LAS VEGAS – Autoantibodies and autoantibody subsets can be particularly helpful for classifying and treating patients with myositis, including those with myositis-associated interstitial lung disease, according to Dr. Chester V. Oddis.
Many autoantibody subsets are phenotypically and clinically well defined, and have clinical relevance, said Dr. Oddis, professor of medicine and associate director of the rheumatology fellowship training program at the University of Pittsburgh.
Serological classification isn’t always accurate or routinely available for all clinicians, but this may change in the near future as improved techniques for autoantibody detection become available, he said at Perspectives in Rheumatic Diseases 2013.
Anti-MDA-5 and interstitial lung disease
One autoantibody that has gained attention in recent years is anti-MDA-5, also known as anti-CADM-140, which is often seen in patients with amyopathic dermatomyositis (ADM).
Patients with ADM represent a subset of dermatomyositis patients who have cutaneous manifestations of dermatomyositis for 6 months or longer and have no clinical evidence of proximal muscle weakness but may have mild serum muscle enzyme abnormalities. More extensive muscle testing in these patients generally demonstrates no or minimal abnormalities. However, these patients should not be considered to have simply a benign cutaneous form of disease; in fact, they have a frequency of malignancy similar to that of patients with classic dermatomyositis (14% in one series of nearly 300 patients, compared with 15% in classic dermatomyositis).
In addition, ADM patients also have a relatively high frequency of lung disease, Dr. Oddis said. In a published review of the literature of nearly 200 patients with ADM, 10% had interstitial lung disease (ILD) – an important point given that the rash of dermatomyositis may be subtle and missed, he noted.
The Asian population seems to be particularly at risk for this complication. Two studies in recent years have demonstrated that Japanese ADM patients with anti-MDA-5 present with rapidly progressive ILD. A 2011 study showed an increased incidence of acute or subacute interstitial pneumonitis in Chinese patients. Other studies have shown similar findings in Korean and other Asian populations, Dr. Oddis noted.
The presence of anti-MDA-5 represents a novel cutaneous phenotype involving palmar papules and cutaneous ulcerations, severe vasculopathy, and rapidly progressive ILD. The target autoantigen in these cases is MDA-5, which is involved in innate immune defense against viruses, he explained, noting that this supports the possibility that a viral trigger plays a role in the disease.
"I think this complication is filtering into the U.S. population, as we have seen it in our myositis cohort," Dr. Oddis said of the anti-MDA-5 association with ADM and severe ILD. He noted that he recently cared for a 70-year-old white male with "double pneumonia" (a finding that "should always raise suspicion of autoimmune ILD") in June of 2012, a rash of dermatomyositis in September of 2012, and vasculitic skin changes in January of 2013. He presented without muscle weakness.
Anti-synthetase syndrome and ILD
Another autoantibody myositis subset involves the anti-synthetases, including PL-7, PL-12, EJ, and Jo-1.
Patients with anti-synthetase syndrome are generally a clinically homogeneous patient population characterized by fever, myositis, arthritis, Raynaud’s phenomenon, mechanic’s hands, and ILD. About 30%-40% of myositis patients have ILD, which is a significant contributor to morbidity and mortality.
Anti-Jo-1 is found in 50%-75% of these patients, and the coexistence of Ro52 may portend worse prognosis, Dr. Oddis said.
There are certain clinical features of ILD in polymyositis and dermatomyositis, including progressive dyspnea with or without nonproductive cough, lack of digital clubbing (unlike in idiopathic pulmonary fibrosis), and lack of pleuritis and pleural effusion in most cases (unlike in systemic lupus erythematosus). However, presentation can be variable, with about one-third of patients developing ILD before muscle or skin manifestations are apparent. Some patients present with acute disease (acute respiratory distress syndrome), and others present with subacute disease that is chronic and slowly progressing or asymptomatic.
It is important to understand when making a diagnosis of autoimmune ILD that not all patients will present with the classic anti-synthetase syndrome, Dr. Oddis said.
In some cases, patients will have an "incomplete" clinical syndrome with ILD alone or ILD with only subtle connective tissue disease findings, myositis-specific autoantibodies in the absence of myositis, and/or a negative antinuclear antibody (ANA) test, he explained.
The initial symptoms in patients may vary depending on the anti-synthetase autoantibody that is present. In a University of Pittsburgh study, for example, Jo-1 was found in 60% of cases; non-Jo-1 synthetase positive cases more often experienced Raynaud’s as their initial symptom, less often experienced muscle and joint problems as their initial symptom, and had a longer delay in diagnosis, compared with Jo-1 patients. Survival was also decreased, compared with Jo-1 patients.