Hélio Yamashita, M.D.- Associate Professor - Dept. of Diagnostic Imaging - UNIFESP - EPM.

Cláudio Len, M.D.- Pediatric Rheumatologist - Dept.of Pediatrics-UNIFESP -EPM.

Maria Teresa Terreri, M.D.- Pediatric Rheumatologist - Dept. of Pediatrics - UNIFESP -EPM.

Section of Pediatric Rheumatology - Discipline of Allergy, Clinical Immunology and Rheumatology - Dept. of Pediatrics - UNIFESP - EPM.

M.O.E. Hilário
Alameda dos Anapurús 1370/144
ZC 04087-004
São Paulo - SP , Brazil
Fax Number : 0055 11 570 1590
E-mail: odete@nox.net

Context: One of the major current challanges related to Juvenile Idiophatic Inflammatory Myopathies is the search for highly sensitive and specific non-invasive methods for diagnosis as well as for follow-up.

Objectives: The aim of our study was to describe typical magnetic resonance imaging findings and to investigate the usefulness of this method in detecting active muscle disease in juvenile dermatomyositis and juvenile systemic lupus erythematosus patients.

Type of study: Transverse, blinded assessment.

Place: Section of Pediatric Rheumatology - Department of Pediatrics (UNIFESP - EPM).

Methods: Thirteen patients (9 girls) with dermatomyositis as well as 13 patients (12 girls) with juvenile systemic lupus erythematosus and 10 normal children (5 girls), were enrolled in the study. The spin-echo in T1, DP, T2 and IR was used in all MRI images. Qualitative and quantitative analysis of gluteus maximus, quadriceps, adductors and flexors were performed and evaluated by two radiologists, blinded to all clinical information.

Results: The different muscle groups presented non-uniform involvement in all patients. The patients with dermatomyositis presented acute and chronic muscular alterations, while those with lupus presented only chronic myopathy, specially atrophy. In the dermatomyositis group, the major alterations were found in the gluteus and flexors regions (signal intensity and fat replacement). The signal intensity was increased in all acute myopathies.

Conclusion: The resonance qualitative and quantitative analysis are useful in detecting clinically active disease in patients with dermatomyositis.

KEY WORDS - Juvenile dermatomyositis, Juvenile systemic lupus erythematosus, Muscle involvement, Magnetic resonance imaging.

INTRODUCTION

Idiopathic inflammatory myopathy syndrome is constituted by a heterogeneous group of diseases, of unknown etiology, which has in common an inflammatory muscle process.

It is characterized by proximal muscular weakness, elevation of seric enzymes related mainly to striated musculature, electromyographic alterations, presence of mononuclear infiltrate in the muscle and absence of recognizable etiology (1). This group of diseases presents a large range of histopathological findings, response to treatment and clinical evolution.

The principal representatives of idiopathic inflammatory myopathies are dermatomyositis, polymyositis and inclusion body myositis. Juvenile dermatomyositis is the most important during infancy, since it is the most frequent and present the most severe muscular inflammation. There are also the myopathies associated to other connective tissue diseases, mainly juvenile systemic lupus erythematosus, scleroderma and juvenile rheumatoid arthritis.

One of the major current challenges related to idiopathic inflammatory myopathies is the search for highly sensitive and specific non-invasive methods for diagnosis as well as for treatment follow-up. Among the image diagnosis methods, magnetic resonance imaging (MRI) has shown itself to be one of the best technics for these purpose and for muscle skeleton disease follow-up (2).

In 1987, Kaufman et al (3), in a study carried out with dermatomyositis patients, observed a correlation between inflammatory muscle activity and some parameters analysed by resonance. In later studies, undertaken mainly with adult patients, the usefulness of this method in the diagnosis of acute and chronic inflammatory muscle diseases was observed (4-6). However, although idiopathic inflammatory myopathies in childhood present their own characteristics, studies using MRI for muscular evaluation are uncommon (7-9). This fact motivated us to study resonance alterations in patients with juvenile dermatomyositis and juvenile systemic lupus erythematosus and to correlate the findings quantitatively and qualitatively, with the presence of inflammatory activity.

