Amyloidosis mimicking rheumatoid arthritis

A 49-year-old man presented a clinical picture suggesting seronegative rheumatoid arthritis. He developed severe joint contractions, pasty synovial swelling, macroglossia and proteinurie. Subsequent investigations disclosed light-chain multiple myeloma and A1-amyloid deposits in synovial tissue and skin. A1-amyloidosis should be considered in the differential diagnosis of patients with seronegative polyarthritis. Clues to the diagnosis of amyloid arthropathy are a carpal tunnel syndrome, early occurrence of joint contractures in combination with a relatively mild synovitis and a low ESR as well as the presence of other possible organ involvement with amyloidosis.     

Amyloidosis and rheumatoid arthritis

In spite of an apparent decrease in its occurrence during the last 2-3 decades, amyloidosis associated with rheumatoid arthritis is a significant cause of increased morbidity and early death in both juvenile- and adult-onset rheumatoid arthritis (RA). Like other forms of reactive amyloidosis, the amyloid fibrils associated with rheumatoid disorders are of the protein AA type, and the acute phase reactant SAA, which is complexed to high density lipoprotein in serum, is its putative precursor. Raised SAA appears to be one of the prerequisites for the development of reactive, AA amyloid. Effective treatment of the underlying disorder i.e. rheumatoid arthritis, which lowers the levels of SAA is, therefore, recommended both as a prophylactic and therapeutic measure against reactive amyloidosis. As renal disease is the most severe and life-threatening consequence of reactive amyloidosis, both hemodialysis and renal transplantation are also to be considered in such patients.     

Sudden cardiac death in patients with rheumatoid arthritis

An increased cardiovascular morbidity and mortality, including the risk of sudden cardiac death(SCD), has been shown in patients with rheumatoid arthritis(RA). Abnormalities in autonomic markers such as heart rate variability and ventricular repolarization parameters, such as QTc interval and QT dispersion, have been associated with sudden death in patients with RA. The interplay between these parameters and inflammation that is known to exist with RA is of growing interest. In this article, we review the prevalence and predictors of SCD in patients with RA and describe the potential underlying mechanisms, which may contribute to this. We also review the impact of biologic agents on arrhythmic risk as well as cardiovascular morbidity and mortality.     

Survival and cause of death in rheumatoid arthritis: a 25-year prospective followup

In a 25-year prospective followup of 209 patients with rheumatoid arthritis, median life expectancy was shortened by 7 years in males and by 3 years in females when compared with the general population. The surplus mortality was associated in decreasing order with the disease itself, associated respiratory, urogenital and general infections, and with upper gastrointestinal tract disease, mainly bleeding.     

Causes of death in patients with rheumatoid arthritis autopsied during a 40-year period

We studied causes of death (CoDs) between 1952 and 1991 assessed by a clinician before autopsy and then determined at autopsy by a pathologist in 369 subjects with rheumatoid arthritis (RA) and 370 subjects without RA (non-RA). We analysed clinical data for RA subjects between 1973 and 1991. In RA subjects, leading autopsy-based CoDs were RA, cardiovascular diseases and infections. Between diagnoses of CoDs by the clinician and those determined by the pathologist, RA subjects had lower agreement than did the non-RA regarding coronary deaths (Kappa reliability measure: 0.33 vs. 0.46). In non-RA subjects, autopsy-based coronary deaths showed a decline since the 1970s with no such decline in RA. Between subjects treated at any time during RA with disease-modifying anti-rheumatic drugs and those without, autopsy-based CoDs were similar. Coronary death being less accurately diagnosed in RA subjects may indicate that coronary heart disease in RA patients often remains unrecognized.     

Analysis of the causes of death in patients with rheumatoid arthritis]

The post-mortem examinations performed from 1943 to 1977 in Tartu were examined for the frequency of rheumatoid arthritis as cause of death. Here was the result that since 1968 in increasing number this clinical picture was observed and that during the last five years it appeared in 1.4% of the cases. As cause of death in patients whose basic disease was rheumatoid arthritis most frequently and uraemia was found either on the basis of an amyloidosis of the kidneys or of a chronic glomerulonephritis. Also the number of fatal complications among a long-lasting glucocorticosteroid therapy is not unconsiderable.     

