Raised serum IgA to common cell envelope antigens supports enterobacterial inductive contribution to pathogenesis of secondary ankylosing spondylitis.

Ankylosing spondylitis (AS) is closely associated with the histocompatibility antigen HLA-B27. Pathogenesis of AS is thought to involve interactions between B27 and certain enterobacterial antigens. However, enterobacterial involvement is uncertain and contested by some. The present paper demonstrates raised serum IgA to a common enterobacterial heat modifiable major outer membrane protein (h-momp; Mr 35,000) in active AS (N = 25; IgA = 1485 +/- 20) compared with controls, who were hospital patients without known arthropathies or gastro-intestinal disease (N = 12; IgA = 548 +/- 59). Serum IgG and IgM did not differ statistically. Raised serum IgA to h-momp might indicate enterobacterial antigenic stimulation from the gastro-intestinal tract and thus support an inductive contribution of enterobacterial antigens to the pathogenesis of secondary AS. It does not necessarily imply direct involvement in the pathogenesis of primary AS. H-momp appears to be a convenient tool for serological studies of AS and at present is likely to be more suitable than other bacterial antigens.

Cyclosporine in rheumatoid arthritis.

The efficacy and toxicity of cyclosporine in the treatment of patients with rheumatoid arthritis (RA) are reviewed. Most of the early trials were restricted to patients with intractable RA. The initial daily dose of cyclosporine was 5 to 10 mg/kg, which is now considered high. Of 283 cyclosporine-treated patients in nine studies, 8% discontinued the drug prematurely because of inefficacy and 17% because of adverse reactions. Cyclosporine improves clinical parameters but does not influence the erythrocyte sedimentation rate. The most important side effects are gastrointestinal intolerance and nephrotoxicity. The former is of minor importance with the present dosage schedule (starting daily dose, 2.5 mg/kg), and increments should follow the principle "go low, go slow." Guidelines are given to avoid or reduce nephrotoxicity. It may be beneficial to administer cyclosporine early in the course of RA.

Ankylosing spondylitis and peripheral joint disease.

We reviewed 13 patients with Ankylosing Spondylitis and radiologically demonstrated peripheral arthritis. Due to seriousness and extensiveness, we could distinguish three subgroups.

Plasma viscosity and erythrocyte sedimentation rate in inflammatory and non-inflammatory rheumatic disorders.

Plasma viscosity (PV) and erythrocyte sedimentation rate (ESR) are considered to reflect the complex of acute phase reactants in inflammations. Both tests were studied with regard to their ability to discriminate between inflammatory and non-inflammatory rheumatic diseases. PV and ESR were measured using the Coulter Viscometer II and the Westergren method, respectively. ESR was found to be a better parameter for rheumatoid arthritis and ankylosing spondylitis than PV, independent of the chosen reference values, age, gender and the hemoglobin level. ESR may still be regarded as an acceptable parameter for monitoring inflammatory rheumatic diseases.

Sequential joint scintigraphy in rheumatoid arthritis.

In this sequential study joint scintigraphy was compared with clinical and röntgenological evaluation in 19 patients with rheumatoid arthritis. Scintigraphy sometimes preceded clinical and radiological abnormalities and scan results were independent of radiological findings showing no differences when large and small joints were compared. Scan findings in 2 patients with arthralgias only were negative, suggesting that arthritis was unlikely.

Chloroquine therapy in patients with recent-onset rheumatoid arthritis: the clinical response can be predicted by the low level of acute-phase reaction at baseline.

If rheumatoid arthritis (RA) patients with a mild disease course could be identified early in the phase of the disease, therapy with less aggressive and probably less toxic antirheumatic drugs seems to be rational. The aim of this study was to investigate which factors at baseline could predict a clinical response (American College of Rheumatology preliminary response criteria) after treatment with chloroquine for 16 weeks. Two hundred and three early RA patients with active disease were treated with oral chloroquine sulphate (Nivaquine) at a daily dose of 300 mg during the first 4 weeks, 200 mg during the second 4 weeks and 100 mg thereafter. One hundred and eighty-three patients (90%) completed the study and 20 patients prematurely discontinued treatment. Of all the patients, 43 patients (21%) met the response criteria. A low level of C-reactive protein (CRP) was the only independent predictor for clinical response [relative risk: 0.97 (95% confidence interval: 0.95-0.98)]. It was concluded that a clinical response to chloroquine therapy in early RA patients can be predicted by a low CRP level at baseline.

[No difference in effectiveness measured between treatment in a thermal bath and in an exercise bath in patients with rheumatoid arthritis]. / Geen verschil in effectiviteit gemeten tussen behandeling in een thermaalbad en in een oefenbad bij patiënten met reumatoïde artritis.

