J. W. J. Bijlsma

Deforming arthropathy or lupus and rhupus hands in systemic lupus erythematosus

OBJECTIVE Although deforming arthropathy in systemic lupus erythematosus (SLE) is characterised by a number of manifestations, definitive criteria for the different forms have not yet been established. To define deforming arthropathy and its different types a study was undertaken of 176 SLE patients. METHODS Using as criterion any deviation from any of the metacarpus finger axes 17 patients (16 women, one man) were identified with clinical deforming arthropathy. These patients were evaluated according to a standardised protocol that covered all known characteristics of deforming arthropathy. By means of “Jaccoud’s arthropathy index” three different forms were identified. RESULTS Three patients had an erosive form of deforming arthropathy (or rhupus hand) such as those seen in frank rheumatoid arthritis (RA), eight patients were identified as having Jaccoud’s arthropathy (or lupus hand), and the remaining six patients had mild deforming arthropathy. Jaccoud’s arthropathy is characterised by severe deformation of the hands (ulnar deviation, swan neck deformities, and Z deformity of the thumb) and feet with multiple non-erosive subluxations, mild aching and little or no evidence of synovitis. All patients, but one, fulfilled just four criteria of the ACR classification and joint symptoms were always found to precede the diagnosis of SLE. Furthermore a remarkable association of Jaccoud’s arthropathy with fetal loss, thrombosis—both venous and arterial—and the presence of antiphospholipid antibodies was found. CONCLUSIONS These data suggest that Jaccoud’s arthropathy represents a subset of SLE. Subdivision of deforming arthropathy into several clinical forms can facilitate the clinical management of this disorder.

Changes in (markers of) bone metabolism during high dose corticosteroid pulse treatment in patients with rheumatoid arthritis.

OBJECTIVE: To examine the effect of high dose corticosteroid pulse treatment (three times 200 mg dexamethasone intravenously in eight days) on calcium and bone metabolism in 17 consecutive patients with active rheumatoid arthritis (RA). METHODS: Bone formation was quantified by measurement of serum alkaline phosphatase, osteocalcin, and carboxyterminal propeptide of type I procollagen (pro-I-CPP) concentrations. Bone resorption was measured by urinary excretion of calcium, hydroxyproline, (free and total) deoxypyridinoline (Dpyr), (free and total) pyridinoline (Pyr), and serum concentrations of the carboxyterminal cross linked telopeptide of type I collagen (I-CTP). Disease activity of RA was measured by erythrocyte sedimentation rate, C reactive protein, and Ritchie and Thompson joint scores. RESULTS: Disease activity was initially high, and decreased during corticosteroid pulse treatment and the following five weeks. Osteocalcin, alkaline phosphatase, and pro-I-CPP concentrations were initially within normal limits, while I-CTP, Dpyr, and Pyr were increased. Osteocalcin and pro-I-CPP concentrations decreased (p < 0.01) during corticosteroid pulse treatment, but rapidly returned to baseline after the treatment. No changes were observed in alkaline phosphatase and urinary excretion of calcium and hydroxyproline. Bone resorption measured by serum I-CTP and urinary excretion of Pyr and Dpyr was unchanged or decreased (p < 0.05-0.01), depending on the time of measurement and the parameter measured. CONCLUSIONS: In these patients with active RA, bone resorption was increased, while bone formation was within normal limits. During high dose corticosteroid pulse treatment, bone formation was only transiently decreased, while markers of bone resorption were unchanged or decreased. Because corticosteroid pulse treatment has only a short term negative effect on bone formation, and because it probably reduces bone resorption, at least partly as a result of the decreased disease activity, the effect of corticosteroid pulse treatment on bone may be assumed to be relatively mild.

Aggressive treatment in early rheumatoid arthritis: a randomised controlled trial

OBJECTIVES To compare three therapeutic strategies using slow acting antirheumatic drugs (SAARDs) in early rheumatoid arthritis (RA), for their disease modifying properties, toxicity, and lag time until treatment effect. METHODS Patients with recent onset RA from six hospitals were randomly assigned to immediate initiation of one of three treatment strategies: (I) a “mild SAARD with a long lag time” (hydroxychloroquine, if necessary replaced by auranofin); (II) a “potent SAARD with a long lag time” (intramuscular gold, if necessary replaced byd-penicillamine); (III) a “potent SAARD with a short lag time” (methotrexate, if necessary replaced by sulfasalazine). Comparisons included two years of follow up. RESULTS All SAARD strategies reduced mean disease activity. A greater percentage of patients improved clinically with strategies II and III than with strategy I: percentages of patients improved on joint score with strategies II and III (79% and 82%, respectively), which was statistically different from strategy I (66%). The same was true for remission percentages: 31% and 24% v 16%, respectively). Longitudinal analysis showed significantly less disability with strategy III, and a lower erythrocyte sedimentation rate with strategy II than with strategy I. In addition, radiological damage after one and two years, was significantly lower in strategies II and III (at two years median scores were 11 and 10v 14 in strategy I, p<0.05). Toxicity was increased in strategy II compared with the other strategies. CONCLUSION Strategy III, comprising methotrexate or sulfasalazine, produced the best results weighing effectiveness and toxicity. Strategy I (hydroxychloroquine or auranofin) was slightly less effective, and strategy II (intramuscular gold or d-penicillamine) was associated with increased toxicity.

