Search Results (89)

Autoimmune bullous diseases (AIBDs), including pemphigus vulgaris (PV), pemphigus foliaceus (PF), and bullous pemphigoid (BP), are mediated by autoantibodies against desmogleins (DSG1, DSG3) or hemidesmosomal proteins (BP180, BP230). While enzyme-linked immunosorbent assay (ELISA) is commonly applied for antibody detection, chemiluminescent immunoassay (CLIA) offers advantages such as a broader dynamic range and higher automation. To compare the diagnostic performance of CLIA and ELISA for detecting autoantibodies in patients with AIBDs, we collected 255 serum samples (92 controls, 84 BP, 69 PV, 10 PF) and 85 blister fluid samples (42 controls, 43 BP). Serum was tested for anti-BP180, anti-BP230, anti-DSG1, and anti-DSG3 antibodies using both assays; blister fluid was tested for anti-BP180 and anti-BP230. Using established cut-offs, the assays demonstrated good diagnostic accuracy for anti-BP180, anti-DSG1, and anti-DSG3 in serum, and excellent concordance (>90%). Receiver operating characteristic analysis revealed acceptable to excellent diagnostic value for both sample types, with CLIA generally achieving a higher area under the curve. Spearman’s correlation and linear regression analyses confirmed moderate to strong agreement between the two methods. In conclusion, CLIA showed strong concordance with and comparable diagnostic accuracy to ELISA for AIBD serodiagnosis. Furthermore, this is the first study to evaluate CLIA for autoantibody detection in blister fluid from BP patients, demonstrating that blister fluid may serve as a less invasive sample type for diagnosis. Our cut-off analysis in a treated cohort also suggested that manufacturer-recommended thresholds may yield false-negative results, highlighting the need for population-specific reference intervals. Full article

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease, predominantly affecting elderly patients with multiple comorbidities. This multicentre retrospective cohort study aimed to characterize the clinical profile, treatment patterns, and drug-associated cases of BP in a real-world setting. The study included 156 patients newly diagnosed with BP between 2020 and 2024 in four dermatology departments in Poland. Diagnosis was based on clinical features, and immunological assessment, including direct immunofluorescence (DIF), ELISA, and BIOCHIP-based indirect immunofluorescence. The mean age at diagnosis was 75.5 ± 10.9 years, and 78.85% of patients had at least one comorbidity, most commonly arterial hypertension, type 2 diabetes mellitus, and dyslipidemia. Severe pruritus was reported in 74.14% of evaluated patients. Blisters and erosions were the predominant clinical manifestations. Topical glucocorticosteroids were the most frequently used treatment, followed by systemic glucocorticosteroids and methotrexate. New drug exposure within 6 months before disease onset was identified in 14.74% of patients and was associated with a shorter time to diagnosis. Drug-associated cases showed lower BP180 ELISA positivity, although this did not remain significant after correction for multiple testing. These findings highlight the clinical complexity of BP and the importance of medication review and direct immunofluorescence in diagnostic evaluation. Full article

