The present findings demonstrated that in patients with PM/DM 18F-FDG PET/CT visual and SUV parameters were useful in discriminating PM/DM from non-muscular diseases as well as showing correlations with serum muscle enzymes.
Kubota et al. demonstrated that a substantial component of 18F-FDG uptake in tumor tissue was due to activity localizing in macrophages, young granulation tissue, and other peri-tumoral inflammatory cell elements with greater 18F-FDG uptake than tumor cells (Kubota et al., 1992). We found that 82% patients with PM/DM had 18F-FDG-positive muscle regions, whereas 93% of the control patients had 18F-FDG-negative muscle regions. Pipitone and colleagues considered 18F-FDG muscle uptake not to be specific for myositis, but rather to likely reflect the intensity of metabolic activity within the affected muscles including the contribution of infiltrating inflammatory cells (Pipitone et al., 2012). Tateyama and Owada and their respective coworkers showed increased 18F-FDG muscle uptake in 60.6% and 33% of patients with PM/DM (Tateyama et al., 2015; Owada et al., 2012). Compared to Tateyama’s and the present studies, the low sensitivity of 18F-FDG PET documented by Owada et al. may have been due to the strict criterion they used for muscle 18F-FDG uptake, namely the liver, as a positivity criterion (Owada et al., 2012). In Tateyama’s and the present studies, the mediastinal blood vessels were chosen instead. We found that the number of positive regions, total score, mean SUVmean, and mean SUVmax in patients with PM/DM were significantly higher than those in control patients. These results are consistent with those of two previous reports (Tanaka et al., 2013; Pipitone et al., 2012). Tateyama et al. demonstrated that mean SUVmean and mean SUVmax in patients with PM/DM were significantly higher than those in patients with amyotrophic lateral sclerosis with similar disabilities (Tateyama et al., 2015). This highlights the potential unique and useful role that 18F-FDG PET may be able to play in the diagnosis of PM/DM.
PM/DM is clinically characterized by symmetrical proximal muscle weakness (Engel and Hohlfeld, 2004). In the present study, 18F-FDG muscle uptake mostly showed a symmetrical distribution in patients with PM/DM, consistent with the results of two previous reports (Tateyama et al., 2015; Owada et al., 2012). These findings statistically verified that the inflammatory muscle damage progresses symmetrically in PM/DM, although muscle lesions are often multifocal in each muscle. Although the exact mechanisms underlying the symmetrical proximal muscle weakness in these patients are unknown, some possible mechanisms that may explain it are involvement of some anatomical factors, including blood vessels and peripheral nerves, or immune or physiological factors of individual muscles that can influence the extent of inflammation (Tateyama et al., 2015).
Although serum CK levels are a major clinical biomarker in PM/DM, they do not always reliably reflect disease activity (Rider and Miller, 1995). Tanaka et al. documented that mean SUVmean correlated with serum CK and aldolase levels (Tanaka et al., 2013). Conflicting results have also been obtained regarding the relation between 18F-FDG SUV parameters and serum CK levels (Pipitone et al., 2012; Tateyama et al., 2015). In the present study, total score, mean SUVmean and mean SUVmax were all significantly correlated with serum CK and aldolase levels. This discrepancy in the significance of 18F-FDG PET parameters may be attributable to differences in different aspects of myositis and/or differences in the imaging protocols and image analyses used in the individual studies. Tateyama’s study included patients shortly after the beginning of corticosteroid therapy (Tateyama et al., 2015). To date, there is still very limited experience of 18F-FDG PET and serum muscle enzyme measurements in patients with PM/DM. Further studies are needed to evaluate the correlation between 18F-FDG PET findings and disease biology in these patients.
Limitations of the present study include small sample size and retrospective design. Magnetic resonance imaging (MRI) findings and muscle biopsy data were not obtained from all patients, and so comparisons of their results and 18F-FDG PET/CT findings were not possible. The most important advantage of 18F-FDG PET/CT is that it can screen the whole body in one scan. We can evaluate the extent of muscle lesions systemically at one time including sites that are not routinely screened by MRI. However, as is well known, 18F-FDG uptake in muscles is influenced by hyperglycemia, uptake by other organs, and voluntary or involuntary muscle movement during the uptake phase (Jackson et al., 2006); therefore, the examination must be conducted under strict conditions.
18F-FDG PET/CT also offers additional benefits in the evaluation of patients with PM/DM. The increased prevalence of malignant tumors in these patients has been well documented (Bohan and Peter, 1975), which necessitates screening investigations at the time of PM/DM diagnosis. 18F-FDG PET/CT can be also useful in determining the activity of interstitial lung disease, which is a possibly critical complication in PM/DM (Owada et al., 2012). In a case report by Renard et al., 18F-FDG muscle uptake in a patient with DM after immunosuppressive therapy nearly normalized (Renard et al., 2012). Further additional large prospective studies are needed to confirm our results and their potential clinical value in patients with this difficult to characterize disease.
