Gut Microbiome Dysbiosis in Patients with Pemphigus and Correlation with Pathogenic Autoantibodies.

BACKGROUND: Pemphigus is a group of potentially life-threatening autoimmune bullous diseases induced by pathogenic autoantibodies binding to the surface of epidermal cells. The role of the gut microbiota (GM) has been described in various autoimmune diseases. However, the impact of the GM on pemphigus is less understood. This study aimed to investigate whether there was alterations in the composition and function of the GM in pemphigus patients compared to healthy controls (HCs). METHODS: Fecal samples were collected from 20 patients with active pemphigus (AP), 11 patients with remission pemphigus (PR), and 47 HCs. To sequence the fecal samples, 16S rRNA was applied, and bioinformatic analyses were performed. RESULTS: We found differences in the abundance of certain bacterial taxa among the three groups. At the family level, the abundance of Prevotellaceae and Coriobacteriaceae positively correlated with pathogenic autoantibodies. At the genus level, the abundance of Klebsiella, Akkermansia, Bifidobacterium, Collinsella, Gemmiger, and Prevotella positively correlated with pathogenic autoantibodies. Meanwhile, the abundance of Veillonella and Clostridium_XlVa negatively correlated with pathogenic autoantibodies. A BugBase analysis revealed that the sum of potentially pathogenic bacteria was elevated in the AP group in comparison to the PR group. Additionally, the proportion of Gram-negative bacteria in the PR group was statistically significantly lower in comparison to the HC group. CONCLUSION: The differences in GM composition among the three groups, and the correlation between certain bacterial taxa and pathogenic autoantibodies of pemphigus, support a linkage between the GM and pemphigus.

Pemphigoid diseases in patients with end-stage kidney diseases: pathogenesis and treatment.

Background: Pemphigoid diseases constitute a group of autoimmune blistering disorders characterized by subepithelial blistering. The association between pemphigoid diseases and both end-stage kidney disease (ESKD) and its treatment is notable. However, there is limited evidence about the management of pemphigoid diseases in patients with ESKD. This systematic review compiled case reports and relevant studies, summarized the underlying mechanisms of pemphigoid diseases in patients with ESKD, and summarized the efficacy of various therapies. Methods: A systematic search of PubMed and Embase was performed for articles published between 1982 to June 2, 2024. Results: Fifty-three case reports and eight relevant studies were included. Triggers for pemphigoids in patients with ESKD included materials used to treat ESKD, immune dysregulation of patients with ESKD, and rejection of renal allograft. Treatment for these patients included removing triggers, as well as administering of corticosteroids, mycophenolate mofetil (MMF), tetracyclines, rituximab, methotrexate, dapsone, azathioprine, cyclosporine, intravenous immunoglobin (IVIG), plasmapheresis, and Janus kinase inhibitors. Conclusion: Removing triggers is the most effective strategy. Despite their suboptimal efficacy, corticosteroids remain the most commonly used agents in this patient population. MMF, tetracyclines, and rituximab are less used but with benefits. There are significant adverse effects associated with methotrexate treatment. Other treatment may also be beneficial and require further investigation. These findings may enable clinicians to optimize the therapeutic approach for these patients.

Factors influencing the outcomes of dermatoses during the COVID-19 outbreak in China: a retrospective study.

