Objective::Pemphigus vulgaris (PV) is a severe autoimmune skin disease, and the role of acetylcholine receptor (AChR) in PV is still unclear. This study aimed to investigate the effects of M3 AChR and α9 AChR interference on acantholysis of keratinocytes, which may provide a deeper understanding of PV pathogenesis.Methods::This was an in vitro experimental study designed to explore the roles of M3 AChR and α9 AChR in PV pathogenesis. Sera from patients with PV and controls were collected from Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2016, to December 30, 2016, and were used to extract PV-immunoglobulin G (IgG). RNA interference was used to silence the M3 AChR gene or α9 AChR gene in HaCaT cells, after which the cells were treated with IgG from PV patients or controls. Changes in the adhesion of HaCaT cells were observed using a cell dissociation assay. Immunofluorescence assay was used to detect the staining patterns of desmosome proteins. Western blot analysis was performed to detect cytoskeleton- or noncytoskeleton-associated desmosome protein levels. The interactions of desmoglein-3 and plakoglobin were qualitatively detected using co-immunoprecipitation, and the p38 MAPK and epidermal growth factor receptor (EGFR) phosphorylation levels were examined. Two-tailed Student’s t-test was used to compare the data of the two groups. Results::With M3 AChR silencing, the HaCaT cells treated with PV-IgG-showed severe acantholysis compared to those with controls’ treatment ( P < 0.001); levels of cytoskeleton-associated desmoglein and plakoglobin were significantly reduced (both P < 0.001), whereas the phosphorylation of EGFR increased ( P = 0.001). In contrast, α9 AChR-silenced HaCaT cells exhibited fewer cell fragments than control HaCaT cells without α9 AChR silencing co-cultured with PV-IgG ( P < 0.001). The co-culture of α9 AChR-silenced cells with PV-IgG suppressed the internalization of desmoglein, and increased levels of cytoskeleton-associated desmoglein-3 and PG ( P < 0.001 and P= 0.002), and a close interaction between desmoglein-3 and plakoglobin was observed by immunoprecipitation ( P = 0.002). The phosphorylation levels of p38 MAPK and EGFR were suppressed by α9 AChR silencing (both P < 0.001). Conclusion::The findings of this study provided evidence that M3 AChR and α9 AChR may play roles in the pathogenesis of PV, demonstrating that M3 AChR exerts a protective role, whereas α9 AChR plays a pro-pathogenic effect in PV-IgG-induced acantholysis.

Introduction: Lupus erythematosus-associated skin disease - papulonodular mucinosis (PNM) is characterized by a diffuse deposition of mucin in the dermis. The relationship between PNM and lupus erythematosus and appropriate treatment is crucial for PNM patients. Aim: To investigate the relationship between systemic lupus erythematosus (SLE) and PNM. Material and methods: We collected clinicopathological, treatment and follow-up data of 13 patients with PNM of the Chinese Academy of Medical Sciences and Peking Union Medical College from 2004 to 2024. According to the diagnostic criteria for SLE, the patients were divided into two groups: the SLE group and non-SLE group who presented with PNM as major manifestations. The similarities and differences between the two groups were summarised and compared. Results: Thirteen patients included 8 (61.5%) males and 5 (38.5%) females, who presented with generalized (61.5%) or localized (38.5%) nodules/plaques with a mean onset age of 39.8 years. Among them, 4 (33.3%) cases accorded with the diagnostic criteria for SLE. As to treatment, the SLE group adopted the regimen of systemic prednisolone, hydroxychloroquine and intralesional triamcinolone acetonide. The rest of patients all received systemic prednisolone, together with some other adjuvant therapy. They all gained improvement of varying degree and to date, no SLE symptoms have developed in 11 patients, while 2 patients have developed arthralgia, oral ulcer and alopecia. Conclusions: Although the clinical presentation varies, the SLE and non-SLE groups of PNM have similar histological features and outcomes, suggesting that these two situations are highly associated.