Patients

Twenty six patients divided into 2 groups were evaluated over a period of 2 years: 13 with dermatomyositis (9 girls) diagnosed according to the Bohan and Peter (1975) criteria (10), with ages ranging from 5.6 to 16.6 years (mean of 11.7 years); 13 patients with juvenile systemic lupus erythematosus (12 girls) according to the American College of Rheumatology criteria (11), with ages ranging from 9.3 to 16.7 years (mean of 13.6 years). The mean disease duration was 4.5 years (ranging from 1.5 to 13.6 y) for dermatomyositis and 3.7 years (ranging from 0.4 to 8.6 y) for lupus patients. We also calculated the mean daily corticosteroid dose for each patient during the last 6 months and correlated it with the MRI findings.

The control group consisted of 10 healthy children and adolescents (5 girls), with ages ranging from 5.0 to 16.0 years (mean of 11.6 years) free of any disease.

Clinical Evaluation

The characterization of inflammatory activity in the dermatomyositis group was based on the clinical parameters of muscular strength and the presence of altered muscle enzymes, particularly the creatine kinase, aspartate aminotransferase, aldolase and lactic dehydrogenase. For lupus patients the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the following score were used (12): mild disease activity (score 1 to 9), moderate (score 10 to 19) and severe (score ³ 20) disease activity. All parents gave informed consent for the study, which had the prior approval of the local ethics committee.

Magnetic Resonance Imaging

To carry out the MRI, a 1.5 Tesla Philips, Gyroscan S15, Release 5.6 equipment was used. We performed T1-weighted and T2-weighted images with spin-echo (SE) sequences and fat supression technique with inversion recovery (IR) sequence. The T1-weighted images were acquired in coronal and axial planes ( SE , TR/TE of 500-640/20ms, 2 to 4 acquisitions, 180 X 256 matrix, 10/10 mm thickness/increase and field of view (FOV) of 350 mm on the axial and 500 mm on the coronal); the T2 images were acquired in axial plane (SE, TR/TE of 2.500/90 ms, 1 acquisition, 204 x 256 matrix, 10/10 mm thickness/increase and FOV of 300 mm; the IR images were acquired in axial plane (TR/TE/TI of 1.900-2000/20/160 ms, 2 acquisitions, 180 x 256 matrix, 10/10 mm and FOV of 300 mm. Each patient and control was submitted to a MRI exam (total of 36). T1-weighted, T2-weighted and IR images were acquired. All images were obtained with the center in the mid-thigh. The muscle groups studied were : gluteus maximus, quadriceps, adductors and flexors. The exams were evaluated by 2 radiologists who carried out qualitative and quantitative analysis of the 4 muscle groups by consensus, with no knowledge of the patient history. For the qualitative analysis in T2-weighted, T1-weighted and IR, 6 types of findings were standardized and given points in accordance with Table 1. The first 4 (signal intensity, chemical shift, peri-muscular edema and signal intensity of subcutaneous fat) are findings of acute alterations and were observed on T2-weighted images. The other 2 parameters were observed on T1-weighted and IR images. With this method the maximum possible score obtained on evaluation of each patient was 21 points. A lower score indicated lesser muscular problems. The analysis of muscular atrophy was made based on the relationship between the muscular diameter of the thigh and the thigh’s total diameter.

The quantitative analysis was undertaken in T2-weighted and the signal intensity of each individual group of muscles was obtained using a region of interest (ROI) of 0.5 cm at the mid point of the thigh and lower third of the hip. The relationship between the intensity of the muscle/fat signal was calculated by means of dividing the signal intensity measurements of the muscular groups by the fat measurements. For each muscle group, the mean of the 3 measurements obtained in the regions of the strongest signal of the section being studied was used.

