Viral and retroviral myositis

Christina M Ulane MD PhD (Dr. Ulane of the Neuromuscular Division in the Neurological Institute of Columbia University Medical Center at New York-Presbyterian Hospital has no relevant financial relationships to disclose.)
Salvatore DiMauro MD, editor. (Dr. DiMauro, Director Emeritus of H Houston Merritt Clinical Center for the Study of Muscular Dystrophy and Related Diseases at Columbia University, has no relevant financial relationships to disclose.)
Originally released February 10, 1995; last updated January 24, 2017; expires January 24, 2020

Overview

Viruses are important causes of viral myositis. In addition to myriad other infections, both viruses and retroviral contributions to retroviruses are well-known human pathogens that can be associated with an inflammatory myopathy. Either by direct infection of muscle or the ensuing inflammatory response, viruses are associated clinically with myositis. Advances in humans have important clinical, antiretroviral, and theoretical implications. The theoretical implications especially stem from the possibility that antiretroviral treatment myositis may also occur as a result of treatment of the initial infection. Theoretically, certain infectious agents could trigger certain “idiopathic” chronic inflammatory myopathies, or their occasional association might shed light on pathogenesis and offer practical treatment strategies for these classic neuromuscular diseases. 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 (among many other neurologic diseases). In this article, the authors discuss the clinical manifestations, pathogenesis, and diagnoses of viral and retroviral myositis.

Key points

 

• Viral myositis manifests with myalgia, weakness, and, rarely, rhabdomyolysis.

 

• Although virtually any virus can cause an acute myositis, influenza virus and enterovirus are most common in North America and Northern Europe.

 

• Acute and subacute viral myositis is mostly benign and self-limited.

 

• Chronic viral myositis is associated with retroviruses and hepatitis viruses.

 

• Basic evaluation of viral myositis is warranted in all patients, but further studies for underlying hereditary myopathies is indicated in certain cases.

Historical note and terminology

The rather broad topic of viral and retroviral contributions to inflammatory myopathy in humans has important clinical and theoretical implications. The theoretical implications especially stem from the possibility that certain infectious agents could be the root cause of certain “idiopathic” chronic inflammatory myopathies or that their occasional association might shed light on pathogenesis and offer practical treatment strategies for these classic neuromuscular diseases. 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 (among many other neurologic diseases).

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 (Sylvest 1934).

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 (Keith 1908).

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 (Fields et al 2007; Collier et al 2011).

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 (Annonymous 1924). 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 (Sylvest 1934). 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 (Weller et al 1950). 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; Christensen et al 1986). The saga re-emerged when antibodies to the Jo-1 antigen, a histidyl-transfer RNA synthetase (Targoff 1990), were found in up to 10% of patients with myositis (Dalakas 1989). 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; Youse et al 1990), 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 (Leff et al 1992; Leon-Monzon and Dalakas 1992). 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 due to influenza virus. 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 (Dalakas 1986; Dalakas et al 1986), followed closely by human cases associated with HIV (Dalakas 1986; Dalakas et al 1986) and later HTLV-I (Morgan et al 1989).

Other viruses. Hepatitis C virus-associated polymyositis or myositis was first reported in 1994 (Matsuya et al 1994), with numerous subsequent reports (Horsmans and Geubel 1995; Ueno et al 1995; Weidensaul et al 1995; Saperstein et al 1999) including 2 cases in which hepatitis C virus RNA was detected in muscle biopsies using polymerase chain reaction (Sola et al 1999; Villanova et al 2000). There were next several case reports of inclusion body myositis co-occurring with hepatitis C virus infection (Alexander and Huebner 1996; Saperstein et al 1999; Yakushiji et al 2004), and in one case reverse transcriptase polymerase chain reaction revealed hepatitis C virus RNA in muscle samples (Yakushiji et al 2004). 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 2 randomized controlled trials (Muscle Study Group 2001; Muscle Study Group 2004; Yakushiji et al 2004).

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