OBJECTIVE: To determine whether hydrotherapy in a thermomineral institution is superior to the same hydrotherapy in an ordinary hospital exercise-bath. DESIGN: Controlled therapeutic trial. SETTING: The thermomineral institution at Arcen and the exercise bath at the Maasland Hospital in Sittard, the Netherlands. PATIENTS AND METHODS: 46 patients with rheumatoid arthritis were treated in a by a skilled physiotherapist, according to a standardized exercise-scheme: 27 were treated in the thermomineral institution and 19 (control-group) in the hospital exercise-bath. Each patient received 12 treatments in 12 weeks. ENDPOINTS PARAMETERS: Morning stiffness, erythrocyte sedimentation rate, Ritchie index, amount of pain, answers to 11 questions concerning the activities of daily life, and psychosocial aspects of the disease. The various subjective and objective parameters were scored by the same physician. RESULTS: Statistically significant improvement was observed in both groups concerning morning stiffness. Other subjective parameters improved, but did not reach significance. Objective parameters did not change significantly. Between-group differences were not found. CONCLUSION: Hydrotherapy has a positive effect on some subjective but not on objective parameters in patients with rheumatoid arthritis, whether it is applied in a thermomineral institution or an ordinary hospital exercise bath.

Isolated lesions of the manubriosternal joint in patients with inflammatory back pain and negative sacroiliac and spinal radiographs.

The prevalence of radiological lesions of the manubriosternal joint was assessed in 151 patients with chronic inflammatory back pain and in 31 controls with non-inflammatory back pain. Nineteen out of these 151 patients and none of the controls showed unequivocal lesions of the manubriosternal joint without accompanying radiological lesions of the sacroiliac joints or the lumbar spine. Thoracic pain and stiffness were present in 7 out of the 19 patients and in 3 out of the 31 controls (P less than 0.05); peripheral enthesopathy was present in 10 out of the 19 patients and in 4 out of the 31 controls (P less than 0.01); none of the patients or controls had rheumatoid factor, subcutaneous nodules, or peripheral arthritis. The suggestion of a "manubriosternal joint syndrome" is warranted by these findings.

A double-blind, randomized trial to compare meloxicam 15 mg with diclofenac 100 mg in the treatment of osteoarthritis of the knee.

Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID), which, in animal tests, displays a high potency for anti-inflammatory and analgesic action. The aim of this study was to investigate the efficacy and tolerability of 15 mg meloxicam in comparison with 100 mg slow-release diclofenac in patients with osteoarthritis of the knee. Two hundred and fifty-eight patients were included in the intent-to-treat analysis; these were randomized into two groups to receive either 15 mg meloxicam (N = 128) or 100 mg diclofenac (N = 130) for a period of 6 weeks. The results with respect to efficacy showed a trend in favor of meloxicam regarding pain on movement, global efficacy and paracetamol consumption, although these differences did not reach statistical significance. The most frequently-occurring adverse events in both groups were of a gastrointestinal (GI) nature. However, there was a higher incidence (26 vs 16%) of GI adverse events in the diclofenac group compared with the meloxicam group. Both drugs were well tolerated when assessed by the patients on a visual analog scale (VAS). Thus, 15 mg meloxicam is an effective and well-tolerated therapy for osteoarthritis and compares favorably with diclofenac 100 mg, a well-established treatment for this indication.

Reversible nephrotoxicity of cyclosporine in rheumatoid arthritis.

Irreversible nephrotoxicity has limited the use of cyclosporine in rheumatoid arthritis (RA). In a randomized clinical trial we compared 26 weeks of cyclosporine (5 mg/kg) and D-penicillamine (250 mg) treatment in 92 patients with RA with a serum creatinine less than 100 mumol/l. We adjusted the starting dose according to clinical response and side effects. During cyclosporine treatment the serum creatinine increased by median 15% (p less than 0.0001 vs baseline), quickly reversible after stopping (median followup: 1.6 years). Six patients stopped cyclosporine prematurely because of nephrotoxicity. In the D-penicillamine group the values remained at baseline.

Enterobacterial involvement in the pathogenesis of secondary ankylosing spondylitis.

Ankylosing spondylitis (AS) is closely associated with the histocompatibility antigen HLA-B27. Pathogenesis of AS is thought to involve interactions between B27 and certain enterobacterial antigens. However, this is uncertain and contested by some. The present paper argues that the presence of statistically raised specific serum IgA to a common enterobacterial heat modifiable major outer membrane protein (h-momp; Mr 35,000) in active AS (N = 25; IgA = 1485 +/- 20) in comparison to controls, most notably hospital patients without known arthropathies or gastrointestinal disease (N = 12; IgA = 548 +/- 59), supports an inductive contribution of enterobacterial antigens to the pathogenesis of secondary AS. Serum IgG and IgM did not statistically differ. Raised specific serum IgA to h-momp might indicate enterobacterial antigenic stimulation from the gastrointestinal tract. It does not necessarily imply direct involvement in the pathogenesis of primary AS. H-momp appears to be a convenient tool for serological studies of AS and at present is likely to be more suitable than other bacterial antigens, notably those with B27-like epitopes. Namely, the confirmed presence in AS of enterobacteria with freely accessible B27-like antigenic epitopes on their cell surface might induce unusual tolerance to these organisms in B27 positive hosts, thus causing chronic inflammation, initially sacroiliitis (and spondylitis) due to the proximity of presacral and para-aortic colon draining lymph nodes, later becoming more generalized (for reasons unclear) to include other lesions (e.g. peripheral arthritis, uveitis, enthesopathies). Thus, antibodies to B27-like antigenic epitopes need not be detectable or may be absent. Also, cellular immune responsiveness to these antigens might be involved.

