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Patients in the U.S. with myositis who are positive for the anti-MDA5 autoantibody are at high risk for developing interstitial lung disease (ILD), a retrospective study found.
ILD developed more commonly among anti-MDA5-positive patients with dermatomyositis (DM) or the variant known as clinically amyopathic dermatomyositis (CADM) compared with patients without the autoantibody (50% versus 25.5%,P=0.043), according to Rohit Aggarwal, MD, of the University of Pittsburgh, and colleagues.
And positivity for the autoantibody was far more prevalent among patients who developed rapidly progressive ILD (87.5% versus 3.7%,P<0.001), the researchers reported online in Arthritis Care & Research.
"Interstitial lung disease in myositis is an under-recognized and deadly complication of this rare autoimmune disease. In classic DM and CADM this is a particularly perplexing and tragic complication worldwide, most notably in several Asian countries," Aggarwal and colleagues wrote.
The two main subtypes of idiopathic inflammatory myopathy are DM and polymyositis, but another group has been described that is characterized by the pathognomonic rash but lacks the muscle features of the disease. This so-called CADM has most often been identified in Asian countries, principally Japan and China, and has been associated with severe ILD among patients positive for the anti-melanoma differentiation-associated gene 5 (MDA5) in those countries.
A U.S. study, however, failed to find an association with rapidly progressive ILD among DM patients who were anti-MDA5 positive.
Therefore, to more fully examine the association and outcomes among patients with both classic DM and CADM who were anti-MDA5 positive in a U.S. population, Aggarwal and colleagues analyzed data from the University of Pittsburgh myositis database, which has been prospectively enrolling patients since 1985.
They identified 61 patients with CADM and matched them according to age and sex with DM patients, then dichotomized the two groups according to anti-MDA5 status.
Lung function data included pulmonary function tests, imaging, and need for supplementary oxygen. ILD was established on imaging, and rapidly progressing ILD was defined as the need for hospitalization, supplementary oxygen, or intubation within 3 months of symptom onset.
The majority of patients were white women, with a mean age of 46. Eight patients in each group (13.1%) were MDA5 positive. Among the 16 antibody-positive patients, 14 were white and two were black. "Interestingly, none of our MDA5+ patients were Asian," the researchers noted.
The incidence of ILD and rapidly progressing ILD was similar in the DM and CADM groups (26% and 31%, 5% and 8%).
Five of seven patients who were MDA5-positive and had rapidly progressing ILD died quickly, three within a month and two within the year. In contrast, only one MDA5-negative patient developed rapidly progressing lung disease and died -- 5.8 years later.
The three MDI5-positive patients with ILD who were able to perform pulmonary function tests at baseline had forced vital capacities (FVC) of 48%, 30%, and 41%, with forced expiratory volume in one second (FEV1) scores of 57%, 37%, and 54%.
In comparison, among the 18 patients with ILD who were anti-MDA5-negative, mean FVC was 79% and mean FEV1 was 84% at baseline.
Survival was lower among anti-MDA5-positive patients, being 67% at 5 and 10 years, compared with anti-MDA5-negative patients, whose survival rates were 92% and 85% at 5 and 10 years, respectively (P=0.007).
The findings of this study suggest that U.S. patients with CADM who are antibody positive are at high risk for rapidly progressive ILD and early mortality.
"Due to the lack of overt muscle weakness, such patients may not be diagnosed and treated in a timely fashion, particularly if the skin rash of DM is subtle or if there are other poorly recognized features of an autoimmune illness," the researchers wrote.
But in this study, both DM and CADM patients who were antibody-positive were at risk of adverse pulmonary outcomes, which was in contrast to what has been seen among Asian patients, among whom the association was only for those with CADM.
"However, there may still be an interaction between anti-MDA5 status and disease subset (CADM vs classic DM) that this study was underpowered to detect," Aggarwal and colleagues noted.
"We conclude that anti-MDA5 is significantly associated with ILD, rapidly progressing ILD, and poor survival in U.S. DM patients. It will be important to expand our understanding of this serious problem in the Caucasian population, including the characterization and study of additional patients."
Two authors disclosed holding a patent on an ELISA kit for anti-MDA5.
This article is brought to RheumNow by our friends at MedPage Today. It was originally published on October 1, 2015.
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