What factors influence functional ability in patients with rheumatoid arthritis. Do they alter over time?

OBJECTIVES: To describe the changes in functional ability (FA) taking place over 5 yr in patients with rheumatoid arthritis (RA) starting disease-modifying anti-rheumatic drug (DMARD) therapy, to investigate the factors having most influence upon FA and to compare these factors at baseline and after 5 yr of treatment. METHODS: Three hundred and sixty-six patients with active RA were studied as part of a 5-yr randomized controlled study of DMARD therapy. FA was assessed by Health Assessment Questionnaire (HAQ) score every 6 months. Multiple linear regression was used to identify factors affecting FA at baseline and at 5 yr. The independent variables used were age, sex, visual analogue scale (VAS) pain, Ritchie articular index, C-reactive protein (CRP), Larsen score and log-transformed morning stiffness (EMS). RESULTS: Mean HAQ score was 1.64 at baseline, improved by 21% at 1 yr and gradually returned towards baseline levels by 5 yr. At baseline only 34% of variance in HAQ score could be explained; the most significant explanatory variables were the Ritchie articular index and CRP. At 5 yr the variance explained was 60%. The Ritchie articular index remained the strongest factor followed by VAS pain, log(10) EMS and Larsen score. CONCLUSIONS: Improvement in function did occur after commencement of the first DMARD therapy but was not maintained to 5 yr. The most consistent factor affecting function was joint tenderness. Global pain and duration of EMS were of lesser importance. Disease activity measures such as the CRP exerted an influence in the earlier, more active stages of disease: radiographic damage assumed greater importance as the arthritis progressed.

Serum soluble interleukin 2 receptor levels and radiological progression in early rheumatoid arthritis.

OBJECTIVE: To investigate the association between serum soluble interleukin 2 receptor (sIL-2R) levels and radiological changes in patients with early rheumatoid arthritis (RA). METHODS: sIL-2R levels from 155 patients with active RA were measured by immunoassay over a 2 year period and the associations with radiological change and other measures of disease activity were analyzed. RESULTS: The area under the curve for sIL-2R is weakly associated with the change in the modified Larsen score over a 2 year period; this is weaker than the association of radiological change with serum C-reactive protein. CONCLUSION: We found no significant association of sIL-2R levels with erosive change in early RA.

Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis.

OBJECTIVE: An elevated acute-phase response is associated with increased radiologic damage in rheumatoid arthritis (RA), but development of damage in previously normal joints ("new joint involvement") has not previously been investigated. This study was undertaken to investigate the hypothesis that when there is suppression of disease activity as judged by the C-reactive protein level, new joint involvement is reduced to a greater extent than is progression in already damaged joints ("damaged joint progression"). METHODS: Three hundred fifty-nine patients with active RA were studied as part of a 5-year randomized, prospective, open-label study of disease-modifying antirheumatic drug therapy. Time-averaged CRP was calculated from samples obtained every 6 months, and patients were divided into groups with CRP values of <6, 6-<12, 12-<25, and > or =25 mg/liter. Radiographs of the hands and feet were scored by the Larsen method; a damaged joint was defined as one with a score of > or =2. RESULTS: The rank correlation between time-integrated CRP and increase in Larsen score was 0.50; the correlation increased to 0.59 for patients entering the study with disease duration of < or =2 years. The percentage of new joint involvement over 5 years varied markedly with time-integrated CRP, from 7.3% in the CRP <6 mg/liter group to 39.1% in the CRP > or =25 mg/liter group (5.4-fold increase). The percentage of damaged joint progression increased from 26.1% in the CRP <6 mg/liter group to 41.6% in the CRP > or =25 mg/liter group (1.6-fold increase). CONCLUSION: The results of this study provide further confirmation that high CRP levels over time are associated with greater radiologic progression. Although radiologic progression still occurred in both previously normal and damaged joints despite the presence of normal CRP levels, this consisted of proportionately less new joint involvement compared with damaged joint progression. These findings support the idea that disease-suppressive therapy should be instituted at an early stage in patients with RA, before erosive damage has occurred.

A long-term five-year randomized controlled trial of hydroxychloroquine, sodium aurothiomalate, auranofin and penicillamine in the treatment of patients with rheumatoid arthritis.