Background: The coronavirus disease 2019 (COVID-19) pandemic subverted people's lives and potentially affected the management and prognosis of pre-existing dermatoses. The study aims to identify factors influencing the outcomes of dermatoses during a rapid and widespread Omicron outbreak in China following the adjustment of the COVID-19 policy. Materials and methods: This retrospective observational study involved outpatients visiting the dermatology department at a tertiary referral hospital in Beijing, China between December 2022 and February 2023. Demographics, COVID-19 characteristics, treatment modalities, and dermatosis outcomes were subjected to statistical analysis. Results: The odds ratio (OR) for vitiligo aggravation during COVID-19 was 0.497 [95% confidence interval (CI): 0.254-0.973, p = 0.038] compared to total patients with various dermatoses. Psoriasis patients with a maximum body temperature (Tmax) over 38.6°C during COVID-19 were 2.833 times more likely to experience dermatosis aggravation (OR: 2.833 [1.029-7.803], p = 0.041). Moreover, autoimmune bullous disease (AIBD) patients receiving biologics treatment exhibited a reduced likelihood of aggravation during the COVID-19 outbreak (OR: 0 [0-0.531], p = 0.011). Conclusion: Vitiligo exhibits lower aggravation rates during COVID-19 than other dermatoses. A higher body temperature during COVID-19 infection can increase the risk of psoriasis aggravation. Biologics treatment reduces the risk of AIBD aggravation during the COVID-19 outbreak.

Comparison of gut microbiota dysbiosis between pemphigus vulgaris and bullous pemphigoid.

OBJECTIVE: Pemphigus vulgaris (PV) and bullous pemphigoid (BP) are two prevalent bullous diseases. Previous studies found that the antibodies of BP could be expressed in the intestinal epithelium and BP was tightly related to inflammatory bowel disease. Therefore, gut microbiota might also play an important role in bullous disease. However, the specific relationship between gut microbiota and bullous diseases remains unknown. Our study aimed to investigate the potential role of gut microbiota in the development and progression of different bullous diseases. METHODS: We conducted a prospective and observational cohort study at Peking Union Medical College Hospital. Untreated BP and PV patients were recruited, along with healthy controls (HC) who were spouses or caregivers of these patients. Fecal samples were collected, followed by 16S rRNA gene sequencing. Bioinformatics analyses were performed to assess the composition and function of gut microbiota. RESULTS: A total of 38 HC, 32 BP, and 19 PV patients were enrolled in this study. Compared to HC, BP, and PV exhibited a distinct gut microbiota composition, especially BP. The gut microbiota changes were mainly observed in the phylum Bacteroidetes, Firmicutes, and Proteobacteria. The ratio of Faecalibacterium to Escherichia-Shigella (F/E ratio) had a considerable predictive value (AUC: 0.705) for recognizing BP from PV. The levels of Faecalibacterium and Enterobacter were correlated to the anti-BP 180 and anti-desmoglein 3. Microbial functional prediction revealed elevated activity in pathways related to gut microbiota translocation significantly increased in BP patients, indicating a potential pathogenetic role in BP. CONCLUSIONS: Our study suggests that the composition of gut microbiota is specific in different bullous diseases and the role of gut microbiota differs. Gut microbiota could help distinguish BP and PV, and might play a role in the pathogenesis of different bullous diseases.

Identification of gut microbiota dysbiosis in bullous pemphigoid under different disease activity.

Bullous pemphigoid (BP) is a severe autoimmune blistering disease affecting patients' quality of life. Gut microbiota (GM) dysbiosis have been investigated to be associated with multiple autoimmune diseases. However, the relationship between GM and BP onset and remission remains to be established by a systematic study. We conducted a study that enrolled 24 patients with BP onset (BP group), 24 patients under remission stage (BP-R group) and 24 healthy controls (HC group). We applied 16S rRNA sequencing on faecal samples and revealed a separation of the microbiota structure. At the family level, Lachnospiraceae, Prevotellaceae and Veillonellaceae were more abundant in the HC and BP-R groups, while Bacteroidaceae, Ruminococcaceae and Enterobacteriaceae were more abundant in the BP group. Bugbase analysis revealed the potentially pathogenic bacteria had an increasing trend in the BP group compared with the HC group and this variation vanished in the BP-R group. At the amplicon sequence variants (ASV) level, Bacteroides ovatus (ASV40) and Veillonella dispar (ASV140) significantly decreased, while Prevotella copri (ASV54) increased in the BP group compared to the HC and BP-R groups. The HC group and BP-R group shared similar abundance. Furthermore, by correlation analysis, we investigated key ASVs correlated with clinical parameters and found some discriminate biomarkers between the BP and BP-R groups. Our study established a dynamic GM profile in BP patients under different disease activity, providing a new direction to understand the role of GM in BP pathogenesis and therapeutic effects.

