• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Arthritis Rheum. Author manuscript; available in PMC Nov 1, 2010.
Published in final edited form as:
PMCID: PMC2793533
NIHMSID: NIHMS154000

Damage Extent and Predictors in Adult and Juvenile Dermatomyositis and Polymyositis Using the Myositis Damage Index

Lisa G. Rider, MD,1 Peter A. Lachenbruch, PhD,2 Jason B. Monroe, MS,1 Angelo Ravelli, MD,3 Imelda Cabalar, MD,4 Brian M. Feldman, MD, MSc,5 Maria L. Villalba, MD,6 Barry L. Myones, MD,7 Lauren M. Pachman, MD,8 Robert M. Rennebohm, MD,9 Ann M. Reed, MD,10 Frederick W. Miller, MD, PhD,1 and for the International Myositis Assessment and Clinical Studies Group (IMACS)11

Abstract

Objective

We validated the Myositis Damage Index (MDI) in juvenile and adult myositis, to describe the degree and types of damage and to develop predictors of damage.

Methods

Retrospective MDI evaluations and prospective assessment of disease activity and illness features were conducted. Juvenile-onset patients (n = 143) were evaluated a median of 18 months after diagnosis; 135 patients were assessed 7–9 months later, and 121 were last assessed 82 months after diagnosis. Adult-onset patients (n = 96) with dermatomyositis (DM) or polymyositis (PM) had a baseline assessment a median of 30 months after diagnosis; 77 had a 6-month follow-up evaluation, and 55 had a final assessment 60 months after diagnosis.

Results

Damage was present in 79% of juvenile and 97% of adult patients. In juveniles, scar, contractures, persistent weakness, muscle dysfunction and calcinosis (23–30%) were most frequent on last evaluation. In adults, muscle atrophy, muscle dysfunction and weakness were most frequent (74–84%). MDI severity correlated with physician global damage, functional disability, weakness and muscle atrophy on MRI. MDI damage scores and frequency were highest in patients with a chronic illness course and in adult patients who died. Predictors of damage included functional disability, active disease duration, onset severity, global activity, and illness features, including ulcerations in children and pericarditis in adults.

Conclusions

Damage is common in myositis patients after a median of 5 years duration in adult-onset and 6.8 years in juvenile-onset patients. The MDI has good content, construct and predictive validity in juvenile and adult myositis.

The idiopathic inflammatory myopathies (IIM) constitute a common cause of acquired myopathy in adults and children. These systemic autoimmune diseases, although treatable with immunosuppressive medications, often result in a chronic illness course, functional disability, and increased mortality (1). Although the mortality rate is relatively low in patients with juvenile dermatomyositis (JDM), up to 40% of them have long-term dystrophic calcification and functional disability (2;3). The five-year mortality rate in adult IIM patients ranges from 5–37%, and their most common causes of death are malignancy, cardiovascular disease, and respiratory failure (reviewed in (4)).

The International Myositis Assessment and Clinical Studies Group (IMACS), a multi-disciplinary consortium of adult and pediatric specialists with interest and expertise in myositis, has defined disease damage as persistent or permanent change in anatomy, physiology, and function, which develops from previously active disease, complications of therapy, or other events (5). IMACS recommended a core set of measures for inclusion in therapeutic trials and clinical studies to assess disease activity and damage, to provide consistency in myositis outcomes (5). IMACS developed the Myositis Damage Index (MDI), which is patterned after the Systemic Lupus International Collaborating Clinics (SLICC)-American College of Rheumatology (ACR) Damage Index (6). The MDI documents persistent changes in 11 organ systems thought to be related to damage. Because severity of damage can differ from extent of damage, IMACS includes a series of visual analog scales to quantify damage severity in a given organ system (7). The MDI was also structured for both pediatric and adult patients, and certain items are scored solely in each population. The MDI has undergone inter-rater reliability testing in adult DM/PM patients (7). The purposes of this study are to describe the degree and types of damage in study populations with longer-term follow-up, to further validate the MDI in patients with adult or juvenile IIM, and to find risk factors for damage.

PATIENTS AND METHODS

Patients and Assessment Methods

This study included 134 patients with JDM and 9 patients with juvenile polymyositis (JPM) <18 years old at diagnosis, as well as 38 patients with dermatomyositis (DM) and 58 patients with polymyositis (PM) ≥18 years old at diagnosis. To qualify for inclusion patients had at least two assessments 6–9 months apart. Patients met probable or definite Bohan and Peter criteria for myositis (8) and were enrolled in NIH institutional review board–approved protocols in compliance with the Declaration of Helsinki. Juvenile and adult IIM patients differed in several demographic and clinical assessment characteristics (Table 1).