Despite the recognized association between bullous pemphigoid (BP) and psoriasis, the clinical and immunological profiles, and inflammation patterns of coexistence remain undefined. We therefore conducted a retrospective cohort study of 140 BP patients without psoriasis (BP alone group) and 24 BP patients with comorbid psoriasis (BP-PsO group) to characterise these features. Average age of BP onset was significantly lower in the BP-PsO group, compared with the BP alone group (median [IQR]: 67.00 [58.00-75.75] years vs. 75.00 [64.00-82.00] years) (p = 0.021). In the BP-PsO group, 21 patients (87.5%) had coexisting active psoriatic plaques and BP lesions. The overall disease activity of BP was comparable between the BP-PsO and BP alone groups, both showing typical BP immunological features. Serum IL-17A level was significantly elevated in the BP-PsO group (median [IQR]: 18.29 [10.39-43.50] pg/mL), compared with the BP alone group (median [IQR]: 10.36 [9.16-12.11] pg/mL) and psoriasis alone groups (median [IQR]: 11.65 [10.10-12.78] pg/mL), and correlated with disease activity. Flow cytometry confirmed enhanced IL-17A response in peripheral blood mononuclear cells from the BP-PsO group, with an elevated proportion of CD4+ IL-17A+ cells and IL-17A+ T follicular helper cells versus corresponding controls. IL-13 was comparably elevated in both the BP-PsO and BP alone groups, relative to psoriasis alone group and healthy controls. In a representative case, inhibition of IL-17A led to concurrent remission of both diseases. BP with psoriasis shares foundational features with idiopathic BP, but represents a distinct clinical entity characterised by a predominant IL-17A signature, highlighting its potential as a therapeutic target.

A woman and avid gardener in her 70s with rheumatoid arthritis who was receiving long-term immunosuppression presented with a 6-month history of progressive papulonodules on her face and extremities. What is your diagnosis?

Bullous pemphigoid (BP) triggers profound functional changes in both immune and non-immune cells in the skin and circulation, though the underlying mechanisms remain unclear. In this study, we conduct single-cell transcriptome analysis of lesional and non-lesional skin, as well as blood samples from BP patients. In lesional skin, non-immune cells upregulate pathways related to metabolism, wound healing, immune activation, and cell migration. LAMP3+DCs from cDC2 show stronger pro-inflammatory signatures than those from cDC1, and VEGFA+ mast cells, crucial for BP progression, are predominantly in lesional skin. As BP patients transition from active to remission stages, blood B cell function shifts from differentiation and memory formation to increased type 1 interferon signaling and reduced IL-4 response. Blood CX3CR1+ ZNF683+ and LAG3+ exhausted T cells exhibit the highest TCR expansion among clones shared with skin CD8+T cells, suggesting their role in fueling skin CD8+T cell clonal expansion. Clinical BP severity correlates positively with blood NK cell IFN-γ production and negatively with amphiregulin (AREG) production. NK cell-derived AREG mitigates IFN-γ-induced keratinocyte apoptosis, suggesting a crucial balance between AREG and IFN-γ in BP progression. These findings highlight functional shifts in BP pathology and suggest potential therapeutic targets. Single-cell analysis reveals bullous pemphigoid alters the function of skin non-immune and immune cells as well as blood lymphocytes, links progression to NK cell IFN-γ/AREG balance, and suggests potential therapeutic targets.

Natural killer (NK) cells are potent mediators of anti-tumor immunity, yet their functions are frequently subverted by tumor microenvironment-driven immunosuppression. Here, it dissects the molecular mechanisms underlying NK cell dysfunction in cutaneous malignancies and identifies a paradoxical cytokine shift in tumor-associated NK cells-reduced production of IFN-γ and TNF-α alongside elevated amphiregulin (AREG), an EGFR ligand linked to tumor progression. Single-cell transcriptomic analysis indicates that this reprogramming correlates with elevated glucocorticoid receptor (GR/NR3C1) pathway activity in tumor-infiltrating NK cells. Functional validation demonstrated that glucocorticoids specifically induce AREG production in NK cells, with tumor-associated prostaglandin E2 (PGE2) augmenting this response. Genetic ablation or pharmacological inhibition of NR3C1 abolished glucocorticoid-driven AREG induction. Moreover, primary GR activation established persistent chromatin accessibility at the AREG locus, sensitizing NK cells to enhanced AREG production upon secondary glucocorticoid exposure. Functionally, AREG counteracts NK cell-mediated tumor apoptosis, while the adoptive transfer of AREG-deficient human NK cells significantly suppressed melanoma, cutaneous squamous cell carcinoma (cSCC), and hepatocellular carcinoma growth in NCG mice. These findings establish the GR-AREG axis as a multi-layered therapeutic target for restoring NK cell anti-tumor function.

