Elderly-onset rheumatoid arthritis: ageing as an independent marker for better joint prognosis

Abstract

To study the contribution of age to the outcome of rheumatoid arthritis (RA), 133 elderly-onset RA (ERA) patients (onset above 60-year-old) were selected out of 2164 out-patients with RA who (i) first visited the hospital within 2 years after onset of the disease, (ii) received no remission inducing drugs previously and (iii) who were treated in this hospital regularly without interruption for more than 2 years. The joint score of ERA patients between initial visit and final visit to the hospital was compared with that of matched 133 younger-onset RA (YRA) patients (onset below 60-year-old). Results indicated that, in ERA, the patients with no active joints requiring no remission inducing drugs were increased on final visit (P < 0.001). Joint score at disease onset or on initial visit to the hospital was similar in the two groups, whereas joint score on final visit was significantly decreased in ERA (P = 0.0001). In ERA, progression of the small joint disease and joint erosion was not accelerated, and the small joint disease was in fact decelerated as compared with YRA (P < 0.0001) during initial visit and final visit. Discriminant function analysis of patients with or without no active joints on final visit reveals that joint erosion, in small joints on initial visit is a predictor of joint prognosis in ERA. The two groups were similar with regards to sex, disease duration, onset type and rheumatoid factor/antinuclear antibody positivity. Thus, older age is an independent marker of better joint prognosis of RA     

Elderly-onset rheumatoid arthritis: ageing as an independent marker for better joint prognosis

To study the contribution of age to the outcome of rheumatoid arthritis (RA), 133 elderly-onset RA (ERA) patients (onset above 60-year-old) were selected out of 2164 out-patients with RA who (i) first visited the hospital within 2 years after onset of the disease, (ii) received no remission inducing drugs previously and (iii) who were treated in this hospital regularly without interruption for more than 2 years. The joint score of ERA patients between initial visit and final visit to the hospital was compared with that of matched 133 younger-onset RA (YRA) patients (onset below 60-year-old). Results indicated that, in ERA, the patients with no active joints requiring no remission inducing drugs were increased on final visit (P<0.001). Joint score at disease onset or on initial visit to the hospital was similar in the two groups, whereas joint score on final visit was significantly decreased in ERA (P=0.0001). In ERA, progression of the small joint disease and joint erosion was not accelerated, and the small joint disease was in fact decelerated as compared with YRA (P<0.0001) during initial visit and final visit. Discriminant function analysis of patients with or without no active joints on final visit reveals that joint erosion, in small joints on initial visit is a predictor of joint prognosis in ERA. The two groups were similar with regards to sex, disease duration, onset type and rheumatoid factor/antinuclear antibody positivity. Thus, older age is an independent marker of better joint prognosis of RA     

Recent onset arthritis in the elderly: a 5 year longitudinal observational study

OBJECTIVE: To study the spectrum of diagnoses, course, and outcome of recent onset arthritis after the age of 60, presenting as rheumatoid arthritis (RA)-like disease. METHODS: A 5 year longitudinal observational study enrolled 92 consecutive patients (median age 73 yrs, 54/38 women/men, median duration of arthritis 12 weeks at inclusion). RESULTS: Forty-eight percent were classified as having RA according to the 1987 American Rheumatism Association criteria, 52% as non-RA (41.4% undifferentiated seronegative polyarthritis, 10.8% oligoarthritis with polymyalgic symptoms). Symmetrical involvement of small and medium size joints was more predominant in the RA (91 and 84%, respectively) than the non-RA patients (58 and 52%). The patients with RA compared to non-RA had more active and serious disease at onset, reflected by significant differences in number of swollen joints (median values 18 and 9, respectively), duration of morning stiffness (75 and 10 min), physician's global assessment of disease activity (45 and 28 mm on visual analog scale), and Health Assessment Questionnaire (HAQ) score for functional disability (1.8 and 1.0). Improvement during the course was observed in disease process variables as well as in HAQ disability score for both RA and non-RA patients. Risk factors for a poor 5 year functional outcome were female sex (OR 4.24), diagnosis of RA (OR 3.28), and baseline HAQ score > or =1.4 (OR 3.52). The median change in radiological progression (Larsen-Dale index) was zero. Twenty patients died during followup, the majority from cardiovascular diseases, infections, and malignancies. Mortality compared to the age and sex matched general population was increased for rheumatoid factor (RF) positive patients (standardized mortality ratio 272). Mortality risk factors within the patient cohort were male sex (OR 4.35), age (OR 1.17), and having RF+ RA (OR 11.93). CONCLUSION: Arthritis in the elderly is a heterogeneous group of arthritides with an overall favorable functional prognosis. The subgroup of women with elderly onset RA with functional disability at onset is at risk for a less favorable functional outcome. Mortality was increased for the patients with RF+ elderly onset RA only.     

