Pemphigus vulgaris (PV) is a rare autoimmune blistering disease mediated by pathogenic autoantibodies. Although both HLA and non-HLA loci contribute to disease susceptibility, their combined roles in immune regulation remain incompletely understood. This study investigated the joint contribution of HLA-DRB1 and FCGR2B variants to PV susceptibility within an integrative immunogenetic framework. Genotype data from 286 individuals (200 controls and 86 PV patients) were analyzed using bias-reduced association models, two-locus genotype combination analyses, and cumulative genetic risk modeling. Gene-gene relationships were explored through epistasis testing, while functional relevance was examined using biological annotation approaches. HLA-DRB1*04:02 and *14:01 were significantly associated with increased PV risk, whereas *11:01 and *16:01 demonstrated protective effects after multiple testing correction (q < 0.05). The FCGR2B c.671T > C (I232T) variant showed a modest effect in single-locus analyses but did not remain statistically significant after correction for multiple testing. Several two-locus genotype combinations involving FCGR2B and HLA-DRB1 were enriched among patients; however, interaction analyses supported an additive immunogenetic architecture rather than epistasis. Genetic risk modeling demonstrated improved discrimination with weighted scores, and explainable machine-learning analysis identified HLA-DRB1 as the dominant predictor, with FCGR2B contributing a secondary modulatory signal. These findings delineate an additive immunogenetic framework underlying PV susceptibility, emphasizing the central role of HLA-DRB1. Although FCGR2B did not retain independent statistical significance after multiple-testing correction, the results suggest a potential modulatory contribution within the broader immunogenetic architecture of PV.

Rare diseases are often overlooked due to their low prevalence and may be classified as "idiopathic" once more common etiologies have been excluded. Nevertheless, rare conditions do occur, and clinicians must remain vigilant in considering them. Pemphigus vulgaris is awell-established autoimmune blistering disorder involving the skin and mucous membranes, with recognized triggering factors such as medications, infections, paraneoplastic processes, and trauma. Postsurgical pemphigus, however, represents an exceptionally rare variant, arising specifically at sites of surgical scarring. Unfortunately, once initiated, the disease frequently extends beyond the scar, involving widespread cutaneous and mucosal surfaces. Although postsurgical pemphigus is trauma related, it must be distinguished from posttraumatic pemphigus, which is associated with blunt physical injury rather than surgical intervention. We present the case of a49-year-old woman who developed postsurgical pemphigus beginning at the scar of aprior thyroidectomy. She achieved partial clinical improvement with systemic therapy consisting of methylprednisolone and azathioprine.

Single amino acid substitutions modulate the function of α9α10 nicotinic acetylcholine receptor.

Clinical Presentations of Pemphigus Vulgaris in Patients with Skin of Color: A Literature Review

Recurrent Pemphigus Vulgaris with Isolated Nail Involvement.

Introduction Autoimmune bullous diseases (AIBDs), comprising pemphigoid and pemphigus diseases, have seen limited therapeutic advances beyond rituximab for pemphigus vulgaris. As novel therapies are evaluated in clinical trials, well-defined, uniform and relevant outcomes with patient involvement are essential. To date, however, patient-reported outcomes remain underrepresented, leaving uncertainty about whether trial results genuinely reflect patients' expectations. This study examines perspectives of patients with AIBD on treatment outcomes and priorities to ensure that future research focuses on what matters most to them. Methods A cross-sectional study was conducted among Dutch patients with AIBD between October 2023 and January 2024, using a self-developed questionnaire with both closed- and open-ended questions to assess patient perspectives on treatment outcomes and priorities, key factors in choosing a treatment, and indicators of treatment success. Results Regarding skin and/or mucous membrane complaints, 'the formation of new blisters and wounds' emerged as the most important complaint a treatment should address for both pemphigoid (43%) and pemphigus (86%) patients. In open-ended questions, patients with pemphigoid most frequently prioritized 'pruritus' (44%), while patients with pemphigus emphasized 'pain' (39%). Most important concerns regarding physical and daily functioning were 'vision problems' (20%), 'sleep disturbances' (20%), and 'self-care difficulties' (23%) for patients with pemphigoid, whereas patients with pemphigus most commonly cited 'eating and/or swallowing difficulties' (57%) and 'daily activity limitations' (41%). Regarding emotional/psychological functioning, both subgroups prioritized 'anxiety and/or worry' as most important concern (pemphigoid: 28%, pemphigus: 43%). Side effects were identified as the most important factor in choosing a treatment (pemphigoid: 41%, pemphigus: 39%). The absence of one or more symptoms and clinical signs (i.e., 'no blisters') was mentioned as the most important indicator of treatment success (pemphigoid: 88%, pemphigus: 91%), although minimal clinical signs (i.e., 'minimal blisters') were also considered acceptable (pemphigoid: 25%, pemphigus: 13%). Conclusion Patients with pemphigoid and pemphigus exhibit some distinct treatment priorities, reflecting their distinct pathomechanisms. Nonetheless, both subgroups consistently prioritize not only the resolution of disease-specific clinical signs but also preservation of physical and psychological well-being, underscoring the need for more holistic and patient-centred outcome measurement to ensure the establishment of meaningful, AIBD subgroup specific treatment outcomes.