Table 1
Demographic features at baseline evaluation and disease characteristics and assessment measures at final evaluation for juvenile and adult patients with idiopathic inflammatory myopathy (IIM)*

We enrolled 143 consecutive patients with juvenile IIM from 12 participating centers in the United States, Canada, and Europe into a natural history study. All patients were assessed a median of 18 months [7–37 months interquartile range (IQR)] after diagnosis; 135 (94%) patients were assessed 7–9 months later, and 121 (85%) had a last available assessment at a median of 82 months [52–108 months IQR] after diagnosis. Patients were evaluated between April 1993 and November 2002. Illness features, laboratory, and disease activity assessment measures were obtained prospectively (9).

Ninety-six patients with adult DM and PM were enrolled in protocols at the National Institutes of Health. Patients had a baseline assessment a median of 30 months after diagnosis [12–57 months IQR]; 77 (80%) had a 6-month follow-up evaluation, and 55 (57%) had a final assessment at a median of 60 months after diagnosis [40–104 months IQR]. Patients were assessed between May 1985 and December 2001. Thirty were enrolled in a natural history study, and 66 were enrolled in treatment protocols [cyclophosphamide (n = 8) (10), methotrexate-azathioprine (n = 27) (11), fludarabine (n = 15) (12), and methimazole (n = 16) (13)].

The MDI was completed retrospectively by participating physicians who were trained in the use of the instrument and its definitions at a workshop and provided with online resources demonstrating the features of cutaneous damage. The MDI consists of 11 scales (including muscular, skeletal, cutaneous, gastrointestinal, pulmonary, cardiovascular, peripheral vascular, endocrine, and ocular organ systems, and infection and malignancy), each with 2–8 items scored as present or absent, as well as a 10-cm visual analog scale (VAS) score for each organ system, anchored at the ends and mid-point, to capture severity of damage in each organ system. An item must be observed for ≥6 months to be scored as present and consistent with damage, and each damage item has been defined. The presence or absence of each item was summed to provide a Total MDI Extent of Damage score (potential range 0–35 in children <12 years, 0–37 in adolescents, and 0–38 in adults). Seven items in the cardiovascular, peripheral vascular, and endocrine systems are assessed only in pediatric or adult patients, related to the age appropriateness of the items. Two items, irregular menses and primary or secondary amenorrhea, are scored only for female patients. The 11 organ system VAS scores were summed to provide a Total MDI Severity score (potential range 0–110). The 10-cm VAS and a 0–4 Likert scale physician global damage scores were recorded separately as previously described (14). In juvenile IIM patients, these scores were assessed during the study visits and, in adult patients, during the record review. The optional items were not included in the current study. The MDI is available at http://www.niehs.nih.gov/research/resources/collab/imacs/diseasedamage.cfm.

We used other assessments of disease severity and damage to assess construct validity of the MDI, including measures of strength, functional disability, serum creatinine, and muscle atrophy assessed by magnetic resonance imaging (MRI), based on studies suggesting that changes in these measures accumulate over time and could reflect disease damage (5). Manual muscle testing (MMT) on a 0–10-point scale was performed in 58 juvenile- and 80 adult-onset patients (15), and the total score was adjusted to a scale of 0–120; physical therapists were blinded to other clinical assessments. The Childhood Health Assessment Questionnaire (CHAQ) and Convery Activities of Daily Living (ADL) were used to assess functional disability in juvenile and adult IIM patients, respectively (16). Serum creatinine, a measure of muscle atrophy (17), was adjusted to a common scale, accounting for gender and age differences, using a lower limit of normal of 0.5 mg/dl for children and 0.7 mg/dl for adults. T1 MRI of the thighs was available in 34 juvenile- and 74 adult-onset patients and was read by one musculoskeletal radiologist (SH) blinded to the clinical assessment; muscle atrophy and fatty infiltration were graded on a 0–4 Likert scale and averaged to provide an overall T1 MRI score (18). Disease course was defined as monocyclic, polycyclic, or chronic continuous if ≥2 years of follow-up after diagnosis was available (19). Duration of active disease was defined as the duration from diagnosis to the date of last assessment at which the myositis remained active, whereas disease duration was defined as the time from diagnosis to last assessment. Mortality status in the adult patients as of February 2008 was obtained using the Social Security Death Index (http://www.deathindexes.com/ssdi.html). Age and gender were not significant predictors of mortality, so mortality was not adjusted based on these variables.

