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Bullous pemphigoid is an autoimmune blistering disease that is characterized by pruritus, cutaneous urticarial plaques, and tense bullae, with mucosal involvement. On histopathology, a subepidermal blister is predominantly evident with eosinophilic inflammatory infiltrates in the upper dermis. In a few bullous dermatoses, milia can manifest at the scar of blistering lesions or in non-lesional skin. Milia are classically associated with epidermolysis bullosa acquisita, porphyria cutanea tarda, and mucous membrane pemphigoid. We report a case of bullous pemphigoid with milia manifesting within healing blistering lesions.

Hailey-Hailey disease (HHD) is a rare, autosomal dominant genodermatosis caused by a mutation of the ATP2C1 gene and presenting as an erosive dermatosis, particularly in the intertriginous areas. Generalized HHD is a rare variant. We present a case of widespread, recalcitrant HHD in a middle-aged woman with a fatal outcome. No other underlying dermatosis was identified, with the possible exception of drug sensitivity to carbamazepine. Diagnosis of HHD was confirmed by histology and genetic studies which showed a c.2395C>T mutation in the ATP2C1 gene. Concurrent pemphigus was excluded. Cases of generalized HHD are extremely rare and present a challenge in diagnosis and management. Increased awareness of this severe clinical variant is needed to improve quality of care for patients with this form of HHD.

We present two middle-aged patients with pruritic, crusted scalp erosions. Skin biopsy showed epidermal acantholysis with IgG and C3 intercellular deposits on direct immunofluorescence, leading to the diagnosis of localized pemphigus vulgaris. Resolution of the lesions without relapse occurred after low doses of oral prednisone and intralesional triamcinolone acetonide.

Background Pemphigus is a rare autoimmune blistering disease with potentially life-threatening consequences. Establishing minimal clinically important differences (MCIDs) for disease severity scores like the Pemphigus Disease Area Index (PDAI) is crucial for assessing treatment efficacy. Objectives To calculate MCIDs for both improvement and deterioration in PDAI scores in patients with pemphigus vulgaris (PV) and pemphigus foliaceus (PF), using the anchor-based method. Methods A total of 41 patients with pemphigus were recruited, with 35 meeting the MCID analysis criteria. The anchor-based method was used to calculate MCIDs for PDAI scores against the 15-point Likert scale and the Physician Global Assessment visual analogue scale (PGA-VAS) anchors. Receiver operating characteristic curves were employed to determine optimal MCID cutpoints with the highest Youden Index (J). The 15-point Likert scale scores the change in disease severity spanning from –7 to +7, designed to quantify the extent of disease improvement/deterioration since the preceding visit. Results The MCID for improvement in PDAI activity scores was 2.65 points using the 15-point Likert scale (78.7% correct classification; sensitivity 75.9%; specificity 73.5%) and 2.5 points using the PGA-VAS as the anchor (78.0% correct classification; sensitivity 84.4%; specificity 68.2%). Given the slightly higher correct classification rate using the 15-point Likert scale anchor, the MCID of 2.65 points was selected for PDAI activity score improvement. In contrast, the MCID for deterioration consistently remained at 2.5 points for the 15-point Likert scale anchor (81.0% correct classification; sensitivity 72.7%; specificity 81.0%) and 2.5 points for the PGA-VAS anchor (70.9% correct classification; sensitivity 69.6%; specificity 76.9%). Conclusions This study marks the inaugural attempt at MCID determination for PDAI scores in pemphigus, filling a critical knowledge gap. The study's calculated MCIDs provide essential benchmarks for clinical trials, treatment evaluation and research design optimization. Future studies should explore international collaborations, to examine potential cross-cultural variations in MCIDs. [ABSTRACT FROM AUTHOR]

Pemphigus is an IgG-mediated autoimmune condition characterized by autoantibodies targeting desmogleins, leading to acantholysis. Current treatments, including systemic corticosteroids and immunosuppressive drugs, are associated with significant adverse effects. Mesenchymal stem cells (MSCs) offer a promising alternative due to their immunomodulatory properties and low immunogenicity. This study evaluates the immunomodulatory effects of dental follicle mesenchymal stem cells (DF-MSCs) obtained from healthy donors on Pemphigus vulgaris (PV) patients and healthy controls by examining T-cell proliferation, apoptosis, cytokine levels, and anti-desmoglein 1/3 IgG profiles. Peripheral blood mononuclear cells (PBMCs) were isolated from twenty-one symptomatic PV patients and eleven healthy volunteers. DF-MSCs were characterized and differentiated into osteocytes, adipocytes, and chondrocytes. Peripheral blood mononuclear cells (PBMCs) were co-cultured with DF-MSCs, and various assays were conducted to evaluate T-cell proliferation, apoptosis, regulatory T cells, cytokine expression, and autoantibody levels. Results showed that DF-MSC co-cultures significantly reduced lymphocyte proliferation (43.58–16.27%), IL-4 (38.06 ng/L to 32.26 ng/L), TNF-α (32.45 ng/L to 29.41 ng/L), and DSG1 (3.29 ng/ml to 3.00 ng/ml) and DSG3 (262.40 ng/ml to 245.08 ng/ml) levels in PV patients. An increase in regulatory T cells (1.22–3.75%), IL-10 (47.46 pg/ml to 54.94 pg/ml), and IFN-γ (12.39 ng/ml to 19.70 ng/ml) was also observed. No significant changes were noted in healthy controls. These findings suggest that DF-MSCs could potentially offer a curative approach for treating pemphigus by restoring immune balance. However, further clinical trials are necessary to confirm their efficacy. [ABSTRACT FROM AUTHOR]

