Six Area, Six Sign Atopic Dermatitis Research Articles

Approach to the Assessment and Management of Adult Patients With Atopic Dermatitis: A Consensus Document. Section II: Tools for Assessing the Severity of Atopic Dermatitis.

Clinicians rely on clinical measures to define the severity of atopic dermatitis and assess outcomes of therapy. These measures can be objective (ie, physician assessments of disease severity) or subjective (ie, patient-reported symptoms and quality of life outcomes). In this review, the most commonly used tools for assessing atopic dermatitis severity in adult patients are presented and compared. These include Eczema Area and Severity Index (EASI); SCORing Atopic Dermatitis (SCORAD); Physician Global Assessment (PGA); body surface area (BSA); Atopic Dermatitis Severity Index (ADSI); Six Area, Six Sign Atopic Dermatitis (SASSAD); Patient Oriented Eczema Measure (POEM); Dermatology Life Quality Index (DLQI); and pruritus Numerical Rating Scale (NRS). Available severity strata for the tools are summarized, although the use of severity strata in clinical practice is not recommended. Since both objective and subjective assessments of disease severity are important to assess, consideration of clinical characteristics such as disease recurrence or persistence, as well as location of the affected areas, should be considered in the overall judgement of disease severity and consideration of therapy choice.

Leukotriene receptor antagonists for eczema.

Leukotriene receptor antagonists for eczema.

EASI p-EASI: Utilizing a combination of serum biomarkers offers an objective measurement tool for disease severity in atopic dermatitis patients

EASI p-EASI: Utilizing a combination of serum biomarkers offers an objective measurement tool for disease severity in atopic dermatitis patients

Immunoglobulin free light chains in adult atopic dermatitis patients do not correlate with disease severity.

BackgroundAlthough total IgE levels have been proposed as a biomarker for disease severity in atopic dermatitis (AD) and are increased in the majority of AD patients, they do not correlate with disease severity during short-term follow-up. During the synthesis of immunoglobulins, free light chains (Ig-FLCs) are produced in excess over heavy chains. In comparison with IgE molecules, Ig-FLCs have a very short serum half-life. Therefore, Ig-FLCs might be more suitable as a biomarker for disease severity during follow-up. Recent studies showed increased serum levels of kappa Ig-FLCs in infants with AD, correlating with disease severity. The aim of this study was to investigate serum kappa Ig-FLC levels in adults with AD, and their correlation to disease severity.MethodsSerum kappa If-FLC and total IgE levels were measured in 82 moderate to severe AD patients and 49 non-atopic controls. Blood was collected from patients before start of treatment with potent topical steroids (European classification: III–IV). 32 patients were treated during a clinical admission, and in this subpopulation a second blood sample was taken after 2 weeks of treatment. Clinical severity was determined by the Six Area Six Sign Atopic Dermatitis (SASSAD) severity score and a panel of serum biomarkers, including thymus and activation-regulated chemokine (TARC).ResultsSerum kappa Ig-FLCs levels in adult AD patients were not increased compared to non-atopic controls. Moreover, we observed no correlation between kappa Ig-FLC serum levels and disease severity determined by SASSAD and a panel of serum biomarkers, including TARC. Serum kappa Ig-FLC levels did also not decrease during treatment.ConclusionThere are no differences in serum kappa Ig-FLC levels between adult patients suffering from moderate to severe AD compared to non-atopic controls. Moreover, serum levels of kappa Ig-FLCs cannot be used as a biomarker for disease severity in adult AD.

House dust mite reduction and avoidance measures for treating eczema.