Statistical methods

Analyses were performed using Stata version 10 (StataCorp LP, College Station, Texas). Analyses describing the frequency of damage and damage scores used data from the last available assessment, whereas construct validation was performed using the first assessment. Continuous and ordinal data were expressed as median and IQR [25%–75%]. Analyses included χ2 to compare percentages, rank sum or Kruskal-Wallis to compare scores, and Spearman rank correlations (rs) for construct validity with a priori assumptions that correlations >0.7 were considered high, correlations 0.4–0.7 moderate, and <0.4 low.

For change in damage over time, a daily rate of change using the first and last assessments was converted to an annual rate of change in damage scores. Generalized Estimating Equations (GEE) (20) were used to predict the Total MDI Extent and Severity of Damage to allow for multiple observations of a patient over time; data from all available assessments were used in these analyses. Demographic features, illness characteristics, and disease activity measures were used to develop predictors of Total MDI Extent and Severity of Damage using GEE modeling, as noted in the footnotes in Table 5, and significant variables from univariate analysis were used to develop multivariable models. Backwards stepping procedures removed variables with P > 0.15 (21) and/or if a variable contained >10% missing data; only patients with complete data were used for GEE modeling. We have not adjusted the probabilities for multiple testing.

Table 5
Predictors of damage in juvenile and adult idiopathic inflammatory myopathies (IIM) using generalized estimated equation (GEE) modeling

RESULTS

Severity of damage by organ systems

Fewer juvenile IIM patients (79.1%) compared with adults (96.9%) had damage based on Total MDI Severity score at last available assessment (P < 0.0001, Table 2). In juvenile IIM patients, the cutaneous system was damaged most frequently, followed by muscular, skeletal, endocrine, and gastrointestinal systems (Table 2). In adult IIM patients, the muscular system was damaged most frequently, followed by pulmonary, gastrointestinal, and cardiovascular systems (Table 2). These organ systems also contributed greatest to the Total MDI Severity in adults.

Table 2
Frequency of damage in juvenile and adult idiopathic inflammatory myopathy (IIM) patients at last available assessment using the Myositis Damage Index (MDI)

Damage in five systems (muscular, gastrointestinal, pulmonary, cardiovascular, and infection), as assessed by the organ system severity of damage scores, was more frequent in adult than juvenile IIM patients. In addition, cutaneous (70.3% versus 43.9%, P = 0.005) and peripheral vascular (10.8% versus 2.3%, P = 0.021) severity of damage were more frequent in adult than juvenile DM patients.

Adult PM and DM patients had similar overall frequency of damage, except that cardiovascular damage was more frequent in PM than DM patients (62.5% versus 21.6%) and, as expected, cutaneous damage was more frequent in adult DM (70.3%) than PM patients (17.9%, P < 0.0001 for each).

Frequency of damage

Fourteen damage items were more frequent in adult IIM patients, and two items were more frequent in juvenile IIM patients (Table 2). In juvenile IIM, the most frequent damage items at the last available evaluation included cutaneous scar, joint contracture, persistent weakness, muscle dysfunction, and calcinosis, each with a frequency of 23–30% (Table 2). In adult IIM patients, muscle atrophy, persistent muscle dysfunction, and muscle weakness were the most frequent damage items on last evaluation (74–84%), followed by dysphagia and impaired lung function (53% and 49%, respectively, Table 2). In adults, all damage items were seen in one or more patients, whereas in juvenile IIM patients all but malignancy were observed.

The same frequencies of damage were generally observed in adult and juvenile DM. However, adult DM patients had cutaneous scar (61.1% versus 27.3%, P < 0.001), poikiloderma (13.9% versus 3.6%, P = 0.018), and thrombosis (8.1% versus 0.7%, P = 0.007) more frequently than juvenile DM patients at last available evaluation.

Adult DM and PM patients had a similar frequency of detectable damage for the Total MDI Extent of Damage on the last available assessment. As expected, four damage items related to the cutaneous system were more frequent in adult DM than PM patients, including calcinosis (34.2% DM versus 3.5% PM, P < 0.0001), alopecia (27% DM versus 5.3% PM, P = 0.003), cutaneous scar (63.2% DM versus 1.8% PM, P < 0.0001), and poikiloderma (10.5% DM versus 0.0% PM, P = 0.023). In contrast, three items related to muscle and cardiovascular damage were more frequent in adult PM than DM patients, including persistent muscle weakness (82.1% PM versus 62.2% DM, P = 0.031), hypertension (36.8% PM versus 13.2% DM, P = 0.018), and ventricular dysfunction (27.3% PM versus 5.3% DM, P = 0.007).

