Autoimmune Blistering Disease Research Articles

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

The Importance of Patient-Focused Drug Development in Pemphigus and Pemphigoid

Bacteriological profile of skin infections in hospitalized patients with pemphigus: A retrospective study of 92 cases

Pemphigus is a rare autoimmune blistering disease affecting the skin and mucosa. Infections are the most frequent complications. One or more bacterial species can be incriminated. The aim of our study was to establish the bacteriological profile of skin infections in patients with pemphigus. This is a retrospective descriptive study spread over a period of 3 years and a half (March 2019 - September 2022) having included patients hospitalized in the dermatology department of the Hassan II University Hospital of Fez for an outbreak of pemphigus with signs of skin infection. During the study period, 92 pus samples from patients with clinically infected pemphigus were received at the microbiology laboratory of the Hassan II University Hospital of Fez. 68% of them were positive with a bacteriologically confirmed infection. The average age of the patients was 53.2 years (20 to 89 years). The sex ratio (female/male) was 1.5. The medical history revealed diabetes in 10 patients (11%). Among the patients included in the study, 16% had at least one infection during their course and 21% of the samples taken were polymicrobial. Most bacterial skin infections detected in our patients were due to Staphylococcus aureus (43% of cases). Our study allowed us to confirm the predisposition to infections in patients with pemphigus. This prompts us to insist on the importance of hygienic care, early diagnosis and treatment of any type of infection.

Mouse models of pemphigus: valuable tools to investigate pathomechanisms and novel therapeutic interventions.

Autoimmune blistering diseases (AIBD) are paradigms of autoantibody-mediated organ-specific autoimmune disorders that involve skin and/or mucous membranes. Compared to other autoimmune diseases, the pathogenicity of autoantibodies in AIBD is relatively well described. Pemphigus is a potentially lethal autoantibody driven autoimmune disorder with a strong HLA class II association. It is mainly characterized by IgG against the desmosomal adhesion molecules desmoglein 3 (Dsg3) and Dsg1. Several murine pemphigus models were developed subsequently, each allowing the analysis of a characteristic feature, such as pathogenic IgG or Dsg3-specific T or B cells. Thus, the models can be employed to preclinically evaluate potentially novel therapies. We here thoroughly summarize past and recent efforts in developing and utilizing pemphigus mouse models for pathomechanistic investigation and therapeutic interventions.

Worldwide epidemiologic factors in pemphigus vulgaris and bullous pemphigoid.

Autoimmune blistering diseases such as bullous pemphigoid (BP) and pemphigus vulgaris (PV) are complex, multifactorial, and polygenic diseases, whose exact pathogenesis is difficult to pinpoint. Research aimed at elucidating the associated epidemiologic risk factors of these two diseases has been hampered by their rare disease status. Further, a lack of centralization and standardization of available data makes the practical application of this information challenging. In order to collate and clarify the available literature we comprehensively reviewed 61 PV articles from 37 different countries and 35 BP articles from 16 different countries addressing a range of disease relevant clinical parameters including age of onset, sex, incidence, prevalence, and HLA allele association. The reported incidence of PV ranged from 0.098 to 5 patients per 100,000 people, while BP ranged from 0.21 to 7.63 patients per 100,000. Prevalence of PV ranged from 0.38 to 30 per 100,000 people and BP ranged from 1.46 to 47.99 per 100,000. The mean age of onset in patients ranged from 36.5 to 71 years for PV and 64 to 82.6 years for BP. Female-to-male ratios ranged from 0.46 to 4.4 in PV and 1.01 to 5.1 in BP. Our analysis provides support for the reported linkage disequilibrium of HLA DRB1*0402 (an allele previously shown to be associated with PV) and DQB1*0302 alleles in Europe, North America, and South America. Our data also highlight that HLA DQB1*0503 (also known to be associated with PV) appears in linkage disequilibrium with DRB1*1404 and DRB1*1401, mainly in Europe, the Middle East, and Asian countries. The HLA DRB1*0804 allele was only associated with PV in patients of Brazilian and Egyptian descent. Only two HLA alleles were reported as associated with BP more than twice in our review, DQB1*0301 and DQA1*0505. Collectively, our findings provide detailed insights into the variation of disease parameters relevant to PV and BP that can be expected to inform future work aimed at unraveling the complex pathogenesis of these conditions across the globe.