BACKGROUND:Anti-p200 pemphigoid is a rare autoimmune blistering disorder with limited data from China. This retrospective study aimed to investigate the clinical and serological characteristics of anti-p200 pemphigoid to enhance disease understanding. METHODS:We analysed 86 confirmed anti-p200 pemphigoid patients, evaluating their clinical manifestations, histopathological findings, and immunoserological profiles. RESULTS:The patients had a mean onset age of 56.92 ± 18.59 years and a male-to-female ratio of 2.31:1. The clinical presentation is highly heterogeneous, mimicking classic BP (57/86, 66.28%), and four cases (4/52, 7.69%) had concurrent psoriasis. Subepidermal blistering with variable dermal infiltrates was observed in 68 cases (68/70, 97.14%): neutrophil-predominant (24.89%), mixed neutrophilic/eosinophilic (31.43%), or eosinophil-predominant (27.14%). The positive rates of DIF, ss-IIF, IB with dermal extract, and IB with laminin γ1 C-terminal domain (LNγ1C) were 94.29% (66/70), 80.23% (69/86), 100% (86/86), and 64.29% (45/70), respectively. CONCLUSIONS:Anti-p200 pemphigoid closely resembles BP clinically but exhibits distinct immunopathological features. The partial reactivity to laminin γ1 (LNγ1) implies antigenic heterogeneity, warranting further investigation.

Background: Conventional systemic corticosteroid therapy for bullous pemphigoid (BP) has been challenged due to severe adverse events. Dupilumab has emerged as an alternative therapeutical option of BP patients. Objectives: To evaluate the efficacy of dupilumab monotherapy and the combination with medium/low-dose corticosteroids for BP treatment. Methods: Thirteen, twenty-four and thirty-two BP patients treated with Dupilumab monotherapy (Dupi group), dupilumab combined with corticosteroids (Dupi + CS group), and corticosteroid monotherapy (CS group), respectively, were retrospectively analyzed for various clinical and laboratory parameters. Results: In the Dupi group, the total Bullous Pemphigoid Disease Area Index (BPDAI) Total, Erosion/Blister, Urticaria/Erythema and Itching NRS scores were all reduced significantly after 2--4 weeks of treatment, but the BPDAI Mucosal Score was not changed significantly at the end of the overextended time of treatment. All the above clinical parameters and many laboratory parameters (including the serum anti-BP180 autoantibodies [IgG] level, blood eosinophil count, and percentage) were significantly reduced in both Dupi + CS and CS groups after treatment, but no statistical differences were found in the reduction rates of these parameters between the two groups. However, the Dupi + CS group had less baseline dose and cumulative dosage of prednisone at the time of disease control, and fewer adverse effects were reported than the CS group. Study limitations: The retrospective design and small clinical sample size of the Dupi group. Conclusions: For BP patients, dupilumab monotherapy based on the treatment of atopic dermatitis can significantly improve skin lesions and pruritus symptoms but may be ineffective for oral mucosal lesions. The combination of dupilumab and medium/low-dose corticosteroids can achieve the same effect of corticosteroid therapy with superior safety. (c) 2024 Sociedade Brasileira de Dermatologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Linear IgA bullous dermatosis (LABD) is an acquired autoimmune subepidermal blistering skin disease characterized by circulating and tissue-bound IgA autoantibodies that recognize epitopes within the hemidesmosomal protein BP180, including its NC16A domain. Histologically, LABD has long been defined by neutrophil infiltration and dermal-epidermal separation. However, the pathogenic roles of anti-NC16A IgA and neutrophils in LABD, as well as their interactions, have not been thoroughly studied. We show that passive transfer of patient-derived anti-NC16A IgA induce clinical and histologic LABD pathology in humanized NC16A mice that are reconstituted locally or systemically with human neutrophils. The lesional skin of mice exhibits significantly elevated levels of the neutrophil chemoattractants CXCL-1 and CXCL-2. Furthermore, we show significantly increased levels of the neutrophil chemoattractant IL-8 in blister fluids of patients with LABD. This study provides direct evidence that anti-NC16A IgA in patients with LABD are pathogenic and interact with neutrophils to mediate tissue injury and subepidermal blister formation. This study further corroborates the importance of neutrophil-mediated tissue injury in LABD disease physiology and establishes a clinically relevant in vivo model system that can be used to systematically dissect the immunopathogenesis of LABD.

