title: Tacrolimus Ointment 0.03% Is Safe and Effective for the Treatment of Mild to Moderate Atopic Dermatitis in Pediatric Patients: Results From a Randomized, Double-Blind, Vehicle-Controlled Study Influence of Pimecrolimus Cream 1% on Different Morphological Signs of Eczema in Infants with Atopic Dermatitis The patient-oriented eczema measure: development and initial validation of a new tool for measuring atopic eczema severity from the patients' perspective. Disease severity and associated family impact in childhood atopic dermatitis Scoring of atopic dermatitis by SCORAD using a training atlas by investigators from different disciplines. ETAC Study Group. Early Treatment of the Atopic Child. Validation of the Eczema Area and Severity Index for atopic dermatitis in a cohort of 1550 patients from the pimecrolimus cream 1% randomized controlled clinical trials programme Symptomatology and growth in infants with cow's milk protein intolerance using two different whey-protein hydrolysate based formulas in a Primary Health Care setting. Cyclosporin in atopic dermatitis: a multicentre placebo‐controlled study Scoring the severity of atopic dermatitis: three item severity score as a rough system for daily practice and as a pre-screening tool for studies. Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis A randomised, double-blind, vehicle-controlled study to evaluate the efficacy and safety of MAS063D (Atopiclair) in the treatment of mild to moderate atopic dermatitis. Morbidity and cost of atopic eczema in Australia Treatment of infants with atopic eczema with pimecrolimus cream 1% improves parents' quality of life: a multicenter, randomized trial. Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis Correlation of eosinophils, eosinophil cationic protein and soluble interleukin-2 receptor with the clinical activity of atopic dermatitis.
abstract: Objective . This study was design ed to compare the safety and efficacy of tacrolimus ointment 0.03 % with vehicle ointment for the treatment of mild to moderate atopic dermatitis ( AD ) in pediatric patients . Methods . A total of 317 patients ( 2–15 years of age ) with mild to moderate AD were r and omized to receive tacrolimus ointment or vehicle ointment twice daily in a 6-week , multicenter , double-blind study . Efficacy evaluations , including the Investigators ' Global Atopic Dermatitis Assessment , eczema area and severity index , percentage of total body surface area affected , and patient assessment of itch occurred at baseline , day 4 , and weeks 2 , 4 , and 6 . Cutaneous adverse events were recorded to evaluate safety . Results . At the end of study , 50.6 % ( 80 of 158 ) of the patients were treated successfully with tacrolimus ointment based on Investigators ' Global Atopic Dermatitis Assessment scores , a significant improvement compared with patients treated with vehicle ointment ( 25.8 % [ 41 of 159 ] ) . The percent improvement from baseline in eczema area and severity index scores was also significantly greater in tacrolimus-treated patients ( 54.8 % ) compared with vehicle-treated patients ( 20.8 % ) . There was also a significant improvement in the percentage of total body surface area affected of tacrolimus-treated patients ( 50.5 % reduction from baseline ) compared with vehicle-treated patients ( 16.4 % ) . Patient itch scores were significantly lower in tacrolimus-treated patients ( 2.1 ) versus vehicle-treated patients ( 3.7 ) . Overall , the incidence of cutaneous adverse events reported was similar for both treatment groups . There was no significant difference in the incidence of burning or stinging between treatment groups . Significantly fewer tacrolimus-treated patients prematurely discontinued from the study because of a cutaneous adverse event in the treatment area or experienced increased itching and erythema at the application site . Conclusion . Monotherapy with tacrolimus ointment 0.03 % is a safe and effective treatment alternative for pediatric patients with mild to moderate AD Background : In the published studies on the efficacy of the topical immunomodulator pimecrolimus , different eczema scores were used , and the impact on morphological key signs of eczema was not analysed . Objective : To compare the influence of pimecrolimus cream 1 % on different st and ard eczema scores in infants with atopic dermatitis and to analyse the impact of treatment on the individual morphological key signs of eczema . Methods :  Pimecrolimus cream 1 % ( n = 129 ) or double-blind vehicle control ( n = 66 ) was administered for 4 