The mortality of rheumatoid arthritis.

OBJECTIVE: To determine the risk and causes of death and to quantify mortality predictors in patients with rheumatoid arthritis (RA). METHODS: RA patients (n = 3,501) from 4 centers (Saskatoon n = 905, Wichita n = 1,405, Stanford n = 886, and Santa Clara n = 305) were followed for up to 35 years; 922 patients died. RESULTS: The overall standardized mortality ratio (SMR) was 2.26 (Saskatoon 2.24, Wichita 1.98, Stanford 3.08, Santa Clara 2.18) and increased with time. Mortality was strikingly increased for specific causes: infection, lymphoproliferative malignancy, gastroenterologic, and RA. In addition, as an effect of the SMR of 2.26, the expected number of deaths was increased nonspecifically across all causes (except cancer), with a large excess of deaths attributable to cardiovascular and cerebrovascular diseases. Independent predictors of mortality included age, education, male sex, function, rheumatoid factor, nodules, erythrocyte sedimentation rate, joint count, and prednisone use. CONCLUSION: Mortality rates are increased at least 2-fold in RA, and are linked to clinical severity.

A double-blind placebo controlled trial of fluoxetine in fibromyalgia.

42 women were randomized to receive either placebo or fluoxetine at 20 mgs per day. Inter and intra group differences in clinical variables were evaluated after 3 and 6 weeks of treatment. Except for self rated anxiety which improved in the placebo treated group at 3 weeks, no differences between groups were noted. For those receiving fluoxetine both AIMS Anxiety (4.0 baseline vs. 3.3, p = 0.04) and Depression scores (2.6 baseline vs. 1.9, p = 0.03) improved at 3 weeks; however, improvement in the Beck Depression Scale did not reach significance (11.8 vs. 9.4, p = 0.34). At 6 weeks, both AIMS Depression (2.6 at baseline and 1.5 at 6 weeks, p = 0.03) and Beck Depression Scales (11.8 at baseline vs. 8.3 at 6 weeks, p = 0.04) showed improvement, as did sleep quality (9.6 vs. 7.6, p = 0.03). But no other variable had a significant change from baseline at either the 3 or 6 week point. Our data do not suggest that fluoxetine improves the signs and symptoms of fibromyalgia.

The prognosis of rheumatoid arthritis and undifferentiated polyarthritis syndrome in the clinic: a study of 1141 patients.

OBJECTIVE: To determine the prognosis of undifferentiated polyarthritis syndrome in the clinic compared with rheumatoid arthritis (RA). METHODS: We identified consecutive patients seen within the first 2 years of disease (and further subset into 6-month groups) diagnosed as having either RA or undifferentiated polyarthritis syndrome at the first clinic visit. Undifferentiated polyarthritis syndrome was characterized by clinical presentation, laboratory data, and American College of Rheumatology (ACR) 1958 and 1987 RA criteria. Followup evaluations were done to determine change in diagnosis, resolution of symptoms, and clinical remission of RA. RESULTS: Undifferentiated polyarthritis syndrome was more common in the clinic than RA (638 vs 503). Of patients with RA 7.6% were symptom free an average of 6.9 years after the first clinic visit. For those with disease onset between 0-6 months and 0-2 years, complete resolution of undifferentiated polyarthritis syndrome occurred in 57.9 and 53.9% of cases, including 46.1 and 35.6% meeting ACR 1987 criteria for RA. Latex positivity was the strongest predictor of failure to resolve subsequently (25.0 and 29.2% resolution) and the best predictor of development of RA (41.7 and 43.1%). CONCLUSIONS: Nonrheumatoid undifferentiated polyarthritis syndrome is more common in the clinic than RA. Undifferentiated polyarthritis syndrome resolves in more than half the cases, while RA remits in 7.6%. Finally, resolution of RA criteria positive undifferentiated polyarthritis syndrome occurs predominantly in those who are seronegative.

