[Seronegative spondylarthropathy: variable manifestations, common characteristics]. / Seronegatieve spondylartropathie: variabele verschijningsvormen, gemeenschappelijke kenmerken.

A 38-year-old man and a 35-year-old woman had a 5 and 15 year history, respectively, of oligoarthritis, enthesitis, tendinitis, bursitis, and uveitis, all of varying severity. The diagnosis of these various features and symptoms, which were initially hard to classify, was undifferentiated spondylarthropathy, a member of the family of HLA-B27-associated seronegative spondylarthropathies. The arthritis of peripheral joints of the woman responded to a conventional disease-modifying antirheumatic drug (methotrexaat), but she eventually developed typical ankylosing spondylitis. The spondylarthropathy of the male patient remained undifferentiated and was refractory to conventional disease-modifying antirheumatic drugs, but it responded very well to the TNFalpha-blocking agent adalimumab. Spondylarthropathy includes several chronic, slowly progressive, inflammatory diseases. The treatment of spondylarthropathy comprises life-style advice, physical therapy, non-steroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and local glucocorticoid injections. Conventional disease-modifying antirheumatic drugs fail to inhibit axial inflammation in spondylarthropathy, in contrast to TNFalpha-blocking agents. Early treatment of patients with severe spondylarthropathy with TNFalpha-blocking agents may prevent structural damage and functional disability.

[Diagnostic image (290). A woman with painful finger joints and swelling]. / Diagnose in beeld (290). Een vrouw met pijnlijke vingergewrichten met zwelling.

A 38-year-old woman with chronic pain of and swelling located at the proximal interphalangeal (PIP) finger joints suffered from 'knuckle pads' or 'Garrod's fatty pads'.

Antimalarial drug induced decrease in creatinine clearance.

OBJECTIVE: To confirm the antimalarial drug induced increase of creatinine to determine the factors contributing to this effect. METHODS: Patients with rheumatoid arthritis (RA) (n = 118) who have used or still use antimalarials (chloroquine or hydroxychloroquine). Serum creatinines prior to antimalarials and serum creatinines during antimalarials were recorded and the creatinine clearance was estimated. RESULTS: The mean creatinine clearance decreased from 99 ml/min to 92 ml/min (p < 0.001) after the start of antimalarial drugs. Fifty-five percent of the patients with chloroquine compared to 15% of the patients with hydroxychloroquine (chi 2 = 17.8; p < 0.001) had more than 10% decrease of the creatinine clearance. Age (beta = 0.004; p = 0.0002) and the kind of antimalarial (beta = 0.095; p = 0.0002) were strong independent predictors of the decrease of the creatinine clearance in the multiple regression analysis. For patients using chloroquine the mean age adjusted decrease of creatinine clearance was 11.2%. CONCLUSION: Antimalarials cause a significant reduction of the creatinine clearance. The use of chloroquine and older age were associated with decreased creatinine clearance. Whether antimalarials affect glomerular filtration or tubular excretion of creatinine remains to be investigated.

Cyclosporine in common clinical practice: an estimation of the benefit/risk ratio in patients with rheumatoid arthritis.

OBJECTIVE: To investigate in common clinical practice the toxicity/efficacy ratio of low dose cyclosporine A (CsA) in patients with advanced rheumatoid arthritis (RA) after 12 months CsA administration. METHODS: One hundred and two patients with RA were included in the study. The initial dose of CsA was 2.5 mg/kg/day, the mean maximum dose was 3.2 mg/kg/day and the dose at 12 months was 2.8 mg/kg/day. RESULTS: Sixty-nine (68%) patients completed 12 months of treatment. Seventeen (17%) patients discontinued for lack of efficacy and 16 (16%) for toxicity (of which 50% for gastrointestinal intolerance). The clinical efficacy variables improved significantly by 36-42% between entry and Month 6 and remained stable thereafter. The C-reactive protein decreased from 43 U/ml at entry to 22 U/ml (p < 0.0001) at 12 months. Forty-four percent of the patients and 47% of the physicians judged the efficacy as good or very good. The median number of adverse events/patient was 3 but most adverse events were either not clinically important or disappeared after dose reduction. Gastrointestinal (GI) intolerance and nephrotoxicity (> 30% increase in serum creatinine) each occurred in 50% of the patients. GI intolerance was transient in 80% of the patients but accounted for 50% of the premature discontinuations for toxicity. Nephrotoxicity persisted in the 50% of the patients in whom it occurred, despite dose reduction. The mean serum creatinine rose from 70 (13) mumol/l at entry to 86 (23) mumol/l at 12 months (23% increase; p < 0.0001), and this increase had been entirely reached after 3 months. Variables that could significantly predict the occurrence of nephrotoxicity could not be identified. CONCLUSION: CsA can be safely and effectively administered to patients with RA for a duration of at least 12 months. An acceptable renal function at entry, close monitoring of the serum creatinine concentration and dose reductions when appropriate are prerequisities.

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.

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.

Lymph node histology simulating T-cell lymphoma in adult-onset Still's disease.

A patient with adult-onset Still's disease (AOSD) underwent lymph node biopsy as part of initial evaluation for fever of unknown origin. The lymph node histology showed a massive, diffuse immunoblastic hyperplasia, simulating T-cell lymphoma. This nodal histology differs from rheumatoid arthritis, where mostly a follicular B-cell reaction predominates. Evaluating fever of unknown origin when one is unacquainted with this massive immunoblastic hyperplasia can lead to the wrong diagnosis of T-cell lymphoma in patients with AOSD.

Comparison of cyclosporine and D-penicillamine for rheumatoid arthritis: a randomized, double blind, multicenter study.

Ninety-two patients with active rheumatoid arthritis (RA) were entered in a randomized double blind study of 24 weeks comparing cyclosporine (initial daily dose 5 mg/kg) with D-penicillamine (initial daily dose 250 mg). The groups were well balanced in baseline characteristics. In the cyclosporine group, 10 patients stopped prematurely, one because of inefficacy. In the D-penicillamine group, 9 patients stopped prematurely, 3 because of inefficacy. The 2 antirheumatic drugs were equally effective in reducing disease activity, except for a significant (p = 0.005) decrease in erythrocyte sedimentation rate with D-penicillamine treatment. We conclude that under the conditions of this trial, cyclosporine can serve as an alternative to D-penicillamine for the treatment of patients with RA.

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.

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.

Effect of cyclosporin on serum creatinine in patients with rheumatoid arthritis.

Serum creatinine levels were measured before, during and after the administration of cyclosporin (Cy) in a double-blind placebo-controlled study in patients with rheumatoid arthritis (RA). The level rose significantly during and after Cy therapy, whereas the initial serum creatinine value did not change in the placebo group. The increase in the Cy group was not correlated with the mean Cy blood level. The rise in serum creatinine during Cy therapy was gradual and was not significantly correlated with the initial creatinine level; relative to the pretreatment value, the post-treatment increase was significantly correlated with the increase during Cy therapy. It is concluded that Cy administration for not more than 6 months, and at a maximum dosage of 10 mg/kg for 2 months, leads to an irreversible loss of more than 10% of renal function in RA patients. The damage may be ascribed to the combination of Cy with other factors compromising the kidneys, e.g., the use of non-steroidal anti-inflammatory drugs in the potentially systemic disorder of RA.