Search Results (68)

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) represent the most prevalent conditions among autoimmune bullous skin diseases, considered a major cause of severe morbidity and, in certain cases, mortality. The hallmark of the two diseases is the presence of autoantibodies directed against proteins located in the basement membrane of the skin, which determines the formation of blisters. In recent years, interest in the role of microbiota in relation to health-disease status has progressively increased. In particular, based on the gut–skin axis, accumulating evidence has emerged on the potential association between the composition and diversity of microbial communities in the gut, skin, and even in the oral cavity and the risk of developing BP and PV. Dysbiosis, characterized by a generally higher relative abundance of Firmicutes and a depletion of probiotics/beneficial species, might contribute to the pathogenesis of both diseases. Despite the still limited number of studies and the need for further large-scale multicenter studies, the knowledge gathered so far is suggestive of a novel modifiable risk factor representing a potential target for adjuvant treatments of these disabling and life-threatening conditions. Full article

Oral Lichen Planus (OLP) is a chronic autoimmune disease with potential overlap with Pemphigus Vulgaris (PV), particularly in erosive forms. Desmoglein 1 and 3 are transmembrane glycoproteins of desmosomes, typically involved in PV. This scoping review aims to evaluate the presence and potential pathogenetic role of anti-desmoglein 1 (Dsg1) and anti-desmoglein 3 (Dsg3) antibodies in OLP. A literature search was conducted on MEDLINE/PubMed, Ovid, and Scopus up to April 2025. Human studies reporting OLP patients with anti-Dsg1 and/or anti-Dsg3 antibodies were included. Data from 11 studies were analyzed by diagnosis, age/sex, oral site involvement, immunofluorescence, and ELISA testing. Erosive OLP was most frequently associated with anti-Dsg1/Dsg3 positivity, mainly in women aged 40–60. Immunofluorescence was positive in some cases, while the ELISA test almost consistently detected anti-Dsg1 and Dsg3 antibodies. However, in many instances, antibody titers did not reach the threshold value, despite the presence being detectable. This finding suggests that anti-Dsg1/Dsg3 antibodies may represent epiphenomena of chronic inflammation in erosive OLP, indicating an immune-serological overlap with PV but lacking direct pathogenicity. Furthermore, the role of Dsg3 in oral squamous cell carcinoma, by promoting enzymes that degrade the extracellular matrix and enhance tumor invasiveness, highlights the complex functions of desmogleins beyond autoimmunity. Full article

Background/Objectives: Mycophenolate mofetil (MMF) has emerged as a valuable immunosuppressive agent used in the management of oral mucocutaneous diseases, particularly in autoimmune and inflammatory conditions, such as pemphigus vulgaris (PV), oral lichen planus (OLP), mucous membrane pemphigoid (MMP), systemic lupus erythematosus (SLE), erythema multiforme (EM) and recurrent aphthous stomatitis (RAS). This review consolidates the current evidence regarding MMF’s efficacy, safety and clinical applications across these conditions. Methods: A comprehensive review of literature was performed, focusing on the mechanism of action, dosing strategies, therapeutic outcomes and adverse effects associated with MMF therapy in oral mucocutaneous diseases. The potential of therapeutic drug monitoring (TDM) in optimizing MMF therapy and minimizing adverse effects was also explored. Results: The review demonstrates that MMF is effective in inducing disease remission in up to 80% of patients with PV, with notable steroid-sparing effects. In OLP, MMF provided significant clinical improvement, especially in patients with severe and refractory forms of the disease. For MMP, MMF showed an 89% response rate, particularly when combined with corticosteroids, though gastrointestinal side effects were noted in some patients. In SLE, MMF was effective in managing both renal and non-renal manifestations, with favorable remission rates observed in patients receiving MMF therapy. For EM, MMF’s effectiveness was limited, with only a small number of patients responding to therapy. In RAS, there is limited evidence of MMF’s efficacy, with only partial improvement in severe cases reported. MMF is a promising immunomodulatory therapy for oral mucocutaneous diseases, particularly in reducing corticosteroid dependence and improving patient outcomes. However, the variability in the study designs, dosages and patient populations complicates the generalization of these findings. Conclusions: There is a pressing need for randomized controlled trials to validate MMF’s efficacy and long-term safety across all disease categories. The integration of therapeutic drug monitoring (TDM) shows potential for improving disease control and minimizing adverse effects, making it a key consideration for future research. Full article