Eczema is an inflammatory skin disease that tends to involve skin creases, such as the folds of the elbows or knees; it is an intensely itchy skin condition, which can relapse and remit over time. As many as a third of people with eczema who have a positive test for allergy to house dust mite have reported worsening of eczema or respiratory symptoms when exposed to dust. To assess the effects of all house dust mite reduction and avoidance measures for the treatment of eczema. We searched the following databases up to 14 August 2014: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2014, Issue 8), MEDLINE (from 1946), Embase (from 1974), LILACS (from 1982), and the GREAT database. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant studies. We handsearched abstracts from international eczema and allergy meetings. Randomised controlled trials (RCTs) of any of the house dust mite reduction and avoidance measures for the treatment of eczema, which included participants of any age diagnosed by a clinician with eczema as defined by the World Allergy Organization. We included all non-pharmacological and pharmacological interventions that sought to reduce or avoid exposure to house dust mite and their allergenic faeces. The comparators were any active treatment, no treatment, placebo, or standard care only. Two authors independently checked the titles and abstracts identified, and there were no disagreements. We contacted authors of included studies for additional information. We assessed the risk of bias using Cochrane methodology. We included seven studies of 324 adults and children with eczema. Overall, the included studies had a high risk of bias. Four of the seven trials tested interventions with multiple components, and three tested a single intervention. Two of the seven trials included only children, four included children and adults, and one included only adults. Interventions to reduce or avoid exposure to house dust mite included covers for mattresses and bedding, increased or high-quality vacuuming of carpets and mattresses, and sprays that kill house dust mites.Four studies assessed our first primary outcome of 'Clinician-assessed eczema severity using a named scale'. Of these, one study (n = 20) did not show any significant short-term benefit from allergen impermeable polyurethane mattress encasings and acaricide spray versus allergen permeable cotton mattress encasings and placebo acaricide spray. One study (n = 60) found a modest statistically significant benefit in the Six Area, Six Sign Atopic Dermatitis (SASSAD) scale over six months (mean difference of 4.2 (95% confidence interval 1.7 to 6.7), P = 0.008) in favour of a mite impermeable bedding system combined with benzyltannate spray and high-filtration vacuuming versus mite permeable cotton encasings, water with a trace of alcohol spray, and a low-filtration vacuum cleaner. The third study (n = 41) did not compare the change in severity of eczema between the two treatment groups. The fourth study (n = 86) reported no evidence of a difference between the treatment groups.With regard to the secondary outcomes 'Participant- or caregiver-assessed global eczema severity score' and the 'Amount and frequency of topical treatment required', one study (n = 20) assessed these outcomes with similar results being reported for these outcomes in both groups. Four studies (n = 159) assessed 'Sensitivity to house dust mite allergen using a marker'; there was no clear evidence of a difference in sensitivity levels reported between treatments in any of the four trials.None of the seven included studies assessed our second primary outcome 'Participant- or caregiver-assessed eczema-related quality of life using a named instrument' or the secondary outcome of 'Adverse effects'.We were unable to combine any of our results because of variability in the interventions and paucity of data. We were unable to determine clear implications to inform clinical practice from the very low-quality evidence currently available. The modest treatment responses reported were in people with atopic eczema, specifically with sensitivity to one or more aeroallergens. Thus, their use in the eczema population as a whole is unknown. High-quality long-term trials of single, easy-to-administer house dust mite reduction or avoidance measures are worth pursuing.

Is There an Additional Value of Inpatient Treatment for Patients with Atopic Dermatitis?

An inpatient treatment and education programme has been developed for patients with difficult to control atopic dermatitis (AD), with the aim of achieving adequate self-management and long-term disease control. This observational study included adult patients diagnosed with difficult to control AD, admitted for a structured inpatient treatment and education programme. The primary outcome was the Six Area, Six Sign Atopic Dermatitis (SASSAD) score. In total, 79 patients (mean ± SD age 38.8 ± 17.1 years) were included. The median duration of hospitalization was 11 days (interquartile range 8-14). The mean percentage decrease in SASSAD score between admission and discharge was 60.7%, of which 64 (81.0%) patients achieved SASSAD50. The mean percentage decrease in SASSAD score was 69.0% during follow-up, of which 63 (79.7%) patients still had a SASSAD50. In the majority of these patients with difficult to control AD the admission resulted in sustained disease control. This could be achieved by optimization of treatment with topical corticosteroids.

