Younger-onset Rheumatoid Arthritis Research Articles

Elderly‐ versus younger‐onset rheumatoid arthritis: Higher levels of ultrasound‐detected inflammation despite comparable clinical disease activity

To compare ultrasound-verified joint inflammation between elderly-onset rheumatoid arthritis (EORA) and younger-onset rheumatoid arthritis (YORA) patients. We conducted a retrospective analysis of 145 consecutive rheumatoid arthritis patients routinely assessed by sonography of wrists, metacarpophalangeal joints, and proximal interphalangeal joints, including semiquantitative scoring of synovial hypertrophy/effusion (SH/E) and power Doppler (PD) signals. Global ultrasound (GU) scores were calculated adding SH/E and PD results. EORA was defined by disease onset at age ≥60 years. Number of tender joints and swollen joints, global assessment of disease activity by physician or patient, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index (SDAI) scores were recorded. Respective values for disease activity were accounted for in group comparisons using SPSS statistical software (version 18.0). Seventy patients were diagnosed with EORA (mean ± SD age 71.0 ± 7.3 years, 81.4% women) and 75 patients with YORA (mean ± SD age 46.8 ± 10.2 years, 86.7% women). EORA patients had higher GU scores (median 18.5 [interquartile range (IQR) 17.0] versus 12.0 [IQR 15.0], P = 0.009) and SH/E scores (median 12.0 [IQR 10.0] versus median 9.0 [IQR 9.0], P = 0.004) than patients with YORA. Patients with EORA were more likely to show PD signals in at least 1 joint than YORA patients (85% versus 72%; odds ratio 3.9 [95% confidence interval 1.3-11.5], P = 0.015). DAS28, CDAI, and SDAI scores did not differ between the groups. The sonographic pattern of joint involvement was similar in both groups, with active inflammation most commonly presenting at the wrists. Ultrasound examination indicated higher inflammatory burden in EORA patients than in YORA patients despite similar clinical disease activity.

Arthritic disease is more severe in older rats in a kaolin/carrageenan-induced arthritis model

This study examined in an arthritis animal model whether elderly onset rheumatoid arthritis (EORA) is a more severe disease than younger onset rheumatoid arthritis. Arthritis was induced by injecting 5% kaolin/carrageenan into the left tibiotarsal ankles of 18-month-old and 4-week-old rats. Various parameters were measured to evaluate the arthritic progression of kaolin/carrageenan-induced arthritis in the rats. Immunohistochemical staining of arthritic joints was performed to determine the degree of inflammation in old and young rats. Measurements of ankle volume and thickness, arthritic index, number of squeaks, and the paw pressure test showed the 18-month-old rats had more severe disease than the young rats in a kaolin/carrageenan-induced arthritis model. The degree of inflammation and MMP-1 expression of arthritic joints in old rats was significantly higher than that of young rats based on histological evaluation with hematoxylin and eosin (H&E) staining and immunochemistry. More severe disease symptoms were found in old rats with EORA, but the molecular mechanisms still remain to be elucidated. Understanding the molecular mechanisms will be helpful to develop clinical protocols to efficiently treat patients with EORA, which is difficult to control with current protocols.

Pattern of Young and Old Onset Rheumatoid Arthritis (YORA and EORA) among a Group of Egyptian Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) differs depending on the age of disease onset. The differences between EORA and YORA are important because they have clinical and therapeutic implications. 1185 patients were ranked after classification according to age at onset of the disease into YORA I (16-40 years), YORA II (41-60 years) and EORA >60 years. All patients groups were compared, based on disease duration, disease activity, severity parameters and drug history. YORA I included 298 patients, 28.85% were males, with mean age of 29.4 ± 6 years and disease duration 4 ± 3.3 y, YORA II included 539 patients, 33.77% males, age 49.7 ± 6.1 y and disease duration 6.5 ± 5.6 y. EORA included 348 RA patients 40.5% males, age 67.1 ± 6.6 y, disease duration 9.95 ± 7.2 y. Activity was increased in EORA compared to YORA I and YORA II, while severity decreased in EORA. ESR, CRP and degree of anemia were higher in EORA. RF titer was higher in YORA. Small joints of the hands and feet were more involved in YORA, while, large joints in EORA. Rheumatoid nodules were increased in YORA I than EORA P = 0.04. Polymyalgia rheumatica was exclusively present in EORA group 25 patients 7.2%. Methotrexate was used in both YORA and EORA, with a higher mean of dosage in YORA than EORA. Multiple DMARDs in EORA was 57.9%, and biologics in 0.8% was which was significantly lower compared with YORA I, 86.3% and 1.7%, with P = 0.001. EORA has more active and less disabling and affects more males than YORA. The use of biologic therapy and combination DMARD therapy was less in EORA.

