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.

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/).

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.

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

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.

JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 21, Issue 2 p. 175-177 CLINICAL LETTER Treatment of refractory pemphigus vulgaris oral lesions 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 Correspondence 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 Correspondence 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.14957AboutPDF 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 No abstract is available for this article. Volume21, Issue2February 2023Pages 175-177 RelatedInformation

Linear IgA/IgG bullous dermatosis (LAGBD) is a relatively rare autoimmune bullous disease characterized by both IgA and IgG antibodies to basement membrane zone. The heterogeneity and pathogenesis of antibodies and the relationship between IgA and IgG in LAGBD have not been fully elucidated. We observed clinical, histological and immunological features of three LAGBD cases at different time points in the disease course. In our cohort, two cases showed IgA antibodies to epidermal antigens vanished when their lesions cleared after 3 months of treatment. One refractory case showed increasing antigens targeted by IgA antibodies with the progression of the disease. Collectively, the results suggest that IgA antibodies may play a major role in LAGBD. In addition, epitope spreading may be related to disease relapse and treatment refractory.

Bullous pemphigoid (BP) is a complex inflammatory process with elevated levels of autoantibodies, eosinophils, neutrophils, and various cytokines. Hematological inflammatory biomarkers can reflect inflammatory state in various diseases. Up to now, the correlations of hematological inflammatory biomarkers and disease activity of BP remain unknown. The purpose of this study was to clarify the associations between hematological inflammatory biomarkers and disease activity of BP. The levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR) and mean platelet volume (MPV) of 36 untreated BP patients and 45 age and gender matched healthy controls were detected by routine blood tests. The correlations between hematological inflammatory markers and clinical characteristics of BP were statistically analyzed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean levels of NLR, PLR, PNR and MPV in 36 untreated BP patients were 3.9, 157.9, 45.7 and 9.4 fl, respectively. Increased NLR (p < 0.001), PLR (p < 0.01), and MPV (p < 0.001) but decreased PNR (p < 0.001) were observed in BP patients when compared with healthy controls. In BP patients, the levels of NLR were positively correlated to BPDAI Erosion/Blister Scores (p < 0.01); and the levels of NLR and PLR were both positively correlated to BPDAI without Damage Score (both p < 0.05) and BPDAI Total Score (both p < 0.05). No correlation was found in other statistical analyses between hematological inflammatory markers and clinical characteristics in BP patients involved in the present study. Therefore, NLR and PLR are positively correlated with disease activity of BP.

The correlation between IgE anti-BP180 NC16A autoantibody and disease activity of bullous pemphigoid (BP) remains disputable. To determine the levels of IgE anti-BP180 NC16A autoantibody and its clinical significance in untreated BP patients. IgG and IgE anti-BP180 NC16A autoantibody in serum and blister fluid samples of 34 untreated BP patients was detected by enzyme-linked immunosorbent assay (ELISA), and correlation with clinical and pathological features of BP were statistically analysed. The Bullous Pemphigoid Disease Area Index (BPDAI) was used to measure disease activity of BP. The mean baseline level of IgG anti-BP180 NC16A autoantibody in serum and blister fluid samples of untreated BP patients was 75.3 U/mL and 1.54 U/mL, respectively (A450, cutoff: 0.126). IgE anti-BP180 NC16A autoantibody was positive in 21.9% serum and 14.7% blister fluid samples of untreated BP patients. IgE anti-BP180 NC16A autoantibody levels in serum samples positively correlated with those from blister fluid samples (r = 0.983, p < 0.05). However, IgE anti-BP180 NC16A autoantibody level in both serum and blister fluid samples of untreated BP patients did not correlate with IgG anti-BP180 NC16A autoantibody, age, extent of elevated peripheral blood eosinophils, BPDAI erosion/blister score, BPDAI urticaria/erythema score, BPDAI pruritus score, BPDAI without damage score, or BPDAI total score (all p > 0.05). No significant correlation was identified between disease activity and positive or negative anti-BP180 NC16A IgE autoantibody. Conclusion: IgE anti-BP180 NC16A autoantibody in both serum and blister fluid samples does not appear to correlate with disease activity of BP.

