Arthritis & Rheumatism (Arthritis Care & Research) Vol. 59, No. 2, February 15, 2008, pp 214 –221 DOI 10.1002/art.23340 © 2008, American College of Rheumatology
ORIGINAL ARTICLE
Preliminary Validation and Clinical Meaning of the Cutaneous Assessment Tool in Juvenile Dermatomyositis ADAM M. HUBER,1 ELIZABETH M. DUGAN,2 PETER A. LACHENBRUCH,3 BRIAN M. FELDMAN,4 MARIA D. PEREZ,5 LAWRENCE S. ZEMEL,6 CAROL B. LINDSLEY,7 ROBERT M. RENNEBOHM,8 CAROL A. WALLACE,9 MURRAY H. PASSO,10 ANN M. REED,11 SUZANNE L. BOWYER,12 SUSAN H. BALLINGER,12 FREDERICK W. MILLER,13 AND LISA G. RIDER,13 IN COOPERATION WITH THE JUVENILE DERMATOMYOSITIS DISEASE ACTIVITY COLLABORATIVE STUDY GROUP
Objective. To provide preliminary validation of the Cutaneous Assessment Tool (CAT), a new tool to assess cutaneous manifestations of juvenile dermatomyositis (DM), and to explore the clinical meaning of CAT scores. Methods. Children with juvenile DM (n ⴝ 113) were assessed at baseline and 7–9 months later (n ⴝ 94). Internal consistency, redundancy, construct validity, and responsiveness of the CAT were examined. CAT scores corresponding to ordinal global assessments were determined. Results. Item-total correlations ranged from 0.27– 0.67 for activity lesions present in >10% of patients; item-domain and domain-total correlations ranged from 0.25– 0.99. Cronbach’s alpha was 0.79 for the CAT activity score and 0.74 for the CAT damage score. As predicted, the CAT activity score correlated strongly with both global disease activity and skin disease activity and moderately with the Childhood Myositis Assessment Scale, whereas the CAT damage score correlated moderately with the physician global disease and skin disease damage scores. Median CAT activity scores of 1, 7, 13, 18, and 31 corresponded to absent, mild, moderate, severe, and extremely severe skin disease activity, respectively. Median CAT damage scores of 0, 1, 2, and 5 correlated with the same descriptions of damage (severe and extremely severe combined). Conclusion. Preliminary validation of the CAT demonstrated good internal consistency, nonredundancy, good construct validity, and appropriate responsiveness. The CAT is a comprehensive, semiquantitative assessment tool for skin disease in juvenile DM.
Juvenile dermatomyositis (DM) is a serious, idiopathic, autoimmune illness that causes inflammation and dys-
function of muscle (1). Cutaneous involvement is a cardinal feature and can represent both disease activity and disease damage of the underlying myositis syndrome or its treatment (2,3).
Supported by the intramural research programs of the National Institute of Environmental Health Sciences and the National Institute of Arthritis and Skin and Musculoskeletal Diseases, NIH, Department of Health and Human Services, Bethesda, Maryland. 1 Adam M. Huber, MD: IWK Health Centre and Dalhousie University, Halifax, Nova Scotia, Canada; 2Elizabeth M. Dugan, MD: Washington Hospital Center, Washington, DC; 3Peter A. Lachenbruch, PhD (current address: Oregon State University, Corvallis): Center for Biologics Evaluation and Research, FDA, Rockville, Maryland; 4Brian M. Feldman, MD, MSc: Hospital For Sick Children and University of Toronto, Toronto, Ontario, Canada; 5Maria D. Perez, MD: Texas Children’s Hospital and Baylor College of Medicine, Houston, Texas; 6Lawrence S. Zemel, MD: Connecticut Children’s Medical Center and University of Connecticut, Hartford; 7Carol B. Lindsley, MD: University of Kansas, Kansas
City; 8Robert M. Rennebohm, MD: Columbus Children’s Hospital and Ohio State University, Columbus; 9Carol A. Wallace, MD: Children’s Hospital and University of Washington, Seattle; 10Murray H. Passo, MD: Children’s Hospital and University of Cincinnati, Cincinnati, Ohio; 11Ann M. Reed, MD: Mayo Clinic, Rochester, Minnesota; 12Suzanne L. Bowyer, MD, Susan H. Ballinger, MD: Riley Children’s Hospital and Indiana University School of Medicine, Indianapolis; 13Frederick W. Miller, MD, PhD, Lisa G. Rider, MD: Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, NIH, Bethesda, Maryland. Address correspondence to Adam M. Huber, MD, Division of Pediatric Rheumatology, IWK Health Centre, 5850 University Avenue, Halifax, Nova Scotia, Canada, B3K 6R8. E-mail:
[email protected]. Submitted for publication January 31, 2007; accepted in revised form August 13, 2007.
