Download antibodies (1:640, speckled pattern), anti-Ro (SS

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. K1,
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-
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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),