Ventricular function abnormalities in active rheumatoid arthritis: a Doppler echocardiographic study

Objective The aim of the present study was to evaluate cardiac involvement in patients with active rheumatoid arthritis (RA).Methods Forty patients with active RA participated. All were submitted to standard Doppler echocardiography and myocardial performance index (MPI) grading.Results There were left and right ventricular diastolic function abnormalities in RA patients. Left ventricular MPI was also significantly higher than in controls (P<0.05). A relationship was found between left ventricular early diastolic (E)/atrial (A) flow velocities (E/A ratio), isovolumic relaxation time (IRT), and disease duration (r=–0.47 and P=0.002, r=0.618 and P=0.000, respectively).Conclusion Diastolic function was impaired in both ventricles in patients with active RA. There was a direct relationship between some of the parameters of left ventricular diastolic function and disease duration as well. These findings suggest a subclinical myocardial involvement in RA patients.     

Silica-related rheumatoid arthritis without lung involvement

 We report a young male with recent onset of rheumatoid arthritis (RA) in whom the remarkable severity of the disease led to additional investigations. The only significant finding was mediastinal lymphadenopathy, without lung involvement. Biopsy of the mediastinal lymph node revealed pathological findings typical of silicosis. To our knowledge, this is the first report of silicosis apparent solely in the mediastinal lymph node of an RA patient. This suggests that lung involvement is not crucial for the development of silica-related arthritis. Received: 20 November 2001 / Accepted: 21 May 2002     

Rheumatoid nodules indicating seronegative rheumatoid arthritis in a patient with gout

 The association of gout and rheumatoid arthritis is rare. We report the case of a patient with gout who presented with rheumatoid nodules indicating seronegative rheumatoid arthritis. Received: 29 July 2002 / Accepted: 4 November 2002     

Cross-sectional and longitudinal study of osteoporosis in patients with rheumatoid arthritis

To elucidate the pathology of osteoporosis associated with rheumatoid arthritis (RA), bone mass measurements were performed in 146 female patients with RA and compared with those in 150 age-matched female patients with osteoarthritis (OA) and postmenopausal osteoporosis (OP). Bone mineral density (BMD) was measured at the lumbar spine (L-BMD), the mid-radius (MR-BMD) and the calcaneus (C-BMD) by dual-energy X-ray absorptiometry (DXA), and at the distal radius by peripheral quantitative computed tomography (pQCT). The RA group showed significantly lower BMD at all sites, except L-BMD, than the OA group. Compared with the OP group, the RA group showed a significantly higher L-BMD but no difference at other sites. BMD in RA decreased with disease severity at all sites and lean body mass was highly correlated with L-BMD and C-BMD. Cross-sectional analysis revealed early bone loss at the distal radius and a decrease of L-BMD, MR-BMD, and C-BMD with disease duration. Longitudinal analysis showed that the annual loss of L-BMD, MR-BMD and C-BMD tended to be lower with increasing disease duration. Glucocorticoid administration had no influence on L-BMD, MR-BMD or C-BMD. We concluded that, unlike postmenopausal osteoporosis, osteoporosis associated with RA is characterised by relatively preserved bone mass in the axial bone and marked loss in the peripheral bone. The risk factors for generalised osteoporosis are a long disease duration, severity of disease, and decreased lean body mass. Received: 8 May 2001 / Accepted: 18 September 2001     

Lack of association of Human T-cell Lymphotrophic Virus Type 1(HTLV-1) infection and rheumatoid arthritis in an endemic area

 In South Africa the association of HTLV-1 infection with myelopathy is well described in Kwa Zulu Natal, which is an endemic area for HTLV-1 infection. Japan also has a high background prevalence of HTLV-1 infection, and a significant association of HTLV-1 infection with rheumatoid arthritis has been reported. This study was undertaken to determine whether there was an association with HTLV-1 infection among black Africans with rheumatoid arthritis (RA) in Kwa Zulu Natal, South Africa. A randomly selected group of 110 black people with RA were studied. The age, sex and duration of disease were recorded and a rheumatoid factor test was performed. The presence of antibodies to HTLV-1 was assessed using an enzyme-linked immunosorbent assay. The integration of proviral DNA in peripheral blood monocytes was also studied using the polymerase chain reaction (PCR). Control data were available from a previously reported community-based study of 1018 subjects from the same geographical area. None of the 110 patients studied were positive for HTLV-1 infection by serology or by PCR. Although HTLV-1 infection is reported as a possible triggering agent for RA in Japan, we failed to detect any excess of HTLV-1 infection in black Africans with RA. Our findings are in agreement with observations in the USA and Europe. Received: 27 December 2001 / Accepted: 22 July 2002 Acknowledgements This project was supported by a grant from the University of Natal Research Fund. We wish to thank Professor A.I. Bhigjee for his encouragement to undertake this study and Sister N.G. Mkhize for assistance with the study.     

