Rheumatology




© Springer International Publishing Switzerland 2017
John R. Burton, Andrew G. Lee and Jane F. Potter (eds.)Geriatrics for Specialists10.1007/978-3-319-31831-8_20


20. Rheumatology



Rebecca L. Manno  and Jason E. Liebowitz2


(1)
Department of Internal Medicine, Division of Rheumatology, Johns Hopkins University, 5501 Hopkins Bayview Circle, Room 1B.13, Baltimore, MD 21224, USA

(2)
Department of Internal Medicine, Johns Hopkins Bayview, 301 Mason F. Lord Drive, Baltimore, MD 21224, USA

 



 

Rebecca L. Manno



Keywords
ElderlyRheumatologyArthritisVasculitisMyositisLate-age onset



20.1 Introduction


Many rheumatic diseases disproportionately affect older individuals . Osteoarthritis is almost universally present among octogenarians, and giant cell arteritis, the most common systemic vasculitis in North America , occurs exclusively in individuals over the age of 50 with a mean age of onset between 70 and 80 years. Rheumatoid arthritis has a prevalence of 2 % in the USA among individuals over the age of 60 [1]. In fact, the earliest recorded description of rheumatoid arthritis was among older individuals in the year 1800 when Dr. A.J. Landre-Beauvais described a severe illness with involvement of the joints, female predominance, a chronic course, and precipitous decline in general health among three patients over the age of 70 [2]. Rheumatic, autoimmune, and musculoskeletal diseases may be common among older individuals, but the care of these patients is far from routine.

Rheumatic diseases, and the medications used to treat them, often affect muscles and joints. This has a profound and unique impact on older individuals who are often already dealing with aging-related musculoskeletal issues that are the consequence of multiple co-morbidities, poor functional status, malnutrition, sarcopenia, and cognitive impairment. Fixed incomes and complicated medication regimens with biologic agents that have rarely been studied in older individuals add layers of complexity to management for both patients and providers. Many of these important issues are not being adequately addressed in our current health care system.

The objective of this chapter is to review the current epidemiologic, diagnostic, and therapeutic data for some of the most common rheumatic conditions among older individuals in the realms of arthritis, myositis, vasculitis, and connective tissue disorders. By highlighting some of the important unanswered questions in the multifaceted care of older patients with rheumatic disease we hope to generate future investigation in these areas. Research in geriatric rheumatology has the potential to generate comprehensive, individualized, and data driven management strategies that will improve quality of life and quality of care for older patients suffering with these conditions.


20.2 Arthritis and the Older Patient



20.2.1 Osteoarthritis



20.2.1.1 Epidemiology


Osteoarthritis (OA) is the most prevalent joint disease in the USA with greater than 33 % (12.4 million) of individuals over age 65 affected [3]. Risk factors for OA include female gender, obesity, joint injury, repetitive use of joints, and family history, but the most important risk factor is advanced age. With a predicted 88.5 million Americans reaching the age of 65 or older by 2050, nearly 30 million individuals in the USA will have OA in the future [4].

Studies evaluating the annual health care costs of OA per individual in the USA have provided a wide range of estimates from $989 to 10,313 per year [5, 6]. Although substantial variation exists across studies, it is universally accepted that this is an expensive problem with the cost of knee OA-related health care estimated to account for approximately 10 % of direct medical costs per individual over their lifetime [5]. OA is undoubtedly a prevalent and costly medical condition which targets older individuals.


20.2.1.2 Diagnosis of OA in Older Individuals


Much like everything else when caring for older patients, there can be a unique level of complexity in diagnosis even for the most routine and common medical conditions, such as OA. Classification criteria for knee OA endorsed by the American College of Rheumatology based on clinical features alone (age, stiffness <30 min, crepitus, bony tenderness, bony enlargement, absence of warmth) has a 95 % sensitivity but only 69 % specificity [7]. Specificity increases to 75 % with the addition of laboratory features (negative autoantibodies, normal ESR, synovial fluid consistent with OA) and to up to 86 % with confirmatory X-ray data [7].

It is the opinion of these authors that clinical features are generally sufficient to diagnose OA in older patients. However, red flags which should prompt further diagnostic investigation with laboratory studies, imaging, and/or arthrocentesis include: joint warmth, joint effusions or dominate involvement of the metacarpophalangeal (MCP) or metatarsophalangeal joints . Particularly in the multi-morbid older adult, a diagnosis of OA (versus other forms of arthritis) may be challenging because of pain and functional impairment from other sources such as neuropathy, myelopathy, or depression. This is an area where additional research and investigation to develop diagnostic arthritis algorithms, specific for older individuals, would be extremely valuable to streamline joint assessments so that management can begin swiftly.


