Pemphigus Disease and Area Index: Unmet needs in the real-world management of pemphigus.

Over the past few decades, a number of scoring instruments have been developed to assess the severity and activity of autoimmune bullous diseases (AIBDs) (Daneshpazhooh et al., 2019; Nili et al., 2020; Nili et al., 2021; Nili et al., 2022). The Pemphigus Disease Area Index (PDAI), developed by the International Pemphigus Definitions Group, is an easy-to-use, quick, and reliable method for determining pemphigus severity. As a reliable and effective tool in clinical trials, PDAI may also have some limitations and might require some revisions to be used on a daily basis. Here, we propose some recommendations to improve the use of PDAI in the clinical setting.

Indirect immunofluorescence on rat bladder epithelium in patients with pemphigus vulgaris with an extended follow-up.

Background: Indirect immunofluorescence (IIF) on rat bladder epithelium (RBE) has been widely used to detect anti-plakin antibodies present in paraneoplastic pemphigus (PNP). However, anti-plakin antibodies have also been found in a group of patients with pemphigus vulgaris (PV). Objectives: To assess the reactivity rate of PV sera in IIF using RBE as substrate and the diagnostic usefulness of the aforementioned test. Methods: Patients diagnosed with PV presenting to Razi Hospital, Tehran, Iran, were recruited. The patients' demographics, disease severity, and response to the initial treatment were recorded. Sera were collected and tested by IIF on RBE and by desmoglein 3/1 (Dsg 3/1) enzyme-linked immunosorbent assay. Patients were followed up closely for a mean of 53.9 months for any evidence of malignancy. Results: Forty-six patients were enroled (mean age of 42.9 years old, 31 females). Nine sera (19.6%) showed reactivity in IIF on RBE. Mean serum anti-Dsg levels did not differ significantly among the two groups with positive and negative IIF results. Negative anti-Dsg3 was related to a higher positive rate in IIF on RBE. There was no significant correlation between the reactivity of IIF on RBE and patients' demographic, clinical, or serological characteristics. Conclusions: IIF on RBE is a sensitive test for detecting antibodies against plakins. However, it has a relatively high false-positive rate in PV, probably due to the epitope spreading phenomenon. This test should be suggested when there is a clinical or immunohistopathological suspicion of PNP and should be interpreted with caution.

Efficacy and safety of biosimilar rituximab in patients with pemphigus vulgaris: a prospective observational study.

Background: The optimal treatment for pemphigus vulgaris (PV) has not been clearly determined yet. Rituximab (RTX) was recently approved for the management of adults with moderate to severe PV. Objectives: This prospective observational study was designed to evaluate the efficacy and safety of biosimilar RTX in PV patients.Methods: The efficacy and safety were evaluated by assessing the pemphigus disease area index (PDAI) score, clinical response and any adverse events (AEs) during at least 12-month follow-up. We evaluated anti-desmoglein (Dsg) 1,3 level at baseline, 3 months and 12 months after RTX infusion.Results: A total of 110 patients treated with biosimilar RTX were enrolled between May 2016 and July 2017. The mean age was 43.58 ± 11.77 years and the mean follow-up time was 16.22 ± 3.45 months. A notable decrease in PDAI score, anti-Dsg 1,3 level and prednisolone dosage was observed. Median delay to achieve complete remission (CR), median duration of CR, and median time to relapse were 3, 9, and 12 months, respectively. Newly diagnosed patients (NDPs) experienced higher rate of CR, longer duration of remission and lower risk of relapse, compared to previously treated patients (PTPs). A total of 47 AEs were observed in 33 (30%) patients, which were mostly mild infusion-related reactions.Conclusion: Administration of biosimilar RTX in PV patients was associated with desirable outcomes in terms of efficacy and safety in both NDPs and PTPs.First-line use of RTX in NDPs was more effective and allowed a rapid tapering of corticosteroid doses compared to PTPs.

Estimated cut-off values for pemphigus severity classification according to pemphigus disease area index (PDAI), autoimmune bullous skin disorder intensity score (ABSIS), and anti-desmoglein 1 autoantibodies.