Background/Objectives: Rheumatoid neutrophilic dermatosis (RND) is a rare extra-articular manifestation of rheumatoid arthritis (RA) with variable clinical presentations. Although typically non-blistering, a rare bullous or vesiculobullous subtype has been described, mainly in patients with seropositive and active RA, and may mimic autoimmune blistering diseases. The objective of this review was to systematically summarize the clinical, histopathological, immunopathological, and therapeutic features of vesiculobullous rheumatoid neutrophilic dermatosis. Methods: A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines utilizing the PubMed, MEDLINE, and Google Scholar databases, which were searched through December 2025. Case reports and case series describing vesiculobullous or bullous RND with extractable patient-level data were included. Non-English articles were translated. Demographic, clinical, histopathological, immunopathological, microbiological, and therapeutic data were extracted and analyzed using Statistica 12.0 software. Results: Results were synthesized descriptively due to clinical heterogeneity and limited sample size. Thirty reported cases were identified, of which 28 non-duplicate cases were included. The mean patient age was 60.8 ± 14.9 years, with a female predominance (male-to-female ratio, 1:2.5). Most patients were of Asian descent (67.9%). Bullous or vesicular lesions most frequently involved the lower legs (64.3%), palms and soles (41.7%), and thighs (35.7%). Rheumatoid factor data were available in 67.9% of patients, all indicating high RA activity. Histopathological examination was reported in 71.4% of cases and most commonly demonstrated a predominantly neutrophilic infiltrate, often dense and extending throughout the dermis, with subepidermal blister formation being the most frequent pattern. Direct immunofluorescence, serological testing for autoimmune bullous diseases, and microbiological investigations were predominantly negative. Dapsone and systemic corticosteroids, alone or combined with RA-specific therapies, were the most commonly used treatments. Conclusions: This review represents the most comprehensive synthesis to date focused exclusively on the bullous/vesiculobullous subtype of RND, highlighting key diagnostic features such as neutrophil-predominant histopathology, negative direct immunofluorescence, and favorable response to dapsone. Full article

Anti-p200 pemphigoid is an autoimmune blistering disease (AIBD) caused by autoantibodies against laminin β4 and/or γ1, and clinically resembles bullous pemphigoid (BP) as well as the inflammatory variant of epidermolysis bullosa acquisita (EBA). All three diseases show IgG and/or C3 deposition along the cutaneous basement membrane zone (BMZ). Although complement activation is central to BP and EBA pathogenesis, its role in anti-p200 pemphigoid remains unclear. To investigate this, we analyzed inflammatory infiltrates in lesional and perilesional skin from anti-p200 pemphigoid patients (n = 11), revealing a neutrophil-predominant pattern, with mixed neutrophil–eosinophil infiltrates in 81% of cases, which contrasted with the eosinophil-rich infiltrates typical of BP. Infiltrating neutrophils expressed C5aR1 and C5aR2. Complement fixation test (CFT) of patient sera demonstrated C3c deposition at the BMZ in 40% (20/50) of anti-p200 pemphigoid cases and 87% (13/15) of BP cases. Patients in both cohorts could be stratified into high, mild, and non-complement-fixating groups. Pharmacological inhibition of C1s (sutimlimab), C3 (compstatin), C5 (tesidolumab), or C5aR1 (avacopan) significantly blocked C3c or C5 deposition in vitro. These findings indicate that selective blockade of the classical, alternative, or terminal complement pathways effectively prevents BMZ complement deposition, highlighting pathway-specific complement inhibition as a potential therapeutic strategy for anti-p200 pemphigoid. Full article

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease. In recent decades, an increasing incidence of BP has been reported. The rationale for this study arises from the limited availability of advanced immunopathological and serological assays for assessing disease activity in bullous pemphigoid across many clinical centers. This systematic review evaluates evidence regarding hematological markers derived from complete blood count (CBC), such as eosinophil count and neutrophil-to-lymphocyte ratio (NLR), in BP patients. The Ovid MEDLINE and EMBASE databases were searched for English-language peer-reviewed papers published until 2 May 2025. Sixteen studies involving 1775 patients were included. Eosinophil count consistently correlated with disease severity, clinical phenotype, treatment response, and relapse risk, while NLR showed potential as a prognostic and therapeutic marker. Given their accessibility and cost-effectiveness, these parameters may have practical value in the routine clinical management of BP. Full article