Bloodstream thrombopoietin in rheumatoid arthritis with thrombocytosis

Thrombopoietin (TPO) is the major regulator of growth and differentiation of megakaryocytes. Recent studies have shown that TPO may also act as an acute-phase reactant, and it has been suggested as a component of inflammatory reactions. In this study our objective was to investigate serum TPO levels in patients with rheumatoid arthritis, a complex chronic inflammatory disorder not uncommonly associated with thrombocytosis. Bloodstream TPO concentrations were assessed in 13 RA patients with platelet counts between 450 and 650 x 10(9)/l, 10 RA patients with platelet counts >650 x 10(9)/l, 15 RA patients with normal platelet counts and 12 healthy controls. RA patients with normal platelet counts had TPO levels comparable with healthy controls. TPO concentrations in patients with mild thrombocytosis were significantly elevated, whereas patients with markedly increased thrombocyte counts had prominently decreased TPO levels. These results indicate that TPO seems to be associated with reactive thrombocytosis in RA patients with active disease. In patients with extremely increased thrombocytosis serum TPO levels might be regulated by increased platelet mass via receptor-mediated uptake and metabolism.     

ACTH expression in synovium of patients with rheumatoid arthritis and Lewis rats with adjuvant arthritis

 Adrenocorticotropic hormone (ACTH) and another pro-opiomelanocortin-derived neuropeptide, β-endorphin (β-End), are stimulated by corticotropin-releasing hormone (CRH) at the anterior pituitary. CRH and β-End have predominantly proinflammatory effects in peripheral inflammatory sites. We have supposed that inflammatory stimuli develop ACTH as well as β-End. In this study, we investigated the expression of ACTH in inflamed synovial tissue from patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and at inflammatory joints with adjuvant-induced arthritis (AA) in female Lewis (LEW/N) rats. The expression of ACTH immunostaining was significantly greater in synovium of RA patients than in that of OA patients (P < 0.0001), and correlated with the extent of inflammatory mononuclear cell infiltration. Extensive and intense intracellular ACTH immunostaining, which correlated with the advance in arthritis score, was observed in the synovial lining layer, inflammatory mononuclear cells, and fibroblast-like cells of synovium and chondrocytes in LEW/N rats with AA. In addition, we performed double immunostaining of the same sections from arthritic joints in rats with anti-ACTH and anti-CRH antibodies. ACTH and CRH colocalized in inflammatory mononuclear cells and fibroblast-like cells. ACTH may play a role in the pathogenesis of RA as well as CRH. Received: July 4, 2001 / Accepted: January 23, 2002 Correspondence to: H. Sano     

Systematic review of NSAID-induced adverse reactions in patients with rheumatoid arthritis in Japan

 A systematic review of randomized controlled clinical trials of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis (RA) patients was conducted to evaluate the risk of NSAID-induced adverse reactions. Double-blind, randomized, controlled trials with 6-week treatments for RA patients were included in the study. The endpoints for the analysis included any adverse reactions, digestive adverse reactions, and upper gastrointestinal (GI) adverse reactions. A fixed-effect model was used for estimation of the risk. Time-to-event analysis of the incidence of adverse reactions was also conducted. A total of 28 trials was included for the analysis, and a total of 30 NSAIDs were used in the trials. The proportion of patients who experienced any adverse reaction was as follows: piroxicam 18.9% (3 trials), diclofenac 18.8% (4 trials), indomethacin 22.1% (14 trials), and aspirin 25.0% (4 trials). The proportion of patients who experienced digestive adverse reactions was as follows: piroxicam 10.2%, diclofenac 10.6%, indomethacin 13.1%, and aspirin 14.1%. Most withdrawals due to adverse reaction occurred during the first 3 weeks after administration of the NSAID. Although the risk of NSAID-induced adverse reaction was different from drug to drug, the risk of adverse reaction was clinically significant. Received: April 24, 2002 / Accepted: September 11, 2002 RID="*"     