Are accelerometers a useful tool for measuring disease activity in children with eczema? Validity, responsiveness to change, and acceptability of use in a clinical trial setting

Actigraphy, which uses accelerometers to record movement, has been proposed as an objective method of itch assessment in eczema. Previous studies have found strong correlations with actigraphy and video surveillance, disease severity and biological markers in patients with eczema. To assess the validity of accelerometer data, its responsiveness to change and the practicality and acceptability of accelerometers when used as an outcome measure in a clinical trial. This study used data collected from 336 participants of the Softened Water Eczema Trial (SWET). Accelerometer data were compared with three standardized scales: Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score, Patient Oriented Eczema Measure (POEM) and Dermatitis Family Impact (DFI). Spearman's rank testing was used for correlations. Only 70% of trial participants had complete data, compared with 96% for the primary outcome (eczema severity - SASSAD). The convergent validity of accelerometer data with other measures of eczema severity was poor: correlation with SASSAD 0·15 (P = 0·02) and POEM 0·10 (P = 0·13). Assessing for divergent validity against quality of life measures, the correlation with the DFI was low (r = 0·29, P < 0·0001). Comparing the change scores from baseline to week 12 for SASSAD, POEM and DFI with the change in accelerometer scores we found low, negative correlations (r = -0·02, P = 0·77; r = -0·12, P = 0·06; and r = -0·01, P = 0·87, respectively). In general, the units were well tolerated but suggestions were made that could improve their usability in children. Actigraphy did not correlate well with disease severity or quality of life when used as an objective outcome measure in a multicentre clinical trial, and was not responsive to change over time. Further work is needed to establish why this might be, and to establish improved methods of distinguishing between eczema-related and eczema-nonrelated movements.

Moderate correlation between quality of life and disease activity in adult patients with atopic dermatitis

Studies assessing the relationship between disease activity and quality of life (QoL) in adults with atopic dermatitis (AD), before and after therapy are lacking. The relation between disease activity and QoL in AD patients was evaluated before (t = 0) and after 6 weeks (t = 6) of treatment with cyclosporin 5 mg/kg. In 54 patients with severe AD, disease activity was assessed using objective Scoring Atopic Dermatitis index (SCORAD), Six Area Six Sign Atopic Dermatitis (SASSAD), 'rule of nines' extent score and serum levels of thymus and activation-regulated chemokine (TARC). Patients filled out the Dermatology Life Quality Index (DLQI). To study the relation between disease activity and QoL, correlations were calculated and regression analysis was performed. At t = 0 there was a small, non-significant correlation between the DLQI and the objective SCORAD, 'rule of nines' or serum TARC levels. At t = 6 the objective SCORAD, serum TARC and the 'rule of nines' score showed moderate and significant correlations with the DLQI (r = 0.34, P = 0.02; r = 0.31, P = 0.03; r = 0.49, P < 0.001). An individual's improvement in disease activity (objective SCORAD, SASSAD and 'rule of nines') with 10 points was associated with an improvement of 1.3, 1.5 and 1.1 points respectively in DLQI. Disease activity correlated better with QoL when disease activity was less severe and disease extent ('rule of nines') correlated better with QoL than disease severity. An individual's improvement of 10 points in disease activity was accompanied by only a small improvement in QoL. Other factors than disease activity may influence QoL in patients with AD.

A multicentre randomised controlled trial and economic evaluation of ion-exchange water softeners for the treatment of eczema in children: the Softened Water Eczema Trial (SWET)