BACKGROUND: Pemphigus is a potentially fatal disease if left untreated. Valid scoring systems and defined cut-off values for classification of patients would help with better management through specified pharmaceutical and non-pharmaceutical treatments. METHODS: In this study, pemphigus patients who were receiving immunosuppressive treatments and had recent disease relapse were recruited for examination of pemphigus disease area index(PDAI), autoimmune bullous skin disorder intensity score (ABSIS), physician global assessment (PGA), autoimmune bullous disease quality of life (ABQoL), anti-desmoglein 1 (anti-Dsg1), and anti-Dsg3 autoantibody titers from December-2017 to February-2018. Cut-off values were estimated using model-based clustering classification and the 25th and 75th percentiles approach, performed separately for the exclusive cutaneous, exclusive mucosal, and mucocutaneous groups. RESULTS: In the 109 included patients, the 25th and 75th percentiles cut-offs were 6.2 and 27 for PDAI score, and 4 and 29.5 for ABSIS score. The model-based analysis resulted in two groups (cut-point:15) for PDAI score, and three groups (cut-points:6.4 and 31.5) for ABSIS score. The groups were significantly different for the PDAI, ABSIS, PGA, and ABQoL values. Based on anti-Dsg1 autoantibody values, the model-based analysis cut-point was 128 and the 25th and 75th percentiles cut-offs were 98 and 182. Anti-Dsg3 autoantibody values did not differentiate between pemphigus severity classes. CONCLUSIONS: Estimated cut-off values based on the anti-Dsg1 level, PDAI, and ABSIS scoring systems could be used to classify patients into different severity grades for better management and prognosis.

Autoimmune Bullous Disease Quality of Life (ABQoL) questionnaire: Validation of the translated Persian version in pemphigus vulgaris.

BACKGROUND: Autoimmune bullous diseases are a group of rare, chronic, blistering diseases, with pemphigus vulgaris (PV) being the most common type in Iran. Skin and mucosal involvement and therapy may have a dismal impact on the quality of life of affected patients. OBJECTIVE: We aimed to assess the validity and reliability of the Farsi (Persian) version of the Autoimmune Bullous Quality of Life (ABQoL) index in Iranian patients with PV. METHODS: Forward and backward translation procedures were used to prepare the Persian version of the ABQoL questionnaire. A total of 180 patients were asked to complete the questionnaires, and 24 cases repeated the test after 2 weeks. For validity and reliability, an exploratory factor analysis was performed along with a parallel analysis to determine the number of factors. The multi-trait, multi-method matrix assessed convergent and discriminant validity. To evaluate internal reliability and reliability over time, Cronbach's alpha and intraclass correlation coefficients were reported. RESULTS: Two factors explained a total variance of 54.9% in the data. The first and second factors comprised questions 1-3, 5, 7, 9, and 12-17 (symptoms-social) and questions 4, 6, 8, 10, and 11 (mucosal-psychological), respectively. The internal reliability of the Persian version of the ABQoL index was also acceptable, with a Cronbach's alpha of .855 for total items, .918 for the first factor, and .6 for the second factor. Our results suggest an acceptable convergent and discriminant validity of the Persian version of the ABQoL questionnaire. CONCLUSION: The Persian version of ABQoL index is a valid and reliable tool to monitor quality of life in patients with PV. Further studies are needed to assess the sensitivity of this instrument to changes in different disease activity and correlation with more general tools for the measurement of quality of life.

Adverse electrocardiographic effects of rituximab infusion in pemphigus patients.

Pemphigus encompasses a group of chronic autoimmune blistering diseases of the skin and/or mucosa. Rituximab (RTX) has shown promising efficacy for the treatment of pemphigus in the past decade. Considering potential cardiac side effects, this study was conducted to assess the effects of RTX on electrocardiogram (ECG) parameters in pemphigus patients. This observational cross-sectional study was conducted in 80 consecutive patients with pemphigus who were eligible for RTX infusion. The patients' heart rhythm was monitored before, during and after RTX infusion and ECG parameters were compared before and after the infusion. Eighty patients were included in the study. The median age of the patients was 42 years. The mean and maximum heart rate (HR) increased significantly after RTX infusion compared with pre-infusion mean and maximum HR. The mean corrected QT (QTc) interval, premature atrial contraction (PAC), and premature ventricular contraction (PVC) counts increased significantly after RTX infusion (P value: 0.009, 0.004 and 0.007 respectively). According to the results of this study, RTX has potential arrhythmogenic side effects including increased mean and maximum HR, QTc interval, PAC and PVC count. However, these findings are minor and should not prevent eligible patients from receiving RTX infusion.

Short-term clinical and serological follow-up with conventional and conformational anti-desmoglein antibodies in treatment-naïve and previously treated patients with pemphigus vulgaris after receiving rituximab.

