ELDERLY-ONSET RHEUMATOID ARTHRITIS

doi:10.1016/S0889-857X(05)70154-X

Rheumatic Disease Clinics of North America

Volume 26, Issue 3, 1 August 2000, Pages 517-526

https://doi.org/10.1016/S0889-857X(05)70154-X Get rights and content

Rheumatoid arthritis (RA) is a systemic, inflammatory disorder affecting primarily women with a peak incidence between 30 and 50 years of age and an average age of onset of 55 years.²⁰ At this time, one third of patients acquire RA after the age of 60, and the prevalence increases with advancing age into the eighth decade. This is particularly important because of the growth of the proportion of older persons in our population and the potential implications for the care of these patients in the next century. If, as some authors have espoused, elderly-onset RA (EORA) beginning after 60 years of age is a distinctly different disorder from younger-onset RA (YORA), physicians must be aware of this and its diagnostic and therapeutic significance.

The following profile of EORA, as distinct from YORA, has evolved from many clinical studies that vary in their design, control groups, and length of follow-up6, 11, 14, 24, 26, 30:

1
More equal sex distribution: Whereas YORA is more common in women than in men by 3:1, in the older group, the ratio is closer to 1:1.
2
Acute onset: In YORA, an insidious onset is the most common. In EORA, there is a tendency for the onset to be acute and infectious-like.
3
More frequent involvement of large, proximal joints (i.e., shoulders): The characteristic presentation of RA is in the small joints of the hands and feet. In EORA, patients are more likely to develop proximal symptoms, more akin to polymyalgia rheumatica (PMR). This is particularly important because there is a strong consideration given to the possibility that EORA and PMR, and even remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome, may be parts of a single spectrum of inflammatory disorders of the elderly.
4
More systemic manifestations and higher ESR at onset: Fatigue, weight loss, and elevated ESR may be manifestations YORA and EORA. They appear, however, to be more prominent in EORA, a fact that might relate to some basic differences in etiology, cytokine profiles or treatment options.
5
Lower frequency of rheumatoid factor (RF) positivity: In YORA, approximately 80% of patients are seropositive. Whereas in some EORA series, this frequency is between 66% and 89%, others show levels as low as 32%. This may reflect differences in study populations or might relate to changes in the immune system that occur with aging.
6
Worse outcome: The greater functional limitation and severity of joint damage in some patients with EORA may be explained by the effect of comorbid disease in the elderly or changes in the balance between damage and repair as people age.

Immunosenescence, genetics, and hormonal factors are probably important variables in the observed difference between EORA and YORA. All these factors have age-related changes that can fundamentally affect how the body responds to disease-causing or -modifying factors.

Section snippets

IMMUNOSENESCENCE

Alterations in the immune system that occur with age are listed below.

Age-related changes in the immune system

•
Thymic involution
•
Changes in functional phenotypic characteristics of T cells
•
Decline in specific antibody responses
•
Age-related defects in apoptosis
•
Cytokine imbalance
•
Deficiencies in antigen processing

Some or all of these might alter the response to antigens or the disease presentation in the aged. With age, the capacity to generate protective immune responses declines, whereas reactivity to autoantigens increases.³⁴ The

GENETICS

There is a well-established association between RA and certain class II major histocompatibility alleles, most specifically DR4. This genetic marker appears to be linked to an increased propensity for and severity of RA and has a strong association with the presence of rheumatoid factor positive RA. Some studies, but not all, have even shown such an association with seronegative disease, regardless of age.

In several studies, EORA patients were HLA-typed.11, 24 All confirmed the same DR4 linkage

HORMONES

The possibility that sex hormones play an important role in the clinical presentation of RA is supported by the fact that the inflammatory process improves significantly during pregnancy in a large proportion of patients.¹⁷ The development of RA is decreased in frequency in patients on oral contraceptives.⁴ Exogenous estrogen administration, however, does not decrease disease activity and the differences in hormone levels between women and men do not correlate with the disease outcome.12, 26

COMORBITIES

In the elderly, RA often coexists with other chronic medical disorders, including atherosclerosis, hypertension, diabetes, osteoarthritis, and osteoporosis. Each of these, by themselves, can alter function, change the structure of bones, joints and muscles, and demand complicated medication regimens. Soft-tissues and fat pads are atrophied and neurologic disorders may occur, leading to an increased propensity to fall and traumatize bones, tendons, ligaments, and muscles. Depression may

CLINICAL MANIFESTATIONS

Many studies have described the clinical features of EORA (Table 1) and they can be divided into those assessing consecutive patients and others that are cross-sectional. The focus on consecutive patients and the use of a younger-onset control group, optimal methodological techniques, are employed in a few studies.¹⁶

The percentage of women in these studies is lower than the 66% to 75% generally reported for RA. One study without a comparison YORA group found that the acute onset and weight loss

