the ST18 gene identified as a potential risk factor for pemphigus in certain populations, suggesting its role as a novel molecular target for therapeutic intervention. This study aimed to detect single nucleotide polymorphisms (SNPs) rs17315309 A/G and rs2304365 C/G in the ST18 gene among Iraqi/Arabic patients with PV. A total of 90 Iraqi subjects participated in this study, including 45 patients diagnosed with PV and 45 healthy controls. SNP analysis was performed using High-Resolution Melt Analysis (HRMA) with Eva Green I Dye. For SNP rs17315309 A/G, the distribution of heterozygous genotypes showed highly significant differences between the patient and healthy groups (P = 0.005), with the mutant G-allele being significantly more prevalent in patients than in the healthy group (P = 0.001). In contrast, for SNP rs2304365 C/G, the distribution of heterozygous and mutant genotypes did not differ significantly between patients and healthy individuals (P = 0.8 and P = 0.3, respectively), with the mutant G-allele also showing no significant difference (P = 0.4). Our data indicate a significant association between PV and the rs17315309 A/G SNP in the ST18 gene among the Iraqi population of Arabic origin. However, no association was found between patients with PV and the rs2304365 C/G SNP in the same gene.

Epidemiology of malignant tumors in patients with pemphigus: an analysis of trends from 1955 to 2021.

BACKGROUND: The incidence of malignant tumors has increased in patients with non-paraneoplastic pemphigus, although there has been no systematic analysis of global epidemiology. OBJECTIVE: To explore the epidemiology of various types of non-paraneoplastic pemphigus associated with malignant tumors. METHODS: Five databases from establishment through October 20, 2023, were searched. STATA SE 17 was used for the data analysis. Subgroup, meta-regression, and sensitivity analyses were used to evaluate the heterogeneity of pooled studies. RESULTS: A total of 6679 participants were included in our meta-analysis from 16 studies. The aggregated prevalence of tumors in patients diagnosed with pemphigus was 8%. The prevalence was 7% in patients with pemphigus vulgaris, 10% in those with pemphigus foliaceus, and 12% in individuals diagnosed with other types of pemphigus. The prevalence was 8% in Asia, 11% in Europe, and 8% in North America. From a country-specific perspective, patients with pemphigus from Israel, Greece, and Germany exhibited a higher prevalence of tumors at 11%. Furthermore, when categorized by the duration of the study period, the highest prevalence was observed in studies spanning 10 to 20 years, at 11%. CONCLUSION: These findings demonstrate the incidence and prevalence of malignant tumors in patients with non-paraneoplastic pemphigus, which may achieve early detection and intervention, and then reduce mortality rates.

The evolution of Pemphigus publications: A bibliometric analysis with research trends and global productivity.

Despite an increase in global research on the subject of Pemphigus, which seriously affects patient health and quality of life, there is no bibliometric research on this subject in literature to date. The aim of this study was to conduct a holistic analysis of scientific articles published on Pemphigus, using bibliometric methods. Articles published on the subject of Pemphigus between 1980 and 2021 were downloaded from the web of science (WoS) database and analyzed using various statistical methods. To determine trend subjects, collaboration between countries, and the most effective studies with citation analyses, visual network maps were obtained with bibliometric analyses. A total of 3034 articles were analyzed. The 3 countries making the greatest contribution to literature were the USA (n:831, 27.3%), Japan (n:402, 13.2%), and Germany (n:221, 7.2%). The 3 most active institutions were Keio University (n:163, 5.3%), Kurume University (n:130, 4.2%) and Tel Aviv University (n:107, 3.5%). The 3 journals publishing the most articles were the British Journal of Dermatology (n: 88), Journal of the American Academy of Dermatology (n:171) and the Journal of Investigative Dermatology (n:143). The 3 leading journals according to the mean number of citations (NC) per article (citation count: CC) were the New England Journal of Medicine (CC:246), the Lancet (CC:143) and the Journal of Cell Biology (CC:133). The author with the most articles published was Hashimoto Takashi (n.168, 5.5%). As a result of cluster analysis, it was seen that 9 different main clusters had been studied on Pemphigus subjects to date (1: desmoglein, 2: paraneoplastic Pemphigus (PNP) - Pemphigus types-desmosome, 3: desmoglein 1 ve 3-autoimmunity, 4: treatment-rituximab, 5: acantholysis-apoptosis, 6: quality of life-remission-relapse, 7: autoantibodies, 8: epidemiology-mortality, 9: corticosteroids). The most commonly studied subjects were determined to be pemphigus vulgaris (PV), pemphigus foliaceus (PF), autoimmunity, rituximab, PNP, desmoglein (desmoglein3-desmoglein1), autoantibodies, acantholysis, autoantibody, treatment, autoimmune disease, desmosome, ELISA, and immunofluorescence. The primary trending topic was rituximab drug, which is used in the treatment of Pemphigus. The other most studied trend topics were azathioprine drug used in treatment, intravenous immunoglobulin treatment, quality of life, mortality rates, Pemphigus herpetiformis, and wound healing.

Direct medical cost related to the management of pemphigus: A pilot Tunisian study.