Is addition of sodium fluoride to cyclical etidronate beneficial in the treatment of corticosteroid induced osteoporosis

OBJECTIVE To investigate whether administration of sodium fluoride (NaF) in addition to cyclical etidronate has a positive effect on bone mineral density (BMD) in patients with established osteoporosis during continued treatment with corticosteroids. PATIENTS AND METHODS 47 patients who were receiving treatment with corticosteroids were included in a two year randomised, double blind, placebo controlled trial. Established osteoporosis was defined as a history of a peripheral fracture or a vertebral deformity, or both, on a radiograph. All patients were treated with cyclical etidronate, calcium, and either NaF (25 twice daily) or placebo. Vitamin D was supplemented in the case of a low serum 25 (OH) vitamin D concentration. BMD of the lumbar spine and hips was measured at baseline and at 6, 12, 18, and 24 months. RESULTS After two years of treatment, the BMD of the lumbar spine in the etidronate/NaF group had increased by +9.3% (95% confidence intervals (CI): +2.3% to +16.2%, p<0.01), while the BMD in the etidronate/placebo group was unchanged: +0.3% (95% CI: −2.2% to +2.8%). The difference in the change in BMD between groups was +8.9% (95% CI: +1.9% to +16.0%, p<0.01). For the hips, no significant changes in BMD were observed in the etidronate/NaF group after two years: −2.5% (95% CI: −6.8% to +1.8%); in the etidronate/placebo group BMD had significantly decreased: −4.0% (95% CI: −6.6% to −1.4%; p<0.01). The difference between the groups was not significant: +1.5% (95% CI: −3.4% to +6.4%). No significant differences in number of vertebral deformities and peripheral fractures were observed between the two groups. CONCLUSION The effect of combination treatment with NaF and etidronate on the BMD of the lumbar spine in corticosteroid treated patients with established osteoporosis is superior to that of etidronate alone.

Effect of sodium fluoride on the prevention of corticosteroid-induced osteoporosis

To investigate whether sodium fluoride (NaF) is able to prevent bone loss in patients treated with corticosteroids (Cs), we performed a randomized, double-masked, placebo-controlled trial with 44 Cs-treated patients without established osteoporosis, defined as the absence of previous peripheral fractures and vertebral deformities on radiographs. The effects of NaF (25 mg twice daily) and placebo on the bone mineral density (BMD) of the lumbar spine and hips were compared at baseline and at 6, 12, 18 and 24 months. After 2 years, the BMD of the lumbar spine had decreased in the placebo group by 3.0% (95% CI: −4.9% to −1.0%;p<0.01); in the NaF group there was a statistically insignificant increase in BMD of 2.2% (95% CI: −0.8% to +5.3%). The difference in the changes in BMD between the two groups was +5.2% (95% CI: +1.8% to +8.6%;p<0.01). In the hips, BMD had decreased after 2 years in both groups: in the placebo group by −3.0% (95% CI: −5.0% to −1.0%;p<0.05) and in the NaF group by 3.8% (95% CI: −6.1% to −1.5%;p<0.01). The difference in the changes in BMD between the two groups was not significant: +0.8% (95% CI: −2.1% to +3.8%). Three vertebral deformities were observed in the placebo group and one in the NaF group (insignificant difference), while no peripheral fractures occurred during the study period. It is concluded that in Cs-treated patients without established osteoporosis NaF prevents bone loss in the lumbar spine but does not have a positive effect on the BMD of the hips.

Short term effects of corticosteroid pulse treatment on disease activity and the wellbeing of patients with active rheumatoid arthritis

OBJECTIVE To investigate the short term effects of corticosteroid pulse treatment (CPT) on disease activity, functional ability, and psychological wellbeing of patients with active rheumatoid arthritis (RA). METHODS Of 66 consecutive patients with active RA admitted for CPT, erythrocyte sedimentation rate, C reactive protein level, haemoglobin concentration, platelet count, duration of early morning stiffness, a joint score, and grip strength were assessed before and after CPT. Additionally, a health status questionnaire was administered. Effects of CPT were expressed as before to after intervention effect sizes and, to place them in perspective, compared with the (long term) effect sizes of disease modifying antirheumatic drug (DMARD) treatment in a historical contrast group of patients with early RA. RESULTS Statistically significant improvement from baseline in disease activity, physical functioning, and psychological wellbeing after CPT was seen, with moderate to large effect sizes, resembling the effects seen after DMARD treatment. Neither depression nor psychosis occurred during and after CPT. CONCLUSION Qualitatively and quantitatively the short term effects of CPT in patients with active established RA on various dimensions of health status resemble the long term effects of conventional DMARD treatment in patients with early RA. Psychological disorders do not seem to be common short term side effects of CPT in patients with active RA.

