Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity.

OBJECTIVE: To define variations in the cellular infiltrate and in the expression of monokines in synovial tissue (ST) from rheumatoid arthritis (RA) patients with different durations of disease and different levels of disease activity. METHODS: The immunohistologic features of synovial biopsy specimens from 31 patients with early RA (< 1 year) and 35 patients with longstanding RA (> 5 years) were compared. The possible associations between these features and local disease activity, as measured by the score for pain in the biopsied knee joint were also evaluated. RESULTS: The immunohistologic features were not dependent on disease duration. We found a positive correlation between the scores for knee pain and the semiquantitative scores for the number of macrophages, as well as the expression of interleukin-6 and tumor necrosis factor alpha, whereas the correlation with the scores for CD4+ T cells was negative. Multivariate analysis showed that these correlations were highly statistically significant (P < 0.003). CONCLUSION: The results do not support the view that inflammatory mechanisms in the synovial tissues of RA patients differ between early and late stages of the disease. The findings presented here are consistent with the concept that early RA is the result of a synovitis process of longer duration and that macrophage-derived cytokines play an important role in maintaining the clinical signs of inflammation.

Outcome of rheumatoid arthritis in relation to age and rheumatoid factor at diagnosis.

Our retrospective followup study reports the outcome of rheumatoid arthritis (RA) in relation to age (under 60 vs 60 years and over) and rheumatoid factor status at diagnosis. A sample of 130 adult patients with RA was assessed at a mean of 5.6 years after diagnosis. At final evaluation disease activity and radiographic damage in seropositive patients were similar in both age groups, but functional capacity was markedly lower in the older onset group, indicating lower functional reserves in this group. In seronegative patients the outcome was favorable in both age groups, especially in the older patients. Seropositive patients in both age groups had more disease activity, a lower functional capacity and more radiographic damage than seronegative patients; these differences were greater in the older onset patients. The mortality in patients with RA compared to the general population (standardized mortality ratio, SMR) was higher in seropositive patients (SMR 2.78, 95% CI 1.70-4.13) but not in seronegative patients (SMR 0.45, 95% CI 0.08-1.13). The relative risk of dying was 6 times higher in seropositive patients than in seronegative patients (95% CI 1.7-20.9).

Comparison of cyclosporine and D-penicillamine for rheumatoid arthritis: a randomized, double blind, multicenter study.

Ninety-two patients with active rheumatoid arthritis (RA) were entered in a randomized double blind study of 24 weeks comparing cyclosporine (initial daily dose 5 mg/kg) with D-penicillamine (initial daily dose 250 mg). The groups were well balanced in baseline characteristics. In the cyclosporine group, 10 patients stopped prematurely, one because of inefficacy. In the D-penicillamine group, 9 patients stopped prematurely, 3 because of inefficacy. The 2 antirheumatic drugs were equally effective in reducing disease activity, except for a significant (p = 0.005) decrease in erythrocyte sedimentation rate with D-penicillamine treatment. We conclude that under the conditions of this trial, cyclosporine can serve as an alternative to D-penicillamine for the treatment of patients with RA.

Is MCTD a distinct entity? Comparison of clinical and laboratory findings in MCTD, SLE, PSS, and RA patients.

Eighteen patients diagnosed as suffering from MCTD were reexamined during follow-up (mean duration 4.6 years). The clinical features of these patients were compared with those of 19 patients with systemic lupus erythematosus (SLE), 11 with progressive systemic sclerosis (PSS) and 22 with rheumatoid arthritis (RA). Considerable overlapping of abnormal features was found between MCTD and the other syndromes. At the end of the follow-up period, 70 per cent of the cases initially diagnosed as MCTD evolved to a more classical connective tissue disease, i.e., either PSS or SLE. Generally, however, the clinical evolution of the individual MCTD patient was not predictable. Abnormal aortic valve calcifications were found in the MCTD group. Four of the 18 MCTD patients were anti-RNP negative at reexamination. There was a tendency for HLA antigens B7 and B8 to be increased in the MCTD group, but this difference was not statistically significant. Three MCTD patients died before they could be reexamined (two of them from pulmonary hypertension with proliferative endarteritis of the lung vessels and one from septicaemia and multiple cerebral infarctions.