Severity and extent of damage

The median Total MDI Severity score was 10.8 [IQR 6.4–20.6] in adult IIM and 0.9 [0.2–4.6] in juvenile IIM patients on last evaluation (P < 0.0001). The median Total MDI Extent score was 1 [IQR 0–3] in juvenile IIM and 6 [IQR 4–9] in adult IIM patients on last evaluation (P < 0.0001).

There was no difference in the Total MDI Extent or Severity scores between adult DM and PM patients. The median cutaneous extent and severity of damage scores were higher in adult DM than PM, and the median cardiovascular extent and severity of damage scores were higher in PM than DM (P < 0.0001 for each), but scores did not differ among the other organ systems.

The Total MDI Severity and Extent scores differed between juvenile and adult DM. For juvenile DM, the median Total MDI Severity score on last assessment was 0.9 [IQR 0.2–4.9], whereas in adult DM it was 10.6 [IQR 5.6–16.2, P < 0.0001], and the median Total MDI Extent score was 1 [IQR 0– 3] in juvenile DM versus 6 [IQR 4–9] in adult DM. Both severity and extent of damage scores were higher in adult compared with juvenile DM patients in muscular, cutaneous, gastrointestinal, pulmonary, and cardiovascular organ systems, whereas in the peripheral vascular system, only the severity of damage score was higher.

Construct validation of the MDI

Using data from the first evaluation, we found that the Total MDI Extent and Severity scores were highly correlated (rs = 0.87 in juvenile IIM and rs = 0.75 in adult IIM, P < 0.0001). In both juvenile and adult IIM patients, the Total MDI Extent and Severity scores correlated highly with the physician global damage score (Table 3). Correlations were generally higher with the Total MDI Severity than MDI Extent score. The CHAQ correlated moderately with Total MDI Severity, as well as with muscular, skeletal, and pulmonary severity of damage subscores in juvenile IIM patients. In contrast, the Convery ADL did not correlate well with Total MDI Severity or Extent of Damage or these organ system subscores. Total MMT also correlated moderately with the Total MDI and muscle severity of damage in juvenile, but not in adult, IIM patients. Serum creatinine, a measure of muscle atrophy (17), correlated inversely with muscle severity of damage in both juvenile and adult IIM patients and with Total MDI Severity in adult IIM patients. Although only some patients had MRI, a T1 MRI score that averaged muscle atrophy and fatty infiltration correlated moderately with muscle severity of damage in juvenile and adult IIM patients and with Total MDI Severity in juvenile IIM patients (Table 3).

Table 3
Construct validity of Myositis Damage Index (MDI) in juvenile and adult idiopathic inflammatory myopathy (IIM) patients

Change in damage over time

Adult IIM patients had a measurable increase in the annual change in the Total MDI Severity score, with a median increase of 2.4 points [IQR 0–6.3], whereas the annual rate of change in the Total MDI Extent of Damage was undetectable (median 0, IQR 0–0.02). For juvenile IIM patients, there was no measurable increase in either score.

Predictive validity of the MDI

The Total MDI Extent and Severity scores were lowest in patients with a monocyclic illness course, intermediate in patients with a polycyclic course, and highest in patients with a chronic continuous course, both in juvenile and adult IIM patients at the last available assessment, but also at the baseline evaluation in juvenile patients (Table 4). In juvenile IIM patients, the proportion of patients with detectable Total MDI Extent and Severity of damage also increased commensurate with disease course [47.2% with a monocyclic illness course vs. 66.7% with a polycyclic illness course vs. 81.2% with a chronic course had a Total MDI Extent of Damage score > 0 on the last evaluation (P = 0.001)]. Trends were similar for Total MDI Severity (P = 0.012).

Table 4
Predictive validity of Myositis Damage Index (MDI) scores with disease course*

In adult IIM patients, the annual rate of change in Total MDI Severity was greatest in those with a chronic illness course (median annual increase in damage, 3.9 points) compared with those with a monocyclic or polycyclic course (median annual increase of 0.5 and 0.0 points, respectively, P = 0.0002). There was no difference in the annual rate of change in Total MDI Severity or Extent by disease course subtype in the juvenile IIM patients.

