Myositis is one of the complications of viral infections. Viral myositis is an illness characterized by muscle weakness and pain associated with elevated muscle enzyme levels and laboratory evidence of viral infection, ideally supported by detection of viral presence in the muscle. Both viruses and retroviruses are well-known pathogens that can be associated with an inflammatory myopathy. Viral myositis results from direct infection of muscle or the ensuing inflammatory response. The treatment of viral myositis overlaps with the treatment of the initial infection. Certain infectious agents have been associated with “idiopathic” chronic inflammatory myopathies and might shed light on pathogenesis and offer practical treatment strategies. This became especially important in the 1990s when HIV and other retroviruses as well as hepatitis C virus were investigated for their role in polymyositis and inclusion body myositis. In this article, the author discusses the clinical manifestations, pathogenesis, and diagnoses of viral and retroviral myositis.
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• Viral myositis manifests with myalgia, weakness, and, rarely, rhabdomyolysis.
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• Although virtually any virus can cause an acute myositis, influenza virus and enterovirus are the most common in North America and Northern Europe.
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• Acute and subacute viral myositis is mostly benign and self-limited.
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• Chronic viral myositis is associated with retroviruses and hepatitis viruses.
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• Basic evaluation of viral myositis is warranted in all patients, but further studies for underlying hereditary myopathies is indicated in certain cases.
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• Myositis and rhabdomyolysis have been described in association COVID-19 infection.
Historical note and terminology
The topic of viral and retroviral contributions to inflammatory myopathy in humans has important clinical and theoretical implications.
The first recognition of a connection between viruses and human muscle disease occurred with coxsackieviruses in 1934 with the epidemic pleurodynia, an ill-defined, self-limited, acute febrile illness with painful thoracic and abdominal muscles (94).
Viral myositis. The word myalgia comes from the Greek mys (“muscle”) and algos (“pain”). One of the first physicians to describe myalgia specifically as muscle pain distinct from neuralgia was Dr. Thomas Inman in a book written in 1860 titled On Myalgia. Descriptions of myalgia in journal articles first began to appear in the early 20th century, and again the focus was on muscle-specific pain and differentiation from other causes of pain (48).
The word virus originates from Latin meaning “poison.” Diseases caused by viruses (such as poliomyelitis and smallpox) have been recognized since ancient Egypt, yet the discovery and definition of viruses did not occur until the latter half of the 19th century. As early as 1840, German anatomist Jacob Henle of Gottingen posited the existence of agents too small to be seen by the light microscope but able to cause disease. Multiple simultaneous discoveries by Chamberland and Pasteur, Iwanowski, and Beijerinck and Mayer led to the knowledge that living agents smaller than all known bacteria and capable of causing disease in both plants and animals could be transmitted through bacteria-free filtrates (35; 15).
Myositis comes from the Greek myo (“muscle”) and itis (“inflammation”). The first description of what was most likely a viral myositis was by Dabney in 1888. He described an epidemic in Charlottesville, Virginia, which he likened to dengue and was characterized by acute severe pleuritic chest pain, also called epidemic pleurodynia, and nicknamed “Devil’s Grip” in the setting of fever and systemic symptoms. In the summer of 1923, an epidemic of likely viral myositis consisted of an acute febrile disease and severe, transient epigastric pain, thought to be diaphragmatic spasm at the Presbyterian Hospital in New York (03). In the 1930s, Dr. Ejnar Sylvest of Denmark described “myositis acute epidemica” and posited that there was an infiltration of the muscles and noted the increased frequency in the summer and autumn months (94). Dr. Thomas Pickles called a similar phenomenon Bornholm disease (named after an island in the Baltic where many cases were seen) and “epidemic myalgia” and even Sylvest disease, whereas others described it as “epidemic pleurodynia.” The localization to the muscle (in particular the diaphragm) was hypothesized given the absence of pleuritic rub or pulmonary findings.
An association between epidemic pleurodynia and a causative viral agent was first found in the late 1940s, and in 1950 the isolation of coxsackievirus from throat washings from prior epidemics as the causative agent (104). This observation was expanded over the ensuing years to patients with inflammatory myopathies who had serological evidence of high viral antibody titers (Tang et al 1975; Travers et al 1977; 13). The saga re-emerged when antibodies to the Jo-1 antigen, a histidyl-transfer RNA synthetase (96), were found in up to 10% of patients with myositis (21). Jo-1 antigen shares structural homology with the genomic RNA of an animal picornavirus, the encephalomyocarditis virus, which suggested a possible molecular mimicry phenomenon. Strengthening the association of viral infection and inflammatory myopathy, enteroviral RNA was found in some cases by in situ hybridization in muscle fibers of some myositis patients (Rosenberg et al 1989; 109), but this could not be verified.
Influenza-associated myositis was first described in 1950s as “myalgia cruris epidemica,” proven to be confirmed with polymerase chain reaction studies (53; 54). The idea of enterovirus replication within the myocytes of chronic inflammatory myopathies fell from favor as studies began focusing on HIV, other retroviruses, and hepatitis C in 1970.
Retroviral myositis. The first report of a retrovirus associated with inflammatory myopathy came in the 1980s with monkeys infected with simian immunodeficiency virus (20; 25), followed closely by human cases associated with HIV (20; 27) and later HTLV-I (70).
Other viruses. Hepatitis C virus-associated polymyositis or myositis was first reported in 1994 (64), with numerous subsequent reports (Horsmans and Geubel 1995; Ueno et al 1995; Weidensaul et al 1995; 91) including two cases in which hepatitis C virus RNA was detected in muscle biopsies using polymerase chain reaction (Sola et al 1999; 101). There were next several case reports of inclusion body myositis co-occurring with hepatitis C virus infection (Alexander and Huebner 1996; 91; 107), and in one case reverse transcriptase polymerase chain reaction revealed hepatitis C virus RNA in muscle samples (107). This led to a Muscle Study Group investigation into interferon beta as a treatment for seronegative inclusion body myositis patients. Unfortunately, this was not found to be effective in two randomized controlled trials (Muscle Study Group 2001; Muscle Study Group 2004; 107).