Pruritic crusted lesions in an 89‐year‐old woman

Pruritic crusted lesions in an 89‐year‐old woman

Retrospective analysis of the long-term therapeutic effectiveness and safety profile of rituximab in the treatment of mucous membrane pemphigoid in a German university center between 2008 and 2019.

The B-cell-depleting anti-CD20 antibody rituximab (RTX) is often used as an adjuvant drug for the treatment of refractory cases of mucous membrane pemphigoid (MMP). This study aims to determine the therapeutic effectiveness and the safety profile of RTX in MMP. The medical records of all cases of MMP treated with RTX between 2008 and 2019 in our university medical center located in northern Germany, which specialized in autoimmune blistering skin diseases, were retrieved and systemically analyzed for treatment responses and potential adverse events over a median period of 27 months. We identified 18 MMP patients who received at least one cycle of RTX to treat MMP. RTX was always used as an adjuvant treatment, and its application did not change concomitant treatments. Under treatment with RTX, 67% of the patients achieved an improvement in their disease activity within 6 months. This was also reflected in a statistically significant reduction in the Mucous Membrane Pemphigoid Disease Index (MMPDAI) activity score. The frequency of infections under RTX treatment increased only slightly. The use of RTX is associated with an attenuation of MMP in a large proportion of MMP patients in our study. At the same time, its application was not found to further increase the susceptibility of the most strongly immunocompromised population of MMP patients to opportunistic infections. Collectively, our results suggest that the potential benefits of RTX outweigh its risks in patients with refractory MMP.

390 Examining the risk factors for worsened glucocorticoid morbidity in a prospective, multicentre, international study of patients with autoimmune blistering diseases

390 Examining the risk factors for worsened glucocorticoid morbidity in a prospective, multicentre, international study of patients with autoimmune blistering diseases

081 NUDT15 variants among Japanese patients with autoimmune blistering diseases: A single-center retrospective observational study

081 NUDT15 variants among Japanese patients with autoimmune blistering diseases: A single-center retrospective observational study

Erosive and ulcerative stomatitis in dogs and cats: which immune-mediated diseases to consider?

Immune-mediated and autoimmune diseases of the skin often present with oral cavity involvement. Autoimmune subepidermal blistering diseases and pemphigus vulgaris are classic examples. While the primary lesions (vesicles and bullae) are relatively specific, these fragile lesions evolve rapidly into erosions and ulcers, which are lesion types that overlap with many diseases. Furthermore, some immune-mediated diseases such as severe adverse drug reactions, lupus diseases, canine uveodermatological syndrome, and vasculitis, may or may not involve the oral cavity, and often nonoral clinical manifestations are more diagnostic. In these situations, disease knowledge combined with signalment, lesion distribution, and history help to narrow the differentials. Surgical biopsy is required for confirmation in most diseases, while immunosuppressive treatments most typically involve glucocorticoids with or without nonsteroidal immunosuppressants.

848 Generality and heterogeneity of HLA associations in autoimmune blistering disease spectrum

848 Generality and heterogeneity of HLA associations in autoimmune blistering disease spectrum

Pemphigus scoring systems and their validation studies – A review of the literature

Pemphigus is a rare autoimmune blistering disease that affects the skin and mucous membranes. Despite recent advances in treatment, pemphigus is associated with high patient mortality and has a significantly negative impact on patients’ quality of life and mental health. Validated scoring systems to accurately measure pemphigus severity are vital for the monitoring of disease activity, evaluation of treatment efficacy and trialing, comparison and introduction of new treatments. This article reviews the existing scoring systems for pemphigus and their validation studies and proposes a future area of research regarding global assessments for simplistic scoring of pemphigus severity.