Background: Pemphigus is a rare autoimmune disease characterized by the formation of blisters on the skin and mucous membranes, caused by autoantibodies against desmoglein, a key protein in cell adhesion. This study aims to compare demographic and clinical criteria between male and female patients with pemphigus referred to a referral hospital, utilizing data from the pemphigus diseases registry. Method: This retrospective cross‐sectional analysis focused on several key aspects age at disease onset, severity (measured by the Pemphigus Disease Area Index [PDAI]), types of pemphigus, duration of disease, and diagnostic criteria including the presence of antidesmoglein antibodies and findings from direct immunofluorescence (DIF). By examining these variables among a cohort selected based on their diagnosis of pemphigus, the study aimed to identify significant gender differences in disease manifestation, diagnosis, and progression. This approach is crucial for tailoring more effective gender‐specific management and treatment strategies for this rare autoimmune condition. Results: In a comprehensive analysis of 1218 pemphigus patients in the year 2021 from the hospital's registry, comprising 543 males (44.6%) and 675 females (55.4%), significant gender differences were identified in 9 out of 44 variables examined. The study revealed that males had a higher age at disease onset, more frequent clinical manifestations in the head, neck, and trunk areas, and greater severity of disease as measured by the PDAI score compared to females. Conversely, females exhibited higher instances of mucosal manifestations and a higher PDAI score for mucosal erosion blister of the lower gingiva. No significant gender differences were found in 21 variables, including the overall age of patients, specific clinical manifestations across various mucous membranes, types of pemphigus, and PDAI scores for mucosal erosions in particular locations, indicating a nuanced gender impact on the presentation and severity of pemphigus that necessitates tailored clinical approaches. Conclusion: The study highlights significant gender differences in the presentation and severity of pemphigus, underscoring the importance of gender‐specific approaches in the diagnosis and management of this condition. The findings contribute valuable insights into the complex nature of pemphigus and underline the necessity for further research to understand the underlying mechanisms driving these differences. [ABSTRACT FROM AUTHOR]

Background: Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease caused mainly by IgG autoantibodies (auto-abs) against the cadherintype adhesion molecules desmoglein (Dsg) 1 and 3. Pathogenic anti-Dsg3 autoabs bind to different Dsg3 epitopes, leading, among others, to signalling that is involved in pathogenic events, such as Dsg3 depletion. As central tools in research on PV, a limited number of antibodies such as AK23 are frequently used by the autoimmune bullous disease community. Methods: Previously, we have introduced a novel Dsg3 EC5-binding antibody termed 2G4 that may potentially serve as a superior tool for numerous PV related analysis. The purpose of this study was to develop a quality-controlled production and verification process that allows I) a continuous quality improvement, and II) a verified and comprehensible overall quality with regard to pathogenic antigenspecific binding in a variety of pemphigus assays for each batch production. Results: Thus, a workflow based on a standardized operating procedure was established. This includes the verification of purity and in-vitro binding capacity (SDS-page, direct and indirect immunofluorescence) as primary parameters, and size analysis by mass-spectrometry and ex-vivo pathogenicity by monolayer dissociation assay. Conclusion: We here present an extensive point-by-point quality controlled IgG production protocol, which will serve as a basis for a standardized antibody assessment in PV research. [ABSTRACT FROM AUTHOR]

The neonatal Fc receptor (FcRn) is important for numerous cellular processes that involve antibody recycling and trafficking. A major function of FcRn is IgG recycling and half-life prolongation, and FcRn blockade results in a reduction of autoantibodies in IgG-mediated autoimmune diseases. In epithelial cells, FcRn functions in processes different from IgG recycling, such as antibody transcytosis in intestinal cells. In pemphigus vulgaris, an autoimmune disease of the epidermis, IgG autoantibodies directed against desmosomal adhesion proteins, especially desmoglein-3 and -1, cause loss of keratinocyte adhesion. We have previously demonstrated that FcRn blockade with efgartigimod, a human Fc fragment with enhanced FcRn binding, significantly reduces the keratinocyte monolayer fragmentation caused by anti-desmoglein-3 antibodies. This points to a direct function of FcRn in keratinocytes, beyond IgG recycling, but the mechanisms have not yet been elucidated in detail. Here, we show that FcRn binding is required for the full pathogenicity of recombinant anti-desmoglein-3 antibodies in keratinocytes, and that antibodies that exhibit enhanced or reduced FcRn affinity due to targeted substitutions in their Fc region, as well as F(ab')2 fragments not binding to FcRn display different degrees of pathogenicity. Blockade of FcRn by efgartigimod only shows a protective effect on keratinocyte adhesion against antibodies capable of binding to FcRn. Furthermore, antibody-induced degradation of desmoglein-3 in keratinocytes does not depend on FcRn, demonstrating that desmoglein-3 degradation and acantholysis are functionally disconnected processes. Our data suggest that the role of FcRn in autoimmune diseases is likely to be versatile and cell-type dependent, thus stressing the importance of further studies on FcRn function in autoimmune diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Autoimmune blistering diseases represent a group of chronic severe, disabling, and potentially fatal disorders of the skin and/or mucous membranes, primarily mediated by pathogenic auto-antibodies. Despite their rarity, these diseases are associated with significant morbidity and mortality and profound negative impact on the patient's quality of life and impose a considerable economic burden. Rituximab, an anti-CD-20 monoclonal antibody, represents the first line of therapy for pemphigus, regardless of severity and a valuable off-label therapeutic alternative for subepidermal autoimmune blistering diseases as it ensures high rates of rapid, long-lasting complete remission. Nevertheless, disease recurrence is the rule, all patients requiring maintenance therapy with rituximab eventually. While innate resistance to rituximab in pemphigus patients is exceptional, acquired resistance is frequent and may develop even in patients with initial complete response to rituximab, representing a real challenge for physicians. We discuss the various resistance mechanisms and their complex interplay, as well as the numerous therapeutic alternatives that may be used to circumvent rituximab resistance. As no therapeutic measure is universally efficient, individualization of rituximab treatment regimen and tailored adjuvant therapies in refractory autoimmune blistering diseases are mandatory. [ABSTRACT FROM AUTHOR]

