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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Objective

To investigate the health-related quality of life (HRQOL) change over time, as measured by the Child Health Questionnaire (CHQ), and its determinants in patients with active juvenile dermatomyositis (DM).

Methods

We assessed patients with juvenile DM at both baseline and 6 months of followup, and healthy children age ≤18 years. Potential determinants of poor HRQOL included demographic data, physician's and parent's global assessments, muscle strength, functional ability as measured by the Childhood Health Assessment Questionnaire (C-HAQ), global disease activity assessments, and laboratory markers.

Results

A total of 272 children with juvenile DM and 2,288 healthy children were enrolled from 37 countries. The mean ± SD CHQ physical and psychosocial summary scores were significantly lower in children with juvenile DM (33.7 ± 11.7 versus 54.6 ± 4.1) than in healthy children (45.1 ± 9.0 versus 52 ± 7.2), with physical well-being domains being the most impaired. HRQOL improved over time in responders to treatment and remained unchanged or worsened in nonresponders. Both physical and psychosocial summary scores decreased with increasing levels of disease activity, muscle strength, and parent's evaluation of the child's overall well-being. A C-HAQ score >1.6 (odds ratio [OR] 5.06, 95% confidence interval [95% CI] 2.03–12.59), child's overall well-being score >6.2 (OR 5.24, 95% CI 2.27–12.10), and to a lesser extent muscle strength and alanine aminotransferase level were the strongest determinants of poor physical well-being at baseline. Baseline disability and longer disease duration were the major determinants for poor physical well-being at followup.

Conclusion

We found that patients with juvenile DM have a significant impairment in their HRQOL compared with healthy peers, particularly in the physical domain. Physical well-being was mostly affected by the level of functional impairment.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

The idiopathic inflammatory myopathies are a group of serious systemic autoimmune conditions. The most common of the pediatric idiopathic inflammatory myopathies is juvenile dermatomyositis (DM), a multisystemic vasculopathy of unknown origin characterized by nonsuppurative inflammation of skeletal muscle and skin, resulting in muscle weakness and fatigue, a skin rash typical of face and extremities, and less frequently by involvement of the bowel, lungs, heart, and rarely the central nervous system (1–5).

Juvenile DM shares many similarities with adult DM, but it is often characterized by a higher incidence of the systemic vasculopathy, lipodystrophy, calcinosis, and chronic relapsing disease course. Although the prognosis of juvenile DM has markedly improved in the last 3 decades with the mortality rate dropping to <2% (5), there are still patients who do not respond to current treatment options and are at risk of developing irreversible damage with an impact on their health-related quality of life (HRQOL) and that of their families.

Recently, it has been suggested that the evaluation of HRQOL should be included in both clinical practice and therapeutic trials (6–15), and several multidimensional HRQOL measures incorporating physical, emotional, mental, and social health dimensions have been developed and validated for use in pediatric rheumatic diseases (16–19).

The primary objective of the present study was to examine the HRQOL change over time of a large cohort of children with active juvenile DM enrolled worldwide by the Paediatric Rheumatology International Trials Organisation (PRINTO) (20), and to compare the results with those obtained in healthy peers from the same geographic areas. A further objective of the study was to identify the determinants of poor HRQOL at baseline and followup.

PATIENTS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Patients were retrieved from the PRINTO juvenile DM database, which includes patients enrolled from June 2001 to March 2004 seen consecutively in pediatric rheumatology centers worldwide who 1) had juvenile DM (i.e., a classic juvenile DM rash plus at least 2 [probable juvenile DM] or 3 [definite juvenile DM] of the other 6 criteria set up by Bohan and Peter) (21, 22), 2) were age <18 years, and 3) were in an active phase of their disease, defined as either the need to start or increase the dose of corticosteroid/immunosuppressive medications. Patients were evaluated at baseline and after 6 months.

