Rheumatoid arthritis as a cause of cardiac compression. Favourable long-term outcome of pericardiectomy

Summary In order to clarify the significance of rheumatoid arthritis (RA) as a cause of cardiac compression, we scrutinized pericardiectomy files of 47 patients over a ten-year period at two university hospitals in Finland. Five patients with RA were found. All the patients with RA were men with seropositive disease and subcutaneous rheumatoid nodules. Two of the patients had pulmonary fibrosis, one had cutaneous vasculitis and three had had rheumatoid pleurisy. There was a mean delay of 10 months from the first cardiac symptom to the diagnosis of cardiac compression, the most common misdiagnosis being primarily a liver disease. On the basis of clinical and operative data, four out of the five patients had constrictive pericarditis and one had an effusive-constrictive form of the disease. The histopathological findings in all cases were consistent with chronic fibrosing pericarditis. A follow-up of seven to seventeen years of four patients has not revealed any signs of recurrent pericardial disease. Our results demonstrate that RA is an important aetiological factor for cardiac compression. The long-term outcome of this manifestation seems to be good after pericardiectomy.     

HLA DR antigens in rheumatoid arthritis

The prevalence and possible prognostic significance of HLA-DR antigens have been studied in 129 patients with seropositive (RF-positive) classical rheumatoid arthritis (RA). HLA-DR4 was increased in RA, whilst HLA-DR2 was decreased, though it was not associated with either low titres of RF or with good prognosis. HLA-DR3-positive patients had the highest prevalence of antibodies to nuclear antigens, and the antigen correlated negatively to the presence of subcutaneous nodules, bony erosions and familial RA. RA patients possessing DR3 thus had some of the characteristics of SLE. HLA-DR5 was not present in male RA patients. An absence of familial RA was observed among DRw8-positive patients.     

Seronegative rheumatoid arthritis.

Measurement of serum rheumatoid factor (RF) by conventional methods in patients with rheumatoid arthritis (RA) has repeatedly identified a subpopulation of patients without detectable RF. Previous investigators have consistently confirmed the association of HLA–DR4 with seropositive RA, but studies of seronegative RA have been limited and contradictory. We studied 140 randomly selected patients from Alabama, all of whom had either classic or definite RA, and we were able to obtain complete HLA typing for 110 of these individuals. Eighty were consistently seropositive (on at least 2 separate occasions) and 30 were consistently seronegative (on at least 3 separate determinations). There was no statistically significant difference between the seronegative RA patients and 123 control subjects in the distribution of DR antigens. In seropositive RA, there was a significant increase in DR4 (P<0.001; relative risk = 8.02; attributable risk = 49.2%) and a significant decrease in DR3 (P<0.001; relative risk = 0.14) and DR7 (0.01>P>0.001; relative risk = 0.33). The clinical data also distinguished between seropositive RA and seronegative RA; subcutaneous nodules (37.5%) and vasculitis (6.3%) were present only in seropositive RA. DR4 positivity did not correlate with any of the clinical variables measured in the seropositive RA group. In contrast, DR4 in the seronegative RA group was associated with more destructive disease. The data suggest that seronegative RA represents a disease entity clinically and immunogenetically distinct from seropositive RA. Moreover, our results indicate that DR4 may be a previously undisclosed marker for disease severity in seronegative RA.     

Regression von peripheren und pulmonalen Rheumaknoten unter Rituximab-Therapie

We report on a retrospective study of 16 rheumatoid arthritis (RA) patients with reduction in size of pulmonary and peripheral rheumatoid nodules following treatment with rituximab (RTX). The 8 female and 8 male patients had an average disease duration of 12.2 years, 88 % were anti-CCP positive and 94 % seropositive. Prior treatment included an average of 2.9 DMARD and 1.4 biological therapies. On average 6.1 rheumatoid nodules were found on hands and elbows and 5 patients had pulmonary nodules. In 6 out of 16 patients the nodules disappeared completely, in 2 patients a pulmonary nodule disappeared. In 10 out of 16 patients the size of the nodules decreased by approximately 50%, 1 out of the 16 patients with significant increase in size and number of nodules prior to RTX therapy showed a reduction in size but no new nodules occurred. The regression in size of the nodules occurred 34.2±39.1 weeks following RTX therapy, correlating with 1.3±0.59 RTX infusion cycles. Overall, increases in size or new nodules were reported in none of the patients. One nodule examined histologically following RTX therapy did not show any specific differences. RTX may lead to a marked reduction in size of rheumatoid nodules in RA patients. More studies are necessary to confirm whether this is an RTX-specific effect.     

