Staffordshire Rheumatology Centre, The Haywood, High Lane, Stoke-on-Trent ST6 7AG, UK
SIR, Arthritis is a rare complication of varicella-zoster virus (VZV) infection in children [1, 2, 3], and most commonly presents as a monoarthritis. Occasionally, infectious VZV has been isolated from synovial fluid [3] and recently viral DNA has been demonstrated in synovial fluid of individuals with suspected varicella arthritis using a polymerase chain reaction-based assay [4]. Arthritis associated with VZV is not well documented in adults, and VZV isolation from the synovial fluid has been reported in only one case of an adult with zoster-associated arthritis [5].
We report the case of a 30-yr-old nurse who attended clinic with a painful, swollen left knee after an episode of chickenpox 2 weeks previously. She had presented with swelling of this joint on three occasions before the varicella infection. The first occasion was 4 yr previously, when she presented with a swollen knee which became progressively more painful. She stopped work for 2 months but it did not settle. Aspiration and injection helped transiently and subsequent arthroscopy revealed an inflamed synovium. At the time there was no evidence of a precipitating infection. Six months after presentation she attended the clinic again with a painful, swollen left knee with a warm effusion. The joint was aspirated and injected with Lederspan (triamcinalone). The synovial fluid total leukocyte count was 5800/mm3 and occasional calcium pyrophosphate dihydrate crystals were present. Other laboratory parameters were normal except for raised C-reactive protein (CRP) (9 mg/l), and the patient was found to be HLA-B27-positive. Voltarol (diclofenac) was prescribed.
At the next two visits the patient was much better and although she sometimes experienced aching in her left knee there was no swelling, fluid or synovitis present. She stopped taking Voltarol. She remained well for several months but then gradually deteriorated, the left knee becoming more painful and swollen again. She experienced aching in the right ankle and synovitis of the left elbow. Forty millilitres of synovial fluid was aspirated from the knee, and analysed. The total leukocyte count was 7200/mm3, with 51% polymorphonuclear cells, 33% lymphocytes and 17% macrophages. No crystals were present. Although there had been no symptoms of precipitating infection, serology for Campylobacter demonstrated an elevation in IgM antibodies, which had a titre of 1:320 (borderline high). All other laboratory tests were normal apart from raised CRP (18 mg/l). On this occasion synovial fluid mononuclear cells were isolated by Ficoll separation. These were incubated with a panel of bacterial antigens (Campylobacter jejuni, Salmonella typhimurium, S. enteriditis, Yersinia enterocolitica, Shigella flexneri, Chlamydia trachomatis), and the proliferation of T cells was measured by tritiated thymidine uptake after 5 days. The highest synovial fluid T-cell response was against Campylobacter [stimulation index (SI) = 56], although significant responses to the other bacterial antigens were seen. No significant responses were seen with peripheral blood T cells. Excess synovial fluid cells were saved and frozen in liquid nitrogen.
The patient's condition improved. She became pregnant, but 6 months after delivery her symptoms returned during an episode of chickenpox. She experienced an aching left knee, though it is not clear whether this was before or after the rash appeared. Two weeks later it became more painful and swollen, along with aching in the right knee and index finger. Both knees were aspirated and injected with Lederspan. The synovial fluid analysis showed a total leukocyte count of 13 400/mm3, with 76% polymorphonuclear cells, 6% lymphocytes and 18% macrophages. There were no crystals present. Synovial fluid mononuclear cells were isolated again and incubated with the same panel of bacterial antigens plus a group of viral antigens: herpes, measles, respiratory syncytial virus, mumps, Coxiella burnetti, influenza A, influenza B, rubella, adenovirus, cytomegalovirus and VZV. The T-cells were incubated for 5 days before addition of [3H]thymidine. T-cell responses to the bacterial antigens were similar to those obtained previously, with the greatest response against Campylobacter (Fig. 1). In the case of the viral antigens, only T cells incubated with the VZV antigen showed a significant response (Fig. 2
), which was similar to that against Campylobacter. Peripheral blood T cells were not tested at this time, but were later found to show a smaller but significant response (SI = 44) to VZV 8 weeks after the chickenpox infection. No responses to bacterial antigens were found in peripheral blood cells. We were unable to detect VZV antigen in synovial fluid or peripheral blood cells using Western blotting and a VZV-specific antibody. The T-cell assay was repeated using the cryopreserved synovial fluid mononuclear cells saved from the previous cell separation (prior to chickenpox) and incubated with the same panel of bacterial and viral antigens. The responses to the bacterial antigens were essentially the same, but there was no response to any of the viral antigens, including the VZV antigen.
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Notes
Correspondence to: D. L. Mattey.
References