For the control group, we used an age-comparable subgroup of 2,288 children extracted from an international convenience sample of 3,315 healthy children, as previously described (18, 19, 23). The healthy children were either local students ages 6–18 years or healthy siblings/friends of patients.

In each center, written or verbal informed consent was obtained from a parent or child, according to the requirements of the local ethic committees. HRQOL, functional ability, disease activity, and response to therapy were assessed in each patient with juvenile DM.

HRQOL assessment.

The national-language version of the parent-administered 50-item version of the Child Health Questionnaire (CHQ; also called the CHQ PF-50) (16, 18, 19) was used to assess HRQOL of children with juvenile DM and healthy children. The CHQ is a generic, parent-administered instrument designed to capture the physical, emotional, and social components of health status in children ages 5–18 years. The CHQ comprises 15 health concepts: global health, physical functioning, role/social limitations-emotional/behavioral, role/social limitations-physical, bodily pain/discomfort, behavior, general behavior, mental health, self-esteem, general health perception, change in health, parent impact-emotional, parent impact-time, family activities, and family cohesion. In addition, 2 summary measures were developed by factor analysis through the aggregation of 10 of the 15 subscales (physical functioning, role/social limitations-emotional/behavioral, role/social limitations-physical, bodily pain/discomfort, behavior, mental health, self-esteem, general health perception, parent impact-emotional, and parent impact-time): the physical summary score (PhS) and the psychosocial summary score (PsS), standardized with a mean ± SD of 50 ± 10. Higher scores on the subscales and summary scores indicated better HRQOL. CHQ scores were calculated using the proprietary algorithms and the SAS programming code created specifically for the CHQ by the developer as detailed in the manual (16).

Functional ability (disability) assessment.

One parent was asked to complete the national-language version of the Childhood Health Assessment Questionnaire (C-HAQ) (18, 19, 24). The scores for each of the 8 functional areas were averaged to calculate the C-HAQ disability index (DI; range 0–3, where 0 = best and 3 = worst). The parent version of the C-HAQ incorporates a double-anchor horizontal 10-cm visual analog scale (VAS) for the assessment of the child's overall well-being (with anchors on 0 = very well and 10 = very poor), and a double-anchor horizontal 10-cm VAS for the assessment of the intensity of the child's pain (with anchors on 0 = no pain and 10 = very severe pain).

Assessment of juvenile DM disease activity.

The following measures, part of the PRINTO/American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) juvenile DM disease activity core set (10), were assessed in each patient by the attending physician: 1) the physician's global assessment of disease activity (measured on a 0–10-cm VAS) (25), 2) muscle strength through the Manual Muscle Testing (MMT) scale (range 0–80) (26) and the Childhood Myositis Assessment Scale (CMAS) (27–29), 3) disease activity through the Disease Activity Score (DAS; range 0–20) (30) and the Myositis Disease Activity Assessment (31), a combined tool that captures the physician's assessment of disease activity of various organ systems via the Myositis Disease Activity Assessment Visual Analog Scale (MYOACT) and the presence or absence of clinical features via the Myositis Intention-to-Treat Activity Index (MITAX), and 4) serum muscle enzymes (creatine kinase, lactate dehydrogenase, aldolase, aspartate aminotransferase, and alanine aminotransferase) (32, 33), standardized based on the normal values provided by each local laboratory as previously described (10, 34).

Evaluation of response to therapy.

The PRINTO juvenile DM definition of improvement (1, 35) classifies as responders all patients who show an improvement of at least 20% in any 3 of the 6 variables of the provisional PRINTO/ACR/EULAR juvenile DM disease activity core set, with no more than 1 of the remaining variables worsening by more than 30%, which cannot be muscle strength.

Statistical analysis.

Descriptive statistics of the patients' characteristics were reported as the mean ± SD for quantitative variables and as the absolute frequency and percentage for qualitative variables.

