- Email: [email protected]
Eosinophil Degranulation and the Release of Eosinophil Peroxidase Contributes to the Induced Inflammation Occurring in Mice Following Skin Exposure to TMA
Abstracts AB265
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Efficacy and Safety of Chitosan Coated Garments on Atopic Dermatitis Management: A Randomized Controlled Trial Cristina Lopes, MD1,2, Jose Soares3, Freni Tavaria4, Milton Severo5, Ana Duarte, MD6, Osvaldo Correia, MD7, Manuela Pintado4, Luis Delgado, MD8, Andre M. Moreira, MD9; 1Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Portugal, Porto, Portugal, 2Allergy Unit, Pedro Hispano Hospital, Matosinhos, Portugal, 3Biology and Fine Chemistry Unit, Biotechnology Faculty, Catholic University, Porto, Portugal, 4Biology and Fine Chemistry Unit, Biotechnology Faculty, Catholic University, Portugal, 5 Medical Faculty , Porto University, Porto, Portugal, 6Epidermis Dermatology Center , Instituto Cuf, Porto, Portugal, 7Epidermis Dermatology Center , Instituto Cuf, Portugal, 8Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Porto, Portugal, 9Allergy and Clinical Immunology Department, Centro Hospitalar S~ao Jo~ao, EPE, Porto, Portugal. RATIONALE: Patients with atopic dermatitis (AD) may benefit from using textiles coated with antiseptic and skin repairing compounds. Chitosan, a natural biopolymer with inhibitory activity against Staphylococcus aureus and immunomodulatory properties has been considered potentially useful in AD management. METHODS: Patients with AD (were randomly assigned in a 1:1 ratio to receive either chitosan coated or placebo cotton long sleeved pyjamas for 8 weeks. Primary efficacy outcome was the change in severity scoring for atopic dermatitis index (SCORAD). Secondary outcomes were the number of patients with minimal clinically detected difference, change in quality of life, daily score of pruritus and sleep loss, need of rescue medication, number of exacerbations, of totally and well-controlled weeks and of adverse events . Microbiological outcomes from five skin regions included changes in number of colony forming units of total staphylococci, Staphylococcus aureus and respective ratio. Analyses were done on an intention-to-treat basis. RESULTS: Of the 102 patients screened, 78 were included aged 30613 years (mean 6SD), 61% female, 77% atopic, with AD for 16610 years . After intervention, patients in chitosan group had a mean relative reduction in SCORAD of 43.8% (95%CI: 30.9 to 55.9), compared with 16.5% (-21.6 to 54.6) in placebo (p5 0.82). Changes in secondary clinical outcomes were similar in both groups. No major imbalances in microbiological profile were observed after the intervention. CONCLUSIONS: Chitosan coated garments are safe for adolescents and adults with atopic dermatitis and reduce AD severity but with no significant differences from placebo.
862
Combination Immunotropic Therapy of Atopic Dermatitis in Children: Cost-Benefit Analysis Vladislava Derkach1,2, Tatiana Slavyanskaya, MD, PhD2,3, Balgamaa Sangidorj3; 1Vladivostok State Medical University, Vladivostok, Russia, 2 Institute of Immunophysiology, Moscow, Russia, 3Peoples’ Friendship University of Russia, Moscow, Russia. RATIONALE: The study was aimed at a cost-benefit analysis (CBA) of various immunotherapy (IT) programmes (Ps) for children (Ch) with AD. METHODS: 94 Ch 3-18 ages with AD having lasted for 1-15 years were examined. All the patients received routine clinical and immuno-allergological examinations. The treatment was conducted in 2 stages: background therapy (BT) and IT. Ch were divided into 3 groups (G): IG (n530) received immunomodulator (IM) on a step-by-step basis in the course dose of 20 mg; IIG (n531) received an accelerated course of parenteral allergen-specific IT (PASIT); IIIG (n533) - a combination IT (CIT) IM+PASIT at an accelerated pace was applied. The quality of life (QOL) of Ch with AD was assessed using the Dermatology Specific Quality of Life (DSQL) questionnaire. The CBA was conducted with due regard to a specific character of the disease, the age composition of the G examined during a current year. RESULTS: The best ratio of high therapeutic effect was recorded in the III G, in which CITwas applied - 88.064.59%. In the IIG, in which PASITwas applied, a high percentage of infectious complications overlay was
recorded what influenced the QOL of Ch with AD. In the IG receiving IM, the therapeutic effect was the lowest. CONCLUSIONS: Including CIT in the AD treatment Ps makes it possible to monitor the disease better, a percentage of side effects being low; moreover, it reduces expenses for BT and provides a high level of QOL.