Background/Objectives: Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disorder with a recognized potential for malignant transformation. While histopathological examination remains the diagnostic gold standard, mucoscopy has emerged as a valuable non-invasive tool for assessing striae patterns, vascular features, and pigmentary alterations. This study aimed to evaluate the mucoscopic characteristics of OLP across different oral mucosal sites and to compare them with other inflammatory oral conditions, assessing their diagnostic relevance. Methods: A retrospective comparative study was conducted on 106 patients, including 33 with histopathologically confirmed OLP and 73 with other inflammatory oral conditions (pemphigus vulgaris, chronic cheilitis, hyperplastic oral candidiasis, leukoplakia, squamous cell carcinoma, pachyonychia congenita, morsicatio buccarum). Mucoscopic evaluation focused on the buccal mucosa, vermilion, and lingual mucosa. Features assessed included background color, white striae patterns, vascular morphology, the presence of erosions, and other features like blunting of the lingual papillae and scales on the vermilion. Statistical analysis was carried out using SPSS 29.0. Results: Reticular striae were highly specific to OLP, particularly on the buccal mucosa (90.9%, p < 0.001). Leukoplakia-like lesions were most prevalent on the lingual mucosa and significantly associated with dotted (p = 0.027) and looped vessels (p = 0.002). Erosions correlated significantly with both dotted (p < 0.001) and linear vessels (p = 0.011), especially in lingual and vermilion lesions. In comparison, control group lesions displayed significantly more globular structures (p < 0.001), veil-like patterns (p < 0.001), and diffuse vascular distributions (p = 0.018), particularly in cheilitis and candidiasis cases. Conclusions: Mucoscopy reveals distinct site-specific patterns in OLP, supporting its role as a non-invasive diagnostic aid. Comparative analysis highlights its utility in differentiating OLP from other inflammatory oral conditions and in identifying lesions with features suggestive of malignant potential. These findings support the integration of mucoscopy into routine clinical practice and warrant further validation through larger, prospective studies. Full article

Autoimmune blistering diseases (AIBDs) involve autoantibodies targeting proteins in the epidermal/epithelial desmosome (pemphigus) or basement membrane zone (pemphigoid). Despite widespread antigen distribution, lesions exhibit a scattered involvement pattern. This study maps the frequency/severity of AIBD lesions on various body parts and investigates whether differential antigen expression contributes to specific predilection sites. We analyzed affected sites presenting blisters/erosions, erythematous/urticarial lesions, and mucosal lesions in bullous pemphigoid (BP-cohort 1, n = 65; BP-cohort 2, n = 119), pemphigus vulgaris (PV, n = 67), and pemphigus foliaceus (PF, n = 20) patients. To assess antigen expression, we conducted indirect immunofluorescence (IF) staining of 11 AIBD antigens from 13 anatomical sites of 10 body donors without AIBD. In BP, blisters/erosions and erythematous/urticarial lesions predominantly affected arms and legs, while PV/PF patients exhibited frequent involvement of buccal mucosa and back, respectively. IF staining identified significant regional differences in BP180, BP230, and integrin β4 expression, although these variations did not correlate with a higher lesion frequency/severity. Other antigens showed consistent expression across all regions. Our findings suggest that predilection sites for BP and PV/PF are largely unaffected by regional variations in antigen expression but may be influenced by factors like microbiota, mechanical stress, sunlight exposure, local immunity, or genetics. Full article

Psoriasis is a chronic inflammatory condition that is polygenic and multisystemic, impacting approximately 2–3% of the global population. The onset of this disease is influenced by an intricate interplay of genetic and environmental factors, predisposing individuals to the psoriasis phenotype. The complex pathogenesis of psoriasis contains certain key aspects found in other autoinflammatory and autoimmune dermatological diseases. Among these, vitiligo, alopecia areata, hidradenitis suppurativa, vitiligo, connective tissue diseases, bullous dermatoses, and atopic dermatitis are conditions that share overlapping immune system dysfunction, making their relationship with psoriasis particularly significant. For our research, we explored various terms including “shared”, “concomitant”, “coincident”, “overlap”, “coexist”, and “concurrent”, in relation to conditions such as “psoriasis”, “alopecia areata”, “hidradenitis suppurativa”, “atopic dermatitis”, “vitiligo”, “bullous pemphigoid”, “pemphigus vulgaris”, “lupus erythematosus”, “dermatomyositis”, and “systemic sclerosis.” Additionally, we used specific search queries like “atopic dermatitis overlapping syndrome” and “psoriasis and vitiligo concomitant disease” in the PubMed and Web of Science databases. While distinct in their clinical presentation, the skin diseases related to psoriasis may become associated, complicating diagnosis and treatment. In this narrative review, the complex pathophysiology of psoriasis is described, along with its close relationship to other skin conditions. This review provides an exhaustive description of both immunological and non-immunological pathways contributing to their development. Understanding the intricate interconnection between psoriasis and these conditions is of interest to scientists in developing novel research directions and to clinicians in providing holistic care, as managing one condition may influence the course of others. Full article

