Search Results (204)

Background: Epidermolysis bullosa (EB) is a complex group of rare, inherited skin disorders that blister easily, imposing substantial burden on patients and carers. There is a lack of published evidence in the UK quantifying health-related quality of life in EB patients and carers as utility values suitable for use in Health Technology Assessment (HTA). Methods: A time trade-off (TTO) study was conducted with 120 UK general public members to estimate utility values for EB patient and primary carer vignettes depicting varying EB severity. An exploratory sub-study involving six carer and clinical experts was conducted to estimate utility values of second carers. Results: 115 general public participants were included in the final TTO analysis. Mean utility values declined as disease severity increased, from 0.82 in the least severe state, to 0.54 in the most severe. Carer utilities were higher than the equivalent patient health states, but with a similar pattern of decreasing utility with increasing EB severity, ranging from 0.85 to 0.64. The secondary carer sub-study, in six respondents estimated a second care burden factor relative to the primary carer of 77%. Conclusions: The utilities estimated for both EB patients and their carers have relevance for future economic evaluations and HTA of new EB therapies. Full article

Rett syndrome (RTT, OMIM 312750) is a complex multisystem neurodevelopmental disorder. Evidence suggests that RTT may have an autoimmune component and inflammatory activation. However, the autoimmune manifestations remain poorly described. Pemphigus foliaceus is a debilitating autoimmune blistering condition caused by IgG autoantibodies that target desmoglein-1 (Dsg1), resulting in widespread skin blistering and lesions. We report a case of pemphigus foliaceus in a 20-year-old female with RTT and discuss its clinical implications. Clinical data obtained from electronic health records were extracted and reviewed. Genetic testing was performed to identify the specific methyl-CpG-binding protein 2 (MECP2) mutation and on an expanded panel of 55 genes associated with pemphigus foliaceus and related blistering disorders. The individual had pemphigus foliaceus, which required immunosuppression, intravenous immunoglobulin (IVIg) therapy, and Rituximab. The disease trajectory was complicated by infections, aspiration pneumonia, and hypoxic cardiac arrest. There was progressive functional decline, and disease control was difficult to achieve, with frequent flares. Genetic testing confirmed a heterozygous pathogenic MECP2 variant (NM_001110792.1:c.952C>T; p.(Arg318Cys)). HLA genotyping identified alleles consistent with the HLA-DRB1*04:02–HLA-DQA1*03:01–HLA-DQB1*03:02 (DR4/DQ8) haplotype. Furthermore, genetic analysis identified a heterozygous DSG1 variant rs12967407. This study reports the first case of pemphigus foliaceus in RTT, expanding the clinical spectrum of RTT beyond its neurodevelopmental phenotype. The DR4/DQ8 haplotype, previously associated with pemphigus susceptibility, supports a background of genetic susceptibility in this individual. No causal association between RTT and pemphigus foliaceus can be inferred from this single case. Rather, this case demonstrates that a rare autoimmune disorder such as pemphigus foliaceus can co-occur with a pathogenic MECP2 mutation. The coexistence of a genetic and autoimmune disease can result in a more complex clinical presentation and treatment course. The case further emphasises the need for increased vigilance in identifying new and emerging systemic pathology alongside RTT. Full article