Bullous Pemphigoid in Older Adults Treated with DPP4i: A Case Series

Bullous pemphigoid (BP) is a rare autoimmune subepithelial blistering disease affecting mostly older adults [1]. Studies have calculated an annual incidence ranging from 2.4% to 21.7% per million population.

Research progress of omalizumab in the treatment of bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune blistering disease associated with anti-BP180 and anti-BP230 antibodies. The pathogenic action mechanism of immunoglobulin E (IgE) antibodies in BP has been studied since the 1970s, and IgE antibodies have gradually been confirmed as being important in BP; therefore, anti-IgE therapy may be a new option for the treatment of BP. Omalizumab, as an IgE monoclonal antibody, has been increasingly used clinically to treat BP in recent years. Here, we collected 35 papers investigating omalizumab for BP treatment in a total of 83 patients, and the vast majority of patients showed varying degrees of improvement after treatment, except for a small number of patients with poor clinical outcomes. The patients were then divided into three groups according to dosing frequency and number of doses. Statistical analysis indicated that dosing frequency had little effect on clinical efficacy. While the groups with different numbers of doses were evaluated, the results concluded that clinical efficacy was affected by the number of doses, but there was no positive correlation between the number of doses and clinical efficacy.

The genetic basis of pemphigus vulgaris

AbstractThe severe autoimmune blistering disease pemphigus vulgaris (PV) is most probably mainly due to autoantibodies directed against desmosomal components of the epithelium, disrupting cell‐cell adhesion. The precise mechanisms underlying the development of the disease are still unknown, and immunosuppressive medications such as corticosteroids, which are linked to potentially serious adverse effects, are still the mainstay of treatment. Ethnic susceptibility and familial incidence hint to a genetic component to the pathophysiology of PV, which, if identified, could further improve our understanding of PV pathogenesis and lead to the discovery of new therapeutic targets for this potentially fatal condition. In this article, we review the evidence supporting a genetic component in PV and discuss the clinical and therapeutic implications of these discoveries.

Nail abnormalities in subepidermal blistering diseases: a cross-sectional study.

Nail involvement in subepidermal autoimmune blistering diseases (SEABD) is not common. Although these changes can be transient, permanent changes can also occur. This study addresses nail involvement manifestations and their associated factors in patients with SEABD. From March 2020 to March 2021, we enrolled 56 patients with SEABD who were being examined at a tertiary skin hospital and checked their nail changes. We investigated the association between the SEABD subtypes and treatments that patients were receiving and the nail abnormalities. Additional factors including age, gender, duration since diagnosis, presence of mucosal involvement, and anti-bp230 and anti-bp180 IgG antibody quantitative levels (in those patients with bullous pemphigoid) were analyzed. The most common nail abnormalities were ridging, onycholysis, and onychoschizia. We observed a lower prevalence of onycholysis in EBA, a lower prevalence of periungual bullae in MMP, and a higher prevalence of scarring loss in EBA. Rituximab and dapsone were effective in preventing onycholysis as well as prednisolone in preventing subungual hematoma. Multiple lesions were found to be more common in the foot digits including great toes, probably because of higher exposure to trauma. In summary, in patients with SEABD and concomitant nail involvement, the underlying disease control, proper treatment, and avoidance of trauma may be helpful.

Adaptive and innate immune pathogenesis of bullous pemphigoid: A review.

Bullous pemphigoid (BP) is an autoimmune blistering disease that primarily affects elderly individuals. The presentation of BP is heterogeneous, typically manifesting as microscopic subepidermal separation with a mixed inflammatory infiltrate. The mechanism of pemphigoid development is unclear. B cells play a major role in pathogenic autoantibody production, and T cells, type II inflammatory cytokines, eosinophils, mast cells, neutrophils, and keratinocytes are also implicated in the pathogenesis of BP. Here, we review the roles of and crosstalk between innate and adaptive immune cells in BP.