Successful treatment of methotrexate induced nodulosis with D-penicillamine.

Accelerated nodulosis is a recognized complication of methotrexate (MTX) therapy in rheumatoid arthritis (RA). We describe 3 patients with accelerated nodulosis treated with D-penicillamine (D-Pen) while continuing MTX. The combination of D-Pen with MTX therapy resulted in regression of subcutaneous nodules in all patients, disappearance of pulmonary nodules in one patient, and resolution of vasculitic lesions in 2 patients. Clinical response was observed within the first few weeks of therapy and usually required moderate doses (500 mg/day). Our observations suggest that addition of D-Pen to MTX therapy can be an alternative therapeutic option for accelerated nodulosis in patients with RA.     

Inhibition of immune precipitation in rheumatic disease. A clinical and laboratory study

Antigen-antibody complexes formed in the presence of serum do not precipitate. This complement-dependent function is impaired in approximately half of all patients with seropositive rheumatoid arthritis (RA) but not in patients with other chronic inflammatory arthropathies. As patients with seropositive RA have normal or elevated serum complement levels, this findings suggests that an inhibitor is present in the serum of these patients. Although degree of impairment of solubilization is correlated with rheumatoid factor (RF) titre, decreases in RF titre in patients receiving gold therapy were not always accompanied by improvement of the solubilization process. Thus we can conclude that impaired solubilization is related to, but may be distinct form, RF. Impaired solubilization was associated with the presence of subcutaneous nodules, but not with other systemic features of RA. Thus this phenomenon may be of pathogenetic importance.     

Is rheumatoid arthritis becoming less severe?

Clinical and laboratory data from 2088 successive outpatient attenders with rheumatoid arthritis (RA) were analysed to determine whether there is a trend to decreasingly severe disease. The results, after allowing for the difficulties in this type of analysis suggest that successive generations of patients with RA are decreasingly likely to become seropositive, erosive or develop subcutaneous nodules. There are no obvious explanations for these findings.     

Recurrent pneumothorax associated with pulmonary nodules after leflunomide therapy in rheumatoid arthritis: a case report and review of the literature

Rheumatoid arthritis (RA) is a multisystem inflammatory disease characterized by destructive synovitis and systemic extraarticular involvement. One of the most common pulmonary manifestations of RA is rheumatoid nodule. Spontaneous pneumothorax also very rare pulmonary finding and could be associated with pulmonary nodules. Antirheumatic drugs, methotrexate, leflunomide (LEF), infliximab and etanercept, were known as risk factors for developing rheumatoid nodule. However, there was no case report of rheumatoid nodule-associated pneumothorax with the use of LEF. We report, first, herein a case of 46-year-old woman with RA who suffered recurrent spontaneous pneumothorax associated with multiple bilateral subpleural cavitary nodules during treatment with LEF. We reviewed the cases of LEF-related pulmonary nodules developed in patients with RA. Thus, we suggested that pneumothorax can be a rare respiratory fatal complication in patients with RA with pulmonary nodules and LEF can be a rare cause of these manifestations.     

