Myocardial dysfunction in rheumatoid arthritis: a controlled tissue-Doppler echocardiography study

OBJECTIVE: To determine the sensitivity and accuracy of tissue-Doppler echocardiography (TDE) to assess myocardial contractility. Heart failure is one of the determinants of the excess in mortality in patients with rheumatoid arthritis (RA). METHODS: Consecutive RA patients with normal clinical cardiac examination were prospectively included and compared to 27 controls. All underwent conventional echocardiography, and systolic and diastolic strain rate (SR) were determined by TDE. RESULTS: Twenty-seven patients with RA were included (mean age 50 +/- 10 yrs, disease duration 8 +/-6 yrs). Mean disease activity score was 4.3 +/- 1.6, C-reactive protein 23 +/- 32 mg/l. When compared to controls (50 +/- 9 yrs), patients with RA had increased left ventricular mass (99 +/- 24 vs 80 +/- 25 g/m2, p = 0.009), and there was a trend for left atrial enlargement (31 +/- 3 vs 29 +/- 6 mm, p = 0.06). Fractional shortening and systolic SR did not differ between groups. Diastolic function, as estimated by the E/A Doppler velocity ratio was similar in both groups (p = 0.18). However, diastolic SR was strikingly reduced in patients with RA versus controls (3.7 +/- 1.3 vs 5.5 +/- 1.1s-1, p < 0.001) with 18/27 patients with RA having marked reduced diastolic SR (SR < 4s-1). None of the RA characteristics was associated with significant differences in TDE measurements. CONCLUSION: TDE identifies impaired diastolic function in patients with RA that may not be detected by conventional measurements.     

Thyroid function and immune profile in rheumatoid arthritis. A controlled study

Summary The aim of our study was to determine the prevalence of thyroid dysfunction and autoimmune abnormalities in rheumatoid arthritis (RA) and to further investigate the possible association between D-penicillamine and autoimmune thyroiditis. For this purpose, one hundred and one unselected consecutive patients with RA and 70 age and sex matched controls were studied prospectively. Evaluation included a complete history and physical examination with special attention to symptoms suggestive of thyroid pathology, routine laboratory and serologic immune profile, plus determination of serum levels of thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), antibodies to thyroid peroxidase (AbTPO) and TSH receptor antibodies (TRAB). Serum thyroxine binding globulin (TBG) was measured in all subjects with high thyroid hormone levels, whereas free T3 and T4 concentrations were determined in all individuals with abnormal T3, T4, TSH or TBG.Six patients with hyperhyroidism, 3 with hypothyroidism and 1 with the euthyroid hyperthyroxinemia (EH) syndrome were found, whereas four of the controls had hyperthyroidism. Thirteen patients and 6 controls had high AbTPO levels whereas no one had high TRAB. No association was detected between thyroid abnormalities and any serologic RA finding. Furthermore, no correlation between thyroid dysfunction and elevated AbTPO's was found.A relatively high prevalence of thyroid dysfunction (9,9%) and subclinical autoimmune thyroiditis (12,9%), the latter indicated by elevated AbTPO's, was found in our RA patients. These figures were higher than those in the control group (5,7% and 8,6% respectively), but the difference did not reach statistical significance. Of further interest may be our finding that, despite anecdotal reports blaming D-penicillamine for cases of autoimmune thyroiditis, the incidence of the latter was similar among recipients and nonrecipients of the drug. Similarly, TRAB were not detected in any patient treated with D-penicillamine.     

Pulse methotrexate therapy in rheumatoid arthritis. A controlled prospective roentgenographic study

