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Scratching in Atopic Dermatitis Has Circadian Rhythm
AB238 Abstracts
746
Hereditary vs Acquired Angioedema: An Actualized Experience with Patients in Puerto Rico.
Rafael H. Zaragoza-Urdaz, MD, PhD; RAFAEL H ZARAGOZA URDAZ MD CSP, San Juan, PR. RATIONALE: To describe clinical characteristics of patients with both HAE and AAE at a private practice in Puerto Rico (PR), their response to newer acute and prophylactic therapies available, the impact on complications in an observational study. METHODS: Patients referred to our practice for evaluation and management of recurrent angioedema. Once the diagnosed treatment (tx) with s/c Icatibant or Ecallantide were offered as rescue therapy and a C1 Inhibitor _1 attacks of angioedema per (human), was offered if the patient had > month, as prophylactic therapy. RESULTS: Overall 46 patients; 37 (80%) were females. Age range 5 to 68y/o. Current tx for HAE: prophylaxis with C1 INH 16 (35%), acute tx with Icatibant or Ecallantide 28 (61%). Effect of tx on attacks/month: no attacks from 3 to 41%, 1-2 attacks from 31 to 37%, 3 to 4 attacks from 45 to _5 from 21 to 13%. Effect of treatments ER visits in last 6mo: no 9%, and > _5 ER visits from 38 to 63%, 1-2 from 31 to 37%, 3 to 4 from 23 to 4%, and > from 19 to 2%. Effect of tx Hospitalizations in last 6mo: no Hospitalizations from 27 to 87%, 1-2 from 4 to 11%, 3 to 4 from 12 to _5 from 4 to 0%. 2%, and > CONCLUSIONS: There has been a dramatic burst of HAE in PR;therefore, it is crucial to expand diagnostic testing to different parts of the island to identify undiagnosed patients, for prompt differentiation to receive pertinent and cost-effective therapeutic interventions.
747
CD300a: A New Player in Atopic Dermatitis?
MONDAY
Laila Karra*, Equal contributors1. Roopesh Singh Gangwar*, Equal contributors1. Tgst Levi1, Yael Minai-Fleminger1, Nanna Fyhrquist2, Vera Leibovic3, Dagmar Simon4, and Francesca Levi-Schaffer, PhD, FAAAAI1; 1The Hebrew University of Jerusalem, Jerusalem, Israel, 2 University of Helsinki, Helsinki, Finland, 3Hadassah Hebrew University Medical Center, Jerusalem, Israel, 4Department of Dermatology, University Hospital Bern, Bern, Switzerland. RATIONALE: CD300a is an inhibitory receptor expressed by mast cells (MCs) and eosinophils. We have previously shown that its expression on eosinophils is upregulated by hypoxia and GM-CSF, hallmarks of inflammation. Atopic Dermatitis (AD) is a chronic inflammatory disease characterized by MCs and eosinophil activation. Therefore, we aimed to investigate a possible involvement of CD300a in AD. METHODS: Skin biopsies and blood leukocytes from AD patients and normal volunteers were stained for CD300a and biopsies also for hypoxia (HIF1a) and blood vessels (PECAM). Human cord blood (CBMC) and mouse bone marrow (BMMC) derived MCs and human peripheral blood eosinophils were incubated under hypoxia or with S. aureus exotoxins for CD300a expression (FACS, WB, RT-PCR). AD (SEB+OVA/skin tape stripping) or peritonitis (SEB) were induced in CD300a-/- and WT mice and disease characteristics followed. RESULTS: AD skin showed increased expression of CD300a particularly in eosinophils and macrophages, hypoxia and increased vascularity. Dermal blood vessel numbers correlated with CD300a+MCs and macrophages. CD300a expression was significantly decreased on blood NK cells and increased on B cells. In vitro CD300a expression on MCs and eosinophils was increased by both hypoxia and exotoxins. In CD300a-/- mice epidermal/dermal thickness and eosinophilia was increased in AD and overall inflammation and characteristic eosinophil infiltration were enhanced in SEB-peritonitis. CONCLUSIONS: CD300a expression is modulated in human AD and its absence in a mouse model of AD and of SEB peritonitis increases inflammation. Targeted activation of CD300a on MCs and eosinophils can be a novel therapeutic approach in AD.