INTRODUCTION
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The Cutaneous Assessment Tool in Juvenile DM Cutaneous manifestations of juvenile DM are important in the assessment of this illness. We have previously demonstrated that global skin disease activity correlates moderately with measures of physical function in children with juvenile DM (4,5). In adults with DM, Hundley et al have demonstrated that active skin disease is associated with reduced quality of life (6). Skin damage caused by chronic skin lesions, such as calcinosis, is an important source of morbidity in juvenile DM, and may be associated with pain, disfigurement, and reductions in quality of life and physical function (7). For these reasons, the assessment of skin disease is part of the core sets of outcomes recommended for studies in adult and juvenile DM (8,9). Both of these proposed core sets recommend the assessment of extramuscular disease in the overall assessment of disease activity and damage. Skin disease is an important component of the measurement of extramuscular disease, and the Cutaneous Assessment Tool (CAT) helps with its comprehensive assessment. We have previously reported on the development and interrater reliability of the CAT, a comprehensive tool for assessing the cutaneous manifestations of adult and juvenile idiopathic inflammatory myopathies (IIM) (10). The goal of the present study was to provide further data on the validity of this tool, including internal consistency, item redundancy, construct validity, and responsiveness, and to provide additional information regarding the clinical meaning of the CAT including the relationship between skin and muscle disease in children with juvenile DM.
PATIENTS AND METHODS Development of the CAT. The CAT was developed by an interdisciplinary group that included adult and pediatric rheumatologists and a dermatologist experienced in the cutaneous assessment of myositis and other autoimmune disorders. Lesions were included that the investigators considered to be important in the assessment of skin activity in IIM. These lesions were consistent with the classification of DM skin lesions described by Sontheimer (3). The CAT comprises 21 items, with 10 representing disease activity, 4 representing disease damage, and 7 that include elements of both disease activity and damage, which are scored separately. This tool can be found on the following Web site: https://dir-apps.niehs.nih.gov/imacs/index.cfm? action⫽home.imacsforms. Each cutaneous lesion listed in the CAT had a specific definition for the lesion and the characteristics to be assessed. Depending on the lesion, there were between 2 and 7 possible responses corresponding to increasing levels of activity or damage. Lesions were weighted by assigning a priori scores based on consensus expert opinion on the relative importance of individual lesions in contributing to activity or damage. Individual activity and damage item scores were summed to calculate the CAT activity score (range 0 –96) and the CAT damage score (range 0 –20). Higher scores corresponded to greater degrees of activity or damage.