To determine whether installation of an ion-exchange water softener in the home could improve atopic eczema in children and, if so, to establish its likely cost and cost-effectiveness. An observer-blind, parallel-group randomised controlled trial of 12 weeks duration followed by a 4-week observational period. Eczema was assessed by research nurses blinded to intervention at baseline, 4 weeks, 12 weeks and 16 weeks. The primary outcome was analysed as intent-to-treat, using the randomised allocation rather than actual treatment received. A secondary per-protocol analysis excluded participants who failed to receive their allocated treatment and who were deemed to be protocol violators. Secondary and primary care referral centres in England (UK) serving a variety of ethnic and social groups and including children living in both urban and periurban homes. Three hundred and thirty-six children (aged 6 months to 16 years) with moderate/severe atopic eczema, living in homes in England supplied by hard water (≥ 200 mg/l calcium carbonate). Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care (group A) for 12 weeks or usual eczema care alone (group B) for 12 weeks. This was followed by a 4-week observational period, during which water softeners were switched off/removed from group A homes and installed in group B homes. Standard procedure was to soften all water in the home, but to provide mains (hard) water at a faucet-style tap in the kitchen for drinking and cooking. Participants were therefore exposed to softened water for bathing and washing of clothes, but continued to drink mains (hard) water. Usual care was defined as any treatment that the child was currently using in order to control his or her eczema. New treatment regimens used during the trial period were documented. Primary outcome was the difference between group A and group B in mean change in disease severity at 12 weeks compared with baseline, as measured using the Six Area, Six Sign Atopic Dermatitis (SASSAD) score. This is an objective severity scale completed by blinded observers (research nurses) unaware of the allocated intervention. Secondary outcomes included use of topical medications, night-time movement, patient-reported eczema severity and a number of quality of life measures. A planned subgroup analysis was conducted, based on participants with at least one mutation in the gene encoding filaggrin (a protein in the skin thought to be important for normal skin barrier function). Target recruitment was achieved (n = 336). The analysed population included 323 children who had complete data. The mean change in primary outcome (SASSAD) at 12 weeks was -5.0 [standard deviation (SD) 8.8] for the water softener group (group A) and -5.7 (SD 9.8) for the usual care group (group B) [mean difference 0.66, 95% confidence interval (CI) -1.37 to 2.69, p = 0.53]. The per-protocol analysis supported the main analysis, and there was no evidence that the treatment effect varied between children with and without mutations in the filaggrin gene. No between-group differences were found in the three secondary outcomes that were assessed blindly (use of topical medications; night-time movement; proportion showing reasonable, good or excellent improvement). Small, but statistically significant, differences in favour of the water softener were found in three of the secondary outcomes that were assessed by participants [Patient-Oriented Eczema Measure (POEM); well-controlled weeks (WCWs); Dermatitis Family Index (DFI)]. The results of the economic evaluation, and the uncertainty surrounding them, suggest that ion-exchange water softeners are unlikely to be a cost-effective intervention for children with atopic eczema from an NHS perspective. Water softeners provided no additional benefit to usual care in this study population. Small, but statistically significant, differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias. Whether or not the wider benefits of installing a water softener in the home are sufficient to justify the purchase of a softener is something for individual householders to consider on a case-by-case basis. This trial demonstrated overwhelming demand for non-pharmacological interventions for the treatment of eczema, and this is something that should be considered when prioritising future research in the field. Current Controlled Trials ISRCTN71423189. This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 8. See the HTA programme website for further project information. Results of this trial are also published at www.plosmedicine.org.

Medium-dose ultraviolet (UV) A1 vs. narrowband UVB phototherapy in atopic eczema: a randomized crossover study

Ultraviolet (UV) A1 and narrowband (NB)-UVB have been reported to be effective treatments for atopic eczema (AE). We aimed to compare the efficacy of medium-dose UVA1 and NB-UVB mono-phototherapy in patients with AE. A randomized double-blind controlled crossover trial (ClinicalTrials.gov Identifier: NCT00419406) was conducted in which patients with AE received a 6-week course of both medium-dose UVA1 and NB-UVB. Clinical efficacy was assessed using the Six Area, Six Sign, Atopic Dermatitis (SASSAD) score and a visual analogue scale for pruritus. Assessment of health-related quality of life was performed using the Skindex-29. Total immunoglobulin E (IgE) and eosinophilic cationic protein (ECP) were evaluated at baseline and after each phototherapy course. Twenty-eight patients who completed both UVA1 and NB-UVB phototherapy courses on an intention-to-treat basis were analysed according to the crossover design. Both interventions were associated with significant clinical improvement but there was no significant difference between treatments with respect to the mean +/- SD relative reduction (RR) of the clinical scores (SASSAD, 43.7 +/- 31.4% vs. 39.4 +/- 24.1%, P = 0.5; pruritus score, 16 +/- 61.8% vs. 25.2 +/- 30.5%, P = 0.5, respectively). There was no significant difference in the mean +/- SD RR of the Skindex-29 after UVA1 and NB-UVB phototherapy (12.7 +/- 18.8% vs. 16.5 +/- 17.6%, P = 0.1). Changes in the total IgE and ECP levels following UVA1 and NB-UVB did not differ significantly (P = 0.3 and P = 0.9, respectively). A 6-week course of NB-UVB and UVA1 phototherapy of AE resulted in significant clinical improvement. With regard to efficacy and tolerability, both phototherapeutic modalities may be considered comparably good.