Chronic inflammatory skin diseases and neurodegenerative disorders share overlapping genetic, immunologic, and metabolic pathways that may predispose individuals to cognitive decline. This review synthesizes current human genomic, transcriptomic, and bioinformatic evidence linking psoriasis, rosacea, atopic dermatitis, and bullous pemphigoid with Alzheimer’s and Parkinson’s disease. Literature from PubMed, IEEE Xplore, and Google Scholar was examined, prioritizing studies integrating genomic, transcriptomic, and proteomic analyses. Among inflammatory dermatoses, psoriasis exhibits the strongest overlap with dementia genetics, with shared susceptibility loci including APOE, IL12B, and HLA-DRB5, and transcriptional regulators such as ZNF384 that converge on IL-17/TNF signaling. Rare-variant and pleiotropy analyses further implicate SETD1A and BC070367 in psoriasis–Parkinson’s comorbidity. Rosacea demonstrates upregulation of neurodegeneration-related proteins SNCA, GSK3B, and HSPA8, together with shared regulatory hubs (PPARG, STAT4, RORA) driving NF-κB/IL-17/TNF-dependent inflammation. In atopic dermatitis, rare FLG variants interacting with BACE1 suggest a mechanistic bridge between barrier dysfunction and amyloidogenic processing. Bullous pemphigoid reveals an HLA-DQB1*03:01-mediated immunogenetic link hypothesis and cross-reactive autoantibodies targeting BP180 (collagen XVII) and BP230, highlighting an autoimmune route of neurocutaneous interaction. Other inflammatory and neurodegenerative diseases with currently weak or limited genetic evidence are also discussed, as they may represent emerging biological pathways or potential therapeutic targets within the skin–brain connection in the future. The aim of this work is to help clarify these genetic links and to advocate for the routine cognitive assessment of affected patients, enabling early detection, improved long-term quality of life, and the potential for timely therapeutic intervention. Full article

Background/Objectives: Bullous pemphigoid (BP) is an autoimmune blistering skin disease. The association between dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) and bullous pemphigoid (BP) has been studied in many countries; however, controversy has arisen from analyzing the related risk factors. The objectives of this study are to assess whether the association between DPP-4 inhibitors and bullous pemphigoid in EudraVigilance is statistically significant and to identify the presence of risk factors found in previous studies in a case/exposure group. Our results will be compared with those obtained from the Food and Drug Administration Adverse Event Reporting System database (FAERS). Methods: A case/control retrospective observational study was performed using data from the European database EudraVigilance. All reports from 2007 to 2024 (a total of 11,451,738 reports) were gathered and filtered by exposure to DPP-4 inhibitors and development of BP or lack thereof. Association was measured using reporting odds ratios with a 95% confidence interval, and Fisher’s exact test was used to obtain p-values, assuming an alpha error of 0.05. Results: The results indicate an association between the consumption of DPP-4 inhibitors and the development of BP (with an odds ratio of 153.5; 95% confidence interval 144.1–163.5; ROR = (a/c)/(b/d); a: 1345 reports of BP associated with DPP-4i; c: 3870 reports of BP associated with other different drugs; b: 25,857 reports of other ADRs and DPP-4i; and d: 11,420,666 reports of ADRs associated with other drugs). The predominant factors in the case/exposure group were male gender (58.6%), age between 65 and 85 years (43.3%), medical history of type 2 diabetes mellitus (30.4%) and consumption of vildagliptin (44.2%). Similar results were found in a prior analysis of the FAERS database (2006–2020). Conclusions: This study provides evidence of the association between the consumption of gliptins and the development of BP. Disproportionality measures were estimated to be higher in the exposure group than in the positive controls. As such, BP could appear after several months of exposure, and dermatological monitoring is crucial. Full article