Comparison of quantitative variables between groups of subjects was made by the Student's t-test or the nonparametric Mann-Whitney U test, as appropriate; comparison of quantitative variables was made by chi-square test or Fisher's exact test, as appropriate. Comparison of paired quantitative data (baseline versus followup) was performed by Wilcoxon's matched pairs signed rank test. All tests were 2-sided and P values less than 0.05 were considered statistically significant.

We anticipated that owing to the large size of the study sample, all comparisons between patients and healthy children could have been statistically significant. The results of comparative analyses with healthy children should, therefore, be interpreted qualitatively rather than quantitatively.

Spearman's rank order correlation coefficients were calculated to evaluate the relationship between the absolute change of clinical measures and the PhS or PsS scores of the CHQ. For the purpose of this analysis, correlation coefficients >0.7 were considered high, from 0.4–0.7 were considered moderate, and <0.4 were considered low.

To evaluate the role of independent determinants of poor HRQOL at baseline and followup, bivariate and logistic regression analyses were carried out. Poor HRQOL was defined as a PhS or PsS score <30 or <40, respectively, which means that patients with a score <30 on the PhS (or PsS) were 2 SDs below the mean of healthy controls, and patients with a score <40 on the PhS (or PsS) were 1 SD below the mean of healthy controls. Predictors were dichotomized according to receiver operating curve cutoff results. Dichotomizing explanatory variables provides the advantage of clinically meaningful odd ratios (ORs) with 95% confidence intervals (95% CIs). Baseline variables that were statistically significant in the bivariate analysis or a priori considered important for the outcome (poor HRQOL at baseline or followup) were entered into the models. In the final logistic regression models, only patients with no missing data were considered (n = 197). Four different logistic models were fitted, taking into account the binary outcome: PhS (or PsS) score <30 versus a PhS (or PsS) score ≥30 at baseline. At followup, the cutoff for the PhS was set to 40 since few patients had scores <30. The step-down strategy for analysis was chosen and consisted of examining the effect of removing variables from the saturated model. The effect was expressed in terms of ORs and 95% CIs. Statistical significance was tested by means of the likelihood ratio test. The Statistica (StatSoft, Tulsa, OK) and Stata, release 7.0 (Stata, College Station, TX) statistical packages were used for the univariate and multivariate analyses, respectively.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Of the 294 patients enrolled, 10 were excluded from the study: 9 had polymyositis without cutaneous manifestations and 1 patient was later diagnosed as having muscular dystrophy. Of the 284 juvenile DM patients, 12 were excluded from the analysis: 9 because they were lost to followup and 3 because they did not have a CHQ evaluation at baseline and followup. The analysis data set was equal to 272 juvenile DM patients from 37 countries.

Table 1 shows the main demographic, clinical, and laboratory features of patients with juvenile DM and the 2,288 age-comparable healthy children at baseline and 6 months of followup. At baseline, patients with juvenile DM had on average a high level of disease activity as shown by the mean values of the baseline physician's global assessments, DAS, MYOACT, MITAX, muscle enzymes, and by the low mean values of both the CMAS and MMT.

Table 1. Demographic and clinical characteristics of study subjects*
 Healthy children (n = 2,288)Juvenile DM patients (n = 272)
BaselineFollowup
  • *

    Values are the mean ± SD unless otherwise indicated. Numbers in parentheses refer to the number of patients who have data for evaluations at baseline and followup. P < 0.0001 for all comparisons between data from baseline and 6 months of followup. DM = dermatomyositis; [UPWARDS ARROW] = higher score denotes worse disease activity; CMAS = Childhood Myositis Assessment Scale; [DOWNWARDS ARROW] = lower score denotes worse disease activity; MMT = Manual Muscle Testing; DAS = Disease Activity Score; MYOACT = Myositis Disease Activity Assessment Visual Analog Scale; MITAX = Myositis Intention-to-Treat Activity Index, A–E version; CK = creatine kinase; LDH = lactate dehydrogenase; AST = aspartate aminotransferase; ALT = alanine aminotransferase; C-HAQ DI = Childhood Health Assessment Questionnaire disability index; CHQ = Child Health Questionnaire.

