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806 Letters to the Editor antibodies (1:640, speckled pattern), anti-Ro (SS-A) antibodies, cryoglobulins (polyclonal ) and antineutrophil cytoplasmic antibodies (ANCA, c-ANCA 78.3 U/l, p-ANCA negative); antibodies to cardiolipin, DNA and ribonucleoprotein were negative. Serum complement levels were normal. Pathological examination of a salivary gland biopsy specimen revealed 10 large lymphoplasmacytic infiltrates in 20 mm2 of tissue. Fibreoptic bronchoscopic examination was normal; bronchial washings and bronchoalveolar lavage specimens contained 150 000 cells/ml with 85% histiocytes. No acidfast bacilli were detected. Cultures were negative. The patient underwent an open biopsy of the middle lobe of the right lung. Gross examination of the specimen showed several discrete nodules. Microscopic examination revealed granulomatous lesions with central parenchymal necrosis in the form of neutrophilic microabscesses, surrounded by histiocytes and vasculitis of medium-sized vessels, typical of WG. DNA from the lung biopsy material tested positive by multiplex polymerase chain reaction for the presence of the 65-kDa gene of the Mycobacterium tuberculosis complex (M. tuberculosis, M. bovis, M. africanum, M. microti). Based on these findings, possible diagnoses for our patient include: (i) primary SS associated independently with limited WG; and (ii) secondary SS as a feature of the syndrome of Wegener’s vasculitis. An association between WG and SS has been investigated in the past [2–6 ]. Several clinical reports and limited clinical studies have indicated that both the limited and the generalized form of WG may involve the sclera, lachrymal glands and salivary glands [5, 6 ]. It has been reported that major salivary gland involvement may be associated with a limited form of WG and a more favourable prognosis; in these cases, whenever pathological examination was performed the findings were highly suggestive of WG [5]. It is generally accepted that limited forms of WG have a more indolent course and are said to have a better prognosis than the classical disease, but may be extremely challenging to recognize and diagnose. Our patient was treated with methylprednisolone and trimethoprim–sulfamethoxazole per os which has proven effective either as monotherapy or with corticosteroids for the induction of remission in limited WG [7]; the drugs have also been used effectively as relapse prophylaxis after remission in patients with generalized WG [7]. The patient responded favourably to this combined treatment and remains in complete remission. In conclusion, the laboratory results presented herein suggest that, in our patient, primary SS and limited WG evolved independently, SS probably preceding the development of WG and running a mild, asymptomatic course. This suggestion is given further support by the fact that, 2 years after diagnosis, our patient is still free of sicca symptoms. G. K, K. S, C. K1, D. L, G. V First Department of Medicine, University of Athens School of Medicine, Laikon General Hospital, Athens and 1Pathology Department, University of Athens School of Medicine, Athens, Greece Accepted 10 January 2000 Correspondence to: G. Vaiopoulos, Vardousion 13, Ampelokipi, Athens 115 26, Greece. 1. Jenette JC, Falk RJ, Andrassy K, Bacon PA, Churg K, Gross WL et al. Nomenclature of systemic vasculitides: Proposal of an International Consensus Conference. Arthritis Rheum 1994;33:187–92. 2. Moutsopoulos HM, Manoussakis MN. Lumping or splitting autoimmune rheumatic disorders? Lessons from Sjögren’s syndrome. Br J Rheumatol 1998;37:1263–4. 3. Bottinger EP, Niles JL, Collins AB, McCluskey RT, Arnaout MA. Antineutrophil cytoplasmic autoantibody-associated vasculitis presenting as Sjögren’s syndrome. Arthritis Rheum 1992;35:1373–6. 4. Ah-See KW, McLaren K, Maran AG. Wegener’s granulomatosis presenting as major salivary gland enlargement. J Laryngol Otol 1996;110:691–3. 5. Lustmann J, Segal N, Markitziu A. Salivary gland involvement in Wegener’s granulomatosis. A case report and review of the literature. Oral Surg Oral Med Oral Pathol 1994;17:254–9. 6. Stavrou P, Deutch J, Rene C, Laws DE, Luqmani RA, Murray PI. Ocular manifestations of classical and limited Wegener’s granulomatosis. Q J Med 1993;86:719–25. 