Pemphigus, a potentially lethal autoimmune skin disease, is mediated by desmoglein-specific antibodies, manifesting cutaneous and mucosal blisters and erosions. The interaction between multiple immune counterparts contributes to the progress of pemphigus. Currently, the emergence of bioinformatic analysis enables investigators to gain a global picture of the pemphigus immune network, based on the exhaustive pedigree annotation of multiple subsets. T helper subsets dominate the landscape as mentioned previously, and innate immune cells have been involved as well. Of particular interests is which phenotype of T cells orchestrates the autoimmune process and chronic inflammation in a certain condition. In this review, the circulatory and peripheral immune cells and cytokine components constituting the immune microenvironment are separately discussed to provide a perspective on pemphigus pathogenesis, with particular reference to insights provided by the bioinformation technique.

Objective To investigate the current status of multidrug-resistant bacteria(MDRO)wound infections in patients with autoimmune bullous diseases(AIBDs),and to analyze their risk factors.Methods A retrospective study was conducted,and inpatients with AIBDs accompanied by wound infections were collected from Hospital of Dermatology,Chinese Academy of Medical Sciences from January 2020 to December 2022.A descriptive analysis was carried out to analyze the basic characteristics of these patients and pathogenic characteristics of MDRO.Univariate and binary logistic regression models were used to analyze independent risk factors for MDRO infections in patients with AIBDs.Differences between the MDRO infection group and common bacterial infection group were analyzed by using t test,Mann-Whitney U test and chi-square test.Results Totally,271 patients with AIBDs accompanied by wound infections were included,including 159 males(58.7％)and 112 females(41.3％),and 142 patients(52.4％)were aged over 60 years.Most patients with AIBDs were diagnosed with pemphigus vulgaris(131 cases,48.3％),or bullous pemphigoid(99 cases,36.5％).Bacterial culture was positive in all the patients,and 74(27.3％)were infected with MDRO;a total of 108 strains of MDRO were detected,with relatively high detection rates of Staphylococcus(82 strains,75.9％)and Enterobacter(15 strains,13.9％).Significant differences were observed between the MDRO infection group and the common bacterial infection group in the duration of hospitalization,involved body surface area,proportions of patients self-modificating drug dosage,proportions of patients topically using antibiotic ointments,proportions of patients using immunosuppressants,duration of glucocorticoid use,maximum dose of glucocorticoids and the first albumin level at admission(all P＜0.05),while there were no significant differences in the gender,age,proportions of patients at first hospitalization,types of AIBDs,duration of education,body mass index,disease duration,proportions of smoking patients,proportions of drinking patients,proportions of patients with comorbid chronic diseases,surgical history,prevalence of hypoalbuminemia,prevalence of mucosal involvement,proportions of patients receiving topical glucocorticoids,proportions of patients using biological agents,duration of antibiotic use,and the first total protein level at admission between the two groups(all P＞0.05).Logistic regression analysis showed that the use of topical antibiotic ointments,use of immunosuppressants,maximum dose of glucocorticoids,and self-modification of drug dosage were independent risk factors for MDRO infections(all P＜0.05).Conclusions The patients with AIBDs were prone to develop MDRO infections in wounds,and Staphylococcus infections were the most common.The use of topical antibiotic ointments,use of immunosuppressants,high dose of glucocorticoids,and self-modification of drug dosage may increase the risk of infections in patients with AIBDs.

BACKGROUND:Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease. Although the phenomenon of epitope spreading has been reported to be common in anti-p200 pemphigoid, the association between its clinical and immunoserological features has yet to be elucidated. OBJECTIVES:Our aim was to compare the clinical and immunoserological characteristics of anti-p200 pemphigoid patients with and without epitope spreading. METHODS:We performed a retrospective cohort study encompassing 30 patients with anti-p200 pemphigoid between January 2015 and December 2022. The clinical and immunoserological characteristics of anti-p200 pemphigoid were analyzed using combined immunoserological assays. RESULTS:Epitope spreading was observed in 11 of 30 patients (36.7%) with anti-p200 pemphigoid. Compared with patients in the non-epitope spreading group, patients in the epitope spreading group showed more heterogeneous clinical presentations (P = 0.018), a higher proportion of mucosal involvement (P = 0.003), higher Bullous Pemphigoid Disease Area Index (BPDAI) scores for skin erosions/blisters (P = 0.018), mucosal erosions/blisters (P = 0.001), activity (P = 0.017) and total scores (P = 0.022), and required a higher initial dose of prednisone for disease control (P = 0.040). CONCLUSIONS:This study supported the idea that anti-p200 pemphigoid was prone to epitope spreading. Anti-p200 pemphigoid patients with epitope spreading are more likely to present heterogeneous clinical phenotypes, frequent mucosal involvement, and a more severe and recalcitrant disease course.

