WASHINGTON, D.C.–Differentiating between subgroups of myositis is a diagnostic challenge for physicians, but using some guiding principles can be helpful, an expert said during a session titled, “Muscle Biology, Myositis and Myopathies: Classification, Treatment and Outcome in Idiopathic Inflammatory Myopathies,” here at the 2012 ACR/ARHP Annual Meeting, held November 9–14. [Editor’s Note: This session was recorded and is available via ACR SessionSelect.]
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Ingrid Lundberg, MD, PhD, professor in the rheumatology unit in the department of medicine at Karolinska University Hospital in Solna, Sweden, drew from a collection of cases to offer pointers in sifting through symptoms and made suggestions that might help physicians pin down the nature of a patient’s disease as specifically as possible.
She also reviewed the latest on therapies for myositis, but said there is no “wonder drug” yet.
Patients with elevated creatine kinase (CK) and muscle weakness cannot be assumed to have myositis, she cautioned. “There are other medical conditions that have to be ruled out, and that was recognized already in the diagnostic criteria,” Dr. Lundberg said. The most important alternatives to consider are drug-induced myopathy, infection-induced myopathy, metabolic myopathy, endocrine myopathy, and muscular dystrophy, she said. “These can be excluded by clinical investigations as well as muscle biopsies,” she said.
Within myositis, doctors have to distinguish among subgroups that are illustrated in the following cases.
A 77-year-old woman presented with a history of hypothyroidism, hypertension, and Sjögren’s syndrome. At age 72, the woman had noticed a slowly progressing muscle weakness in her legs, but no pain. She had trouble walking, experiencing repeated falls and a fractured ankle.
After five years of problems, she came to the hospital and had difficulty getting up from a chair, trouble swallowing, and had atrophy of her thigh muscles. A manual muscle test—like a joint count but for the muscles—found profound weakness, with a score of 58 out of 80.
A muscle biopsy showed degenerating fibers, inflammatory cells, and rimmed vacuoles, all of which were signs of inclusion body myositis.
The biopsy can be a crucial part of the diagnosis, Dr. Lundberg said. “Muscle biopsy is essential in the diagnostic workup of myopathies, both to exclude other noninflammatory myopathies like muscle dystrophy … but also to identify subgroups like inclusion body myositis,” she said.
She also said that patients who present with weakness in the finger flexors should be considered for inclusion body myositis.
A 38-year-old man had seen a skin rash on his hand, along with arthralgia, in August of 2004. By November, he’d developed a cough and breathlessness. Those symptoms had worsened within a few months, and he’d developed mild muscle weakness, too.
Tests found his CK levels were normal. He was also found to have interstitial lung disease (ILD), which was rapidly progressing, and the man was positive for SSA/anti-Ro antibodies.
He was found to be major histocompatibility complex (MHC) class I positive on muscle fibers in the muscle biopsy investigated by immunohistochemistry, as well as positive for anti-MDA5, an antibody recently found to be associated with dermatomyositis, which was determined to be the patient’s diagnosis.
Dr. Lundberg said that a normal CK and normal histopathology do not exclude dermatomyositis, and that an MRI and testing for myositis-specific antibodies can be helpful.
More specifically, this patient could be classified as having clinically amyopathic dermatomyositis, with a skin rash typical of dermatomyositis, but combined with rapidly progressing ILD and the presence of anti-MDA5 antibodies.
She also said a link between ILD and myositis has been increasingly recognized, with ILD in 60% to 70% of dermatomyositis and polymyositis cases—and, in fact, it might be the first clinical symptom of myositis. Anti-MDA5 antibodies may be associated with a rapidly progressive ILD.
Another similar subgroup is antisynthetase syndrome, characterized by ILD, myositis, arthritis, fever, Raynaud’s disease, and an association with the HLA-DRB1 allele. It can be found in dermatomyositis and polymyositis. Eight antibodies are linked with this subgroups—the most common is anti-Jo-1.
At about age 44, a man was diagnosed with polymyositis. He had developed atrial fibrillation from the time he was 35; by 44, he had arm and leg weakness, along with myalgia. A muscle biopsy had found degenerating and regenerating fibers but no inflammatory cell infiltrates, and he was MHC class I positive in his muscle fibers.
He was treated, but at age 57, he still had profound muscle weakness, and had developed swallowing problems and atrophy of the hamstrings, but a muscle biopsy from the quadriceps is normal.
The man was then found to be antinuclear antibody negative but anti–signal recognition particle positive and was diagnosed with immune-mediated necrotizing myopathy, a disorder characterized by cardiac involvement and treatment-resistant myositis.
Dr. Lundberg said it’s important to be aware of cancer-associated myositis. No particular kind of cancer is overrepresented, and there are no specific clinical features to look for. But, she said that if a dermatomyositis is treatment resistant, an underlying malignancy should be considered. There is an association with the anti–TIF1 gamma antibody, which is not yet commercially available.1
As far as myositis treatments go, there have been few randomized controlled trials, so case series are the main guide.
Dr. Lundberg said the targeting of B cells has shown some promise. In the RIM trial (Rituximab in the Treatment of Refractory Adult and Juvenile Dermatomyositis and Adult Polymyositis), a multicenter trial involving 200 patients, the time to improvement endpoint wasn’t met, but overall, 83% of the patients met the definition of improvement.2 Twenty-six percent of patients suffered a serious adverse event, mainly infections. There was also a glucocorticoid-sparing effect between baseline and the study’s conclusion.
“What we can conclude, I think, from this study is that B cells may be important in the pathogenesis of myositis and targeting B cells may be effective in treatment-resistant [polymyositis or dermatomyositis] cases,” Dr. Lundberg said.
Antitumor necrosis factor therapy has led to mixed results, and an interleukin-1 blockade has shown some promise, she said. “We need to identify subgroups with shared disease mechanisms” to make potential therapies more beneficial, she said.
Therapy with a more clear benefit is physical exercise, she said.
Patients with chronic polymyositis or chronic dermatomyositis who underwent seven weeks of resistance exercise showed improved strength and that genes involved in inflammation were downregulated.3
“What we know about physical exercise in myositis today is that it’s safe, it can really improve muscle performance and strength, can improve your oxygen uptake, and it might reduce inflammation.”
Thomas Collins is a freelance medical journalist based in Florida.
- Labrador-Horrillo M, Martínez MA, Selva-O’Callaghan A, et al. Anti-TIF1γ antibodies (anti-p155) in adult patients with dermatomyositis: Comparison of different diagnostic assays. Arthritis Rheum. 2012;71:993-996.
- Oddis CV, Reed AM, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: A randomized placebo-phase trial. Arthritis Rheum. 2013;65:314-324.
- Dastmalchi M, Alexanderson H, Loell I, et al. Effect of physical training on the proportion of slow-twitch type I muscle fibers, a novel nonimmune-mediated mechanism for muscle impairment in polymyositis or dermatomyositis. Arthritis Rheum. 2007;15;57:1303-1310.