It’s also important to measure electrolytes (calcium, phosphorus, magnesium, sodium), too much or too little of which can disrupt the orderly contraction and relaxation of muscle. Although he has recommended the forearm ischemic test in the past, Dr. Wortmann is less enthusiastic about it now, except as a screen for some forms of glycogen storage disease. Electromyography (EMG) results can be problematic because the test is operator dependent. Open dialogue with the person conducting the test can yield valuable information and the results of an EMG are often used as a mechanism to identify sites for muscle biopsy. Dr. Wortmann prefers to use magnetic resonance imaging (MRI), especially T2 and short T1 inversion recovery (STIR) images, to identify potential biopsy sites.
Finally, Dr. Wortmann advised rheumatologists obtaining a muscle biopsy to ensure that they collect enough tissue to conduct histology, histochemistry, electron microscopy, and even constituent analyses, if needed. Some patients tolerate the biopsy well, but for others it is very painful, and therefore it is preferable to avoid a repeat biopsy, he said.
Following Dr. Wortmann, Dr. Plotz gave a succinct five-minute history of the major discoveries in myositis, beginning with Ernst L. Wagner’s first case description in 1863 and Heinrich Unverricht’s published papers on polymyositis and dermatomyositis in 1887 and 1890. He sketched the history of inclusion body myositis, of which the first clear description surfaced in 1989, and described the advances in autoantibodies, as well as disease models including anti-Jo-1. Despite advances, new perspectives and new investigators are desperately needed, he said. Several cooperative groups offer hope for progress, notably the European-based Paediatric Rheumatology International Trials Organization (PRINTO), which is now conducting a five-year trial in patients with juvenile dermatomyositis, comparing prednisone alone with prednisone/methotrexate and prednisone/cyclosporine combination therapies (more information is available at http://www.printo.it). Dr. Plotz lauded the growing cooperation between rheumatologists and neurologists on clinical investigations in adult and pediatric myositis.
Tracking the Anatomic Footprint
As if on cue, the next speaker was Steven A. Greenberg, MD, PhD, professor of neurology and codirector of the neurology trials unit at Brigham and Women’s Hospital and Harvard Medical School in Boston, a leading investigator in dermatomyositis and inclusion body myositis, two well-defined entities within the larger group of diseases grouped under the term polymyositis.
Dr. Greenberg described what he calls the “anatomic footprint” of dermatomyositis: perifascicular atrophy (also termed perimysial myofiber injury) and tubuloreticular inclusions. For the past 25 years, investigators have attributed these muscle fiber injuries to ischemia. When Dr. Greenberg began his investigations profiling messenger RNA transcripts in muscle biopsy specimens, he found no increased abundance of transcripts that are up-regulated by ischemia or epoxia in dermatomyositis. “In dermatomyositis,” he noted, “we see injured muscle fibers with neither of these elements. There are no T cells invading these muscle fibers; there’s no antibody that is bound to them. Instead, there appear to be type 1 interferon-inducible transcripts and proteins that are produced inside these muscle fibers. So, this looks like a disease in which cells are being injured from the inside by molecules of the innate immune system, whose normal function is viral defense. But when they’re produced chronically and inappropriately in tissues, it’s possible that they injure tissues. How they do that is uncertain.”