Senear–Usher syndrome, or pemphigus erythematosus (PE), is a rare autoimmune disorder characterized by the coexistence of features from both lupus erythematosus (LE) and pemphigus foliaceus (PF). We describe a 41-year-old patient initially diagnosed with cutaneous and then systemic lupus erythematosus (SLE), who after a few years developed new skin lesions: erythematous and erosive eruptions partially covered by crusts located on the trunk and flaccid blisters on the extremities. Direct immunofluorescence of perilesional skin revealed deposits of IgG in the intercellular space of the epidermis and granular deposits of C3 at the dermo–epidermal junction. Additional testing, revealing autoantibodies against the intercellular space of the epidermis, and direct immunofluorescence (DIF) examination allowed a diagnosis of pemphigus vulgaris coexisting with lupus. Further, DIF study revealed granular deposits of immunoglobulin G (IgG) in the intercellular spaces of the epidermis and granular deposits of the C3 along the basement membrane. Clinical appearance led to suspicion of Senear–Usher syndrome. in this patient. This case report explores the diagnostic challenges posed by the patient’s overlapping symptoms and immunological findings, suggesting an infrequent manifestation of Senear–Usher syndrome or a combination of SLE and pemphigus vulgaris. The case highlights the complexity of chronic inflammatory skin diseases and the need for tailored treatment approaches in such cases. Despite temporary improvement, the patient experienced relapses. We performed a descriptive literature review of the case reports of PE published in the last 24 years and prepared a summary of the characteristics, emphasizing the importance of proper recognition, clinical features, and treatment of this uncommon syndrome. Full article

The diagnostic utility of immunohistochemistry on paraffin-embedded sections in bullous disorders is useful when frozen tissue is not available. In pemphigus vulgaris and pemphigus foliaceus, an intercellular lace-like staining pattern of IgG4 on lesional tissue by immunohistochemistry has been described, with a comparable sensitivity and specificity to direct immunofluorescence on perilesional tissue. This study aimed to evaluate the staining pattern of IgG4 in non-immunobullous disorders to highlight the potential pitfalls when using this stain. In this study, we conducted a retrospective review of our institution’s database of non-immunobullous disorders where immunohistochemistry of IgG4 was performed to rule out pemphigus. We identified 27 cases where IgG4 immunohistochemistry was performed and observed intercellular IgG4 staining in some cases of Grover disease, bullous impetigo, irritated dermal hypersensitivity reaction, acantholytic actinic keratosis, and graft versus host disease. Our results indicate that the interpretation of IgG4 staining by immunohistochemistry in cutaneous acantholytic disorders should be approached with caution. Confirmation on cryosections with direct immunofluorescence study results is important in these settings. Full article

Background/Objectives: Pemphigus comprises a diverse group of disorders within the autoimmune bullous dermatoses (AIBDs) spectrum. Among these, pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are the most commonly encountered variants. Despite its rarity, this condition can pose a life-threatening risk. We aimed to assess clinical characteristics, comorbidities, medication, as well as the treatment of various types of pemphigus in pemphigus patients. Methods: We gathered data from 69 patients treated in the Department of Dermatology in the years 2016–2023. The investigation included sex, age at diagnosis, type of pemphigus, comorbidities and medications, presence of neoplasms and treatment of pemphigus, as well as enzyme-linked immunosorbent assay (ELISA) and direct immunofluorescence (DIF) results. The data were statistically analyzed with the p-value set at 0.05. Results: The study group comprised 69 patients, including 41 women and 28 men. The mean age at diagnosis was 56.89 years +/− 15.42 years. A total of 79.31% of the patients were diagnosed with PV and the following 26.09% with PF. The most common comorbidities were arterial hypertension, hypercholesterolemia, and diabetes mellitus. The dominant treatment regimen was the systemic use of glucocorticosteroids (GCSs; 90% and 94% of PV and PF patients, respectively). More than half of the patients received at least one GCS-sparing treatment, including dapsone and rituximab. We observed a significantly frequent presence of IgG deposits in DIF in patients with PF (p = 0.0217) and a subsequent correlation between the concurrent presence of IgG deposits in DIF and anti-DSG1 antibodies in ELISA testing (p = 0.0469). The combination of IgG, IgG1, IgG4, and C3 deposits was more often existent in PF patients (p = 0.0054) and the combination of IgG4 and C3 deposits in PV patients (p = 0.0339). We also found a positive correlation between the level of anti-DSG1 antibodies and the age at diagnosis (p = 0.0298). Conclusions: Patients with pemphigus are very often diagnosed with significant comorbidities and take diverse medication, which shows that the treatment of pemphigus should follow a multidisciplinary approach. Accurate analysis of the clinical condition of the patients, as well as the results of the ELISA panel or DIF, is crucial for a successful diagnostic and therapeutic process. Full article