RESULTS

Muscular weakness was observed in 9/13 patients (68%) with dermatomyositis, of which 6 (46%) presented elevated muscular enzymes. The neck flexor muscles were the most affected. Creatine kinase was the most frequently altered enzyme (83%). Disease activity was characterized in 46% of patients.

We did not observe any clinical muscle impairment or muscular enzyme elevation in patients with lupus. As regards SLEDAI, 4 patients presented mild disease activity, 5 moderate and 4 severe disease activity.

MAGNETIC RESONANCE IMAGING - The frequency of alterations observed in the qualitative analysis was significantly higher in patients with dermatomyositis when compared to the lupus patients and controls     (Figure 1). Within the variables studied, the muscle signal intensity and the chemical shift presented most alterations, although there had been no significant statistical difference (Table 2). The statistical analysis showed a significant association (p<0.05) between the presence of acute findings and the dermatomyositis group. One interesting observation was the high frequency of chronic alterations in patients with lupus instead of acute alterations.

In relation to muscular atrophy, the greatest involvement was observed in patients with dermatomyositis: this was less pronounced in patients with lupus and not present in the controls (Figure 2). Quantitative analysis showed greater involvement of gluteus maximus and quadriceps in dermatomyositis patients as compared to controls.

In Figure 3 we can observe the mean of the muscle/fat relationship of the muscular groups of patients with dermatomyositis, lupus and controls. The correlation between MRI, muscular weakness and elevation of muscle enzymes was determined only for patients with dermatomyositis, since the alterations were not observed in the lupus group. As for muscular weakness, a statistically significant association was found with the acute alterations and a tendency of association with the chronic alterations of the qualitative analysis. The patients with dermatomyositis and more accentuated muscular weakness presented a higher muscle/fat relationship and therefore greater involvement in the quantitative analysis (p=0.008).

The increase of muscular enzymes also showed a significant correlation with the acute changes observed in the MRI qualitative analysis (p=0.004). Qualitative analysis variables only presented a statistical significant correlation with the biochemical shift analysis (p< 0.05).

Quantitative analysis showed a statistically significant correlation between the higher values of the muscle/fat relationship and the elevation of muscular enzymes (p=0.015). In the dermatomyositis group the mean daily corticosteroid dose was 0.59 mg (0 to 1.2 mg/kg/day) and higher doses only presented correlation with muscle/fat relationship (quantitative analysis). In the lupus group we did not observe correlation between the mean corticosteroid dose (0.47 mg/kg/day) and the MRI findings.

DISCUSSION

We evaluated 13 patients with juvenile dermatomyositis, 13 patients with juvenile systemic lupus erythematosus and 10 normal children and adolescents, using MRI exams with spin-echo technique, with T1-weighted, T2-weighted and IR (fat suppression) images. The aim of this study was to correlate the clinical and laboratory alterations with the MRI findings. The study was performed with 2 types of analysis, the qualitative and the quantitative.

Characterization of disease activity in our dermatomyositis group was based on changes of muscular strength associated to the presence of elevated muscles enzymes, which may be discussed. As we know, the muscular enzymes does not correlate well with muscular strength, rash, and neither with muscular biopsy, in some patients (13). On the other hand muscular weakness, in chronic patients, may just reflect muscular atrophy and fibrosis related to continuous or chronic-recurrent inflammatory disease. In spite of all these considerations we decided to employ this criterion, since it is widely used in the literature (3,5,14).

Disease activity was diagnosed in 46% of our patients with dermatomyositis. All lupus patients presented disease activity, that ranged from mild to severe, which was expected, since the group was heterogeneous in terms of disease duration and type of involvement (15,16). We did not observe clinical muscle involvement (muscle weakness) in these patients as described by other authors (17,18).