215 Patients and procedures. A total of 113 patients with juvenile DM with definite or probable myositis (based on the criteria by Bohan and Peter [11]) whose age at onset was ⬍18 years were assessed by 11 pediatric rheumatologists at 10 tertiary care pediatric rheumatology centers. Prior to enrolling patients in the study, all assessors reviewed a detailed 35-mm slide atlas defining the cutaneous manifestations of the IIM. All assessors also attended 1 or 2 training sessions at meetings of the Juvenile Myositis Disease Activity Collaborative Study Group. This cohort was consecutively enrolled at any point in their disease course, as previously described (4,5,12). At the time of enrollment, participants had a median disease duration of 19 months (range 0 –137 months, 25th–75th percentile 8 –33 months), a median global disease activity measured by a 10-cm visual analog scale (VAS) of 2.1 cm (range 0 –9.7 cm, 25th–75th percentile 0.6 – 4.3 cm), and a median global disease damage of 1.2 cm (range 0 –10 cm, 25th–75th percentile 0 –1.5 cm). In 94 children, a second assessment was performed 7–9 months later. Institutional review board approval was obtained at each center, and informed consent was obtained from all participants’ parents/legal guardians. At each assessment, standardized history, physical examination, and laboratory investigations were obtained. Physician global assessments of disease activity and damage and skin disease activity and damage were obtained using a 10-cm VAS (12). These were completed by the examining physician at the same time as the CAT. Physician global skin disease activity and damage were also assessed separately with 5-item ordinal scales as previously described (12). The Childhood Myositis Assessment Scale (CMAS) (5,13), the Childhood Health Assessment Questionnaire (C-HAQ) (4), and manual muscle testing (MMT) (4) were obtained as previously described. Due to age and time constraints, MMT was not obtained in all children. Serum levels of at least 1 muscle-associated enzyme were measured (creatinine kinase, lactic acid dehydrogenase, or aldolase). To facilitate comparison, all values were divided by the upper limit of normal for the laboratory in which the test was performed. Statistical analysis. All analyses were performed using the statistical program SAS, release 8.02 (SAS Institute, Cary, NC). Internal consistency was assessed using 2 methods. First, adjusted item-total, item-domain, and domaintotal Spearman’s correlations were calculated. These correlations were adjusted by performing the calculation with each item or domain sequentially removed from the domain or total score. Second, Cronbach’s alpha was calculated for the total scores, and with each item deleted from the total score. Cronbach’s alpha was calculated using standardized variables. Cronbach’s alpha scores ⬎0.70 were considered to show good internal consistency (14). Redundancy of items was assessed using 2 methods. First, Spearman’s correlations among activity items and damage items were calculated. Values ⬎0.70 were considered to show high degrees of redundancy between items. Second, Cronbach’s alpha was calculated for the CAT ac-
216 tivity and damage scores. Values ⬎0.90 were considered to show redundancy within the tool (15). Construct validity of the CAT was assessed by Spearman’s rank correlations of the CAT activity and damage scores with other measures of disease activity and damage. A priori predictions about the strength of correlations of the CAT activity and damage scores with other measures were made. Spearman’s correlations ⱖ0.70 were defined as strong, whereas correlations ⱖ0.40 and ⬍0.70 were defined as moderate and correlations ⬍0.40 were defined as poor. Specifically, it was predicted that the CAT activity score would correlate strongly with physician global skin disease activity, correlate somewhat less strongly with physician global disease activity, correlate moderately with measures of muscle function (CMAS, C-HAQ, MMT), and correlate poorly with measures of disease damage (physician global skin disease and overall disease damage) and serum levels of muscle enzymes. It was predicted that the CAT damage score would correlate strongly with physician global skin disease damage, somewhat less strongly with