Mortality and survival in rheumatoid arthritis: a 25 year prospective study of 100 patients.

One hundred patients with classical (52) or definite (48) rheumatoid arthritis (RA) at one year after onset were followed up for 25 years. By then 63 had died, in one third of whom RA had either directly caused or contributed to death. These patients, at one year after onset of arthritis, had a higher proportion with classical RA and more functional impairment than the rest. Thirty five of the surviving 37 patients were seen for review. Eleven were well with no functional impairment. At one year after onset they had a lower erythrocyte sedimentation rate (ESR) and higher haemoglobin than the others, in whom a poorer outcome was associated with a persistently raised ESR and lower haemoglobin. The initial Rose-Waaler titre was a poor prognostic guide, but a better functional outcome was associated with conversion to seronegativity or a marked fall in rheumatoid factor level.

Course and prognosis of early rheumatoid arthritis.

Lessons learned from a 20 year prospective study of 100 Rheumatoid Arthritis (RA) patients are considered. Forty six had died and the causes of death are discussed and correlations with early features; the findings in the survivors and the patterns of the course of arthritis and treatment are described. A loss of life expectancy was observed: the 9 patients whose deaths were due to RA or its systemic complications, died some 15 years prematurely; the 8 in whom RA contributed to death died some 10 years prematurely and in the 29 in whom death was unrelated to RA, death was premature by about 5 years. Already after 1 year of arthritis the functional capacity was reduced in those patients who later died due to RA or in whom RA or its treatment contributed to death. The men died earlier than the women and overall mortality in men was higher despite a younger age at onset. Patients with persistently high ESR and strong seropositivity for rheumatoid factor also did badly. Of the patients, who had died, the functional capacity at last review before their deaths was noted. It appears that already 1-8 years before their deaths 35% of the patients were confined to chair or bed (Steinbröcker grade IV) and 24% markedly restricted (grade III). These figures show that prognosis of RA patients referred to a rheumatologist is probably worse than generally suggested. Rheumatoid arthritis is a severely disabling and potentially lethal disease.

The natural history of rheumatoid arthritis over 20 years. Clinical symptoms, radiological signs, treatment, mortality and prognostic significance of early features.

A 20 year follow up is reported on 100 patients with definite or classical rheumatoid arthritis when they were all initially seen within one year of the onset of arthritis. Forty-six patients have died and in 17 death was due to or related to RA. Mortality was greater in men than in women and in patients who had classical rather than definite RA at one year. Thirty of the surviving 54 patients have either no or only moderate restriction of physical activity. Those who had definite RA at one year are now better as regards functional capacity and joint score than those who had classical RA. In general the titre of the Rose test has tended to fall and those who have become seronegative have done better than those remaining seropositive.

HLA and rheumatoid arthritis: a combined analysis of 440 British patients.

Four hundred and forty unrelated British Caucasoid patients with rheumatoid arthritis (RA) have been HLA typed for class I and class II antigens. Analyses of HLA antigen associations were performed on the overall group and in patient subsets selected according to particular disease parameters or sex, or both. The results confirm previously reported positive associations of HLA-DR4, Dw4, and DRw53 and negative associations of HLA-DR2 and DR7 with RA. Patients subsets with severe erosions, seropositivity, and features of extra-articular disease showed a stronger association, also confirming earlier reports. The link between HLA and disease severity was emphasised by a significant trend of increased Dw4 frequency with increasing severity of radiological erosions. In addition, a positive association of RA with HLA-A2 was observed and a strong negative association with DR3. The frequency of HLA-B27 was significantly increased in patients with subluxation of the spine. Differences were observed between male and female patients in relation to the HLA association. In men an increase in the frequency of the haplotype HLA/Dw4/DR4/Bw62/Cw3/A2 was observed. This showed no relationship with parameters of disease severity other than extra-articular disease. In women only class II antigens (DRw53/Dw4/DR4) showed an increased frequency. This increase was strongly associated with disease severity. A significant decrease of this class II association was observed with increasing age of disease onset; this was not seen in men.

The natural history of rheumatoid arthritis: a fifteen year follow-up study. The prognostic significance of features noted in the first year.