Early rheumatoid arthritis patients: relationship of age

The aim of this study was to investigate if age at disease onset comprises a separate parameter for disease expression, prognosis, and outcome in early rheumatoid arthritis (RA) patients. Four hundred thirty-eight patients with early RA (disease duration less than 1 year) were studied. All of them fulfilled the American College of Rheumatology criteria for RA. The demographic, clinical, laboratory, radiologic, and therapeutic characteristics of the disease at diagnosis and during and at the end of follow-up (time period 1981-2000) were analyzed according to age at disease onset (young patients aged less than 60 years at disease onset vs elderly patients aged more than 60 years at disease onset). We found 317 young and 121 elderly patients with early RA. The male:female ratio, which was 1:3.2 in the young patients, was nearly equal in the elderly (1:1.4). In addition, at disease onset elderly patients showed more severe joint involvement (decreased grip strength) associated with high titers of acute phase response (erythrocyte sedimentation rate and C-reactive protein) than the younger patients. However, there were no differences between the two groups in the numbers of tender and swollen joints or acute phase response at the end of the study period. Furthermore, no differences were seen between the two groups concerning the presence of rheumatoid factor. Finally, the two patient groups showed the same degree of radiological changes and functional ability and were treated similarly, except for more frequent corticosteroid use in the elderly. We conclude that elderly patients present with more severe joint involvement at disease onset. However, at the end of the study, no differences were seen concerning radiological changes and functional ability. It seems that age at disease onset does not influence the clinical course and outcome of early RA patients.     

Inspiratory muscle strength and respiratory drive in patients with rheumatoid arthritis

In 15 patients with rheumatoid arthritis (RA) and in 12 age- and sex-matched normal subjects, we evaluated inspiratory muscle strength and respiratory control system. Inspiratory muscle strength was assessed by measuring maximal inspiratory pressure (MIP). Respiratory drive was assessed by evaluating surface electromyographic activity of the diaphragm (EMGd) during both room-air breathing and hypercapnic rebreathing. Compared to the predicted value (mean +/- 1.65 SD), MIP was significantly reduced in nine patients (60%). All told, we noticed a significant inverse relationship in the patients between MIP and duration of steroid therapy (p less than 0.01). During room-air breathing, both EMGd and mouth occlusion pressure (P0.1), expressed both in actual values and as percentage of MIP, were significantly greater in patients than in the normal control group (p less than 0.001 for both). Both EMGd and P0.1 (%MIP) response slopes to CO2 were significantly greater in patients than in the normal control group (p less than 0.01 and p less than 0.001, respectively) and significantly related to the functional stage of disease. During quiet breathing and for a PETCO2 of 60 mm Hg, both EMGd (p less than 0.01 and p less than 0.05, respectively) and P0.1 (%MIP) (p less than 0.01 and p = 0.001, respectively) were inversely related to MIP. These results indicate that RA patients may exhibit inspiratory muscle weakness and increased respiratory drive. Steroid myopathy and rheumatoid myositis could explain the reduction in MIP, whereas neural afferents arising from respiratory muscle, lung, or joint receptors could be involved in the observed increase in neural drive.     

Clinical assessment of disease activity in rheumatoid arthritis: evaluation of a functional test.

A cross sectional analysis of the correlation between clinical, laboratory, and radiological markers of disease activity in 98 patients with classical rheumatoid arthritis (RA) is reported. The median age was 38 years, the median age at onset of disease 29 years, and the median duration of disease seven years. The Keitel function test (KFT) showed good correlation with the Ritchie articular index (RAI) (p less than 0.0001; r = 0.5) and the disability questionnaire (DQ) (p less than 0.0001; r = 0.6). The RAI and DQ correlated weakly with laboratory variables, while the KFT showed significant correlation with the erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and plasma viscosity (PV) (p less than 0.001; r = 0.4; 0.3; 0.4). Only the KFT showed significant correlations with bone mass measurements (p less than 0.01; r = -0.3; -0.4), and the Larsen index at the right wrist (p less than 0.0001; r = 0.4). Consensus analysis suggested that the KFT is a useful single clinical test of disease activity in RA. The hand functional index (HFI), a component of the KFT, showed significant correlation with the total KFT (r = 0.9). Prospective drug trials are needed to establish the value of the HFI in the monitoring of patients with RA.     