Adult IIM patients who died (n = 25) had higher Total MDI Severity and Extent scores at last available assessment than surviving patients (n = 69, P = 0.038). For example, the median Total MDI Severity score at last follow-up was 14.2 [IQR 8.0–26.9] in those who died versus 9.4 [IQR 6.1–17.1] in patients alive as of February 2008. Patients who died had greater damage in the cardiovascular (median severity of damage 1, IQR 0.0–3.2) and pulmonary systems (median severity of damage 1.2, IQR 0.0–4.3) than those who were living as of February 2008 (median 0, IQR 0.0–1.1 and median 0.1, IQR 0.0–4.0, respectively, P = 0.007 and 0.004, respectively). The cardiovascular severity of damage score was also higher at first assessment in those who died versus those who lived (median 0.6, IQR 0.2–2.6 versus median 0, IQR 0.0–0.75, P = 0.0012), and the median pulmonary extent of damage score was higher at first assessment in those who died than in those who lived (median 1.5, IQR 0.0–2.0 versus median 0.5, IQR 0.0–2.0, P = 0.049).

The annual rate of change of Total MDI Severity was greater in those who died compared with those who lived (median increase 5.1, IQR 2.7–9.7 versus 0.9, IQR 0.0–4.3, P = 0.0006). However, there was no difference in the rate of change in the Total MDI Extent of Damage. The annual rate of increase in cardiovascular and pulmonary organ system severity of damage scores was higher in those who died (median annual increase 1.0 and 4.3) compared with those who lived (median annual change 0.0 and 0.1, P = 0.007 and 0.004, respectively).

Predictors of myositis damage

In juvenile IIM patients, predictors of the Total MDI Severity in a multivariable model included Steinbrocker functional class, the CHAQ score, the presence of gastrointestinal or cutaneous ulcerations, extramuscular activity, and duration of active disease (Table 5). Except for duration of active disease, each of these was also a significant predictor of the Total MDI Extent of Damage in a multivariable GEE model.

In adult IIM patients, significant predictors of the Total MDI Severity in a multivariable model included severity at diagnosis and presence of pericarditis, whereas physician global disease activity and serum creatine kinase level were weak negative predictors of damage severity (Table 5). Illness severity at onset, pericarditis, and delay to diagnosis were multivariable predictors of the Total MDI Extent (Table 5).

DISCUSSION

We found that damage, as measured by the MDI, was detectable in most patients with juvenile IIM and almost all patients with adult IIM with a median follow-up of 6.8 years in juvenile-onset patients and 5 years in adult-onset myositis patients. The MDI appears to perform well and is a valid tool to assess damage in both juvenile and adult IIM. It has good content validity, with almost every item endorsed. There is good construct validity; damage severity correlates well with physician global damage, muscle atrophy detected by MRI, and functional disability and strength in juvenile IIM patients. The MDI has good predictive validity, with higher damage scores and greater frequencies of damage in patients with a chronic illness course and in adult patients who died. Although the Total MDI Extent and Severity scores correlate highly and may be redundant measures, the Total MDI Severity appears more sensitive in detecting damage, in its correlations with other illness features, and in detecting change in damage over time. Because the items constituting the Total MDI Extent provide a detailed assessment of the underlying factors contributing to damage, we currently recommend that both be used together.

Although possible referral biases and variations in the demographic, illness severity features, and composition of the juvenile and adult IIM study populations preclude definitive conclusions about the differences in the frequency or severity of damage in these two populations, they differ in notable ways. In juvenile IIM patients, primary features of damage are cutaneous scarring, calcinosis, joint contractures, persistent weakness, and muscle dysfunction, each with a frequency of 23–30% at last available assessment. Conversely, adult IIM patients have more muscle atrophy, persistent muscle dysfunction, and muscle weakness as well as more persistent dysphagia and impaired lung function than juvenile IIM patients. Damage scores and the rate of accrual of damage are also higher in adult than juvenile IIM patients, although juvenile IIM patients had longer median disease duration (6 years) than adult IIM patients (4.3 years). This finding differs from systemic lupus erythematosus (SLE), in which greater damage and rate of damage accrual were found in an inception cohort of childhood-onset versus adult SLE patients (22).

We found separate predictors of damage in juvenile and adult IIM. Predictors of Total MDI Severity included disease duration, functional disability, extra-muscular activity, and the presence of ulcerations for juvenile patients, versus illness severity at diagnosis and pericarditis for adult patients. Factors such as age, race, illness characteristics, and autoantibody status were predictors of damage in univariable but not multivariable analyses. In studies of damage in SLE, similar factors predict damage in adult and juvenile SLE (2327). We did not examine the effects of treatment on damage, but in patients with SLE, corticosteroid usage and use of additional immunosuppressive agents, such as cyclophosphamide, did affect damage (28). We plan further analyses using propensity scores to examine the effects of therapies on damage in myositis (29).