Background/Objectives: Wells’ syndrome (WS) is an uncommon cutaneous disease with unknown etiology. Itchy bullous lesions and erythematous plaques characterize the bullous WS (BWS), a rare subtype of the syndrome. We describe the case of a woman affected by chronic lymphocytic leukemia who developed BWS and responded to the classic corticosteroid treatment. We also systematically reviewed the literature, analyzing the clinical, laboratory, and histological features and treatments of this rare disease. Methods: We used the databases Ovid MEDLINE, PubMed, and EMBASE with the following search terms: ((bullous Wells’ syndrome [MeSH Terms]) OR (eosinophilic cellulitis)) OR (bullous eosinophilic dermatitis) to identify and compare case reports of BWS. Results: We analyzed 28 patients, including our case. They were primarily female adults with a median age of 44.92 years. Blood eosinophilia was common, and histologically, the tissue samples showed an eosinophilic-neutrophilic dermal infiltrate. From a clinical perspective, the bullae were typically associated with or preceded by other lesions, primarily urticarial plaques, and mainly involved the extremities. Possible triggering agents of BWS include medications, insect bites, malignancies, and autoimmune/infectious diseases. Systemic steroids constituted the first-line treatment. Recent studies described the efficacy of the anti-interleukin-5 monoclonal antibody Mepolizumab in refractory cases of WS. Conclusions: Diagnosis of BWS is often challenging due to the rarity of the disease, clinical polymorphism, and multiple differential diagnoses. Integrating clinical features with laboratory and histopathological findings is essential for achieving a definitive diagnosis. Although the causal link between WS and underlying neoplastic/autoimmune/infective conditions is not always present, this possibility should be taken into account and investigated for the best patient management. Full article

Background/Objectives: Secondary syphilis typically presents with a non-pruritic maculopapular rash. However, vesicular and bullous manifestations are exceedingly rare in adults and may mimic autoimmune blistering diseases. The objective of this report is to describe atypical presentation of secondary syphilis with predominant vesiculobullous lesions and to emphasize the importance of including syphilis in the differential diagnosis of blistering skin diseases. Methods: We describe the case of a 46-year-old bisexual man with syphilis of unknown duration who presented with recurrent polymorphic skin eruptions, predominantly bullous and vesicular in nature. Clinical examination, serologic testing, and histopathologic evaluation were performed to establish the diagnosis. Results: Serologic tests confirmed active syphilis infection. A brief review of similar reported cases was conducted to highlight the clinical variability of vesiculobullous syphilis. Conclusions: Atypical vesiculobullous presentations of secondary syphilis pose significant diagnostic challenges and may be mistaken for autoimmune blistering disorders. Clinicians should maintain a high index of suspicion for syphilis in patients with polymorphic or blistering eruptions, particularly in those with risk factors for sexually transmitted infections. Awareness of these uncommon manifestations can facilitate timely diagnosis and appropriate treatment. Full article

Background: Oral pemphigus is a rare autoimmune blistering disorder predominantly affecting the mucous membranes, particularly in older adults. Despite therapeutic advances, the chronic, painful, and recurrent nature of oral pemphigus vulgaris substantially impairs patients’ quality of life (QoL). Patient-reported outcomes (PROs) offer valuable insights into the subjective burden of the disease; however, data on PROs in older adults with oral pemphigus are scarce. Objective: To assess QoL in older adults diagnosed with oral pemphigus using validated PRO measures and to identify key clinical factors associated with QoL deterioration. Methods: A cross-sectional pilot study was conducted involving 10 participants aged 60 years or older with confirmed oral pemphigus vulgaris. Participants completed the Oral Pemphigus–Specific Quality of Life Questionnaire (OP-QoLQ) and the Dermatology Life Quality Index (DLQI). Clinical severity was evaluated using the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Statistical analyses explored correlations between disease severity, treatment regimens, and QoL outcomes. Results: Most participants reported moderate to severe QoL impairment, with eating difficulties and emotional distress being the most frequently mentioned issues. Higher ABSISs and longer disease duration were significantly correlated with poorer OP-QoLQ and DLQI outcomes (Spearman’s ρ up to 0.80; p ≤ 0.021). Systemic corticosteroid therapy was more frequently reported among those with advanced disease, although treatment-related adverse effects may contribute to reduced QoL. Conclusion: Oral pemphigus substantially compromises QoL in older adults, with both disease- and treatment-related factors playing important roles. These findings support the integration of PROs into the multidisciplinary management of older adults with oral pemphigus vulgaris. Full article