weeks . The Eczema Area and Severity Index ( EASI ) , Investigators ’ Global Assessment ( IGA ) and Scoring Atopic Dermatitis Index ( SCORAD ) were determined and were correlated with each other . Results : Following treatment with pimecrolimus , the EASI , IGA and SCORAD were significantly reduced on day 29 as compared with the vehicle group ( p < 0.001 , p < 0.001 , p = 0.002 , respectively ) . There was a close correlation between EASI , IGA and SCORAD . The single parameters of the EASI were already significantly decreased by day 4 in the pimecrolimus group as compared to vehicle ( each p < 0.001 ) . Conclusion : Treatment with pimecrolimus 1 % cream leads to a rapid improvement of all morphological signs of eczema . The close correlation of different scores was shown for the first time OBJECTIVE To develop a simple , valid , repeatable , and readily underst and able patient-oriented assessment measure for monitoring disease activity in children and adults with atopic eczema . DESIGN Qualitative semistructured patient interviews identified a list of symptoms of atopic eczema . These symptoms were quantitatively analyzed in a larger patient population to identify which symptoms were important to patients and amenable to monitoring as part of a scoring system . SETTING The outpatient Department of Dermatology at the Queen 's Medical Centre , University Hospital , Nottingham , Engl and , and 5 local general practice s. PATIENTS Four hundred thirty-five patients with atopic eczema . RESULTS Seven symptoms were incorporated into the final patient-oriented eczema measure using a simple 5-point scale of frequency of occurrence during the previous week , with a maximum total score of 28 . Validity testing against the Dermatology Life Quality Index , Children 's Dermatology Life Quality Index , and patients ' global severity assessment s showed good correlation ( r = 0.78 , r = 0.73 , and r = 0.81 , respectively ; P<.001 ) . Internal consistency was high ( Cronbach alpha = 0.88 ) , and test-retest reliability was good , with 95 % of scores falling within 2.6 points on repeat testing ( mean score difference , 0.04 ; SD , 1.32 ) . Individual variables in the measure demonstrated sensitivity to change during a 4-week in-clinic period and an 18-week r and omized controlled clinical trial . CONCLUSION The patient-oriented eczema measure is a practical self-assessed measurement tool for monitoring aspects of atopic eczema that are important to patients in routine clinical practice or in the clinical trial setting Aim : To examine the association between childhood atopic dermatitis ( AD ) severity and family impact at baseline and after an intervention by a physician specialist , using vali date d measures of both severity and family impact . Methods : Cross sectional self administered survey of parent – caregivers of 49 r and omly selected children with AD ; 35 parents were available for follow up .  Family impact was measured using a modified AD Family Impact Scale completed by the parent – caregiver . The child ’s disease severity was measured using both the investigator ’s assessment via the Eczema Area and Severity Index ( EASI ) and the caregiver ’s assessment via the recently vali date d Self Assessment Eczema Area and Severity Index ( SA-EASI ) . Results : The parent – caregiver ’s assessment of severity of the child was the most significant correlate of the family impact of the child ’s AD ( p = 0.65 at baseline and p = 0.38 at follow up ) . In multivariate regression models , the parent – caregiver ’s estimate of severity remained the single strongest predictor of family impact before and after receipt of dermatologist care , as well as the difference in impact between pre and post-dermatologist care . Conclusions : There is evidence to support the ability of parent – caregivers of children with AD to accurately determine severity of their child ’s AD ; perceived severity is the driver of the family impact of this condition . Treatment of a child by a physician specialist is associated with reductions in both perceived severity , as well as family impact of this condition The ETAC ( Early Treatment of the Atopic Child ) study , a multi-national double-blind placebo-controlled r and omized trials , has been in progress since 1994 . Fifty-six centers in Europe and Canada participate in this study . A total of 817 children with atopic dermatitis [ AD ] were recruited . The severity of AD was scored using the SCORAD ( objective criteria ) . Ninety-eight investigators ( mostly pediatricians ) were trained by