Antibodies to Enterobacteriaceae in ankylosing spondylitis.

Serological studies on ankylosing spondylitis (AS; N = 82) show that although statistically more AS patients than controls (N = 24) may possess elevated serum titres to enterobacteria such as Salmonella, Shigella and Yersinia, this does not necessarily imply enterobacterial involvement in AS, as other groups without enteritis or arthropathies that frequent health care facilities (N = 72) may also display this phenomenon, presumably due to increased exposure. Moreover, an inventory of all detectable antibody reactivities to the separated cell envelope antigens of five enterobacterial species suspected of involvement in AS (notably Enterobacter, Klebsiella, Salmonella, Shigella and Yersinia) failed to reveal statistical associations with AS. This might be explained, assuming that the aetiology of AS entails a set of enterobacteria rather than a few individual species. It is proposed that serological studies on AS should be supported by additional information, e.g. that of the faecal carriage, and that these combined studies encompassing other enterobacteria, in addition to Klebsiella, might be fruitful.

Lyme borreliosis: a very infrequent cause of arthritis of undetermined aetiology in the southern part of The Netherlands.

Seventy-three patients with undiagnosed arthritis of undetermined aetiology, 94 patients with classified arthritis (rheumatoid arthritis, ankylosing spondylitis, etc.) and 70 controls were studied for clinical and serological manifestations of Lyme borreliosis. The patients were recruited from the three rheumatology units in the most southern part of The Netherlands. A clinical diagnosis of possible Lyme borreliosis was made in seven of 73 patients with arthritis of undetermined aetiology, in four of 94 patients with classified arthritis and in one of the controls. A definite diagnosis of Lyme borreliosis could be made in only one patient who belonged to the arthritis of undetermined aetiology group. This patient had erythema migrans, arthritis of the knee joint and showed positive antibodies to B. burgdorferi. In the southern part of The Netherlands, Lyme arthritis does not seem to be a frequent cause of arthritis of undetermined aetiology.

Longterm cyclosporine therapy in rheumatoid arthritis.

Sixteen patients who had shown a good clinical response to cyclosporine therapy during a randomized 6-month double blind study comparing cyclosporine with D-penicillamine in active rheumatoid arthritis, had an opportunity to participate in an open study with cyclosporine. The initial daily dose of cyclosporine was 5 mg/kg. Before the planned maximal duration of 18 months, there were 6 premature discontinuations, 2 because of inefficacy, 2 because of side effects, and 2 for other reasons. During the study there was an improvement in all clinical variables. Even under the strict conditions of our trial there was an irreversible loss of about 15% of renal function. Suggestions are given to minimize the chance of nephrotoxicity.

A randomized, double-blind, 24-week controlled study of low-dose cyclosporine versus chloroquine for early rheumatoid arthritis.

OBJECTIVE: To investigate whether low-dose cyclosporin A (CSA) is safe and effective in comparison with chloroquine (CQ) in patients with early rheumatoid arthritis (RA). METHODS: We performed a randomized, double-blind study comparing CSA with CQ in patients with early RA (duration < 2 years) who had had active disease for at least 3 months. Forty-four RA patients with a mean disease duration of 6 months were randomly allocated to receive CSA (initial dosage 2.5 mg/kg/day, maintenance dosage 3.6 mg/kg/day) or CQ (initial dosage 300 mg/day, maintenance dosage 100 mg/day) for 24 weeks. RESULTS: Five patients (2 taking CSA and 3 taking CQ) discontinued the study prematurely. Intention-to-treat analysis disclosed a decrease in the swollen joint count by 7 in both groups. The erythrocyte sedimentation rate and C-reactive protein level did not change significantly. CSA and CQ were tolerated equally well, although mild paraesthesia occurred more frequently in the CSA-treated group. The serum creatinine level increased by 13 mumoles/liter (95% confidence interval [95% CI] 4, 22) in the CSA group and by 6 mumoles/liter (95% CI 1, 11) in the CQ group (difference not statistically significant). CONCLUSION: Both CSA and CQ are effective in alleviating the symptoms of active early RA. There is only slightly impaired renal function after 24 weeks of drug administration of either drug in patients with early RA.