physician global disease damage, and poorly with physician global skin disease activity and overall disease activity, based on the predicted poor relationship between skin disease activity and damage. Congruence of observed Spearman’s correlations with those predicted was taken as evidence of construct validity (4,5,15). Responsiveness of the CAT was assessed with the standardized response mean (SRM) for the CAT activity and damage scores (16). A physician global assessment of skin disease activity of at least 0.8 cm was considered an external standard of change in activity. A value of 0.8 cm was chosen based on work suggesting that a 0.8-cm improvement in a pain VAS is associated with the perception of improvement in children with arthritis (17). The SRM was calculated for patients who met the external standard of change (CAT activity score only) and for the entire group of children (both scores). For comparison, the SRMs for the physician global disease and skin disease activity and damage assessments were also calculated. SRM values of 0.8 were considered large, 0.5 moderate, and 0.2 small (16). The clinical meaning of CAT scores was assessed by calculating the CAT activity and damage scores corresponding to the 5-item skin disease activity and damage ordinal scores. Discordance in the degree of skin and muscle disease activity was assessed by constructing 3 ⫻ 3 tables of low, medium, and high skin disease activity versus low, medium, and high muscle disease activity for both baseline and followup visits. Discordance was defined as the presence of high or low skin disease activity with low or high muscle disease activity, respectively. For skin disease activity, low was defined as a CAT activity score ⱕ7 (median CAT activity score for mild skin disease activity) and high was defined as a CAT activity score ⱖ18 (median CAT activity score for severe skin disease activity). For muscle disease activity, low was defined as a CMAS score ⱖ45 (median CMAS score associated with mild disability [5]) and high was defined as a CMAS score ⱕ30 (median CMAS score associated with moderate disability [5]). The proportion of patients with less substantial discordance (difference in skin and muscle disease activ-
Huber et al ity of one step only, such as low skin disease activity with moderate muscle disease activity) was also calculated. Marginal homogeneity for the baseline and followup 3 ⫻ 3 tables was assessed using the Stuart-Maxwell test, which tests the null hypothesis that the marginal proportions of the table are the same for both variables.
RESULTS The median CAT activity score was 7 (25th–75th percentile 3–11, range 0 – 44). The median CAT damage score was 1 (25th–75th percentile 0 –1, range 0 –13). Internal consistency. Item-total correlations for the CAT ranged from 0.02 to 0.67 for the activity items and from 0.001 to 0.29 for the damage items (Table 1). The items with low correlations were generally those present in few patients, and they improved to a minimum of 0.27 (P ⬍ 0.05) for lesions with ⬎10% endorsement. Itemdomain correlations for the activity items ranged from 0.25 to 0.99 and increased to a minimum of 0.42 (P ⬍ 0.05) for lesions with ⬎10% endorsement. As expected, itemdomain and domain-total correlations were higher than item-total correlations. The standardized Cronbach’s alpha for the CAT activity score was 0.79, demonstrating good internal consistency. When individual items were removed from the calculation of the CAT activity score, the resulting standardized Cronbach’s alpha scores ranged from 0.77 to 0.81. The standardized Cronbach’s alpha for the CAT damage score was 0.74, also demonstrating good internal consistency. When individual items were removed from the calculation of the CAT damage score, the resulting standardized Cronbach’s alpha scores ranged from 0.67 to 0.76. Redundancy. Spearman’s correlations of individual activity lesions with other activity lesions were all ⬍0.60 (range 0.001– 0.59), while the correlations of individual damage lesions with other damage lesions were all ⬍0.70 (range 0.02– 0.66). As noted above, Cronbach’s alpha for the CAT activity and damage scores did not exceed 0.90. These results suggest that the items in the CAT are not overly redundant. Construct validity. Consistent with