Elderly onset rheumatoid arthritis

Elderly-onset rheumatoid arthritis (EORA), defined as rheumatoid arthritis (RA) with the onset at the age > or =60 differs sligthy at presentation from younger-onset RA (YORA) by a more equal sex distribution, a higher frequency of an acute onset, more frequent involvement of large joints, especially of the shoulder, and higher disease activity. Longitudinal studies have shown greater disease activity, more severe radiographic damage and functional decline in patients with EORA than in those with YORA. These differences were only found in seropositive patients. In seronegative EORA patients a less severe course of the disease and a better outcome have been observed, with the clinical manifestations of polymyalgia rheumatica or remitting seronegative symmetrical synovitis with pitting edema. This article is a review of available data concerning differences between EORA and YORA.

Interleukin-1RN gene polymorphisms in elderly patients with rheumatic inflammatory chronic conditions: Association of IL-1RN*2/2 Genotype with polymyalgia rheumatica

The objective of this study was to investigate whether there is an association between IL1RN polymorphism and disease susceptibility for three age-related inflammatory conditions: polymyalgia rheumatica (PMR), giant cell arteritis (GCA), and elderly-onset rheumatoid arthritis (EORA). A tandem-repeat polymorphism within IL1RN intron 2 was analyzed in 139 PMR, 69 GCA, and 156 RA patients (75 with EORA) as well as in 437 healthy subjects, together with the in vitro production of IL-1β. Our results showed that the IL1RN*2/2 genotype was more frequent in PMR patients compared with controls ( p = 0.032, odds ratio = 1.785, 95% confidence interval = 1.047–3.044) and GCA patients ( p = 0.008, odds ratio = 4.661, 95% confidence interval = 1.352–16.065). We found no difference in the distribution of genotypes between PMR and EORA or between EORA and controls. However, the frequency of the IL-1RN*2/2 genotype had a tendency to be higher in patients with EORA compared with young onset RA. The presence of IL1RN*1 or IL1RN*2 allele was not associated with severity of the disease in PMR and GCA patients and did not influence the production of IL-1β. In conclusion, the IL1RN*2 polymorphism in a homozygous state was associated with an increased susceptibility to PMR and may give some clues for a differential therapy with GCA.

Increased numbers of CD5+ B cells and T cell receptor (TCR) gamma delta+ T cells are associated with younger age of onset in rheumatoid arthritis (RA).

Patients presenting with RA before the age of 45 years (younger onset) are known to have more aggressive disease compared with patients presenting after the age of 65 years (older onset). Coordinated expansion of circulating CD5+ B cell and TCR gamma delta+ T cell levels has been reported in patients with RA. This study assesses the peripheral blood levels of these two cell types in RA patients with younger and older onset of disease. CD5+ B cell levels were significantly elevated in the younger onset RA group (26.6+/-4.5%) compared with the older onset RA group (14.2+/-1.2%; P<0.01). TCR gamma delta+ T cell levels were also significantly raised in the young patients (4.0+/-0.9%) compared with elderly patients (1.6+/-0.2%; P<0.01). T cell levels (CD3+) were similar in both groups (young 66.4+/-3.3%; old 74.3+/-3.4% (mean+/-s.e.m.); NS). Total B cell levels (CD19+) were also similar in these groups (7.7+/-0.7% versus 8.9+/-1.8%; NS). A significant positive correlation was observed between the CD5+ B and TCR gamma delta+ T cell types in the patients (r=0.72, P<0.05). Compared with age-matched normal controls, the younger onset patients had similar CD5+ B cell and TCR gamma delta+ T cell levels to the elderly controls (CD5+ B cells 30.2+/-3.0%; TCR gamma delta+ T cells 3.0+/-0.8%). Conversely, older onset RA patients had CD5+ B cell levels similar to the young controls (12.3+/-1.9%). Spontaneous in vitro synthesis of immunoglobulins (IgM, IgA and IgG) and rheumatoid factors (IgM and IgA isotypes) were not significantly different in both patient groups. The coordinate expansion of circulating CD5+ B cells and gamma delta+ T cells seen in patients with RA presenting before 45 years of age and not after 65 years of age may suggest a potential role for these cells in more aggressive disease states.