  • P < 0.001 when comparing patients at baseline and healthy children.

  • Measured on a 10-cm visual analog scale.

  • §

    P < 0.0001 when comparing patients at baseline and healthy children.

  • Measured on a 10-cm visual analog scale. P < 0.0001 when comparing patients at baseline and healthy children.

Age at study visit, years9.2 ± 2.69.1 ± 4.0 
Age at onset of juvenile DM, years7.6 ± 3.9 
Disease duration, years1.5 ± 2.2 
Female, no. (%)1,119/2,239 (50.0)173 (63.6) 
Physician's global assessment of the patient's overall disease activity[UPWARDS ARROW] (n = 265) 5.4 ± 2.41.8 ± 2.3
CMAS score[DOWNWARDS ARROW] (range 0–52; n = 266) 25.7 ± 14.341.7 ± 11.3
MMT score[DOWNWARDS ARROW] (range 0–80; n = 261) 45.4 ± 19.465.0 ± 17.7
DAS[UPWARDS ARROW] (range 0–20; n = 270) 12.0 ± 3.65.5 ± 3.9
MYOACT score[UPWARDS ARROW] (range 0–10; n = 254) 2.1 ± 1.40.6 ± 0.8
MITAX score[UPWARDS ARROW](range 0–63; n = 255) 18.2 ± 12.14.2 ± 5.5
Physician's global assessment of muscle activity[UPWARDS ARROW] (n = 267) 5.3 ± 2.81.6 ± 2.4
Physician's global assessment of extraskeletal disease activity[UPWARDS ARROW] (n = 268) 2.8 ± 3.71.0 ± 1.8
CK[UPWARDS ARROW] (normal 0–150 units/liter; n = 260) 1,494 ± 3,162123.2 ± 427.0
LDH[UPWARDS ARROW] (normal 50–150 units/liter; n = 246) 386 ± 450160.8 ± 100.9
Aldolase[UPWARDS ARROW] (normal 0–6 units/liter; n = 118) 22 ± 366.3 ± 7.6
AST[UPWARDS ARROW] (normal 0–35 units/liter; n = 247) 128 ± 20326.8 ± 23.6
ALT[UPWARDS ARROW] (normal 0–35 units/liter; n = 261) 79 ± 12723.3 ± 43.6
C-HAQ DI score[UPWARDS ARROW] (range 0–3; n = 259)§0.2 ± 0.31.7 ± 0.90.6 ± 0.7
Parent's global assessment of the child's overall well-being[UPWARDS ARROW] (n = 253)0.2 ± 1.03.6 ± 3.01.7 ± 2.1
Parent's global assessment of the child's overall pain[UPWARDS ARROW] (n = 254)0.2 ± 0.75.2 ± 2.91.1 ± 1.7
CHQ physical summary score (n = 211)§54.6 ± 4.133.7 ± 11.747.0 ± 9.4
CHQ psychosocial summary score (n = 211)§52.0 ± 7.245.1 ± 9.049.4 ± 7.7

The mean ± SD level of disability as measured by the C-HAQ DI was 1.7 ± 0.9 in the juvenile DM group and 0.2 ± 0.3 in the healthy children (P < 0.0001). The most impaired C-HAQ categories (mean score >1.7) in juvenile DM patients were dressing, arising, hygiene, reach, and activities. Likewise, the parent's ratings of the intensity of the child's pain and the child's overall well-being were worse in the juvenile DM group when compared with the healthy children (P < 0.0001 for all comparisons).

Both disease activity and disability measures improved after 6 months of treatment (P < 0.0001 for all changes). According to the PRINTO definition of improvement for juvenile DM, 228 patients (83.8%) were classified as responders, with the remaining 44 (16.2%) classified as nonresponders. At baseline there were no statistically significant differences between responders and nonresponders for either disease activity or disability measures.

