The efficacy and safety of low-dose rituximab in the treatment of pemphigus vulgaris: a cohort study.

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

Case Report: Prurigo nodularis-like linear IgA/IgG bullous dermatosis: a case report and literature review.

Linear IgA/IgG bullous dermatosis (LAGBD) is a rare autoimmune subepidermal bullous disorder characterized by linear deposition of concurrent IgA and IgG autoantibodies along the basement membrane zone (BMZ). The clinical features of LAGBD can be diverse, including tense blisters, erosions, erythema, crusting and mucosa involvement, while papules or nodules are generally absent. In this study, we present a unique case of LAGBD, which showed prurigo nodularis-like clinical appearance on physical examination, linear deposition of IgG and C3 along the basement membrane zone (BMZ) in direct immunofluorescence (DIF), IgA autoantibodies against the 97-kDa and 120-kDa of BP180 and IgG autoantibodies against the 97-kDa of BP180 by immunoblotting (IB), while BP180 NC16a domain, BP230, and laminin 332 were negative by enzyme-linked immunosorbent assay (ELISA). After administration of minocycline, the skin lesions improved. We performed a literature review of LAGBD cases with heterogeneous autoantibodies and found clinical presentations of most cases resemble bullous pemphigoid (BP) and linear IgA bullous disease (LABD), which is consistent with previous reported findings. We aim to increase our understanding of this disorder and to enhance the importance of applying immunoblot analyses and other serological detection tools in clinic for precise diagnosis as well as accurate treatment strategy of various autoimmune bullous dermatoses.

Lactobacillus rhamnosus ameliorates acne vulgaris in SD rats via changes in gut microbiota and associated tryptophan metabolism.

Background: The depletion of beneficial bacteria in the gut has been found in patients with acne vulgaris, and in previous studies, the supplement of Lactobacillus rhamnosus led to the improvement of adult acne. Nevertheless, the potential mechanism of L. rhamnosus in the amelioration of acne vulgaris has not been elucidated yet. Methods: To mimic the human intestinal environment, a pseudo-germ-free rat model was used, and then gut microbiota from healthy individuals and acne patients were transplanted into rats. The effects of L. rhamnosus and tryptophan (Trp) metabolites on a rat acne model were investigated by gavage. Then, 16S rRNA analysis and targeted measurement of metabolites were performed to discover the differences in gut microbiota and metabolites between groups. Finally, HaCaT cells pretreated with Cutibacterium acnes were employed to validate the effect and mechanism of Trp metabolites on acne. Results: L. rhamnosus significantly improved acne-like symptoms in rats by suppressing the level of inflammatory cytokines such as IL-1ß, IL-6, and TNF-α. L. rhamnosus induced an increase in the production of indole-3-acetic acid (IAA) and indole via targeted Trp metabolic analyses. Furthermore, L. rhamnosus promoted bacterial diversity and also enhanced the Firmicutes/Bacteroidota (F/B) ratio, which was positively related to both IAA and indole. Finally, the roles of IAA and indole in alleviating acne vulgaris were confirmed both in vitro and in vivo, which could be reversed by AhR inhibitors. Conclusion: Our study demonstrated that L. rhamnosus could exert its therapeutic effects on acne vulgaris by modulating the gut microbiota and regulating associated Trp metabolites.

Applications of single-cell RNA sequencing in atopic dermatitis and psoriasis.

Single-cell RNA sequencing (scRNA-seq) is a novel technology that characterizes molecular heterogeneity at the single-cell level. With the development of more automated, sensitive, and cost-effective single-cell isolation methods, the sensitivity and efficiency of scRNA-seq have improved. Technological advances in single-cell analysis provide a deeper understanding of the biological diversity of cells present in tissues, including inflamed skin. New subsets of cells have been discovered among common inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis. ScRNA-seq technology has also been used to analyze immune cell distribution and cell-cell communication, shedding new light on the complex interplay of components involved in disease responses. Moreover, scRNA-seq may be a promising tool in precision medicine because of its ability to define cell subsets with potential treatment targets and to characterize cell-specific responses to drugs or other stimuli. In this review, we briefly summarize the progress in the development of scRNA-seq technologies and discuss the latest scRNA-seq-related findings and future trends in AD and psoriasis. We also discuss the limitations and technical problems associated with current scRNA-seq technology.

Serum Leptin and Adiponectin: Indicators of Cardiovascular Disease Secondary to Psoriasis.