Despite comparable disease severity, patients with elderly-onset rheumatoid arthritis (EORA) receive less 'aggressive' treatment than those with younger-onset rheumatoid arthritis

Despite comparable disease severity, patients with elderly-onset rheumatoid arthritis (EORA) receive less 'aggressive' treatment than those with younger-onset rheumatoid arthritis

Despite comparable disease severity, patients with elderly-onset rheumatoid arthritis (EORA) receive less 'aggressive' treatment than those with younger-onset rheumatoid arthritis

Despite comparable disease severity, patients with elderly-onset rheumatoid arthritis (EORA) receive less 'aggressive' treatment than those with younger-onset rheumatoid arthritis

Late onset rheumatoid arthritis: Clinical and laboratory comparisons with younger onset patients

We aimed to compare the clinical and laboratory profiles of the patients presenting late onset rheumatoid arthritis (LORA) with younger onset rheumatoid arthritis (YORA) patients. During the period between January 1995 and December 2004, 124 patients with LORA were identified from a retrospective chart review of inpatients and outpatients. They were compared with 150 YORA patients examined during the same period including their clinical and laboratory findings. The mean ages of the patients with LORA and YORA were 71.7 ± 5.9 years, and 52.1 ± 11.5 years, respectively. The gender ratio (female/male) was 1.48 in LORA and 2.85 in YORA ( p = 0.012). The average ages of the disease onset were 42.2 ± 10.4 years in YORA and 68.4 ± 4.6 years in LORA. The duration of the diagnosis was longer in LORA than in YORA (20.7 ± 14.3 months versus 10.3 ± 6.2 months, p < 0.001). Rheumatoid arthritis (RA) duration was shorter in LORA than in YORA (43.5 ± 64.4 months versus 126.3 ± 101.0 months, p < 0.001). Although LORA patients had more significant frequent shoulder joint involvements ( p < 0.001), proximal interphalangeal (PIP), metacarpophalangeal (MCP), elbow, metatarsophalangeal (MTP) and ankle involvements were common in YORA. Wrist, knee and hip involvements were not different in the groups. Classical rheumatoid hand deformities, interstitial lung disease and Sjögren's syndrome (SS) were significantly lower in LORA than in YORA. LORA patients had more common weight loss, myalgia, lymphadenopathy, polymyalgia rheumatica (PMR)-like syndrome and neuropathy. The frequencies of RF, ANA, anti-SSA/Ro and anti-SSB/La positivities were lower in LORA than in YORA, whereas elevated erythrocyte sedimentation rates (ESR), C-reactive protein (CRP) and anemia associated with chronic disease were higher in LORA. Patients with LORA, according to the accepted international criteria, present with different clinical and laboratory profiles when compared with younger patients. These results suggest that age may influence the presentation of RA at onset.

Perturbations of hypothalamic-pituitary-gonadal axis and adrenal androgen functions in rheumatoid arthritis: an odyssey of hormonal relationships to the disease.