The adaptor molecule DNAX-activating protein of 12 kDa (DAP12) is broadly expressed in innate immune cells, but its role in autoimmunity remains unclear due to its dual regulatory functions. We investigated the contribution of the DAP12 pathway to bullous pemphigoid (BP), the most common autoimmune blistering disease, using a mouse model induced by transfer of anti-type XVII collagen (Col17) IgG. Repeated anti-Col17 IgG injections over 12 days produced comparable disease activity in DAP12-deficient and wildtype mice (n = 17/group), indicating that disease induction occurs independently of DAP12 signaling. Flow cytometry and immunofluorescence analysis of lesional skin further revealed a strong upregulation of the DAP12-associated triggering receptors expressed on myeloid cells (TREM) 1 in wildtype BP lesions, whereas TREM2⁺ cell frequencies in anti-Col17 IgG-treated wildtype and DAP12 knock-out animals were significantly lower than in healthy controls. Additional flow cytometry analysis demonstrated altered inflammatory infiltrates with notably reduced frequencies of Siglec-f⁺ eosinophils in DAP12-deficient vs. wildtype lesional skin. In addition, pharmacological inhibition of PI3Kδ, a downstream kinase of the DAP12/TREM pathway, did not affect disease progression in anti-Col17 IgG-induced BP. Collectively, these findings indicate that while DAP12 signaling modulates local immune cell composition, the DAP12/TREM1/2-axis does not influence overall disease activity in experimental BP. Full article

Background and Objectives: While pemphigus vulgaris (PV) and bullous pemphigoid (BP) have been linked to autoimmune comorbidities, the spectrum and specificity of these associations remain uncertain. We aimed to investigate the prevalence and patterns of autoimmune diseases (AIDs) in patients with PV and BP compared with age- and sex-matched controls. Materials and Methods: We conducted a bicenter, retrospective case–control study including 287 PV patients with 1148 matched controls and 284 BP patients with 1137 matched controls. Autoimmune comorbidities were identified through medical record review, and disease-specific as well as system-level associations between PV, BP, and AIDs were assessed. Results: Overall AID prevalence was lower in PV (9.4%) and BP (8.1%) than in controls (18% and 15%, respectively; p < 0.001 and p = 0.002). PV was associated with Graves’ disease (adjusted OR: 3.16, 95% CI: 1.24–8.06), especially in females. BP was associated with Hashimoto thyroiditis (adjusted OR: 2.51, 95% CI: 1.33–4.75), particularly in males. System-level analyses revealed that cutaneous and multisystem AIDs were less frequent in both PV and BP (p < 0.001 for each and p = 0.001 for each, respectively), whereas endocrine AIDs were more frequent in BP (p = 0.038). Thyroid antibody positivity did not differ significantly between patients and controls. Limitations include retrospective design, possible overrepresentation of cutaneous AIDs in dermatology-based controls, and lack of external validation. Conclusions: Our findings suggest that PV and BP may be associated with selective, sex- and phenotype-specific autoimmune comorbidity patterns rather than a generalized autoimmune burden. Further prospective studies are needed to confirm these exploratory associations and clarify their temporal relationships. Full article