Amyloidosis associated with rheumatoid arthritis after total joint replacement]

Rheumatoid arthritis patients who had secondary amyloidosis have been studied retrospectively. There were eight patients out of 105 rheumatoid arthritis patients who had total joint replacement surgery from 1979 to 1990 in our institute. The grade of inflammation, renal and hepatic function have been compared with the RA patients without amyloidosis pre- and post- operatively. All of eight patients was female, and their average age at the diagnosis of amyloidosis was 57.8 year-old (range 4-76 year-old). The average preoperative period was 14.4 years (range 4-27 years), and the secondary amyloidosis had been diagnosed at the time of 3.8 years (range 1-9 years) after operation. The major clinical features leading to the diagnosis were gastrointestinal disturbance in six cases and renal dysfunction in two cases. The data of the renal function of amyloidosis patients showed slightly lower than that of the RA patients without amyloidosis, and showed significantly decrease postoperatively. The white blood cell (WBC) count was higher at the time of operation in the amyloidosis patients and showed continuous increase postoperatively. Lansbury index, alpha 2-globulin and WBC count did not improve in the amyloidosis patients during three years after operation. On the contrary, the patients without amyloidosis improved in these clinical data during the same period. Three amyloidosis patients died of renal failure and one died of bronchopneumonia. The average survival period was 1.8 years (range 1-5 years) after diagnosis of amyloidosis, and was 6.3 years (range 2-10 years) after operation in these four patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Death rate and causes of death in patients with rheumatoid arthritis.

Patients with rheumatoid arthritis, 500 males and 500 females, aged 40 years or over, and an age- and sex-matched control population were observed over a 3-year period. During the follow-up, 122 RA patients and 69 controls had died. The most common causes of death in RA patients were cardiovascular diseases (57 patients), renal failure (27 patients), infections (19 patients), and malignant neoplasms (11 patients); in the controls, the respective data are: cardiovascular diseases (35 people), malignant neoplasms (21 people), accidents (7 people), and infections (5 people).     

Motivation as a determinant of physical activity in patients with rheumatoid arthritis

Objective

A sufficient level of physical activity is important in reducing the impact of disease in rheumatoid arthritis (RA) patients. According to self‐determination theory, the achievement and maintenance of physical activity is related to goal setting and ownership, which can be supported by health professionals. Our objective was to examine the association between physical activity and the extent to which RA patients 1) believe that physical activity is a goal set by themselves (autonomous regulation) or by others (coerced regulation) and 2) feel supported by rheumatologists (autonomy supportiveness).

Method

A random selection of 643 RA patients from the outpatient clinics of 3 hospitals were sent a postal survey to assess current physical activity level (Short Questionnaire to Assess Health‐Enhancing Physical Activity), regulation style (Treatment Self‐Regulation Questionnaire), and the autonomy supportiveness of their rheumatologists (modified Health Care Climate Questionnaire).

Results

Of the 271 patients (42%) who returned the questionnaire, 178 (66%) were female, their mean ± SD age was 62 ± 14 years, and their mean ± SD disease duration was 10 ± 8 years. Younger age, female sex, higher education level, shorter disease duration, lower disease activity, and a more autonomous regulation were univariately associated with more physical activity. Hierarchical multiple regression analyses demonstrated that younger age and a more autonomous regulation were significantly associated with a higher physical activity level (P = 0.000 and 0.050, respectively).

Conclusion

Regulation style was a significant determinant of physical activity in RA patients. This finding may contribute to further development of interventions to enhance physical activity in RA patients.     

Death rates and causes of death in patients with rheumatoid arthritis: a population-based study

OBJECTIVE: To assess the mortality and causes of death in a cross-sectional population-based study of 1042 patients with rheumatoid arthritis (RA). METHODS: In 1988, 604 RA patients [470 females (F), 134 males (M)] and 457 age- and sex-matched controls (352 F, 105 M) were examined prospectively (participants) and 438 (183 F, 81 M) non-participant RA patients retrospectively. In 1999, vital status and causes of death were determined. Mortality in the total RA population was compared to that in the general population, and that among participant RA patients to their matched controls. RESULTS: A total of 384 (37%) RA patients and 71 (16%) controls died. RA patients had increased mortality compared to the general population (standardized mortality ratios SMR 2.64) or controls (1.71). This was observed in both sexes. Over 40% of deaths in all groups were due to cardiovascular diseases. RA patients were at increased risk of dying of urogenital, gastrointestinal, respiratory and cardiovascular diseases, infections, and cancers when compared to the general population or controls. CONCLUSIONS: Our results show that a cross-sectional cohort of RA patients had an increased risk of death from various causes.     

