Presence Of Extra-articular Features Research Articles

Hypereosinophilic Syndrome Associated with the Onset of Rheumatoid Arthritis: A Case Report

Idiopathic hypereosinophilic syndrome (HES) is a disorder characterized by the sustained overproduction of eosinophils and multiple organ damage. Rheumatologic manifestations of HES are infrequent, but persistent eosinophilia is observed in approximately 10% to 40% of patients with rheumatoid arthritis (RA). This finding may be a result of the RA itself and is often associated with active disease and the presence of extraarticular features. We describe the case of a 48-year-old man affected by HES who subsequently developed RA. Both HES and RA responded rapidly to the corticosteroid and methotrexate therapy. In this patient, the initiation of RA and HES was related, suggesting a common pathogenetic link between these two diseases.

Pain assessment in clinical Rheumatology

The diagnostic approach in clinical practice in Rheumatology is mainly based on the recognition of pain origin. Patient's experience of pain may be similar in different diseases involving bones, joints, tendons, muscles or peripheral nervous system. The analysis of some characteristics of pain may be helpful in the diagnostic approach. In this perspective pain must be analysed according to the type, localization, occurrence, elicitation and concomitant clinical signs. In the majority of cases this analysis allows a preliminary differential diagnosis which is essential to drive further assessments. The diagnostic approach to arthropaties is based on a group of indicative criteria which include diffusion of the arthropathy, the involved sites, the course of the joint disease, the joint damage, the history of preceding events and the presence of extra-articular features which accompany joint disease. This kind of clinical approach helps the clinician in saving time and reducing costs of diagnosis by driving any further investigation.

Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA

Autoantibodies in rheumatoid arthritis (RA) are useful both for diagnosis and prognosis. Antibodies directed against citrullinated antigens have recently been shown to predict development of RA as well as poor outcome in early arthritis. Data on their role in established RA is limited. We studied the association of various autoantibodies in RA with its severity. A total of one hundred and twenty nine-patients with established RA was enrolled and sera were collected and stored at -70 degrees C. Data regarding erosions, deformities, and extra-articular features were collected. IgM rheumatoid factor (RF) was measured using nephelometry and value above 20 U was considered positive. IgA RF was measured by enzyme-linked immunosorbent assay (ELISA) and value above the mean+/-2 SD of normal healthy control was taken as positive. Anti-keratin antibody (AKA) was detected by indirect immunofluorescence assay using rat esophagus as substrate. Anti-cyclic citrullinated peptide (CCP) antibodies were measured by commercial ELISA and a value above 5 U was considered as positive. The prevalence of various autoantibodies was: IgM RF 82.2%, anti-CCP antibodies 82.2%, AKA 51.9%, and anti IgA RF 45%. The concordance rate of anti-CCP antibodies with IgM RF was 83%, with AKA 68%, and with IgA RF 60.5%. All but one patient positive for AKA were positive for anti-CCP antibodies. The presence of IgM RF, AKA, and anti-CCP antibody was associated with joint erosions and deformities. None of the antibodies had any association with presence of extra-articular features. No association of IgA RF was seen with erosions, deformities, or extra-articular features. Among 23 seronegative RA patients, 11 were positive for anti-CCP antibodies and 6 were AKA positive. The presence of anti-CCP antibodies was associated with presence of deformities (p<0.05). Anti-CCP antibodies are present in majority of patients with established RA including seronegative patients. Both anti-CCP and AKA, in addition to conventional marker like IgM RF, are associated with severe erosive disease.

Extra-articular manifestations of rheumatoid arthritis: risk factors for serious gastrointestinal events.

