Assessment of hydro-saline retention in bullous pemphigoid patients treated with super-potent topical corticosteroids.

INTRODUCTION: Super-potent topical corticosteroids (CS) are the mainstay of treatment for bullous pemphigoid. Since super-potent topical CS have systemic effects due to their transcutaneous absorption, we assessed whether super-potent CS were responsible for hydro-saline retention (HSR) in bullous pemphigoid patients. PATIENTS AND METHODS: From 2015 to 2017, patients with newly-diagnosed bullous pemphigoid treated using clobetasol propionate cream at a starting daily dose of 20 to 40 g were subsequently included in a prospective study. HSR was assessed by longitudinally measuring extracellular water (ECW) volume using bioimpedance analysis (BodyStat QuadScan 4000®) from Day 0 to Day 30 after the initiation of topical CS. Other parameters related to HSR such as weight, blood pressure, natriuresis and proteinuria, were also recorded. RESULTS: Twenty-nine patients (14 men and 15 women) of mean age 81.8 ±â€¯9.3 years were included and analysed. The mean ECW volume decreased from Day 0 to Day 7 (18.1 ±â€¯4.2 vs 16.7 ±â€¯2.7, p = 0.0094) and was maintained from Day 7 to Day 30 (16.8 ±â€¯2.8 vs 17.0 ±â€¯3.4 L; p = 0.8040). Patient weight loss at Day 30 (69.9 ±â€¯13.6 vs 72.5 ±â€¯14.2 kg, p = 0.0085) was closely correlated with the decrease in ECW volume (r = 0.6740, p < 0.0001). No significant changes in natriuresis, 24-hour proteinuria or blood pressure were observed from Day 0 to Day 30. CONCLUSION: We found no evidence of HSR in bullous pemphigoid patients treated with super-potent topical CS. Conversely, ECW volume decreased from Day 0 to Day 30, which was correlated with patient weight loss.

International multicentre observational study to assess the efficacy and safety of a 0·5 mg kg-1 per day starting dose of oral corticosteroids to treat bullous pemphigoid.

BACKGROUND: European guidelines propose a 0·5 mg kg-1 per day dose of oral prednisone as initial treatment for bullous pemphigoid (BP). We assessed the safety and efficacy of this regimen depending on BP extent and general condition of the patients. METHODS: In a prospective international study, we consecutively included all patients diagnosed with BP. Patients received a 0·5 mg kg-1 per day dose of prednisone, which was then gradually tapered 15 days after disease control, with the aim of stopping prednisone or maintaining minimal treatment (0·1 mg kg-1 per day) within 6 months after the start of treatment. The two coprimary endpoints were control of disease activity at day 21 and 1-year overall survival. Disease severity was assessed according to the Bullous Pemphigoid Disease Area Index (BPDAI) score. RESULTS: In total, 198 patients were included between 2015 and 2017. The final analysis comprised 190 patients with a mean age of 80·9 (SD 9·1) years. Control of disease activity was achieved at day 21 in 119 patients [62·6%, 95% confidence interval (CI) 55·3-69.5]; 18 of 24 patients (75%, 95% CI 53·3-90·2), 75 of 110 patients (68·8%, 95% CI 59·2-77·3) and 26 of 56 patients (46.4%, 95% CI 33·0-60·3) had mild, moderate and severe BP, respectively (P = 0·0218). A total of 30 patients died during the study. The overall Kaplan-Meier 1-year survival was 82·6% (95% CI 76·3-87·4) corresponding to 90·9%, 83·0% and 80·0% rates in patients with mild, moderate and severe BP, respectively (P = 0·5). Thresholds of 49 points for BPDAI score and 70 points for Karnofsky score yielded maximal Youden index values with respect to disease control at day 21 and 1-year survival, respectively. CONCLUSIONS: A 0·5 mg kg-1 per day dose of prednisone is a valuable therapeutic option in patients with mild or moderate BP whose general condition allows them to be autonomous.

A fast and effective approach for the discrimination of garlic origin using wooden-tip electrospray ionization mass spectrometry and multivariate classification.