our predictions, the CAT activity score correlated strongly with both physician global disease and skin disease activity, moderately with the CMAS and the C-HAQ, and poorly with physician global disease and skin disease damage and serum muscle enzymes (Table 2). Correlation of the CAT activity score with the MMT was poor, which was somewhat lower than predicted. The correlations of the CAT damage score with the physician global disease and skin disease damage scores were moderate, which were somewhat lower than predicted. Correlations of the 2 most frequently observed damage lesions with physician global disease and skin disease damage were no better (rs ⫽ 0.20, P ⫽ 0.03 and rs ⫽ 0.29, P ⫽ 0.005, respectively, for atrophy or hypopigmentation/ hyperpigmentation in the distribution of Gottron’s papules
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Table 1. Item-to-total and item-to-domain correlations for activity and damage lesions of the Cutaneous Assessment Tool (CAT) (n ⴝ 113)*
Activity lesions Characteristic lesions domain 1A Gottron’s papules or sign erythematous changes 2A Heliotrope Erythematous lesions domain 3A Malar/facial erythema 4A Linear extensor erythema 5A V sign 6A Shawl sign 7A Non-sun exposed erythema 8A Erythroderma Vasculopathic lesions domain 9A Livedo reticularis 10A Ulceration 11A Mucous membrane lesions 12A Periungual capillary loop changes Hand lesions domain 13A Mechanic’s hands 14A Cuticular overgrowth Other active lesions domain 15A Subcutaneous edema 16A Panniculitis 17A Alopecia Damage lesions 1D Atrophy or hypo/hyperpigmentation in a distribution Gottron’s papule or sign 2D Atrophy or hypo/hyperpigmentation in a distribution heliotrope 3D Atrophy or hypo/hyperpigmentation in a distribution malar/facial erythema 4D Atrophy or hypo/hyperpigmentation in a distribution linear extensor erythema 5D Atrophy or hypo/hyperpigmentation in a distribution V sign 6D Atrophy or hypo/hyperpigmentation in a distribution shawl sign 7D Atrophy or hypo/hyperpigmentation in a distribution non-sun exposed erythema 18D Poikiloderma vasculare atrophicans 19D Calcinosis 20D Lipoatrophy 21D Depressed skin scarring
Proportion (no. with lesion)
Item-total correlation
Itemdomain correlation
0.56 (63) 0.52 (59)
0.60† 0.67†
0.85† 0.89†
0.52 (59) 0.10 (11) 0.12 (14) 0.15 (17) 0.18 (20) 0.04 (4)
0.56† 0.36† 0.46† 0.47† 0.44† 0.27‡
0.89† 0.42† 0.54† 0.62† 0.61† 0.33‡
0.08 (9) 0.04 (5) 0.24 (27) 0.64 (72)
0.12 0.25‡ 0.39† 0.48†
0.34‡ 0.36† 0.58† 0.83†
0.03 (3) 0.41 (46)
0.14 0.27‡
0.32‡ 0.99†
0.12 (14) 0.01 (1) 0.04 (5)
0.37‡ 0.02 0.14
0.86† 0.25‡ 0.50†
of
0.26 (29)
0.22‡
NA
of
0.11 (12)
0.001
NA
of
0.06 (7)
0.17‡
NA
of
0.03 (3)
0.27‡
NA
of
0.03 (3)
0.29‡
NA
of
0.04 (4)
0.15
NA
of
0.03 (3)
0.25‡
NA
0.04 (5) 0.15 (17) 0.06 (7) 0.12 (13)
0.14 0.07 0.10 0.13
NA NA NA NA
Domain-total correlation
0.70†
0.60†
0.54†
0.26‡
0.36‡
* Item-to-total correlations are with the CAT activity score for activity lesions and with the CAT damage score for damage lesions. Item-to-domain correlations are not available (NA) for damage items, because there is only a single damage domain in the CAT. All correlations are Spearman’s rank. † P ⬍ 0.0001. ‡ P ⱖ 0.0001 and ⬍ 0.05.
or sign; rs ⫽ 0.67, P ⬍ 0.0001 and rs ⫽ 0.56, P ⬍ 0.0001, respectively, for calcinosis). Correlations with physician global disease and skin disease activity were poor, consistent with predictions. Responsiveness. The SRM for the CAT activity score was 0.67 (95% confidence interval [95% CI] 0.42, 0.92) for those children who improved ⬎0.8 cm in physician global assessment of skin disease activity (n ⫽ 63). The SRM was 0.52 (95% CI 0.32, 0.72) for all children with a 7–9-month followup evaluation (n ⫽ 94). These values represent mod-
erate responsiveness. In comparison, the SRMs for physician global disease and skin disease activity were 0.54 (95% CI 0.31, 0.77) and 0.50 (95% CI 0.27, 0.73), respectively. The SRM for the CAT damage score was 0.02 (95% CI – 0.18, 0.22) for all children with a 7–9-month followup evaluation (n ⫽ 94). This represents essentially no responsiveness, which was expected over the duration of this study. Similarly, the SRMs for physician global disease and skin disease damage were 0.12 (95% CI – 0.08, 0.32) and 0.25 (95% CI 0.02, 0.48), respectively.