Differently from most studies published in the literature, which in general use 4 MRI parameters , we analysed 6 types of findings for qualitative analysis: increase in muscle signal intensity, increase of chemical shift, peri-muscular edema, increase in the intensity of the subcutaneous fat signal, muscular atrophy and muscular fat replacement. The frequency of 5 findings in qualitative analysis of MRI (with the exception of atrophy) in the dermatomyositis group had no significant statistical difference, which may indicate that all the variables could have the same degree of importance . However, we must take into account that our patients were in different stages of activity. "Increase in the signal intensity" was able to detect patients with greater disease activity, presenting 80% of sensibility and 75% of specificity. These results are similar to those of Fujino et al (17), who observed an alteration in signal intensity in 7 of 8 patients with active dermatomyositis. The "chemical shift" detected alterations in 7 patients, 6 of them were in disease activity, showing thereby a sensitivity of 85.7% and a specificity of 83.3% in the detection of disease activity.

Muscular atrophy and fat replacement are qualitative analysis findings associated to chronic muscular processes. The cause of muscular atrophy in dermatomyositis is multifactorial and may be due to chronic inflammation with important muscular impairment, reduction of physical activity during disease activity and long term corticotherapy with elevated doses (18). It is probable that these 3 factors contributed to the presence of muscular atrophy in 11 of ours 13 (84%) patients with dermatomyositis. The remaining patients were not active and using low doses of corticosteroids.

Due to the small number of findings in patients with lupus, we did not carry out a statistical analysis. Nevertheless, it is interesting to note that 41% of the total qualitative analysis findings occurred in one patient, who, at the time of the exam, presented reactivation of the disease, with intense general manifestations and moderate disease activity (SLEDAI), although with no alterations of muscular enzymes or muscular strength. In lupus patients chronic alterations predominated, represented mainly by muscular atrophy. This finding could be explained by some factors, such as the reduction of physical activity, prolonged corticotherapy with high doses, and perhaps the existence of a subclinical myopathy.

In summary, 12 of 13 patients (92.3%) with dermatomyositis presented some degree of involvement in the resonance qualitative analysis whereas the enzyme alteration were observed in 6 (46%). In Park et al study (19), the qualitative analysis alterations were present in 81.8% of patients, whereas the enzyme alterations amounted to 27%. These figures suggest that resonance is capable of detecting muscular involvement in patients with no clinical or enzyme alterations, perhaps by detecting subclinical disease activity and muscular scarring involvement. Some studies of patients with disease activity found resonance alterations in 100% of cases (14,20).

Quantitative analysis, in general, is correlated to acute alterations of muscular involvement or active disease (21). In our study we observed significant differences among dermatomyositis, lupus and controls in 2 muscular groups (gluteus maximus and quadriceps). In Hernandez et al study (20), the mean of the muscle/fat relationship of 4 muscle groups of 4 children, was evaluated at onset and 6 months after the start of treatment. These authors observed significant differences between the mean of the muscle/fat relationship of the gluteus maximus, adductors and quadriceps of patients with dermatomyositis. The difference between our findings and those of Hernandez et al (20), may have occurred because of the heterogeneous muscles involvement, different degrees of disease activity and longer disease duration observed in our patients. In our study, the muscle/fat relationship mean varied between 0.42 and 0.46. In Hernandez et al (20) study, the mean values at the time of diagnosis were between 0.76 and 1.17 in the 4 muscular groups. After 6 months of treatment they observed a reduction in these relationships (0.41 to 0.61). This demonstrates that the muscle/fat relationship (quantitative analysis) is related to acute processes and that there is a tendency to normalization of this relationship during treatment.

CONCLUSIONS

In conclusion, our data show that resonance is an usefull method in the detection of muscular involvement and in the follow-up of patients with idiopathic inflammatory myopathies; it can be used in diverse ways because it is able to differentiate normal from pathologic musculature, to define acute and chronic muscle alterations and to detect and graduate muscle involvement in relation to disease activity. As well, it is a non-invasive, radiation free, painless exam which can be used repeatedly.

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Acknowledgments
We wish to express our thanks to Dra. Yara Juliano and Dr. Neil Ferreira Novo for statistical assistance. This study was supported by CNPq.