J ALLERGY CLIN IMMUNOL FEBRUARY 2017
748
Scratching in Atopic Dermatitis Has Circadian Rhythm
Anna Fishbein1, Phyllis Zee2, Jennifer Beaumont3, Brendon Lin4, and Amy S. Paller, MD5; 1Lurie Children’s Hospital, CHICAGO, 2Northwestern University, chicago, 3Northwestern University, Statistics, chicago, 4Lurie Children’s Hospital, Chicago, 5Northwestern University Feinberg School of Medicine, Chicago, IL. RATIONALE: Nocturnal eczema flares are severely pruritic and sleep disturbing, yet timing of flares is not well established. Our hypothesis is that eczema has a circadian rhythm, with scratching episodes peaking within the first few hours after sleep onset. METHODS: Case control study with children ages 6-17 years with moderate/severe AD, controlled asthma and AR (n519), and age matched controls (n511). Scratch and sleep were assessed via validated actigraphy (Actiwatch Spectrum) measured for 5-7 consecutive days/nights. Generalized least squares models, with cubic spline for smoothing, were fit to the data. RESULTS: Children with AD (65% male, SCORAD m558622(mean+SD)) versus controls had significantly more minutes of wake after sleep onset (m598653 v. 50630, p50.01). However, the interaction between group and timing was not significant (p50.37). Yet, the average amount of movement (scratch) in children with AD was increased compared to controls (p<0.0001) and had a clear timing pattern that differed from control patients (p<0.01). These activity bouts clustered in AD around 2-5 hours after sleep, with peak scratch 3 hours after sleep onset. CONCLUSIONS: Most nocturnal scratch behavior in AD is 2-5 hours after sleep onset, peaking at 3 hours. Overnight awakenings did not have a specific rhythm in AD. This pattern of timing in nocturnal eczema suggests a circadian rhythm to pruritus. Further research into the circadian rhythm of AD might answer the fundamental question about the etiology of AD flares.
746
Hereditary vs Acquired Angioedema: An Actualized Experience with Patients in Puerto Rico.
Rafael H. Zaragoza-Urdaz, MD, PhD; RAFAEL H ZARAGOZA URDAZ MD CSP, San Juan, PR. RATIONALE: To describe clinical characteristics of patients with both HAE and AAE at a private practice in Puerto Rico (PR), their response to newer acute and prophylactic therapies available, the impact on complications in an observational study. METHODS: Patients referred to our practice for evaluation and management of recurrent angioedema. Once the diagnosed treatment (tx) with s/c Icatibant or Ecallantide were offered as rescue therapy and a C1 Inhibitor _1 attacks of angioedema per (human), was offered if the patient had > month, as prophylactic therapy. RESULTS: Overall 46 patients; 37 (80%) were females. Age range 5 to 68y/o. Current tx for HAE: prophylaxis with C1 INH 16 (35%), acute tx with Icatibant or Ecallantide 28 (61%). Effect of tx on attacks/month: no attacks from 3 to 41%, 1-2 attacks from 31 to 37%, 3 to 4 attacks from 45 to _5 from 21 to 13%. Effect of treatments ER visits in last 6mo: no 9%, and > _5 ER visits from 38 to 63%, 1-2 from 31 to 37%, 3 to 4 from 23 to 4%, and > from 19 to 2%. Effect of tx Hospitalizations in last 6mo: no Hospitalizations from 27 to 87%, 1-2 from 4 to 11%, 3 to 4 from 12 to _5 from 4 to 0%. 2%, and > CONCLUSIONS: There has been a dramatic burst of HAE in PR;therefore, it is crucial to expand diagnostic testing to different parts of the island to identify undiagnosed patients, for prompt differentiation to receive pertinent and cost-effective therapeutic interventions.
747
CD300a: A New Player in Atopic Dermatitis?