Tamibarotene (AM80) is an agonist of retinoic acid receptor alpha. It is licensed in Japan for the treatment of acute promyelocytic leukemia. Results from preclinical models suggest that tamibarotene might also be effective in the treatment of diverse autoimmune diseases. The effect of tamibarotene on autoimmune diseases of the skin, however, has not been explored. We therefore examined the effect of tamibarotene on disease in the antibody-transfer mouse model of bullous pemphigoid (BP)-like epidermolysis bullosa acquisita (EBA), a prototypical example for pemphigoid diseases. Pemphigoid diseases are a group of autoimmune blistering skin diseases driven by autoantibodies and the recruitment and activity of granulocytes in the dermis. In sharp contrast to its effect in models of other autoimmune diseases, tamibarotene aggravated EBA pronouncedly. At the peak of disease, skin inflammation in tamibarotene-treated mice involved, on average, 1.6-fold more of the total body surface compared to vehicle-treated mice. Tamibarotene markedly reduced the recruitment of regulatory T cells (T_regs) into the dermis. This blunted the counterregulatory mechanisms that normally curb skin inflammation in this model. The effect aligns with previous reports describing tamibarotene-mediated downregulation of skin-homing receptors on T_regs. In addition, tamibarotene prolonged the responsiveness of aging neutrophils to immune complexes in vitro, providing another mechanism that may exacerbate EBA. Collectively, our results suggest that tamibarotene may elicit detrimental effects in patients with EBA by abolishing the recruitment of T_regs into skin. This warrants great caution when using tamibarotene in patients with EBA and possibly other pemphigoid diseases. Full article

The COVID-19 pandemic has highlighted intricate associations between SARS-CoV-2 infection and autoimmune skin diseases (ASDs). This review examines the bidirectional relationship between COVID-19 and ASDs including hidradenitis suppurativa, psoriasis, atopic dermatitis, alopecia areata, autoimmune bullous diseases, cutaneous and systemic lupus erythematosus, systemic sclerosis, dermatomyositis, and lichen planus. Current evidence indicates that SARS-CoV-2 may precipitate or worsen ASDs via mechanisms such as molecular mimicry, dysregulated cytokine signaling, and enhanced Th1/Th17 immune responses, leading to loss of self-tolerance and autoantibody production. Epidemiological studies have identified increased incidence and flares of psoriasis, hidradenitis suppurativa, and other ASDs following both COVID-19 infection and vaccination, with mRNA vaccines associated with a higher risk of flare in hidradenitis suppurativa compared with non-mRNA vaccines. Notably, severe COVID-19 is associated with a greater risk of new-onset autoimmune disease, and patients with pre-existing inflammatory skin conditions may have increased susceptibility to SARS-CoV-2 infection but experience less severe COVID-19 courses. These findings underscore the need for ongoing surveillance and mechanistic studies to clarify the immunopathogenic links between SARS-CoV-2 and ASDs and inform management strategies for affected patients in the context of both infection and vaccination. Full article

Background/Objectives: Anti-p200 pemphigoid is a rare and likely underdiagnosed autoimmune blistering disorder. Laminin γ1 and laminin β4 have been implicated as potential target antigens in its pathogenesis. Recently, a novel indirect immunofluorescence assay targeting anti-laminin β4 antibodies has been developed, demonstrating high sensitivity and specificity, and offering a valuable tool for improved diagnosis. Methods: Of the 451 patients, 21 were selected for further laboratory analysis based on medical records. Sera from 10 patients, which showed a positive direct immunofluorescence (DIF) result and negative results in multiplex enzyme-linked immunosorbent assays (ELISAs) and/or mosaic six-parameter indirect immunofluorescence (IIF) for various autoimmune bullous diseases, were tested for the presence of anti-laminin β4 antibodies. Additionally, sera from 11 patients with positive DIF and positive ELISA for antibodies against BP180 and/or BP230 were analyzed. Results: Among the 10 patients with positive DIF and negative ELISA and/or mosaic six-parameter IIF, 6 sera were positive for anti-laminin β4 antibodies. These patients presented with atypical clinical features. In contrast, all 11 sera from patients with both positive DIF and positive ELISA for BP180 and/or BP230 were negative for anti-laminin β4 antibodies. Conclusions: In patients with a positive DIF result but negative ELISA and/or mosaic six-parameter IIF findings, testing for anti-laminin β4 antibodies should be considered. Furthermore, in cases presenting with atypical clinical features—such as acral distribution of lesions, intense pruritus, or erythematous–edematous plaques—the possibility of anti-p200 pemphigoid should be included in the differential diagnosis. Full article