Assessment of HRQOL.

The CHQ was completed at baseline or at followup by 266 of 272 parents (97.8% of patients); the CHQ PhS and PsS scores could be calculated at baseline and at followup in 211 patients (77.6%).

As shown in Table 1, at baseline the mean ± SD CHQ PhS score was significantly lower in children with juvenile DM than in healthy children (33.7 ± 11.7 versus 54.6 ± 4.1; P < 0.0001). Likewise, the mean ± SD CHQ PsS score was significantly lower in children with juvenile DM than in healthy children (45.1 ± 9.0 versus 52 ± 7.2; P < 0.0001). There was a statistically significant improvement for both summary measures at 6 months of followup (P < 0.0001), with the PhS reaching a mean ± SD value of 47.0 ± 9.4 and the PsS reaching 49.4 ± 7.7.

Figure 1 shows the mean values of the 15 subscales of the CHQ and the PhS and PsS in juvenile DM patients at baseline and followup and in healthy children. Compared with healthy children, at baseline juvenile DM patients had statistically significantly lower values for all CHQ health concepts (P < 0.0001) except for family cohesion, which was comparable to the mean value of the healthy subjects. As seen in Figure 1, the most impaired CHQ health concepts (<2 SDs of the means of healthy children) at baseline for either responders or nonresponders were global health, physical functioning, role/social limitations-emotional/behavioral, and role/social limitations-physical. Bodily pain/discomfort, change in health, parent impact-emotional, and family activities were <2 SDs of the mean of healthy children only in the patients who were subsequently classified as responders.

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Figure 1. Health-related quality of life evaluation of children with juvenile dermatomyositis (JDM) at baseline and after 6 months, as compared with healthy children. identifies the 10 subscales of the Child Health Questionnaire (CHQ) that are used to calculate the physical (PhS) and psychosocial (PsS) summary scores. Bars show the mean values of the 15 subscales (range 0–100) and the 2 summary scores (norm-based values with mean ± SD of 50 ± 10) of the CHQ, the PhS and the PsS, at baseline and followup. Higher scores indicate better health. Arrows show the CHQ subscales whose baseline values are 2 SDs below the mean of healthy controls.

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For summary measures at baseline, 88 (41.7%) of 211 patients had a PhS <30 (2 SDs below the mean of healthy controls) and 12 (5.7%) of 211 patients had a PsS <30, whereas 145 (68.7%) of 211 patients had a PhS <40 (1 SD below the mean of healthy controls) and 53 (25.1%) of 211 patients had a PsS <40 (responders and nonresponders combined).

At baseline, patients who were subsequently classified as responders showed worse values for most CHQ health concepts and summary measures when compared with the nonresponders. The differences in HRQOL between responders and nonresponders were statistically significant for the following health concepts: global health (P < 0.01), physical functioning (P < 0.001), role/social limitations-emotional/behavioral (P < 0.05), bodily pain/discomfort (P < 0.001), self-esteem (P < 0.01), change in health (P < 0.0001), parent impact-emotional (P < 0.05), and the CHQ PhS (P < 0.05).

At 6 months of followup, in the responders group there was a statistically significant improvement in all CHQ subscales and in the 2 summary scores (P < 0.0001), with the exception of family cohesion. However, despite improvement, there was still a statistically significant difference (P < 0.001) between the juvenile DM responders and the healthy children for most of the CHQ subscales, with the exception of behavior, general behavior, and family cohesion, which were comparable to the mean value of the healthy subjects; mental health at followup was still significantly lower in the responders group with respect to healthy subjects (P = 0.03). The HRQOL of patients classified as nonresponders did not improve or worsen for most CHQ health concepts; the only statistically significant improvement over time in the nonresponders was observed for role/social limitations-physical and change in health (P = 0.04 and 0.003, respectively).