Dupilumab effectively and rapidly treats bullous pemphigoid by inhibiting the activities of multiple cell types.

Background: Bullous pemphigoid (BP) is an autoimmune skin-blistering disease. Systemic corticosteroids remain the first line treatment for moderate-to-severe BP with the potential for severe adverse events. Dupilumab has emerged as an alternative option for BP patients. Objective: We evaluated the efficiency and safety of dupilumab on BP treatment and explored a mode of drug action in depth. Methods and results: A multicenter retrospective cohort included 20 BP patients who received dupilumab with or without systemic corticosteroid in dupilumab group, and 20 matched BP patients who received corticosteroid alone in conventional group. Serum samples were collected from 20 patients (10 from dupilumab group and 10 from conventional group) at baseline and week 4. Compared to systemic corticosteroid alone, dupilumab with or without systemic corticosteroid was similarly efficacious in clinical remission at week4 (complete remission plus partial remission: 100%) and week24 (complete remission plus partial remission:100%), but allowing significant decreases in the cumulative doses of corticosteroids with reducing the incidence of adverse events. However, dupilumab did not decrease BP180 antibody despite an obvious clinical improvement. Comparative plasma proteomic analysis performed before and after treatment in 3 BP patients from dupilumab group revealed that drug use was associated with 30 differentially expressed proteins, including 26 down-regulated and 4 up-regulated proteins. The former consisted of immune related proteins involved in T/B cell interactions (inducible T-cell co-stimulator ligand, ICOSL) and in the activation of eosinophils (PRG2), mast cells (S100A12), and complement (CR2). TARC and ICOSL levels correlated with BP severity in patients who received either dupilumab or conventional treatment. Conclusion: Dupilumab has similar efficacy in treating BP as conventional drugs, by inhibiting the activities of many types of immune cells and complement, and regulating the interactions between T and B cells.

Successful treatment of alopecia universalis with abrocitinib: a case report.

Abrocitinib, a highly selective inhibitor of Janus kinase 1 (JAK1), has been approved for the treatment of moderate-to-severe atopic dermatitis (AD). Patients with alopecia universalis (AU) co-morbid with AD receiving abrocitinib achieved clinical remission for both diseases. We report a case of a patient with AU after drug reaction with eosinophilia and systemic symptoms (DRESS) who responded well to abrocitinib therapy at a dose of 100 and 200 mg once daily. In addition, we reviewed cases of alopecia after DRESS and explored the underlying mechanisms for alopecia areata (AA) being an autoimmune sequela. The therapeutic effects of JAK inhibitors for AA may involve downstream cytokines, such as IFN-γ and IL-15. Abrocitinib may be a promising therapeutic option for recalcitrant AU.

Anti-interleukin 4 receptor α antibody for the treatment of Chinese bullous pemphigoid patients with diverse comorbidities and a 1-year follow-up: a monocentric real-world study.