Pemphigus is a group of autoimmune mucocutaneous bullous disorders characterized by acantholysis resulting from autoantibodies targeting epithelial cell surface antigens. Studies reflect the presence of nail manifestations in some patients and suggest a potential correlation with clinical severity. This study examines the overall prevalence and characterizes the diverse manifestations of nail changes in pemphigus. We searched Cochrane, MEDLINE, EMBASE, and LILACS from 1990 to June 26, 2023 for studies reporting different nail changes in pemphigus patients. Data were collected and pooled to obtain proportions of the prevalence of nail changes in patients with pemphigus and subgroup analysis for pemphigus foliaceous and pemphigus vulgaris. The risk of bias was assessed with the Joanna Briggs Institute Checklist. Of 321 studies screened, 14 studies with 1,208 patients were included. Paronychia (n = 185) and Beau's lines (n = 104) were the most common nail changes identified. The pooled prevalence of nail disease in pemphigus patients was 0.389 (number of studies; [95% CI]: n = 9; [0.160–0.680], with high heterogeneity between studies (I2 = 95.0%, P < 0.001). Subgroup analysis revealed the highest prevalence in pemphigus foliaceous at 0.342 (n = 3; [0.109–0.688]) and pemphigus vulgaris at 0.396 (n = 5; [0.114–0.769]). Nail changes exhibited varied temporal relationships with disease onset and flares, preceding, concurrent, or following these events. Correlation with disease severity was noted, although discrepancies between studies were reported. Nail changes in pemphigus, particularly pemphigus vulgaris and pemphigus foliaceous, may be underrecognized. Observations regarding temporal associations and potential correlations with disease severity highlight the diagnostic and prognostic implications of nail changes in pemphigus. The limitations of this study include study heterogeneity and possible bias. Further research to establish the correlation of the presence and severity of nail changes on the overall disease course would be helpful. [ABSTRACT FROM AUTHOR]

Objective: Two-sample Mendelian randomization (TSMR) was employed to examine the association between lipidome and five inflammatory skin diseases. Method: To evaluate the association between various molecular subtypes of lipidome and the risk of five inflammatory skin diseases, we analyzed a comprehensive GWAS dataset comprising 179 lipidome. The Two-Sample Mendelian Randomization (TSMR) method was employed to investigate causal relationships. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test. Additionally, a sensitivity analysis was conducted to evaluate the influence of individual single nucleotide polymorphisms on Mendelian Randomization study. Results: Using 179 serum lipidome as exposures and five common inflammatory skin diseases as outcomes, we investigated their associations in this large-scale study. Our findings reveal significant impacts of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases. Glycerophospholipids were protective against pemphigus but predominantly posed risks for other inflammatory skin diseases. Specifically, phosphatidylcholine (16:0_0:0) exhibited the most significant risk association with lichen planus (OR = 1.25, 95% CI 1.11–1.40, P < 0.001). Conversely, glycerolipids showed no effect on lichen planus but were protective against pemphigus while potentially posing risks for other conditions. Triacylglycerol (46:2) showed the most substantial risk association with vitiligo (OR = 1.99, 95% CI 1.35–2.93, P < 0.001). Furthermore, sphingomyelins had no effect on atopic dermatitis but posed potential risks for other inflammatory skin diseases. Sphingomyelin (d40:1) notably emerged as a significant risk factor for pemphigus (OR = 1.91, 95% CI 1.37–2.66, P < 0.001). Conclusions: This study has elucidated the potential harmful effects of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases, while also providing valuable insights for future research into the pathophysiology, prevention and treatment of these conditions. [ABSTRACT FROM AUTHOR]