20.2.1.3 Management of OA in Older Individuals


There are multiple guidelines that have been published by highly reputable professional organizations [American College of Rheumatology (ACR) ; European League Against Rheumatism (EULAR) ; Osteoarthritis Research Society International (OARSI) ; European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) ] with regard to the treatment of OA (specifically knee OA). There is agreement among these guidelines that OA management requires a combination of non-pharmacologic and pharmacologic (oral, topical, intra-articular) treatments [8].

Patient education, weight loss, and exercise programs are universally recommended, although the effects of these interventions on early symptoms and long-term disease modification remain controversial [8]. Even a modest 5 % reduction in weight among patients with BMI ≥25 and knee OA has been shown to produce small, but significant, improvements in physical function [9]. Exercise is a critical component of any weight loss program, but often weight loss is not an appropriate goal for older individuals with OA because of co-morbid conditions such as sarcopenia and frailty . Thankfully the benefits of exercise extend well beyond weight loss for OA management.

Exercise is one of the few OA treatments that has consistently demonstrated efficacy in reducing pain, disability and improving joint function. For these reasons, it is universally accepted that it should be an integral part of any OA treatment plan for older adults [8]. A recent systematic review and meta-analysis of 48 exercise trials concluded that the optimal exercise program for individuals with knee OA entails supervised sessions three times per week with fitness goals of improving aerobic capacity, quadriceps strength, and lower extremity performance [10]. However, barriers are often encountered when trying to implement an exercise program for older adults with OA. Advanced, symptomatic OA may prevent moderate to strenuous exercise, and co-morbidities such as heart disease or neuropathy can make conventional exercise programs challenging. In our opinion, the solution is to create a customized and creative OA exercise program based on the individual needs of the older patient. For some older patients, this may include aquatic therapy, tai chi or yoga. All exercise programs should include a resistance exercise component.

Perhaps one of the biggest barriers to implementing an exercise program for older individuals with OA is physicians themselves. In a survey of primary care physicians, geriatricians were among the medical specialties that counseled patients the least (22 %) on aerobic exercise [11]. Recommendations for strength training were low among all physician groups, although doctors who exercise are more likely to counsel their patients to exercise [11]. In a balanced factorial experiment among primary care physicians in the USA who were presented with a case of diagnosed knee OA, only 30 % made recommendations to the patient for exercise [12]. Physician education on how to prescribe exercise for the management of OA is a large unmet need which should be improved upon to optimize care for older arthritis patients.

The objective of pharmacologic treatment for OA is to manage symptoms, because there is not a single disease modifying OA agent on the market. Acetaminophen (≤3 g per day) remains first line therapy for OA [8, 13]. However, when acetaminophen is not sufficient to control OA symptoms, then nonsteroidal anti-inflammatory drugs (NSAIDs) may be recommended. Topical NSAIDs have minimal systemic side effects and are a very good option for older individuals with OA. Prescribing oral NSAIDs becomes much more complex. Oral NSAIDs have a greater impact on pain, stiffness, and physical function compared to acetaminophen, but worrisome side effects such as gastrointestinal bleeding, renal and cardiovascular toxicity often limit their use in the geriatric population [14]. The long-term use of NSAIDs for a chronic medical condition, such as OA, is generally not recommended for older patients (>75 years) because of these adverse effects [15]. However, if NSAIDs are to be used for the management of OA in an older patient, then using the lowest dose possible for the shortest amount of time possible is prudent. Data from a meta-analysis suggest a two to threefold increase in relative risk of gastrointestinal complications with daily high dose NSAIDs compared to low or medium doses, except for celecoxib [16]. The use of concomitant gastroprotective agents, such as proton pump inhibitors, may decrease the GI risk but does not negate it. ESCEO recommends cycles of NSAIDs instead of “chronic” use which is a feasible approach for older patients although there are no specific recommendations on duration or dose cutoffs [17]. Some NSAIDs are considered higher risk or less cost-effective than others for older individuals. Indomethacin, in particular, is more likely than other NSAIDs to have adverse CNS effects and should be avoided in elderly patients [15]. Using an Osteoarthritis Policy Model, a recent investigation found naproxen and ibuprofen more cost-effective than opioids or celecoxib for the treatment of OA among multi-morbid older adults [18]. Other oral analgesic agents such as opioids, duloxetine and tramadol may have a role for the management of OA in carefully selected older patients, although thoughtful consideration should be given to dosage and side effect monitoring because of the potential for these agents to cause dizziness, lower the seizure threshold, and cause severe constipation [8, 13, 15, 17].

