Search Results (112)

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

Lipid peroxidation (LPO) is a biochemical process through which lipids are subjected to a peroxidation reaction in the presence of free radicals. The process can cause alterations in biological membranes and the formation of substances harmful to the body that can form aggregates with proteins and nucleic acids. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) are the main products of LPO. These compounds have cytotoxic and genotoxic properties and contribute to the pathogenesis of various diseases. This research focuses on the correlation between LPO and skin diseases. For some skin diseases, such as psoriasis, vitiligo, and alopecia, LPO products have been shown to have a clear role in the pathogenesis of the disease. Lipid aldehydic products like MDA and 4-HNE can enhance inflammation by stimulating pro-inflammatory genes and producing cytokines. Furthermore, these products can stimulate cell death and increase oxidative stress. For other diseases (atopic dermatitis, urticaria, pemphigus, and melanoma), the role of LPO is unclear, even if the levels of LPO biomarkers are elevated in proportion to the severity of the disease. LPO can also be exploited to counteract the proliferation of neoplastic cells. Therefore, enhancing LPO would play an adjuvant role in the therapy of neoplastic diseases such as melanoma. In particular, the therapeutic implication resulting from the role of LPO products in the cytotoxicity induced by photodynamic therapy used for the adjuvant treatment of melanoma could be of interest in the future. Full article

Pemphigus-associated interstitial lung disease (P-ILD) is a severe complication observed in pemphigus patients that is characterized by pulmonary interstitial inflammation and fibrosis. This study investigated the role of anti-desmoglein (Dsg) 1/3 antibodies in P-ILD pathogenesis and evaluated the therapeutic potential of molecular hydrogen (H₂). Using a BALB/cJGpt mouse model, we demonstrated that anti-Dsg 1 antibodies, but not anti-Dsg 3 antibodies, induced interstitial inflammation and fibrosis. Immunofluorescence staining confirmed IgG deposition in the alveolar epithelium, suggesting immune complex formation and epithelial damage. Gene expression analysis revealed elevated pro-inflammatory cytokines (IL-1β, IL-13) and upregulated pro-fibrotic markers (α-SMA, S100A4, TGF-β, and collagen genes) in P-ILD progression. Elevated oxidative stress and impaired ROS metabolism further implied the role of oxidative damage in disease pathogenesis. To assess H₂’s therapeutic potential, hydrogen-rich water was administered to P-ILD mice. H₂ treatment significantly reduced oxidative stress, attenuated interstitial inflammation, and prevented pulmonary fibrosis. These protective effects were attributed to H₂’s antioxidant properties, which restored the pro-oxidant–antioxidant balance. Our findings underscore the critical role of anti-Dsg 1 antibodies and oxidative stress in P-ILD and highlight H₂ as a promising therapeutic agent for mitigating anti-Dsg 1 antibody-induced lung injury. 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

Background: Patients suffering from a new variant of endemic pemphigus foliaceus in El Bagre, Colombia, South America (El Bagre-EPF) produce autoantibodies (Abs) to different proteins in the skin (frustre form), as well as to those in other organs (Senear–Usher-like and systemic forms). Here, we hypothesize whether patients’ autoantibodies play a role in triggering epicardium and pericardium autoimmunity and pathogenicity. We based this hypothesis on knowing that these patients frequently show clinical symptoms of the chest and heart, and we hypothesize that the autoantibodies of this disease are the main contributors to the base of the pericardial conditions of these patients. Materials and Methods: A case-control study for testing the sera of patients affected by El Bagre-EPF (n = 45) and matched controls from the endemic area (n = 45) was conducted to evaluate reactivity with the pericardial tissue. Patients’ necropsies were tested by immunohistochemistry (IHC), in El Bagre-EPF patients (n = 7) and matched controls. Results: The sera from most El Bagre-EPF patients displayed polyclonal autoreactivity with both layers of the pericardium, i.e., fibrous pericardium and serous pericardium (mainly to cell junctions and sensory nerve formations), as well as with the neurovascular cell junction branches. Controls were negative (p < 0.1). These reactivities were detected by IIF, CM, and IHC using secondary Abs against total IgG, IgM, Kappa and lambda, C3C of the complement, fibrinogen, and albumin. Furthermore, Abs against MIZAP, ARVCF, desmoplakin I-II, and p0071 colocalized with the Abs of El Bagre-EPF (p < 0.1). Conclusions: Patients affected by El Bagre-EPF produce autoantibodies directed against molecules present in the cell junctions of the pericardium and adnexal structures. Further studies will focus on the clinical significance of these findings. Full article