At followup, 14 (6.6%) of 211 patients had a PhS <30 (2 SDs below the mean of healthy controls) and 47 (22.3%) of 211 patients had a PhS <40 (1 SD below the mean of healthy controls), whereas 4 (1.9%) of 211 patients had a PsS <30 and 23 (10.9%) of 211 patients had a PsS <40.

Relationship between HRQOL and physical disability.

Figure 2 depicts the mean values and 95% CIs of the CHQ PhS and PsS in juvenile DM patients compared with healthy children, and is divided into 2 groups according to the level of disability, as measured by the C-HAQ DI (≤1.6 versus >1.6) at baseline. Among patients with juvenile DM, there were 124 (46.1%) of 269 subjects with a C-HAQ score ≤1.6, and 145 (53.9%) of 269 subjects with a C-HAQ score >1.6; almost all of the healthy children (99.4%) had a C-HAQ score <1.6 (only 13 [0.6%] of 2,234 had a C-HAQ score >1.6). This analysis shows that both summary measures of the CHQ accurately reflect the disability levels among patients with juvenile DM and clearly discriminate juvenile DM patients from healthy children, irrespective of the level of disability. However, the discriminatory ability of the PhS was higher than that of the PsS, with juvenile DM patients having less impairment in psychosocial well-being than in physical well-being.

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Figure 2. Mean baseline values (●) and 95% confidence intervals (whiskers) of the A, physical (PhS) and B, psychosocial (PsS) summary scores of the Child Health Questionnaire (CHQ) in children with juvenile dermatomyositis (JDM) and in healthy children, categorized according to the presence of a Childhood Health Assessment Questionnaire (C-HAQ) score ≤1.6 or >1.6. The broken line shows a PhS or PsS 2 SDs below the mean of healthy children. Of note, the boxes for healthy children with C-HAQ scores ≤1.6 and >1.6 are overlapping.

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Absolute change correlation between HRQOL and juvenile DM activity severity measures.

Spearman's correlations for the CHQ PhS absolute change were high with C-HAQ score (r = −0.73), and moderate with the change in muscle strength evaluated by the CMAS (r = 0.61), the parent's assessment of the child's overall well-being (r = −0.58), the physician's global assessment of muscle activity (r = 0.53), the physician's global assessment of the overall disease activity (r = −0.46), the MMT (r = 0.50), the DAS (r = −0.42), and the parent's assessment of the intensity of the child's pain (r = −0.49). All other correlations for the CHQ PhS were poor, as well as all correlations between the CHQ PsS and juvenile DM severity measures (r = −0.14 to r = −0.28).

The better relationship of CHQ physical well-being in juvenile DM patients with functional ability, disease activity, muscle strength, and parent's assessment of overall well-being at baseline was further confirmed after categorization of these measures into increasing levels of severity according to their respective quartile values. As shown in Figure 3, both CHQ summary scores showed progressive worsening with increasing level of severity, with this effect being much more pronounced for the PhS score. Similar findings were obtained for other juvenile DM severity measures (data not shown).

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Figure 3. Relationship between the physical (PhS) and psychosocial (PsS) summary scores of the Child Health Questionnaire (CHQ) at baseline and A, the physician's global assessment of disease activity, B, the parent's global assessment of the child's overall well-being, C, muscle strength as measured by the Childhood Myositis Assessment Scale, and D, disease activity level as measured by the Disease Activity Score, categorized into 4 levels of severity according to their respective quartile values. VAS = visual analog scale.

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Bivariate analysis for the identification of determinants of poor HRQOL at baseline and followup.

On bivariate analysis, all baseline variables reported in Table 1 were significantly associated (P < 0.01) with poor physical well-being (PhS <30), with the exception of age at study visit, sex, and aldolase. Baseline predictors for poor physical well-being at followup (P < 0.01) were identified using a PhS score of 40 as a cutoff, since only 14 (6.6%) of 211 patients had a PhS score <30 as previously described. Predictors included physician's global assessment of the patient's overall disease activity, DAS, MYOACT, MITAX, C-HAQ DI, PhS, and parent's assessment of the child's well-being and pain.