Background: Bullous pemphigoid (BP) is a common subepidermal bullous disorder that lacks adequate treatment alternatives. Dupilumab, an anti-interleukin (IL) 4 receptor α antibody blocking Th2 molecules IL-4 and 13, has been used off-label and shown to be effective in refractory BP cases. Methods: BP patients with various disease severities and comorbidities were included in this case series. All patients received dupilumab alone or in combination with immunosuppressants in a real-world setting. Complete remission (CR) was defined as the absence of pruritus symptoms and previous BP eruptions, with only hyperpigmentation patches and without newly occurring lesions for at least 4 weeks. Disease relapse was classified as the appearance of three or more new lesions within 1 month or at least one large urticarial or eczematous lesion that did not resolve within a week. Findings: Ten individuals were enrolled in this case series. Pruritus symptoms and BP eruptions improved significantly in nine patients (90%). Seven patients (70%) attained CR, including all mild-to-moderate (100%) cases and three of six (50%) severe BP cases. At the dupilumab monotherapy stage, eosinophilia was observed in two severe cases. One patient out of seven (14.3%) relapsed after 1 year of follow-up after CR. Conclusion: Treatment of BP with diverse comorbidities with anti-IL-4 receptor α antibody provides further credentials to a prospective randomized study. More impressive efficacy and safety profiles were observed in patients with mild-to-moderate disease after 1 year of follow-up. Eosinophilia may occur in patients receiving dupilumab monotherapy.

Severe acute respiratory syndrome coronavirus 2 infection in patients with autoimmune bullous diseases in China.

Patients with autoimmune bullous diseases (AIBDs) are considered to be immunocompromised and, consequently, they may be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and have poorer outcomes. However, the risk and repercussions of SARS-CoV-2 infection in patients with AIBDs have not been fully understood. Therefore, we aimed to investigate the risk factors of SARS-CoV-2 infection and the impact of SARS-CoV-2 on patients with AIBDs. From December 2022 to January 2023, all patients with AIBDs who visited our clinic were enrolled in this study. Meanwhile, web-based questionnaires and telesurveys were used as supplements. Information about patients' demographics, comorbidities, SARS-CoV-2 infection, and vaccination, as well as AIBD status and treatments were collected and analyzed. The diagnosis of SARS-CoV-2 infection was based on a positive polymerase chain reaction test, and/or an antigen test, or the presence of typical symptoms in conjunction with an epidemiological history. Finally, 95 patients with AIBDs were enrolled, including 47 cases of pemphigus and 48 cases of pemphigoid cases, and 73 had symptoms consistent with coronavirus disease 2019. Common symptoms after SARS-CoV-2 infection were fever (80.8%), fatigue (75.0%), cough (71.2%), muscle/joint pain (49.3%), and sore throat (45.2%). No significant differences were found between SARS-CoV-2-infected and asymptomatic patients. Patients who had hypertension (p = 0.034), hyperlipidemia (p = 0.017), or more than two comorbidities (p = 0.011) were more likely to develop pneumonia after infection. Patients with pemphigus who did not achieve disease control (p = 0.045) or had an oral corticosteroid dose ≥15 mg/day (p = 0.024) and patients with pemphigoid with a disease duration ≥2 years (p = 0.037) were more prone to AIBDs aggravation. In conclusion, patients with AIBDs are generally susceptible to SARS-CoV-2 infection. Individuals with newly diagnosed AIBDs, uncontrolled disease, and a higher corticosteroid dose are more susceptible to disease exacerbation.

[Interpretation of 2021 French Guidelines for the Therapeutic Management of Bullous Pemphigoid].

Bullous pemphigoid (BP) is a common autoimmune subepidermal bullous disease.The diagnosis of BP relies on clinical manifestation,histopathology,direct and indirect immunofluorescence,and serological assay.In the past two decades,topical corticosteroids and systemic and/or topical corticosteroids were the major therapeutic options for localized/mild/moderate and extensive/severe BP,respectively.In 2021,several experts from the French Study Group on Autoimmune Bullous Skin Diseases collaboratively issued the updated guidelines for the therapeutic management of BP based on evidence-based medicine.The guidelines fully detailed the updated therapeutic options for extensive BP,BP of limited extent,localized form of BP,corticosteroid-dependent BP,and drug-induced/associated BP.In particular,systemic corticosteroids are no longer the first-line treatment for extensive BP.We interpret the guidelines to assist dermatologists in the comprehensive management of BP and promote the standardization of BP treatment.