Study Objective: To assess whether weekly pulse methotrexate therapy alters radiographic progression of joint disease in patients with rheumatoid arthritis. Design: Prospective, controlled study. Hand, wrist and foot roentgenograms obtained before, at the onset of, and during methotrexate treatment were scored for degree of joint-space narrowing and erosions by three rheumatologists using a standard method. Patients: Sequential sample of 24 patients with active definite or classical rheumatoid arthritis and previous unsuccessful treatment; of these, 3 were excluded due to drug ineffectiveness; 2, due to side effects; and 1, due to refusal to take methotrexate. Interventions: Treatment with nonsteroidal anti-inflammatory drugs and prednisone was continued. Methotrexate was given weekly to control clinical evidence of disease in patients. Measurements and Main Results: After having had an average of 30 months of therapy, the 18 patients who continued to receive methotrexate therapy showed significant (p less than 0.05) clinical improvement, as evidenced by their decreased joint counts and joint scores, duration of morning stiffness, pain scales, and sedimentation rates. Despite patients' prolonged clinical improvement, the mean rate of development of erosions and joint-space narrowing during methotrexate therapy was not significantly different from the rate of radiographic progression before methotrexate therapy (0.043 compared with 0.041; p greater than 0.05). Conclusions: Weekly pulse methotrexate is effective for the long-term management of clinical disease activity in patients with refractory rheumatoid arthritis but may not be a disease-modifying agent by roentgenographic criteria.     

Thyroid dysfunction in systemic lupus erythematosus and rheumatoid arthritis: Its impact as a cardiovascular risk factor

IntroductionThyroid dysfunction and autoantibodies have been frequently associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).Aim of the workTo assess thyroid function and anti-thyroid antibodies in both diseases and elucidate the effects of the thyroid dysfunction on the clinical parameters, disease activity and cardiovascular risk.Patients and methodsForty SLE and forty RA female patients in addition to twenty controls were included. Free thyroxine (FT3), free triiodothyronine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase antibodies (TPOabs), anti-thyroglobulin antibodies (TGabs), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL) and intima-media thickness (IMT) were measured. Disease activities were assessed in both diseases. In RA patients, the anti-cyclic citrullinated peptide (anti-CCP) was evaluated.ResultsA significantly higher TSH level was found in SLE patients compared to RA patients and controls. No significant difference was present between the RA patients and controls. Anti-TPOabs and anti-TGabs were more frequently detected in SLE (85% and 55%) compared to RA (50% and 37.5%). Abnormal thyroid function tests were detected in SLE, RA patients and controls in 52.5%, 17.5% and 10%, respectively. Subclinical hypothyroidism was the most common abnormality present followed by clinical hypothyroidism then euthyroid sick syndrome in both SLE and RA patients. A positive anti-CCP and high disease activity score (DAS28) in RA were among the strongest independent determinants of cardiovascular disease.ConclusionThyroid dysfunction is frequent in SLE and RA patients. Those with thyroid dysfunction had increased cardiovascular risk.     

Methotrexate in rheumatoid arthritis. a five-year prospective multicenter study

Objective. To evaluate the efficacy and tolerability of oral methotrexate (MTX) in rheumatoid arthritis (RA) in a long-term prospective trial. Methods. One hundred twenty-three patients with RA who completed a 9-month multicenter randomized trial comparing MTX and auranofin enrolled in this 5-year prospective study of MTX. Results. Significant (P = 0.0001) improvement compared with baseline was noted in all clinical disease variables, functional status, and the Westergren erythrocyte sedimentation rate (ESR). “Marked improvement” occurred in 87 (71%) and 85 (69%) of the patients, respectively, in the joint pain/tenderness index and the joint swelling index at the last evaluable visit. Forty-four patients (36%) withdrew during the study. Eight (7%) withdrew due to lack of efficacy, and 8 (7%) due to adverse experiences, including 1 patient with cirrhosis. At 5 years, 64% of patients were still taking MTX and completed the study. Conclusion. This large prospective study of long-term MTX treatment demonstrates sustained clinical response and improvement in the Westergren ESR and functional assessment scores, with an acceptable toxicity profile.     

Salicylate ototoxicity in patients with rheumatoid arthritis: a controlled study.

Tinnitus or subjective hearing loss, or both, were reported by 61 of 134 (45%) patients with rheumatoid arthritis (RA) taking regular salicylates and by 73 of 182 (40%) untreated healthy subjects. In the patients with RA mean salicylate levels were not higher in those with tinnitus than in those without tinnitus, but levels were significantly higher in those with subjective hearing loss than in those with no symptoms. Twenty five per cent of the patients with RA had tinnitus or subjective hearing loss with salicylate levels less than 1.42 mmol/l. Audiometric responses in 31 patients correlated poorly with symptoms. Tinnitus and subjective hearing loss may be too non-specific to be reliable as tools for adjusting the salicylate level into the therapeutic range.     