Cause of death in rheumatoid arthritis

A series of 489 consecutive patients with definite or classical rheumatoid arthritis was followed for a mean of 11.2 years. Cohort-analysis of the series showed a three-fold increase in mortality overall in comparison with age- and sex-specific rates in the general population. In patients first seen in hospital early in the course of the disease (less than 5 years from onset), the excess of deaths from circulatory, respiratory and musculoskeletal disorders was highly significant. Malignant disease and digestive system disorders accounted for a small excess of borderline significance. Patients who were referred later (greater than 5 years from onset) experienced, in addition, a highly significant excess of deaths from infections and disorders of the digestive and genito-urinary system but not from malignant neoplasms.     

Glycosaminoglycans are a potential cause of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory disease of connective tissue with unknown etiology. We investigated whether aberrant immune responses to glycosaminoglycans (GAGs), a major component of joint cartilage, joint fluid, and other soft connective tissue, causes this disease. Here we show that injection of GAGs such as hyaluronic acid, heparin, and chondroitin sulfates A, B, and C induce arthritis, tendosynovitis, dermatitis, and other pathological conditions in mice. We developed a technique by staining tissue specimens with fluorochrome- or biotin-labeled GAGs to visualize the direct binding between cells and GAGs. We discovered that inflammatory infiltrates from the affected tissue are dominated by a distinct phenotype of GAG-binding cells, a significant portion of which are CD4(+) T cells. GAG-binding cells seem to be expanded in bone marrow of GAG-immunized mice. Furthermore, we identified GAG-binding cells in inflamed synovial tissue of human patients with RA. Our findings suggest that carbohydrate self-antigenic GAGs provoke autoimmune dysfunctions that involve the expansion of GAG-binding cells which migrate to anatomical sites rich in GAGs. These GAG-binding cells might, in turn, promote the inflammation and pathology seen both in our murine model and in human RA.     

Cause of death in patients with rheumatoid arthritis with particular reference to azathioprine.

Three hundred and eleven patients with classical or definite rheumatoid arthritis were observed over an 11-year period. This group is of particular interest since 214 patients were given cytotoxic therapy, 203 were treated with azathioprine (52 of these also received chlorambucil or cyclophosphamide), and 11 were treated with cyclophosphamide or chlorambucil alone. Forty-six patients died. This is an excess mortality compared with the expected rate for the general population matched with respect to age and sex. The death rate was higher than expected in the age group 45-64 years but lower in those aged 75 years or over. There were more deaths from neoplasia and ischaemic heart disease in the younger age group. One patient died of lymphosarcoma; treatment had been with corticosteroids, gold, and chloroquine. No other tumours of the reticuloendothelial system were recorded, and no patient developed leukaemia.     

Infectious causes of death in patients with rheumatoid arthritis: an autopsy study

OBJECTIVE: To study mortality from infections and accuracy of pre-mortem diagnoses in patients with rheumatoid arthritis (RA) autopsied during a 40-year period. METHODS: We investigated infectious causes of death, findings at autopsy, and clinicians' estimation of cause of death in 369 consecutively autopsied RA and 371 autopsied non-RA patients with same sex, age at death, and year of autopsy. We also compiled clinical features of RA patients from medical records available and examined the association between these and infectious causes of death. RESULTS: Deaths from any infection were more frequent in RA (36%) than in non-RA (26%) patients. In both groups, respiratory and urinary tract infections were the most common infectious causes of death. More RA patients died from urinary tract infections than non-RA patients. In approximately half of the patients in both groups, infection as a cause of death was unrecognized before death, with no major change occurring over the 40-year study period. CONCLUSIONS: Infections, especially respiratory and urinary tract infections, are frequent causes of death in RA patients. The high proportion of undiscovered infections as a cause of death highlights the diagnostic difficulty. With a decreasing number of autopsies being performed at present, greater numbers of infections may be under-reported.