Background The mechanism of livedoid vasculopathy (LV) remains unknown.Objectives To investigate the association between coagulation factors and LV and to assess the efficacy and safety of rivaroxaban in the treatment of patients with LV.Methods From May 2019 to July 2022, 89 patients with LV and 35 healthy controls were included in a cross-sectional cohort to measure the levels of coagulation factors. In addition, 55 patients with LV treated with rivaroxaban were included in a treatment cohort to assess the complete remission rate of ulcers (n = 44) and retiform purpura (n = 11) within 12 weeks.Results In the cross-sectional cohort, the activities of coagulation factor X in patients with LV were significantly higher than those in healthy controls: median 110.5% [interquartile range (IQR) 97.5-127.0%] vs. 101.3% (IQR 91.6-115.6); P = 0.05. In addition, coagulation factor X activities in the progressive stage were higher than at the stable stage: median 111.6% (IQR 102.3-132.5) vs. 105.4% (IQR 92.9-118.8); P = 0.04. Moreover, coagulation factor X activities were higher at the progressive stage than at the stable stage in a subgroup of 20 patients with LV (P = 0.04). In the treatment cohort taking rivaroxaban, 91% (40/44) of patients with ulcers achieved complete remission within 12 weeks, and 73% (8/11) of patients with retiform purpura achieved complete remission within 12 weeks. Mild side-effects occurred in 25% of patients (14/55), including menorrhagia (n = 10), gingival bleeding (n = 3) and haemorrhage (n = 1).Conclusions Coagulation factor X was associated with the incidence and severity of LV in this study. In addition, rivaroxaban was an effective and safe treatment for ulcers and retiform purpura in people with LV. This study found that coagulation factor X is associated with the incidence and severity of livedoid vasculopathy (LV). In addition, as an inhibitor of factor Xa, rivaroxaban was an effective and safe treatment for ulcers and retiform purpura in patients with LV. Importantly, the early administration of rivaroxaban for retiform purpura prevented its progression to ulcers.

Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly. The standard treatment of BP patients with systemic corticosteroid have some potential serious side effects. Up till now, there is still lack of novel treatment for BP patients. Baricitinib, a selective Janus kinase (JAK) 1 and 2 inhibitor, has been used to treat rheumatoid arthritis, alopecia areata, and COVID-19. Successful treatment of refractory BP by JAK inhibitors has been reported in sporadic cases. In this study, we reported 8 BP patients treated with baricitinib. The patients after treatment were followed up for 3-24 months, with an average of 9.1 months. All 8 cases achieved disease control and the mean disease control period was 3 weeks (1-6 weeks). The bullous pemphigoid disease area index total (21.2 ± 13.0 to 2.5 ± 4.3, p<0.01), erosion/blister (6.0 ± 7.7 to 0.2 ± 0.5, p<0.05), urticaria/erythema (10.2 ± 11.9 to 0.0 ± 0.0, p=0.06), mucosal erosion/blister (10.0 ± 6.4 to 4.5 ± 5.1, n=4, p=0.25) and itching NRS (3.6 ± 3.5 to 0.0 ± 0.0, p=0.06) scores were all reduced after 2 months’ treatment. Seven of 8 patients achieved complete remission during tapering at month 3 and did not experience relapse during the follow-up period. The serum levels of anti-BP180 autoantibodies (IgG) were reduced significantly (77.1 ± 47.8U/mL to 40.1 ± 37.1U/mL, n=6, p<0.05) after 3 months’ treatment. During the follow-up period, only one patient experienced mild elevation of serum creatinine level after 3 months’ treatment of baricitinib, which returned to normal through discontinuation of the medication. In conclusion, this study demonstrated that low-dose, short-term administration of baricitinib is effective and safe for treating BP patients.