863
Eosinophil Degranulation and the Release of Eosinophil Peroxidase Contributes to the Induced Inflammation Occurring in Mice Following Skin Exposure to TMA Huijun Luo, PhD1, Cheryl A. Protheroe1, Emily D. Blum, PhD2, Allison Fryer, PhD3, Nancy A. Lee, PhD1, David B. Jacoby, MD2, James J. Lee, PhD1; 1Mayo Clinic Arizona, Scottsdale, AZ, 2Oregon Health and Science University, Portland, OR, 3Oregon Health & Science University, Portland, OR. RATIONALE: Contact reactions to allergens and non-classical allergen toxicants such as trimellitic anhydride (TMA) are accompanied by the specific accumulation of eosinophils (and associated eosinophil degranulation), localized skin inflammation, and concomitant increases in sitespecific itch responses. We have recently shown that TMA-induced skin inflammation as well as increases in dermal sensory innervation and the concomitant increase in itching were each eosinophil-dependent events. This demonstrates that a necessary link exists between eosinophils and allergen-induced skin inflammation but does not implicate responsible mechanism. METHODS: Wild type (BALB/c), eosinophil deficient PHIL, and eosinophil peroxidase (EPX) as well as major basic protein (MBP-1) knockout mice were used in a TMA contact hypersensitivity model. High definition videography was used to record the extent of induced itching, prior to measuring local inflammation and the recovery of tissue biopsies for gene expression, histology, immunohistochemistry staining, and imaging of skin innervation. RESULTS: EPX knockout mice displayed decreases the skin inflammation (i.e., decreases in eosinophil accumulation, mast cell activation, and skin thickness) that were similar to the reduced inflammatory events (relative to wild type controls) occurring in eosinophil deficient PHIL mice. More importantly, these mice also displayed decreases in itching. Significantly, MBP-1 knockout mice showed no difference in any of these parameters compared with wild type mice, demonstrating differential effector functions mediated by the release of specific secondary granule proteins. CONCLUSIONS: The release of EPX (but not MBP-1) by skin eosinophils appears to be a causative mechanism contributing to the inflammation and itching that occurs following exposure to the nonclassical allergen TMA.
TUESDAY
861
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Efficacy and Safety of Chitosan Coated Garments on Atopic Dermatitis Management: A Randomized Controlled Trial Cristina Lopes, MD1,2, Jose Soares3, Freni Tavaria4, Milton Severo5, Ana Duarte, MD6, Osvaldo Correia, MD7, Manuela Pintado4, Luis Delgado, MD8, Andre M. Moreira, MD9; 1Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Portugal, Porto, Portugal, 2Allergy Unit, Pedro Hispano Hospital, Matosinhos, Portugal, 3Biology and Fine Chemistry Unit, Biotechnology Faculty, Catholic University, Porto, Portugal, 4Biology and Fine Chemistry Unit, Biotechnology Faculty, Catholic University, Portugal, 5 Medical Faculty , Porto University, Porto, Portugal, 6Epidermis Dermatology Center , Instituto Cuf, Porto, Portugal, 7Epidermis Dermatology Center , Instituto Cuf, Portugal, 8Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Porto, Portugal, 9Allergy and Clinical Immunology Department, Centro Hospitalar S~ao Jo~ao, EPE, Porto, Portugal. RATIONALE: Patients with atopic dermatitis (AD) may benefit from using textiles coated with antiseptic and skin repairing compounds. Chitosan, a natural biopolymer with inhibitory activity against Staphylococcus aureus and immunomodulatory properties has been considered potentially useful in AD management. METHODS: Patients with AD (were randomly assigned in a 1:1 ratio to receive either chitosan coated or placebo cotton long sleeved pyjamas for 8 weeks. Primary efficacy outcome was the change in severity scoring for atopic dermatitis index (SCORAD). Secondary outcomes were the number of patients with minimal clinically detected difference, change in quality of life, daily score of pruritus and sleep loss, need of rescue medication, number of exacerbations, of totally and well-controlled weeks and of adverse events . Microbiological outcomes from five skin regions included changes in number of colony forming units of total staphylococci, Staphylococcus aureus and respective ratio. Analyses were done on an intention-to-treat basis. RESULTS: Of the 102 patients screened, 78 were included aged 30613 years (mean 6SD), 61% female, 77% atopic, with AD for 16610 years . After intervention, patients in chitosan group had a mean relative reduction in SCORAD of 43.8% (95%CI: 30.9 to 55.9), compared with 16.5% (-21.6 to 54.6) in placebo (p5 0.82). Changes in secondary clinical outcomes were similar in both groups. No major imbalances in microbiological profile were observed after the intervention. CONCLUSIONS: Chitosan coated garments are safe for adolescents and adults with atopic dermatitis and reduce AD severity but with no significant differences from placebo.
