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Summary: 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. What is already known about this topic? Superpotent topical corticosteroids are the gold standard treatment for bullous pemphigoid (BP), whatever the severity.High doses of oral corticosteroids are effective but poorly tolerated in patients with BP.Medium doses of oral corticosteroids are effective in paucibullous BP, but their efficacy in severe forms has not yet been assessed. What does this study add? Medium doses of oral corticosteroids have poor efficacy in severe BP.A baseline Bullous Pemphigoid Disease Area Index score < 50 and a Karnofsky score ≥ 70 are predictors of treatment efficacy and low mortality, respectively. Linked Comment: H.Y. Lee. Br J Dermatol 2021; 185:1093–1094. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is characterized by immune dysregulations and an impaired skin barrier, including abnormalities in lipid organization. In the stratum corneum (SC), β-glucocerebrosidase (GBA) mediates transformation of glucosylceramide (GlcCER) into ceramide (CER) and cholesterol into glucosylcholesterol (GlcChol). Alteration in GBA activity might contribute to skin barrier defects in AD., Objectives: To investigate GBA activity in the SC of children with AD before and after topical corticosteroid therapy and to compare it with healthy controls; to determine SC levels of GlcCER- and CER-containing hydroxysphingosine base (GlcCER[H] and CER[H], respectively) and GlcChol; and to relate them to disease severity, skin barrier function and the local cytokine milieu., Methods: Lipid markers and cytokines of innate, T helper 1 and T helper 2 immunity were determined in SC collected from healthy children and from clinically unaffected skin of children with AD, before and after 6 weeks of therapy with topical corticosteroids. AD severity was assessed by Scoring Atopic Dermatitis and skin barrier function by transepidermal water loss (TEWL)., Results: Baseline GBA activity and GlcChol levels were increased in children with AD but declined after therapy. CER[H] levels and the CER[H] to GlcCER[H] ratio were increased in AD. GBA activity and GlcChol correlated with TEWL and levels of multiple cytokines, especially interleukin-1α and interleukin-18. GlcChol was strongly associated with disease severity., Conclusions: We show increased GBA activity and levels of GlcChol in AD. Our data suggest an important role of inflammation in disturbed lipid processing. GBA activity or GlcChol might be useful biomarkers in the monitoring of therapeutic responses in AD. What is already known about this topic? Patients with atopic dermatitis (AD) have a reduced skin barrier, mainly caused by altered lipid organization. The mechanisms underlying these lipid anomalies are not fully understood but likely reflect both genetic abnormalities in AD skin and the local cutaneous inflammatory environment. What does this study add? We show increased activity of the ceramide-generating enzyme β-glucocerebrosidase in AD. Activity of this enzyme was correlated with the local cytokine milieu and declined after local corticosteroid therapy. We show that glucosylcholesterol levels in the stratum corneum are increased in AD. The function of glucosylcholesterol and the physiological consequences of increased levels are not clear yet; however, its levels were strongly correlated with skin barrier function: high transepidermal water loss strongly correlated with high levels of glucosylcholesterol. What is the translational message? Correction of cutaneous inflammation largely restores alterations in lipid metabolism in the stratum corneum of infants with AD., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

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., (© 2021 British Association of Dermatologists.)