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.

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.

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.

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.

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.

The management of pemphigus vulgaris and mucous membrane pemphigoid in a joint oral medicine and dermatology clinic: a five-year narrative review.

Pemphigus disease and mucous membrane pemphigoid are autoimmune blistering diseases (AIBDs) which may involve both oral and extra-oral tissues. The Bristol Joint Oral Medicine and Dermatology Combined Clinic was set up in 2014, with the primary aim of improving the standard of care for patients with AIBDs. This interdisciplinary approach aimed to address the medical management challenges due to the multisite nature of these AIBDs.We present a narrative report of the clinical work undertaken within this clinic, focused on the management of this patient cohort within a five-year span (2017-2022). This report outlines the multisite nature of AIBDs and the range of topical and systemic treatments that were employed to achieve adequate disease control and optimise outcomes for patients. We reflect on the experiential benefits of this multidisciplinary clinic extended beyond immediate patient benefits to areas such as specialist training, both from a dermatologist's and oral physician's perspective.

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.

Superficial and Bullous Neutrophilic Dermatoses: Sneddon-Wilkinson, IgA Pemphigus, and Bullous Lupus.

Sneddon-Wilkinson disease (SWD), IgA pemphigus, and bullous systemic lupus erythematosus (BSLE) are superficial and bullous neutrophilic dermatoses. They are all characterized by sterile neutrophilic infiltrate but differ in the level of skin affected and presence of autoantibodies. Both SWD and IgA pemphigus present with grouped flaccid pustules and have epidermal involvement; it is unclear whether they are distinct or exist on a spectrum of the same disease. IgA pemphigus is distinguished from SWD by positive direct immunofluorescence showing intercellular IgA deposition. BSLE presents with tense bullae, dermal neutrophilic infiltrate, and direct immunofluorescence showing linear IgG deposition along the dermal-epidermal junction.

Immune-mediated oral mucosal pathology: a comprehensive review and update for clinicians - part II.

The oral mucosa can be involved in a wide variety of mucocutaneous conditions that may present primarily in the mouth or affect other cutaneous or mucosal sites. Many of these conditions are immune mediated and typically present as inflammatory mucosal pathology. Patients experiencing such conditions usually seek medical evaluation and treatment due to the associated pain and discomfort, and occasionally taste disturbance or dysphagia and the overall deterioration in the oral health-related quality of life. These conditions share some common features and there could be some overlap in their clinical presentation, which can lead to delays in diagnosis and proper management of patients. Clinicians dealing with such disorders, including dermatologists, need to be aware of the oral manifestations of mucocutaneous conditions, their clinical features, underlying mechanisms, diagnostic approaches, and treatment options, as well as the recent advances in the research on these conditions. This review provides a comprehensive, evidence-based reference for clinicians, with updated insights into a group of immune mediated conditions known to cause oral mucosal pathology. Part one will cover oral lichen planus, erythema multiforme and systemic lupus erythematosus, while part two will cover recurrent aphthous stomatitis, pemphigus vulgaris and mucous membrane pemphigoid, in addition to the less common disorders linear IgA disease, dermatitis herpetiformis and epidermolysis bullosa.

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.

Sustained Remission Without Corticosteroids Among Patients With Pemphigus Who Had Rituximab as First-Line Therapy: Follow-Up of the Ritux 3 Trial.

Importance: The Ritux 3 trial demonstrated the short-term efficacy and safety of first-line treatment with rituximab compared with a standard corticosteroid regimen in pemphigus. No data on the long-term follow-up of patients who received rituximab as first line are available. Objective: To assess the long-term efficacy and safety of the Ritux 3 treatment regimen. Design, Setting, and Participants: This 7-year follow-up study of the Ritux 3 trial included patients with pemphigus from 25 dermatology departments in France from January 1, 2010, to December 31, 2015. Exposure: Patients were initially randomized in the rituximab plus prednisone group or prednisone-alone group. Main outcomes and measures: The primary outcome was the 5- and 7-year disease-free survival (DFS) without corticosteroids, assessed by Kaplan-Meier curves. Secondary outcomes were occurrence of relapse, occurrence of severe adverse events (SAEs), and evolution of antidesmoglein (Dsg) antibody enzyme-linked immunosorbent assay values to predict long-term relapse. Results: Of the 90 patients in the Ritux 3 trial, 83 were evaluated at the end of follow-up study visit (44 in the rituximab plus prednisone group; 39 in the prednisone-alone group) with a median (IQR) follow-up of 87.3 (79.1-97.5) months. Forty-three patients (93%) from the rituximab plus prednisone and 17 patients (39%) from the prednisone-alone group had achieved complete remission without corticosteroids at any time during the follow-up. Patients from the rituximab group had much longer 5- and 7-year DFS without corticosteroids than patients from the prednisone-alone group (76.7% and 72.1% vs 35.3% and 35.3%, respectively; P < .001), and had about half the relapses (42.2% vs 83.7%; P < .001). Patients who received rituximab as second-line treatment had shorter DFS than patients treated as first line (P = .007). Fewer SAEs were reported in the rituximab plus prednisone group compared with the prednisone-alone group, 31 vs 58 respectively, corresponding to 0.67 and 1.32 SAEs per patient, respectively (P = .003). The combination of anti-Dsg1 values of 20 or more IU/mL and/or anti-Dsg3 values of 48 or more IU/mL yielded 0.83 positive predictive value and 0.94 negative predictive value to predict long-term relapse. Conclusions and Relevance: In this secondary analysis of the Ritux 3 trail, first-line treatment of patients with pemphigus with the Ritux 3 regimen was associated with long-term sustained complete remission without corticosteroid therapy without any additional maintenance infusion of rituximab.

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.