Sexual dysfunction in rheumatoid arthritis patients: arthritis and beyond

Rheumatoid arthritis treatment has been shown to improve quality of life. There is little data regarding the impact of the disease and treatments on sexual function. The aim of this study was to describe the results of an assessment of sexual activity/sexual satisfaction of rheumatoid arthritis patients, identify the sexual dysfunction features, and assess their association with disease activity/disease activity parameters and other systemic risk factors/comorbidities. Consecutive rheumatoid arthritis patients attending the outpatient rheumatology clinic completed the multidimensional patient-reported outcome measures questionnaire. There are three questions screening for sexual dysfunction: patients who ticked any of the boxes were further assessed. Men completed the Sexual Health Inventory for Men; whereas women completed the Female Sexual Function Index. All patients underwent clinical assessment of disease activity parameters and cardiovascular risk. Among 231 rheumatoid arthritis patients included in this study, 49/91 (53.8%) men and 64/140 (45.7%) women reported sexual dysfunction. Among men, erectile dysfunction significantly correlated (p < 0.01) with pain score, cardiovascular disease, age, disease activity, fatigue score, intramuscular steroid injection, and tender joint count. Among women, sexual dysfunction was significantly correlated (p < 0.01) with occurrence of secondary Sjogren's syndrome, pain score, cardiovascular disease, hip joint involvement, disease activity, and tender joint count. Sexual dysfunction is common among rheumatoid arthritis patients. Erectile dysfunction in men, and problems with orgasm, arousal, and satisfaction in women, were the most prevalent manifestations. The significant correlation of sexual dysfunction with CVD may help to identify patients at high risk of cardiovascular disorders.     

Feverfew in rheumatoid arthritis: a double blind, placebo controlled study.

Feverfew, reputed by folklore to be effective in arthritis, has in vitro properties that could be beneficial in the control of inflammatory disease. Forty one female patients with symptomatic rheumatoid arthritis received either dried chopped feverfew (70-86 mg) or placebo capsules once daily for six weeks. Allocation was random and not known by patient or observer. Variables assessed included stiffness, pain (visual analogue scale), grip strength, articular index, full blood count, erythrocyte sedimentation rate, urea, creatinine, C reactive protein, complement breakdown products (C3dg), rheumatoid factor titre, immunoglobulins (IgG, IgA, IgM), functional capacity, and patient and observer global opinions. One patient (placebo) withdrew after three days and was not included in the analysis. Treatment and placebo groups (20 patients each) were well matched at entry. No important differences between the clinical or laboratory variables of the groups were observed during the six week period. This study therefore shows no apparent benefit from oral feverfew in rheumatoid arthritis.     

Subclinical renal dysfunction in rheumatoid arthritis

We studied renal function in 35 patients with chronic, seropositive rheumatoid arthritis (RA), of whom 7 had vasculitis, 10 had hypergammaglobulinemia, and 18 had neither of these 2 conditions. Findings included a decreased glomerular filtration rate in 8 patients, (micro)proteinuria in 11, a defective urine concentration in 10, and increased urinary tubular enzyme levels in 15. These results indicate that subclinical renal dysfunction is common in patients with chronic, seropositive RA. In addition, vasculitis and hypergammaglobulinemia were not identified as risk factors for renal dysfunction in the RA patients studied.     