This study was performed to retrospectively evaluate the efficacy of oclacitinib (OC) (Apoquel; Zoetis) as a treatment option for pemphigus foliaceus (PF), pemphigus vulgaris (PV) and mucous membrane pemphigoid (MMP). To determine if OC can reduce or replace the corticosteroid use in dogs with PF, PV and MMP. There were no animal subjects. Multicentre retrospective study reviewing medical records from two institutions for dogs diagnosed with PF, PV or MMP and prescribed OC between 2014 and 2025. Twenty-one dogs diagnosed with PF, PV or MMP via histopathological results were included. OC alone was effective in eight of 18 PF dogs at a median dose of 0.65 mg/kg/day per os (range 0.5-1.9 mg/kg/day p.o.). Five dogs reached clinical remission, and three reached partial remission. One PV dog and the MMP dog each reached clinical remission with OC alone at 0.7 mg/kg/day and 0.24 mg/kg every other day, respectively. OC was a corticosteroid-sparing agent or adjunctive therapy in seven of 18 PF dogs at a median dose of 0.6 mg/kg/day (range 0.4-2.4 mg/kg/day). One PV dog reached partial remission at OC 1.9 mg/kg/day and prednisone 1.8 mg/kg/day yet died from pancreatitis. OC was ineffective in three of 18 PF dogs at a median dose of 1.0 mg/kg/day p.o. (range 0.9-1.2 mg/kg/day p.o.). Statistical significance was not analysed. OC is an effective sole therapeutic agent or adjunctive therapy in a subset of dogs with PF, PV or MMP. The long-term safety of higher doses of OC is unknown.

Nature's Bandage: A Memorable Rescue of Severe Pemphigus Vulgaris in a Resource-Limited Setting.

Pemphigus vulgaris is a low-prevalence autoimmune disorder characterized by vesiculobullous lesions affecting the skin and mucous membranes. Lesions in the oral mucosa can be the initial manifestations of the disease and highlight the importance of the dentist in early diagnosis. The objective of this study is to report a clinical case of pemphigus vulgaris with oral lesions in a 44-year-old female patient with no comorbidities. Intraoral physical examination revealed ulcerated lesions throughout the oral cavity, accompanied by bullous lesions, ulcerations, and crusts on the skin. The patient reported having had the lesions for four months, with no conclusive diagnosis. These lesions made eating difficult and resulted in marked weight loss and the need for hospitalization. During hospitalization, the diagnosis was established by the medical and dental team based on clinical characteristics and medical history, followed by histopathological confirmation. Oral lesions were treated with 0.12% chlorhexidine digluconate mouthwash and laser photobiomodulation, combined with systemic corticosteroid therapy, resulting in significant remission. Therefore, dentists' knowledge of the clinical and histopathological characteristics of pemphigus vulgaris is essential for early diagnosis and effective treatment, promoting patient health and quality of life. Further studies should be conducted to optimize management strategies for oral lesions in patients with pemphigus vulgaris.

