Seasonal and residential clustering at disease onset of anti-MDA5-associated interstitial lung disease

Nishina, Naoshi; Sato, Shinji; Masui, Kenichi; Gono, Takahisa; Kuwana, Masataka

doi:10.1136/rmdopen-2020-001202

Cited by 48 publications

(32 citation statements)

References 26 publications

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“…A detailed epidemiologic study from Japan revealed that cases of anti-MDA5 DM were clustered in the rural areas around the Kiso river with a link to detection of Coxsackie virus in the water with a seasonality from October to March [36,37]. Similar case clustering has been reported around the Yangtze river in the Jiangsu province in China.…”

Section: Environmentalsupporting

confidence: 52%

Understanding and managing anti-MDA 5 dermatomyositis, including potential COVID-19 mimicry

2021

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Anti-Melanoma Differentiation-Associated gene 5 (MDA-5) Dermatomyositis (MDA5, DM) is a recently identified subtype of myositis characteristically associated with Rapidly Progressive Interstitial Lung Disease (RP-ILD) and unique cutaneous features. We reviewed PubMed, SCOPUS and Web of Science databases and selected 87 relevant articles after screening 1485 search results, aiming to gain a better understanding of the pathophysiology, clinical features, diagnosis, and treatment approaches of anti-MDA-5 DM described in the literature. The etiopathogenesis is speculatively linked to an unidentified viral trigger on the background of genetic predisposition culminating in an acquired type I interferonopathy. The clinical phenotype is highly varied in different ethnicities, with new clinical features having been recently described, expanding the spectrum of cases that should raise the suspicion of anti-MDA-5 DM. Unfortunately, the diagnosis is frequently missed despite excessive mortality, calling for wider awareness of suspect symptoms. RP ILD is the major determinant of survival, treatment being largely based on observational studies with recent insights into aggressive combined immunosuppression at the outset.

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Section: Environmentalsupporting

confidence: 52%

Understanding and managing anti-MDA 5 dermatomyositis, including potential COVID-19 mimicry

2021

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“…It is also interesting to note that a geographical distribution of the disease has also been reported in Japan, with an increased prevalence of anti-MDA5 DM in patients living in rural areas as opposed to urban areas as well as in patients residing near freshwater ( 103 , 104 ).…”

Section: Pathogenesis Of the Diseasementioning

confidence: 75%

“…The hypothesis of a viral trigger of anti-MDA5 DM is suggested by epidemiological studies that highlighted a seasonal distribution of the disease. Classically, anti-MDA5 DM onset follows a seasonal repartition with an epidemic period in fall and winter, a peak in late winter and spring and a dip in summer, following respiratory virus epidemic period ( 102 , 103 ). In the hypothesis of a viral infection as a possible initiator of autoimmunity, the scenario could involve an activation of MDA5 in the infected cells, leading to IFN-I production and increased levels of MDA5, followed by an excessive local apoptosis favored by a specific genetic background (intronic variant of WDFY4).…”

Section: Pathogenesis Of the Diseasementioning

confidence: 99%

Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies

2021

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Anti-MDA5 dermatomyositis is a rare systemic autoimmune disease, historically described in Japanese patients with clinically amyopathic dermatomyositis and life-threatening rapidly progressive interstitial lung disease. Subsequently, the complete clinical spectrum of the disease was enriched by skin, articular and vascular manifestations. Depending on the predominance of these symptoms, three distinct clinical phenotypes with different prognosis are now defined. To date, the only known molecular component shared by the three entities are specific antibodies targeting MDA5, a cytosolic protein essential for antiviral host immune responses. Several biological tools have emerged to detect these antibodies, with drawbacks and limitations for each of them. However, the identification of this highly specific serological marker of the disease raises the question of its role in the pathogenesis. Although current knowledge on the pathogenic mechanisms that take place in the disease are still in their enfancy, several lines of evidence support a central role of interferon-mediated vasculopathy in the development of skin and lung lesions, as well as a possible pathogenic involvement of anti-MDA5 antibodies. Here, we review the clinical and biological evidences in favor of these hypothesis, and we discuss the contribution of emerging therapies that shed some light on the pathogenesis of the disease.

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“…In genetically susceptible individuals, viral, bacterial, and parasitic infections have been suspected to induce autoimmunity and even exacerbate existing autoimmune conditions (129). Epidemiological data shows that subsets of polymyositis (PM) and DM patients defined by various myositis-specific antibodies tend to develop disease at specific times of the year (82,130). This seasonal clustering of disease onset could be indicative of a common environmental trigger such as infection (82).…”

Section: Dm and Infectionsmentioning

confidence: 99%

Environmental triggers of dermatomyositis: a narrative review

et al. 2021

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Dermatomyositis (DM) is an autoimmune disease that affects the skin, lungs, and muscle. Although the pathogenesis of DM is not completely understood, several environmental triggers have been linked to DM onset or flare. This article specifically examines the effects of herbal supplements, drugs, infections, ultraviolet (UV) radiation, and environmental pollutants on the onset or exacerbation of DM. Herbal supplements such as Spirulina platensis, Aphanizomenon flos-aquae, Chlorella, Echinacea, and Alfalfa have been implicated and are frequently used in health foods. Medications such as hydroxyurea, TNF-α inhibitors, immune checkpoint inhibitors (ICI), and penicillamine, as well as certain viral infections, such as parvovirus B19, coxsackie virus, polyomavirus, Epstein-Barr virus (EBV), hepatitis, influenza, and human immunodeficiency viruses (HIV) have been associated with DM onset. Bacterial infections and vaccinations have also been linked to the development of DM. Additional environmental factors, including UV radiation and air pollutants, such as silica, biological/mineral dust, and particulate air matter from vehicle and industrial emissions, may also play a role in DM pathogenesis. Overall, there is general agreement that an autoimmune attack of the skin, muscle, and lungs in DM can be triggered by various environmental factors and warrants further investigation.

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Seasonal and residential clustering at disease onset of anti-MDA5-associated interstitial lung disease

Cited by 48 publications

References 26 publications

Understanding and managing anti-MDA 5 dermatomyositis, including potential COVID-19 mimicry

Understanding and managing anti-MDA 5 dermatomyositis, including potential COVID-19 mimicry

Dermatomyositis With Anti-MDA5 Antibodies: Bioclinical Features, Pathogenesis and Emerging Therapies

Environmental triggers of dermatomyositis: a narrative review

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