Table 15.3 (continued) Author and year of
publication Country of origin Study type
Total number of
patients studied Serologic findings Appenzeller et al. (2008)
[20]
Brazil Nested case-control
study
76 Similar frequency of ANA; higher prevalence of anti SSA/Ro
Lalani et al. (2010) [18] Canada Cross-sectional 1,528 Lower frequency of anti-RNP,
anti-Sm antibodies and hypoco- mplementemiaSimilar frequency of anti-DNA antibodies
a Compared to younger-onset disease patients
myalgias, pleurisy, rash, and fever in association with the presence of antinuclear antibodies; central nervous system and renal involvement are rare. Although antinuclear anti- bodies occur in the majority of these patients, anti-double stranded DNA antibodies are rare [25]; the typical finding includes the presence of antihistone antibodies, which may be present in up to 95% of patients [42]. The absence of antinuclear antibodies should not preclude the diagnosis of drug-induced lupus; in these cases, the resolution of symp- toms within weeks (or months) of discontinuation of the offending drug is of particular value in the diagnosis of this condition [43]. Since first recognized almost 50 years ago in association with hydralazine therapy [44], numerous medi- cations have been added to the list of drugs associated with the induction of lupus. Depending mostly in the number of cases reported, such associations range from weak (only few cases reported) to strong (procainamide, hydralazine) [45, 46]. Typically, drug-induced lupus does not require specific treatment as the clinical and serological manifesta- tions of this condition usually subside once the suspected drug is discontinued [25].
141 15 Systemic Lupus Erythematosus in Elderly Populations
Indices to measure disease activity in SLE have been validated and their reproducibility, validity, and sensitivity to change compared [57]. As shown in Table 15.4 [10–12, 14, 15, 17, 18, 20, 21, 23, 24, 28, 35], in only few studies disease activity in late-onset lupus patients has been evaluated. In two of them [12, 15], disease activity was found to be lower in patients whose disease began later in life. This is not unex- pected since late-onset lupus patients tend to have less major organ involvement and variable laboratory findings, hypoco-
mplementemia among them, which constitute elements of disease activity indices [58, 59].
Despite this apparent benign course, this group of patients may not have such a good prognosis in terms of morbidity.
The health status of lupus patients does not only relate to disease activity, but also to damage resulting from the dis- ease itself, concomitant morbidities, and treatment compli- cations. Several studies have shown the negative impact that age, in particular age at disease onset, has on damage accrual
Table 15.4 Disease outcomes in late-onset lupusa
Authors and year of publication Country of origin Study type
Total number of
patients studied Salient findings Disease activity
Formiga et al. (1999) [15] Spain Medical records review 100 Lower disease activity at presenta- tion and during the first year since diagnosis
Bertoli et al. (2006) [12] USA Nested case control study within a longitudinal cohort
217 Lower disease activity at cohort enrollment and over time
Padovan et al. (2007) [35] Italy Longitudinal cohort 255 Similar disease activity
Appenzeller et al. (2008) [20] Brazil Nested case-control study 76 Lower disease activity at cohort enrollment and over time
Lalani et al. (2010) [18] Canada Cross-sectional 1,528 Higher disease activity per the
SLAM (but not the SLEDAI).
Similar number of patients flaring per year
Damage accrual
Maddison et al. (2002) [11] International (North America, Europe, Korea)
Medical records review (Case-control study)
241 Higher damage accrual
Sayarlioglu et al. (2005) [24] Turkey Medical records review 120 Similar damage accrual
Mok et al. (2005) [17] Hong Kong Longitudinal cohort 285 Similar damage accrual
Bertoli et al. (2006) [12] USA Nested case-control study within a longitudinal cohort
217 Late-onset lupus is a predictor of any damage
Padovan et al. (2007) [35] Italy Longitudinal cohort 255 Higher damage
Mak et al. (2007) [23] Hong Kong Medical records review 287 Higher renal damage
Appenzeller et al. (2008) [20] Brazil Nested case-control study 76 Higher damage
Lalani et al. (2010) [18] Canada Cross-sectional 1,528 Damage accrual higher but not
significant Health-related quality of life
Bertoli et al. (2006) [12] USA Medical records review (Case-control study)
217 Similar health-related quality of life Mortality
Ballou et al. (1982) [28] USA Medical records review 138 Similar mortality
Costallat and Coimbra (1994) [14] Brazil Medical records review 272 Lower mortalityb
Pu et al. (2000) [21] Taiwan Medical records review
(Case-control study)
194 Higher mortality rate Boddaert et al. (2004) [10] France Medical records review
(Case-control study)
161 Higher mortality rate
Mok et al. (2005) [17] Hong Kong Longitudinal cohort 285 Higher mortality rate
Bertoli et al. (2006) [12] USA Nested case-control study within a longitudinal cohort
217 Late-onset lupus is a predictor of mortality
Appenzeller et al. (2008) [20] Brazil Nested case-control study 76 Higher mortality rate
a Compared to younger-onset disease patients
b Compared to childhood-onset patients
[5, 11, 12, 17, 20, 23–25]. Using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [60], Bertoli et al. found late- onset lupus to be a predictor of any irreversible damage in patients from the LUMINA cohort [12]; damage seems to be more evident in the ocular (cataracts), musculoskeletal (deforming arthritis and osteoporosis with fractures), cardio- vascular (coronary artery disease and ventricular dysfunction) [11], and renal (end-stage renal disease) [19, 23] domains. It is possible that these observations are merely reflecting the result of the interaction of aging per se plus the specific effect of lupus in this older population [11]. For example, both age and SLE [61] are well-recognized risk factors for the occur- rence of coronary artery disease. Late-onset lupus is also associated with the occurrence of other comorbidities not included in the damage index, such as hypothyroidism, hyper- tension, and venous thrombotic events [12, 62].