Purpose: In order to diagnose mucous membrane pemphigoid (MMP) and pemphigus vulgaris (PV) with gingival expression, clinical data must be compared with immunohistochemical data obtained using direct immunofluorescence (DIF). It is therefore essential to carry out a good quality mucosal biopsy for this vital additional test. To date, no study has been able to effectively guide clinicians in their choice of oral site for biopsy to guarantee the efficient contribution of DIF to diagnosis. We propose a systematic review of the literature and a meta-analysis to clarify this issue. Materials and Methods: Electronic databases and bibliographies of articles were searched in April 2023. The primary outcome was the rate of DIF + contribution to diagnosis according to the location of the oral site biopsied. Results: 16 studies were included. Gingival biopsies showed a rate of DIF + 100% [97%-100%] p = 0.998 I2 = 0.0% with no heterogeneity for PV, and 90.2% [66.5%-100%] p < 0.001 I2 = 89.6% with high heterogeneity for MMP. For the other oral sites, this rate was 95.7% [87.4%- 100%] p = 0.011 I2 = 73.0% with moderate heterogeneity for PV, and 87.4% [70.1%- 98.7%] p < 0.001 I2 = 92.6% with high heterogeneity for MMP. In addition, meta-regression confirmed the significant association between the appearance of the biopsied mucosa and the rate of DIF + in MMP (p < 0.001), with no influence on residual heterogeneity. Conclusion: The nature of the oral mucosa biopsied does not influence the rate of DIF + to diagnosis. The choice of biopsy site should only take into account the characteristics of the clinical picture and the benefit/risk balance of the surgical protocol. The sample must be taken in healthy aeras as close as possible of active lesions: on the gingiva if the MMP and PV are strictly gingival, on the alveolar mucosa if the whole gingiva is altered and on any healthy mucosa if a large number of oral sites are affected. Clinical trials: CRD42023392345. [ABSTRACT FROM AUTHOR]

Gut microbiota dysbiosis has been linked with numerous autoimmune disorders and inflammatory skin pathologies. The present study is a narrative review aiming to examine dysregulations in the gut microbiota of patients with pemphigus and bullous pemphigoid, exploring how these alterations may contribute to diseases' development and/or progression. Significant alterations in the composition of intestinal micro-biota were identified in patients with pemphigus and bullous pemphigoid: reduction in short-chain fatty acid-producing bacteria: Faecalibacterium prausnitzii, Lachnospiraceae and Coprococcus spp., which are known for their anti-inflammatory effects, and increased abundance of Escherichia coli, Shigella spp., Klebsiella spp., Bacteroides fragilis and Flavonifractor spp., which are recognized for their pro-inflammatory impact. The composition of gut microbiota might influence the pathogenesis of autoimmune bullous diseases. Modified levels of bacteria could become innovative biomarkers for the detection of high-risk individuals, monitoring disease progression and predicting response to treatment. Furthermore, regulating bacterial levels might have therapeutic effects in diminishing inflammation and disease advancement, potentially serving as future therapeutic strategies. [ABSTRACT FROM AUTHOR]

In this study, we aimed to examine the relationship between the serum cytokine levels of patients with pemphigus vulgaris (PV) and the Pemphigus Disease Area Index (PDAI), along with the presence of anti‐desmoglein (Dsg) 1 antibody, anti‐Dsg3 antibody and co‐infection among patients with pemphigus vulgaris. This retrospective study included 62 PV patients and 59 healthy individuals who attended the Second Affiliated Hospital of Kunming Medical University from November 2014 to November 2022. The serum concentrations of cytokines and chemokines were assessed using the Luminex 200 System (a high‐throughput cytokine detection method). Additionally, anti‐Dsg1 and anti‐Dsg3 antibodies were determined through enzyme‐linked immunosorbent assay, while disease severity was evaluated using the PDAI scoring system. The PV group exhibited elevated levels of Th1 cytokines (such as interleukin (IL)‐1RA, IL‐1β, IL‐2, IL‐12p70, GM‐CSF, TNF‐α, IL‐18, IFN‐γ), Th2 cytokines (IL‐5, IL‐10, IL‐13) and Th17/Th22‐related cytokines (IL‐17A, IL‐22) compared to the healthy control group (p < 0.05). Conversely, the levels of chemokines (macrophage inflammatory protein‐1 alpha (MIP‐1α), stromal cell‐derived factor‐1 alpha (SDF‐1α), interferon‐inducible protein‐10 (IP‐10), Regulated on Activation in Normal T‐Cell Expressed And Secreted (RANTES), growth‐regulated on‐gene‐alpha (GRO‐α), MIP‐1β) and Th2 (IL‐31) were lower in the PV group compared to the healthy control group (p < 0.05). No significant differences were observed in other cytokines and chemokines (p > 0.05). Additionally, IL‐7, IFN‐γ, IL‐18 and GRO‐α showed positive correlations with PDAI, IL‐6 correlated positively with anti‐Dsg3 antibody levels, and IL‐12p70, IL‐18, and IFN‐γ correlated positively with anti‐Dsg1 antibody levels. Furthermore, IL‐15 exhibited a positive association with skin infections. PV patients have elevated levels of various cytokines and chemokines, and there are different degrees of elevation in cytokines and chemokines associated with the activation of various T cell subsets. PDAI and the Dsg1 antibody levels are mainly related to the Th1‐related cytokines. [ABSTRACT FROM AUTHOR]

Pemphigus foliaceus (PF) is an autoimmune blistering disorder which affects the superficial layers of the epidermis with rare mucosal involvement. We present the case of a 12‐year‐old girl with PF involving the eyes and eyelids. A literature review of pediatric nonendemic PF revealed another two cases with ocular manifestations. Eyelid involvement is an uncommon feature of PF that should be properly identified and treated. [ABSTRACT FROM AUTHOR]

The article focuses on assessing whether sites of primary lesions in pemphigus vulgaris (PV) are more susceptible to relapse. It identifies the anatomical locations where initial lesions occur and determines if these same sites are more likely to experience relapses. It suggests that tissue-resident memory T cells may play a significant role in this phenomenon, potentially explaining why certain sites are recurrently affected.