Background: To explore the role and clinical significance of serum adiponectin and leptin levels in patients with psoriasis accompanied by atherosclerosis. Methods: Eighty patients diagnosed with psoriasis in our dermatology department and 40 healthy people in our physical examination centre were included as the study group and control group, respectively. All the included patients underwent fasting blood and serum tests. Levels of adiponectin, leptin, and the blood lipid content; colour Doppler ultrasonography of both common carotid arteries, internal carotid and external carotid arteries; and intimal-medial thickness (IMT) and carotid plaque were evaluated. Results: In the study group, the leptin level increased, and the serum adiponectin level decreased; these levels were statistically significantly different compared with those in the control group (t = 6.774, P < 0.001 and t = -3.511, P < 0.05, respectively). IMT was negatively correlated with adiponectin levels (r = -0.378, P < 0.001) and positively correlated with leptin levels (r = 0.581, P < 0.001). Conclusions: The imbalanced expression of serum and adiponectin levels will aggravate psoriasis and promote the occurrence of atherosclerosis. Serum levels can be used to assess the disease severity, detect vascular lesions early, and prevent the development of psoriasis to cardiovascular disease.

Correlation of catecholamine content and clinical influencing factors in depression among psoriasis patients: a case-control study.

OBJECTIVE: Our study sought to investigate the clinical influencing factors of psoriasis patients with depression, and analyze whether the content of monoamine neurotransmitters in plasma was correlated with depression incidence among psoriasis patients. METHODS: Ninety patients with psoriasis and 40 healthy volunteers (aged from18 to 60) were recruited and interviewed with a piloted questionnaire in both groups to obtain relevant information. The catecholamine in plasma from the two groups was analyzed by radioimmunoassay. The data were analyzed by SPSS statistical software. RESULTS: The mean Hamilton Depression Scale (HAMD) and mean Athens Insomnia Scale (AIS) scores of the psoriasis patients were higher than the control group. Dopamine content in the plasma was lower (comparing psoriasis patients without depression and the control group, and was negatively correlated with HAMD, AIS, and Psoriasis Area and Severity Index (PASI) scores in the psoriasis patients with depression. There was no significant difference in the epinephrine and norepinephrine contents in all groups. PASI scores were positively correlated with HAMD scores in psoriasis patients. The low dopamine content, Dermatology Life Quality Index, and high PASI scores were the risk factors for depression among the psoriasis patients. CONCLUSION: Psoriasis patients have a significantly higher risk of depression than healthy people, and higher PASI scores were linked to a higher incidence of depression. The dopamine levels of patients were influenced by both psoriasis and depression. The risk factors for depression in psoriasis patients are low dopamine levels in the plasma, severe skin lesions, and lower quality of life.

Efficacy, Safety, and Pharmacoeconomic Analysis of Adalimumab and Secukinumab for Moderate-to-Severe Plaque Psoriasis: A Single-Center, Real-World Study.

INTRODUCTION: A growing number of biologics have recently been approved in China for psoriasis treatment, and some of these are eligible for Chinese medical insurance, resulting in a significant increase in the number of patients receiving these biologics. Nevertheless, real-world data on the efficacy and safety of biologics for treating moderate-to-severe plaque psoriasis in Chinese patients are limited, and relevant pharmacoeconomic studies are lacking. Therefore, we performed a prospective, single-center study to evaluate the efficacy and safety of adalimumab (ADA) and secukinumab (SEC) in real-world practice. A cost-effectiveness analysis (CEA) was also conducted. METHODS: Participants were enrolled between January 2019 and December 2020 at the West China Hospital, Sichuan University. Baseline and follow-up assessments were conducted, and an appropriate statistical analysis was performed. RESULTS: A total of 183 patients were included. At week 12, the number of patients achieving a psoriasis area and severity index reduction of 75% (PASI 75) with SEC treatment was higher than that with ADA and methotrexate (MTX) (SEC versus ADA versus MTX, 90.59% versus 58.70% versus 17.14%, respectively). Adverse events (AEs) were reported in 44.83% and 56.36% of patients in the SEC and ADA groups, respectively. The cost-effectiveness ratio in the SEC group was 46,311.83 Chinese yuan(CNY), compared with 17,580.92 CNY in the ADA group. CONCLUSION: In real-world practice, SEC and ADA are effective and safe for moderate-to-severe plaque psoriasis treatment in Chinese patients. On the basis of drug prices during our study period without considering access to health insurance, ADA was more cost-effective in real-world practice. Adalimumab and secukinumab are two monoclonal antibodies used for the treatment of psoriasis, which target different cytokines in the pathogenesis. A growing number of biologics have recently been approved in China for psoriasis treatment including adalimumab and secukinumab, which are eligible for Chinese medical insurance, resulting in a significant increase in the number of patients receiving these biologics. With the purpose of evaluating its efficacy and safety in the real world, we registered the data of eligible patients in West China Hospital, Sichuan University over the past two years and conducted statistical analysis. In order to provide different therapeutic strategies for patients based on case-specific needs and access to financial resources, we performed pharmacoeconomic analyses to evaluate the cost-effectiveness of the two drugs. Our study demonstrated that adalimumab and secukinumab were effective and safe for moderate-to-severe plaque psoriasis in Chinese patients in the real-world practice. Based on drug prices during our study period and without taking into consideration access to health insurance, ADA was more cost-effective in real-world practice.