Pemphigus foliaceus: A rare blistering skin lesion

Pemphigus foliaceus is a benign variety of pemphigus group. It is a rare autoimmune blistering disease that affects the skin without mucosal involvement. It can present in endemic and sporadic form; whereby endemic form is common in Brazil and Tunisia, known as fogo selvagem. There was no previous case reported in Malaysia. We report a case of a 43-year-old man, who presented with generalized extensive blisters and vesicles that form crust and scale. The full evaluation established the diagnosis of pemphigus foliaceous. Delay in diagnosis can lead to poor outcomes. Primary care practitioners should be aware of this since the condition can mimic eczema, specifically photodermatitis.

Recurrent hemorrhagic bullae of the oral mucosa

Recurrent hemorrhagic bullae of the oral mucosa

The Role of Non-Neuronal Acetylcholine in the Autoimmune Blistering Disease Pemphigus Vulgaris

The importance of acetylcholine (ACh) in keratinocyte adhesion and acantholysis has been investigated over the last three decades, particularly in the pathophysiology of autoimmune blistering dermatoses. Pemphigus vulgaris (PV) is an autoimmune blistering skin disease where autoantibody-mediated suprabasilar intraepidermal splitting causes flaccid blisters and non-healing erosions of the oral mucosa and sometimes also of the skin. Historically, acantholysis in PV was thought to be driven by anti-desmoglein (Dsg) antibodies. Herein, we describe the role of autoantibodies against keratinocyte muscarinic and nicotinic acetylcholine receptors, as well as the annexin-like molecule pemphaxin that also binds ACh, in the immunopathogenesis of PV. The identification of targets in this disease is important, as they may lead to novel diagnostic and therapeutic options in the future for this potentially deadly disease.

Lymphocyte-predominant lesional inflammatory infiltrates of the skin are associated with mucosal-dominant phenotype in pemphigus.

Pemphigus is a potentially life-threatening autoimmune blistering disease. To date, studies assessing the association of histopathology with clinical phenotype are lacking. We sought to evaluate the main histopathologic findings and, also, the potential links between cutaneous inflammatory infiltrates and clinical characteristics in pemphigus. We conducted a retrospective cohort study in patients diagnosed with pemphigus vulgaris (PV) and pemphigus foliaceus (PF) in a referral center for autoimmune blistering diseases. A total of 124 patients were included in the study (97 had PV and 27 had PF). On biopsy specimens, PV was more frequently associated with the "row of tombstones" feature (36.1% vs. 11.1%, p=0.013), and PF was associated with acanthosis (44.4% vs. 23.7%, p=0.034). Acantholysis was found in the upper half of the epidermis in PF (96.3% vs. 5.15%, p < 0.001), as opposed to the lower half in PV (75.2% vs. 0%, p=0.002). Patients with lymphocyte-predominant inflammatory infiltrates in lesional skin specimens presented with a higher frequency of the mucosal-dominant phenotype (25.5% vs. 9.1%, p=0.014), higher-density cellular infiltrate (100% vs. 41.6%, p < 0.001), and more frequent acantholytic cells (42.6% vs. 23.4%, p=0.025). Neutrophil-predominant infiltrates in specimens from lesional skin were linked to a milder disease based on median Pemphigus Disease Area Index (38.9% vs. 13.2%, p=0.036) and Autoimmune Bullous Skin Disorder Intensity Score (20.2 vs. 36.3, p=0.019), while eosinophil-predominant inflammatory infiltrates were more often associated with eosinophilic spongiosis (100% vs. 23.1%, p=0.014). Lymphocyte-predominant infiltrates in lesional skin specimens of pemphigus patients predict a mucosal-dominant phenotype, while neutrophil-predominant infiltrates are associated with a milder disease.