Measurement of gold treatment effect in clinical practice: evidence for effectiveness of intramuscular gold therapy.

OBJECTIVE: To determine the extent of efficacy of intramuscular (im) gold in clinical practice. METHODS: Ninety-eight patients who received im gold treatment for at least 1 year were assessed during ordinary clinic visits over the 12 month period following gold initiation. Assessments included joint counts, erythrocyte sedimentation rate (ESR), morning stiffness, visual analog scale (VAS) patient pain, VAS patient global, grip strength, prednisone dose, hemoglobin, and Stanford Health Assessment Questionnaire (HAQ) disability index. RESULTS: All outcome measures showed significant improvements at one year by standardized pretest posttest differences (effect size) and by measurement of the area under the curve (AUC). Important improvement (at least 50% improvement) was common: joint count (63.3%), global severity (41.1%), ESR (48.2%), grip strength (42.7%) HAQ disability (45.3%), and morning stiffness (72.2%). Effect sizes were substantial, even after correcting for placebo effect and withdrawals. Overall improvement was clinically significant, amounting to the equivalent of 2 months without pain or disability. CONCLUSION: Patients receiving gold for 12 months improved significantly and importantly in all measures studied. Improvement was clinically significant, amounting to the equivalent of 2 months without pain or disability. The degree of improvement was similar to, but somewhat greater, than that seen in controlled clinical trials, and could not be explained by regression to the mean.

The sense of coherence questionnaire in patients with rheumatic disorders.

Aaron Antonovsky's Sense of Coherence (SOC) questionnaire with its 3 subscales is designed to measure strengths within individuals that allow them to survive in the face of extreme stresses, including chronic illness. We administered the SOC to 1333 patients with rheumatic disorders. Although the instrument had high alpha reliability, factor analysis did not support the concept of distinct subscales. The SOC was strongly related to the Arthritis Impact Measurement Scales anxiety and depression scores (r = -0.63 to -0.69), less strongly related to clinical variables (r = -0.20 to -0.33), and was minimally related to demographic variables. When psychological variables were controlled for, almost no association between the SOC and clinical variables remained (r = 0.06). Whether the SOC will be more useful than standard psychological instruments awaits the result of ongoing studies.

Clinical and health status measures over time: prognosis and outcome assessment in rheumatoid arthritis.

We studied clinical and health status measures in 561 patients with rheumatoid arthritis (RA). Two hundred sixty-four patients were seen within 2 years of disease onset and followed for an additional 2 years. Four other groups were each followed for 5 years, and had disease durations of 2-7, 7-12, 12-17, and 17-22 years, respectively, at the first clinic visit. Functional disability developed very early in the course of RA and continued to worsen at about an equal rate over 22 years. Anxiety, pain scores, and self-assessed severity also increased with time, but erythrocyte sedimentation rate (ESR), morning stiffness, and joint counts were unchanged. Treatment resulted in reduction in joint counts and in nonsignificant improvements in ESR, stiffness, and psychological scores. But functional loss increased in each time period in spite of treatment. Variables most effective in controlled clinical trials are not effective as longterm measures of RA outcome.

The assessment and prediction of functional disability in rheumatoid arthritis.

We assessed functional disability with the Stanford Health Assessment Questionnaire Functional Disability Index (FDI) in 1,274 patients with rheumatoid arthritis (RA) followed longitudinally for up to 12 years. The rate of functional loss increased sharply after the first clinic visit. Half of patients with RA (median survival time) will reach FDI scores of about 1 in 2 years, 2 in 6 years, and 2.5 in 10 years after the first clinic visit, levels that correspond to moderate, severe and very severe loss of functional ability. Functional outcomes may be predicted by simple demographic and clinical assessments, the best of which are self-assessed measures of global severity, pain and function.

The misdiagnosis of gout and hyperuricemia.