Influence of patient education on exercise compliance in rheumatoid arthritis: a prospective 12-month randomized controlled trial

OBJECTIVE: To determine the effect of education on the exercise habits of patients with rheumatoid arthritis (RA) after 6 and 12 months. METHODS: We studied 208 outpatients recruited between June 2001 and December 2002. This was a prospective controlled randomized trial. The active group received a multidisciplinary education program, including training in home-based exercises and guidelines for leisure physical activity (PA). The control group received a booklet added to usual medical care. Compliance with home-based exercises was defined as a practice rate >or= 30% of the prescribed training. Compliance with leisure PA was defined as >or= 20% increase in Baecke questionnaire score. Additional assessments involved possible predictors of compliance and changes with regard to the compliance. RESULTS: At 6-month followup, home-based exercise and leisure PA compliance were significantly higher [13.5% vs 1%, respectively (p = 0.001); and 28.2% vs 13.8% (p = 0.02)], but were not at 12 months. Predictors of leisure PA compliance at 6 months included participating in the active group (odds ratio 2.74, 95% CI 1.17 to 6.38) and previous low leisure PA (OR 6.01, 95% CI 2.47 to 14.61), with decreased fatigue (FACIT-F mean -2.94 +/- 8.04 vs -0.1 +/- 7.25 for noncompliant subjects; p = 0.04) and improved psychological status (Arthritis Impact Measurement Scale mean -1.25 +/- 3.12 vs 0.11 +/- 3.39; p = 0.03). CONCLUSION: Education of patients with RA may increase compliance especially with leisure PA, particularly when it is poor at baseline, but these effects are limited and short-term.     

Disease activity and lipids in rheumatoid arthritis: a prospective study

BackgroundAtherosclerotic cardiovascular disease (CVD) is the major cause for mortality in rheumatoid arthritis (RA). Dyslipidemia is an important risk factor for CVD and is influenced by the disease activity of RA. There is paucity of data on this subject in Indian patients with RA.ObjectivesTo study the lipid levels in patients with RA and their relation with disease activity.MethodThe prospective study was carried out at a tertiary care centre in northern India.ResultsThe study population included 96 patients with RA. Using the “high” cut-off values of National Cholesterol Education Programme–Adult Treatment Panel (NCEP-ATP III) as many as 38.5% (37/96) of patients exhibited dyslipidemia. Low high-density lipoprotein cholesterol (HDL-C) was the commonest abnormality seen in 34.3% of (33/96) patients. Disease activity scores (DAS-28) were at baseline and on a follow-up visit after 3 months they were 4.9 (1.02) and 4.4 (0.9), respectively (P = 0.003). With a decline in disease activity, a rising trend was observed for all lipids, statistically significant only for HDL. DAS-28 showed significant negative correlation with TC, r = 0.302 (0.003) and LDL-C, r = 0.274 (0.007). For HDL and TG, the correlation was not significant.ConclusionLipid abnormalities are common in Indian patients with RA. Low HDL is the commonest abnormality. Disease activity is negatively related with lipids.     

Aspirin-induced hepatotoxicity in juvenile rheumatoid arthritis a prospective study

Recent reports of and our own experience with biochemical alterations of liver function secondary to salicylate therapy stimulated this prospective study. Thirty-four children with juvenile rheumatoid arthritis, 6 children with acute cartilagenous necrosis of the hip following slipped capital femoral epiphysis, and 2 children with ulcerative colitis and hip disease who were on salicylates were followed over a period of 1–27 months with serial determinations of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), lactic dehydrogenase (LDH), alkaline phosphatase (AP), bilirubin, and serum salicylate. Prothrombin time was measured in 14 children. Twenty-two of 34 children with rheumatoid arthritis and none of the 8 controls demonstrated abnormalities of various liver functions at serum salicylate levels between 7.0 and 43 mg%. Three children demonstrated severe abnormalities characterized by marked elevation of SGOT, SGPT, LDH, and AP, prolongation of prothrombin time, and epistaxis. This type of reaction occurred within 5–14 days of initiation of aspirin therapy and occurred at serum salicylate levels between 18 and 43 mg%. Moderate changes in various liver function tests were observed in 19 other children. None of those children who were tested showed prolongation of prothrombin time. The serum salicylate level in this group varied between 7.0 and 38.2 mg%. The abnormal liver function tests returned to normal in 6 children upon withdrawal of aspirin and in 12 others even when salicylates were continued. Therefore, despite the occurrence of biochemical abnormalities following chronic salicylate therapy, it does not appear to be necessary to discontinue their use except in those children who develop bleeding.     