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

Epidermolysis bullosa (EB) comprises a group of rare inherited genodermatoses characterized by fragility and blistering of the skin and mucous membranes, chronic wounding, and significant morbidity including increased risk of squamous cell carcinoma in severe subtypes. Key unmet priorities include reducing diagnostic latency, establishing objective wound monitoring, enabling early detection of malignant transformation within chronic ulcerations, and developing therapies that durably modify disease progression. Artificial intelligence (AI) encompassing machine learning (ML), and deep learning (DL) is increasingly integrated into EB research and clinical practice to address these unmet needs. This structured narrative review synthesises current evidence on AI applications in EB spanning genetic diagnostics, wound assessment, inflammatory endotyping, drug repurposing, and emerging therapeutic technologies, and integrates evidence from registered clinical trials. In genomics, DL-based splicing prediction models and variant prioritisation frameworks accelerate pathogenic variant detection and reduce diagnostic latency. In wound care, convolutional neural networks-based platforms enable automated lesion segmentation and remote monitoring, while multimodal AI models predict healing trajectories and support stratification of wounds by chronicity. Computational transcriptomic analyses have identified candidate repurposing agents by reversing pathogenic gene expression signatures in EB tissue. Emerging convergence of AI with biosensors-integrated wound dressings and three-dimensional bioprinting of genetically corrected skin substitutes represents a transformative future direction. Translational barriers include limited EB-specific training datasets, algorithmic bias across diverse skin phototypes, the interpretability deficit of DL systems, and evolving regulatory frameworks for AI as a medical device. Expansion of internationally interoperable EB disease registries with standardised wound imaging protocols is identified as the single most impactful intervention to accelerate AI adoption. A minimum endpoint set for AI-assisted EB wound assessment, incorporating wound area trajectory, wound type classification, tissue composition, and paired patient-reported pain and itch scores, is proposed to standardise outcome reporting across future studies. 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: Epidermolysis bullosa (EB) comprises a heterogeneous group of rare inherited skin-fragility disorders in which even minimal trauma can cause blistering, chronic wounds, scarring, and functional impairment. After surgical release of EB hand deformities, wound coverage is challenging because autologous split-thickness skin grafting creates an additional donor-site wound in already fragile tissue. This preliminary case series reports our single-center pediatric experience using intact fish skin grafting (iFSG) as an adjunct after EB hand surgery. Methods: We conducted an observational case series of five pediatric patients with dystrophic EB, including eight operated hands, treated between December 2022 and December 2025. iFSG was applied after the release of contractures and/or pseudosyndactyly. Primary outcomes were time to complete re-epithelialization, need for re-application, need for autologous grafting, and early complications. Secondary outcomes included dressing-related pain assessed with an age-appropriate visual analog scale during awake dressing care, dressing burden, and early recurrence signals. Results: The iFSG application was feasible in all cases. One localized second application was required, and no patient required autologous split-thickness skin grafting. Mean dressing-related pain was 1.6 on the visual analog scale, and mean time to complete re-epithelialization was 47.6 days. No allergic reactions occurred. Healing was slower in the two most severe bilateral mitten-hand cases, and one patient developed limited dorsal disepithelialization attributed to prolonged dressing contact on extremely fragile skin. One partial recurrence of pseudosyndactyly was observed during follow-up without the need for revision surgery. Conclusions: iFSG was feasible in this small preliminary pediatric dystrophic EB hand surgery series and may provide a biologically active scaffold that supports secondary closure while avoiding autologous donor-site creation. Because of the rarity of the disease, the limited sample size, the absence of a comparator group, and the limited follow-up, these findings should be interpreted cautiously. Larger multicenter studies with standardized functional, pain, recurrence, and caregiver-reported outcomes are needed to define the role of iFSG in EB hand reconstruction. ABILHAND-Kids was also administered to patients/caregivers and suggested encouraging perceived improvement in postoperative hand use and independence in daily activities. Full article

White pine blister rust disease (WPBR), caused by Cronartium ribicola, ranks among the most destructive pathogens of five-needle pines. We developed a hydroxynaphthol blue (HNB)-based Loop-mediated isothermal amplification (LAMP) assay enabling rapid, visual detection of C. ribicola directly following DNA extraction. LAMP primers targeting the internal transcribed spacer (ITS) region were designed and validated through in silico comparison with related Cronartium species and in vitro testing against sympatric forest fungi. The optimized 25 μL reaction contained 8.0 mM Mg²⁺, 1.0 mM dNTPs, and an inner-to-outer primer ratio of 8:1, with amplification conducted at 62 °C for 40 min. Positive amplification produced a distinctive color transition from purple to sky blue, enabling visual interpretation without instrumentation. Under the tested conditions, the assay achieved a detection limit of 460 ± 3.2 fg/μL genomic DNA—a 10-fold improvement over conventional PCR in concentration-based sensitivity. Assay applicability was evaluated using 211 field-collected Pinus armandii samples sourced from China. Detection efficiency varied significantly across tissue types. Symptomatic bark exhibited a substantially higher positive detection rate (68.97%, 95% CI: 49.2–84.7%) compared to needles from symptomatic trees (18.75%, 95% CI: 4.1–45.7%). Among asymptomatic samples, 3.75% of bark samples tested positive for C. ribicola DNA, whereas all needle samples were negative. Geographically, positive detections clustered at several discrete sampling sites in southwestern China, predominantly at elevated elevations. The established LAMP-HNB assay provides a rapid, visually interpretable diagnostic tool for early detection and quarantine monitoring of WPBR following DNA extraction. Beyond its practical utility, this assay establishes valuable baseline data for targeted disease surveillance in the context of evolving climate conditions. Full article