ABSTRACT Pemphigus vulgaris (PV), a chronic autoimmune blistering disorder, frequently affects highly visible regions such as the face, scalp, and upper body, potentially altering body image and increasing social appearance anxiety (SAA). The psychosocial pathways linking lesion visibility and localization to SAA, however, remain insufficiently examined. This analytical cross-sectional case�control study compared SAA levels between 150 PV patients with visible lesions and 150 age- and sex-matched controls, and explored associations between SAA and illness perception, anxiety, depression, self-esteem, and dermatology-specific quality of life. Participants completed the Social Appearance Anxiety Scale (SAAS), Hospital Anxiety and Depression Scale (HADS), Dermatology Life Quality Index (DLQI), Brief Illness Perception Questionnaire (B-IPQ), Rosenberg Self-Esteem Scale (RSES), and a Visual Analog Scale (VAS) for perceived severity. Group comparisons, Pearson correlations, one-way ANOVA by lesion visibility and location, and moderation analysis (PROCESS Model 1: HADS-A � VAS ? SAAS) were performed. PV patients demonstrated significantly higher SAA than controls (55.8?�?10.2 vs. 21.3?�?8.8; p?0.001). Within patients, SAA correlated positively with HADS-A, DLQI, and B-IPQ, and negatively with self-esteem. General anxiety moderated the relationship between perceived severity and SAA (interaction 0.18, p=0.006), indicating greater distress among highly anxious individuals. Lesion visibility showed a clear gradient, with face, scalp, and neck lesions producing the highest SAA (ANOVA F(3,146) = 8.02, p?0.001). Findings highlight lesion visibility and localization as key determinants of SAA in PV and suggest that integrating psychological screening into dermatologic care may help address elevated appearance-related distress.

Background: Pemphigus diseases are rare autoimmune blistering disorders mediated by pathogenic autoantibodies directed mainly against desmoglein 1 and desmoglein 3. Although most cases are considered idiopathic, external triggers that can disrupt immune tolerance have been described. Vaccination has been discussed as a potential precipitating factor in autoimmune skin diseases. However, the relationship between vaccination and the induction of pemphigus-related autoantibodies has not been comprehensively summarized. Methods: We conducted a narrative review of all available studies published in the last 25 years identified through medical databases, excluding studies on COVID-19 vaccinations. Reports describing either new-onset pemphigus or exacerbation of preexisting pemphigus with a temporal association to vaccination were included. Clinical characteristics, vaccine type, latency period, direct immunofluorescence findings, and ELISA results for desmoglein autoantibodies were analyzed. In addition, we present our own clinical-laboratory experience illustrating this issue. Results: The current evidence consists predominantly of case reports and small case series. Published cases describe pemphigus vulgaris and pemphigus foliaceus occurring after vaccinations against influenza, hepatitis B, tetanus, diphtheria, pertussis, rabies, and other routinely administered immunizations. The latency period most often ranged from several days to a few weeks. Immunopathological findings were consistent with classical pemphigus diseases, including intercellular IgG deposits in the epidermis and circulating autoantibodies against desmoglein 1 and/or desmoglein 3. Our patient was a 78-year-old woman who developed cutaneous form of pemphigus vulgaris, diagnosed with direct immunofluorescence (DIF) and multiplex ELISA, 10 days after diphtheria-tetanus-pertussis vaccination. The patient had a positive family history of autoimmune blistering disease, namely mucous membrane pemphigoid. Conclusions: Based on the currently available evidence, a direct causal relationship between vaccination and pemphigus diseases cannot be established. Nevertheless, accumulated clinical and serological observations suggest that vaccination may act as a triggering factor in genetically or immunologically predisposed individuals, possibly by amplifying pre-existing subclinical autoreactive immune responses. Further population-based and mechanistic studies are required to clarify this association, while the overall benefits of vaccination remain substantial.

Skin diseases frequently coexist with other disorders, such as metabolic syndrome, diabetes mellitus, depression, psoriatic arthritis, and cardiovascular disease. Altered levels of distinct chemokines, like CCL5/RANTES, CXCL12/SDF-1a, CCL7/MCP-3, CCL2/MCP-1, CXCL1/GROa, and the eotaxin family, contribute to the development and/or exacerbation of inflammation, which is a common feature of numerous skin diseases as well as metabolic syndrome. The pathological and molecular connections between chronic inflammatory skin diseases and metabolic syndrome are increasingly recognized as being driven by shared inflammatory pathways, oxidative stress, and adipokine dysregulation. While systemic inflammation acts as a common thread, the precise mechanisms for some conditions remain partially understood. Nevertheless, the exact pathological and molecular connections between skin diseases (i.e., psoriasis, atopic dermatitis, pemphigus vulgaris, acute and chronic spontaneous urticaria, bullous pemphigoid, squamous cell carcinoma, alopecia areata, systemic sclerosis, discoid lupus erythematosus, diffuse large B-cell lymphoma) and metabolic syndrome are not yet fully understood. This narrative review summarizes the robust association between various chronic inflammatory skin diseases and metabolic syndrome in the context of pro-inflammatory chemokines.