Chondroitin sulfate (CS) and glucosamine sulfate (GS) are natural compounds containing glycosaminoglycans that have demonstrated some symptom amelioration in OA [19]. There is wide heterogeneity in the regulatory status and labeling of commercial forms of these compounds in the USA compared to Europe, which may be why the pooled results from several high quality studies have failed to demonstrate significant effects on pain [20]. The 2012 ACR guidelines do not universally recommend CS or GS for knee OA [21], but the 2003 EULAR guidelines do endorse their use [22]. More research is needed on these compounds before widespread use among older adults with OA can be universally recommended, although the general safety of CS and GS make them an attractive therapeutic option in this high risk population.

Intra-articular injections, either with corticosteroids or hyaluronic acid, may be a therapeutic strategy for older individuals with OA, particularly of the knee. The frequency with which intra-articular steroid injections are administered is generally determined by symptom severity. In an important OA study, patients with knee OA were randomized to receive intra-articular injections every 3 months with either 40 mg triamcinolone or saline [23]. No detrimental effects were observed to the knee structure or joint space at this dosing interval [23]. Further, the group that received intra-articular corticosteroid injections had significant improvements in pain and stiffness compared to saline injections [23]. A dosing interval of every 3–6 months for corticosteroid injections to manage OA is generally considered safe.

The routine use of hyaluronics for OA management is controversial as evidenced by the varied recommendations from key professional societies [8]. In a recent systematic review and meta-analysis of 137 randomized controlled trials of adults with knee OA, all intra-articular therapies (corticosteroid, hyaluronic acid, or placebo) were superior in improving pain, stiffness, and function compared to oral agents (acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib, oral placebo) [24]. Of note, in this evaluation even intra-articular placebo was comparable to oral therapies which raise interesting questions about the placebo-effect in OA trials and perhaps other pain pathways involved in OA [24]. In general, intra-articular therapies are a great therapeutic option for older individuals with OA because of their effectiveness and relative safety, although, for multi-joint OA, this is not a practical approach.


20.2.1.4 Surgical Management of OA


Surgical management for OA becomes an option once medical therapies have been exhausted. As of 2010, the prevalence of total hip replacements and total knee replacements among 80-year-old Americans was 5.26 and 10.38 %, respectively [25]. Treatment with total knee replacement can alleviate pain and improve function. Ninety-five patients with knee OA were randomized to receive total knee replacement (mean age 65.8 ± 8.7 years) or nonsurgical treatment (mean age 67.0 ± 8.7 years) which consisted of five interventions: exercise, education, dietary advice, use of insoles and pain medication. The surgical intervention group demonstrated superior pain relief and functional improvement after 12 months compared to nonsurgical treatment. Interestingly, the nonsurgical intervention group still had significant improvement in pain and function with only 26 % progressing to total knee replacement the following year [26]. As expected, the serious adverse events in the surgical group were higher [26]. The data for arthroscopic debridement of OA affected joints or meniscectomy is more controversial with randomized controlled trials showing similar benefit to sham control or optimized physical and medical therapies [27, 28].

Ultimately, the decision regarding surgery for OA management requires careful consideration of surgical risk versus quality of life and functional benefits. For older individuals who often have multiple joints affected by OA, the implication of post-operative immobility, pain and rehabilitation on other arthritic joints should also be considered. Importantly, OA nonsurgical management should be continued post-operatively in order to maintain the health of all joints affected with OA.


20.2.2 Rheumatoid Arthritis



20.2.2.1 Epidemiology


An estimated 0.5–1 % of the population in the USA has rheumatoid arthritis (RA), and the largest proportion of these patients are older adults [29]. The Rochester Epidemiology Project of Olmsted County suggests there has been an increase in the overall incidence of RA among adult women from 1995 to 2007 compared to the previous 4 decades with a peak annual incidence of RA among individuals aged 65–74 years (89 per 100,000) [30]. Although late-age onset RA remains less common, the estimated annual incidence in the USA among those aged ≥85 years is 54 per 100,000 people is still mark edly higher than the youngest age group (18–34 years) with an incidence of 8.7 per 100,000 [30].


20.2.2.2 Clinical Features and Differential Diagnosis in Older Individuals


The hallmark clinical feature of RA is a symmetric inflammatory polyarthritis which involves the small joints of the hands, wrists, and feet. Patients typically recount a history of morning stiffness, joint swelling, and systemic constitutional symptoms. This may occur with an indolent course over several months or with sudden onset. There have been conflicting reports of the elderly or late-age onset RA phenotype in the literature, but it is undisputable that the full spectrum of clinical manifestations of RA can present in older individuals [3134]. Most importantly, RA can be equally as severe in the old as in the young with erosions, joint destruction, and profound disability occurring within just 3 years after diagnosis [35].