7. Reinhold-Keller E, DeGroot K, Rudert H, Nolle B, Heller M, Gross WL. Response to trimethoprim/sulfamethoxazole in Wegener’s granulomatosis depends on the phase of the disease. Q J Med 1996;89:15–23. Rheumatology 2000;39:806–808 An unusual case of adult varicella-associated arthritis S, 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 ), Letters to the Editor 807 F. 1. Synovial fluid T-cell responses to bacterial antigens 2 weeks after varicella infection. The stimulation index represents the mean counts per minute (c.p.m.) in the presence of antigen divided by mean c.p.m. without antigen. Phytohaemagglutinin (PHA) was used as a positive control. CM, control medium without antigen. F. 2. Synovial fluid T-cell responses to viral antigens 2 weeks after varicella infection. Only VZV caused a significant T-cell response. CM, control medium without antigen. PHA, phytohaemagglutinin (positive control ). 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 thymid- 808 Letters to the Editor ine 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. This is an unusual case of synovitis. Our results suggest that the latest episode may have been precipitated by the varicella infection, though it is possible that it was coincidental since the patient already had a history of recurrent synovitis. The development of synovitis after infection was more typical of a reactive arthritis than the type of arthritis associated with varicella, which normally develops at the same time or very shortly after the first signs of clinical infection. Nonetheless, the T-cell studies showed that synovial fluid cells had become responsive to VZV antigen, which they had not been prior to varicella infection. Peripheral blood T cells also remained responsive to VZV antigen for at least 8 weeks after infection. However, it is not clear whether the arthritis was triggered directly by the VZV itself or whether the viral infection somehow caused reactivation of the response to bacterial antigens such as Campylobacter. The latter explanation would require that long-term survival of such bacteria had taken place at some site (e.g. the gut), or that reinfection with bacteria had occurred. It is also possible that there may have been some cross-reactivity of T cells with antigens from VZV, Campylobacter and other bacteria, though differences between viral and bacterial antigens may make this unlikely. Although the exact mechanisms are unclear, this case strongly suggests that different bacterial and viral stimuli may trigger synovitis in the same joint at different points in time. E. E, P. T. D, D. L. M Staffordshire Rheumatology Centre, The Haywood, High Lane, Stoke-on-Trent ST6 7AG, UK Accepted 10 January 2000 Correspondence to: D. L. Mattey. 1. Ward JR, Bishop B. Varicella arthritis. J Am Med Assoc 1970;212:1954–6. 2. Mulhern LM, Friday GM, Perri JA. Arthritis complicating varicella infection. Pediatrics 1971;48:827–9. 3. Priest JR, Urick JJ, Groth KE, Balfour HH Jr. Varicella arthritis documented by isolation of virus from joint fluid. J Pediatr 1978;93:990–2. 4. Stebbing S, Highton J, Croxson MC, Powell K, McKay J, Rietveld J. Chickenpox monoarthritis: demonstration of varicellazoster virus in joint fluid by polymerase chain reaction. Br J Rheumatol 1998;37:311–3. 5. Amoura I, Fillet A, Huraux J, Bourgeois P. Isolation of varicella zoster virus from the synovial fluid of a patient with herpes zoster arthritis. Arthritis Rheum 1993;39:1329. Rheumatology 2000;39:808–810 Soluble adhesion molecules in rheumatoid arthritis S, The expression of cell adhesion molecules is up-regulated (or induced) by pro-inflammatory cytokines, and may have a central role in the mechanism of immune-mediated inflammation [1]. In rheumatoid arthritis (RA), pro-inflammatory cytokines such as tumour necrosis factor-a (TNF-a), interleukin-1 (IL-1), IL-6, and IL-8 are produced in excess [2], and they may induce the expression of cell adhesion molecules on endothelial cells and leucocytes [3]. More recently, soluble isoforms of several types of cellular adhesion molecules have been described [4], and previous reports have shown increased levels of serum soluble intercellular adhesion molecule-1 (sICAM-1), sICAM-3 and sP-selectin in RA [5–7]. However, in some cases the data are contradictory, especially regarding their association with disease activity. We analysed 35 patients (28 females, age: 47.0 ± 15.2 yr; mean ± ..) with RA according to American Rheumatism Association (ARA) criteria [8]. Patients received anti-rheumatic medications including non-steroidal anti-inflammatory drugs (NSAIDs) (n = 35); remittive agents, gold, penicillamine, antimalarials, sulphasalazine (n = 25); methotrexate (n = 3), and prednisolone (<10 mg/day; n = 9). Clinical variables included: disease duration (43.2 ± 38.1 months),