Non-gonococcal infectious arthritis: a retrospective study.

In a retrospective study the outcome of non-gonococcal infectious arthritis was evaluated in 76 adult patients admitted to the Leiden University Hospital between 1970 and 1984. The mortality rate was 12%, and complete recovery was achieved in only 19 of the 76 patients (25%). Each of the following had a significantly unfavourable influence on the residual joint function: duration of infection more than 14 days, female sex, presence of rheumatoid arthritis, and presence of a joint prosthesis.

Reticular erythematous mucinosis syndrome in a patient with polyarthritis.

A patient with seronegative oligoarthritis who developed the reticular erythematous mucinosis (REM) syndrome is described. This syndrome is considered to be a dermatological entity unrelated to systemic disorders. Aggravation of the rash by exposure to sunlight and a good response to anti-malarial agents suggest a relationship with rheumatological disorders, e.g. rheumatoid arthritis and systemic lupus erythematosus. Dermatologists consulted by a patient with the REM syndrome should be aware of the possibility of an associated rheumatological disease.

Renal scleroderma, value of clinical markers.

The occurrence of renal scleroderma (RSc) was sought retrospectively in 36 consecutive patients with scleroderma, seen in a single rheumatology unit, over a 12-year period. The diagnosis RSc was considered when at least one of the following findings was present: systolic blood pressure greater than or equal to 95 mmH, proteinuria greater than or equal to 0.5 gr/24 hr., and creatinine clearance less than or equal to 50 ml/min.: at least one of these features was found in 16 patients. Hypertension was the most frequent feature of RSc (15 out of 16 patients). Two forms of hypertension were observed. Firstly: malignant hypertension occurring early in the course of RSc, seen in 5 patients, 4 of whom rapidly developed terminal renal insufficiency. Secondly: a moderate hypertension, seen in 10 patients with a more favourable outcome, occurring on average 53 months after the diagnosis of scleroderma was made. Proteinuria was only seen in association with malignant hypertension. Renal impairment occurred in 7 patients. Of the 36 patients with scleroderma, 14 died; 10 of these 14 patients had RSc. Thus the death rate in patients with RSc was very high, whereas only 4 out of 20 died in the group without RSc.

Cervical myelopathy in rheumatoid arthritis.

Results obtained in 43 Rheumatoid arthritis (RA) patients with cervical myelopathy are described; all patients showed several alarm signs together with neurological disturbances. Thirty-four cases were operable; nine patients were not operated upon for various reasons (refusal, and general condition). In the surgically treated patients, the changes were localized in the C1-C2 area (n = 20), in the area below C2 (n = 5), or in both (n = 9). The patients were put on skull traction pre- and post-operatively and nursed on a circo-electric bed. Pre-operatively, the duration of traction varied from a few days to weeks (mean 3 weeks). Post-operatively, the patients were given continuous skull traction for 2 1/2-3 months. This procedure yielded neurological improvement and a stable graft in all but two patients. On follow-up, recurrence of neurological complaints was seen in nine patients, in four due to a new slip at a lower level. Three of these cases were reoperated with good results. Twenty-three patients have died: four 'early' (one pre-operatively and three within 6 weeks post-operatively) and 19 'late'. The mean duration of follow-up was 4.5 years. In those who died 'late', the cause of death was due to the effects of an unstable graft in two cases and in the others the causes were not related to changes in the cervical spine. In the 10 patients who are still alive the mean duration of follow-up is 5 years. The nine patients who were not operated upon all died within a year, 4 of them due to consequences of cord compression. If cervical spondylodesis is feasible in an RA patient with myelopathy, the procedure is advocated.

A synovectomy trial and the history of early knee synovitis in rheumatoid arthritis. A multicentre study.