Several auto-immune diseases have been linked to vitamin D deficiency as a contributing environmental factor. Its pleiotropic effects on the immune system, especially its essential role in maintaining immune tolerance, make the vitamin D pathway of great interest. In this study, we focused on Pemphigus foliaceous (PF) in Tunisian population. we aimed to quantify the Serum 25[OH]D levels using chemiluminescence assay and to analyze the differential expression of the VDR, CYP27B1 and CYP24A1 genes in the circulating blood cells and lesional skin tissue of PF patients using Q-PCR. A genetic explanation was then sought to explore any direct relationship between tag polymorphisms and the inherited features of PF. Results confirmed a vitamin D hypovitaminosis in Tunisian PF patients. Interestingly, a differential gene expression correlated to the disease stratification was noted. Indeed, at the systemic level, an upregulation of VDR and CYP27B1 genes was observed in healthy controls compared to PF patients. Notably, in lesional skin tissue, the clinical and serological remission phase was correlated with high transcriptional levels of the VDR gene and conversely a drop in expression of the CYP24A1 gene. Genetic analysis indicated the involvement of the most appealing polymorphisms, rs2228570 and poly (A) microsatellite, in PF etiopathogenesis. Indeed, CAC13 haplotype was associated with a higher risk of PF development. Our findings suggest that alterations in the vitamin D-VDR pathway may influence PF physiopathology, making this pathway a potential target for pharmacological modulation, especially for cortico-resistant PF patients. [ABSTRACT FROM AUTHOR]

This article discusses the potential therapeutic target MKK3 in blister formation in pemphigus, a condition characterized by autoantibody-mediated disruption of keratinocyte adhesion. The study aims to understand the roles of MKK3 and MKK6 in pemphigus and evaluate their inhibition as a treatment approach. Immunohistochemical analysis of skin specimens from pemphigus patients showed pronounced expression of phosphorylated MKK3 and p38 MAPK, indicating their involvement in pemphigus pathogenesis. In vitro studies using an MKK3 inhibitor demonstrated improved cell-cell adhesion and reduced blister formation. Targeting MKK3 may offer a promising alternative treatment option for pemphigus and other autoimmune and inflammatory conditions. [Extracted from the article]

Objective: This study aims to conduct an extensive analysis of autoimmune bullous diseases, particularly pemphigus vulgaris and bullous pemphigoid, in Shanghai, China, from 2016 to 2023. It seeks to understand the demographic profiles, comorbidities, mortality rates, risk factors, and socioeconomic impacts associated with autoimmune bullous disease. Methods: A cross-sectional study design was employed, enrolling 1,072 patients. Diagnostic measures included clinical manifestations, histopathology, direct immunofluorescence, and serologic tests. The study also involved a detailed socioeconomic analysis and evaluation of occupational risks. Results: The findings highlight a significant occupational risk in industries requiring enhanced safety measures, with a notable prevalence of autoimmune bullous disease among workers in these sectors. A considerable portion of the patients were from low-income backgrounds with limited literacy, indicating the economic burden of autoimmune bullous disease. A key discovery of the study is the potential pathological link between autoimmune bullous disease and interstitial lung disease. Conclusion: This research, one of the first comprehensive studies on autoimmune bullous disease in China, underscores the need for targeted healthcare strategies and further investigation into autoimmune bullous disease, particularly its relationship with interstitial lung disease. [ABSTRACT FROM AUTHOR]

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.

Abstract Hailey-Hailey disease is a rare genodermatosis described in 1939, with an autosomal dominant inheritance pattern, characterized by compromised adhesion between epidermal keratinocytes. It has an estimated prevalence of 1/50,000, with no gender or race predilection. It results from a heterozygous mutation in the ATP2C1 gene, which encodes the transmembrane protein hSPA1C, present in all tissues, with preferential expression in keratinocytes. Mutations in the ATP2C1 gene cause changes in the synthesis of junctional proteins, leading to acantholysis. It usually begins in adulthood, with isolated cases at the extremes of life. It manifests as vesico-bullous lesions mainly in the flexural areas, which develop into erosions and crusts. Chronic lesions may form vegetative or verrucous plaques. Pruritus, a burning feeling and pain are common. It evolves with periods of remission and exacerbation, generally triggered by humidity, friction, heat, trauma and secondary infections. The diagnosis is based on clinical and histopathological criteria: marked suprabasal acantholysis, loosely joined keratinocytes, giving the appearance of a “dilapidated brick wall”, with a few dyskeratotic cells. The acantholysis affects the epidermis and spares the adnexal epithelia, which helps in the differential diagnosis with pemphigus vulgaris. Direct immunofluorescence is negative. The main differential diagnoses are Darier disease, pemphigus vegetans, intertrigo, contact dermatitis, and inverse psoriasis. There is no cure and the treatment is challenging, including measures to control heat, sweat and friction, topical medications (corticosteroids, calcineurin inhibitors, antibiotics), systemic medications (antibiotics, corticosteroids, immunosuppressants, retinoids and immunobiologicals) and procedures such as botulinum toxin, laser and surgery. There is a lack of controlled clinical trials to support the choice of the best treatment.