Survival has dramatically improved in SLE patients during the past few decades [63]; however, a higher proportion of patients with late-onset lupus die compared to patients with early onset disease [10, 12, 17, 20, 21]. Age, especially age at disease onset, has consistently been reported as a risk factor for early mortality among SLE patients [10, 12, 62]. The pro- portion of deaths related to active lupus is similar [12] or even lower [10] in late-onset lupus patients compared to younger patients; factors other than the disease itself may therefore account for this poorer outcome. The presence of comorbid conditions, especially those resulting in higher degrees of damage accrual may be, at least in part, responsible for the higher mortality rates found in this patient group [10, 49, 64].
In fact, cardiovascular disease accounted for the mortality excess observed in late-onset lupus patients in the study by Bertoli et al. [12]. The studies of disease activity, damage, health-related quality of life and mortality are summarized in Table 15.4 [10–12, 14, 15, 17, 18, 20, 21, 23, 24, 28, 35].
Conclusions
SLE is being increasingly recognized among elderly popula- tions. The so-called late-onset lupus seems to conform a quite defined subset of patients; a more insidious and less defined disease presentation, less of a female predominance along with less severe clinical manifestations are distinctive among these patients. Although the disease runs a more benign course, the intermediate (damage accrual) and long- term (survival) prognosis is worse among the elderly com- pared to its younger counterpart. The interaction of the disease per se and the accrual of comorbid conditions, espe- cially cardiovascular disease, may be responsible for the higher mortality rates reported in this patient group.
Treatment decisions, therefore, should be cautiously taken
according not only to the clinical manifestations, but also to the presence of other comorbidities and concomitant phar- macological interventions.
Acknowledgments The work of Drs. Guillermo Pons-Estel and Paula Burgos was supported by a Supporting Training Efforts in Lupus for Latin American Rheumatologists (STELLAR) award funded by Rheuminations, Inc.
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Y. Nakasato and R.L. Yung (eds.), Geriatric Rheumatology: A Comprehensive Approach, 145 DOI 10.1007/978-1-4419-5792-4_16, © Springer Science+Business Media, LLC 2011
Abstract As the number of people who are over the age of 60 years is growing in the general population, the prevalence of disability from rheumatoid arthritis (RA) is also on the rise. This is an important health concern for patients, their families, and society. This review highlights various aspects of elderly onset RA (EORA), including differences from younger onset RA (EORA), diagnostic and prognostic factors, differential diagnosis, and treatment modalities. There are challenges associated with diagnosis and treatment in the early onset rheumatoid arthritis patients. Knowledge about various aspects of early onset rheumatoid arthritis and further research into better diagnostic and therapeutic methods will help diminish the affects of this disabling disease in the older population.
Keywords Elderly onset rheumatoid arthritis • Younger onset rheumatoid arthritis • Diagnosis • Prognosis treatment
Introduction
Rheumatoid arthritis (RA) is a progressive, systemic inflam- matory disease that targets synovial tissues. Left unchecked and untreated, RA can cause significant morbidity and accel- erated mortality. RA is the most common inflammatory arthritis in adults, with a peak age of onset between 40 and 60 years of age. However, as remission is uncommon, it has become appreciated that the prevalence of RA increases at least through age 85. The prevalence of rheumatoid arthritis among persons 60 years of age and older has been estimated at around 2% [1]. In the general population of elderly persons, arthritic complaints are most frequently associated with osteoarthritis (OA), classically considered a degenerative and noninflammatory form of arthritis. However, various forms of inflammatory arthritis, including RA, gout, calcium
pyrophosphate deposition disease (CPPD) or pseudogout, polymyalgia rheumatica (PMR), and even inflammatory forms of OA are commonly encountered as well. A major concern shared among various arthritic disorders is their potential to diminish elderly patients’ functional status, and therefore, their independence. Pain, stiffness, and even con- stitutional symptoms can contribute to immobility, weakness, and increased falls. These can in turn lead to decreased quality and even quantity of life.
Even though there has been progress in deciphering the cellular and molecular mechanism of RA, the etiology is still not fully defined. RA is characterized by synovial and vascular proliferation with the formation of pannus tissue [2]. The synovium thickens due to increased number of acti- vated immune cells. These cells produce a host of inflamma- tory mediators, notably proinflammatory chemokines and cytokines that help drive synovial proliferation. The secre- tion of these cytokines as well as enzymes, such as matrix metalloproteinases (MMPs), can cause tissue destruction with damage to articular cartilage and adjacent bone–repetition above [3].