The 2010 ACR/EULAR classification criteria for rheumatoid arthritis apply to all age groups and provide a scoring system to diagnose definite RA based on synovitis, autoantibodies, evidence of systemic inflammation, and duration of symptoms [36]. Importantly, other causes of arthritis must be ruled out before applying these RA classification criteria, and thus the differential diagnosis for polyarthritis in an older individual should be considered carefully. OA and RA often occur concomitantly in older individuals. Bony hypertrophy from Heberden’s and Bouchard’s nodes can make clinical assessment of synovitis challenging, so evaluation for other features of RA becomes critical. The presence of prolonged morning stiffness, MCP and wrist arthritis, autoantibodies and inflammatory synovial fluid are important clues to the presence of RA even in a patient with multi-joint OA. Crystalline arthropathies (gout, pseudogout) are common RA mimics in older individuals, especially in their more advanced phases when multiple joints are involved. Tophaceous deposits may be mistaken for rheumatoid nodules or Heberden’s and Bouchard’s nodes. In such cases, joint aspiration and synovial fluid analysis for the presence or absence of monosodium urate and/or calcium pyrophosphate crystals are necessary to make the correct diagnosis. Remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) is a rare inflammatory arthritis which occurs almost exclusively in individuals over the age of 60. RS3PE is an RA mimic that does not progress to joint erosions or deformities. Patients with RS3PE respond very well to therapy with corticosteroids, but the association between RS3PE and malignancy obligates evaluation for an occult cancer [37]. Finally, other autoimmune conditions which have arthritis as a key component and occur with frequency in older individuals, namely dermatomyositis, scleroderma and Sjogren’s syndrome, should be considered if additional rheumatic features such as skin rash, sicca, muscle weakness or Raynaud’s are also present.


20.2.2.3 Laboratory Features in Older Individuals with RA


RA is a chronic autoimmune condition, and generally laboratory studies will reflect systemic inflammation. An unexplained anemia of chronic disease, thrombocytosis, and hypoalbuminemia in an older individual with articular symptoms should prompt consideration of RA. Rheumatoid factor (RF) is present in 50–90 % of patients with RA. However, it is also one of the most common autoantibodies found in the healthy elderly population without RA. The prevalence of RF in the general older population (≥60 years) ranges from 10 to 48 % [3840]. RF lacks specificity for RA as it is found in a multitude of other common conditions. When presented with an older patient who has a positive RF and arthralgias, the following conditions should be considered in addition to RA: subacute bacterial endocarditis, paraproteinemias (monoclonal gammopathy of unknown significance, multiple myeloma), hepatitis C infection, cryoglobulinemia, and Sjogren’s syndrome [4143]. Anti-citrullinated peptide antibodies (ACPA) , which include anti-cyclic citrullinated antibodies (anti-CCP), are much more specific for RA (up to 98 %) compared to RF [42, 44]. Therefore, ACPA may be more useful diagnostically for older patients. In addition to being specific for RA, ACPA antibodies are prognostic for aggressive erosive disease, even among older individuals [4547].

In a study using data from the Department of Defense Serum Repository it was found that the preclinical period for RA, defined as the time during which RF and/or ACPA are positive but clinical symptoms are not present, lengthens as the age at RA diagnosis increases [48]. The clinical significance of this is not clear. However, it opens the door to interesting areas for future investigation regarding the interactions between an aging immune system, genetic and environmental exposures on the emergence of a clinical phenotype and autoantibodies in RA.


20.2.2.4 Cardiovascular Disease and RA


Cardiovascular disease (CVD ) is common among older individuals, and it is the leading cause of death in RA [49]. Hence, this is an extremely important co-morbidity to be aware of while managing the care of an older RA patient. CVD can be subtle in RA. Individuals with RA are less likely to report angina and more likely to have unrecognized myocardial infarction and sudden cardiac death compared to age-matched individuals without RA [50]. Traditional cardiovascular risk factors should be carefully monitored in older RA patients and medications with associated cardiovascular risk (such as NSAIDs) used with extreme caution. Finally, there is an association between RA disease activity (joint pain severity and systemic inflammation) and CVD risk [51].


20.2.2.5 RA Management for the Older Patient


The treatment of RA has been revolutionized over the past 15 years. Early and appropriate treatment with disease modifying anti-rheumatic drugs (DMARDs) in order to achieve a goal of low disease activity or remission (treat to target) is now the standard of care for RA management. This approach is outlined in the 2015 ACR Guidelines for the Treatment of Rheumatoid Arthritis [52]. In these recent ACR guidelines, DMARDs should be selected based on disease severity, disease activity, and important co-morbidities [52]. There are no absolute contraindications to any DMARDs in older individuals, and the approach to RA management should never be adjusted based on advanced chronologic age alone. Yet older patients are significantly less likely to receive DMARDs compared to their younger counterparts despite data which support comparable disease severity and duration [5356]. Older individuals (≥65 years) with RA who are not seen by a rheumatologist are more likely to be treated with glucocorticoids alone and not prescribed DMARDs [57].