Acceleration of atherosclerosis during the course of rheumatoid arthritis

Patients with rheumatoid arthritis (RA) are predisposed to atherosclerosis and cardiovascular disease. This is thought to be caused in part, by exposure to chronic systemic inflammation during the course of the disease. We hypothesized that RA disease duration augments the effect of age on atherosclerosis. We measured the carotid artery intima-media thickness (IMT) in 631 consecutive RA patients. We ascertained age, sex and disease duration, established CV risk factors, RA clinical manifestations and markers of inflammation. We used multivariable regression to model IMT, with age as the independent variable. We then added RA duration quartile x age interaction terms to estimate the IMT-age relationship within RA duration strata. We found that the rate at which the IMT increased per unit of age steepened in proportion to the RA duration, from 0.154 mm/10 years among patients with RA for 7 years or less, to 0.295 mm/10 years among patients with RA for 20 years or more (P相似文献   

The temporal relationship of Raynaud's phenomenon and features of connective tissue disease in rheumatoid arthritis

OBJECTIVE: In a prospective cohort study we examined the relationship between Raynaud's phenomenon (RP) onset and other connective tissue disease (CTD) characteristics in rheumatoid arthritis (RA) to determine if RP is predictive of RA severity and associated with other CTD signs, and if late onset RP in RA has an effect on prognosis compared to other patients with RA. METHODS: Using a standardized assessment, data were collected on 328 subjects with RA [mean age 60.3 +/- 0.7; 77% women; 76% erosions, 75% positive rheumatoid factor (RF)] seen at one London, Ontario, rheumatology clinic. The data included RA disease duration; presence and duration of RP; presence of nodules, joint damage, telangiectasia, and sclerodactyly; and RF status (+/-), RF value, antinuclear antibodies, and E-nuclear antibodies. RESULTS: The mean RA disease duration was 12 +/- 0.6 years. Seventy-one (22%) had RP and the mean RP duration was 9.2 +/- 1.5 years. Patients presented with RP a mean of 3.8 +/- 1.4 years after the diagnosis of RA. RP status was positively associated with the presence of sclerodactyly (p < 0.001), but not nodules or erosions. Higher RF values were associated with longer RA disease duration (p < 0.002) and longer RP duration (p < 0.01). CONCLUSION: Idiopathic RP may have a different clinical effect on RA than secondary RP; the latter is correlated with more severe RA. Sclerodactyly is associated with erosive arthritis and RP in RA. Higher RF values were indicative of increased RA and RP duration.     

Older age onset rheumatoid arthritis with or without osteoarthritis.

The clinical features of a group of 79 patients with older age onset rheumatoid arthritis (ORA) were compared with those of a group of 414 patients with younger age onset rheumatoid arthritis. The ORA group contained approximately equal numbers of men and women, were less rheumatoid factor positive, had a raised erythrocyte sedimentation rate, lower HLA-DR4 positivity, and a tendency towards larger joint involvement at the onset of the disease. These features have been reported by many authors except for the lower DR4 positivity. Of these features, the lower prevalence of rheumatoid factor positivity and the tendency towards larger joint involvement at the onset were characteristic of a subset of patients with ORA who had had osteoarthritis before the onset of rheumatoid arthritis. It is suggested that osteoarthritic large joints may be susceptible to the occurrence of rheumatoid synovitis at the onset of the disease, but that the osteoarthritis inducing factor may be negatively related to the progression of rheumatoid arthritis.     

Factors influencing mortality in rheumatoid arthritis

The prognosis in rheumatoid arthritis respecting mortality was studied in a consecutive series of 489 hospital patients over a period of 18 years. The relative risk of mortality was raised in both men (2.6; p less than 0.001) and women (3.4; p less than 0.001). In the women the relative risk was also influenced by prior duration of RA and was characterised by a diminution in risk 5-9 years after first presentation. Relative risks for men were more uniformly distributed over time. Annual excess mortality rates were strongly associated with age at first presentation in women, the rate increasing with increasing age in both the group seen within 5 years of onset of disease (chi 2(1) for trend = 30.4; p less than 0.001) and in the later referral group (chi 2(1) = 34.0; p less than 0.001). A similar but much less marked effect was observed in men in the early referral group (chi 2(1) = 13.7; p less than 0.001) only. These results suggest that initially women may have a milder form of disease and that hormonal status may affect prognosis. Future long-term therapeutic studies in RA should take into account the prognostic factors of age, sex and duration of disease.     