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

Desmosomes are specialized cell–cell junctions that play a crucial role in maintaining the structural integrity of both cornifying and non-cornifying epithelium. Disruption of desmosomal cohesion in autoimmune, infectious, and other diseases is typically associated with acantholysis, often leading to intraepidermal blisters and erosions. In recent decades, genetic mutations have been identified that impair desmosomal integrity to varying degrees, giving rise to a spectrum of genodermatoses. These conditions, which include palmoplantar keratoderma, epidermolysis bullosa, and ichthyoses, can range from mild to severe, with some forms being syndromic and life-threatening. We investigated dermatopathologic changes in patients with mutations in genes encoding desmosomal proteins seen in consultations at our genodermatoses unit. A series of cases, including keratosis palmoplantaris areata et striata (striated palmoplantar keratoderma type 1), Carvajal–Huerta syndrome, severe dermatitis–multiple allergies–metabolic wasting (SAM) syndrome, ectodermal dysplasia–skin fragility syndrome, and inflammatory peeling skin disease, was examined histologically and, when necessary, immunohistochemically. Findings from our cohort were compared with histopathological consultation cases from our dermatopathology laboratory and previously published cases in the literature. Through these observations, we defined a distinct form of acantholysis associated with desmosomal protein mutations, which we term “desmosomal-type acantholysis.” We outline the spectrum of this newly characterized pattern and highlight its differences from conventional forms of acantholysis. Furthermore, for the first time, we describe incidental cases where “desmosomal-type acantholysis” appears sporadically in solitary acanthoma and in association with a melanocytic nevus. Full article

Background and Clinical Significance: Congenital erythropoietic porphyria (CEP), also known as Günther disease, is a rare autosomal recessive porphyria caused by a deficiency of uroporphyrinogen III synthase, leading to the accumulation of phototoxic type I porphyrins. CEP classically presents in infancy with severe photosensitivity, blistering, scarring, and hemolytic anemia; however, significant phenotypic variability has increasingly been recognized. Case Presentation: We report a 32-year-old woman diagnosed with CEP in early infancy who demonstrated persistently and profoundly elevated erythrocyte porphyrin levels over more than a decade, yet who followed a relatively non-mutilating clinical course. Genetic testing identified a low-penetrance intronic UROS variant typically associated with erythropoietic protoporphyria, underscoring diagnostic challenges and genotype–phenotype discordance. The patient experienced marked improvement in photosensitivity and burning pain after initiation of afamelanotide, without the need for transfusion therapy or stem cell transplantation. Conclusions: This case highlights the heterogeneity of CEP, the importance of long-term biochemical follow up, and the potential role of afamelanotide in improving quality of life for selected patients with CEP. 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

Background and Objectives: Pemphigus vulgaris (PV) is a rare autoimmune blistering disease caused by IgG au-toantibodies against desmoglein 1 and/or desmoglein 3, leading to flaccid blisters on the skin and mucous membranes. The course of PV during pregnancy represents a special clinical challenge due to immunological changes accompanying physiological immunosuppression and the need to protect the developing fetus. Materials and Methods: To analyze the current state of knowledge, a literature review was performed covering the years 2015–2025. Publications describing PV diagnosed during pregnancy or in neonates were screened, and nine case reports discussing ten patients meeting the inclusion criteria were selected for detailed analysis. In this study, we also present our own clinical case of PV in pregnancy to complement the literature review and provide practical insight into disease management. Results: In most cases, the disease was diagnosed in the first trimester of pregnancy, and the most common symptoms were flaccid blisters and erosions of the oral mucosa. The diagnosis was confirmed by direct immunofluorescence (DIF) and ELISA testing. The first-line treatment remained systemic glucocorticosteroids (GCS), mainly prednisolone, which is considered the safest. In resistant cases, intravenous immunoglobulins (IVIg) were used, which were considered effective and safe, though their use may limit the transplacental transfer of autoantibodies to the fetus. In newborns, the symptoms rarely occurred, were mild, and resolved spontaneously. Drugs with proven teratogenic effects, such as methotrexate, cyclophosphamide, and mycophenolate mofetil, are contraindicated during pregnancy. In the case of rituximab therapy, it is recommended to postpone pregnancy for at least 12 months after the completion of treatment to minimize the potential risk of immunosuppression in the newborn. Conclusions: The treatment of PV during pregnancy requires close interdisciplinary cooperation. Therapy should be carefully individualized, taking into account both therapeutic efficacy and fetal safety. Perhaps then, pregnancy-related pemphigus diseases, given their peculiarities, should be classified as a distinct variety within the desmosomal type of autoimmune blistering diseases. 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