This paper presents the combination of wooden-tip electrospray ionization mass spectrometry (WTESI-MS) and multivariate pattern recognition methods (principal component analysis, PCA and partial least squares discriminant analysis, PLS-DA) for the rapid and reliable discrimination, via chemical fingerprints, of garlic origin. A total of 312 garlic samples grown in different countries (Brazil, China, Argentina, Spain, and Chile) were studied. The methodology was based on a direct sampling approach, which relies on loading the sample by penetrating the garlic cloves with a pre-wetted wooden tip, followed by direct prompt analysis by WTESI-MS. Thus, no sample preparation is needed, which prevents the degradation of important metabolites and increases the analytical throughput. Parameters that affects the WTESI were optimized and the best performance in terms of signal stability and intensity was achieved using the positive ion mode. Most of the ions in WTESI mass spectra were assigned to amino acids, sugars, organosulfur compounds, and lipids. The discriminative model showed good performance (accuracy rates between 81.9% and 98.6%) and enabled identifying diagnostic ions for garlic samples from different origins. The differentiation and classification of garlic origin is of major importance as this food flavoring product is widely consumed, with worldwide trade representing billions of dollars every year, and is very often the subject of fraud.

International validation of the Bullous Pemphigoid Disease Area Index severity score and calculation of cut-off values for defining mild, moderate and severe types of bullous pemphigoid.

BACKGROUND: The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES: The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS: Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS: In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P < 0·004), but not with anti-BP230 antibodies (r = 0·17, P = 0·15). CONCLUSIONS: This study suggests cut-off values of 20-57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.

Chemodiversity of Essential Oils from Nine Species of Celastraceae.

Extracts and compounds obtained from several species of Celastraceae family are reported as potential sources of drugs due to their diverse pharmacological properties. Nevertheless, essential oil composition from these species is still little known. This work aimed at the analysis of essential oils obtained from different Brazilian Celastraceae species. A total of seventeen oils were obtained using hydrodistillation process and analyzed by gas chromatography/mass spectrometry (GC/MS). Principal component analysis (PCA) allowed the identification of a chemical composition pattern among the analyzed essential oils. Some compounds were more frequent among Celastraceae species, such as cis- and trans-linalool oxide (14/17 oil samples), nerylacetone (13/17), linalool (11/17), ß-ionone (10/17), α-ionone (9/17), nerolidol (10/17), decanal (10/17), and dodecanoic acid (10/17). These results contribute to the chemophenetics of Celastraceae species.

Comparison of real costs in the French healthcare system in newly diagnosed patients with pemphigus for first-line treatment with rituximab vs. standard corticosteroid regimen: data from a national multicentre trial.

BACKGROUND: Rituximab has been demonstrated to be highly effective as a first-line treatment for moderate-to-severe pemphigus; however, its high cost can be considered a limitation of this treatment. OBJECTIVES: To compare direct costs of two regimens, rituximab + short-term prednisone vs. prednisone alone, tested in the Ritux3 trial. METHODS: Patients were randomly assigned to receive 2 g of rituximab and two 500-mg maintenance infusions at month 12 and month 18 along with low doses of prednisone for 3-6 months, or high doses of prednisone alone tapered over 12-18 months. We estimated the direct costs related to (i) protocol (treatments, consultations, hospitalizations); (ii) unfavourable disease course (relapse); and (iii) adverse events in both treatment groups during a 3-year follow-up. RESULTS: Annual individual cost discrepancies related to drugs decreased from +€3597 to -€1589 from the first to the third year, which corresponded to an initially higher cost in the rituximab group, counterbalanced during follow-up by costs related to treatment of patients with persistent disease activity/relapses in the standard corticosteroid (CS) group. Individual costs relating to treatment of adverse events were higher in the standard CS group (€4352) than in the rituximab group (€2468). Overall, mean individual total cost over the 3 years of follow-up was €13 997 in the standard CS arm vs. €14 818 in the rituximab arm, corresponding to a difference of €821 more per patient (+6%). CONCLUSIONS: First-line treatment of pemphigus with rituximab results in a slightly greater cost compared with a standard CS regimen. What's already known about this topic Rituximab is the most effective treatment for moderate-to-severe pemphigus. Rituximab cost might be considered as a limitation of this treatment. What does this study add? After 3 years of follow-up, mean individual total cost for a patient with first-line treatment with rituximab was €14 818 vs. €13 997 with standard corticosteroids (CS), resulting in a slightly higher cost of €821 (+6%). The initially greater cost of rituximab was counterbalanced by costs related to management of flares/relapses in patients treated with a standard CS regimen.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.