Does age bias the aggressive treatment of elderly patients with rheumatoid arthritis?

OBJECTIVE: Age bias has been reported to result in undertreatment of elderly patients with various medical conditions. We investigated whether a similar bias exists in the treatment of elderly patients with rheumatoid arthritis (ELDRA) compared to matched younger controls (YRA). METHODS: We performed an analysis of our RA clinical research registry to determine whether any differences exist between ELDRA and YRA patients with respect to use of combination disease modifying antirheumatic drugs (DMARD), biologic agents, corticosteroids, and nonsteroidal antiinflammatory drugs (NSAID). We also determined whether any difference in clinical status could be identified. RESULTS: Forty-nine female ELDRA subjects (age > 70 yrs) with insurance were matched for sex, insurance status, and duration of disease to YRA subjects (< 60 yrs). No statistically significant difference was noted in number of DMARD currently in use (1.24 +/- 0.78 vs 1.24 +/- 0.69, p = 1.00), or number of patients using biologic agents (25 vs 30; p = 0.31), corticosteroids (16 vs 11; p = 0.26), or NSAID (26 vs 36; p = 0.06). ELDRA and YRA patients also reported similar pain (judged using a visual analog scale, VAS; 3.5 +/- 2.6 cm vs 3.4 +/- 2.2 cm), fatigue (VAS 3.2 +/- 2.7 cm vs 3.9 +/- 2.9 cm), global assessment (VAS 2.8 +/- 2.2 cm vs 3.5 +/- 2.6 cm), and Health Assessment Questionnaire disability scores (0.82 +/- 0.5 vs 0.73 +/- 0.5). CONCLUSION: In this cohort of elderly patients with RA, we detected no bias in the use of RA treatment compared with younger controls. Clinical RA measures also showed that these elderly patients with RA were faring at least as well as the younger controls; they were not relatively undertreated.     

Interleukin abnormalities in recently active rheumatoid arthritis

Peripheral blood lymphocytes (PBL) from 14 patients with rheumatoid arthritis (RA) produced increased amounts of interleukin (IL) (p less than 0.05) as measured in a mouse thymocyte assay and showed enhanced proliferation in response to an IL containing supernatant (p less than 0.05) when compared with 9 age matched controls. Both enhanced IL production (p greater than 0.01) and responsiveness (p less than 0.002) were seen exclusively in a subgroup of 7 patients with a recent onset or exacerbation of their disease. PBL from RA patients with equally active disease which had been unchanged for more than 6 months produced and responded to IL normally. There was a direct correlation between IL production and responsiveness (r = 0.69, p less than 0.005). These 2 distinct IL abnormalities appear to reflect disease initiating or exacerbating factors in RA.     

Class-specific rheumatoid factors, DR antigens, and amyloidosis in patients with rheumatoid arthritis.

Class-specific rheumatoid factors (RFs) were measured by enzyme immunoassay in 59 patients with rheumatoid arthritis complicated by systemic amyloidosis (RA+A), 47 patients with rheumatoid arthritis without amyloid (RA), 106 patients with other rheumatic diseases (juvenile rheumatoid arthritis, systemic lupus erythematosus, Sjögren''s syndrome), and 55 blood donors. The patients with RA+A were characterised by a high prevalence of RF negativity; the IgM RF concentration was raised in only 18 of the 59 patients (31%, p less than 0.001 v RA), the IgG RF concentration in 20 of 59 (34%, p less than 0.001 v RA), and the IgA RF concentration in 24 of 59 (41%, p less than 0.001 v RA). A higher prevalence of HLA-DR4 (p less than 0.001) and a lower prevalence of DR2 (p less than 0.05) were found among 48 tested patients with RA+A when compared with a control panel consisting of 500 blood donors. No significant differences in the prevalence of DR1-DR7 or B27 antigens were observed, however, between patients with RA with or without amyloid.     