Rheumatoid arthritis (RA) is a heterogeneous disease with a diverse spectrum of manifestations and course of illness. Multiple factors are believed to contribute to its etiology. Nevertheless, consistent features are observed across populations, which include (1) increased familial or immunogenetic risk in younger-onset disease; (2) female predisposition, particularly during child-bearing ages; (3) predictable clinical improvement during pregnancy and worsening postpartum; and (4) increased incidence with aging, which suggest that hormonal factors influence the disease. In 1974, serum was prospectively obtained from pre-RA cases, 4 to 20 (mean = 12.0) years prior to onset of disease and concurrently from controls (CN) matched (4 CN per 1 RA) on age (+/- 2 years), race (all Caucasians), and entry menopausal status (EMS). CN have no known rheumatic disease. Pre-RA were divided into subgroups, according to EMS, i.e., premenopausal vs. non-premenopausal (peri- or post-menopausal), and either age at entry in 1974 or age at onset of RA. For example, one 3-way subgrouping includes: I. Entry premenopausal and RA onset < age 50 years; II. Entry premenopausal and RA onset age 50+ years, and III. Entry postmenopausal. The 11 youngest pre-RA (I) had a mean entry age of 29 years and RA onset of 41 years. An alternative 4-way subgrouping (a, b, c, d) divided the female subjects into premenopausal (last menstrual period [LMP], 0-31 days) and non-premenopausal major groups, as well as younger vs. older subgroups within the major EMS categories. The younger premenopausal women in each subgrouping system, that is, I or a, overlap almost entirely. Assays (RIA) of the major sex hormones were performed, e.g., luteinizing hormone (LH); follicle stimulating (FSH); estradiol (E2); progesterone (P4); and total testosterone (T); as well as adrenal hormones, including androstenendione (A4); dehydroepiandrosterone (DHEA); its sulfate (DHEAS); and cortisol (C). A significantly lower entry mean serum DHEAS level (mumol/L) was found in the pre-RA subgroup I, than in the 43 CN (2.14 +/- 0.47 vs. 3.62 +/- 0.37, respectively, (p = 0.033). The 25 older pre-RA and 100 CN (subgroups II and III) showed close mean DHEAS levels (1.89 +/- 0.30 and 1.94 +/- 0.14, respectively, p = 0.45). The serum DHEAS levels in pre-RA vs. CN subgroups were validated in a second reference laboratory. Also, the youngest pre-RA subgroup (I) showed a significant dissociation between entry serum DHEAS and cortisol levels (r = -0.660, p = 0.027), which differed (p = 0.017) from its matched CN, and from the older pre-RA (p = 0.004). Analyses of results based upon subgroupings by EMS and entry age (a, b, c, d) showed similar results. No significant differences were found between pre-RA and CN groups in levels of serum cortisol, other adrenal steroids, or the sex hormones assayed. In a sample of younger premenopausal women, significantly low serum DHEAS levels were found 4 to 20 years prior to onset of RA. Dissociation of serum cortisol and DHEAS levels was also found in the youngest, but not older, pre-RA subjects. The data suggest that subtle adrenal cortical dysfunction, manifested mainly by adrenal androgen (AA) deficiency, may either predispose to younger-onset RA or be a long-term marker in a minority subgroup of women.

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

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

Synovial fluid levels of proinflammatory interleukins and their inter-relationships in elderly vs younger onset rheumatoid arthritis.

Elderly-onset rheumatoid arthritis (EORA) is thought to be different from younger-onset disease (YORA) for many reasons, including a more elevated acute phase response and a more abrupt onset; both events are mainly regulated by pro-inflammatory interleukins (ILs), in particular, IL-1, IL-6 and IL-8. To compare the synovial fluid (SF) levels of these ILs, and their relationship to local inflammation as well as the acute phase response, erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) in the two RA subsets, we determined white blood cell (WBC) number, total protein (TP), IL-1beta, IL-6 and IL-8 concentrations in the SF of 50 patients, 15 with EORA and 35 with YORA. Both ESR and CRP were higher in EORA than in YORA. IL-6 was higher in SF of EORA (2111.37 +/- 1425.03 pg/mL) than YORA (1077.53 +/- 757.62 pg/mL, p = 0.002), while no difference was observed for SF IL-1beta and IL-8. There was a weak correlation between SF IL-6 and IL-1beta in EORA, whereas SF ILs and CRP and/or ESR did not show any correlation in both groups. Our study indicates that in EORA, as in other diseases occurring in the elderly, there are elevated levels of IL-6. Higher SF levels of IL-6 may be, at least in part, responsible for the different behavior of EORA with respect to YORA.

Elderly-onset rheumatoid arthritis

Elderly-onset rheumatoid arthritis (EORA), defined as rheumatoid arthritis (RA) with onset at age 60 years or over, differs slightly at presentation from younger-onset RA (YORA) by a more equal gender distribution, a higher frequency of acute onset with systemic features, more frequent involvement of the shoulder, and higher disease activity. Longitudinal studies have showed more disease activity, radiographic damage, and functional decline in patients with EORA than in those with YORA. These differences were only found in seropositive patients. Seropositive EORA was reported to be associated with HLA-DR4, in contrast to seronegative EORA. Possible heterogeneity in the pathogenesis of seronegative EORA is supported by the recognition of subsets that overlap with the clinical manifestations of other syndromes such as polymyalgia rheumatica and remitting seronegative symmetrical synovitis with pitting edema. In addition, crystal-induced arthritis and inflammatory osteoarthritis may be difficult to distinguish from EORA. The efficacy and toxicity of second-line drugs is similar in both age groups, but in the elderly caution is needed with the use of nonsteroidal antiinflammatory drugs and prednisone.

Differences in Autoantibody Levels in Older Onset vs Younger Onset Rheumatoid Arthritis

Differences in Autoantibody Levels in Older Onset vs Younger Onset Rheumatoid Arthritis