INTRODUCTION: Pemphigus is a therapeutically challenging disease with high morbidity and economic burden. First-line prescription of rituximab remains limited in Tunisia due to its high cost. Systemic steroids remain the standard of care but are associated with a major risk of morbidities and higher treatment costs. AIM: To assess the direct medical costs of pemphigus in Tunisia. METHODS: Retrospective estimation of direct medical costs during the 18 months following the diagnosis using the "bottom-up approach" in the Dermatology Department of Hedi Chaker Hospital, Sfax, Tunisia. RESULTS: Total medical costs were estimated at 38745.7 €, with an average cost of 1 210 € per patient and per year: paraclinical investigations (46%), medical treatment (30%), hospitalization (21%) and outpatient visits (3%). The average cost was the highest in the age group of 15-24 years (1553 €). Treatment costs related to corticosteroid-induced morbidity were estimated at 1208 €. CONCLUSIONS: The management of pemphigus in Tunisia needs to be adapted to take into account the health economic analysis in order to reduce overall disease costs and the burden of steroid-induced morbidities.

Concordance of clinical, histopathologic and direct Immunofluorescence findings in patients with intraepidermal immunobullous disorders.

Objective: To determine the concordance among clinical, histopathological and immunofluorescence as diagnostic methods for intraepidermal immunobullous disorders. METHODS: The prospective cross-sectional study was conducted at the Institute of Skin Diseases, Karachi, from December 2020 to December 2022, and comprised adult patients of either gender presenting with complaints of bullae, vesicles, pustules and crusts on the skin or mucous membrane. Diagnostic findings of each patient as obtained by clinical assessment, microscopy and direct immunofluorescence were compared. Data was analysed using SPSS 19. RESULTS: Of the 81 patients, 41(50.6%) were males and 40(49.4%) were females. The overall median age was 35 years (interquartile range: 23 years), with 66(75%) patients aged 19-55 years. The predominant body site involved was the trunk 49(60.5%), followed by mucosa 26(32.1%). Clinical diagnosis detected 80(98.7%) cases, compared to 76(93.8%) by microscopy and 81(100%) by direct immunofluorescence. Conclusion: Direct immunofluorescence was found to be the gold standard for a confirmatory diagnosis of intraepidermal immunobullous disorders, especially when clinical and histopathology findings were inconclusive.

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.

Single-cell sequencing reveals distinct immune cell features in cutaneous lesions of pemphigus vulgaris and bullous pemphigoid.

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are two common subtypes of autoimmune bullous disease (AIBD). The key role of circulating autoreactive immune cells contributing to skin damage of AIBD has been widely recognized. Nevertheless, the immune characteristics in cutaneous lesions remain unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell VDJ sequencing (scRNA-seq) to generate transcriptional profiles for cells and T/B cell clonetype in skin lesions of BP and PV. We found that the proportions of NK&T, macrophages/ dendritic cells, B cells, and mast cells increased in BP and PV lesions. Then, BP and PV cells constituted over 75% of all myeloid cell subtypes, CD4+ T cell subtypes and CD8+ T cell subtypes. Strikingly, CD8+ Trm was identified to be expanded in PV, and located in the intermediate state of the pseudotime trajectory from CD8+ Tm to CD8+ Tem. Interestingly, CD8+ Tem and CD4+ Treg highly expressed exhaustion-related genes, especially in BP lesions. Moreover, the enhanced cell communication between stromal cells and immune cells like B cells and macrophages/ dendritic cells was also identified in BP and PV lesions. Finally, clone expansion was observed in T cells of BP and PV compared with HC, while CD8+ Trm represented the highest ratio of hyperexpanded TCR clones among all T cell subtypes. Our study generally depicts a large and comprehensive single-cell landscape of cutaneous lesions and highlights immune cell features in BP and PV. This offers potential research targets for further investigation.

From neglect to spotlight: the underappreciated role of B cells in cutaneous inflammatory diseases.

The skin, covering our entire body as its largest organ, manifests enormous complexities and a profound interplay of systemic and local responses. In this heterogeneous domain, B cells were considered strangers. Yet, recent studies have highlighted their existence in the skin and their distinct role in modulating cutaneous immunity across various immune contexts. Accumulating evidence is progressively shedding light on the significance of B cells in maintaining skin health and in skin disorders. Herein, we integrate current insights on the systemic and local contributions of B cells in three prevalent inflammatory skin conditions: Pemphigus Vulgaris (PV), Systemic Lupus Erythematosus (SLE), and Atopic Dermatitis (AD), underscoring the previously underappreciated importance of B cells within skin immunity. Moreover, we address the potential adverse effects of current treatments used for skin diseases, emphasizing their unintentional consequences on B cells. These comprehensive approaches may pave the way for innovative therapeutic strategies that effectively address the intricate nature of skin disorders.

Pemphigus Vulgaris Successfully Treated With Bromocriptine.

Pemphigus vulgaris (PV) is an autoimmune blistering skin condition primarily treated with immunosuppressive agents. We describe a case of PV successfully treated with nonconventional treatment, bromocriptine mesylate. Bromocriptine has been used in human trials showing beneficial therapeutic effects in managing autoimmune conditions. The results from experimental trials and the low toxicity of bromocriptine in comparison with immunosuppressive agents form a solid rationale for investigating its role in controlling PV.  J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7720e.