The observation of decreased use of DMARDs in the elderly has multiple etiologies; however, lack of DMARD efficacy in older RA patients is not among them. In a recent study of 151 methotrexate naïve older RA patients (mean age 75 years) in whom an aggressive treat to target approach using methotrexate, TNFα-inhibitors (TNFi) , and/or tocilizumab was utilized, there was a high treatment adherence rate (76 %) and 50 % achieved structural remission (change in van der Hejde-modified total Sharp score ≤0.5), 63 % achieved functional remission (HAQ-DI ≤0.5), and 51 % achieved low disease activity (DAS28-ESR ≤3.2) over 52 weeks [58]. The most common serious adverse events were infections which occurred in 13 % of patients and required discontinuation of RA therapy in only three patients [58]. Modern day RA therapeutics can be effective in the elderly and remission can be achieved in this age group. This study is commendable in that it begins to explore the application of current treatment paradigms to older RA patients with co-morbidities. It opens the door for future studies to examine intensive (or less intensive) treatment regimens specific to older RA patients.

Co-morbidities, risk of infection, and drug interactions are all important considerations in DMARD selection for older RA patients. In addition, we propose the following medication precautions. Methotrexate remains the first line DMARD for all patients with RA regardless of age. Potential methotrexate hepatotoxicity can be worsened by concomitant medications (such as statins) or fatty infiltration of the liver, issues not uncommon among older individuals. Methotrexate is renally excreted, and creatinine should be calculated for all older patients in whom it is being considered and doses adjusted as appropriate [59]. Of particular importance in older individuals are methotrexate-induced CNS side effects such as headache, altered mood, or memory impairment [60]. This rare complication has been described primarily among older RA patients (>60 years) and should be monitored for closely in this population.

Leflunomide shares many of the same adverse effects as methotrexate in terms of hepatotoxicity and cytopenias. However, the gastrointestinal side effects of leflunomide can be severe and indolent in older individuals. Anorexia, nausea, and diarrhea may occur with drug initiation or in a subtle manner in the weeks following even small dose escalations. Weight loss in the absence of gastrointestinal symptoms has been attributed to leflunomide and often prompts fruitless, but expensive and exhaustive, evaluations for malignancy and infections [61]. The mechanism for leflunomide-associated weight loss is not known, but it seems to occur predominately in older individuals. Awareness of these leflunomide toxicities in older RA patients can prevent extensive and invasive workups.

Glucocorticoids are often used in the treatment of RA, typically as a bridge to DMARD therapy. The use of low-dose glucocorticoids chronically (defined as ≤10 mg/day prednisone equivalent), usually in combination with synthetic (non-biologic) DMARD therapy, is controversial. There are data which suggest improvements in structural outcomes and symptom severity with low-dose steroid use [62]. The risks with corticosteroids are well established in older patients and include infection osteoporosis, hyperglycemia, hypertension, and cataracts. However, many glucocorticoid side effects correspond with high doses [63]. The risk benefit ratio of low-dose glucocorticoids, specifically for older RA patients, has not been assessed. We propose that the risk assessment for the use of low-dose prednisone in older individuals with RA may be unique. In elderly RA patients, co-morbidities, infection risk, and specific DMARD toxicities may limit the use of synthetic and biologic DMARDs in select older patients. Therefore, in very specific cases, low-dose prednisone may be a reasonable option. Future research regarding the utility of low-dose glucocorticoid therapy and algorithms for its use (or not) in older RA patients will be important to guide future recommendations.

Biologic DMARDs have revolutionized the treatment of RA. TNFi have demonstrated equal efficacy among older and younger RA patients with a comparable safety profile regardless of age [64, 65]. Risk of infection is always a concern when treating older RA patients with TNFi. Whether or not infection risk with TNFi is influenced by age alone remains a matter of debate. A large retrospective cohort study of older Canadian RA patients (>66 years) in a nested case–control analyses demonstrated an increased risk of infection associated with TNFi, although the greatest infectious risk was attributed to prednisone with an associated dose response [66]. In a study using data from the US Medicare and Medicaid population, the rate of serious infections among older RA patients on TNFi was found to occur at a constant rate (~1–4 infections per 100 person years) above the rate predicted by age, co-morbidity, and other factors that contribute to infections independent of exposure to biologics [67]. These data support the observation that the increased risk of infection with TNFi is constant across age groups, although the background risk of infection is higher among older individuals in general. In summary, older RA patients should be educated about infections and closely monitored for infections while on treatment with TNFi, but this general risk alone should not be a reason to withhold TNFi therapy from the elderly.