Abstract Background Anti-desmoglein (Dsg)1 is produced in pemphigus foliaceus (PF), affecting exclusively the skin. Pemphigus vulgaris (PV) shows the production of anti-Dsg3 in the mucosal form, and anti-Dsg1 and 3 in the mucocutaneous form. Anti-Dsg3 autoantibodies have been rarely reported in PF. Objectives To determine the factors associated with the production and pathogenicity of anti-Dsg3 in PF. Methods Comparative analytical study of three patients groups: 16 PF-anti-Dsg3+, and 42 PF-anti-Dsg3(-) and 22 PV treatment-naïve cases. Serum was used in the anti-Dsg1 and 3 ELISA, and in immunoblotting (IB) with human epidermis extract. The expression of Dsg1 and 3 in paraffin sections was analyzed by immunohistochemistry (IHC). HLA-DRB1 alleles were compiled from a database. Results In the PF-anti-Dsg3+ group: age range similar to that of the PV group (p > 0.9999); predominance of the generalized form of PF (p = 0.002); anti-Dsg3 titers lower than those of PV (p < 0.0001); IB confirmed Dsg3 identification in one (8.33%) of 12 patients; IHC showed exclusive cytoplasmic internalization of Dsg1; HLA-DRB1 alleles of susceptibility to PF, with the absence of alleles associated with PV, in the five typed patients. Study limitations Most of the patients in the PF-anti-Dsg3+ group were undergoing treatment. Conclusion The presence of anti-Dsg3 antibodies in PF was related to older age (comparable to that of PV) and the generalized form of PF. The non-pathogenicity of anti-Dsg3 antibodies in PF can be attributed to the low serum anti-Dsg3 titers, the lack of Dsg3 internalization as detected by IHC, and the absence of PV-associated HLA-DRB1 alleles.

Abstract Background Rituximab (RTX) has been utilised off‐label for a variety of dermatological indications beyond pemphigus vulgaris. Efficacy has been reported in other immunobullous disorders, inflammatory dermatoses and connective tissue diseases. Objectives To assess the off‐label use of RTX in our centre with respect to indications, frequency and duration of treatment, efficacy, and adverse events. Methods Charts were retrospectively reviewed for all patients who received dermatologist‐prescribed RTX infusions off‐label at our centre between 2009 and 2022. Efficacy was categorised based on reported percentage reduction of disease activity: very good (75%–100%), good (50%–74%), partial (25%–49%) and none (0%–24%). Results Twenty‐nine patients received RTX off‐label during this time period. Infusions were discontinued in 28% (n = 8), due to insufficient clinical response. Median treatment duration for those on 6‐12‐monthly regular infusions was 2.4 years (range 0.5–11 years). Indications included cutaneous lupus (n = 9), mucous membrane pemphigoid (n = 5), pyoderma gangrenosum (n = 6), lichen planus (n = 2), dermatomyositis (n = 1), livedoid vasculitis (n = 1), sarcoidosis (n = 1), bullous pemphigoid (n = 1), pemphigus vulgaris, foliaceus and vegetans (n = 1 each). Clinical improvement was documented in 79% (n = 23); very good in 48% (n = 14), good in 17% (n = 5), and moderate in 14% (n = 4). Clinical efficacy in immunobullous disorders was 100% (9/9), 67% in cutaneous lupus (6/9), 33% in pyoderma gangrenosum (2/6), and 50% in lichen planus (1/2). No side effects were documented for 79% (n = 23). Adverse peri‐infusion events were seen in three patients (10%). Four patients died during follow up; one due to neutropenic sepsis with a background of advanced malignancy, and three due to Covid‐19. Conclusions RTX was prescribed for multiple off‐label dermatological indications, often for recalcitrant disease. Responses were good overall, with a reassuring safety profile. Three patients died of Covid‐19; knowledge of the impact of RTX on the immune response and efficacy of vaccines is expanding and will continue to inform guidelines for RTX use in the post‐Covid era.

Background: Rituximab (RTX) is considered the first-line treatment for pemphigus vulgaris (PV), which is a B-cell-mediated acquired autoimmune disease. However, no consensus on the optimum dosage has been achieved. Objectives: To investigate the efficacy and safety of low-dose RTX (a single infusion of 500mg) for the treatment of PV, a cohort study was conducted for patients with PV, along with a 12-month follow-up following the administration of RTX. Methods: Patients with moderate or severe PV were divided into group A (low-dose RTX combined with corticosteroids) and group B (corticosteroids alone). Data on complete remission (CR) rates, doses of corticosteroids, cumulative doses of corticosteroids at the third, sixth, and twelfth months, pemphigus disease area index and adverse effects (AEs) were collected. Results: Forty-four patients with moderate or severe PV were enrolled in this study (19 in group A and 25 in group B). Patients treated with low-dose RTX had higher CR rates, lower doses of corticosteroids at the third, sixth, and twelfth months, lower cumulative doses of corticosteroids at the sixth and twelfth months, and fewer AEs than those who received corticosteroids alone. Conclusions: This study indicated that low-dose RTX may be a beneficial and secure therapy option for patients with moderate to severe PV. [ABSTRACT FROM AUTHOR]