Of 9,108 consecutive new patients seen in an outpatient rheumatology clinic, 155 (1.7%) were diagnosed as having gout. But 164 (1.8%) had been incorrectly diagnosed as having gout in the community. Misdiagnosis was more likely in those with psoriatic arthritis (odds ratio 3.841, 1.944-7.590) and pseudogout (odds ratio 4.152, 2.422-7.119) and less common in patients with nonspecific arthralgias (odds ratio 0.536, 0.326-0.881). Seventy-six percent of incorrectly diagnosed patients received allopurinol while slightly more than 15% were treated with uricosuric agents.

The latex test revisited. Rheumatoid factor testing in 8,287 rheumatic disease patients.

Rheumatoid factor (RF) testing by latex fixation in 8,287 outpatients yielded a sensitivity of 81.6% and 78.0% at titers of 1:20 and 1:80, respectively, and a specificity against noninflammatory rheumatic disorders (NIRD) of 96.6% and 97.9% and against NIRD plus inflammatory disorders of 95.2% and 96.8%, respectively. The predictive value of a positive test result at the clinic prevalence rate for rheumatoid arthritis (RA) (16.4%) was approximately 80%, and was 70% at 10% prevalence and 10% at 1% prevalence. No associations of RF with age or sex were found in non-RA patients. RF titers increased minimally with age in RA patients and were higher in men than in women. This study suggests that latex testing is far more specific than has been believed and that the titer is not spuriously increased with age.

The effect of age on methotrexate efficacy and toxicity.

We studied the clinical course of 235 patients with rheumatoid arthritis (RA) receiving methotrexate (MTX) over a mean of 1.9 years. Both older (greater than 65 years) and younger (less than or equal to 65 years) patients demonstrated clinical improvement, but older patients had greater improvement in erythrocyte sedimentation rate and hemoglobin than younger patients. Most assessments of laboratory abnormalities and symptoms suggestive of toxicity did not differ between age groups. But more gastrointestinal complaints and pulmonary complaints were reported in older patients, associations that have been noted in older patients not treated with MTX as well. Our data indicate that treatment that includes MTX is effective in older patients with RA, and that older patients improve at least as much as younger.

Marital status in rheumatoid arthritis and other rheumatic disorders: a study of 7,293 patients.

Divorce has been considered to be increased in rheumatoid arthritis (RA), perhaps as a result of the stress of serious chronic illness. We studied marital status in 7,293 consecutive rheumatic disease patients attending an outpatient rheumatic disease clinic. Divorce was associated with age, sex, population size, and ethnic origin, but when these factors were controlled for, divorce was not more common in the 1,267 patients with RA. Age and sex adjusted divorce percentages for RA and non-RA patients were 6.9 and 6.8 compared with a U.S. percentage of 7.6. Patients with RA, however, were almost 5 times less likely to be remarried after divorce than patients with osteoarthritis.

Analysis of methotrexate treatment effect in a longitudinal observational study: utility of cluster analysis.

We studied 235 patients with rheumatoid arthritis (RA) beginning therapy with methotrexate utilizing a k-means clustering algorithm. Four groups were identified: mild RA (Group 3), very severe RA (Group 4), and 2 groups intermediate in severity (Groups 1 and 2). Group 2, the largest of the clusters (n = 89), appeared to have greater tolerability of RA as measured by severity and psychological variables, and took the drug almost twice as long as other groups, although improvement was not greater nor side effects fewer. All groups improved over a mean of 1.9 years, and the degree of improvement was not related to the initial severity classification. Improvement occurred almost equally in all clusters, and the relative ranking of the groups was maintained at study closure.

Termination of slow acting antirheumatic therapy in rheumatoid arthritis: a 14-year prospective evaluation of 1017 consecutive starts.

