Clinical and pathologic aspects of arthritis due to Ross River virus and other alphaviruses

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Abstract
Arthritogenic alphaviruses are globally distributed mosquito-borne RNA viruses causing epidemics of polyarthritis/arthralgia, with disease emerging or reemerging and increasingly being reported in travelers. This article summarizes the current knowledge of these diseases, focusing on recent developments in the understanding of Ross River virus disease. Alphaviral arthritides have often been blamed for protracted chronic illnesses. However, validated quality-of-life questionnaires and exhaustive searches for differential diagnoses showed that Ross River virus disease, although severe at onset, progressively resolved over 3 to 6 months. Many patients did experience long-term disease lasting more than 12 months, but in nearly all cases this was due to other conditions, primarily unrelated rheumatic conditions or depression. There is no indication that alphaviral arthritides predispose to other conditions; thus, patients whose Ross River virus disease has actually resolved may be underdiagnosed for other conditions. Ross River virus polyarthritis probably arises from inflammation associated with productive viral infections in synovial macrophages, which persist despite neutralizing antibodies and antiviral cytokine responses. Persistence may be facilitated by downregulation of cytokine responses by virus-antibody complexes binding to Fc receptors and induction of interleukin-10. How virus escapes neutralizing antibodies remains unclear but may involve phagocytosis of apoptotic virus-infected cells and infection of the phagocyte via the phagosome. Diagnosis of alphaviral arthritides is complicated by nonspecific symptoms and the lack of commercial serodiagnostic kits, except for Ross River and Barmah Forest virus infections in Australia. Differential diagnoses should be actively pursued, especially if symptoms persist. Treatment with nonsteroidal anti-inflammatory drugs appears largely effective, with no evidence of long-term sequelae or relapse.