Expression of Thymic Stromal Lymphopoietin in Immune-Related Dermatoses.

Thymic stromal lymphopoietin (TSLP), long known to be involved in Th2 response, is also implicated in multiple inflammatory dermatoses and cancers. The purpose of this study was to improve our understanding of the expression of TSLP in the skin of those dermatoses. Lesional specimens of representative immune-related dermatoses, including lichen planus (LP), discoid lupus erythematosus (DLE), eczema, bullous pemphigoid (BP), psoriasis vulgaris (PsV), sarcoidosis, and mycosis fungoides (MF), were retrospectively collected and analyzed by immunohistochemistry. Morphologically, TSLP was extensively expressed in the epidermis of each dermatosis, but the expression was weak in specimens of DLE. In a semiquantitative analysis, TSLP was significantly expressed in the epidermis in LP, BP, eczema, PsV, sarcoidosis, and MF. TSLP expression was higher in the stratum spinosum in LP, eczema, BP, PsV, and MF and higher in the stratum basale in sarcoidosis and PsV. Moreover, we found positive TSLP staining in the dermal infiltrating inflammatory cells of BP, PsV, and sarcoidosis. Our observation of TSLP in different inflammatory dermatoses might provide a novel understanding of TSLP in the mechanism of diseases with distinctly different immune response patterns and suggest a potential novel therapeutic target of those diseases.

[Clinical Characteristics and Gene Mutations in 186 Cases of Kindler Syndrome].

Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(r=0.234,P=0.023),palmoplantar keratoderma(r=0.325,P=0.001),webbing/pseudoainhum(r=0.247,P=0.016),dysphagia(r=0.333,P=0.001),urethral stricture(r=0.280,P=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(χ2=11.292,P=0.001)and anal stenosis(χ2=4.014,P=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).

Coexistence of Anti-p200 Pemphigoid and Psoriasis: A Systematic Review.

Background: A close association between psoriasis and anti-p200 pemphigoid has been demonstrated by numerous studies. However, the clinical characteristics of patients suffering from these two entities have not yet been well-elucidated. Objective: This study aimed to review the case reports and case series, summarizing clinical features and therapeutic strategies in patients suffering from anti-p200 pemphigoid and psoriasis. Methods: A systematic review was conducted by searching PubMed, EMBASE, and Web of Science databases for studies published in English involving patients with psoriasis and anti-p200 pemphigoid on 6 September 2021. All case reports and case series reporting patients diagnosed with anti-p200 pemphigoid and psoriasis were included in this systematic review. Results: A total of 21 eligible studies comprising 26 anti-p200 pemphigoid patients with preceding psoriasis were included in the qualitative synthesis. The average age at blisters eruption was 62.5 years, and the mean duration between the two entities was 15.6 years. Twenty-four percent of patients developed bullous lesions during UV therapy. Clinical manifestation of bullae and/or vesicles was recorded in all patients, and the trunk (94.7%) was most frequently involved, with only 15.8% reporting mucosal involvement. Epitope spreading was detected by immunoblotting in 33.3% of patients. All the patients reached completed remission during the course of disease, with 36.8% experiencing at least one relapse. Monotherapy of prednisolone was the leading therapeutic approach (n=6, 31.6%) required for disease control, but 5 (83.3%) of them suffered from blister recurrence after tapering or ceasing corticosteroid. Conclusion: Most of the clinical aspects of patients with anti-p200 pemphigoid and psoriasis were similar to what was demonstrated in previous articles on anti-p200 pemphigoid. Nevertheless, compared with other anti-p200 pemphigoid cases without psoriasis, a clinical manifestation pattern with more frequent involvement of the trunk and less mucosal involvement was illustrated in those with psoriasis. Generally, monotherapy is sufficient for a complete remission for such patients. However, one or more relapses have been recorded in a considerable portion of patients, especially those prescribed with prednisolone. It reminded us to be more cautious during a tapering of medication.