In our study, damage scores were higher at two time points in adult IIM patients who died compared with those who survived. Although the cause of death in these patients is unknown, cardiovascular and pulmonary damage scores were also higher at two different time points in patients who died versus patients who survived, suggesting good predictive validity of the MDI on overall survival. Cardiovascular disease and respiratory failure, including pneumonia, are common causes of death in adult IIM patients (4). In children, the mortality rate is relatively low, but the correlation of damage scores with disease course subtype, a marker of long-term morbidity (2), also suggests good predictive validity. In patients with SLE, high damage scores and early accumulation of damage, using the SLICC–ACR Damage Index, predict later mortality (30).

The MDI provides a single instrument for evaluating both juvenile and adult patients and can be used throughout a patient’s lifetime (30;31). The instrument was developed by adult and pediatric specialists who recognized that certain items of damage are applicable only to pediatric or adult patients, particularly in the cardiovascular, peripheral vascular, and endocrine systems, and should be scored only in the appropriate age group. For example, growth failure and pubertal delay were present in 14% and 3.5% of juvenile IIM patients, respectively, which is comparable to frequencies observed in pediatric SLE patients using a modification of the SLICC–ACR Damage Index (32). A strength of the MDI is that, since damage might be reversible, particularly in children, it defines damage not as irreversible change but as persistent change due to a non-inflammatory or scarring process (30).

Our study is the first to describe the spectrum of damage in both juvenile and adult IIM and to identify risk factors for damage in myositis. However, its limitations are as follows: the MDI was completed retrospectively through medical record review, which could underestimate the extent of damage or inaccurately reflect the severity of damage. Of note, however, Bernatsky et al. demonstrated good agreement between retrospectively and prospectively completed SLICC–ACR Damage Index in patients with SLE (33). Although the pediatric portion of the study was conducted at multiple centers, the participating investigators received training in the use of the instrument, hence inter-rater reliability for the MDI has been reasonably good (7). The juvenile and adult IIM populations were not inception cohorts and differed in their demographic features, illness severity and characteristics, and enrollment centers. We used consecutive patients to attempt to decrease selection bias; however, there may have been a greater extent or severity of damage in using a referral population from these centers. A prospective inception cohort would provide better ability to directly compare damage in juvenile and adult IIM patients, as has been done in SLE (22). Finally, the rate of change of damage was estimated based on conversion to an annual rate of change. This could over- or underestimate the actual rate of damage accrual, as the rate of change might not be constant but could increase with longer disease duration, as in patients with SLE (34).

In summary, this report on the frequency and spectrum of damage in patients with juvenile and adult IIM shows that damage is common in patients who have had myositis for a median of 6.8 years in juvenile-onset patients and 5 years in adult-onset myositis patients. We have shown that the MDI has good content, construct, and predictive validity, and the scores change as expected over time in both juvenile and adult IIM patients. Risk factors for myositis damage include functional disability, duration of active disease, illness severity at diagnosis, global or extra-muscular activity, and important features of the illness, such as the presence of ulcerations in children or pericarditis in adults. The study of damage in myositis using the MDI should help us better understand the long-term outcomes of patients with myositis and potentially lead to new therapeutic approaches to treat and prevent these complications.

Acknowledgments

Supported in part by the intramural research programs of the National Institute of Environmental Health Sciences and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD. Peter Lachenbruch was supported in part by a grant from the Cure JM Foundation. Lauren Pachman was supported in part by a grant from the Arthritis Foundation. Ann Reed and IMACS Group contributors who are not employed by the US government were supported by NIAMS, NIH grant 1R21AR048349-01.

We thank Drs. Kathleen Coyle and Michael Ward for critical reading of the manuscript and Lisa Maroski for assistance in manuscript preparation.