Baseline variables significantly associated (P < 0.01) with poor psychosocial well-being (PsS <30) were MMT and C-HAQ DI. There were no baseline predictors for poor psychosocial well-being at followup.

Logistic regression analysis for the identification of determinants of poor HRQOL at baseline and followup.

All variables significantly associated with the outcomes in bivariate analyses were entered into the logistic regression procedures. In the final logistic regression models, only patients with no missing data either in the determinants or in the outcome variables (PhS) were entered (n = 197).

Table 2 shows the best-fitting model obtained from the evaluation of the determinants of poor HRQOL, measured by the PhS (at baseline and followup).The strongest determinants of poor physical well-being (PhS <30) at baseline were parent's assessment of the child's well-being >6.2 (OR 5.24), a C-HAQ DI score >1.6 (OR 5.06) and, to a lesser extent, low levels of CMAS and high levels of alanine aminotransferase. The strongest determinants for poor physical well-being at followup (PhS <40) were a C-HAQ DI score >1.6 (OR 3.29) and a disease duration >1 year (OR 2.35). Results of the logistic regression analysis did not change when we adjusted for baseline PhS score. It was not possible to identify any predictor for poor psychosocial well-being both at baseline and followup.

Table 2. Best-fit logistic regression models obtained from the evaluations of the determinants of poor health-related quality of life, as measured by the PhS of the CHQ*
 PhS <30 at baselinePhS <40 at followup
  • *

    Values are the odds ratio (95% confidence interval) unless otherwise indicated. PhS = physical summary score; CHQ = Child Health Questionnaire; C-HAQ = Childhood Health Assessment Questionnaire; CMAS = Childhood Myositis Assessment Scale; ALT = alanine aminotransferase; ROC = receiver operating curve.

  • P < 0.001.

  • P < 0.01.

  • §

    P < 0.05.

No. (%) (n = 197)82 (41.6)44 (22.3)
C-HAQ disability index >1.65.06 (2.03–12.59)3.29 (1.57–6.87)
Parent's global assessment of the child's well-being >6.25.24 (2.27–12.10) 
CMAS ≤213.54 (1.42–8.81) 
ALT level >34 units/liter2.99 (1.33–6.69) 
Disease duration at first visit >1 year 2.35 (1.13–4.88)§
Area under the ROC0.890.66

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

We evaluated a sample of patients with active juvenile DM and compared their HRQOL status with that of healthy peers of a similar age from the same geographic area. The results show that compared with healthy controls, children with juvenile DM have poorer physical and psychosocial well-being, with a more pronounced effect on physical health. The HRQOL impairment was more evident in the health concepts of global health, physical functioning, role/social limitations-emotional/behavioral, role/social limitations-physical, and bodily pain/discomfort; furthermore, the PhS was equally impaired, being 2 SDs below the mean of healthy controls. The scales related to the child's psychosocial well-being (behavior, general behavior, mental health, and self-esteem) yielded values comparable to those of healthy controls, whereas a greater impairment was observed in the areas related to the impact of the disease on parent impact-emotional, parent impact-time, and family activities. This observation indicates that families are emotionally concerned about their child's physical well-being and that the disease significantly influences the parent's daily life. However, family cohesion resulted in values similar to those of healthy children, indicating little overall intrafamilial relationship disruption. Notably, the same HRQOL areas previously described were also found to be mostly affected in children with juvenile idiopathic arthritis (23, 36) and juvenile systemic lupus erythematosus (37).

A greater impairment in HRQOL was observed in associations with increasing levels of disease activity (physician's global evaluation, muscle enzymes, DAS, etc.), decreased muscle strength and endurance (CMAS and MMT), as well as with a parent's worsened evaluation of the child's overall well-being and pain, with the effect being more pronounced on physical well-being than on psychosocial well-being.