Objective:To analyze clinical and immunoserological features of patients with anti-p200 pemphigoid.Methods:Clinical data were collected from patients with confirmed anti-p200 pemphigoid in Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2015 to October 2021, and their clinical and immunoserological characteristics were retrospectively analyzed.Results:Seven patients with anti-p200 pemphigoid were included. Indirect immunofluorescence on salt-split skin (IIF-SSS) showed that serum IgG antibodies of the 7 patients were located in the dermis of the salt-split skin, and Western blot analysis with dermal extracts as substrates revealed a protein band with a relative molecular mass of 200 000. Four patients presented with classic bullous pemphigoid-like skin lesions, 2 initially presented with eczematous lesions, and 1 presented with linear IgA bullous dermatosis-like skin lesions. Circulating IgG antibodies could recognize the recombinant laminin γ1 C-terminal region in 6 cases. Four patients received different doses of systemic glucocorticoids, 1 of whom was resistant to high-dose systemic glucocorticoids (equivalent to 1.4 mg·kg -1·d -1 prednisone) ; 2 responded well to minocycline and dapsone; 1 was lost to follow-up. Four patients achieved complete remission and discontinued the treatment at a mean follow-up of 22.5 months; 2 received complete remissiona on minimal therapy at a mean follow-up of 8 months. Conclusion:Patients with anti-p200 pemphigoid presented with heterogeneous clinical manifestations, and the recombinant C-terminal fragment of laminin γ1 can serve as a reliable antigen substrate for the detection of autoantibodies in patients with anti-p200 pemphigoid; some patients can eventually achieve complete remission off treatment.

To the Editor: Pemphigus vulgaris (PV) and herpes simplex virus (HSV) infections mainly manifest as erosions in the oral mucosa; so, it is difficult to identify HSV infection in oral lesions of PV. PV is mainly treated with immunosuppressants, which may reactivate and disseminate HSV. 1 Demitsu T. Kakurai M. Azuma R. Hiratsuka Y. Yamada T. Yoneda K. Recalcitrant pemphigus foliaceus with Kaposi's varicelliform eruption: report of a fatal case. Clin Exp Dermatol. 2008; 33: 681-682 Crossref PubMed Scopus (18) Google Scholar Therefore, it is necessary to explore the clinical features of HSV infection in patients with PV with oral lesions.