Diastolic function abnormalities in active rheumatoid arthritis evaluation by conventional Doppler and tissue Doppler: relation with duration of disease

Objective The aim of this study was to evaluate left ventricular diastolic function in patients with active rheumatoid arthritis (RA), analyzing conventional Doppler and tissue Doppler echocardiographic imaging (TDI) which is a new echocardiographic application, with special regard to disease duration. Methods Fifty-two patients with active RA and 47 healthy persons were included in this study. Duration of disease ranged from 3 to 324 months (mean 76±85 months). All patients and the control group were evaluated by M-mod, two-dimensional, conventional Doppler echocardiography and TDI. Results Among conventional Doppler transvalvular mitral flow parameters, late diastolic flow velocity (A) and deceleration time (DT) values were higher in patients with RA than that in the control group (p<0.001). E (early diastolic flow velocity)/A ratio was found to be lower in patients with RA than that in the control group (p<0.001). Mitral annular early diastolic velocity (E _m), among TDI parameters, was found to be lower in patients with RA than that in the control group (p<0.001). E _m/A _m (mitral annular late diastolic velocity) ratio was found to be lower in RA patients compared with that in the control group (p<0.001). The relation was found between A (r=0.43, p=0.001), DT (r=0.30, p=0.03), E/A ratio (r=0.40, p=0.004), E _m (r=0.32, p=0.02), E _m/A _m ratio (r=0.30, p=0.03), and E/E _m (r=0.32, p=0.02), with disease duration in patients with RA. Conclusion At present, it is concluded that active RA patients, in the absence of clinical evidence of heart disease, show diastolic dysfunction characterized by impaired E/A ratio, E _m/A _m ratio, and DT. The relation between diastolic dysfunction and disease duration suggests a subclinical myocardial involvement. This study has been accepted as a poster presentation at the Annual European Congress of Rheumatology “EULAR 2004” (Berlin, Germany, 9–12 June 2004     

Doppler echocardiographic evaluation of left ventricular function

Invasive measurements of maximum acceleration of aortic blood flow are sensitive indicators of left ventricular function. Doppler echocardiography provides noninvasive measurements of aortic blood flow acceleration. Our studies establish the accuracy of Doppler-derived indices of aortic blood flow velocity for evaluation of left ventricular function. Doppler-derived peak velocity and mean acceleration showed excellent correlation with invasively measured peak left ventricular dP/dt and maximum aortic blood flow (dQ/dt) under varying heart rate, preload, afterload, and inotropic states. Similar correlations were observed between Doppler-derived peak velocity and mean acceleration and invasively measured left ventricular dP/dt and dQ/dt under conditions of varying degrees of myocardial ischemia. Thus, Doppler echocardiography provides an accurate noninvasive method to evaluate left ventricular performance.     

Ultrasound and clinical evaluation of quadricipital tendon enthesitis in patients with psoriatic arthritis and rheumatoid arthritis

Enthesitis is an inflammatory lesion of the tendon, ligament and capsular insertions into the bone, and it is a fundamental element in the diagnosis of spondyloarthropathies. Sonography is the method of choice for studying periarticular soft tissues because it is capable of detecting both the early (oedema, thickening) and the late alterations (erosions and enthesophytes); it is also an inexpensive, biologically harmless and easily repeatable technique. The aim of this study was to compare the prevalence of quadricipital enthesitis in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, and to document any clinical and echostructural differences in this lesion between the two diseases. The results show that enthesitis is more frequent in PsA patients, more than half of whom are asymptomatic. Knee inflammation was found in the PsA patients with enthesitis regardless of the concomitant presence of joint effusion; none of the RA patients suffered from enthesitis alone. Quadricipital enthesitis is more frequent in male patients. There was no significant correlation between the presence of peripatellar psoriatic lesions and enthesitis. Sonographic examinations of patients with enthesitis revealed that those with RA had dominantly inflammatory lesions, whereas PsA patients also showed major new bone deposition. Received: 24 January 2001 / Accepted: 15 October 2001     