Rituximab is an attractive biologic option for older individuals with RA because of the ease of administration. In a study of 1709 RA patients treated with rituximab from a French multicenter prospective cohort, patients in the 65–75 year age group had the highest percentage of responders at 12 months [68]. Patients in the >75 year age group had the lowest response rates. The incidence of severe infections was highest in the oldest age group (26.5 %) and decreased accordingly (19.5 % age 65–74 years; 6.8 % 50–64 years; 5 % <50 years) in the younger strata [68]. It cannot be established if the increased number of infections was attributable to rituximab or aging alone from these data.

Tocilizumab , an IL-6 inhibitor, demonstrated a good short-term safety profile among a retrospective cohort of older (≥65 years) French RA patients; however, after 6 months of treatment older RA patients were less likely to have a high EULAR response category (representing low disease activity) compared to their younger counterparts [69]. Tofacitinib , a janus kinase inhibitor, is the first oral biologic agent. There are no data specifically regarding the use of tofacitinib in older RA patients, but the very high rates of zoster infection with this biologic agent are worthy of consideration in an elderly population [70, 71]. There are no data specifically for the use of abatacept or anakinra among older RA patients.

Screening for latent tuberculosis (TB) risk is always advised before starting any biologic therapy. Among older RA patients, a positive TB screen (PPD or quantiferonTB gold testing) will raise important clinical management issues regarding treatment with isoniazid (INH), which carries considerable risk of hepatitis among older individuals [72]. Data using a Markov decision analytic model examining the risk of INH versus the risk of TB reactivation found that withholding prophylaxis prior to TNFi may be an appropriate option in low-risk elderly RA patients [73]. These decisions need to be considered carefully and discussed with the patient and family members.

In summary, while risks associated with traditional and biologic DMARD treatment in older RA patients are real, these are generally manageable and preventable with careful patient selection, education, and close monitoring. The risk of undertreating older adults with RA is significant and may lead to CVD, precipitous functional decline, and poor quality of life.


20.2.2.6 Special Considerations in Older Patients with RA


Older RA patients have a higher prevalence of age related syndromes (cognitive impairment, depression, falls, urinary incontinence, malnutrition) compared to younger RA patients [74]. Risk factors for the presence of geriatric syndromes among elderly RA patients include high RA disease activity, long disease duration, and functional impairment as measured by the Health Assessment Questionnaire (HAQ) [74]. Functional impairment, as measured by HAQ, increases with age among the general population and is highest among female RA patients over age 70 [75, 76]. Evaluation for geriatric syndromes is not routine practice for rheumatologists. Further, it is not included as a component of instruments frequently used to measure RA disease activity, such as the CDAI or DAS28. Such instruments focus primarily on the number of tender and swollen joints, ESR/CRP values and general disease activity impressions alone. These authors propose that consideration of geriatric syndromes in the routine assessment of older individuals with RA by rheumatologists when evaluating disease activity could have important benefits. For example, when making a decision about the treatment regimen for an 87-year-old RA patient, if cognitive impairment is recognized then complicated RA regimens, such as triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine would be quickly ruled out. However, if cognition is not considered in the evaluation of an older RA patient with mild-moderate cognitive impairment, then this issue may be easily overlooked. Geriatric syndromes are intimately tied to RA because of the synergistic effects on functional status, nutrition, and co-morbidities. There is great opportunity for research in care models and care delivery systems which incorporate co-management of RA and geriatric syndromes to optimize the health of this vulnerable population. See Chap. 8, for additional information on detection of geriatric syndromes suitable for research and clinical care.

Work disability can be a serious problem for individuals with RA. In a study using data from the National Data Bank for Rheumatic Diseases, a longitudinal study of RA outcomes, a sample of approximately 2500 patients with RA age 55–64 years demonstrated significantly higher rates of premature work cessation and lower employment rates compared to age-matched controls [77]. As expected, early workforce withdrawal had a significant impact on the financial security of these patients in their retirement years [77]. In a subsequent study (from the same data source) using a nested case–control design, older age was the most prominent predictor of work disability among individuals with RA [78]. These findings demonstrate the effect of this chronic disease on finances, work satisfaction, quality of life, and retirement planning for individuals aging with RA as they transition into the seventh and eighth decades of life. Health care providers should recognize these issues that are unique to older RA patients in order to formulate comprehensive, yet feasible, treatment plans for their geriatric patients.