Comparing Clinical Outcomes of Steroid-Sparing Therapy With Rituximab Versus Rituximab Alone in Pemphigus.

BACKGROUND: Previous clinical trials have demonstrated that rituximab therapy combined with conventional steroid-sparing therapy (SST) has increased rates of disease control for mucous membrane pemphigoid compared with rituximab alone. However, limited data is available regarding the role of SST with rituximab therapy in pemphigus. OBJECTIVE: This study aimed to examine clinical outcomes in pemphigus patients treated with rituximab with SST versus without the addition of SST. METHODS: A retrospective chart review was performed for adult pemphigus patients in the Southeastern US at Emory between January 1, 2011, and December 31, 2021. Primary outcomes, including time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, and time to relapse after a rituximab cycle, were compared between patients on SST and patients without SST.  Results: Following rituximab therapy, there was no difference in time to remission, time to prednisone dose of 10 mg or less, time to cessation of prednisone therapy, or time to relapse for patients with or without SST. LIMITATIONS: Our study is limited by its retrospective decline, setting at a single academic center, and inclusion of a high proportion of patients with moderate disease. CONCLUSIONS: The use of SST with rituximab dosing did not improve clinical outcomes related to time to remission, reduction in prednisone dosing, or relapse. These data provide further evidence for the use of rituximab in the majority of pemphigus patients without the need for SST. J Drugs Dermatol. 2024;23(3):e97-e99    doi:10.36849/JDD.7949e.

Alterations of circulating free fatty acids in patients with pemphigus vulgaris.

Free fatty acids (FFA) have gained research interest owing to their functions in both local and systemic immune regulation. Changes in the serum levels of anti-inflammatory short chain fatty acids (SCFA), primarily derived from the gut microbiota, and pro-inflammatory medium (MCFA) and long (LCFA) chain fatty acids, derived from either the gut microbiota or the diet, have been associated with autoimmunity. Circulating FFA were retrospectively analysed by a gas chromatography-mass spectrometry method in the serum of 18 patients with pemphigus vulgaris (PV) at the baseline and 6 months (n = 10) after immunosuppressive treatments, and 18 healthy controls (HC). Circulating FFA were correlated with the Pemphigus Disease Area Index (PDAI) and serum concentrations of interferon-gamma (IFN-γ), Interleukin (IL)-17A, IL-5, IL-10 and IL-21. Principal Component analysis computed on FFA abundances revealed significant differences in the profile of SCFA (p = 0,012), MCFA (p = 0.00015) and LCFA (p = 0,035) between PV patients and HC, which were not significantly changed by immunosuppressive treatments. PV patients showed a significantly lower serum concentration of propionic (p < 0.0005) and butyric (p < 0.0005) acids, SCFA with anti-inflammatory functions, while hexanoic (p < 0.0005) and hexadecanoic (p = 0.0006) acids, pro-inflammatory MCFA and LCFA respectively, were over-represented. Treatments induced a significant decrease of hexanoic (p = 0.035) and a further increase of hexadecanoic (p = 0.046) acids. Positive correlations emerged between IFN-γ and acetic acid (Rho = 0.60), IFN-γ and hexanoic acid (Rho = 0.46), IL-5 and both hexadecanoic acid (Rho = 0.50) and octadecanoic acid (Rho = 0.53), butyric acid and PDAI (Rho = 0.53). PV was associated with a remarked imbalance of circulating FFA compared to HC. The serum alterations of SCFA, MCFA, and LCFA may contribute to promoting inflammation in PV. Deeper insights into the immunomodulatory functions of these molecules may pave the way for personalized dietary interventions in PV patients.

Doxycycline monotherapy for pyoderma vegetans: a case report.

Background: Pyoderma vegetans (PV) is a rare neutrophilic dermatosis of unknown etiology. Currently, there are no treatment guidelines for PV. Systemic steroids are often used as first-line therapy, but recurrence upon discontinuation or tapering is common.Materials and methods: We tested the efficacy of doxycycline at a dose of 200 mg/d to treat resistant PV.Results: After 4 weeks of treatment we noticed a significant improvement in the clinical appearance of PV.Conclusions: Our case demonstrates the potential utility of doxycycline as a systemic steroid-sparing agent in the treatment of PV.

Characterization and Management of Amicrobial Pustulosis of the Folds, Aseptic Abscess Syndrome, Behçet Disease, Neutrophilic Eccrine Hidradenitis, and Pyostomatitis Vegetans-Pyodermatitis Vegetans.

Neutrophilic dermatoses are a broadly heterogeneous group of inflammatory skin disorders. This article reviews 5 conditions: amicrobial pustulosis of the folds, aseptic abscess syndrome, Behçet disease, neutrophilic eccrine hidradenitis, and pyostomatitis vegetans-pyodermatitis vegetans.The authors include up-to-date information about their epidemiology, pathogenesis, clinicopathologic features, diagnosis, and management.