Ultrasound and clinical evaluation of quadricipital tendon enthesitis in patients with psoriatic arthritis and rheumatoid arthritis

Enthesitis is an inflammatory lesion of the tendon, ligament and capsular insertions into the bone, and it is a fundamental element in the diagnosis of spondyloarthropathies. Sonography is the method of choice for studying periarticular soft tissues because it is capable of detecting both the early (oedema, thickening) and late alterations (erosions and enthesophytes); it is also an inexpensive, biologically harmless and easily repeatable technique. The aim of this study was to compare the prevalence of quadricipital enthesitis in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, and to document any clinical and echostructural differences in this lesion between the two diseases. The results show that enthesitis is more frequent in PsA patients, more than half of whom are asymptomatic. Knee inflammation was found in the PsA patients with enthesitis regardless of the concomitant presence of joint effusion; none of the RA patients suffered from enthesitis alone. Quadricipital enthesitis is more frequent in male patients. There was no significant correlation between the presence of peripatellar psoriatic lesions and enthesitis. Sonographic examinations of patients with enthesitis revealed that those with RA had predominantly inflammatory lesions, whereas PsA patients also showed major new bone deposition. Received: 24 January 2001 / Accepted: 16 January 2002     

Carpal collapse in patients with rheumatoid arthritis

The inflammation of the wrist and carpal collapse play an important role in the deformity of the rheumatoid hand and leads to functional limitation. The aim of this study was to evaluate carpal collapse and related clinical variables in patients with rheumatoid arthritis (RA). Carpal height ratio (CHR) indicating the degree of carpal collapse was measured in 33 female RA patients with a mean age of 41.9±10.3 years and 30 female healthy control subjects with a mean age of 40.5±9.2 years. The normal range of the carpal collapse was defined in our study population and the incidence of carpal collapse was determined. The correlation between carpal collapse and clinical and laboratory variables including pain by visual analog scale, Ritchie articular index, erythrocyte sedimentation rate, C-reactive protein, health assessment questionnaire indicating functional status, and Larsen roentgenological evaluation were determined. Subgroup analyses were also performed in patients with and without carpal collapse. The mean disease duration of the patients was 12.4±5.5 years. The mean CHR index of the patients was significantly lower than in the control group (0.47±4.3 and 0.54±1.4 respectively). CHR <0.48 was defined as carpal collapse in our study group. Seventeen patients (51.5%) had carpal collapse in the patient group. None of the clinical or laboratory variables except levels of disease duration and Larsen score was correlated with carpal collapse as represented by CHR. The best related clinical variable with carpal collapse was found as duration of disease. The mean duration of disease and the Larsen score were significantly higher in patients with carpal collapse than those without collapse. Other clinical parameters and functional status were similar between patients with and without carpal collapse. In conclusion, although various clinical parameters and functional disability in patients with RA may not be correlated with radiological malalignment, the carpal collapse may be more common in RA than is generally recognized.     

Predictors of hand function in patients with rheumatoid arthritis

Objectives. The aims of this study were to determine: (1) what factors predict patient self-estimated hand function; (2) what factors predict actual hand function; and (3) the relationship among actual hand function, patient estimates of hand function, and self-assessed activities of daily living (ADL). Methods. Fifty-two patients with rheumatoid arthritis completed wrist and hand mobility measures, grip strength, pain, stiffness, and estimated hand function tests, along with the Sollerman Grip Function Test (actual hand function), Health Assessment Questionnaire (HAQ), and subscales of the Arthritis Impact Measurement Scales (AIMS). Results. Grip strength and stiffness were the strongest predictors of self-estimated hand function. Flexion and extension deficits in digits II through V were the strongest predictors of actual hand function. Actual hand function and self-estimated hand function were significantly correlated with each other and with the HAQ and AIMS subscales. Conclusions. Measures of deficit are the most useful in predicting actual hand function, whereas measures of strength and flexibility are most useful for estimated hand function.     