The COVID-19 pandemic has encouraged the rapid development and licensing of vaccines against SARS-CoV-2. Currently, numerous vaccines are available on a global scale and are based on different mechanisms of action, including mRNA technology, viral vectors, inactive viruses, and subunit particles. Mass vaccination conducted worldwide has highlighted the potential development of side effects, including ones with skin involvement. This review synthesizes data from 62 manuscripts, reporting a total of 142 cases of autoimmune blistering skin diseases (AIBDs) following COVID-19 vaccination, comprising 59 cases of pemphigus and 83 cases of bullous pemphigoid. Among the 83 bullous pemphigoid cases, 78 were BP, with additional cases including 2 oral mucous membrane pemphigoid, 1 pemphigoid gestationis, 1 anti-p200 BP, and 1 dyshidrosiform BP. The mean age of affected individuals was 72 ± 12.7 years, with an average symptom onset of 11 ± 10.8 days post-vaccination. Notably, 59% of cases followed vaccination with BNT162b2 (Pfizer-BioNTech), 51.8% were new diagnoses, and 45.8% occurred after the second dose. The purpose of our review is to analyze the cases of pemphigus and bullous pemphigoid associated with COVID-19 vaccination and to investigate the pathogenetic mechanisms underlying the new development or flare-up of these diseases in association with vaccination. Our results show that the association between COVID-19 vaccines and AIBDs is a possible event. Full article

Autoimmune bullous diseases (AIBDs) are a group of conditions marked by the formation of blisters and erosions on the skin and mucous membranes. It occurs in all age groups, slightly more often affecting women. Several factors may be linked to the development of AIBDs, with nutrition being one of them. The literature mentions various food products and food ingredients acting as disease modifiers. Given the complex relationship between bullous diseases and nutrition, the current literature on AIBDs has been reviewed, with an emphasis on the influence of dietary modifications, various diets, and the nutritional consequences of these conditions. This review summarizes the role of nutrition in the pathogenesis and treatment of the following AIBDs: (i) pemphigus, (ii) bullous pemphigoid and mucous membrane pemphigoid, (iii) dermatitis herpetiformis, and (iv) epidermolysis bullosa acquisita. Several nutrients and dietary factors have been studied for their potential roles in triggering or exacerbating AIBDs. The key nutrients and their potential impacts include thiols and bulb vegetables (Allium), phenols, tannic acid, tannins, phycocyanin, isothiocyanates, all trans-retinoic acids, cinnamic acid, and walnut antigens. Many patients with ABIDs may require supplementation, particularly of vitamin D and B₃, calcium, potassium, zinc, selenium, and cobalt. In addition, various diets play an important role. A soft diet is recommended for individuals with issues in the oral cavity and/or esophagus, particularly for those who experience difficulties with biting or swallowing. This approach is commonly used in managing pemphigus. A high-protein, high-calcium diet, DASH (Dietary Approaches to Stop Hypertension), and the Mediterranean diet are utilized during long-term glucocorticoid therapy. However, in dermatitis herpetiformis it is advisable to follow a gluten-free diet and eliminate iodine from the diet. When it comes to herbal supplements, Algae (Spirulina platensis), Echinacea, and St. John’s wort (Hyperitum perforatum) enhance the ABIDs, while Cassia fistula may be recommended in the treatment of erosions in pemphigus vulgaris. Fast foods enhance the development of ABIDs. However, the pathomechanism is not yet fully understood. Future researchers should more precisely define the relationships between nutrients and nutrition and blistering diseases by also looking at, i.e., genetic predispositions, microbiome differences, or exposure to stress. Full article