OBJECTIVE: To compare the efficacy of hydroxychloroquine, penicillamine, sodium aurothiomalate and auranofin in the treatment of active rheumatoid arthritis over a period of 5 yr. METHOD: Five hundred and forty-one patients with definite or classical rheumatoid arthritis were entered into an open randomized controlled trial with a flexible dose regimen designed to reflect clinical practice. Decisions to stop treatment with any one of the disease-modifying anti-rheumatic drugs (DMARDs) were based on an agreed trial protocol which defined criteria for adverse reactions and therapeutic failure. The managing physicians' decisions were confirmed in a separate monitor clinic. RESULTS: The proportion of patients who remained on their first DMARD or who were in remission at 5 yr was 53% for penicillamine, 34% for sodium aurothiomalate, 31%, for auranofin and 30% for hydroxychloroquine (P < 0.001). In patients who stayed on their first DMARD, all groups showed a 30-50% improvement in C-reactive protein, erythrocyte sedimentation rate, Ritchie Index and joint stiffness, and a deterioration in their Larsen score. There was no evidence of physician bias to explain the larger proportion of patients remaining on penicillamine for 5 yr. CONCLUSION: Despite the increased popularity of sulphasalazine and inmmunosuppressives, the drugs in this study continue to be used worldwide. The natural history of rheumatoid arthritis requires long-term follow up to establish drug efficacy. Evidence is needed as to whether the newer regimens will prove to be more effective and safer in the longer term than the commonly prescribed DMARDs. The data from this trial will provide a reference for comparison with future studies.

Influence of the HLA-DRB1 locus on susceptibility and severity in rheumatoid arthritis.

We examined HLA-DR genotype risk in 288 patients with rheumatoid arthritis who were carefully categorized for disease severity. Five hundred ethnically-matched bone-marrow donors were controls. A hierarchy of positive allelic associations was noted with DRB1*0401 (p < 10(-38), *0404,8 (p < 10(-43), *0405 (p < 10(-8), *10 (p < 10(-3) and *0101,2 (p < 10(-2), while DRB1*0403 was negatively associated (p = 0.02). The DRB1 genotype relative risks (and 95% CIs) for RA were: *0404,5,8/*0404,5,8 = 36.2 (15-87), *0401/*0404,5,8 = 31.3 (18-55), *401/*0401 = 18.8 (11-35), *0101,2/*0404,5,8 = 6.0 (2-14), *0101,2/*0401 = 6.4 (3-12), *0101,2/*0101,2 = 1.3 (0.3-6), *10/*0404,5,8 = 27.8 (5-148), *10/*0401 = 20.8 (5-89), *10/*0101,2 = 22.3 (5-96), *0404,5,8/DRX = 5.0 (3-8), *0401/DRX = 4.7 (3-7), *0101,2/DRX = 2.3 (1.4-4), *10/DRX = 3.4 (0.8-14). No significant correlation of DRB1 genotypes was found with severity of RA as judged by nodules or articular erosions.

Idiopathic recurrent non-suppurative focal myositis: a report of two cases.

We describe two patients with acute recurrent focal myositis affecting discrete muscle groups. Sepsis was initially suspected in both cases and excluded only after surgical intervention. Spontaneous remissions occurred and extensive investigations have not demonstrated a precipitating cause.

An epidemiological and clinical investigation of pulmonary function and respiratory symptoms in patients with rheumatoid arthritis.

Several studies have investigated lung function in patients with rheumatoid arthritis but have reached different conclusions. The main discrepancy has been between airways disease reported in 38-65 per cent of patients and interstitial pulmonary disease reported in 30-41 per cent. These variable results have probably arisen because specific lung disorders have often been diagnosed on the basis of non-specific tests of lung function which, when considered in isolation, are subject to different interpretations. We adopted a combined epidemiological and clinical approach to investigate lung function and respiratory symptoms in patients with rheumatoid arthritis. Epidemiological data showed that rheumatoid arthritis is associated with a mild restrictive lung defect with reductions in mean FEV1 and FVC of 0.26 l and 0.29 l respectively and a normal FEV1/FVC ratio. The reduction in mean maximum mid-expiratory flow rate of 0.34 l/s could be explained on the basis of lung restriction and there was no evidence of widespread airways dysfunction other than that which could be explained by cigarette smoking. The clinical study showed that abnormal lung function tests in individual patients were caused by a heterogeneous group of conditions which are frequently caused, or exacerbated, by cigarette smoking. Cigarette smoking, and not the rheumatoid process, was the most frequent cause of abnormal lung function in rheumatoid arthritis.

Precision of Larsen grading of radiographs in assessing progression of rheumatoid arthritis in individual patients.

A study was designed to evaluate observer variation in the assessment of radiographic deterioration of individual patients using the Larsen grading system. Radiographs of hands and feet of 52 patients were assessed by three observers. Each patient had paired films taken one year apart which were assessed together for change in score. To assess within-observer variation each set of films was read twice by all observers. The average progression was 11.6 (SD 9.0). Analysis of the source of variation showed the single observer replication SD to be 3.7 but that for different observers to be 5.5. This may be interpreted as indicating that to achieve 95% confidence of detecting a true change an increase in Larsen score of 8 is required if the same observer assesses or up to 11 if a different observer assesses.

Systemic lupus erythematosus presenting as pneumococcal septicaemia and septic arthritis.

A 50 year old woman presented with pneumococcal septicaemia, septic arthritis, and a lobar pneumonia and was subsequently diagnosed as having systemic lupus erythematosus. The blood film and splenic 99mTc sulphur colloid uptake were normal, although selective functional hyposplenism was shown by the impaired clearance of immunoglobulin coated erythrocytes. Systemic lupus erythematosus presenting with fulminating pneumococcal sepsis in the presence of selective defects in spleen function is previously unreported.