The Comparison between Objective and Subjective Severity Scores of Atopic Dermatitis

RationaleMethods of measuring extent and severity of atopic dermatitis (AD) are based on assessment of signs and symptoms. Many scoring systems were validated, but they might not represent subjective severity of patients. The purpose of this study is to compare the subjective with the objective severity of scoring systems.MethodsFifty children (26 males, 24 females, aged between 3 months and 12 years) with AD were recruited by the pediatric allergy center at Soonchunhyang university hospital from June 1, 2007 to July 31, 2007. We checked their SCORAD (SCORing Atopic Dermatitis) score, EASI (Eczema Area and Severity Index) score, SASSAD (Six Area, Six Sign Atopic Dermatitis) score, Parental visual analog scale (PaVAS, 0-10 point), and Investigator's VAS (INVAS,0-10 point). We analyzed and compared each score with scales.ResultsSCORAD score had a strong correlation with EASI and SASSAD score (r = 0.84 vs 0.92). EASI score showed significant correlation with SASSAD score (r = 0.86). PaVAS was found to be less correlated with SCORAD, EASI and SASSAD scores (r = 0.37, 0.23, 0.33), whereas INVAS showed greater correlations with SCORAD, EASI and SASSAD score (r = 0.6, 0.52, 0.52). It demonstrated that established severity scoring systems has a greater correlation with severity by investigator's view-point but less correlation with subjective severity by patients'.ConclusionsEstablished scoring system or indices are generally reflect the objective severity by investigators. Therefore physicians should consider the patients' subjective severity when they take care of atopic dermatitis. RationaleMethods of measuring extent and severity of atopic dermatitis (AD) are based on assessment of signs and symptoms. Many scoring systems were validated, but they might not represent subjective severity of patients. The purpose of this study is to compare the subjective with the objective severity of scoring systems. Methods of measuring extent and severity of atopic dermatitis (AD) are based on assessment of signs and symptoms. Many scoring systems were validated, but they might not represent subjective severity of patients. The purpose of this study is to compare the subjective with the objective severity of scoring systems. MethodsFifty children (26 males, 24 females, aged between 3 months and 12 years) with AD were recruited by the pediatric allergy center at Soonchunhyang university hospital from June 1, 2007 to July 31, 2007. We checked their SCORAD (SCORing Atopic Dermatitis) score, EASI (Eczema Area and Severity Index) score, SASSAD (Six Area, Six Sign Atopic Dermatitis) score, Parental visual analog scale (PaVAS, 0-10 point), and Investigator's VAS (INVAS,0-10 point). We analyzed and compared each score with scales. Fifty children (26 males, 24 females, aged between 3 months and 12 years) with AD were recruited by the pediatric allergy center at Soonchunhyang university hospital from June 1, 2007 to July 31, 2007. We checked their SCORAD (SCORing Atopic Dermatitis) score, EASI (Eczema Area and Severity Index) score, SASSAD (Six Area, Six Sign Atopic Dermatitis) score, Parental visual analog scale (PaVAS, 0-10 point), and Investigator's VAS (INVAS,0-10 point). We analyzed and compared each score with scales. ResultsSCORAD score had a strong correlation with EASI and SASSAD score (r = 0.84 vs 0.92). EASI score showed significant correlation with SASSAD score (r = 0.86). PaVAS was found to be less correlated with SCORAD, EASI and SASSAD scores (r = 0.37, 0.23, 0.33), whereas INVAS showed greater correlations with SCORAD, EASI and SASSAD score (r = 0.6, 0.52, 0.52). It demonstrated that established severity scoring systems has a greater correlation with severity by investigator's view-point but less correlation with subjective severity by patients'. SCORAD score had a strong correlation with EASI and SASSAD score (r = 0.84 vs 0.92). EASI score showed significant correlation with SASSAD score (r = 0.86). PaVAS was found to be less correlated with SCORAD, EASI and SASSAD scores (r = 0.37, 0.23, 0.33), whereas INVAS showed greater correlations with SCORAD, EASI and SASSAD score (r = 0.6, 0.52, 0.52). It demonstrated that established severity scoring systems has a greater correlation with severity by investigator's view-point but less correlation with subjective severity by patients'. ConclusionsEstablished scoring system or indices are generally reflect the objective severity by investigators. Therefore physicians should consider the patients' subjective severity when they take care of atopic dermatitis. Established scoring system or indices are generally reflect the objective severity by investigators. Therefore physicians should consider the patients' subjective severity when they take care of atopic dermatitis.