Appendix: IMACS participants and other contributors

Elizabeth M. Adams, MD, National Institute of Allergy and Immunology and Infectious Diseases, NIH, DHHS, Bethesda, MD; Susan H. Ballinger, MD, Suzanne L. Bowyer, MD, Riley Children’s Hospital, Indianapolis, IN; Olivia Gomez, MD, NIEHS, NIH, Bethesda, MD; Michael O. Harris-Love, PT, PhD, Minal S. Jain, PT, Galen O. Joe, MD, Department of Rehabilitation Medicine, Clinical Center, NIH, Bethesda, MD; Suvimol Hill, MD, Department of Radiology, Clinical Center, NIH, Bethesda, MD; Laura James-Newton RN, PhD, NIEHS, NIH, Bethesda, MD; Carol B. Lindsley, MD, University of Kansas, Kansas City, KS; Maria D. Perez, MD, Texas Children’s Hospital and Baylor College of Medicine, Houston, TX; Murray H. Passo, MD, Children’s Hospital and University of Cincinnati, Cincinnati, OH; Paul H. Plotz, MD, NIAMS, NIH, Bethesda, MD; Carol A. Wallace, MD, Children’s Hospital and University of Washington, Seattle, WA; Lawrence S. Zemel, MD, Connecticut Children’s Medical Center and University of Connecticut, Hartford, CT.

