What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study.

BACKGROUND: The Eczema Area and Severity Index (EASI) is an investigator-assessed instrument measuring the severity of clinical signs in atopic dermatitis (AD). The EASI was identified as one of the best-validated outcome measures for AD; however, no previous studies address how to interpret the EASI score for clinical use. OBJECTIVES: To evaluate the interpretability and the ease of use of the EASI. METHODS: A retrospective analysis of paediatric and adult patients with AD was performed. Interpretability was evaluated by stratifying the EASI scores according to the Investigator's Global Assessment. The severity strata displaying the highest kappa coefficient of agreement were then selected as the recommended EASI band. The time to administer the EASI was recorded in a subgroup of patients. RESULTS: The suggested severity strata for the EASI are as follows: 0 = clear; 0·1-1·0 = almost clear; 1·1-7·0 = mild; 7·1-21·0 = moderate; 21·1-50·0 = severe; 50·1-72·0 = very severe (κ = 0·75). The EASI was also found to be acceptable in terms of ease of use, with assessments by trained investigators taking approximately 6 min. CONCLUSIONS: Our study provides the first guide for interpreting the EASI score. It enables translation of the EASI numerical output into an AD global severity state that should be more meaningful to providers and patients. Along with a short administration time, the EASI demonstrates adequate feasibility, further supporting its use in clinical trials.

Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME).

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure.

A randomized controlled double-blind investigation of the effects of vitamin D dietary supplementation in subjects with atopic dermatitis.

BACKGROUND: Subjects with atopic dermatitis (AD) have defects in antimicrobial peptide (AMP) production possibly contributing to an increased risk of infections. In laboratory models, vitamin D can alter innate immunity by increasing AMP production. OBJECTIVE: To determine if AD severity correlates with baseline vitamin D levels, and to test whether supplementation with oral vitamin D alters AMP production in AD skin. METHODS: This was a multi-centre, placebo-controlled, double-blind study in 30 subjects with AD, 30 non-atopic subjects, and 16 subjects with psoriasis. Subjects were randomized to receive either 4000 IU of cholecalciferol or placebo for 21 days. At baseline and day 21, levels of 25-hydroxyvitamin D (25OHD), cathelicidin, HBD-3, IL-13, and Eczema Area and Severity Index (EASI) and Rajka-Langeland scores were obtained. RESULTS: At baseline, 20% of AD subjects had serum 25OHD below 20 ng/mL. Low serum 25OHD correlated with increased Fitzpatrick Skin Type and elevated BMI, but not AD severity. After 21 days of oral cholecalciferol, mean serum 25OHD increased, but there was no significant change in skin cathelicidin, HBD-3, IL-13 or EASI scores. CONCLUSIONS: This study illustrated that darker skin types and elevated BMI are important risk factors for vitamin D deficiency in subjects with AD, and highlighted the possibility that seasonality and locale may be potent contributors to cathelicidin induction through their effect on steady state 25OHD levels. Given the molecular links between vitamin D and immune function, further study of vitamin D supplementation in subjects with AD is warranted.

Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells.

BACKGROUND: The increased susceptibility of patients with atopic dermatitis (AD) to disseminated viral skin infections such as eczema herpeticum (ADEH+) is poorly understood. OBJECTIVES: The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections. MATERIALS AND METHODS: In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ (n = 24) compared with AD without a history of viral infections (ADEH-) (n = 20) before and after treatment with herpes simplex virus (HSV). RESULTS: We found that interferon (IFN)-γ expression after HSV treatment was lower in the CD8+ T cells and monocytes from patients with ADEH+ compared with patients who are ADEH- or nonatopic. Given the induction of CD8+ T cells as the result of antigen presentation by human leucocyte antigen (HLA) class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (odds ratio = 1·91, P = 0·02, 125 ADEH+ and 161 ADEH- subjects). CONCLUSIONS: These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype.

A safety assessment of branched chain saturated alcohols when used as fragrance ingredients.

The Branched Chain Saturated Alcohol (BCSA) group of fragrance ingredients was evaluated for safety. In humans, no evidence of skin irritation was found at concentrations of 2-10%. Undiluted, 11 materials evaluated caused moderate to severe eye irritation. As current end product use levels are between 0.001% and 1.7%, eye irritation is not a concern. The materials have no or low sensitizing potential. For individuals who are already sensitized, an elicitation reaction is possible. Due to lack of UVA/UVB light-absorbing structures, and review of phototoxic/photoallergy data, the BCSA are not expected to elicit phototoxicity or photoallergy. The 15 materials tested have a low order of acute toxicity. Following repeated application, seven BCSA tested were of low systemic toxicity. Studies performed on eight BCSA and three metabolites show no in vivo or in vitro genotoxicity. A valid carcinogenicity study showed that 2-ethyl-1-hexanol is a weak inducer of liver tumors in female mice, however, the relevance of this effect and mode of action to humans is still a matter of debate. The Panel is of the opinion that there are no safety concerns regarding BCSA under the present levels of use and exposure.