Serious upper gastrointestinal events are an important threat to patients with arthritis who are treated with non-steroidal anti-inflammatory drugs (NSAIDs). In this study risk factors for serious upper gastrointestinal events are identified in patients with possible or definite rheumatoid arthritis (RA). A retrospective analysis of factors that might contribute to the risk of serious upper gastrointestinal events was performed in a cohort of 2315 consecutive patients with possible or definite RA. The relative influences of disease severity, drug treatment, particularly with corticosteroids, and history of peptic ulceration were analysed with a conditional logistic regression model for the 106 patients with serious upper gastrointestinal intestinal events and for an equal number of control patients who were matched for age, gender, number of criteria for RA, and disease duration. The incidence rate for serious upper gastrointestinal events was 4.0/1000 patients in each year. The study reconfirmed that age over 60 years, history of peptic ulceration, and use of corticosteroids are risk factors. The presence of extra-articular manifestations of RA was associated with a two to 11-fold increase in the risk for serious upper gastrointestinal events. This risk was independent of the use of corticosteroids. Disease severity, in particular the presence of extra-articular features, may be an important factor in the pathogenesis of upper gastrointestinal ulceration in patients with RA who are treated with NSAIDs.

Uptake and degradation of soluble aggregates of IgG by monocytes of patients with rheumatoid arthritis: relation to disease activity.

Monocytes from patients with rheumatoid arthritis (RA) and rheumatoid vasculitis have a diminished ability to degrade soluble complexes of aggregated IgG in the absence (mediated by Fc receptors) as well as in the presence of complement (C) (mediated by (Fc + C) receptors). To investigate whether a relation exists between the receptor mediated degradation of aggregated IgG by adherent monocytes and disease activity a longitudinal study was performed in 79 patients with RA and rheumatoid vasculitis over a period of 16 months. Adherent monocytes were incubated in vitro with 125I labelled IgG aggregates of restricted size in the absence or presence of fresh serum and the percentage of catabolised IgG aggregates was measured. Cross sectionally the degradation of aggregated IgG by monocytes, mediated by Fc and (Fc + C) receptors, correlated significantly with disease activity as scored by the Ritchie articular index, the presence of extra-articular features, and circulating immune complexes. A high number of Fc receptors on monocytes correlated with diminished degradation, whereas high numbers of complement receptors 1 and 3 correlated with enhanced degradation of aggregated IgG mediated by both Fc and (Fc + C) receptors. The degradation of aggregated IgG by monocytes did not correlate with disease activity in individual patients followed up longitudinally. When patient groups were formed according to the results of longitudinal studies, however, degradation of aggregated IgG mediated by Fc and (Fc + C) receptors was significantly decreased in patients with rheumatoid vasculitis and in patients with active RA in comparison with patients with inactive RA and healthy controls. Patients with active RA and rheumatoid vasculitis also expressed significantly more Fc receptors and less complement receptors on the monocytes than patients with inactive RA. Drug treatment did not correlate with receptor expression or the degradation of aggregated IgG by monocytes either in cross sectional or longitudinal studies. It is concluded that in RA disease activity is related to receptor expression and the degradation of soluble immune aggregates by monocytes.

IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELISA in rheumatoid arthritis.

One hundred patients with rheumatoid arthritis (RA), of whom 73 were seropositive by latex or Waaler-Rose (WR) assays, or both, 100 healthy subjects, and 102 diseased controls (22 patients with systemic lupus erythematosus (SLE) and 80 with bronchial asthma) were evaluated for the presence of IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF by an enzyme linked immunosorbent assay (ELISA). Ninety two per cent, 65%, 68%, and 66% of the patients with RA were found to be positive for IgM, IgA, IgE, and IgG respectively. A positive correlation existed between the levels of IgM RF and IgA RF on the one hand and disease activity on the other, and the levels of IgM RF and IgA RF correlated with the levels of circulating immune complexes as measured by a C1q binding assay. The presence of extra-articular features also correlated positively with the levels of IgA RF and IgE RF. Five out of six patients with Sjögren's syndrome had very high levels of IgA RF. Of 47 patients typed for HLA-DR, DR1 and DR2 were significantly more frequent in those with the highest levels of IgM RF. Conversely, DR3 was associated with low levels or absence of IgA RF and IgE RF. These results suggest that immune response genes may regulate the level of different RF isotypes. The frequencies of IgM, IgA, IgE, and IgG RF were 59%, 36%, 9%, and 27% respectively in SLE and 25%, 2.5%, 70%, and 59% in bronchial asthma.

Serum immune complexes containing IgA appear to predict erosive arthritis in a longitudinal study in rheumatoid arthritis.

