Viral myositis as a close mimicker of polymyositis

Viruses can induce myositis through persistent infections, molecular mimicry, production of immune complexes, immune dysregulation, or other mechanisms. Self limited viral myositis is more common among children and has been seen to be mostly associated with influenza A and B. We report a case of 15-year-old boy who presented with proximal muscle weakness following 3 weeks after an episode of fever. Muscle necrosis was evident from the raised creatine kinase levels and myoglobinuria. The patient improved slowly over a period of weeks without any treatment except for adequate hydration.

Keywords: Myoglobinuria, polymyositis, rhabdomyolysis, viral myositis

Myositis, defined as an inflammation of the muscle, is characterized by pain, tenderness, swelling, and weakness of a voluntary group of muscles. The etiology includes autoimmune conditions, genetic disorders, medications, electrolyte imbalances, endocrine disorders, and infections. Infectious myositis may be due to a wide variety of pathogens including bacteria, viruses, parasites, and fungi. Bacterial myositis presents as focal muscle infection, whereas viruses and parasites tend to cause diffuse disease with generalized myalgias and multifocal myositis. Viruses can induce myositis through persistent infections, molecular mimicry, production of immune complexes, immune dysregulation, or other mechanisms. The viruses implicated are influenza A/B, parainfluenza, coxsackie, herpes simplex, Ebstein Barr, cytomegalovirus, and adenovirus. Although associated with spontaneous recovery in most cases, potentially dangerous complications such as rhabdomyolysis, myoglobinuria, acute renal failure, cardiac arrhythmias, and compartment syndrome have been associated with significant morbidity. ^[1] Efforts to culture viruses from muscle, however, have been unsuccessful. We report a case of self limited myositis associated with rhabdomyolysis in a young boy.

A 15-year-old boy suffered a brief bout of fever, rhinitis, sore throat, and myalgia 3 weeks prior to admission. Two weeks after the initial episode, he developed pain and tenderness in his proximal muscles, more prominent after physical activity. His strength gradually deteriorated until he developed difficulty in walking, getting up from a sitting position and combing his hair. The physical examination was essentially normal except for tenderness to palpation and a decrease in strength in the proximal muscles of his upper and lower limbs and the neck muscles. Laboratory results were notable for a CK-MM of 24845 U/L, a urine myoglobin of 2302 U/L and mildly elevated transaminases. The renal function tests were normal with a serum creatinine of 1 mg/dl. Detailed immunologic screening for connective tissue disorder yielded negative results. Human immunodeficiency virus (HIV), hepatitis virus, influenza virus, enterovirus, and coxsackie virus screens were negative. The electromyogram showed myopathic pattern in the affected muscles. The results of the nerve conduction studies were normal. The muscle biopsy specimen demonstrated an inflammatory infiltrate. No inclusion bodies or viral particles were seen.

Corticosteroid treatment was considered for probable polymyositis but was deferred pending observation for spontaneous resolution of possible viral myositis.Adequate hydration remained the mainstay of treatment. The CK-MM and urine myoglobin levels returned to normal in 2 weeks. The patient’s clinical recovery continued over a course of a few weeks and full muscle strength was regained by 1 month after discharge. The renal profile remained normal throughout the length of the disease.

The diagnosis of viral myositis as a cause of rhabdomyolysis is primarily suspected on a clinical basis. The classic triad of muscle pain, weakness, and cola colored urine is rarely seen. Rhabdomyolysis can occur as a result of exertion, crush injuries, seizures, drug abuse, alcohol, viruses, and statin use. ^[1],[2] The patient described had no history of exposure to myotoxins or any evidence of prior muscle dysfunction or connective tissue disorder. Although the serologic evidence for viral infection was inconclusive, the presence of prodromal illness and the absence of other causes suggested a previous viral infection.

Numerous infections can cause myositis with viruses being the most common. Self limited viral myositis is more common among children and has been seen to be mostly associated with influenza A and B. Children may be more susceptible to muscle involvement due to influenza virus’s tropism toward more immature muscle cells, as seen in animal studies. ^[3] Boys are more commonly affected with a 2:1 predominance. ^[4] First clinically described as myalgia crurisepidemica in the 1950s, ^[5] influenza infections can cause sudden onset of calf pain and severe myalgias. Associated with very high CK levels, muscle involvement is more common with influenza B infections, perhaps due to the presence of NB protein used for viral entry, which makes influenza B viruses more myotropic than influenza A viruses. ^[6]

Laboratory tests reveal an elevated creatine kinase, lactic dehydrogenase and aspartate aminotransferase. A necrotising myositis has been suspected in a number of patients with influenza. Muscle fibers containing structures with features of the influenza virion has been detected under the electron microscope. Histopathological examination of muscle reveals degeneration and necrosis, with little inflammatory infiltrates. Patchy involvement is seen in mild cases. ^[3],[4]

Hudgson and Walton stress the cardinal feature of viral myositis to be severe muscle pain particularly in the limb girdles and the paravertebral musculature with little or no muscle weakness, and recovery within days. ^[7] In the case described, proximal muscle weakness was prominent, muscle necrosis was evident from the raised creatine kinase levels, and the patient improved slowly over a period of weeks rather than in days. Literature states that the time from the viral illness to the onset of symptoms may vary from a few days to 3 weeks. During the flare of the disease, the serum CK will usually increase weeks before overt muscle weakness develops. Conversely, with treatment induced remission, concentration of the enzyme decrease to normal before objective improvement in strength. ^[8] Serum myoglobin can be a useful marker of muscle damage and is elevated at least as frequently as the serum CK, and is cleared by the kidney. Once the symptoms start, rhabdomyolysis and local tissue damage may be precipitated and intensified with exercise. ^[1] Supportive evidence for a viral etiology can be obtained from serologic studies, culture of throat swabs, and culture of stool specimens. Rarely has a virus been isolated from a muscle biopsy specimen.

Pathogenetic mechanisms to explain viral associated myositis include direct viral invasion of myocytes, viral myotoxic cytokines, and autoimmune myositis. Direct viral invasion and disruption of myocytes could account for acute rhabdomyolysis shortly after a viral illness, whereas a delayed onset of weakness may be due to self limited autoimmune myositis. ^[9] The mechanism for acute renal failure include direct toxic effects of myoglobin, the deposition of myoglobin casts causing proximal tubular necrosis and alterations in renal blood flow leading to renal ischemia. ^[2],[10] Neither the levels of CK nor myoglobinuria can predict the development of acute renal failure.

Polymyositis is the closest differential of viral myositis. Numerous infections can cause a myopathy and many may be confused with polymyositis. Inflammatory myopathies may be primary, with connective tissue disease, infections, graft vs host disease, eosinophilic myositis, macrophage myositis, sarcoidosis and systemic vasculitis. They present as severe myalgias associated with very high CK levels and non specificmyopathic changes including fibre necrosis and inflammatory cell infiltration on muscle biopsy. Increase in the serum CK in an otherwise stable patient serves as a potential warning of a disease exacerbation, assuming there is no intercurrent process such as muscle injury, hypothyroidism, or medications used to explain the abnormality. However, both infectious myositis and polymyositis can present with similar biochemical parameters, electromyograms, and muscle biopsy picture. Therefore the diagnosis remains primarily clinical. Viral myositis should be suspected when the patient presents with weakness of acute or subacute onset after an antecedent upper respiratory or gastrointestinal infection. If spontaneous remission occurs, the diagnosis of self-limited viral myositis becomes evident and steroid treatment can be avoided.

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.120997