Work capacity of patients with inflammatory joint diseases. An eight-year follow-up study

In a prospective study of recent arthritis, 103 patients had rheumatoid arthritis (RA), 63 seronegative oligoarthritis (SO), 67 reactive arthritis (REA), 20 ankylosing spondylitis (AS), and 13 psoriatic arthritis (PA). At the 8-year check-up, 36% of patients with RA were at work, compared with 69% in PA (p less than 0.002), and 85-90% in AS, SO, and REA (p less than 0.001). Correspondingly 43% of the RA patients were disabled by arthritis, compared with 23% in PA (NS), 15% in AS (p less than 0.005), none in SO, and 4% in REA (p less than 0.001). No significant differences in work capacity were noted between patients with PA, AS, SO or REA. In RA, the educational backgrounds of patients unable to work (44 patients) and able to work (37 patients) did not differ from each other or from the overall population of Finland, but a significantly (p less than 0.01) smaller number of patients with arduous work were able to continue at work. The mean age of 49 years for RA patients unable to work differed highly significantly (p less than 0.001) from the 35 years of RA patients at work. However, the weightiest cause of limited work capacity was severity of disease.     

Sex: a major predictor of remission in early rheumatoid arthritis?

BACKGROUND: The treatment goal of early rheumatoid arthritis is remission. This study reports remission rates in clinical practice using a cohort of patients with early rheumatoid arthritis. METHODS: 698 patients with early rheumatoid arthritis were included. Mean age at inclusion was 58 years and mean disease duration was 6.4 months; 64% of the patients were women, 56% were positive for antibodies to cyclic citrullinated peptide and 60% were positive for rheumatoid factor. Remission was defined as a disease activity score <2.6, with or without ongoing treatment with drugs for rheumatoid arthritis. RESULTS: After 2 years, 261 of 689 patients were in remission (37.9%), and after 5 years, the remission rate was 38.5%. However, only 26.1% were in remission at both these time points. Multiple logistic regression analyses found sex to be a main predictor for remission. Thus, significantly fewer women were in remission after 2 years (32.1% v 48%, p = 0.001) after 5 years (30.8% v 52.4%, p = 0.001) and at both these time points (19.1% v 39.3%, p = 0.001). Although disease activity was not with certainty more pronounced in women at onset of disease, the disease course became markedly worse in women. The disparity in remission frequency between women and men could not be explained by differences in disease duration, age or treatment with disease modifying antirheumatic drugs or glucocorticoids. CONCLUSIONS: Early remission of rheumatoid arthritis by 28-joint Disease Activity Score<2.6 was as frequent or more frequent in this study than in most previous reports. Importantly, women had more severe disease with a considerably lower remission rate than men, although the disease activity before treatment seemed similar.     

Older versus younger onset rheumatoid arthritis: results at onset and after 2 years of a prospective followup study of early rheumatoid arthritis.

The influence of age at onset was studied in a prospective followup of early rheumatoid arthritis (RA). Patients greater than or equal to 60 years (n = 71) showed significantly more often an onset in both large and small joints and higher disease activity at the start compared with patients less than 60 years (n = 142). The higher disease activity was still present after 2 years of followup (greater than or equal to 60 years, n = 46, less than 60 years, n = 101); as well, there was a tendency towards more radiographic damage. Rheumatoid factor (RF) and DR4 were comparable in both age groups. Our data show a more severe course in older age RA. This disagreement with the literature is probably due to the fact that many studies are cross sectional with unbalance of RF in the 2 age groups.     

Articular chondrocalcinosis in seropositive rheumatoid arthritis. Comparison with a control group

The prevalence of articular chondrocalcinosis was studied in a group of 100 patients with seropositive rheumatoid arthritis (RA). Articular chondrocalcinosis was observed less frequently (3%) than in a control group (19%) of 221 age and sex matched patients with low back pain or extraarticular rheumatism. This difference is statistically significant (p less than 0.001). Articular chondrocalcinosis occurred in the older patients with RA, and was observed in those with the shortest duration of the disease.     

Tolerance and effectiveness of anti-tumor necrosis factor alpha therapies in elderly patients with rheumatoid arthritis: a population-based cohort study

OBJECTIVE: Limited data have been published on tolerance to and efficacy of classic or biologic disease-modifying antirheumatic drugs in elderly patients with rheumatoid arthritis (RA). The goal of the present study was to evaluate the tolerance to and effectiveness of anti-tumor necrosis factor (anti-TNF) agents in elderly patients (> or =65 years old) with RA (ERA) in comparison with younger patients (YRA). METHODS: The Swiss Clinical Quality Management program for RA is a longitudinal population-based cohort. All patients who had received at least 1 dose of anti-TNF agents between January 1997 and November 2005 were included and categorized according to their age. Tolerance was assessed by analyzing discontinuation rates of anti-TNF agents. Effectiveness of these agents was assessed by analyzing RA disease activity (Disease Activity Score in 28 joints [DAS28]) and functional disability (Health Assessment Questionnaire [HAQ]) after anti-TNF initiation. RESULTS: Among 1,571 patients with RA treated with anti-TNF agents, 344 were > or =65 years of age at treatment initiation. Drug discontinuation rates (median time 3 years) and mean change in DAS28 scores at 2 years (-0.65 versus -0.58) were identical in ERA and YRA. However, HAQ score improved significantly less in ERA (-0.02) than in YRA (-0.1) and a subsequent analysis revealed that this finding was essentially due to patients >75 years of age. CONCLUSION: Age in itself should not interfere with the decision to treat elderly patients with RA with anti-TNF agents. In a subset of patients ages >75 years, no functional improvement according to HAQ should be expected despite improvements in disease activity.     