BackgroundThe manifestations of bullous pemphigoid (BP) and herpes simplex virus (HSV) infection are similar in oral mucosa, and the laboratory detection of HSV has some limitations, making it difficult to identify the HSV infection in oral lesions of BP. In addition, the treatments for BP and HSV infection have contradictory aspects. Thus, it is important to identify the HSV infection in BP patients in time.ObjectiveTo identify the prevalence and clinical markers of HSV infection in oral lesions of BP.MethodsThis prospective cross-sectional descriptive analytical study was conducted on 42 BP patients with oral lesions. A total of 32 BP patients without oral lesions and 41 healthy individuals were enrolled as control groups. Polymerase chain reaction was used to detect HSV. Clinical and laboratory characteristics of patients with HSV infection were compared with those without infection.ResultsA total of 19 (45.2%) BP patients with oral lesions, none (0.0%) BP patients without oral lesions, and four (9.8%) healthy individuals were positive for HSV on oral mucosa. Among BP patients with oral lesions, the inconsistent activity between oral and skin lesions (p=0.001), absence of blister/blood blister in oral lesions (p=0.020), and pain for oral lesions (p=0.014) were more often seen in HSV-positive than HSV-negative BP patients; the dosage of glucocorticoid (p=0.023) and the accumulated glucocorticoid dosage in the last 2 weeks (2-week AGC dosage) (p=0.018) were higher in HSV-positive BP patients. Combining the above five variables as test variable, the AUC was 0.898 (p<0.001) with HSV infection as state variable in ROC analysis. The absence of blister/blood blister in oral lesions (p=0.030) and pain for oral lesions (p=0.038) were found to be independent predictors of HSV infection in multivariable analysis. A total of 14 (73.7%) HSV-positive BP patients were treated with 2-week famciclovir and the oral mucosa BPDAI scores significantly decreased (p<0.001).ConclusionHSV infection is common in BP oral lesions. The inconsistent activity between oral and skin lesions, absence of blister in oral lesions, pain for oral lesions, higher currently used glucocorticoid dosage, and higher 2-week AGC dosage in BP patients should alert physicians to HSV infection in oral lesions and treat them with 2-week famciclovir in time.

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 21, Issue 2 p. 175-178 CLINICAL LETTER Behandlung refraktärer oraler Läsionen bei Pemphigus vulgaris Hanmei Zhang, Hanmei Zhang Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYuan Wang, Yuan Wang Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorSuo Li, Suo Li Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorSuying Feng, Corresponding Author Suying Feng [email protected] Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China Korrespondenzanschrift Suying Feng, MD, Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangwangmiao Street 12, Nanjing, China Email: [email protected]Search for more papers by this author Hanmei Zhang, Hanmei Zhang Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorYuan Wang, Yuan Wang Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorSuo Li, Suo Li Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, ChinaSearch for more papers by this authorSuying Feng, Corresponding Author Suying Feng [email protected] Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, China Korrespondenzanschrift Suying Feng, MD, Department of Dermatology, Hospital for Skin Diseases and Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangwangmiao Street 12, Nanjing, China Email: [email protected]Search for more papers by this author First published: 20 February 2023 https://doi.org/10.1111/ddg.14957_gAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Volume21, Issue2February 2023Pages 175-178 RelatedInformation