During a continuous 14-year observation period we prospectively recorded clinical data on all patients with rheumatoid arthritis (RA) attending an outpatient clinic. Six hundred seventy-one patients received 1017 new administrations of slow acting antirheumatic drugs during more than 2000 patient years of observation. The median time to discontinuation for intramuscular gold, auranofin, hydroxychloroquine or penicillamine was 2 years or less, but was 4.25 years for methotrexate (p = 0.008 vs all other drugs combined). Adverse reactions were a more common reason for discontinuation than efficacy, and both were less common in patients taking methotrexate (p less than 0.01). Neither disease duration, disease severity, or demographic factors were useful predictors of discontinuation. Since controlled clinical trials do not provide long-term outcome assessments, measurement of time to termination is a practical tool to estimate drug inefficacy.

The clinical value of the Stanford Health Assessment Questionnaire Functional Disability Index in patients with rheumatoid arthritis.

We administered the Stanford Health Assessment Questionnaire functional disability questionnaire to a cohort of 400 patients with rheumatoid arthritis (RA) every 6 months during a mean followup of 3.1 years. Simple classification into 3 groups based on Functional Disability Index (FDI) scores (0-1, 1.1-2, 2.1-3) identified patients with increasingly more severe scores for clinical, psychological, and demographic variables; and FDI scores at entry predicted increased inpatient and outpatient utilization of services, and mortality. The FDI provided important and clinically useful current and predictive information regarding RA status, utilization of services, and mortality that was not available through conventional testing. Our data suggest that such information can be easily and inexpensively obtained.

Pain, functional disability, and psychological status: a 12-month study of severity in fibromyalgia.

We mailed monthly questionnaires regarding fibromyalgia symptoms to 75 patients during a one-year period. Fibromyalgia symptoms in individual patients were generally stable over time as assessed by repeated measures and slope analyses, but patients clearly differed from one another in symptom severity. Pain, psychological status, and functional disability, but not sleep disturbance or morning stiffness, were the independent explanatory factors for disease severity in regression models. Functional disability has not been recognized previously as an important factor in fibromyalgia severity, but our data suggest that it should be assessed as a process and outcome measure in future fibromyalgia studies.

Socioeconomic impact of fibrositis. A study of 81 patients with primary fibrositis.

Demographics and health service utilization were studied for 81 patients with fibrositis during 1985. Patients reported high levels of pain, mild disability, and moderate impairment of global health. Work disability was limited and only 6.3 percent described themselves as disabled. Employed patients were able to work full work weeks. Utilization of outpatient medical services was increased compared with that of control subjects and national averages during the study year, but was consistent with other rheumatic disorders such as osteoarthritis and low back pain. Medication usage was limited and seemed appropriate. Very high hospitalization rates were noted prior to diagnosis of fibrositis, both for musculoskeletal and non-musculoskeletal hospitalizations, but these rates dropped during the post-diagnosis study year.

The epidemiology of tender points: a prospective study of 1520 patients.

Tender point examinations were performed on 1520 consecutive patients with various rheumatic diseases. The mean tender point count was 2.1 (3.6 SD). Four or more tender points were found in 22.9%, 7 or more in 13.6%, 12 or more 4.3%, but 60.1% had no tender points. The tender point count increased gradually with age, reaching a maximum at age 70. Women had more tender points than men, Caucasians more than blacks or Hispanics. Isolated regional clusters of tender points occurred at the shoulder girdle in 7.8%, and the knees in 7.4%. Correlation between tender points and associated peripheral joint tenderness was poor.

Fibrositis: symptom frequency and criteria for diagnosis. An evaluation of 291 rheumatic disease patients and 58 normal individuals.

We administered a 17-item symptom questionnaire modified from Campbell to 155 patients with fibrositis diagnosed at 3 centers, each using different criteria sets. A high degree of agreement in symptom proportions was found among centers. "Fibrositic" symptoms were also common in 136 patients with a variety of rheumatic diseases but not in the 58 normal individuals studied. Symptoms distinguished fibrositis patients from normals easily, but had insufficient specificity to distinguish them from other rheumatic disease patients. The tender point count better separated fibrositic and nonfibrositic patients than historical criteria. No combination of questions and tender point count performed better than the tender point count alone.