References

1. Danko K, Ponyi A, Constantin T, Borgulya G, Szegedi G. Long-term survival of patients with idiopathic inflammatory myopathies according to clinical features: a longitudinal study of 162 cases. Medicine (Baltimore) 2004;83(1):35–42. [PubMed]
2. Huber AM, Lang B, LeBlanc CM, Birdi N, Bolaria RK, Malleson P, et al. Medium- and long-term functional outcomes in a multicenter cohort of children with juvenile dermatomyositis. Arthritis Rheum. 2000;43(3):541–9. [PubMed]
3. Sallum AM, Pivato FC, Doria-Filho U, Aikawa NE, Liphaus BL, Marie SK, et al. Risk factors associated with calcinosis of juvenile dermatomyositis. J Pediatr (Rio J) 2008;84(1):68–74. [PubMed]
4. Lundberg IE. Mortality in idiopathic inflammatory myopathies. Clin Exp Rheumatol. 2008;26 (suppl 51):S109–S114. [PubMed]
5. Miller FW, Rider LG, Chung YL, Cooper R, Danko K, Farewell V, et al. Proposed preliminary core set measures for disease outcome assessment in adult and juvenile idiopathic inflammatory myopathies. Rheumatology. 2001;40:1262–73. [PubMed]
6. Gladman D, Ginzler E, Goldsmith C, Fortin P, Liang M, Urowitz M, et al. The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus. Arthritis Rheum. 1996;39:363–9. [PubMed]
7. Isenberg DA, Allen E, Farewell V, Ehrenstein MR, Hanna MG, Lundberg IE, et al. International consensus outcome measures for patients with idiopathic inflammatory myopathies. Development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford) 2004;43(1):49–54. [PubMed]
8. Bohan A, Peter JB. Polymyositis and dermatomyositis. Parts 1 and 2. N Engl J Med. 1975;292:344–7. 3403–407. [PubMed]
9. Rider LG, Giannini EH, Harris-Love M, Joe G, Isenberg D, Pilkington C, et al. Defining clinical improvement in adult and juvenile myositis. J Rheumatol. 2003;30(3):603–17. [PubMed]
10. Cronin ME, Miller FW, Hicks JE, Dalakas M, Plotz PH. The failure of intravenous cyclophosphamide therapy in refractory idiopathic inflammatory myopathy. J Rheumatol. 1989;16:1225–8. [PubMed]
11. Villalba L, Hicks JE, Adams EM, Sherman JB, Gourley MF, Leff RL, et al. Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens. Arthritis Rheum. 1998;41:392–9. [PubMed]
12. Adams EM, Pucino F, Yarboro C, Hicks JE, Thornton B, McGarvey C, et al. A pilot study: use of fludarabine for refractory dermatomyositis and polymyositis, and examination of endpoint measures. J Rheumatol. 1999;26:352–60. [PubMed]
13. Cabalar I, Villalba ML, Sherman J, Yarboro C, Cintas H, Koziol D, et al. A pilot study of the effect of methimazole, a drug that down-regulates MHC class I, on dermatomyositis and polymyositis. Arthritis and Rheumatism. 2001;44:S353.
14. Rider LG, Feldman BM, Perez MD, Rennebohm RM, Lindsley CB, Zemel LS, et al. Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies: I. Physician, parent, and patient global assessments. Juvenile Dermatomyositis Disease Activity Collaborative Study Group. Arthritis Rheum. 1997;40(11):1976–83. [PubMed]
15. Harris-Love M, Shrader JA, Koziol D, Pahlajani N, Jain M, Smith M, et al. Distribution and severity of weakness among patients with polymyositis, dermatomyositis and juvenile dermatomyositis. Rheumatology. 2009;48:134–139. [PMC free article] [PubMed]
16. Huber AM, Hicks JE, Lachenbruch PA, Perez MD, Zemel LS, Rennebohm RM, et al. Validation of the Childhood Health Assessment Questionnaire in the juvenile idiopathic myopathies. J Rheumatol. 2001;28:1106–11. [PubMed]
17. Rider LG, Miller FW. Laboratory evaluation of the inflammatory myopathies. Clin Diagn Lab Immunol. 1995;2:1–9. [PMC free article] [PubMed]
18. Summers RM, Brune AM, Choyke PL, Chow CK, Patronas NJ, Miller FW, et al. Juvenile idiopathic inflammatory myopathy: Exercise-induced changes in muscle at short inversion time inversion-recovery MR imaging. Radiology. 1998;209:191–6. [PubMed]
19. Bingham A, Mamyrova G, Rother KI, Oral E, Cochran E, Premkumar A, et al. Predictors of acquired lipodystrophy in juvenile-onset dermatomyositis and a gradient of severity. Medicine (Baltimore) 2008;87(2):70–86. [PMC free article] [PubMed]
20. Hardin JW, Hilbe JM. Generalized Estimating Equations. Boca Raton, Florida: Chapman & Hall/CRC; 2003.
21. Bendel RB, Afifi AA. Comparison of stopping rules in forward stepwise regression. J Amer Stat Assoc. 1977;72:46–53.
22. Brunner HI, Gladman DD, Ibanez D, Urowitz MD, Silverman ED. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008;58(2):556–62. [PubMed]
23. Ravelli A, Duarte-Salazar C, Buratti S, Reiff A, Bernstein B, Maldonado-Velazquez MR, et al. Assessment of damage in juvenile-onset systemic lupus erythematosus: a multicenter cohort study. Arthritis Rheum. 2003;49(4):501–7. [PubMed]
24. Alarcon GS, Roseman JM, McGwin G, Jr, Uribe A, Bastian HM, Fessler BJ, et al. Systemic lupus erythematosus in three ethnic groups. XX. Damage as a predictor of further damage. Rheumatology (Oxford) 2004;43(2):202–5. [PubMed]
25. Yee CS, Hussein H, Skan J, Bowman S, Situnayake D, Gordon C. Association of damage with autoantibody profile, age, race, sex and disease duration in systemic lupus erythematosus. Rheumatology (Oxford) 2003;42(2):276–9. [PubMed]
26. Al-Mayouf SM, Al Sonbul A. Influence of gender and age of onset on the outcome in children with systemic lupus erythematosus. Clin Rheumatol. 2008;27:1159–62. [PubMed]
27. To CH, Petri M. Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus? Arthritis Rheum. 2005;52(12):4003–10. [PubMed]
28. Brunner HI, Silverman ED, To T, Bombardier C, Feldman BM. Risk factors for damage in childhood-onset systemic lupus erythematosus: cumulative disease activity and medication use predict disease damage. Arthritis Rheum. 2002;46(2):436–44. [PubMed]
29. Fessler BJ, Alarcon GS, McGwin G, Jr, Roseman J, Bastian HM, Friedman AW, et al. Systemic lupus erythematosus in three ethnic groups: XVI. Association of hydroxychloroquine use with reduced risk of damage accrual. Arthritis Rheum. 2005;52(5):1473–80. [PubMed]
30. Dayal NA, Gordon C, Tucker L, Isenberg DA. The SLICC damage index: past, present and future. Lupus. 2002;11(4):261–5. [PubMed]
31. Hiraki LT, Benseler SM, Tyrrell PN, Hebert D, Harvey E, Silverman ED. Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study. J Pediatr. 2008;152(4):550–6. [PubMed]
32. Gutierrez-Suarez R, Ruperto N, Gastaldi R, Pistorio A, Felici E, Burgos-Vargas R, et al. A proposal for a pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index based on the analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus. Arthritis Rheum. 2006;54(9):2989–96. [PubMed]
33. Bernatsky S, Clarke A, Abrahamowicz M, Neville C, Karp I, Pineau CA. A comparison of prospective and retrospective evaluations of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for systemic lupus erythematosus. J Rheumatol. 2005;32(5):820–3. [PubMed]
34. Cassano G, Roverano S, Paira S, Bellomio V, Lucero E, Berman A, et al. Accrual of organ damage over time in Argentine patients with systemic lupus erythematosus: a multi-centre study. Clin Rheumatol. 2007;26(12):2017–22. [PubMed]
PubReader format: click here to try

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...