PROGNOSIS

There are not many studies addressing prognostic factors in EORA. One study shows persistent arthritis in 39% of seropositive patients versus 6% of seronegatives.¹³ The former patients required more disease modifying antirheumatic drugs (DMARD). Another study showed that the seropositive patients had more swollen joints, radiological damage, and mortality than seronegative patients.²⁶ The differences in outcome between seronegative and seropositive patients were more pronounced in the EORA

DISEASE COURSE AND OUTCOME

Most studies show that disease activity remains high 2 to 6 years after diagnosis.14, 27 This is consistent with studies looking at RA patients regardless of age at onset; more radiologic damage, and functional decline were found in older-onset seropositive, but not seronegative RA patients.¹⁴ Other factors may contribute to the worse prognosis in a cohort of EORA patients, most importantly comorbities. Most RA patients have the intercurrent illnesses and serious medical conditions that occur

DIFFERENTIAL DIAGNOSIS

Viral polyarthritis and seronegative spondyloarthropathies are diseases of young adulthood even though rarely can present in elderly patients. Crystal arthritis, inflammatory osteoarthritis (OA) and malignancy-associated arthritis usually occur later in life. Differential diagnosis can be rather difficult given that elderly patients may have several problems at the same time. Previously published series on EORA, especially seronegative EORA patients, most likely included patients with other

THE ASSOCIATION BETWEEN RA, PMR AND RS₃PE SYNDROME

Seronegative EORA makes up 1% to 48% of the EORA patients, depending on the series.13, 14, 27 There are two syndromes that may be indistinguishable from seronegative EORA: polymyalgia rheumatica (PMR) and the syndrome of remitting seronegative symmetrical synovitis with pitting edema (RS₃PE syndrome) (Table 3).

PMR and EORA may well be overlapping disease entities. Elderly patients with seronegative RA have PMR-like symptoms more often than seropositive patients.²⁴ They also can have alternating

TREATMENT

Treatment indications for rheumatoid arthritis are not different for the elderly patient, however, problems with decline in cognitive function, coexistent illness, polypharmacy, and compliance should be considered when starting treatment with potentially toxic therapeutic agents used in RA.

Nonsteroidal anti-inflammatory (NSAID) medications are commonly used in EORA patients and caution is needed. Elderly are particularly susceptible to gastrointestinal, CNS, and renal side effects. The

SUMMARY

It is appreciated that age has a modifying effect on the clinical presentations of disorders such as hyperthyroidism and systemic lupus erythematosus. Similarly in EORA, there seems to be a change in the disease phenotype when it is compared to YORA. These differences are significant not only in highlighting the importance of the aging process on the immune system but also because they have medical and therapeutic implications.

Improved classification has greatly improved our understanding and

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: Address reprint requests to Yusuf Yazici, MD, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021

^*: Division of Rheumatology, Department of Medicine, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York

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ELDERLY-ONSET RHEUMATOID ARTHRITIS

Section snippets

IMMUNOSENESCENCE

GENETICS

HORMONES

COMORBITIES

CLINICAL MANIFESTATIONS

PROGNOSIS

DISEASE COURSE AND OUTCOME

DIFFERENTIAL DIAGNOSIS

THE ASSOCIATION BETWEEN RA, PMR AND RS3PE SYNDROME

TREATMENT

SUMMARY

Semin Arthritis Rheum

Semin Arthritis Rheum

Semin Arthritis Rheum

J Chronic Dis

Clin Rheum Dis

Semin Arthritis Rheum

Age- and sex-related differences in antigen-induced arthritis in C57B1/10 mice

Arthritis Rheum

Second-line (disease-modifying) treatment in rheumatoid arthritis: Which drug for which patient?

Ann Rheum Dis

Benign rheumatoid arthritis of the aged

BMJ

Erosive osteoarthritis: A longitudinal, comparative study of 24 cases

Br J Rheumatol

Second-line antirheumatic drugs in the elderly with rheumatoid arthritis: A post hoc analysis of three controlled trials

Pharmacotherapy

The clinical features of elderly-onset rheumatoid arthritis

Arthritis Rheum

DR4 prevalence related to the age at disease onset in female patients with rheumatoid arthritis

Ann Rheum Dis

Oral contraceptive treatment for rheumatoid arthritis: An open study in 10 female patients

Br J Rheumatol

The relation of polymyalgia rheumatica to rheumatoid arthritis

J Rheumatol

Older versus younger onset rheumatoid arthritis: Results at onset and after 2 years of prospective follow-up study of early rheumatoid arthritis

J Rheumatol

Older age onset rheumatoid arthritis with or without osteoarthritis

Ann Rheum Dis

Rheumatoid arthritis in the elderly: Is it a different disease?

Am J Med

THE ASSOCIATION BETWEEN RA, PMR AND RS₃PE SYNDROME