This study evaluated the CD4+ T-cell role in mediating post-Rituximab Pemphigus vulgaris (PV) relapse, comparing CD4+ count and CD4+/CD20+ ratio between patients who achieved remission and those who relapsed. The clinical course of 27 PV patients treated with Rituximab was evaluated after a 32-month median follow-up. CD4+ and CD20+ counts and CD4+/CD20+ ratio were longitudinally collected at treatment start date (T0), at 2-month intervals after Rituximab, until B-cell repopulation, at B-cell repopulation, at 6-, 12-, and 24-month intervals after repopulation, and at the end of follow-up or at relapse. Patients were administered Rituximab as adjuvant therapy: 16 (59%) relapsed while 11 (41%) achieved clinical remission. Higher CD4+ count (p = 0.02*) and CD4+/CD20+ ratio (p = 0.004**) were found at B-cell repopulation in patients experiencing remission. Moreover, a significant difference (p = 0.002**) in post-repopulation CD4+ T-cell course was found between groups, with patients in clinical remission reporting a mean decrease of 233.5 cells/μL during follow-up and relapsing patients experiencing a mean increase of 539.4 cells/μL and reaching the maximum CD4+ value at relapse. Lower CD4+ T-cell value at repopulation and increasing post-repopulation CD4+ T-cell count were predictive of disease relapse suggesting a time-dependent role of CD4+ T cells in post-Rituximab PV reactivation.

Deep laryngeal involvement occurs in 10% to 40% of patients with pemphigus vulgaris and can cause life-threatening airway complications. However, fiber-optic laryngoscopy-the standard detection method-is invasive and causes patient discomfort. Evidence-based criteria for determining which patients require laryngoscopic examination are lacking. To develop and internally validate a clinical prediction model for deep laryngeal involvement in patients with pemphigus vulgaris. Retrospective cohort study of consecutive patients with pemphigus vulgaris evaluated at Rabin Medical Center, a tertiary dermatology referral center in Israel, between January 2015 and December 2022. All patients had a confirmed pemphigus vulgaris diagnosis based on clinical presentation, histopathology, and direct immunofluorescence as well as complete laryngoscopic examination data. Data analysis was performed from January to November 2024. The primary outcome was deep laryngeal involvement confirmed by flexible fiber-optic laryngoscopy. A prediction model was developed using Firth penalized logistic regression with multiple imputation for missing data and bootstrap validation for internal validation. Among 247 patients with pemphigus vulgaris (mean [SD] age, 61.5 [15.7] years; 135 [54.7%] female), 49 (19.8%) had deep laryngeal involvement confirmed by laryngoscopy. Three clinical predictors were identified: hoarseness (odds ratio [OR], 2.50 [95% CI, 1.10-5.69]), dysphagia (OR, 6.22 [95% CI, 2.78-13.92]), and Pemphigus Disease Area Index score with a significant sex interaction (P = .03). A simplified scoring system stratified patients into low-risk (0-1 points; 0% observed involvement), intermediate-risk (2-3 points; 15.3%), and high-risk (≥4 points; 66.7%) categories. The model achieved an area under the receiver operating characteristic curve of 0.78 (95% CI, 0.71-0.84), with a negative predictive value of 92.6%. In this study, the clinical prediction model using routinely assessed parameters achieved good discrimination and high negative predictive value. If externally validated, this tool may help identify low-risk patients who can safely defer laryngoscopy while prioritizing higher-risk patients for evaluation.