three members of the European Task Force on Atopic Dermatitis [ ETFAD ] to st and ardize their objective SCORAD scoring ( system developed by the ETFAD ) . The experts selected photographs and prepared a training atlas . The percentages of photographs assessed by the 98 non-expert investigators below , within and above the range of evaluations by the three experts were calculated . Taking over and underscoring together , edema/papulation was the easiest intensity item to score ( 82 % within the range by the experts ) . The global symptom score , as well as lichenification , edema/papulation , oozing and excoriation registered by physicians with dermatological experience were not statistically significantly different from those by other . Erythema was statistically significantly better scored by those with dermatological experience . The results of the Euclidean Distance method showed that the item excoriations gave the largest distance . Erythema and excoriations were scored better by dermatologically experienced physicians ( t-test , p = 0.042 and p = 0.063 respectively ) , but lichenification was better scored by non-dermatologically experienced physicians ( p = 0.013 ) . The extent of surface area involved in the disease was calculated on 3 sets of photographs . Most evaluations by the 98 nonexpert investigators were within the range of the experts . Dermatologically experienced physicians scored significantly better than the others ( t-test , p = 0.006 ) . This training program is useful for st and ardizing the scoring in AD and indicates that SCORAD can be used by investigators from different disciplines Objective To vali date the Eczema Area and Severity Index ( EASI ) by assessing its internal consistency , reliability and sensitivity to change and by correlating it to other efficacy parameters . Both growth and the course of allergic symptoms were evaluated in 79 infants with cow 's milk protein intolerance , aged three months or younger , diagnosed by st and ard elimination/provocation and treated with a whey-hydrolysate based infant formula : Nutrilon Pept or Pepti Junior .  The efficacy of both products , in terms of symptomatology and growth , was compared with each other . The products differ in fat source ( Pepti Junior 50 % of its fat as MCT , Nutrilon Pepti normal LCT fat blend ) and the presence of lactose ( Pepti Junior : lactose free ; Nutrilon Pepti : 40 % of its carbohydrate as lactose ) . The study was part of a large project that aim ed at st and ardising the approach towards cow 's milk protein intolerance in Baby Health Clinics . Nearly 50 Baby Health Clinics participated in this project . In this study , growth and symptomatology ( skin , respiratory tract , gastrointestinal tract ) were monitored during an intervention period of at least 10 weeks . Infants in both feeding groups showed normal growth , and in at least 80 % of the infants an improvement of the overall symptomatology could be seen during the intervention period . Most profound were the decreases in prevalence and severity of eczema and infantile colic . No differences in efficacy were found in this study between the two infant formulas . It was concluded that the exclusive use of either whey hydrolysate based infant formula result ed in an improvement of allergic symptoms and in normal growth in infants diagnosed by elimination/provocation for cow 's milk protein intolerance in a Primary Health Care setting Summary The efficacy of cyclosporin ( S and immun ® ) given in a daily dose of 5 mg/kg for 6 weeks in  severe atopic dermatitis  was confirmed in this double‐blind , placebo‐controlled , short‐term study . Of the 46 patients included in the study , 23 were r and omized to receive cyclosporin and 23 to receive placebo Different scoring systems have been developed to determine the severity of atopic dermatitis .  The SCORAD ( SCORing Atopic Dermatitis ) , one of the best vali date d systems , is suited for clinical trials , but is too complicated and time consuming for routine clinical use . The TIS score  ( Three Item Severity score ) , a simplified system , is based on the evaluation of erythema , oedema/papulation and excoriation on a scale from 0 to 3 . In order to determine the value of the TIS score we conducted a prospect i ve study in 126 children with mild to severe atopic dermatitis . Both the  TIS score and the SCORAD  were assessed by trained investigators . Interobserver agreement was investigated in 20 children by comparing the independently performed scores of three investigators . A positive correlation