Ultrasound Guided Synovial Biopsy of the Wrist

Seven patients (4 female and 3 male, mean age 46) with arthritis of the wrist (n = 7) without known etiology were evaluated. High-definition ultrasound equipment was used for localization of synovial hypertrophy, suitable for ultrasound guided biopsy without risk. A 18-gauge diameter Tru-cut biopsy needle was used in an automated gun. Two passes were performed with continuous guidance of the needle-tip. In all patients representative synovial tissue was obtained in adequate amount. No complications were encountered. Ultrasound guided biopsy is proposed as an effective technique which can be performed with low patient discomfort on an outpatient basis.

Chronic wrist pain: diagnosis and management. Development and use of a new algorithm

OBJECTIVE Chronic wrist pain can be difficult to manage and the differential diagnosis is extensive. To provide guidelines for assessment of the painful wrist an algorithm was developed to encourage a structured approach to the diagnosis and management of these patients. METHODS A review of the literature on causes of chronic wrist pain was undertaken; history taking, physical examination and imaging studies were evaluated systematically to determine which of the many potential conditions was the cause of the wrist pain. Chronic wrist pain was subdivided into pain of probable intra-articular or extra-articular origin. By means of this classification a clinical algorithm was developed to establish a diagnosis and its clinical usefulness was tested in a prospective study of 84 patients presenting to our outpatient clinic. RESULTS A definite diagnosis could be established in 59% (49 of 84) of the cases by careful history taking, extensive physical examination, plain radiographs, ultrasound examination and bone scintigraphy. In 19% of the cases (16 of 84) a probable diagnosis was made resulting in a total figure 78% (65 of 84). Additional imaging studies (arthrography, magnetic resonance imaging and computed tomography) increased the definite diagnoses to 70% (59 of 84). CONCLUSION The algorithm proved easy to use and by the use of careful history taking, thorough physical examination and simple imaging techniques (ultrasonography and scintigraphy) a diagnosis was made in 78% of cases.

Magnetic resonance imaging of the femoral head to detect avascular necrosis in active rheumatoid arthritis treated with methylprednisolone pulse therapy

Efficacious management of patients with avascular necrosis of bone (AVN) necessitates the identification of patients with a high risk of collapse of the femoral head. In this prospective study we imaged both hips of 10 patients with active rheumatoid arthritis, who were treated with methylprednisolone pulse therapy. MRI and conventional radiography were performed before MP-pulse therapy and 6 and 12 months thereafter. Two patients showed unilateral changes, compatible with AVN. One patient became symptomatic and revealed characteristic radiographic abnormalities. The other patient remained asymptomatic and the MRI appearance returned to normal after 6 months.

Lack of a clear disease modifying activity of celecoxib in treatment of end-stage knee osteoarthritis: a rondomized observer blinded clinical trial

Objective: To evaluate the in vivo disease modifying activity of the selective COX-2 inhibitor celecoxib, compared to no-treatment and naproxen, treating end-stage knee osteoarthritis, using detailed ex vivo tissue analyses. Methods: Patients (n=172) with end-stage knee OA were randomized to 4 groups and treated for 4 weeks prior to knee replacement surgery: celecoxib 2dd200mg, naproxen 3dd250mg, celecoxib 2dd200mg stopped 3 days prior to surgery, or no-treatment. Cartilage and synovial tissue collected during surgery were analyzed ex vivo, with cartilage proteoglycan release as primary outcome. Additionally, several markers of synovial inflammation and clinical effects were determined. Results: Data of 138 patients could be analyzed, 34 patients were lost for several reasons. The expression of COX-2 in both cartilage and synovial tissue was statistically significant decreased in patients treated with celecoxib (p=0.017 and p=0.001) respectively), indicating the drug has reached the knee joint within the treatment period. Nonetheless, no significant effect on proteoglycan release, retention or content was found. Synovial inflammation markers did not show any statistically significant decrease although nitric oxide levels in celecoxib treated patients suggest a beneficial effect of celecoxib compared to no treatment. WOMAC scores did not statistically significant improve after treatment; though celecoxib treated patients reported a slightly higher WOMAC pain score compared to non-treated patients. Conclusion: No direct effect on cartilage upon short term in vivo treatment of knee OA patients with celecoxib could be detected, although decreased expression of COX-2 confirmed its intra-articular availability. Effects on synovial inflammatory mediators and clinical outcome seemed only limited. As such the previous reported disease modifying effects of celecoxib in in vitro and pilot clinical studies could not unambiguously be confirmed.