One hundred patients with definite or classical rheumatoid arthritis have been followed since the early months of their disease; after 15 years the 65 surviving patients were reviewed. Their functional capacity had fallen by comparison with reviews made 3 and 11 years after onset, but half were still unimpaired or only moderately so (grade 1 and 2). The number of affected joints had risen to an average of 8 joints in men and 13 in women, but the ESR and the titre of the Rose test were lower than in the first year. Haemoglobin levels had risen in men, but fallen in women. The first-year titre of the Rose test proved to be of great prognostic significance, regarding ARA grading and number of affected joints after 15 years, but it did not correlate with the functional capacity. However, the functional capacity at 3 years correlated significantly with its value at 11 and 15 years. Patients with rheumatoid nodules were significantly worse than the remainder in many respects. A positive Schirmer test, showing diminished tear secretion, did not relate to any of the clinical parameters. The medical and surgical treatment is briefly reviewed.

Cause and age at death in a prospective study of 100 patients with rheumatoid arthritis.

A series of 100 patients with rheumatoid arthritis (RA), first seen in the early months of their disease, have now been followed up for 18 years, and 43 have died. Rheumatoid disease directly caused death in 9, and the disease or its treatment contributed to death in 7. These 16 patients were younger at onset and younger at death than the 27 in whom death was unrelated to RA. Of clinical features noted 1 year after the onset of RA a worse ARA grading and a worse functional capacity were already evident in those 16 patients. Conversely, the 57 still surviving had a better ARA grading and a better functional capacity after 1 year than those who died. The survivors were also significantly younger than the rest at the onset of RA. The death rate throughout the follow-up period was higher in the patients graded as 'classical' than those graded as 'definite' RA after 1 year of disease.

Basilar artery aneurysm and Anderson-Fabry disease.

A case of basilar artery aneurysm is described. The patient had a family history of similar aneurysms and also of a rare spingolipidosis, Anderson-Fabry disease.

Radiological study of cervical spine and hand in patients with rheumatoid arthritis of 15 years' duration: an assessment of the effects of corticosteroid treatment.

Radiological abnormalities in the cervical spine were assessed in detail in a group of 62 patients with rheumatoid arthritis of approximately 15 years' duration, of whom 33 had been treated with corticosteroids and 29 had not. The 10 criteria of damage described by Bland (1974), which include subluxation, correlated as a whole with the severity of the disease in general but not with the duration of corticosteroid treatment. Subluxation alone, whether assessed in the cervical spine as a whole or in the atlanto-axial joint alone, was less closely related to disease activity, was on average greater in patients treated with corticosteroids, and tended to increase in relation to the duration of treatment. Corticosteroid treatment thus tends to produce, over the course of years, a degree of subluxation in addition to that caused by the disease itself. Radiological signs of damage to the metacarpophalangeal (MCP) joints and carpal bones correlated with both the degree of damage and the degree of subluxation in the cervical spine as well as with corticosteroid treatment. Mutilans deformity at the MCP joints was associated with subluxation in the neck and with corticosteroid treatment.

Arthritis with sigmoid volvulus and HL-A B27.

A 43-year-old male developed seronegative polyarthritis after a short attack of diarrhoea. For about two years before he had experienced intermittent abdominal pain, distension and constipation. Laparotomy showed a chronic sigmoid volvulus for which sigmoid colectomy was performed. Post-operatively he had no further bowel symptoms, no further arthritis and there was radiological improvement of involved joints. Tissue typing showed HL-A B27 antigen.

Naturally occurring anti-inflammatory factors in the synovial fluids of patients with rheumatic disease and their possible mode of action.

Evidence has been shown that pathological synovial fluid contained a substance capable of stabilizing rat liver lysosomes which was partly inactivated by treatment with trypsin and by storage. Such synovial fluid also appeared to contain a substance which labilized lysosomes and which was more stable than the stabilizing substance. (2) The lysosomal stabilizing substance described above was nondialysable and migrated electrophoretically with the alpha and beta globulins to which class it has been tentatively ascribed. (3) Pathological synovial fluid contained proteases which were active at acid pH and at neutral pH. It also appeared to contain a substance capable of inhibiting these proteases. (4) Alpha2-Macroglobulin has been detected in pathogenic synovial fluid.