'Rhupus' syndrome

Occasionally patients with overlapping features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), termed "rhupus," have been encountered. We wanted to ascertain the frequency of such patients and determine whether they represent a unique overlap syndrome. Of approximately 7000 new patients evaluated over 11 years, we identified six patients who had, on the average, 6.7 American Rheumatism Association criteria for RA and 4.2 criteria for SLE. Criteria for RA included chronic symmetric arthritis with morning stiffness (six patients); subcutaneous nodules (two patients); positive rheumatoid factors test (four patients); and radiologic erosions (four patients). The criteria for SLE included malar rash (three patients); discoid lupus erythematosus (two patients); biopsy-proved nephritis (one patient); photosensitivity (one patient); leukopenia/thrombocytopenia (four patients); positive antinuclear antibodies or lupus erythematosus cell test (six patients); hypocomplementemia (two patients); and abnormal results from skin biopsy (two patients). During observations of up to ten years, the conditions of three patients were stable or improved, one died, and two were unavailable for follow-up. Patients usually did not have conditions that evolved to classic rheumatic disease patterns. Rhupus was not common and did not occur more frequently (0.09% prevalence among our patients) than expected from chance concurrence of SLE and RA (calculated at 1.2%). These observations confirm that rhupus indeed exists as a syndrome manifested by patients sharing features of probable coincidental concurrence of RA and SLE, but not as a unique clinical pathologic or immunologic syndrome. Appreciation of these patients with rhupus is important since their therapy and outcome differ from those having RA or SLE alone.     

HLA and disease manifestations in rheumatoid arthritis--a Canadian experience

Forty-eight Canadian patients with rheumatoid arthritis (RA) were tissue typed for class 1 (HLA-A, B, and C) and class 2 (HLA-DR and DQ) antigens in an attempt to identify HLA associations and to relate them to disease manifestations and drug toxicity. HLA-DR4 was found with a significantly higher frequency among patients with RA than in the control population. DR4 correlated with presence of rheumatoid nodules and pulmonary manifestations, and was more frequent among patients who had vasculitis. All 4 patients who died were DR4 positive. DR2 and DR7 were less frequent in our patients. There was no association between the presence of DR3 or DR4 and drug toxicity.     

Clinical and immunogenetic studies in rheumatoid arthritis from northern India

A total of 258 patients with classic rheumatoid arthritis seen over a 7-year period were included in this study. The majority of the patients had relatively mild disease at the time of presentation. The incidence of extraarticular manifestations such as subcutaneous nodules, vasculitis, amyloidosis and pulmonary involvement was low although one or two pulmonary function test parameters were abnormal in some. Seventy patients were tested for all three subclasses of rheumatoid factors - IgM, IgG and IgA. Of these, 23 patients had all three whilst four had only IgG. The 62 patients who had most typical and severe manifestations were typed for four major HLA loci A, B, C and DR. Of these 42 (67.7%) had DR4 antigen while DR3 antigen was detected in 14 (22.6%).     

Factors associated with the development of vasculitis in rheumatoid arthritis: results of a case-control study.

OBJECTIVE: To investigate those characteristics of patients with rheumatoid arthritis (RA) that are associated with the development of rheumatoid vasculitis (RV). METHODS: Demographic and clinical data of 69 patients who had been diagnosed as having RV were compared with those of 138 contemporaneous control patients with RA who were not suspected to have vasculitis. Vasculitis was confirmed histologically in 96% of the subjects with RV. RESULTS: Variables associated with the development of RV were: 1) male gender, presence of increased serum concentrations of rheumatoid factor, joint erosions, subcutaneous nodules, number of disease modifying antirheumatic drugs previously prescribed, treatment (ever) with D-penicillamine or azathioprine; 2) presence of nail fold lesions and any other extrarticular feature one year before the time of diagnosis of RV; 3) treatment with corticosteroids at the time of diagnosis of RV. CONCLUSIONS: The development of RV is associated with male gender, extra-articular features, and a severe course of RA as indicated by the presence of joint destruction and need for intensive treatment with antirheumatic drugs. The strongest association was found with the presence of increased concentrations of rheumatoid factor.     

Rheumatoid nodules without rheumatoid arthritis

Summary Four female patients with rheumatoid nodules are described who had no other clinical manifestations of rheumatoid disease. Only one of the patients was seropositive for the rheumatoid factor and HLA-DR4. Nosologic aspects of such isolated rheumatoid nodules are discussed.     