Similarly, a greater impairment in physical rather than in psychosocial well-being was observed when HRQOL summary scores were analyzed according to the level of physical disability, as measured with the C-HAQ DI. Patients with moderate to severe functional impairment (C-HAQ DI score >1.6) (38) had a CHQ PhS 1 SD below the mean of healthy children. However, independent of their level of disability, all patients had a CHQ PsS within the normal range. This suggests that muscle weakness, which is a typical feature of the active phase of the disease, has a negative impact on activities of daily living, and this in turn leads to a poorer HRQOL, as measured with the CHQ PhS but not with the PsS.

When HRQOL was analyzed according to the PRINTO juvenile DM definition of response, at baseline responders showed a trend toward worse values for all CHQ health concepts and summary measures when compared with the nonresponders. After 6 months of treatment, the HRQOL of the responders improved significantly, reaching values comparable to those of healthy controls. On the contrary, the nonresponders group did not change their HRQOL baseline status, irrespective of the treatment received. This observation, along with the high correlation between change in physical well-being and disability and the moderate correlation with the change in disease activity parameters, suggests that patients with the worst physical well-being and disease activity at baseline are the ones toward whom effective treatment could have the greater probability of success.

The relevant impact of physical disability on physical well-being was confirmed by logistic regression modeling results, which indicated that the baseline C-HAQ scores were the strongest determinants of poor HRQOL both at baseline and followup. Other determinants of poor physical well-being were the parent's global assessment of the child's overall well-being, level of muscle strength, muscle enzymes, and disease duration. No determinants for poor psychosocial well-being were identified.

Taken together, the results show that children with juvenile DM have a greater impairment in physical well-being than in psychosocial health, and that physical disability, as the most important determinant of HRQOL, should be the main target of therapeutic intervention. It is difficult to compare the results of our study with the literature since, to the best of our knowledge, no publications have evaluated the impact of juvenile DM on HRQOL.

We must acknowledge the limitations of the study due to its cross-sectional nature and the lack of child-reported evaluation of HRQOL. Furthermore, calculations of the CHQ summary measures were based on US population normative values (16). We did not collect information about the patients' ethnicities and socioeconomic background, which may affect HRQOL as well. However, the wide geographic area of the patients' enrollment ensures that most of the non–disease-related factors were incorporated and that therefore, our results are likely to be valid for the majority of children with juvenile DM.

In summary, we found that patients with juvenile DM have a significant impairment in their HRQOL as compared with healthy peers, particularly in the physical domain. Physical well-being was mostly affected by the level of functional impairment, indicating that prevention of physical disability is one of the most important objectives of therapeutic interventions in juvenile DM.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

Dr. Ruperto had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study design. Pistorio, Ravelli, Martini, Ruperto.

Acquisition of data. Apaz, Saad-Magalhães, Ravelli, de Oliveira Sato, Marcantoni, Meiorin, Filocamo, Pilkington, Maillard, Al-Mayouf, Prahalad, Fasth, Joos, Schikler, Mozolova, Ruperto.

Analysis and interpretation of data. Pistorio, Ravelli, Filocamo, Fasth, Landgraf, Martini, Ruperto.

Manuscript preparation. Apaz, Saad-Magalhães, Pistorio, Ravelli, Marcantoni, Filocamo, Pilkington, Maillard, Prahalad, Fasth, Schikler, Mozolova, Landgraf, Martini, Ruperto.

Statistical analysis. Pistorio, Landgraf, Ruperto.

Acknowledgements

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES

We would like to thank the following investigators who participated in the study: Ruben Cuttica and Graciela Espada from Argentina, and Patricia Woo from the UK. We are indebted to the PRINTO members for data collection, and to the families of the juvenile DM patients and of the healthy children who generously volunteered to participate in these studies.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. PATIENTS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. Acknowledgements
  9. REFERENCES
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