20.3 Myositis and Myopathy in Older Individuals



20.3.1 Idiopathic Inflammatory Myopathies



20.3.1.1 Epidemiology


Muscular weakness is a common complaint among older individuals. The differential diagnosis for weakness is broad and includes nutritional deficiencies, poor conditioning, frailty, and metabolic derangements such as thyroid dysfunction or anemia. However, objective findings such as rash, fever, dyspnea, dysphagia, elevation in creatine kinase (CK), and measurable impairments in muscular strength should raise red flags for a systemic autoimmune myopathic process.

The idiopathic inflammatory myopathies (IIM) , which include dermatomyositis, polymyositis, and immune-mediated necrotizing myopathies, are relatively rare with an estimated incidence of 1.16–19/million/year and prevalence of 2.4–33.8 per 100,000 individuals [79]. The incidence of IIM increases with age and peaks in 35–44 and 55–64 year old age groups [8082]. Age is an important predictor of mortality in IIM and may convey a poorer prognosis overall with regard to treatment response [8385].


20.3.1.2 Clinical Features of IIM in Older Adults


Few studies have investigated the clinical presentation and phenotype of IIM among older individuals. A retrospective study of 23 older (median age 69 years) patients with IIM compared to younger (age <65 years) adults found similar frequencies of myalgias, muscle weakness, skin manifestations, and interstitial lung disease [84]. Older patients had more esophageal dysfunction [84]. A case–control study of 21 older IIM patients (mean age 69.9 years) compared to 21 younger (mean age 46.4 years) patients yielded similar findings with the exception of lower CK at diagnosis among the older group [86].

The association between IIM and cancer is well established with advanced age being a key risk factor. Individuals with cancer-associated myositis are generally older, have a dermatomyositis phenotype and shorter survival [84, 8688]. In a retrospective study of 139 patients with a new diagnosis of dermatomyositis, 8.6 % were diagnosed with cancer within 12 months. Age at dermatomyositis onset was significantly older (by more than 15 years) among those who developed a malignancy compared to those who did not [89]. The risk of malignancy with IMM is thought to be greatest within the first year of diagnosis and does not normalize to the general population even after 5 years [90]. Therefore, a careful and thorough search for cancer should be performed in older individuals who develop a new IIM, particularly dermatomyositis.


20.3.2 Statins and Myopathy


At least 60–80 % of Medicare beneficiaries with coronary heart disease are currently on statin therapy [91]. Overall, statin-induced myopathy is rare with a spectrum of myotoxicities that range from mild myalgias without CK elevation to rhabdomyolysis [92, 93]. Genetic variants and undiagnosed metabolic myopathies can predispose individuals to statin-associated myopathy [9496]. Additional risk factors for the development of high CK levels while on treatment with a statin include older age (>65 years), diabetes, and male gender [97]. Several medications frequently prescribed for older patients such as verapamil, macrolide antibiotics, and amiodarone may also increase the risk of statin myotoxicity [98].

The National Lipid Association Statin Safety Assessment Task Force recommends obtaining baseline CK levels in adults at high risk for developing a statin-related myotoxicity [99]. Older adults, particularly those with polypharmacy or on medications which may increase myotoxicity risk when given concomitantly with a statin, fall into this category. Repeat CK measurements are not necessary unless the patient develops muscle symptoms. The presence of intolerable muscle symptoms, with or without CK elevation, should prompt discontinuation of the drug. In most instances, this should be sufficient to resolve the statin myopathy within a relatively short period of time (<2 months). Then if the symptoms resolve, a thoughtful discussion with the patient, the generalist, and cardiologist about the long-term benefit and burden of reinstituting a statin must occur so the patient’s goals of care can be honored.

In cases of persistent muscle symptoms, despite termination of statin therapy, the patient may be suffering from an autoimmune process that is a distinct clinical entity from self-limited statin-associated myopathy and can be further evaluated with serologic testing. Specifically, patients should be tested for antibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) . The presence of these antibodies is highly suggestive of an immune-mediated necrotizing myopathy that may have been “unmasked” in the presence of statin therapy. Individuals with anti-HMGCR myopathy have proximal muscle weakness, very high CK levels (mean 10,000 IU/L) and a necrotizing myopathy on muscle biopsy [100, 101]. Additionally, despite its name, anti-HMGCR antibodies are frequently, but not always, associated with statin-triggered autoimmune myopathy. In fact, studies have shown that 33–56 % of anti-HMGCR-positive patients had no prior exposure to statins [101, 102]. It is not yet known what triggers the IIM in these non-statin exposed individuals. Although there is no established age association with anti-HMGCR at this time, it is clear that the prevalence of statin exposure increases with age, thereby placing older individuals at disproportionate risk.


