Influenza A (H1N1) induced-myopathy: an important extrapulmonary complication

Abstract

Skeletal or voluntary muscles represent, in the aggregate, approximately 40 to 45% of the weight of our body. Regarding the prominence and visibility of muscle function, disorders of voluntary muscles would be immediately apparent. However, disorders of the muscular system, the myopathies, in some cases, may go undiagnosed for long periods. Even when myopathy is considered and a diagnosis is made, the assessment of its course and the clinical state of the affected individual may at times be difficult to delineate with precision, even when an inflammatory myopathy is considered1. The inflammatory myopathies constitute a heterogeneous and large group of disorders, and they are the most common form of acquired myopathies. Some are focal and confined to one muscle or group of muscles, while others are widespread and involve the limb and axial muscles in a multifocal fashion. The inflammatory myopathies may be further classified etiologically into those that occur due to a known infective organism (viral, bacterial, fungal, or parasitic) and the idiopathic inflammatory myopathies, whose etiology is uncertain, but in many of which there is strong evidence that the muscle damage is immunogically mediated2. Despite the existence of several types of virus inflammatory myopathy (virus myositis) in animals, the occurrence of this type of infective muscle inflammation in man has had an uncertain status. Influenza A and B viruses can cause widespread outbreaks of human disease with devastating consequences. Influenza A viruses are classified based on the characteristics of two surface glycoproteins, hemagglutinin (H1 to H15), and neuraminidase (N1 to N9). All subtypes have been detected in viruses recovered from aquatic birds, which are the natural reservoir for influenza viruses. So far, only H1, H2, and H3 and N1 and N2 are associated with large-scale influenza outbreaks among humans. The WHO recently declared that the novel influenza H1N1 virus was responsible for the 2009 flu pandemic. As the virus continues to spread globally and affect more individuals, more complications of this virus infection are being recognized. In 1896, Leichtenstern first described the association as ‘muscular neuralgias’ affecting the back, thighs, and calves of patients3. Influenza-associated myopathy has been a well-known phenomenon, mainly in pediatric patients, but it has been rarely reported in adults. Most cases are described during large influenza epidemics. Isolated cases and small clusters of influenza A (H1N1)-induced myocarditis, alone or in conjunction with pericarditis or rhabdomyolysis, have been reported. A severe necrotizing myopathy with myoglobinuria has rarely been reported in influenza4-8. Although, in a recent prospective cohort study of 152 patients in England, measurement of cardiac troponins I and T to detect myocardial injury was used, none of the 12% of patients with elevated creatine kinase levels had evidence of cardiac involvement, suggesting that rhabdomyolysis is more common than myocarditis9. The pathogenesis of this influenza A form of myopathy is uncertain. Direct invasion of the muscle by the virus has been postulated, and the susceptibility of human muscle to the virus was demonstrated in tissue culture10. However, convincing evidence of viral invasion in vivo remains to be presented. Skeletal-muscle biopsies generally do not reveal direct viral infection. In patients with severe myalgia in the calves and with high creatine kinase (CK), degenerative Federal University of Sao Paulo – Paulista School of Medicine (UNIFESP/EPM), Department of Neurology and Neurosurgery – Division of Neuromuscular Disorders, Sao Paulo SP, Brazil.