To the Editor: Laboratory diagnostic methods of bullous pemphigoid (BP) include direct immunofluorescence (DIF) microscopy, BP180 NC16A enzyme-linked immunosorbent assays (ELISA), and indirect immunofluorescence using salt-split skin (ssIIF) in our daily clinical practice. Immunofluorescence (IF) studies are important parts of the laboratory workup for BP. DIF is regarded as the gold standard for BP diagnosis; however, it is not specific and can also be found in other acquired autoimmune subepidermal blistering dermatosis. ssIIF was found to have a specificity of 100% for BP diagnosis and in some guidelines, it is recommended to perform ssIIF in every patient with clinically suspected BP.[1] To date, it is still not defined whether ssIIF can be used as a routine diagnosis method of BP. The BP180 NC16A ELISA is a practical and reliable diagnostic test for BP; however, the false-positive results of BP180 NCA6A ELISA were recently reported in a wide range of dermatoses, which might cause its uncertainty in the diagnosis of BP. Thus, we conducted a single center retrospective study to compare diagnostic values of these tests for BP from Hospital for Skin Diseases, Chinese Academy of Medical Sciences between January 2014 and January 2019. It was approved by the local medical ethical committee (No. 2017-KY-022) and consent was obtained from patients prior to serum collection. In this study, we analyzed the data of 569 patients who were tested by ssIIF, DIF, BP180 NC16A ELISA and histopathology at the initial disease stage prior to systemic therapy, and were followed for at least 1 year, and BP diagnosis was made on the basis of the following criteria: (1) tense bullae on body without scaring, and Nikolsky sign is negative; (2) histopathological finding shows subepidermal blister formation; (3) DIF shows linear deposits of IgG and/or C3 along the basement membrane zone (BMZ); (4) ssIIF shows linear IgG and/or C3 reaction with the epidermal side of BMZ in the salt-split skin; (5) index value of BP180 ELISA is more than 9 U/mL. Diagnosis of BP requires at least two columns, (4) and (5), or requires three columns, (1), (2), and (3) if it meets one column of (4) and (5). Based on these diagnosis criteria, 164 of 569 suspected BP patients were diagnosed with BP, and the remaining 405 patients were used as non-BP controls. Study flowchart and characteristics of patients are described in Supplementary Figure 1, https://links.lww.com/CM9/B92 and Supplementary Table 1, https://links.lww.com/CM9/B92. Sensitivity and specificity were calculated for assessing diagnostic values of DIF, ssIIF and BP180 NC16A ELISA, and Kappa test was used to evaluate the consistency between these tests. Measurement data were shown as mean ± standard deviation, and were compared by Mann-Whitney U test or paired t-test. Numeration data with rate or composition ratio were analyzed by McNemar test, χ2 test or Fisher's exact test. Statistical analyses were done using SPSS statistics 22 (IBM Corp, Armonk, NY, USA). All tests were two-sided, and P < 0.05 was considered as statistically significant. For diagnosis of BP, the sensitivity of DIF, ssIIF, and BP180 ELISA were 78.05%, 97.56%, 93.90%; and their specificity were 93.58%, 99.75%, and 95.55%, respectively [Supplementary Table 2, https://links.lww.com/CM9/B92]. In previous studies, the specificity of DIF and ssIIF was 98% to 99%, 97% to 100%, and the sensitivity was 88% to 91%, 73% to 97%, respectively.[2,3] The specificity of DIF was similar to the findings of the studies mentioned above, and further proved that DIF was not specific enough for BP diagnosis. Some researchers found routine serration pattern analysis can help to improve the specificity of DIF in BP. The sensitivity of DIF in our data is lower than the studies mentioned above, and the reason may be due to availability of serologic test data, or ethnic differences, which was supported by another domestic article, and their positive rate of DIF is 82%.[4] Some researchers found IgG4 testing may be helpful in definitively diagnosing BP in patients with negative or equivocal linear IgG deposition on DIF.[5] In this study, the high specificity of ssIIF was consistent with the reports mentioned above, and the sensitivity was similar to the recent study from 13 international centers,[3] but higher than the previous report.[2] The relative higher sensitivity may be caused by transporting and tackling skin tissue timely which can avoid protein denaturation and degradation. Given all the data of ssIIF on BP diagnosis, we considered ssIIF as a valuable method for BP diagnosis. In the present study, we found that BP180 ELISA results were negative in 6.1% BP patients, which might be caused by lower titers of anti-BP180 NC16A antibodies or existence of autoantibodies recognizing BP180 on non-NC16A domain and/or BP230 in BP sera. The results indicated that it needed to be combined with IF to avoid a misdiagnosis. Next, the sensitivity and specificity of combined tests were analyzed. The sensitivity of ssIIF/BP180 ELISA (91.66%) is statistically significantly higher than those of ssIIF/DIF (75.61%), DIF/BP180 ELISA (71.95%), and the specificities of three combined tests are all 100% [Supplementary Table 2, https://links.lww.com/CM9/B92]. These results indicated that combined tests could obtain perfect specificity, although the sensitivity is decreased a little bit, and combination of ssIIF/BP180 ELISA has the highest sensitivity in BP diagnosis. In addition, Kappa coefficients between ssIIF/BP180 ELISA, ssIIF/DIF, and DIF/BP180 ELISA were 0.86, 0.706, 0.622, respectively (all P < 0.001). And BP180 ELISA was positively correlated with ssIIF in BP patients [Supplementary Table 3, https://links.lww.com/CM9/B92]. The limitation of this study is the absence of diagnostic criteria as a reference standard for the diagnosis of BP. Patients were diagnosis as BP by at least both positive ssIIF and positive BP180 NC16A ELISA, or a combination of clinical bulla, subepidermal bulla on routine histopathology and positive DIF with either positive ssIIF or positive BP180 NC16A ELISA which may bias the sensitivity and specificity of these three diagnostic methods. In summary, ssIIF could be used as a routine laboratory diagnosis method for BP, and the combination of ssIIF and BP180 ELISA is better for diagnosis of BP. Funding This work was supported by grants from Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (Nos. CIFMS-2017-I2M-1-017, CIFMS-2021-I2M-1-059), and Scientific Research Project of Jiangsu Provincial Health Commission (No. ZD2021035). 4njkmnjm Conflicts of interest None.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune subepidermal blistering disease. Currently, researches on LABD are still limited, and most are case reports. This review summarizes research advance in etiology and pathogenesis, clinical and histopathological manifestations, diagnosis and treatment of LABD.