Screening for hydroxychloroquine retinal toxicity: is it necessary?

All the patients (73) in the Rheumatology Department five year study of second line therapy who have taken hydroxychloroquine (Plaquenil) for rheumatoid arthritis for longer than 18 months were reviewed. These patients have their treatment dosage carefully monitored and have been receiving regular ophthalmic examinations. Most patients still taking the drug were assessed with a battery of tests for evidence of retinal toxicity. No retinal toxicity causing visual loss was found. On the basis of these results and a review of the recent literature we no longer routinely screen patients for hydroxychloroquine retinal toxicity in Cardiff.

Unilateral palsy of the hypoglossal nerve in a patient with tuberculosis of the first cervical vertebra.

A 26-year-old female developed a unilateral hypoglossal nerve palsy in association with tuberculosis of the first cervical vertebra. The extensive soft tissue and bony abnormalities were demonstrated only by computerized axial tomography. Involvement of the hypoglossal nerve within the skull by tuberculous granulation tissue was the most likely mechanism for the nerve palsy.

Significant changes in Ritchie scores.

A study was designed to establish the reliability of assessing joint tenderness in rheumatoid arthritis. Reliability both within and between observers was measured and the 95% confidence intervals (CI) for a change in score calculated. Forty-two patients were assessed by two metrologists over a 14-week period using three subjects per week. Results showed close agreement within and between metrologists. The 95% CI for repeat measures by the same metrologist was +/- 8.5 and +/- 12 by a different metrologist. Taking a change of 5 in the score as clinically significant, the 95% CI for a clinically significant change would be +/- 14 with one observer and +/- 17 when a different observer repeated the assessment. It is recommended that other centres should establish their own CI for a change in scores when undertaking clinical trials.

European double-blind multicenter study comparing isoxicam and indomethacin in treatment of degenerative joint disease.

A three-month, double-blind, indomethacin-controlled, European multicenter study of isoxicam (Maxicam), a nonsteroidal anti-inflammatory drug, was conducted in 365 patients who had degenerative joint disease of the knee or hip. Patients were randomly assigned to receive one of two treatments: isoxicam, 133 mg per day (Week 1), 166 mg per day (Week 2), and 200 mg per day (Weeks 3 to 12); or indomethacin, 100 mg per day (Week 1), 125 mg per day (Week 2), and 150 mg per day (Weeks 3 to 12). Efficacy measurements included, for patients with knee or hip involvement, intensity of starting pain on motion, pain on walking, night pain, overall assessment by physician and patient, and global assessment at the end of treatment; maximal extension and flexion (knee); extent of pain-free abduction and maximal abduction (hip). The results of the efficacy measurements favor isoxicam over indomethacin, although the differences are not statistically significant. The isoxicam group had significantly fewer adverse reactions than the indomethacin group.

A case of sarcoid arthritis in a child.

An 8-year-old girl presented with dyspnoea, weight loss, erythema nodosum, and an arthritis. A diagnosis of sarcoidosis with joint involvement was made. The clinical features of this unusual arthritis in a child and the response to corticosteroid therapy are described.

Gold in the treatment of rheumatoid arthritis -- why, when and how?

The use of gold salts is reviewed and discussed in terms of rationale (Why), indications and side-effects compared to other disease suppressives (when), and different types of gold and their modes of administration (How).

The effect of gold salts on the phagocytic activity of synovial macrophages in organ culture.

The effect of the gold salt, gold sodium thioglucose, has been studied on the phagocytic activity of tissue macrophages in synovium excised from patients with rheumatoid arthritis (RA) and maintained as explants in organ culture. Specimens of synovial membrane were taken for culture from synovial tissue excised from the knee joints of 22 patients with RA undergoing surgery and 14 menisectomy controls. Glass coverslips coated with yeast were placed on the synovium and the specimens maintained in organ culture. The phagocytic activity was assessed by counting the percentage of macrophages containing yeast on the coverslip removed after 24 hr in culture. The effect of gold salts was assessed by adding gold sodium thioglucose at concentrations of 3 and 30 microgram/ml to the medium, and using sodium thioglucose as an additional control. Results (means %) indicated significantly higher phagocytic activity in RA macrophages (68.6) compared with controls (40.1), p smaller than or equal to 0.001. Gold thioglucose significantly suppressed phagocytosis at 3 microgram/ml (48.0) p smaller than 0.01, and at 30 microgram/ml (47.7) p smaller than 0.02 in RA but had not effect on control synovium. Sodium thioglucose had no significant effect on phagocytosis at either concentration on RA synovium.

Systemic lupus erythematosus, repeated abortions, and thrombocytopenia.

A case is described of severe thrombocytopenia in a pregnant patient with mild SLE. Three previous pregnancies had ended in abortion. Attempts to reverse the thrombocytopenia with steroids, plasmapheresis, and splenectomy failed, the platelet count returning to normal immediately after the death of the fetus at 20 weeks gestation.