The results of a randomized synovectomy trial are reported and the history of early knee synovitis in 121 patients with rheumatoid arthritis is described. Conservative treatment (rest in splints, non-steroidal anti-inflammatory drugs and gold or an anti-malaria agent) for 4-5 months led to improvement in 81 of the 121 patients with early knee synovitis. In one-third of these 81 patients, the improvement continued, according to their own and the doctor's opinion, during 5 years of follow-up. Ten of the 22 patients who fulfilled the criteria for the synovectomy trial were operated upon. They showed improvement for 4 years. Over the 5-year period, two-thirds of the group were constantly seropositive or seronegative and in the other third the serology varied, but such that at each assessment 50% of the group were seropositive. Radiologically, all of the patients showed deterioration. The surgical group deteriorated more slowly for the first 2-3 years, but then showed the same pattern as the other groups. The disappearance of the clinical features of synovitis does not mean that radiological deterioration has ceased.

Chronic synovitis with marked infiltration of granulocytes in a patient with an unusual development of systemic lupus erythematosus.

The case described concerns a patient initially presenting the clinical symptoms of rheumatoid arthritis, including the presence of nodules, and slowly developing into systemic lupus erythematosus (SLE). Besides the signs of chronic inflammation in the synovial tissue, many granulocytes and PAS-positive macrophages were present. At electronmicroscopy the basal membranes of the vessels were multilaminated and the endothelial cells enlarged while many macrophages contained large clumps of electrondense material which could easily be interpreted as rough endoplasmatic reticulum (RER) of plasma cells. Immunoflourescence studies showed deposition of immunoglobulins and complement in the vessel walls of the synovium, thus suggesting an immune-complex pathogenesis.

Ankylosing spondylitis and inflammatory bowel disease. III. Clinical characteristics and results of histocompatibility typing (HLA B27) in 50 patients with both ankylosing spondylitis and inflammatory bowel disease.

A study was made, in co-operation with several gastroenterology and rheumatology centres, of the clinical and genetic characteristics (HLA B27) of 50 patients suffering from both inflammatory bowel disease (38 Crohn's disease (CD), 12 ulcerated colitis (UC)) and ankylosing spondylitis (AS), the latter diagnosis being established according to the New York criteria. 20 CD (52.6%) and 8 UC (66.7%) patients were HLA B27 positive. The presence of HLA B27 was studied in relation to clinical parameters, such as first occurrence of symptoms of AS or inflammatory bowel disease (IBD), a history of peripheral arthritis, iridocyclitis, and a positive history of AS or IBD. Our patients were found to have heterogeneous clinical features: on one side of the spectrum a group of cases was distingiushed with the typical characteristics of idiopathic AS, often being HLA B27 positive. On the other side a smaller group of HLA B27 negative patients was observed, with severe intestinal inflammatory pathology, lacking most of the typical clinical features of idiopathic AS ('secondary' form of AS). Finally, between these two extremes a group of patients was found with less pronounced clinical or genetic characteristics. These different clinical and histocompatibility patterns suggest a mixed aetiopathogenesis of AS in IBD patients. Such a 'syndrome' of AS might harbour both idiopathic AS and forms of AS 'secondary' to the intestinal inflammatory pathology.

Pathology of the cervical spine in rheumatoid arthritis: a controlled study of 44 spines.

Cervical spines (with occiputs) of 44 patients with rheumatoid arthritis (RA) were compared with 44 control spines from patients without RA, matched for sex and age. There were six severe and seven slight atlanto-axial dislocations (both horizontal and vertical, two of which had been treated surgically) in the RA group and none in the control group. Ankylosis, synchondrosis, syndesmosis, bone erosions, and redness of synovial tissue in the atlanto-axial, atlanto-occipital and cervical intervertebral joints were more frequent in the RA group than in the control spines. The lesions permitting the best discrimination between the RA and control groups were used to calculate an overall score for the whole cervical spine. Sixteen of the 44 RA patients scored higher than the highest control value; only nine scored lower than the median control score. A higher score than the average value found for the RA spines was obtained by the male patients, the patients with seropositivity or subcutaneous nodules, the patients treated with corticosteroids, the patients who died in the Department of Rheumatology, and those whose death was related to the RA itself or to the treatment given.