Early deaths with thrombolytic therapy for acute myocardial infarction in corticosteroid-dependent rheumatoid arthritis

Intravenous thrombolytic therapy has become standard treatment for acute myocardial infarction (AMI). We describe three patients with long-standing seropositive rheumatoid arthritis (RA) on chronic corticosteroid therapy who experienced very early (1-6 h) mortality after the use of intravenous thrombolytic therapy for the treatment of AMI. All three patients likely experienced electromechanical dissociation (EMD). Their charts were evaluated in depth, and the literature was reviewed in regard to possible etiopathologic mechanisms. Within 1-6 h of apparently successful thrombolytic therapy for AMI, these three patients experienced sudden and profound bradycardia and hypotension and could not be resuscitated. The potential occurrence of EMD in all three patients raises the possibility of accelerated myocardial rupture, as EMD is one of the clinical hallmarks of this condition. As suggested by the three clustered cases, this heretofore undescribed association between sudden unexpected cardiac death and thrombolytic therapy for AMI in patients with seropositive, corticosteroid-dependent RA suggests that further study and observation are needed. This deleterious association, if verified, has important implications for the treatment of AMI in patients who have RA and are corticosteroid dependent.     

Acute destruction of the hip joints and rapid resorption of femoral head in patients with rheumatoid arthritis

We report three rheumatoid arthritis (RA) cases with acute destruction of hip joint and rapid resorption of femoral head. The condition occurred in less than 6 months and closely resembled rapid destructive coxarthrosis. All three patients were postmenopausal women with active RA who had been taking steroids. Two of the patients were taking prednisolone (PSL) of over 20 mg as maximum dose per day, and all patients were resistant to disease-modifying anti-rheumatic drugs (DMARDs). Other than the problems of their hip joints, one had a giant bursitis around the pathological side of the hip joint, another had multiple rheumatoid nodules and skin infarction, and the other suffered from insufficiency fracture of the contralateral femoral subcapital lesion. As a result, all of them had total hip arthroplasty. We recommend taking repetitive radiographs for RA patients with continuing severe hip pain.     

Echocardiographically guided pericardiocentesis for treatment of clinically significant pericardial effusion in rheumatoid arthritis

OBJECTIVE: To assess the safety and efficacy of echocardiographically guided pericardiocentesis for patients with rheumatoid arthritis (RA) and hemodynamically significant pericardial effusion. METHODS: We identified 16 patients with RA who underwent 18 echocardiographically guided pericardiocentesis procedures at our institution over a 20-year period. Clinical and laboratory characteristics of the patients, response to treatment, complications, and need for future pericardial surgery were abstracted from the echocardiography database. RESULTS: Ten patients were men and 6 were women (mean age, 62 yrs; range, 36-75 yrs). On average, patients were diagnosed with RA 11 years before pericardial disease developed. Twelve of 15 patients were seropositive for rheumatoid factor, 10 patients had radiographic evidence of erosions, and 7 patients had rheumatoid nodules. Cardiac tamponade was present in 11 of the 18 cases. Mean volume drained on the first pericardiocentesis was 504 +/- 264 ml (range 120-1000 ml). The fluid was an exudate with a mean protein concentration of 5 g/dl (range 3.3-51.1 g/dl). All cultures and cytologic findings were negative for bacteria and neoplastic cells. No serious complications resulted from echocardiographically guided pericardiocentesis. For 11 patients, a catheter was placed for intermittent drainage over an average of 3 days. Seven patients ultimately required a more definitive surgical procedure. CONCLUSION: Echocardiographically guided pericardiocentesis is a safe and effective treatment for this uncommon but serious complication of RA.     

An inhibitor of complement-mediated prevention of immune precipitation in rheumatoid arthritis — relationship to disease activity and systemic manifestations

Summary In normal serum complement prevents precipitation of antigen-antibody complexes (PIP). However rheumatoid arthritis (RA) serum contains an inhibitor of this complement-mediated function. We have undertaken two prospective studies in order to look for any relationship between the presence and levels of inhibitory activity in sera and synovial fluids (SF) of patients with RA and disease activity (study A), and the presence of systemic manifestations (nodules and vasculitis) of RA (study B). In study A, levels of inhibitory activity were highest in the sera and synovial fluids of patients with seropositive RA. However there was no correlation between the inhibitory levels and indices of generalised disease activity (articular index, erythrocyte sedimentation rate (ESR), haemoglobin, white cell and platelet counts). Local joint tenderness score correlated weakly with the inhibitory level in SF (P<0.05). There was no correlation, however, with either the SF protein concentration or white cell count. In study B, PIP was shown to be lower in patients with the systemic manifestations of RA than in those with purely articular manifestations. PIP was particularly low in those patients with vasculitis compared to those with subcutaneous nodules. Serum levels of inhibitory activity were highest in patients with vasculitis and lowest in those with articular disease only, whereas patients with nodules had intermediate levels. Our conclusion is that inhibition of immune precipitation is not associated with disease activity, but is associated with the extra-articular manifestations of RA. The inhibitory factor may play a role in the pathogenesis of RA.     