Vaccination survey in patients with rheumatoid arthritis: a cross-sectional study

The objective of this study is to evaluate the vaccination status in rheumatoid arthritis (RA) patients during routine clinical practice, data from a German non-interventional cross-sectional study. In this prospective study, patients with rheumatoid arthritis were interviewed using a standardized questionnaire focusing on vaccination. Available vaccination documents were evaluated, and titers for common vaccination antigens (hepatitis B, rubella, mumps, measles, diphtheria, tetanus) were analyzed with special regard to the underlying treatment and age of patients. A total of 301 RA patients treated with conventional DMARDs alone (cohort I, n?=?125), TNF-blocking agents (cohort II, n?=?117), or B-cell depletion with rituximab (cohort III, n?=?59) have been studied. Significantly more patients in the biologic cohorts II and III were aware of an increased risk of infections (I: 67.7%, II: 83.8%*, III: 89.9%*, P?<?0.05). Pneumococcal vaccination rate was significantly higher (I: 20.2%, II 36.8%* and III: 39.0%*, P?<?0.05) compared with cohort I. Differences were less evident for influenza. Significantly more patients ≥60?years of age have been vaccinated against Streptococcus pneumoniae and influenza. An obvious discrepancy existed between vaccination awareness and actual vaccination rates for all cohorts. No significant differences in vaccination titers could be seen between the three cohorts. Awareness of infectious complications was more present in patients treated with biologicals, and also, the rate of patients vaccinated against Streptococcus pneumoniae increased significantly depending on the underlying treatment. Nevertheless, there was a discrepancy between vaccination awareness and actual vaccination rates for all cohorts.     

Methotrexate in rheumatoid arthritis: a prospective study in Israeli patients with immunogenetic correlations.

In a prospective open study 44 Israeli patients with rheumatoid arthritis were treated with weekly low dose methotrexate (MTX) for up to 36 months. Nine patients withdrew from the study: six because of side effects and three due to inefficacy. One patient died of septicaemia following septic arthritis. Significant improvement, graded by Ritchie articular index, grip strength, physician's global assessment, erythrocyte sedimentation rate (ESR), and platelet counts, was noticed in response to treatment. Seronegative patients had a better clinical response. Transient gastrointestinal symptoms were common and correlated with increases of serum aspartate transaminase (AST). HLA-DR1 and DR7 were significantly associated with increased serum AST concentrations.     

Effect of a collective educational program for patients with rheumatoid arthritis: a prospective 12-month randomized controlled trial

OBJECTIVE: To evaluate the effect on health and functional status of an 8-week group-education program for rheumatoid arthritis (RA) in addition to usual medical care. METHODS: All consecutive inpatients and outpatients with RA (ACR criteria) were asked to participate in this randomized, prospective, controlled trial. The educational intervention consisted of 8 weekly ambulatory sessions, each lasting 6 hours. Followup was undertaken after 1 year. The primary criterion for judging effectiveness was the Health Assessment Questionnaire (HAQ) score; secondary criteria consisted of coping, medical knowledge, patient global satisfaction, and quality of life scores before the intervention and after 1 year. RESULTS: We asked 1242 inpatients and outpatients to participate in the study: 208 (16.75%) agreed (104 in each group). At baseline, there was no statistically significant difference between the 2 groups. After 1 year, no statistically significant difference was observed between the 2 groups in change in HAQ score: -0.04 +/- 0.46 (education group) vs -0.06 +/- 0.47 (control group) (p = 0.79). Statistically significant differences were found in 3 domains: patient coping (-1.22 +/- 5.55 vs -0.22 +/- 3.81; p = 0.03), knowledge (3.42 +/- 4.73 vs 0.73 +/- 3.78; p < 0.0001), and satisfaction (10.07 +/- 11.70 vs 5.72 +/- 13.77; p = 0.02), all of which were better for the group attending the education sessions. CONCLUSION: Despite improvements in patient coping, knowledge, and satisfaction, the education program was not found to be effective at 1 year. There may have been methodological problems relating to the sensitivity of questionnaires and patient selection, and tailored educational interventions should be considered.