A clinical and biochemical evaluation of prednisolone in patients with active rheumatoid arthritis

Summary Fifteen patients with active rheumatoid arthritis who had not previously received oral corticosteroids were recruited into an open study using the Leeds Human Model Screening System to assess whether prednisolone has any activity as a second-line agent. The daily dose of prednisolone was 10 mg/day, and all patients completed the full study duration of 24 weeks, with only one patient requiring a dose reduction to 7.5 mg. Patients were then recruited into a further open study during which dosage reduction of 1 mg/month was attempted. Patients were assessed using six clinical and six laboratory variables, and statistically significant improvement (P<0.01) was seen in seven of 12 variables at 24 weeks. After 48 weeks, two variables showed statistically significant improvement at P<0.01, with improvement in a further four variables significant at P<0.05. This degree of change ranks prednisolone below established second-line agents such as sodium aurothiomalate and d-penicillamine but ahead of non-steroidal anti-inflammatory drugs, suggesting that in addition to their known anti-inflammatory properties corticosteroids may have some action as second-line agents.     

Antibodies to type II collagen and their association with HLA DR1 alleles in Japanese patients with rheumatoid arthritis

 To investigate whether immunological responses to type II collagen (CII) play an important role in the pathogenesis of rheumatoid arthritis (RA), the presence of anti-CII antibodies was examined by enzyme immunoassay in 130 Japanese patients with RA, 10 systemic lupus erythematosus (SLE) patients, and 30 healthy subjects. In addition, the HLA-DRB1 genes of 40 RA patients were determined, and their association with positive findings of anti-CII antibodies was examined. A significantly high frequency of positive findings of anti-CII antibodies was detected in sera from RA patients (19%, P < 0.05) in comparison with that in sera from healthy subjects (3%). High frequencies of DRB1^*0405 and 0101 alleles were observed in the 40 RA patients examined (40.0% and 30.0%, respectively). Patients with DRB1^*0101 had a significantly higher rate of positive findings of anti-CII antibodies than those without DRB1^*0101 (66.7% and 28.6%, respectively, P < 0.05). No such association was observed for DRB1^*0405. From these findings, we suggest that immunological responses to CII may play an important role in the development of arthritis in some RA patients. Received: April 9, 2002 / Accepted: June 13, 2002 Acknowledgment We thank Dr. T. Sakamaki, Division of Clinical Research, Sakura National Hospital, Japan, for technical assistance and useful advices on HLA typing. Correspondence to:T. Sumida     

Image-guided surgery for cervical disorders in rheumatoid arthritis

 This study demonstrated that frameless stereotaxy can be applied safely to cervical disorders caused by rheumatoid arthritis (RA). Sixteen patients with cervical instability including atlantoaxial instability due to RA underwent instrumentation surgery under an image-guidance system from February 2000 through May 2001. Neural and vascular injuries were evaluated, and postoperative computed tomography (CT) was used to determine the accuracy of screw placement. There were no neurovascular complications, and screw placement was highly accurate. Image-guidance systems are useful tools for preoperative planning and application of transarticular and pedicular screw placement in the cervical spine of patients with RA. Received: December 1, 2001 / Accepted: April 17, 2002 Correspondence to:A. Seichi     

Doppler sonographic evaluation of effect of treatment with infliximab (Remicade) for rheumatoid arthritis

Synovial vascularization in the knee joints of six patients with rheumatoid arthritis who were treated with infliximab was evaluated by Doppler sonography. Power Doppler sonography demonstrated a significant reduction of color flow signals (P < 0.05), and spectral Doppler sonography demonstrated a significant increase in vascular resistance (P < 0.05) at week 6 (after three injections) evaluation of the therapy. A significant decrease in the number of tender joints (P < 0.05) and C-reactive protein value (P < 0.05) was also observed in these patients.     

Bilateral tibia and fibula fractures in a patient with rheumatoid arthritis

A 52-year-old woman with rheumatoid arthritis treated with low-dose steroids developed bilateral distal tibia and fibula fractures over a 15-month period. Her bone density was within osteopenic levels. Such fractures are an unusual but increasingly recognised complication of rheumatoid disease and its treatment, although there is often diagnostic delay. Bilateral fractures are particularly rare. A high level of clinical suspicion is required for early diagnosis. Received: 19 June 2000 / Accepted: 26 January 2001