862
Combination Immunotropic Therapy of Atopic Dermatitis in Children: Cost-Benefit Analysis Vladislava Derkach1,2, Tatiana Slavyanskaya, MD, PhD2,3, Balgamaa Sangidorj3; 1Vladivostok State Medical University, Vladivostok, Russia, 2 Institute of Immunophysiology, Moscow, Russia, 3Peoples’ Friendship University of Russia, Moscow, Russia. RATIONALE: The study was aimed at a cost-benefit analysis (CBA) of various immunotherapy (IT) programmes (Ps) for children (Ch) with AD. METHODS: 94 Ch 3-18 ages with AD having lasted for 1-15 years were examined. All the patients received routine clinical and immuno-allergological examinations. The treatment was conducted in 2 stages: background therapy (BT) and IT. Ch were divided into 3 groups (G): IG (n530) received immunomodulator (IM) on a step-by-step basis in the course dose of 20 mg; IIG (n531) received an accelerated course of parenteral allergen-specific IT (PASIT); IIIG (n533) - a combination IT (CIT) IM+PASIT at an accelerated pace was applied. The quality of life (QOL) of Ch with AD was assessed using the Dermatology Specific Quality of Life (DSQL) questionnaire. The CBA was conducted with due regard to a specific character of the disease, the age composition of the G examined during a current year. RESULTS: The best ratio of high therapeutic effect was recorded in the III G, in which CITwas applied - 88.064.59%. In the IIG, in which PASITwas applied, a high percentage of infectious complications overlay was
recorded what influenced the QOL of Ch with AD. In the IG receiving IM, the therapeutic effect was the lowest. CONCLUSIONS: Including CIT in the AD treatment Ps makes it possible to monitor the disease better, a percentage of side effects being low; moreover, it reduces expenses for BT and provides a high level of QOL.
863
Eosinophil Degranulation and the Release of Eosinophil Peroxidase Contributes to the Induced Inflammation Occurring in Mice Following Skin Exposure to TMA Huijun Luo, PhD1, Cheryl A. Protheroe1, Emily D. Blum, PhD2, Allison Fryer, PhD3, Nancy A. Lee, PhD1, David B. Jacoby, MD2, James J. Lee, PhD1; 1Mayo Clinic Arizona, Scottsdale, AZ, 2Oregon Health and Science University, Portland, OR, 3Oregon Health & Science University, Portland, OR. RATIONALE: Contact reactions to allergens and non-classical allergen toxicants such as trimellitic anhydride (TMA) are accompanied by the specific accumulation of eosinophils (and associated eosinophil degranulation), localized skin inflammation, and concomitant increases in sitespecific itch responses. We have recently shown that TMA-induced skin inflammation as well as increases in dermal sensory innervation and the concomitant increase in itching were each eosinophil-dependent events. This demonstrates that a necessary link exists between eosinophils and allergen-induced skin inflammation but does not implicate responsible mechanism. METHODS: Wild type (BALB/c), eosinophil deficient PHIL, and eosinophil peroxidase (EPX) as well as major basic protein (MBP-1) knockout mice were used in a TMA contact hypersensitivity model. High definition videography was used to record the extent of induced itching, prior to measuring local inflammation and the recovery of tissue biopsies for gene expression, histology, immunohistochemistry staining, and imaging of skin innervation. RESULTS: EPX knockout mice displayed decreases the skin inflammation (i.e., decreases in eosinophil accumulation, mast cell activation, and skin thickness) that were similar to the reduced inflammatory events (relative to wild type controls) occurring in eosinophil deficient PHIL mice. More importantly, these mice also displayed decreases in itching. Significantly, MBP-1 knockout mice showed no difference in any of these parameters compared with wild type mice, demonstrating differential effector functions mediated by the release of specific secondary granule proteins. CONCLUSIONS: The release of EPX (but not MBP-1) by skin eosinophils appears to be a causative mechanism contributing to the inflammation and itching that occurs following exposure to the nonclassical allergen TMA.
TUESDAY
861