Tolerance and effectiveness of anti–tumor necrosis factor α therapies in elderly patients with rheumatoid arthritis: A population‐based cohort study

Objective

Limited data have been published on tolerance to and efficacy of classic or biologic disease‐modifying antirheumatic drugs in elderly patients with rheumatoid arthritis (RA). The goal of the present study was to evaluate the tolerance to and effectiveness of anti–tumor necrosis factor (anti‐TNF) agents in elderly patients (≥65 years old) with RA (ERA) in comparison with younger patients (YRA).

Methods

The Swiss Clinical Quality Management program for RA is a longitudinal population‐based cohort. All patients who had received at least 1 dose of anti‐TNF agents between January 1997 and November 2005 were included and categorized according to their age. Tolerance was assessed by analyzing discontinuation rates of anti‐TNF agents. Effectiveness of these agents was assessed by analyzing RA disease activity (Disease Activity Score in 28 joints [DAS28]) and functional disability (Health Assessment Questionnaire [HAQ]) after anti‐TNF initiation.

Results

Among 1,571 patients with RA treated with anti‐TNF agents, 344 were ≥65 years of age at treatment initiation. Drug discontinuation rates (median time 3 years) and mean change in DAS28 scores at 2 years (–0.65 versus –0.58) were identical in ERA and YRA. However, HAQ score improved significantly less in ERA (–0.02) than in YRA (–0.1) and a subsequent analysis revealed that this finding was essentially due to patients >75 years of age.

Conclusion

Age in itself should not interfere with the decision to treat elderly patients with RA with anti‐TNF agents. In a subset of patients ages >75 years, no functional improvement according to HAQ should be expected despite improvements in disease activity.     

Prognostic factors for the development of rheumatoid arthritis and other connective tissue diseases in patients with palindromic rheumatism

OBJECTIVE: Palindromic rheumatism is characterized by attacks of acute arthritis of short duration. In the long term, a substantial proportion of patients will develop rheumatoid arthritis (RA) or other connective tissue diseases, but the determinants of subsequent chronic disease have not been adequately established. We identify clinical prognostic factors for the development of RA and other connective tissue diseases in patients with palindromic rheumatism in a retrospective cohort study. METHODS: The medical records of 4900 patients with arthritis referred from 1986 to 1996 to 3 rheumatologists at an academic center were reviewed. One hundred sixty patients were diagnosed as having palindromic rheumatism. After review, 127 complied with diagnostic criteria for palindromic rheumatism. Disease duration was estimated as time of first attack until the last consultation, or the development of RA or other connective tissue disease. Survival analysis including Cox regression was used to identify clinical variables associated with the risk of developing RA or other connective tissue disease, adjusting for varying disease duration. RESULTS: Sixty-five percent of the patients were female. Age at onset was 40+/-12 years. Mean disease duration was 6+/-6 years, and mean followup by the rheumatologists was 40+/-45 months. Joints more frequently affected were wrist, knee, and metacarpophalangeal. Forty-three patients (34%) subsequently developed a connective tissue disease including 36 (28%) RA, 3 (2%) systemic lupus erythematosus, and 4 (3%) other connective tissue diseases. In the final Cox regression model the hazard ratio for development of a connective tissue disease in the presence of a positive rheumatoid factor (RF) was 2.9 (p = 0.002), for proximal interphalangeal (PIP) joint involvement 2.4 (p = 0.02), for wrist involvement 2.5 (p = 0.05), for female sex 2.2 (p = 0.05), and for age at onset 1.03 (per year) (p = 0.001). Female patients with positive RF and involvement of the hands had an 8-fold risk of developing disease, compared with patients with one or fewer of these features. CONCLUSION: Positive RF and early involvement of the wrist and PIP joints predict the subsequent development of RA or other connective tissue disease in patients with palindromic rheumatism, and identify a group of patients at increased risk.