Relationship between EASI and SCORAD severity assessments for atopic dermatitis

Abstract

Atopic dermatitis (AD) manifestations are heterogeneous, with variable lesional severity and extent. A systematic review was performed by Harmonizing Outcome Measures in Eczema,1Schmitt J. Spuls P.I. Thomas K.S. Simpson E. Furue M. Deckert S. et al.The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials.J Allergy Clin Immunol. 2014; 134: 800-807Abstract Full Text Full Text PDF PubMed Scopus (203) Google Scholar an international consensus group aimed at standardizing outcome assessments in AD trials, and informed that its recommendation for Eczema Area and Severity Index (EASI) be included in the core outcome set, but use of Scoring AD (SCORAD) was also encouraged for clinical trials.1Schmitt J. Spuls P.I. Thomas K.S. Simpson E. Furue M. Deckert S. et al.The Harmonising Outcome Measures for Eczema (HOME) statement to assess clinical signs of atopic eczema in trials.J Allergy Clin Immunol. 2014; 134: 800-807Abstract Full Text Full Text PDF PubMed Scopus (203) Google Scholar Nevertheless, they were developed independently with different methods and target populations, and fundamentally different approaches. Understanding the gaps and relationship between EASI and SCORAD is imperative for the appropriate design and interpretation of clinical research studies. We hypothesized that there are differences between EASI and SCORAD, particularly in patients with localized moderate-severe lesions, as well as xerosis and oozing that are assessed in SCORAD but not in EASI. We performed a prospective, dermatology practice–based, observational study to determine the relationship between EASI and SCORAD. Adolescents and adults (≥13 years) completed the patient-oriented eczema measure (POEM) and were evaluated with a medical history and total body skin examination by a dermatologist (J.S.). Subjects were enrolled from September 2014 to June 2016. The study was approved by the institutional review boards of Northwestern University and informed consent was waived. AD was diagnosed using the Hanifin and Rajka2Hanifin J. Rajka G. Diagnostic features of atopic dermatitis.Acta Derm Venereol (Stockh). 1980; 92: 44-47Google Scholar diagnostic criteria. AD severity was assessed using the EASI,3Hanifin J.M. Thurston M. Omoto M. Cherill R. Tofte S.J. Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group.Exp Dermatol. 2001; 10: 11-18Crossref PubMed Scopus (449) Google Scholar SCORAD, objective-SCORAD (oSCORAD),4Kunz B. Oranje A.P. Labreze L. Stalder J.F. Ring J. Taieb A. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis.Dermatology. 1997; 195: 10-19Crossref PubMed Google Scholar and POEM. Distribution of AD lesions was collected using a standardized checklist. Data analysis was performed using SAS version 9.4 (SAS Institute, Cary, NC). Statistical significance was determined on the basis of 2-sided P < .05. Complete data analysis was performed. EASI, oSCORAD/SCORAD, and POEM were not normally distributed. Correlations were performed using Spearman correlations. Mann-Whitney U tests were used to compare oSCORAD/SCORAD scores among patients with low EASI scores with or without xerosis, oozing/weeping, or localization of moderate-severe lesions to specific body sites. Additional details of AD assessments are presented in the Methods section in the Online Repository at www.jacionline.org. Linear regression models were constructed with (1) oSCORAD/SCORAD as the dependent variables and EASI as the independent variables and (2) POEM as the dependent variable and oSCORAD/SCORAD and EASI as the independent variables. Based on visual inspection of scatter plots, a nonlinear relationship was examined. Linear and multiple orders of spline functions were tested and retained on the basis of best statistical fit. A penalized-spline term with 1 knot was the best-fitting model. Inclusion of the penalized-spline term in the regression models allowed for a nonlinear relationship between variables. Overall, 388 patients (mean age, 41.3 ± 16.8 years; range, 13-93 years) with a total of 678 encounters