Environmental Factors in Myositis: A Link?

Allergies & Asthma

The development of a subtype of inflammatory myopathy characterized by interstitial lung disease and positivity for a specific autoantibody was influenced by seasonality and place of residence, Japanese researchers found.

Among patients with polymyositis or dermatomyositis (PM/DM) and the associated interstitial lung disease, symptom onset occurred most often from October to March for those with the myositis-specific anti-melanoma differentiation-associated gene 5 (MDA5) antibody, which has been linked with severe and often lethal lung disease, according to Masataka Kuwana, MD, of the Nippon Medical School Graduate School of Medicine in Tokyo, and colleagues.

In addition, according to their study online in RMD Open: Rheumatic & Musculoskeletal Diseases, PM/DM-associated interstitial lung disease occurred significantly more often among patients with the anti-MDA5 antibody who lived near a body of fresh water.

Dermatomyositis and polymyositis are idiopathic myopathies that can affect muscles, skin, joints, and lungs, and interstitial lung disease is one of the main causes of death in these patients.

“The etiology of PM/DM remains unknown, but it is believed that the disease occurs as a result of exposure to environmental factors in genetically susceptible individuals,” the researchers wrote.

One environmental factor that has been recognized is preceding infection, especially of the respiratory and gastrointestinal tracts.

The anti-MDA5 antibody, a pattern recognition protein that detects viral RNA, may trigger autoimmunity through an innate response to viral exposure. Seasonal differences also have been observed among patients with certain myositis-specific antibodies such as anti-Jo-1 and anti-aminoacyl-tRNA synthetase (anti-ARS).

Moreover, a previous study of patients positive for anti-MDA5 found that the majority resided in rural areas and near a major river.

Therefore, to explore the potential influence of these environmental and host factors on PM/DM-associated interstitial lung disease, Kuwana and co-authors analyzed data from a multicenter Japanese myositis cohort that included almost 500 incident cases of the myositis-associated lung disease during the years 2011 to 2015.

The seasonal analysis included 365 patients, and the geographic analysis included 481. Participants were grouped according to antibody status: those who were positive for anti-MDA5, those who were positive for anti-ARS, and those who were negative for both autoantibodies.

At baseline, anti-MDA5-positive patients were younger and had shorter duration of disease, and were classified as most often having clinically amyopathic DM. They also had lower levels of serum creatine kinase and higher levels of ferritin.

Muscle symptoms were uncommon in all three groups, though greater in the anti-MDA5/ARS-negative group.

The rate of 6-month survival was only 68% among the anti-MDA5-positive group compared with 96-99% in the other two groups (P<0.01).

In the seasonal analysis of the overall study population, there was no noticeable pattern, the team found. Nor was there any significant pattern observed for the anti-ARS-positive group or the anti-MDA5/ARS-negative group. However, for the anti-MDA5-positive group, disease onset peaked in January and was increased throughout the months of October through March.

The geographic analysis relied on postal codes and Google maps to determine the distance from patients’ place of residence and the nearest waterfront, which could be freshwater or saltwater.

Patients in the anti-MDA5-positive group lived significantly closer to any waterfront (≤1.75 km), especially to freshwater, than the anti-ARS-positive or anti-MDA5/ARS-negative groups, the investigators noted.

The finding of time and space clustering supports the concept that infection may play a role in anti-MDA5-positive PM/DM-associated interstitial lung disease, the researchers noted. Possible explanations for this include transmission of viruses by vectors such as mosquitoes inhabiting freshwater locales, or pathogenic processes in the host such as activation of NF-κβ and upregulation of type I interferon and inflammatory cytokines such as interleukins 6, 8, and 18 following the recognition of viral RNA by MDA5.

In addition, the lung disease may be triggered by exposure to RNA viruses such as picornavirus, paramyxovirus, West Nile virus, and coronaviruses in anti-MDA5-positive individuals.

Further studies are needed to more fully explore the potential environmental triggers of this “devastating condition,” the authors concluded.

A limitation of the study, they said, was the possibility of unreliable history reporting among participants.

Disclosures

The study was supported by the Japanese Ministry of Health, Labor and Welfare.

The authors reported holding patents for the anti-MDA5 antibody measurement kit, and having financial relationships with AbbVie, Actelion, Asahi Kasei, Astellas, Boehringer Ingelheim, Bayer, Chugai, Eisai, Corbus, CSL Behring, Janssen, MBL, Mitsubishi Tanabe, Mochida, Nippon Shinyaku, Novartis, Pfizer, Ono, Reata, Takeda, Teijin, and UCB.

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