was found between the TIS score and the SCORAD ( Rank Spearman r(s)=0.86 ; p<0.0005 ) . The item which correlated best with the SCORAD was excoriation ( r(s)=0.72 ; p<0.0005 ) followed by oedema/papulations ( r(s)=0.66 ; p<0.0005 ) . Interobserver agreement which was calculated by Cohen 's kappa ( kappa ) was " excellent " for SCORAD ( kappa=0.82 ; p<0.001 ) and " fair " for TIS score ( kappa=0.58 ; p<0.01 ) . We conclude that the TIS score is a rough , though reliable and simple system for scoring  atopic dermatitis . It is particularly suitable in general practice , for routine clinical use and for screening purpose s in clinical trials . For research purpose s , the objective SCORAD offers a more detailed and comprehensive assessment A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids , azathioprine , and photochemotherapy .  33 patients took part in a double-blind ,  placebo-controlled  , crossover study to assess the efficacy and safety of cyclosporin ( 5 mg/kg per day ) in adults with severe refractory atopic dermatitis . Treatments were given for eight weeks each with one group ( n = 16 ) receiving placebo followed by cyclosporin and another ( n = 17 ) receiving cyclosporin and then placebo .  Disease activity , extent of disease , sleep and itch , topical steroid use , and adverse events were assessed every two weeks . Both extent and activity of dermatitis were significantly improved ( p less than 0.001 ) as were subjective measures of disease .  20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo  , although no patient required withdrawal from the study . Cyclosporin therapy led to an increase in the mean serum urea , creatinine , and bilirubin concentrations , although only the rise in bilirubin was significant ( p = 0.001 ) . Our results confirm that cyclosporin is a safe and effective short-term treatment for severe , refractory atopic dermatitis MAS063D ( Atopiclair is a hydrolipidic cream that has been developed for the management of atopic dermatitis ( AD ) . The putative active ingredients of MAS063D are hyaluronic acid , telmesteine , Vitis vinifera , glycyrrhetinic acid . A five-week study in 30 adult patients with mild to moderate AD showed that MAS063D offered significant benefits over a vehicle-only control . MAS063D improved the total body area affected ( 17.2 % -- > 13.2 % , p < 0.001 ) , itch score ( 2.7 -- > 1.3 on a 10-point scale , p = 0.001 ) and EASI score ( 28.3 -- > 24.3 , p = 0.024 ) after 22 days treatment compared to baseline . The patients ' opinion of MAS063D ( patient 's view of itch control , and view of study substance ) was rated by participating patients as significantly better than control ( p = 0.008 , p = 0.042 respectively ) . Based on these preliminary results in a small scale study , it is suggested that MAS063D is a possible new treatment option for improving signs and symptoms in adults with mild to moderate AD The severity , morbidity and financial costs of atopic eczema ( AE ) were assessed during a 1‐year prospect i ve study of a cohort of 85 people aged 14–63 years ( mean 36 years ) with the disease . A dermatologist examined each participant using the Six Area Six Sign Atopic Dermatitis severity scoring system to classify severity . Participants completed a  Dermatology Life Quality Index ( DLQI ) , a Nottingham Eczema Severity Score ( NESS ) and an ongoing diary of health‐care consultations and treatment costs . Follow up by mail to each participant was conducted every 2 months and participants completed a NESS , a DLQI and a diary of costs incurred . The DLQI data revealed that 36 % spent over 10 min per day applying treatments , 28 % indicated that AE influenced the clothes they wore , 21 % felt embarrassed by their skin and 15 % reported problems with treatments . There appeared to be a relationship between increased morbidity and increased severity . The average annual out‐of‐pocket cost for products used for treatment was A$ 425 , ranging from A$ 13.50 to over A$ 2000 per individual . The average out‐of‐pocket cost for medical consultations was A$ 120 , ranging from zero to over A$ 800 per individual . Although there were concerns about the reproducibility of the severity and morbidity measures , the data showed that AE can have substantial effects both financially and from a personal perspective for those affected Atopic eczema begins primarily in infancy or early childhood , and sleep loss due to night-time pruritus can have a considerable impact on patients ' and parents ' quality of life ( QoL ) . In this study , infants ( n = 196 ) with mild to severe atopic eczema were r and omized 2:1 , double-blind , to receive either pimecrolimus cream 1 % ( Elidel , Novartis Pharma , Nürnberg , Germany ) or the corresponding vehicle bid for 4 wk , followed by a 12 wk , open-label phase and a 4 wk , treatment-free , follow-up period . The parents ' QoL was measured at baseline and at the end of the double-blind phase , using the question naire ' QoL in Parents of Children with Atopic Dermatitis ' ( PQoL-AD ) , thus data presented here refer to the initial 4-wk treatment phase only . After 4 wk of double-blind treatment , an increase in the mean percentage change from baseline in eczema area and severity index of 71.5 % was observed with pimecrolimus , compared with 19.4 % with vehicle . The increase in efficacy was paralleled by the following mean percentage changes from baseline in the five domains of the question naire in pimecrolimus and vehicle , respectively : psychosomatic well-being : 14.6 % vs. 6.2 % ; effects on social life : 6.7 % vs. 2.3 % ; confidence in medical treatment : 10.0 % vs. 3.7 % ; emotional coping : 16.1 % vs. 6.5 % ; acceptance of disease : 19.6 % vs. 7.0 % . Analysis ( ancova ) of the dependent variable difference from baseline and the covariate baseline value revealed values of p < 0.05 for all five domains , despite the very short duration of the study . It is concluded that improvements in  atopic eczema in infants achieved by treatment with pimecrolimus have a significant beneficial effect on the QoL of parents Treatment of atopic dermatitis with essential fatty acids remains controversial . A double-blind , placebo-controlled , parallel-group study was done to investigate the response of patients with atopic dermatitis to essential fatty acid supplements .  Patients with atopic dermatitis were r and omised to receive evening primrose oil , evening primrose oil and fish oil , or placebo for 16 weeks . Disease activity was monitored by clinical severity scores recorded by the investigator , topical steroid requirement , and symptom scores recorded by subjects . Of 123 subjects recruited , 102 completed the treatment period . No improvement with active treatment was demonstrated . Our study , which avoided the method ological and analytical problems of previous studies , found no effect of essential fatty acid supplementation in atopic dermatitis To evaluate the correlation with the clinical activity of atopic dermatitis ( AD ) we investigated prospect ively cellular and serological parameters such as eosinophils , eosinophil cationic protein ( ECP ) , soluble IL-2 receptor ( sIL-2R ) , soluble CD23 ( sCD23 ) and lactate dehydrogenase ( LDH ) in peripheral blood of 37 AD patients on admission to and discharge from the Department of Dermatology at the University Hospital in Zurich . On admission the actual clinical skin condition as measured by the skin intensity score ( SIS ) was significantly correlated with eosinophils ( p less than 0.005 ) , ECP ( p less than 0.05 ) and sIL-2R ( p less than 0.001 ) . During the observation period a significant improvement in the clinical status as measured by the SIS was observed in all AD patients ( p less than 0.001 ) . A significant decrease in sIL-2R ( p less than 0.005 ) , which was most pronounced in the group of AD patients receiving systemic steroids , together with a decrease in eosinophils and ECP but not in sCD23 and LDH could be demonstrated between admission and discharge . In addition , a slight but significant increase in peripheral blood lymphocytes ( p less than 0.005 ) and monocytes ( p less than 0.01 ) was noted . Comparing the ' extrinsic ' ( n = 32 ) and the ' intrinsic ' ( n = 5 ) types of AD no significant differences with regard to the above mentioned parameters were found . Our data indicate that cellular and serological parameters such as eosinophils , ECP and sIL-2R reflect the clinical activity of AD and may therefore give further insights into the pathogenesis of this disease
target: CLINICAL IMPLICATION S Only SCORAD , EASI , and POEM currently perform adequately .
background: BACKGROUND Valid and reliable outcome measurements are a prerequisite for evidence -based practice .
  The comparative validity and reliability of outcome measurements for assessing atopic eczema ( AE ) severity is unclear .
  OBJECTIVE We sought to assess the validity , reliability , sensitivity to change , and ease of use of outcome measurements for AE .
  We also sought to give recommendations on which outcomes to use in clinical research and for clinical monitoring .