were included in the study, including 266 females (69.3%) and 247 whites (64.7%) (Table I).Table ISubjects' characteristics (n = 388)VariableValueAge (y), mean ± SD41.3 ± 16.8Female sex, n (%)266 (69.3)Race/ethnicity, n (%) Caucasian/white247 (64.7) African-American/black46 (12.0) Hispanic24 (6.3) Multiracial/other65 (17.2)Insured, n (%)311 (80.4) Open table in a new tab EASI and oSCORAD were strongly correlated with each other (ρ = 0.92; P < .0001), but only moderately with POEM (ρ = 0.46 and 0.44; P < .0001). There were nonlinear relationships of EASI with SCORAD (r2linear = 0.73; r2nonlinear = 0.85) (Fig 1, A), oSCORAD (r2linear = 0.78; r2nonlinear = 0.87) (Fig 1, B), and POEM (r2linear = 0.14; r2nonlinear = 0.33) (Fig 1, C), which were significantly better depicted using higher order polynomial functions (P < .0001) and improvement of model fit (Fig 1, A). For EASI of 5 or less, there was a broad range of oSCORAD (0-48; mean ± SD, 13.0 ± 7.9), SCORAD (0-60; mean ± SD, 19.3 ± 10.4), or POEM (0-28; mean ± SD, 7.8 ± 5.8). Similarly, SCORAD was strongly correlated with POEM (ρ = 0.56; P < .0001). For EASI of 5.1 to 72, there were linear relationships with oSCORAD, SCORAD, and POEM. In contrast, oSCORAD (r2linear = 0.27; r2nonlinear = 0.20) and SCORAD (r2linear = 0.29; r2nonlinear = 0.30) had linear relationships with POEM with no substantial improvement in model fit, respectively (Fig 1, D and E). EASI of 5 or less was unable to discriminate between severe localized lesions and mild extensive lesions, with broad ranges of scores for erythema (0-3), edema/papulation (0-2), lichenification (0-3), scratching (0-3), oozing/weeping (0-2), xerosis (0-3), and body surface area (0%-62%; mean ± SD, 5.9 ± 7.6). Patients with EASI of 5 or less had significantly higher oSCORAD scores when xerosis was versus was not present (22.2 ± 9.1 vs 15.0 ± 10.7; Mann-Whitney U test, P < .0001), particularly moderate-severe (score of 2-3) versus mild xerosis (score of 1) was present (26.1 ± 13.1 vs 21.7 ± 8.3; P = .04). The presence of oozing/weeping was associated with significantly higher oSCORAD (32.1 ± 9.1 vs 18.4 ± 9.8; P < .0001). There were no significant differences for the relationship between EASI and oSCORAD/SCORAD across races/ethnicities (white, black, Hispanic, multiracial/other), sex (male, female), and age (adolescent, adult) (P ≥ .16). Patients with EASI of 5 or less had significantly higher oSCORAD when moderate-severe versus no-mild lesions were localized to the face (29.3 ± 9.5 vs 18.1 ± 9.9; P < .0001), eyelids (30.5 ± 11.2 vs 18.4 ± 9.8; P < .0001), neck (31.4 ± 10.8 vs 18.7 ± 10.0; P < .0001), hands (30.9 ± 9.5 vs 18.5 ± 10.0; P < .0001), and feet (34.4 ± 12.9 vs 19.1 ± 10.3; P = .02). The present study shows a complex relationship between EASI and oSCORAD/SCORAD and several limitations of both measures. Xerosis and/or oozing/weeping were associated with significantly higher oSCORAD, but low EASI. This is because xerosis and oozing/weeping are scored in oSCORAD, but not in EASI. Patients with low EASI had higher oSCORAD secondary to localized moderate-severe lesions, and higher POEM scores. EASI assesses 4 AD signs and weights them to the BSA-affecting 4 sites. oSCORAD/SCORAD assesses 6 AD signs separately from BSA, with representative lesional intensity comprising 76%/61% of the total score. Thus, patients with localized moderate-severe lesions may have high oSCORAD, but low EASI. Selection of a representative lesion in oSCORAD/SCORAD might bias toward reporting more severe disease. However, this does not appear to be the case because oSCORAD/SCORAD showed a closer relationship with POEM than with EASI. EASI and SCORAD were not perfectly correlated with POEM. Although each of these is a validated AD outcome measure, it may be that no single assessment is adequate for assessing the full severity and/or burden of AD. Of note, the 3 signs most closely associated with patient-reported AD severity (erythema, excoriation, and edema/papulation)5Charman C.R. Venn A.J. Williams H. Measuring atopic eczema severity visually: which variables are most important to patients?.Arch Dermatol. 