Background/Objectives: Hailey–Hailey disease (HHD) is an uncommon genodermatosis with autosomal dominant inheritance caused by loss-of-function mutations in the ATP2C1 gene, which lead to disruption in keratinocyte adhesion and intraepidermal acantholysis. The chronic nature of the disease, its frequent recurrences and the lack of specific treatment pose real challenges in the long-term management of these patients. Recent studies have evaluated the effect of dupilumab, a human monoclonal antibody that blocks interleukin-4 and -13 receptor in refractory HHD, with very promising results. The aim of this study was to review the published data on the use of dupilumab for the treatment of HHD, to present our own experience in the field, and to discuss the mechanisms underlying dupilumab’s beneficial effects in HHD and the future treatment perspectives. Methods: A search of the medical literature on the use of dupilumab in the treatment of HHD was conducted. The terms “Hailey–Hailey disease”, “benign familial pemphigus”, “benign chronic pemphigus”, and “dupilumab” were searched across multiple databases (Medline, Chrocane Library, EMBASE) from inception until 30 September 2024. Results: To date, six manuscripts describing 11 refractory HHD cases treated with dupilumab have been published. All the patients experienced significant clinical improvement. The authors reported sustained disease quiescence in seven patients (64%), monitored for 5 to 24 months. None of the patients experienced adverse effects related to dupilumab. To the existing evidence, we add a new case of recalcitrant HHD successfully treated with dupilumab. Conclusions: Mounting evidence indicates dupilumab as a safe and efficient therapeutic alternative in patients with severe, refractory HHD. However, the long-term efficacy of dupilumab and the optimal therapeutic regimen for HHD are yet to be determined. 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

Background and Objectives: Congenital syphilis remains a significant global health concern, with severe morbidity and mortality if undiagnosed and untreated. Although many infants appear asymptomatic at birth, subtle clinical signs—including bullous lesions (congenital bullous syphilis, also known as pemphigus syphiliticus)—may facilitate early detection. Recognizing this rare manifestation is crucial for timely intervention, reducing serious outcomes. Materials and Methods: We systematically reviewed Medline (PubMed), Embase, and the Cochrane Central Register of Controlled Trials from inception to December 2024 for cases of congenital bullous syphilis, also known as pemphigus syphiliticus. We extracted demographic, clinical, laboratory, radiological, treatment, and outcome data. Additionally, we included clinical information from a newly documented case of congenital bullous syphilis managed in our center. Results: Twenty-four cases of congenital syphilis with bullous lesions were identified, twenty with sufficient detail for analysis. Patients presented three distinct clinical patterns: confined palmoplantar lesions, acrally distributed lesions, and diffuse bullous-erosive involvement. Despite variable severity, cutaneous manifestations provided a key diagnostic clue. Nontreponemal and treponemal serologic tests were central to diagnosis, supported by maternal screening and imaging. Intravenous penicillin G was the most frequently employed therapy. While most infants achieved remission, severe respiratory involvement was associated with mortality. Our new case aligned with these findings, demonstrating full resolution after appropriate antibiotic therapy. Conclusions: Bullous syphilis, though rare, is an important early sign of congenital syphilis. Prompt recognition and diagnosis—enabled by diligent maternal screening, targeted neonatal testing, and careful clinical examination—are essential to initiate timely penicillin therapy and prevent severe complications or death. This review underscores the need for heightened clinical vigilance and adherence to established guidelines for syphilis screening and treatment during pregnancy, ultimately improving neonatal outcomes. 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

Drug development faces significant financial and time challenges, highlighting the need for more efficient strategies. This study evaluated the druggability of the entire human proteome using Fpocket. We identified 15,043 druggable pockets in 20,255 predicted protein structures, significantly expanding the estimated druggable proteome from 3000 to over 11,000 proteins. Notably, many druggable pockets were found in less studied proteins, suggesting untapped therapeutic opportunities. The results of a pairwise pocket similarity analysis identified 220,312 similar pocket pairs, with 3241 pairs across different protein families, indicating shared drug-binding potential. In addition, 62,077 significant matches were found between druggable pockets and 1872 known drug pockets, highlighting candidates for drug repositioning. We repositioned progesterone to ADGRD1 for pemphigus and breast cancer, as well as estradiol to ANO2 for shingles and medulloblastoma, which were validated via molecular docking. Off-target effects were analyzed to assess the safety of drugs such as axitinib, linking newly identified targets with known side effects. For axitinib, 127 new targets were identified, and 46 out of 48 documented side effects were linked to these targets. These findings demonstrate the utility of pocket similarity in drug repositioning, target expansion, and improved drug safety evaluation, offering new avenues for the discovery of new indications and side effects of existing drugs. 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