BACKGROUND: Pemphigus vulgaris (PV) is a blistering, life-threatening autoimmune disease. Ethylenediaminetetraacetic acid (EDTA)-treated desmoglein (Dsg) enzyme-linked immunosorbent assay (ELISA) has recently been suggested to detect nonpathogenic antibodies. Rituximab (RTX) is now considered a first-line treatment for PV. OBJECTIVE: The primary and secondary aims were to evaluate anti-Dsg and EDTA-treated anti-Dsg ELISA and clinical response before and 3 months after RTX in treatment-naïve and previously treated patients, respectively. In addition, we compared the short-term efficacy of RTX between these groups. METHODS: Seventy-five patients with PV who received RTX (500 mg weekly for 4 weeks or 1000 mg 2 weeks apart) and prednisolone were followed for 3 months. Thirty-seven treatment-naïve newly diagnosed (group A) and 38 relapsed patients (group B) were included. Disease activity was scored with the Pemphigus Disease Area Index (PDAI). Clinical response was also assessed. Serum samples were collected at two points and examined for anti-Dsg1/3 and EDTA-treated anti-Dsg1/3. Conformational anti-Dsg values were calculated by subtracting EDTA-treated from conventional anti-Dsg values. RESULTS: The correlation of conventional and conformational anti-Dsg values was perfect (correlation coefficient > 0.98; p < .001) at every time point for both anti-Dsgs. There was no difference with regard to PDAI and anti-Dsg values between the two groups at baseline. The frequency of responders was significantly higher in group A (100%) than in group B (89%; p = .006). Three patients relapsed, and five patients had persistent disease activity in group B. After 3 months, conventional and conformational anti-Dsg values were significantly higher in group B compared with group A (anti-Dsg3: p = .017 and .021, respectively; anti-Dsg1: p = .014 and .016, respectively). Total and scalp PDAI were significantly lower in group A than in group B (p = .042 and .016, respectively). CONCLUSION: EDTA-treated anti-Dsg ELISA had no added value. Using RTX as first-line treatment in patients with PV appears to be associated with better clinical response and immunologic profile than delayed treatment in the short term.

Oral Candida colonization and plaque type psoriasis: Is there any relationship?

AIM: The potential role of superantigens derived from microbial agents could be considered in the pathogenesis of psoriasis, but the association between Candida albicans and psoriasis severity is still controversial. The present study was designed to compare the prevalence of oral candidiasis in a group of psoriatic patients and healthy patients, and its correlation with psoriasis severity. METHODS: Seventy psoriatic patients with no history of systemic treatment and 70 closely-matched control patients underwent oral examination. Scraping of oral mucosa to detect Candida species was done using a sterile cytobrush. RESULTS: Candida was detected in the oral cavity of 20% of patients with psoriasis and 2.8% of control cases (P = .002), but none had clinical features of oral candidiasis. Candida albicans was the only species isolated from the oral cavity of both groups. No correlation was found between sex, age, phototherapy, and presence of oral candidiasis. There was a positive correlation between psoriasis severity and colony count (P < .001). CONCLUSIONS: The prevalence of oral candidiasis is higher in psoriatic patients and is associated with disease severity. It is not exactly clear whether oral candidiasis can aggravate psoriasis or if psoriasis can predispose patients to oral candidiasis.

Central Nervous System and Limb Embolism Concurrence due to Atrial Myxoma: A Case Report .

Cardiac myxomas are the most common cardiac tumors with diverse nonspecific clinical manifestations. A 78-year-old man presented to the emergency department with complaints of pain and coldness of the left lower extremity. The left femoral artery pulse was detected, while the pulses of the left popliteal, dorsalis pedis, and posterior tibialis arteries were absent. No blood inflow was detected in the superficial and deep femoral, popliteal, and anterior and posterior tibialis arteries. Thrombectomy was performed, and a fatty-like mass from the bifurcation of the common femoral artery and a thrombotic mass from the proximal portion of the superficial and deep femoral arteries were removed. The pulsatile inflow and palpable pulses of the left femoral, popliteal, dorsalis pedis, and posterior tibialis arteries were restored after surgery. The histological findings of the embolus were suggestive of a cardiac myxoma. The patient's consciousness and lower limb blood flow improved gradually. He was discharged from the hospital with full awareness and improved lower extremity muscle function 2 weeks after surgery.