A double‐blind, placebo‐controlled trial of montelukast in adult atopic eczema

Montelukast is an antagonist of cys-leukotriene receptors used mainly in the treatment of asthma- and seasonal-allergic rhinitis. Initial reports concerning the use of montelukast in atopic dermatitis (AD) have been encouraging, although not consistent. We have undertaken a randomized, double-blind, parallel-group, placebo-controlled trial to investigate further the efficacy of montelukast in the treatment of atopic eczema. Following a screening visit, subjects received placebo treatment for 2 weeks in a single-blind phase, followed after visit 2 by an 8-week, double-blind period of treatment with montelukast 10 mg daily or placebo. Subjects were patients aged 16-60 years under our care for treatment of AD of moderate severity, defined by a six-area, six-sign atopic dermatitis (SASSAD) score in the range 12-50. Response to treatment was assessed by investigators and by subjects using a seven-point scale, with response defined as marked improvement or better. In addition, the SASSAD score was used to monitor the severity of clinical signs. The proportion of skin involved was estimated and visual analogue scales were used to record the severity of pruritus and sleep disturbance. Topical corticosteroid usage was recorded using a five-point scale. Adverse events were recorded. Sixty subjects were recruited and 54 completed the study. The treatment groups were well matched for disease severity at baseline (SASSAD scores were 25 and 29 in the montelukast and placebo groups, respectively). There were no significant differences between the treatment groups in any of the parameters used to assess treatment response. The improvement in mean SASSAD score from baseline (visit 2) to the end of treatment was marginally superior in the placebo group, 1.41 points on montelukast vs. 1.76 on placebo, a difference of 0.35 (95% confidence interval -6.1 to 6.8). Adverse events were generally of a mild nature except for a brief septicaemic illness in one subject receiving montelukast. The data do not support previous reports of efficacy of montelukast in treatment of AD.

Low basal serum cortisol in patients with severe atopic dermatitis: potent topical corticosteroids wrongfully accused