Background: Ocular predominant mucous membrane pemphigoid (oMMP) is a severe subtype of autoimmune blistering disease (AIBD), which can result in scarring and vision loss. The diagnosis of oMMP is challenging as patients often have undetectable levels of circulating autoantibodies by conventional assays. Likewise, the principal autoantigen in oMMP has been an area of debate. Methods: In this preliminary experiment, we performed Phage Immunoprecipitation Sequencing (PhIP-seq) on sera from patients with oMMP, as well as non-ocular MMP, bullous pemphigoid, and mucocutaneous-type pemphigus vulgaris. Results: We identified several autoantigens unique to oMMP relative to other AIBDs. We then cross-referenced these antigens against previously published single-nuclei datasets, as well as the International Mouse Phenotyping Consortium Database. Several protein hits identified in our study demonstrated enriched expression on the anterior surface epithelia, including TNKS1BP1, SEC16B, FNBP4, CASZ1, GOLGB1, DOT1L, PRDM 15, LARP4B, and RPL6. Likewise, a previous study of mouse knockout models of murine analogs CASZ1, HIP1, and ELOA2 reported that these mice showed abnormalities in terms of the ocular surface and development in the eyes. Notably, PhIP-seq failed to identify the canonical markers of AIBDs such as BP180, BP230, desmogleins 1 and 3, or integrin β4, indicating that the patient autoantibodies react with conformational epitopes rather than linear epitopes. Conclusions: oMMP patients demonstrate a unique autoantibody repertoire relative to the other AIBDs. Further validation of the identified autoantibodies will shed light on their potentially pathogenic role. Full article

Background: Desquamative gingivitis is a clinical manifestation often associated with various mucocutaneous disorders, characterized by red, painful, and friable gingiva. It is predominantly seen in middle-aged to elderly females and is typically linked to autoimmune conditions such as lichen planus, pemphigoid, and pemphigus, among others. Due to the chronic pain and difficulty in maintaining personal oral hygiene, professional care becomes crucial. Methods: This article explores the application of guided biofilm therapy as a novel, gentle approach for managing desquamative gingivitis, focusing on three clinical cases. This therapy employs erythritol-based powders for biofilm removal, offering a less abrasive and more comfortable alternative to traditional mechanical plaque removal techniques. Results: The cases demonstrate the effectiveness of guided biofilm therapy in reducing discomfort and improving clinical outcomes in desquamative gingivitis patients, particularly those suffering from mucous membrane pemphigoid, pemphigus vulgaris, and oral lichen planus. Conclusions: The guided biofilm approach underscores the importance of tailored periodontal therapy in managing nonplaque-induced gingival lesions, improving patient compliance and oral health outcomes. Full article

Autoimmune blistering diseases of the pemphigus and pemphigoid groups are immune-mediated disorders due to circulating pathogenetic autoantibodies. Multiple human leukocyte antigen (HLA) genes have been associated with predisposition to these disorders. HLA-Cw6 is involved in antigen presentation processes and has been linked to psoriasis. The aim of our study was to investigate the association between the presence of the HLA-Cw6 allele and susceptibility to pemphigus vulgaris and bullous pemphigoid. A genetic study in vitro with a cross-sectional design was performed enrolling forty patients with pemphigus vulgaris and forty patients with bullous pemphigoid. The detection of HLA-Cw6 was performed through the EUROArray test on DNA obtained from whole blood samples. The polymorphism was detected in 3/40 genotypes in the pemphigus vulgaris group and in 4/40 genotypes of patients with bullous pemphigoid, unveiling a non-statistically significant different frequency in pemphigus (p = 0.6368) and in pemphigoid (p = 0.62) compared to the reference frequency from the literature of 0.086. Further research is needed to better investigate the role of HLA-Cw6 in immune-mediated diseases and to identify novel genetic markers associated with susceptibility to autoimmune blistering diseases and with disease severity and response to immunosuppressive therapies. Full article

Background and Objectives: Dapsone (DP) is employed in the management of various skin conditions, including autoimmune bullous diseases to non-enzymes (n-eAIBDs). This study aimed to assess the advantages and safety profile of DP treatment in n-eAIBDs patients. The evaluation focused on clinical remission, reduction in glucocorticosteroid (GCS) usage, and adverse incidents during a 12-month observation in a dermatology department at a Central European university. Materials and Methods: Our retrospective study included forty-one patients who met the inclusion criteria, comprising nineteen with pemphigus vulgaris, nine with pemphigus foliaceus, four with bullous pemphigoid, and nine with mucous membrane pemphigoid, including one patient with Brunsting–Perry pemphigoid. Patients received 25–50 mg/day of DP along with oral GCSs for a year, with a subsequent dose reduction where feasible. Results: The mean decreases in prednisone-equivalent dosages across all groups after 2, 6, and 12 months of DP treatment were 45.66%, 65.77%, and 63.03%, respectively. Throughout the 12-month observation period, 21.62% of patients experienced a relapse, while the remaining patients attained either complete or partial remission with minimal therapy. Adverse incidents were observed in 29.27% of patients; these were mild or moderate, and no severe negative effects were observed. Conclusions: DP is an effective and affordable choice to support the treatment of n-eAIBDs, but it may not be sufficient for long-term management in certain patients with severe n-eAIBDs. Full article