{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T20:54:45Z","timestamp":1765486485883,"version":"3.40.5"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cosmetic Dermatology"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rosacea is a very common, chronic inflammatory disease characterized by flushing, erythema and inflammatory lesions. Increased oxidative stress plays a relevant pathogenetic role in Rosacea. Intracellular Glutathione (GSH) is the main scavenger protective mechanism against increased oxidative stress. An altered GSH metabolism in Rosacea has been described. GSH\u2010C4 is a modified GSH molecule characterized by a better intracellular bioavailability and longer half\u2010life. A daily cream (E\u2010AR) containing GSH\u2010C4 (0.1%) with beta\u2010Glycyrrhetic (0.5%) and azelaic acids (10%), with an SPF of 30, is available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>In a pilot, prospective, two\u2010center, assessor\u2010blinded study we evaluate the efficacy and the tolerability of E\u2010AR cream in subjects with mild to moderate Rosacea treated for 8 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>The main outcomes were the Investigator Global Assessment (IGA) 7\u2010point score (from 0, completely clear; to 6, severe) and the clinical and instrumental erythema severity score (ESS) (from 0 to 4) evaluated in a blinded fashion (randomly coded photographs) at baseline, after 4 (only clinical) and 8 weeks (clinical and instrumental). VISIA evaluation for erythema and lesion counts and ANTERA 3D analysis for skin haemoglobin concentration (a parameter associated with inflammation) were also performed at the same time points. Analysis of primary outcomes was performed on an intention\u2010to\u2010treat basis. Tolerability was evaluated at week 4 and 8 recording spontaneously reported side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty subjects (22 women and 8 men; mean age 38 years) were enrolled after their written informed consent. Twenty\u2010six (87%) subjects completed the study phases. Four subjects stopped prematurely the trial due to low skin tolerability (n=3) or lost to follow\u2010up (n=1). At baseline, mean (SD) IGA score was 2.6 (0.9). At week 4, IGA score decreased (NS) to 2.3 (1.2). IGA score decreased significantly (p=0.0001) at week 8 to 1.2 (1) (mean difference 1.3; 95% CI of the difference from 0.9 to 1.7) in comparison with the baseline. The inflammatory mean (SD) lesion count, evaluated clinically, were 5.1(2.5) at baseline, 2.8 (1.9) at week 4, and 1.9 (1.7) at week 8 (<jats:italic>P<\/jats:italic>=0.0001; ANOVA Test), representing a 63% reduction. This reduction was confirmed by inflammatory lesions count performed on VISIA pictures (from 4.5 at baseline to 1.7 lesions at week 8). Similar evolution was observed for the clinical and instrumental ESS with a reduction of 56% (clinical) and 48% (VISIA), respectively, at week 8 in comparison with the baseline. ANTERA 3D photographs confirmed the positive evolution observed clinically with a significant reduction (\u201024%) in hemoglobin content: from 1.88 at baseline to 1.44 at week 8.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This new GSH\u2010C4, beta\u2010glycyrrethic and azelaic acids cream has shown to be efficacious in mild to moderate rosacea subjects. Local tolerability is in line with other anti\u2010rosacea treatments.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jocd.13707","type":"journal-article","created":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T01:23:12Z","timestamp":1599182592000},"page":"1197-1203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy and tolerability of a cream containing modified glutathione (GSH\u2010C4), beta\u2010Glycyrrhetic, and azelaic acids in mild\u2010to\u2010moderate rosacea: A pilot, assessor\u2010blinded, VISIA and ANTERA 3\u2010D analysis, two\u2010center study (The \u201cRosazel\u201d Trial)"],"prefix":"10.1111","volume":"20","author":[{"given":"Federica","family":"Dall\u2019Oglio","sequence":"first","affiliation":[{"name":"Dermatology Clinic University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Puviani","sequence":"additional","affiliation":[{"name":"Dermatology Service Medica Plus Modena Modena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7559-1202","authenticated-orcid":false,"given":"Massimo","family":"Milani","sequence":"additional","affiliation":[{"name":"Cantabria Labs Difa Cooper Medical Department Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Micali","sequence":"additional","affiliation":[{"name":"Dermatology Clinic University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-018-1857-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2230.2003.01179.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12556"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/WOX.0b013e3182439613"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0753-3322(03)00043-X"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0781.2006.00220.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/095632020401500204"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.09.033"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.4103\/0022-3859.52846"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13555-016-0133-6"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-4632.2004.02137.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.01.008"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1993.tb00261.x"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.10608"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.5114\/ada.2018.76228"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2008.10.014"},{"issue":"3","key":"e_1_2_10_18_1","first-page":"13","article-title":"Ultraviolet light and rosacea","volume":"74","author":"Murphy G","year":"2004","journal-title":"Cutis"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-2494.2004.00241.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.122"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02850193"},{"issue":"1","key":"e_1_2_10_22_1","first-page":"26","article-title":"Rosacea, reactive oxygen species, and azelaic acid","volume":"2","author":"Jones DA","year":"2009","journal-title":"J Clin Aesthet Dermatol"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1586\/17469872.2.5.523"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajme.2017.09.001"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(97)00146-4"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4827(03)00012-0"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2012.931"},{"key":"e_1_2_10_28_1","first-page":"1","article-title":"Antioxidant enzymes and human health","author":"Krishnamurthy P","year":"2012","journal-title":"Antioxidant Enzyme"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.2000.01651.x"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/15569527.2018.1517124"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0968-0004(81)90084-0"},{"issue":"7","key":"e_1_2_10_32_1","first-page":"95","article-title":"Regulation of glutathione synthesis","volume":"36","author":"Lu SC","year":"2000","journal-title":"Curr Top Cell Regul"},{"key":"e_1_2_10_33_1","unstructured":"Benatti et al.United States US 20070270349A1 (12) Patent Application Publication (10) Pub. 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