Objective:To optimize indirect immunofluorescence on salt-split skin (IIF-SSS), and to evaluate its performance in detection of bullous pemphigoid (BP) antibodies.Methods:Normal human foreskin and non-foreskin skin tissues were used to prepare salt-split substrates under 3 different experimental conditions: traditional group rotated at 4 ℃ for 48 - 72 hours, low-temperature immersion group soaked at 4 ℃ for 48 - 72 hours, room-temperature immersion group soaked at 25 ℃ (range: 23 - 27 ℃) for 24 hours. Serum samples were obtained from 20 patients with bullous pemphigoid (BP) in Hospital of Dermatology, Chinese Academy of Medical Sciences between August 2019 and August 2020, and subjected to IIF on the intact skin or salt-split substrates by using a multiple dilution method. Paired-sample t test was used for comparisons of means between two paired samples. Results:No dermal-epidermal separation was observed in the substrates prepared in the low-temperature immersion group at 48 - 72 hours, while dermal-epidermal separation occurred in the lower lamina lucida of the foreskin and non-foreskin substrates in the room-temperature immersion group and the traditional group. For the 20 patients with BP, the reciprocal end-point titers ( M[ Q1, Q3]) detected with the salt-split non-foreskin skin and salt-split foreskin in the room-temperature immersion group, and with the salt-split non-foreskin skin in the traditional group were 5 120 (2 560, 17 920), 1 280 (640, 2 560), 1 280 (640, 2 560), respectively. Moreover, 19 (95%) patients with BP showed that the reciprocal end-point titers detected with the substrates in the room-temperature immersion group were 1 - 5 times those in the traditional group ( t = 8.04, P<0.001), suggesting that the performance of salt-split skin in the room-temperature immersion group was superior to that in the traditional group in the detection of BP antibodies; however, there was no significant difference in the reciprocal end-point titers of BP antibodies between the salt-split foreskin in the room-temperature immersion group and salt-split non-foreskin skin in the traditional group ( t<0.001, P>0.05). The reciprocal end-point titers in 20 BP sera detected by conventional IIF on the intact non-foreskin skin and foreskin were 320 (160, 640) and 480 (160, 1 120), respectively; the reciprocal end-point titers detected by IIF on the salt-split foreskin and non-foreskin skin in the room-temperature immersion group, as well as on the salt-split non-foreskin skin in the traditional group, were all consistent with or 1 - 7 times higher than those detected by conventional IIF ( t = 6.47, 14.83, 5.26, respectively, all P<0.001) . Conclusion:The soaking method at room temperature 25 ℃ (23 - 27 ℃) for preparing salt-split substrates has advantages of short duration and simple procedure, and the sensitivity of IIF-SSS using the substrates prepared by this method is equal or superior to the traditional salt-split method for detecting BP antibodies.

Objective:To evaluate the value of indirect immunofluorescence on salt-split skin (IIF-SSS) in the diagnosis of bullous pemphigoid (BP) .Methods:A single-center clinical retrospective study was conducted. Totally, 163 patients with newly diagnosed BP were collected from Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2013 to January 2019, so were 404 controls, including 161 with pemphigus, 67 with eczema, 26 with drug eruption, 23 with erythema multiforme, 18 with prurigo nodularis, etc. Blood samples were collected before the treatment, and IIF-SSS, BP180 NC16A enzyme-linked immunosorbent assay (ELISA) and direct immunofluorescence (DIF) assay were performed to evaluate the value of IIF-SSS in the diagnosis of BP. Measurement data were compared by using t test and Mann-Whitney test, and enumeration data were compared by using chi-square test and Fisher′s exact test or McNemar test. Results:The number of cases positive for IIF-SSS, BP180 NC16A ELISA and DIF assay was 160, 153 and 127 respectively in the BP group, and 0, 18 and 26 respectively in the control group. The sensitivities of IIF-SSS, BP180 NC16A ELISA and DIF assay for the diagnosis of BP were 98.15%, 93.86% and 77.91% respectively, and their specificities were 100%, 95.54% and 93.56% respectively. There was strong consistency in the diagnosis of BP between IIF-SSS and DIF (Kappa coefficient= 0.767, P < 0.001) . Conclusion:IIF-SSS has relatively high sensitivity and specificity for the diagnosis of BP, and can serve as a routine method for diagnosing BP.

层黏连蛋白332(Laminin-332,Ln-332)是基底膜的主要成分之一,它是真表皮连接处锚定复合物中的关键分子,在维持基底膜完整性中发挥重要作用.该蛋白作为配体可与细胞跨膜蛋白整合素α6β4、α3β1等相互作用,参与细胞的黏附、迁移.在正常皮肤中,Ln-332通过与整合素α6β4及Ⅶ型胶原连接,将半桥粒附着于真皮.当基底膜遭到破坏时,Ln-332分泌快速增加,与整合素α3β1结合,作为细胞迁移的支架,促进角质形成细胞向创面迁移,从而加速伤口愈合.编码Ln-332的相关基因突变可导致交界性大疱性表皮松解症;而对Ln-332不同亚基的自身抗体可引起抗Ln-332型黏膜类天疱疮.此外,研究发现Ln-332可促进某些上皮来源肿瘤的侵袭、转移,参与形成肿瘤微环境.

黏膜类天疱疮是指一组慢性、异质性、自身免疫性表皮下水疱病,主要累及口腔、眼睛等黏膜,其特点是具有形成瘢痕的风险.患者体内存在抗基底膜带的自身抗体,分别是针对BP180、BP230、层粘连蛋白332、整合素α6β4,和Ⅶ型胶原,其中BP180的羧基端、层粘连蛋白332被认为是主要的自身抗原.诊断主要基于临床表现、组织病理及免疫学检查.治疗上应根据受累部位,疾病严重程度及进展速度,选择合适的治疗方案,为了尽量减少不可逆的损害,多学科合作诊疗是必要的.