Pemphigus vulgaris (PV) is an autoimmune blistering disorder that is caused by the loss of desmosomal cell-cell adhesion, initiated by the binding of IgG antibodies against the desmosomal components desmoglein (DSG)1 and DSG3. DSG3-reactive CD4+ T helper (Th) cells, in particular follicular Th cells, play a central role in autoantibody production by DSG3-specific B cells. In this study, we challenged the concept that distinct DSG3-reactive CD4+ T-cell subsets are critical in PV pathogenesis, utilizing phenotypical and functional state-of-the-art ex vivo assays. Using HLA class II-tetramer staining and activation-induced marker assay, we found an overall increase of circulating follicular Th and peripheral Th cells, another subset with the capacity to promote autoantibody production by B cells, in patients with PV compared with those in healthy controls. Within the DSG3-reactive T-cell population, Th17/circulating follicular Th17/peripheral Th17 cells represented the dominant subset, followed by a Th2/circulating follicular Th2/peripheral Th2-like cell signature. Upon ex vivo stimulation with overlapping peptides of DSG3, we found both an activated IL-17-producing CD4+ T-cell subset and an increased frequency of CD4+ T cells producing IL-21 in active PV. In summary, our findings demonstrate a preponderance of autoreactive type 17 and type 2 T-cell subsets in PV, which may serve as therapeutic targets.

Radiotherapy-induced pemphigus vulgaris: a challenging case of extensive mucocutaneous ulcerations and literature review.

Boom or Bust: Clinical Trials in Pemphigus and Other B-Cell-Mediated Autoimmune Diseases.

Pemphigus vulgaris (PV) is a rare, chronic autoimmune blistering disorder affecting the skin and mucous membranes. It is characterized by the production of IgG autoantibodies against desmoglein-1 and desmoglein-3, which are essential components of desmosomes responsible for cell-to-cell adhesion in the epidermis. Loss of adhesion between keratinocytes leads to acantholysis and the formation of painful blisters and erosions, commonly beginning in the oral cavity before involving the skin. PV most frequently affects middle-aged individuals and shows higher prevalence among certain ethnic groups, including those of Mediterranean and Ashkenazi Jewish descent. Diagnosis is confirmed by clinical features, histopathology, and direct immunofluorescence studies. Early diagnosis and prompt treatment with systemic corticosteroids and immunosuppressive agents, such as azathioprine or rituximab, significantly reduce morbidity and mortality. Although once associated with high fatality rates, advances in immunotherapy have markedly improved patient prognosis.

Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are rare autoimmune bullous diseases (AIBDs) of unknown etiology. Genetic and environmental factors have been described to trigger autoimmunity. The latter include exposure to pesticides and industrial pollutants. To investigate the incidence of AIBDs in Liguria (Northern Italy) and to assess the association between exposure to pesticides and working in agriculture and AIBDs. We conducted a retrospective observational study on the incidence of AIBDs in the decade 2014-2024 in the Liguria region. Moreover, we conducted a retrospective case-control study on patients in the province of Imperia, where the highest incidence of AIBDs was found, using a questionnaire to assess exposure to environmental and occupational risk factors. The mean annual incidence of AIBDs (PV 0.026/1000 inhabitants and BP 0.102/1000 inhabitants) in Liguria was higher than the European incidence values. In Imperia the incidence of BP was significantly higher than the Ligurian incidence (p=0.0015). The retrospective case-control study found that the exposure in domestic settings to pesticides and having worked in agriculture were associated to higher risk of developing PV. The present study supports and suggests the association between pesticides exposure and the development of PV.

Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease characterized by acantholysis (the loss of cell-cell adhesion of keratinocytes) and the formation of non-healing suprabasal intraepidermal blisters. The progression of keratinocyte acantholysis in PV is complex. Interleukin-37 (IL-37), which functions through receptor binding, exerts a protective role in PV. However, the specific receptor mediating the effect of IL-37 in PV and the underlying mechanisms remain unclear. The present study found elevated levels of IL-37, a natural suppressor of innate inflammatory and immune responses, in patients with PV. IL-37 treatment directly suppressed both acantholysis and apoptosis in keratinocytes. Mechanistic investigations using co-immunoprecipitation revealed that IL-37 binds to interleukin-1 receptor 8 (IL-1R8). Knockdown of IL-1R8 (or IL-18Rα) abolished the inhibitory effects of IL-37 on acantholysis and apoptosis. Furthermore, the IL-37/IL-1R8 complex suppressed epidermal growth factor receptor (EGFR) signaling, and reduced the expression of TNF-alpha-converting enzyme (ADAM17). Activation of EGFR using specific agonists reversed the IL-37-mediated reduction in acantholysis and apoptosis in HaCaT cells. In conclusion, IL-37 treatment markedly attenuated keratinocyte dissociation and apoptosis in PV through the IL-1R8/ADAM17/EGFR pathway. These findings provide novel mechanistic insights into the immunoregulatory functions of IL-37.