Importance Dupilumab is a theoretically novel therapy for bullous pemphigoid (BP). However, its effectiveness and safety have yet to be confirmed in a large-scale study. Objective To assess the efficacy and safety of dupilumab in patients with BP and evaluate factors that potentially affect short-term and long-term outcomes. Design, Setting, and Participants A retrospective cohort study was conducted from January 1, 2021, to July 31, 2022. The median (IQR) follow-up period was 24.6 (11.5-38.4) weeks. This multicenter study was performed in 6 dermatology departments of the National Autoimmune Bullous Diseases Cooperative Group of China. Adult patients with BP that received 300 mg of dupilumab every 2 weeks following an initial dose of 600 mg were included. Patients were eligible if they had a clinical presentation of BP combined with immunological or pathological evidence. Patients with drug-induced BP, with less than 4 weeks of follow-up, and who received dupilumab or any other biologics within 6 months were excluded. Main Outcomes and Measures The primary outcome was the proportion of patients who achieved disease control within 4 weeks. Disease control was defined as the absence of new lesions and pruritus, combined with the healing of existing lesions. Complete remission rates, relapse rates, changes in Bullous Pemphigoid Disease Area Index (BPDAI) scores, itching numerical rating scale (NRS) scores, laboratory results within 64 weeks, and adverse events (AEs) were also assessed. Results Among 146 patients (median [IQR] age, 73 [64-85] years; 86 [58.9%] male patients) included in the study, 127 (87.0%) patients achieved disease control within 4 weeks, with a median (IQR) time of 14 (7-14) days. A total of 52 (35.6%) patients achieved complete remission, and 13 (8.9%) patients relapsed during the observation period. The complete remission rate and cumulative relapse rate at week 64 were 62.5% (5 of 8) and 30.9%, respectively. There was rapid and sustained improvement in clinical indicators and laboratory examination results after dupilumab treatment, including BPDAI scores, itching NRS scores, serum anti-BP180 and anti-BP230 antibodies, total IgE levels, and eosinophil count. Of these 146 patients, 107 (73.3%) did not report any AEs. The most common AEs were infections and eosinophilia. Serum anti-BP180 antibody levels of greater than 50 relative units (RU)/mL (OR, 3.63; 95% CI, 0.97-12.61; P = .045) were associated with 4-week disease control, and male patients were more likely to relapse (HR, 10.97; 95% CI, 1.42-84.92; P = .02). Conclusions and Relevance In this retrospective cohort study, dupilumab treatment was associated with improved clinical symptoms in patients with BP. The safety profile was favorable, although concurrent infection and eosinophilia might pose potential concerns. This study suggests that patients with anti-BP180 antibody levels of at least 50 RU/mL and female sex may respond better.

目的 总结表现为环状红斑水疱的自身免疫性表皮下水疱病的临床、组织病理、免疫血清学及治疗特点.方法 回顾性分析2015-2022年就诊于中国医学科学院皮肤病医院表现为环状红斑水疱的自身免疫性表皮下水疱病患者的资料.结果 共纳入患者25例,男10例、女15例,年龄(39.21±24.65)岁,包括线状IgA大疱性皮病9例,大疱性类天疱疮7例,抗P200类天疱疮5例,获得性大疱性表皮松解症4例,20例(80％)有不同程度瘙痒.15例(60％)出现真皮组织嗜酸性粒细胞浸润,11例(44％)外周血嗜酸性粒细胞计数增加,7例(28％)同时有嗜酸性粒细胞组织浸润和外周血嗜酸性粒细胞升高.盐裂皮肤-间接免疫荧光及免疫印迹实验显示,9例同时存在抗基底膜带IgG及IgA抗体,包括4例大疱性类天疱疮、1例线状IgA大疱性皮病、2例抗P200类天疱疮、2例获得性大疱性表皮松解症;5例同时存在多种抗基底膜带靶抗原的抗体.7例大疱性类天疱疮均予系统糖皮质激素治疗,其中5例联合免疫抑制剂,2例联合米诺环素;线状IgA大疱性皮病、抗P200类天疱疮、获得性大疱性表皮松解症患者对抗炎药物及氨苯砜治疗敏感.结论 多种类型自身免疫性表皮下水疱病均可有环状红斑、水疱表现,需根据血清学检查结果鉴别诊断.

Mucous membrane pemphigoid (MMP) is a type of subepithelial autoimmune bullous disease, affecting various mucosae, occasionally with skin lesions. Both diagnosis and treatment of MMP are difficult. Although multiple autoantigens have been identified for MMP, the pathogenesis of MMP is still unclear. In this study, we presented a female MMP case with extensive oral mucosal lesions and skin lesions, particularly on the extremities. IgG and IgA autoantibodies against multiple autoantigens including BP180, laminin 332, integrinα6β4 and desmoglein 3, and IgM autoantibodies against BP180 were identified during the disease course. Compared with IgG autoantibodies, the levels of IgA autoantibodies against various autoantigens decreased more significantly with improvement of clinical features after the initiation of treatments. Our findings indicated the importance of comprehensive autoantibody screening for different immunoglobulin types and autoantigens at multiple time points for the precise diagnosis of various autoimmune bullous diseases, and the significant involvement of IgA autoantibodies into the pathogenesis of MMP.