20.3.3 Inclusion Body Myositis


Inclusion body myositis (IBM ) is a common mimic of inflammatory myositis in older adults. It rarely occurs among individuals less than age 50, and it has a male predominance [103]. Slow, progressive, asymmetric muscular weakness is common and can initially appear very similar to polymyositis. However, IBM has key clinical features which distinguish it from the inflammatory myopathies, such as distal weakness in the wrist and deep finger flexors with sparing of wrist and finger extensors. Facial weakness and dysphagia may also be present [103105]. A diagnosis of IBM can be made on the basis of clinical features, muscle pathology and new biomarkers with relatively high specificity but varying sensitivity, according to current diagnostic categories [106]. Distinguishing IBM from IIM is extremely important because immunosuppressive and immunomodulatory agents, which are highly effective in treating IIM, have not shown efficacy in IBM and may be detrimental [104]. Resistance exercise and orthoses are the primary treatment modalities for IBM [107].


20.3.4 An Approach to Diagnosis and Management of Older Patients with Myopathy


When faced with an older patient who has symptoms of weakness, we propose a systematic approach to diagnosis and management. Diagnostic precision is key because without an accurate diagnosis the wrong or unnecessary treatment may be prescribed to an elderly frail individual which could be devastating. Although diagnostic testing in this evaluation may be extensive and include imaging and invasive procedures, such as muscle biopsy and EMG/NCS, the acquisition of data will be valuable when teasing out the source of this vague common complaint in older patients.

On physical exam the pattern of objective weakness (proximal vs distal) can narrow the differential diagnosis if it is consistent with IIM, IBM, or spinal cord pathology (myelopathy). The presence of a new rash, Raynaud’s phenomenon, inflammatory arthritis with synovitis or cuticular abnormalities (abnormal nailfold capillary microscopy) in an older individual with muscular complaints suggests an immune-mediated process. A thorough review of a patient’s medication and supplement lists, particularly the presence (or absence) of statin therapy, may reveal a single myotoxic agent or medications which when used together predispose to myopathy. Laboratory data, namely myositis-specific autoantibodies, thyroid studies, and CK measurements, are incredibly useful although these need to be interpreted in the context of the clinical picture. Normal or very minor CK elevations in older patients with sarcopenia, low BMI, and weakness may be highly significant. Similarly, elevated CK (above the upper limit of normal) in a very physically active older individual with high muscle mass, normal strength and who engages in resistance training may be a normal finding.

Therapeutic interventions for myopathy in older adults are targeted at the disease process. For IIM (including anti-HMGCR immune-mediated necrotizing myopathy ), immunosuppression with corticosteroids, methotrexate, intravenous immunoglobulins, and other agents is standard of care. Adverse events which may be seen more frequently in older individuals include volume overload, infection (typical and opportunistic), cognitive impairment, and anorexia. Regular surveillance for these complications should be conducted routinely.

Resistance exercise should be a part of the treatment plan for every patient with IIM or IBM. Multiple studies, including randomized controlled trials, have demonstrated safety and efficacy of resistance exercise in IIM and IBM [108, 109]. Little is known specifically about how to tailor resistance training programs to the needs of older adults with myopathy, and this is an important area for future investigation. We propose that a resistance exercise program with a focus on large muscle groups (legs, back, chest) in order to improve functional mobility and increase muscular strength should be prescribed routinely for older individuals with myopathy as a standard part of their treatment plan.


20.4 Vasculitis in Older Individuals



20.4.1 Giant Cell Arteritis and Polymyalgia Rheumatica


Giant cell arteritis (GCA ) is a systemic inflammatory disease that occurs almost exclusively in the elderly. It is the most common form of systemic vasculitis in older persons in North America with an annual incidence which is highest among those over age 70 [110, 111]. Common symptoms of cranial GCA are headache, jaw claudication, and diplopia with the latter two symptoms having the highest positive predictive value for a positive temporal artery biopsy [112]. Jaw claudication is a red flag in older patients, because it is associated with a high likelihood of visual symptoms in GCA [113]. Large-vessel GCA may occur with cranial GCA or independently. Large-vessel GCA can present with indolent non-specific symptoms such as arthralgias, myalgias, fever, and/or limb claudication. GCA should always be considered in the evaluation of an older patient with fever of unknown origin or unexplained laboratory evidence of inflammation (high ESR/CRP, hypoalbuminemia, anemia of chronic inflammation) and systemic symptoms [114]. An accurate diagnosis of GCA is important in order to avoid unnecessarily treating older patients with high dose corticosteroids. Temporal artery biopsies (bilateral, >1 cm length) and imaging of the aorta can provide important data for diagnostic certainty [115118]. MRI, CT angiography, or PET-CT can be useful to demonstrate aortitis in a patient in whom GCA is suspected but the temporal artery biopsy is negative or in a patient presenting with signs and symptoms of large-vessel GCA alone.

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Aug 25, 2017 | Posted by in GERIATRICS | Comments Off on Rheumatology

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