Background: Scoring systems play a crucial role in dermatology by providing objective measurements of disease severity, treatment efficacy, and outcome comparisons. In autoimmune blistering diseases (AIBDs), standardized scoring systems are essential for accurate evaluations; however, there is currently a lack of consensus on scoring methods. Objective: This literature review explores scoring systems in AIBDs by tracing their development, addressing challenges, and highlighting their role in defining endpoints, regulatory considerations, and clinical trials. Materials and Methods: Existing scoring systems for AIBDs, such as the Pemphigus Disease Area Index, Autoimmune Bullous Skin Disorder Intensity Score, Pemphigus Oral Lesions Intensity Score, Oral Disease Severity Score, and Pemphigus Vulgaris Activity Score, are examined for their validity, reliability, and responsiveness. The Bullous Pemphigoid Disease Area Index for bullous pemphigoid is also discussed. The concept of minimal clinically important differences is explored to determine clinically significant improvements in disease severity. Conclusion: This review provides a comprehensive understanding of the central role of scoring systems in dermatology and their implications for research and clinical practice in AIBDs.

Pemphigus in pregnancy is a special clinical scenario that has potential consequences on both maternal and fetal outcomes. Being an autoimmune disease with Th2 preponderance, pemphigus is expected to flare in pregnancy, especially in the first two trimesters. Fetal outcomes like stillbirth and neonatal pemphigus have been reported, the latter being a consequence of a transient transplacental transfer of autoantibodies. Management needs to be individualized keeping the risk/benefit ratios of therapies in mind while optimizing maternal and fetal health. It is crucial to have appropriate counseling regarding conception for women with pemphigus in the child-bearing period because the probability of adverse materno-fetal outcomes is higher if the disease is severe.

Background: Autoimmune bullous diseases are associated with high morbidity and mortality. Traditionally, systemic corticosteroids and conventional immunosuppressive agents have been the mainstay of treatment, but their broad immunosuppressive effects and long-term complications have prompted the exploration of newer more targeted therapies. Materials and Methods: This review explores the evolving landscape of therapeutic options for immunobullous diseases, with a particular focus on pemphigus, bullous pemphigoid (BP), and mucous membrane pemphigoid, by searching PubMed, clinicaltrials.gov, and Cochrane databases for published literature from 2014 to 2023. Results/Discussion: We discuss emerging treatments for pemphigus such as B cell modulatory drugs, anti-inflammatory drugs, those inhibiting autoantibody half-life or blister-inducing activity, and stem cell therapy, while offering insights into the level of evidence, potential benefits, and limitations of each approach. The role of biologics and novel therapies like rituximab, omalizumab, and dupilumab in reshaping the management of BP is also discussed. Conclusion: The article highlights the need for further research, clinical trials, and comparative studies to determine the most effective and safest treatment options for patients with immunobullous diseases.

Abstract Objective This study aims to conduct an extensive analysis of autoimmune bullous diseases, particularly pemphigus vulgaris and bullous pemphigoid, in Shanghai, China, from 2016 to 2023. It seeks to understand the demographic profiles, comorbidities, mortality rates, risk factors, and socioeconomic impacts associated with autoimmune bullous disease. Methods A cross-sectional study design was employed, enrolling 1,072 patients. Diagnostic measures included clinical manifestations, histopathology, direct immunofluorescence, and serologic tests. The study also involved a detailed socioeconomic analysis and evaluation of occupational risks. Results The findings highlight a significant occupational risk in industries requiring enhanced safety measures, with a notable prevalence of autoimmune bullous disease among workers in these sectors. A considerable portion of the patients were from low-income backgrounds with limited literacy, indicating the economic burden of autoimmune bullous disease. A key discovery of the study is the potential pathological link between autoimmune bullous disease and interstitial lung disease. Conclusion This research, one of the first comprehensive studies on autoimmune bullous disease in China, underscores the need for targeted healthcare strategies and further investigation into autoimmune bullous disease, particularly its relationship with interstitial lung disease.

Background: Pemphigus is a potentially life-threatening autoimmune blistering disease which characteristically affects skin and mucosae. Pulse therapy for the treatment of pemphigus has been in vogue for several years and considered better than conventional corticosteroids. Aims and objectives: This study was conducted to evaluate the efficacy and safety of pulse therapy in pemphigus patients treated over a period of 10 years. Materials and Methods: This retrospective study was based on medical records of Pemphigus patients treated at Department of Dermatology from January 2008 to December 2017. Diagnosis of pemphigus was made on clinical ground, Tzanck smear and histopathology of skin/mucous membrane lesions. Patients were put on DCP/DAP depending on the completion of family. Results: A total of 124 patients were included in the study. Age of patients ranged from 18 years to 72 years with mean of 41.21±12.71 years. Amongst 124 patients, 114 (92%) had pemphigus vulgaris and 10 (8%) had pemphigus foliaceous. 89 patients received DCP and 35 patients received DAP therapy. Number of pulses received by patients in phase I ranged from 4 to 27, average being 8.16±4.63. 106 patients completed the phase I of which 83 completed the phase II. 54 patients had successfully completed phase III of which 22 are currently in phase IV and 28 patients have completed their five year follow up period and considered as cured. Conclusion: Pulse therapy is a cheap and easily available mode of therapy in treatment of pemphigus in India even in the present era of modern molecules like Rituximab. With pulse therapy, it is now possible to induce and maintain remission, and achieve cure, provided the patients strictly adhere to the prescribed schedule.