Fifty seven patients with rheumatoid arthritis (RA) were studied longitudinally, and the presence of rheumatoid factor (RF) and various types of immune complexes (IC) was correlated with joint activity and the presence of extra-articular features (EAF). In a cross sectional study it was found that the levels of circulating IC and RF correlated significantly with joint disease activity and the presence of EAF. Longitudinally, levels of IC measured by the C1q binding activity and IC containing IgG and IgM correlated significantly with fluctuations in joint disease activity, whereas IC containing IgG and IgA correlated with the occurrence of EAF. RF and IC levels, however, did not predict the clinical course of the disease. IC containing C3 and C4 were found infrequently and were only present in patients with active rheumatoid vasculitis (RV). The continuous presence of these IC appeared to be linked to the recurrence of vasculitis, irrespective of treatment. Significantly more erosions of hands and feet were found after one year follow up in those RA patients who presented early (disease duration less than one year) who initially had a raised serum IgA IC level (r = 0.72; p less than 0.005).

Androgenic Status and Sexual Function in Males with Rheumatoid Arthritis and Ankylosing Spondylitis

The pituitary-testicular axis was investigated in 31 males with rheumatoid arthritis (age range 19-60 years, median 55 years) and 33 males with ankylosing spondylitis (age range 22-55 years, median 37 years) and compared with a control group of 95 normal male volunteers. Using analysis of covariance, patients with rheumatoid arthritis showed significantly lower serum testosterone (p less than 0.05) and derived free testosterone (p less than 0.01) concentrations and significantly higher serum LH and FSH concentrations (p less than 0.05) compared with controls. All patients had normal serum prolactin and cortisol concentrations. Serum testosterone correlated with ESR, haemoglobin concentrations and rheumatoid factor titres (r = -0.448, p less than 0.02; r = 0.440, p less than 0.02; r = -0.360, p less than 0.05 respectively) in the rheumatoid patients. Although there was a significant negative correlation between ESR and haemoglobin concentrations (p less than 0.005) in the patients with ankylosing spondylitis, neither variable correlated with serum testosterone concentrations. There was no association between testicular dysfunction and the presence of extra-articular features of rheumatoid arthritis. Ten patients (33 per cent) with rheumatoid arthritis and four (13 per cent) with ankylosing spondylitis admitted to periods of impotence while 15 (50 per cent) of the former and 12 (39 per cent) of the latter had periods of decreased libido. There was no evidence for increased rates of infertility in either group.

Frequency of HLA-Dw3 in juvenile rheumatoid arthritis.

We have prospectively examined 46 consecutive unrelated children with JRA, 28 females and 18 males, for HLA‐A, ‐B, ‐Dw1, and ‐Dw3 antigens. The data were analyzed according to mode and age of onset, as well as presence of extraarticular features. Patients with JRA were found to have an elevated frequency of HLA‐B27 (26% vs. 8% of controls, P &lt; 0.01). This elevated frequency of HLA‐B27 was noted in patients with either a pauciarticular or polyarticular onset and consistent with previous observations, was more common in males than females. However, the most striking associations in JRA were apparent when the MLC‐defined locus HLA‐Dw3 was studied. The total patient population had a 46% frequency of HLA‐Dw3 as compared with 24% in controls (P &lt; 0.01). Moreover, when the group of 46 children was subdivided, the HLA‐Dw3 frequency of patients with polyarticular disease was 64% as compared with 21% in pauciarticular disease (P &lt; 0.01). Further, although the frequency of HLA‐B8 was similar in JRA to that in the control panel, a significant degree of linkage disequilibrium was shown to exist between HLA‐B8 and HLA‐Dw3. No such linkage was shown to exist between HLA‐B27 and either HLA‐Dw1 or Dw3. Although we have not multiplied the P value by the number of HLA‐A, ‐B and ‐D antigens, we suggest that the presence of the MLC‐defined locus HLA‐Dw3 is significantly elevated in children with polyarticular mode of onset of JRA and suggest that further definition of lymphocyte‐dependent loci may aid in understanding the mechanism of pathogenesis as well as the classification and prognosis of childhood onset arthritis.