ARTHRITIS & RHEUMATISM Vol. 43, No. 2, February 2000, pp 365–369 © 2000, American College of Rheumatology DETECTION OF VIRAL RIBONUCLEIC ACID AND HISTOLOGIC ANALYSIS OF INFLAMED SYNOVIUM IN ROSS RIVER VIRUS INFECTION MURIEL SODEN, HELEN VASUDEVAN, BRENDA ROBERTS, ROBERT COELEN, GARY HAMLIN, SUBASH VASUDEVAN, and JUSTIN LA BROOY Objective. To document the histology of Ross River virus (RRV) arthritis and to examine inflamed synovium for viral RNA. Methods. Biopsy tissue from the inflamed knees of 12 patients with RRV infection was studied using conventional and immunostaining techniques. Reverse transcriptase–polymerase chain reaction technology was used to probe for the presence of viral RNA in the synovial biopsy samples and in serum. Results. Hyperplasia of the synovial lining layer, vascular proliferation, and mononuclear cell infiltration were the main histologic changes. RRV RNA was found in knee biopsy tissue that was obtained from 2 patients at 5 weeks after the onset of symptoms. Conclusion. RRV RNA was identified in inflamed synovium more than a month after symptoms began. Inflammation was apparent in the absence of detectable virus in the majority of patients. Ross River virus (RRV) is an alphavirus trans- mitted to human hosts by a variety of mosquitoes, including Aedes aegypti and Culex annulirostris (1). It is the most common cause of viral arthritis in Australia, with 1,000 people being affected by it each year (2). RRV infection is usually recognized as an acute clinical illness that is characterized by the triad of polyarthritis, fever, and a maculopapular rash (3,4), although infec- tions may be subclinical. The arthritis may involve most of the joints, but more commonly affects the wrists, knees, ankles, and hands. The symptoms characterizing acute RRV infection vary in duration and may be followed by persistent or recurrent episodes of arthralgia and fatigue that last more than a year in a significant proportion of individuals (4). Notwithstanding the prolonged period of time during which symptoms of RRV infection can persist, the virus has been identified in patients only during the first week of disease. It can be cultured from serum before the appearance of antibody, which is usually detectable within 7–10 days after the appearance of symptoms. Viral antigen has been identified in synovial fluid monocytes and macrophages in the first week of symptoms (5). Studies of the skin rash that may accom- pany infection have demonstrated RRV antigen in the basal epidermal and eccrine duct cells, but again, only early in the disease (6). Information regarding the pathology of RRV infection in joints is limited. The synovial fluid, which has been more extensively studied than the synovium itself, has a predominantly mononuclear cellular infil- trate throughout the disease course. This is observed in patients with other viral arthritides (4), but is in contrast to the predominantly neutrophilic infiltrate observed in patients with rheumatoid arthritis and other inflamma- tory arthropathies (7). Information on synovial mem- brane histology is limited to a single published report on tissue obtained during the first week of infection from 1 patient with RRV synovitis (8). That report did not provide a detailed histologic profile. Repeated attempts to isolate or demonstrate the virus in inflamed joints have failed, except for one demonstration of viral anti- gen in synovial fluid monocytes obtained during the first week of illness (5). Thus, at the outset of this study, knowledge of the basic immunopathology of the arthritis of RRV infec- Supported by the Arthritis Foundation of Australia and Rotary Health Research funding. Muriel Soden, MD, Helen Vasudevan, BASc, Brenda Rob- erts, PhD, Robert Coelen, PhD, Gary Hamlin, PhD, Subash Vasude- van, PhD, Justin La Brooy, MD: University of Queensland, Townsville, Australia. Address correspondence to Justin La Brooy, MD, Depart- ment of Medicine (North Queensland Clinical School), University of Queensland, Townsville, Queensland 4810, Australia. Submitted for publication December 9, 1998; accepted in revised form October 12, 1999. 365