Reliability and validity of the Chinese version of the Patient Health Questionnaire-9 (C-PHQ-9) in patients with psoriasis: a cross-sectional study.

OBJECTIVE: To evaluate the clinical reliability and validity of the Chinese version of the Patient Health Questionnaire-9 (C-PHQ-9) in patients with psoriasis. DESIGN: Cross-sectional study. SETTING: Tertiary care centre. PARTICIPANTS: Patients with psoriasis who have not been diagnosed with depression (n=148; mean age 43.37±17.46 years; 31.19% female). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measures considered in this study were the C-PHQ-9 and the Hamilton Depression Scale (HAMD). The American Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) was used as the gold standard for the diagnosis of depression. Cronbach's α and test-retest reliability after 1 week were evaluated using reliability analysis, and criterion and structural validity were assessed using validity analysis. Receiver operating characteristic (ROC) analysis was performed to identify the best demarcation score and diagnostic accuracy. RESULTS: Compared with DSM-V (27.27%), both C-PHQ-9 (39.19%) and HAMD (31.01%) had higher rates for detecting depression. The mean completion time for C-PHQ-9 evaluation (2.02±0.84 min) was significantly less than that for HAMD (23.37±3.21 min, p<0.001). The Cronbach's α coefficient for the C-PHQ-9 was 0.938. The correlation coefficients of the nine items with the total scale ranged from 0.540 to 0.854, and the mean inter-item correlation coefficients ranged from 0.376 to 0.933. After a week, the retest coefficient was 0.955 (p<0.01). Principal component factor analysis showed that C-PHQ-9 identified a unifactorial structure. The best cut-off point was 9 points, with a sensitivity of 98.00% and a specificity of 90.80%. The area under the ROC curve was 0.979 (95% CI 0.968 to 0.991). CONCLUSION: C-PHQ-9 has good reliability and validity in patients with psoriasis and can be used for primary screening of patients with psoriasis and depression. This scale has obvious time and labour advantages over the HAMD and should be considered for use in clinical practice.

Hyper IgE syndrome associated with novel and recurrent STAT3 mutations: Two case reports.

RATIONALE: Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency presenting as two forms including autosomal dominant HIES (AD-HIES) and autosomal recessive HIES (AR-HIES), which are mainly caused by mutations in STAT3 and DOCK8, respectively. To date, only about 500 cases have been reported worldwide including 37 cases in China. The spectrum and prevalence of mutations and molecular pathogenesis in HIES remain poorly understood. PATIENT CONCERNS: Here we reported two Chinese children presenting clinical manifestations of HIES. DIAGNOSIS: Based on medical history, clinical manifestations, and laboratory findings, a diagnosis of HIES was made for both children. Targeted next-generation sequencing (NGS) identified a novel heterozygous deletion of 15 bp (c.1960_1974del, p.G654_D658del or alternatively c.1966_1980del, and p.G656_D660del), and a recurrent missense mutation (c.1144C>T, p.R382W) in STAT3 in the two patients, respectively. INTERVENTIONS: The two patients have been given the successful treatment of skin infections with cefaclor. OUTCOMES: Both patients have been under follow-up for more than 6 months, with no signs of recurrent infections. LESSONS: Our results extend the spectrum of STAT3 mutations associated with ADHIES and highlight the value of targeted NGS in confirming diagnosis of genetic disorders.