Case report: Successful treatment of non-bullous lichen planus pemphigoides with dupilumab.

Lichen planus pemphigoides (LPP) is a rare autoimmune bullous disease, characterized by the coexistence of lichen planus and subepidermal bullae. However, the minority of LPP patients present with papules rather than vesicles or blisters, which is defined as non-bullous LPP. The diagnosis of LPP relies on manifestations, histopathology, serological assay, and direct immunofluorescence of linear disposition of IgG and/or C3 at the basement membrane zone. Up to now, no standard therapeutic strategies have been proposed for the treatment of LPP. Herein, we describe an uncommon non-bullous LPP patient with widespread papules and erythema, probably induced by vaccination. During hospitalization, he had a poor response to the conventional treatment of topical and systemic corticosteroids, and his condition was finally alleviated by the addition of dupilumab. For LPP patients with a traditional medication failure, or who were not suitable for a higher dose of corticosteroids, a combination with dupilumab could be an alternative option.

Paradoxical phenomena of bullous pemphigoid induced and treated by identical biologics.

Objective: This study aimed to investigate the clinical features of biologics-induced bullous pemphigoid (BP) and the therapeutic effects of those agents for BP, exploring the underlying pathophysiological mechanisms. Methods: We searched PubMed, Web of Science, and Elsevier for studies involving pemphigoid patients treated with or induced by identical biologics published in English from January 2009 to April 2022. Results: Seventeen cases of drug-induced BP associated with anti-tumor necrosis factor (aTNF)-α therapies, one with interleukin (IL)-17 inhibitors, and seven with IL-12/IL-23 or IL-23 inhibitors were enrolled. Time to cutaneous toxicity varied among different types of agents, and the characteristics of clinical examinations were similar to idiopathic BP. Discontinuation of the culprit drugs and initiation of topical or systemic corticosteroids were adequate in most cases. Several monoclonal antibodies above have also been reported for the treatment of refractory or recurrent BP, especially concurrent with psoriasis. Conclusion: Biologics for immune-related diseases, including TNF-α, IL-17, and IL-12/IL-23 or IL-23 inhibitors, can both induce and treat BP, which might be associated with a helper T cells Th1/Th2 imbalance, complicated inflammatory networks, and a specific individual microenvironment, suggestive of a new perspective on the therapeutic algorithms of BP. There have been numerous reports about biologics inducing or treating BP. We have taken note of this phenomenon and focused on biologics with both pathogenetic and therapeutic effects on BP. Our review summarized the clinical characteristics of associated cases, trying to figure out the underlying mechanisms of this paradoxical phenomenon and to provide an integrated perspective and new therapeutic alternatives for BP.

Efficacy and safety of tetracyclines for pemphigoid: a systematic review and meta-analysis.

The aim of this review was to evaluate the efficacy and safety of tetracyclines for treatment of pemphigoid. We searched PubMed, EMBASE, Ovid, Web of Science, and the Cochrane Library for studies involving pemphigoid patients treated with tetracyclines published in English before 29 February 2020. References of included studies were also screened to widen the scope of the literature search. Data regarding predefined clinical outcomes of 341 patients from 77 studies were extracted and analyzed. A meta-analysis was conducted on the basis of 4 studies including 2 randomized controlled trials and 2 comparative studies. The patients had a mean age of 74.60 ± 13.18 years, 45.4% were males, and 54.6% were females. There were 185 patients with mild-to-moderate and 143 patients with severe disease. The average initial doses were 1.62 ± 0.39 g/day for tetracycline, 0.20 ± 0.01 g/day for doxycycline, and 0.11 ± 0.05 g/day for minocycline. The average time on tetracyclines was 3.74 ± 5.99 months, and 261 (81.3%) patients reported partial or complete remission. Relapses occurred in 72 (28.3%) cases. Adverse effects were experienced by 130 (41.9%) patients. The pooled ORs for short-term effectiveness, relapse, adverse effects, and 1-year survival in patients treated with oral tetracyclines vs. systemic corticosteroids were 0.40 (95% CI, 0.22-0.76), 0.69 (95% CI, 0.44-1.10), 0.47 (95% CI, 0.27-0.82) and 2.02 (95% CI, 1.16-3.50), respectively. Compared to doxycycline and minocycline, tetracycline was significantly associated with better treatment outcomes and fewer adverse effects (p < 0.05). This review revealed tetracyclines' efficacy and safety in pemphigoid treatment and may offer support for clinical use of tetracyclines in pemphigoid.

Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases.

Thymic stromal lymphopoietin (TSLP) was initially demonstrated to be critical in regulating inflammatory responses among various allergic disorders (such as atopic dermatitis, food allergy, and asthma). Although two isoforms (short form and long form) of TSLP have been demonstrated in human tissues, the long form of TSLP (lfTSLP) is strongly implicated in the pathogenesis of allergies and cutaneous immune-mediated diseases. The immunomodulatory activity of lfTSLP varies widely, driving T helper (Th) cells polarizing Th2 and Th17 immune responses and inducing itch. Moreover, lfTSLP is closely associated with skin fibrosis, epidermal hyperplasia, angiogenesis, and homeostatic tolerogenic regulations. This review highlights significant progress from experimental and clinical studies on lfTSLP in cutaneous immune-mediated diseases (atopic dermatitis, psoriasis, bullous pemphigoid, systemic sclerosis, chronic spontaneous urticaria, Behçet's disease, vitiligo, rosacea, systemic lupus erythematosus, and alopecia areata). We also offer original insights into the pleiotropic properties of the cytokine TSLP in various pathophysiological conditions, with significant clinical implications of TSLP-targeted therapies for immune-mediated skin diseases in the future.

[Clinical Analysis of Eight Cases of Pemphigus with High Titers of Anti-desmoglein Antibodies in Remission].

Objective To investigate the clinical manifestations,diagnosis,treatment,and laboratory examination characteristics of 8 pemphigus patients with high titers of anti-desmoglein antibodies in remission. Methods A retrospective study was conducted for the pemphigus patients diagnosed and treated in the department of dermatology from January 2013 to September 2020.The patients should have the serum anti-desmoglein antibodies ≥150 U/ml in remission or the antibody levels dropped less than 20%(calculated based on the maximum detection limit of 150 U/ml)of their initial ones detected before treatment,and the clinical and laboratory data of patients eligible for the inclusion criteria were collected. Results Among the 134 pemphigus patients with available follow-up data during this period,a total of 8 patients met the criteria,with the follow-up period of 21-85 months and the remission duration of 18-70 months.They all received less than or equal to 10 mg/d prednisone and had high titers of anti-desmoglein antibodies.At their first visit,the number of patients with positive anti-desmoglein 1/desmoglein 3 antibodies was 7.Two patients still had high titers of anti-desmoglein 1 antibodies 19 months and 21 months after they achieved remission,and 5 patients had high titers of anti-desmoglein 3 antibodies in 18-70 months.There was one patient showing high titers of both antibodies,especially for anti-desmoglein 1 antibodies.This patient relapsed after 19 months' remission while other patients were still in clinical remission. Conclusions Some pemphigus patients showed persistent high titers of anti-desmoglein antibodies in remission.Anti-desmoglein 3 antibodies were more common to keep positive,while high titer of anti-desmoglein 1 antibodies was less observed.The high titer of anti-desmoglein 1 antibodies had a correlation with recurrence.For the pemphigus patients with long-term clinical remission but high antibody titer,the dosages of corticosteroids should be adjusted carefully according to their actual clinical manifestations and the positive antibody type.For the patients with high titer of anti-desmoglein 1 antibodies,the dosage reduction of corticosteroids should be appropriately slower.