This document is a letter to the editor discussing the management of pemphigus vulgaris and foliaceus, two types of autoimmune blistering diseases. The authors mention the use of rituximab, a medication commonly used to treat these conditions, and its effectiveness in achieving complete remission. They also discuss the potential for relapse and the use of repeated cycles of rituximab to prolong remission. The authors reference previous studies and guidelines on the topic. [Extracted from the article]

Introduction: The review article explores the evolving role of Bruton's tyrosine kinase (BTK) inhibitors in immune-mediated dermatological conditions, addressing significant gaps in current treatment approaches. Areas Covered: The review comprehensively discusses the mechanisms of action of BTK inhibitors, including irreversible and reversible inhibitors. Clinical applications of BTK inhibitors in dermatological diseases such as pemphigus, chronic spontaneous urticaria (CSU), hidradenitis suppurativa (HS), systemic lupus erythematosus (SLE), and atopic dermatitis are explored, highlighting recent advancements and ongoing clinical trials. Potential advantages of BTK inhibitors over existing therapies and challenges in translating preclinical findings to clinical outcomes are discussed. Expert Opinion/Commentary: BTK inhibitors represent a promising therapeutic avenue for immune-mediated dermatological conditions, offering oral administration, targeted pathway inhibition, and a favorable safety profile compared to biologic therapies. Ongoing research and clinical trials hold the potential to address unmet needs and reshape the therapeutic landscape in dermatology. Plain Language Summary: Our manuscript explores how a new class of medications called Bruton tyrosine kinase (BTK) inhibitors could revolutionize the treatment of skin conditions caused by the immune system. These conditions, like chronic spontaneous urticaria (CSU), pemphigus, and systemic lupus erythematosus (SLE), often lack effective treatments. BTK inhibitors work by targeting specific pathways in the immune system, offering hope for patients with these challenging conditions. We reviewed clinical trials and research studies to understand how BTK inhibitors could benefit patients. One significant advantage of BTK inhibitors is their ability to provide targeted therapy, meaning they can specifically block the faulty immune responses driving these conditions without affecting the entire immune system. This targeted approach could lead to fewer side effects compared to current treatments, such as corticosteroids or immunosuppressants, which can have widespread effects on the body. Overall, BTK inhibitors represent a promising new approach to treating immune-mediated skin conditions. With further research and development, they could offer safer and more effective alternatives to current treatments, improving the lives of patients worldwide. [ABSTRACT FROM AUTHOR]

Pemphigus foliaceus (PF) is a superficial form of pemphigus. Treatment options for PF resemble pemphigus vulgaris, including glucocorticosteroids, immunosuppressive agents and rituximab et al. These treatment approaches can effectively improve the condition but may also be accompanied by high risks of side effects. Therefore, it is crucial to find a safe and effective treatment options for patients with PF. It will not only benefit/be necessary for patients who refuse glucocorticosteroids or immunosuppressive agents treatments, but also for patients who cannot be treated with glucocorticosteroids or immunosuppressive agents. Herein, we reported a case of PF that was treated with apremilast without systemic glucocorticosteroids or immunosuppressive agents. A 54-year-old woman presented with itchy erythema and erosions on the trunk for more than 1 month. The patient applied mometasonefuroate cream without improvement for a duration of two weeks. The past history of diabetes mellitus and atrophic gastritis was reported. Physical examination revealed scattered erythematous macules and erosions on the trunk. No mucosal involvement was observed. The condition was assessed by the pemphigus disease area index and numerical rating scale, with baseline scores of 7 and 8, respectively. Histopathological examination showed acantholysis and intraepithelial blister. Direct immunofluorescence revealed the presence of IgG and Complement 3 deposition between the acanthocytes with the reticular distribution. Based on enzyme-linked immunosorbent assay results, the levels of Dsg1 and Dsg3 antibodies were 28.18 and 0.26 kU/L respectively. The diagnosis of PF was made. This patient was successfully treated with apremilast without systemic glucocorticosteroids or immunosuppressive agents. The patient has continued with apremilast 30mg once daily for maintenance and no adverse events related to apremilast such as gastrointestinal side effects were observed during the 9-month follow-up period. In conclusion, apremilast therapy without systemic glucocorticosteroids nor immunosuppressive agents might provide an effective alternative to management of mild PF without obvious side effect. [ABSTRACT FROM AUTHOR]

This manuscript reviews the significant skin manifestations of Lewy body disease, including Parkinson's disease and dementia with Lewy bodies, and the diagnostic utility of skin biopsy. Besides classic motor and cognitive symptoms, non-motor manifestations, particularly dermatologic disorders, can play a crucial role in disease presentation and diagnosis. This review explores the intricate relationship between the skin and Lewy body disease. Seborrheic dermatitis, autoimmune blistering diseases (bullous pemphigoid and pemphigus), rosacea, and melanoma are scrutinized for their unique associations with Parkinson's disease, revealing potential links through shared pathophysiological mechanisms. Advances in diagnostic techniques allow the identification of promising biomarkers such as α-synuclein in samples obtained by skin punch biopsy. Understanding the dermatologic aspects of Lewy body disease not only contributes to its holistic characterization but also holds implications for innovative diagnostic approaches. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]