Topical corticosteroids are used extensively to treat inflammatory skin disorders including atopic dermatitis (AD). Several studies have described temporary reversible suppression of hypothalamic-pituitary-adrenal function. However, sound evidence of permanent disturbance of adrenal gland function is lacking. To relate basal cortisol levels to prior use of topical corticosteroids and disease activity in patients with moderate to severe AD and to investigate the effect on basal serum cortisol levels of topical corticosteroid treatment during hospitalization. Two groups of patients with AD were evaluated: 25 inpatients with severe AD who required hospitalization (group 1) and 28 outpatients with moderate to severe AD (group 2). In group 1, morning basal serum cortisol levels were measured twice, at admission and at discharge; in group 2, morning basal serum cortisol levels were measured once. Use of topical corticosteroids in the 3 months prior to the cortisol measurement was recorded and disease activity was monitored using the Six Area, Six Sign Atopic Dermatitis (SASSAD) score and serum thymus and activation-regulated chemokine (TARC) levels. On admission, basal cortisol levels in group 1 were significantly (P < 0.001) decreased in 80% of the patients. In group 2, the basal cortisol levels were normal in all but three patients. Comparing the two groups, group 1 on admission had a significantly lower cortisol level than that of group 2 (P < 0.001). Disease activity in group 1 on admission was significantly higher than that of group 2 (P < 0.001). There was no difference in use of topical corticosteroids in the 3 months before cortisol measurement. At discharge in group 1 there was a significant increase (P < 0.0001) of basal cortisol levels and a significant (P < 0.001) decrease in disease activity reflected by the decrease in serum TARC levels and SASSAD score. Disease activity, rather than the use of topical corticosteroids, is responsible for the low basal cortisol values in patients with severe AD.

An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema

Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2.5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. On average, disease activity improved by 52% from baseline (95% confidence interval 45-60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as 'marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted.

Killed Mycobacterium vaccae suspension in children with moderate‐to‐severe atopic dermatitis: a randomized, double‐blind, placebo‐controlled trial

The hygiene hypothesis is often proposed to explain the high prevalence of atopy in the western world. Dysregulation of the immune system may result from inadequate exposure to micro-organisms such as mycobacteria. A small trial suggested that a killed extract of Mycobacterium vaccae ameliorates atopic dermatitis (AD). To confirm in a large clinical trial whether killed M. vaccae ameliorates AD in 5-16-year-old children. This was a randomized, placebo-controlled, double-blind, multi-centre study of the effect of intradermal injection of killed M. vaccae (0.1 or 1 mg) on patients, aged 5-16, with moderate-to-severe AD. Patients were followed up for 24 weeks. The primary end point was the change in severity of AD at 12 weeks, assessed using the six area, six-sign, atopic dermatitis (SASSAD) score. Secondary end points included changes in disease extent, patient's global assessment and children's dermatology life quality index. There were 166 patients randomized. The mean SASSAD score fell to a similar degree at week 12 in all treatment arms: from 33 to 24, (26%) in the high-dose group, from 30 to 23 (25%) in the low-dose group and from 36 to 27 (24%) in the placebo group (P>0.05). Secondary end points followed the same trend. Adverse events were generally those expected to occur in this population. Injection site reactions occurred in 32 patients at week 4. M. vaccae was no more effective than the placebo in ameliorating the severity of AD.

Azathioprine dosed by thiopurine methyltransferase activity for moderate-to-severe atopic eczema: a double-blind, randomised controlled trial

Atopic eczema affects 1-2% of adults, and can cause considerable morbidity. We aimed to assess the safety and efficacy of azathioprine as systemic monotherapy for moderate-to-severe atopic eczema, and the therapeutic importance of the thiopurine methyltransferase (TPMT) polymorphism (a key determinant of azathioprine-induced myelotoxicity) by using TPMT enzyme activity to establish azathioprine dose. We did a parallel-group, double-blind, placebo-controlled trial in an outpatient setting. Minimisation was used to assign 63 patients with active disease despite optimum topical therapy to treatment with azathioprine (n=42) or placebo (n=21) for 12 weeks. As maintenance treatment, patients with heterozygous range TPMT activity received azathioprine 1.0 mg/kg daily, compared with 2.5 mg/kg daily in patients with normal TPMT activity. For the first 4 weeks, all participants received lower azathioprine doses (0.5 and 1.0 mg/kg daily, respectively) to reduce gastrointestinal side-effects. The primary measure of clinical response was disease activity assessed by the SASSAD (six area six sign atopic dermatitis) score. Analysis was by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN58943280. 54 (86%) participants completed the study; two (3%) withdrew from the placebo group and seven (11%) from the azathioprine group. At week 12, there was a 37% (12.0 unit) improvement in mean disease activity with azathioprine compared with a 20% (6.6 unit) improvement with placebo (17% [5.4 unit] difference, 95% CI 4.3-29%). This finding was accompanied by significant improvements in patient-reported itch, area of involvement, global assessment, and quality of life. Between participants there was a wide variation in response to the drug. Generally, azathioprine was well tolerated, although two individuals developed drug hypersensitivity. Participants with heterozygous range TPMT activity responded to azathioprine in similar proportions to other participants, but none developed bone-marrow toxicity. TPMT-based dosing seemed to reduce predicted toxicity, and drug efficacy was maintained. Treatment with azathioprine as systemic monotherapy produces clinically relevant improvement in moderate-to-severe atopic eczema that remains active despite optimum therapy with topical corticosteriods. We believe the study of azathioprine as systemic monotherapy for atopic eczema has major advantages, which should allow clarification of the relation between azathioprine effectiveness and metabolite profiles in other inflammatory diseases.