MONDAY
Laila Karra*, Equal contributors1. Roopesh Singh Gangwar*, Equal contributors1. Tgst Levi1, Yael Minai-Fleminger1, Nanna Fyhrquist2, Vera Leibovic3, Dagmar Simon4, and Francesca Levi-Schaffer, PhD, FAAAAI1; 1The Hebrew University of Jerusalem, Jerusalem, Israel, 2 University of Helsinki, Helsinki, Finland, 3Hadassah Hebrew University Medical Center, Jerusalem, Israel, 4Department of Dermatology, University Hospital Bern, Bern, Switzerland. RATIONALE: CD300a is an inhibitory receptor expressed by mast cells (MCs) and eosinophils. We have previously shown that its expression on eosinophils is upregulated by hypoxia and GM-CSF, hallmarks of inflammation. Atopic Dermatitis (AD) is a chronic inflammatory disease characterized by MCs and eosinophil activation. Therefore, we aimed to investigate a possible involvement of CD300a in AD. METHODS: Skin biopsies and blood leukocytes from AD patients and normal volunteers were stained for CD300a and biopsies also for hypoxia (HIF1a) and blood vessels (PECAM). Human cord blood (CBMC) and mouse bone marrow (BMMC) derived MCs and human peripheral blood eosinophils were incubated under hypoxia or with S. aureus exotoxins for CD300a expression (FACS, WB, RT-PCR). AD (SEB+OVA/skin tape stripping) or peritonitis (SEB) were induced in CD300a-/- and WT mice and disease characteristics followed. RESULTS: AD skin showed increased expression of CD300a particularly in eosinophils and macrophages, hypoxia and increased vascularity. Dermal blood vessel numbers correlated with CD300a+MCs and macrophages. CD300a expression was significantly decreased on blood NK cells and increased on B cells. In vitro CD300a expression on MCs and eosinophils was increased by both hypoxia and exotoxins. In CD300a-/- mice epidermal/dermal thickness and eosinophilia was increased in AD and overall inflammation and characteristic eosinophil infiltration were enhanced in SEB-peritonitis. CONCLUSIONS: CD300a expression is modulated in human AD and its absence in a mouse model of AD and of SEB peritonitis increases inflammation. Targeted activation of CD300a on MCs and eosinophils can be a novel therapeutic approach in AD.
J ALLERGY CLIN IMMUNOL FEBRUARY 2017
748
Scratching in Atopic Dermatitis Has Circadian Rhythm
Anna Fishbein1, Phyllis Zee2, Jennifer Beaumont3, Brendon Lin4, and Amy S. Paller, MD5; 1Lurie Children’s Hospital, CHICAGO, 2Northwestern University, chicago, 3Northwestern University, Statistics, chicago, 4Lurie Children’s Hospital, Chicago, 5Northwestern University Feinberg School of Medicine, Chicago, IL. RATIONALE: Nocturnal eczema flares are severely pruritic and sleep disturbing, yet timing of flares is not well established. Our hypothesis is that eczema has a circadian rhythm, with scratching episodes peaking within the first few hours after sleep onset. METHODS: Case control study with children ages 6-17 years with moderate/severe AD, controlled asthma and AR (n519), and age matched controls (n511). Scratch and sleep were assessed via validated actigraphy (Actiwatch Spectrum) measured for 5-7 consecutive days/nights. Generalized least squares models, with cubic spline for smoothing, were fit to the data. RESULTS: Children with AD (65% male, SCORAD m558622(mean+SD)) versus controls had significantly more minutes of wake after sleep onset (m598653 v. 50630, p50.01). However, the interaction between group and timing was not significant (p50.37). Yet, the average amount of movement (scratch) in children with AD was increased compared to controls (p<0.0001) and had a clear timing pattern that differed from control patients (p<0.01). These activity bouts clustered in AD around 2-5 hours after sleep, with peak scratch 3 hours after sleep onset. CONCLUSIONS: Most nocturnal scratch behavior in AD is 2-5 hours after sleep onset, peaking at 3 hours. Overnight awakenings did not have a specific rhythm in AD. This pattern of timing in nocturnal eczema suggests a circadian rhythm to pruritus. Further research into the circadian rhythm of AD might answer the fundamental question about the etiology of AD flares.