2005; 141 (discussion 51): 1146-1151Crossref PubMed Scopus (53) Google Scholar are present in EASI and oSCORAD/SCORAD. Low EASI scores encompass a heterogeneous group of patients, including some having fairly extensive milder lesions and localized moderate-severe lesions. Studies of mild AD that use low EASI scores as an inclusion criterion may enroll a diverse mixture of patients with different extent and lesional severity. These results shed light on the interpretation of EASI scores in the mild range. Previous interpretability studies found that EASI scores of 0 to 7.0 encompass almost clear or mild AD,6Leshem Y.A. Hajar T. Hanifin J.M. Simpson E.L. What the Eczema Area and Severity Index score tells us about the severity of atopic dermatitis: an interpretability study.Br J Dermatol. 2015; 172: 1353-1357Crossref PubMed Scopus (150) Google Scholar yet this encompasses a heterogeneous group of patients. In EASI, the lowest surface area category is quite broad at 1% to 9% and equally weights cases with a 1-cm plaque or 9% of the body site affected. EASI may be a poorer measurer than oSCORAD when assessing patients with more limited disease. Alternatively, it is possible that oSCORAD/SCORAD is a poor measure of mild disease with too broad a range of values. We believe this to be less likely, because unlike EASI, the oSCORAD/SCORAD scores had linear relationships with POEM. Nevertheless, inclusion of xerosis in the oSCORAD/SCORAD might reduce its responsiveness, because xerosis may be present in the absence of active AD lesions. Moreover, assessing xerosis can be challenging in clinical trials because it varies by the frequency, vehicle, and time of last application of emollients/moisturizers. In conclusion, the present results provide further support for the inclusion of oSCORAD and/or SCORAD in addition to EASI in clinical trials. oSCORAD/SCORAD correlated better with POEM than did EASI. However, the merits of assessing both EASI and SCORAD in trials has to be weighed against the excess burden of data collection for investigators and patients, as well as difficulties in training investigators in how to assess both scales. This research was presented at the Society of Investigative Dermatology 2017 annual meeting in Portland, Oregon. AD severity was assessed using the EASI (4 signs [erythema, excoriation, edema/papulation, lichenification] on 4 body sites; score range, 0-72),E1Hanifin J.M. Thurston M. Omoto M. Cherill R. Tofte S.J. Graeber M. The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. EASI Evaluator Group.Exp Dermatol. 2001; 10: 11-18Crossref PubMed Scopus (781) Google Scholar SCORAD (6 signs [erythema, excoriation, edema/papulation, oozing/crusting, lichenification, dryness] for a representative lesion, surface area assessed on 8 body sites, pruritus and sleeplessness; score range, 0-103), and oSCORAD (6 signs [erythema, excoriation, edema/papulation, oozing/crusting, lichenification, dryness] on 8 body sites, no symptoms; score range, 0-83),E2Kunz B. Oranje A.P. Labreze L. Stalder J.F. Ring J. Taieb A. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis.Dermatology. 1997; 195: 10-19Crossref PubMed Scopus (853) Google Scholar and POEM (7 symptoms; score range, 0-28). For oSCORAD/SCORAD, a representative lesion of most of the patient's eczema was selected for assessment of lesional intensity, but not the worst or best-looking lesion. POEM is the recommended core outcome instrument for capturing patient-reported symptoms by the Harmonizing Outcome Measures in Eczema (HOME) group.E3Spuls P.I. Gerbens L.A. Simpson E. Apfelbacher C.J. Chalmers J.R. Thomas K.S. et al.POEM a core instrument to measure symptoms in clinical trials: a HOME statement.Br J Dermatol. 2017; 176: 979-984Crossref PubMed Scopus (116) Google Scholar POEM took less than 1 to 7 minutes to complete (mean, 1.2 minutes). We did not formally record the time it took to administer EASI and oSCORAD/SCORAD. EASI and oSCORAD generally took 2 to 7 and 3 to 8 minutes, respectively, with an additional 1 minute for assessment of symptoms in SCORAD.