Effects of pimecrolimus cream 1% in the treatment of patients with atopic dermatitis who demonstrate a clinical insensitivity to topical corticosteroids: a randomized, multicentre vehicle-controlled trial.

BACKGROUND: Colonization with Staphylococcus aureus in atopic dermatitis (AD) is often associated with worsening of clinical symptoms. Staphylococcus aureus produces superantigens that contribute to cutaneous inflammation and corticosteroid (CS) resistance. OBJECTIVES: To investigate the relationship between CS insensitivity, S. aureus colonization and superantigen production in AD, and to explore the efficacy of pimecrolimus cream in CS-insensitive AD. METHODS: This was a randomized, double-blind, vehicle-controlled, multicentre, parallel-group study. Seventy-three patients with AD, aged 2-49 years, who had a documented clinical insensitivity to topical CS, were recruited. The primary efficacy parameters combined laboratory (including S. aureus colonization, superantigens) and clinical assessments [including Eczema Area and Severity Index (EASI), whole body Investigator's Global Assessment (IGA), pruritus assessment score, patient's assessment score of disease control]. RESULTS: An increase in S. aureus counts correlated with worsening of clinical score (week 6 vs. baseline) when assessed by IGA, pruritus severity and patient assessment. The presence of superantigens correlated with this worsening. During the 6-week double-blind phase, disease improvement in the pimecrolimus cream group was demonstrated by decreasing EASI scores compared with vehicle. Mean EASI scores for the head and neck showed greater improvement in the pimecrolimus cream group than in the vehicle group at all observed time points. CONCLUSIONS: In a cohort of patients with clinical insensitivity to CS there was a significant positive correlation between S. aureus and disease severity. Results suggest that for some of these patients, treatment with pimecrolimus cream 1% is useful, especially in the head/neck area.

A toxicologic and dermatologic assessment of cyclic acetates when used as fragrance ingredients.

An evaluation and review of a structurally related group of fragrance materials.

A toxicologic and dermatologic assessment of related esters and alcohols of cinnamic acid and cinnamyl alcohol when used as fragrance ingredients.

An evaluation and review of a structurally related group of fragrance materials.

A toxicologic and dermatologic assessment of ionones when used as fragrance ingredients.

An evaluation and review of a structurally related group of fragrance materials.

A toxicologic and dermatologic assessment of salicylates when used as fragrance ingredients.

An evaluation and review of a structurally related group of fragrance materials.

Novel treatment of chronic severe hand dermatitis with bexarotene gel.

BACKGROUND: Hand dermatitis is an eczematous inflammation of the hands that is related to occupation or to routine activities. It often becomes chronic, and in some patients may become severe and disabling. Topical corticosteroids are effective treatment, particularly for milder forms, but they often lose effectiveness with time and can produce skin atrophy. OBJECTIVES: To evaluate bexarotene gel topical therapy for safety, tolerability and efficacy in patients with chronic hand dermatitis. METHODS: A phase I-II open-label randomized clinical study of bexarotene gel, alone and in combination with a low- and a mid-potency steroid, was conducted in 55 patients with chronic severe hand dermatitis at two academic clinics. RESULTS: Patients using bexarotene gel monotherapy reached a 79% response rate for > or = 50% clinical improvement and a 39% response rate for > or = 90% clearance of hands. Adverse events possibly related to treatment in all patients were stinging or burning (15%), flare of dermatitis (16%) and irritation (29%). Thirteen patients (24%) withdrew early, including two for related adverse events and five for inadequate response. CONCLUSIONS: Bexarotene gel appears to be safe, tolerated by most patients, with useful therapeutic activity in chronic severe hand dermatitis.

Safe treatment of head/neck AD with tacrolimus ointment.

BACKGROUND: Atopic dermatitis(AD) with head and neck involvement is common and therapeutically challenging. METHODS: Efficacy and safety data specific to treatment of head/neck regions with tacrolimus ointment (Protopic) from three double-blind, randomized, vehicle-controlled studies are reported. A total of 631 adult and 352 pediatric patients with moderate to severe atopic dermatitis applied the vehicle, 0.03% or 0.1% tacrolimus ointment twice daily to affected areas for up to 12 weeks. RESULTS: Significant improvements from baseline to end of treatment for signs of atopic dermatitis (erythema, edema, excoriation, oozing, scaling, and lichenification) were noted for head/neck and non-head/neck areas treated with either 0.03% or 0.1% tacrolimus ointment (p<0.001). Within each treatment group, the overall 12-week adjusted incidence rate of application site adverse events was similar for both head/neck and non-head/neck areas. The incidence of common adverse events such as pruritus, "skin burning", erythema, infection, and skin tingling in head/neck areas was comparable to that observed in non-head/neck areas within each treatment group. The overall prevalence of application site adverse events decreased rapidly during the first few days of treatment. CONCLUSION: Tacrolimus ointment is a safe and effective treatment for atopic dermatitis on the head and neck.