The value of SCORAD and beyond. Towards a standardized evaluation of severity?

The clinical scoring systems of atopic dermatitis were analysed and compared. Some biological parameters that can correlate with the clinical score were also reviewed. After the definition of the disease based on validated clinical criteria, the second necessity was the availability of reliable severity scores to allow clinicians to verify the course of the disease and the efficacy of treatments. After many proposals, the SCORAD (SCORing Atopic Dermatitis), that required more than three years of work, was the first one that was validated. SCORAD is freely available from an internet site and can be easily calculated using dedicated software. EASI (Eczema Area and Severity Index) score has also been validated but it has been modified twice. Simpler systems include SASSAD (Six Area, Six Sign Atopic Dermatitis) and TIS score (Three-Item Severity score). In parallel, biological parameters were investigated. Eosinophil cationic protein, circulating basophils, major basic protein, soluble E-selectin, antistaphylococcal enterotoxin B, immunoglobulin E titres and macrophage-derived chemokine, can correlate significantly with the clinical score. The clinicians will not benefit directly from laboratory techniques and will employ clinical scores.

Efficacy and tolerability of borage oil in adults and children with atopic eczema: randomised, double blind, placebo controlled, parallel group trial

Objective To study the efficacy and tolerability of borage oil, which contains a high concentration of γ linolenic acid, in children and adults with atopic eczema.Design Single centre, randomised, double...

Reliability testing of the Six Area, Six Sign Atopic Dermatitis severity score

The Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score is an objective atopic eczema severity index designed principally to assess response to treatment in therapeutic trials. Validity has been demonstrated in single and multicentre clinical trials, although data on the reliability of the index have not previously been published. To assess inter- and intraobserver variability of the SASSAD index. Six observers with experience in the assessment of atopic eczema were each asked to score disease severity in six patients with moderate to severe atopic eczema using the SASSAD index. Repeat observations were carried out on randomly selected patients by each observer to estimate intraobserver variation. The interobserver variation in total SASSAD scores for each patient ranged from 7 to 30 (median 15.5) out of a maximum possible score of 108. The intraclass correlation coefficient ri for the total scores among all six observers was quite high at 0.70, although interobserver agreement for individual components of the index was poor to moderate. The maximum recorded intraobserver variation in total SASSAD score in any of the examined patients was 8 units. As with many other tested atopic eczema scoring indices, the SASSAD index is subject to significant interobserver variation, reflecting the difficulties in reliably assessing eczema severity objectively.

Six area, six sign atopic dermatitis (SASSAD) severity score: a simple system for monitoring disease activity in atopic dermatitis.

The Six Area, Six Sign Atopic Dermatitis severity score has proved to be a simple and effective system for recording and monitoring disease activity in atopic dermatitis. The score is obtained by grading six signs (erythema, exudation, excoriation, dryness, cracking and lichenification), each on a scale of () (absent), 1 (mild), 2 (moderate), or 3 (severe), at each of six sites; arms, hands, legs, feet, head and neck, trunk. The maximum score is 108.