Acute destruction of the hip joints and rapid resorption of femoral head in patients with rheumatoid arthritis

Abstract

We report three rheumatoid arthritis (RA) cases with acute destruction of hip joint and rapid resorption of femoral head. The condition occurred in less than 6 months and closely resembled rapid destructive coxarthrosis. All three patients were postmenopausal women with active RA who had been taking steroids. Two of the patients were taking prednisolone (PSL) of over 20?mg as maximum dose per day, and all patients were resistant to disease-modifying anti-rheumatic drugs (DMARDs). Other than the problems of their hip joints, one had a giant bursitis around the pathological side of the hip joint, another had multiple rheumatoid nodules and skin infarction, and the other suffered from insufficiency fracture of the contralateral femoral subcapital lesion. As a result, all of them had total hip arthroplasty. We recommend taking repetitive radiographs for RA patients with continuing severe hip pain.     

Multiple myeloma masquerading as severe seropositive rheumatoid arthritis with subcutaneous nodules and mononeuritis multiplex

Multiple myeloma can rarely mimic seronegative rheumatoid arthritis (RA). We report a 55‐year‐old woman who presented with longstanding deforming polyarthritis with extensive subcutaneous nodules, tenosynovitis, anti‐cyclic citrullinated peptide positivity and mononeuritis multiplex. Even though the clinical picture was consistent with seropositive RA, the absence of bone erosion or joint space narrowing on hand and knee radiographs led us to question the diagnosis of RA. Further investigation revealed a diagnosis of multiple myeloma with cutaneous amyloid deposits, based on serum immunofixation, bone marrow aspiration and biopsy of a subcutaneous nodule. The only clue to suspect myeloma from the basic investigations and clinical examination was mild hypercalcemia. This case serves to reiterate the need to maintain a heightened suspicion for other diagnoses even when RA appears most likely.     

HLA DRB1* alleles in rheumatoid nodulosis: a comparative study with rheumatoid arthritis with and without nodules

Rheumatoid nodulosis (RN) is a rare condition associating rheumatoid nodules, episodes of arthritis, cystic bone lesions and, generally, positive rheumatoid factors (RF). It is considered a benign variant of rheumatoid arthritis (RA). In this study, we determined the HLA DRB1^* alleles of our RN patients and compared the distribution of these alleles to those of 74 healthy controls and 104 RA patients with and without nodules. Four RN patients were observed. All had subcutaneous nodules and RF were negative in three patients. Of the 104 RA patients, 18 had nodules (nodRA). Systemic manifestation (including vasculitis, peripheral neuropathy or lung involvement) were found in seven of these nodRA cases (33.8%) and most had positive RF and erosive changes on X-rays. Only one RN patient had a RA-associated allele (DRB1^*0101). The frequencies of the HLA DRB1^* alleles encompassing the “rheumatoid” shared epitope were similar to those of other RA series: ^*0101, 34.6% (P=0.03 compared with controls); ^*0401, 26.9% (P<0.0001); ^*0404, 12.5% (P=0.04); ^*0405, 4.8% (P=0.8); ^*1001, 8.6% (P=0.5). Of the nodRA and seronegative RA patients, 77.7% and 53.3%, respectively, presented the shared epitope. Thus, there was a tendency to decreased expression of the RA-associated alleles in RN (25%) compared with nodRA and seronegative RA patients. This study is restricted by the small number of tested RN patients, but the results suggest that the RA-associated alleles are poorly expressed in RN. Received: 29 September 1997 / Accepted: 13 February 1998