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Table 2. Summary of evaluation of the construct validity of the Cutaneous Assessment Tool (CAT) activity and damage scores in juvenile dermatomyositis* Spearman’s correlation
Physician global assessment of skin disease activity Physician global assessment of disease activity Childhood Myositis Assessment Scale Childhood Health Assessment Questionnaire Total manual muscle testing score Physician global assessment of skin disease damage Physician global assessment of disease damage Serum creatinine kinase Serum aldolase Serum lactate dehydrogenase
N
CAT activity score
CAT damage score
96
0.83†
0.20‡
98
0.77†
0.14
98 96
⫺0.48† 0.40†
⫺0.19 0.13
50 95
⫺0.36‡ 0.18
⫺0.38‡ 0.53†
113
0.13
97 72 65
0.03 0.13 0.37‡
0.52† ⫺0.06 ⫺0.11 ⫺0.19
* Construct validity was assessed using Spearman’s rank correlations of the CAT activity and damage scores with other measures of disease activity and damage. † P ⬍ 0.0001. ‡ P ⱖ 0.0001 and ⬍ 0.05.
Clinical meaning of CAT scores. Figures 1 and 2 show the CAT activity and damage scores, which correspond to 5-point ordinal global assessments of skin disease activity and damage. The median CAT activity scores (25th–75th percentiles), which corresponded to “no evidence of skin disease activity,” “mild,” “moderate,” “severe,” and “very severe skin disease activity,” were 1 (0 –3), 7 (4 –9), 13 (10 –20), 18 (12–33), and 31 (27–39), respectively. The median (25th–75th percentiles) CAT damage scores, which corresponded to “no evidence of skin disease damage,” “mild,” “moderate,” and “severe or very severe skin
disease damage,” were 0 (0 –1), 1 (0 –2), 2 (1– 4), and 5 (3– 6), respectively. When discordance of skin and muscle disease was considered, the results shown in Table 3 were obtained. Five (5%) of 98 children were discordant at baseline, with either high skin disease activity and low muscle disease activity or high muscle disease activity and low skin disease activity. Forty-six (47%) of 98 patients had minor discordance (for example, low skin disease activity with moderate muscle disease activity); 47 (48%) of 98 patients were concordant at baseline, with the same category of skin and muscle disease activity. At the followup visit, 1
Figure 1. Cutaneous Assessment Tool (CAT) activity score versus 5-point ordinal assessment of skin disease activity. Shaded area represents the 25th–75th percentiles and the horizontal lines within the shaded area are the median. The ends of the whiskers represent the minimum and maximum values and the circles represent outliers.
Figure 2. Cutaneous Assessment Tool (CAT) damage score versus 5-point ordinal assessment of skin disease damage. Shaded area represents the 25th–75th percentiles and the horizontal lines within the shaded area are the median. The ends of the whiskers represent the minimum and maximum values and the circles represent outliers.
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Table 3. Relationship between skin disease activity, measured using the Cutaneous Assessment Tool (CAT) activity score, and muscle disease activity, measured using the Childhood Myositis Assessment Scale (CMAS)* CMAS score
CAT activity score Baseline visit (n ⫽ 98) Low skin activity (ⱕ7) Medium skin activity High skin activity (ⱖ18) Totals (%) Followup visit (n ⫽ 83) Low skin activity (ⱕ7) Medium skin activity High skin activity (ⱖ18) Totals (%)
Low muscle activity (>45)
Medium muscle activity
High muscle activity (
