US Pharm. 2009;34(4):22-24. 

Rheumatoid arthritis (RA), the most common inflammatory arthritis, is a chronic autoimmune disease and an important cause of disability in seniors.^1-3 Medications for RA account for approximately 10% of the total cost of treating a patient with this condition (excluding monitoring).² When comparing patients of similar age and gender, the cost of treating a patient with RA is three times as high as the medical care for a patient without this illness.²

While RA usually presents between the ages of 25 and 50, its prevalence increases with advancing age up to 80 years and new cases may occur even in the very old.^3-5 Worldwide, RA affects approximately 1% of the population and affects women two to three times more often than men.^4,6 In patients age 15 to 45, women predominate by a 6:1 ratio; in seniors older than 60 years, the sex ratio is approximately equal.² The course of this condition is unpredictable, and its progression is most rapid during the first through sixth year after diagnosis.¹ Permanent abnormalities of the joint develop within 10 years in 80% of patients.¹ 

RA is associated with both joint and systemic symptoms. Inflammation of the peripheral joints is typically symmetric and induces progressive destruction of the joint itself and its surrounding structures.^1,3,7 The joints primarily affected by RA are in the hands (e.g., wrists, proximal interphalangeal [PIP], and metacarpophalangeal [knuckles]), the feet (e.g., metatarsalphalangeal and interphalangeal), and larger joints (e.g., elbows, shoulders, knees).^3,7 In contrast to RA, primary osteoarthritis (OA) usually affects the distal interphalangeal and PIP joints of the fingers, first carpometacarpal joint at the base of the thumb, cervical and lumbar spine, hips, knees, and toes; OA usually spares the metacarpophalangeal joints (knuckles), wrists, elbows, shoulders, and ankles.^3,7

Symptoms develop insidiously over several weeks to months.² Underlying pain coexists with changing symptoms; physical, psychological, and spiritual health are affected.⁶ The patient complains of pain and stiffness in the affected joints, especially upon awakening; muscle aches and stiffness may precede joint swelling.^2,4 Most patients experience malaise and anorexia; fever and night sweats are occasionally reported.³ Since no single physical sign or test is used to make the diagnosis of RA, diagnostic criteria, including laboratory tests (e.g., rheumatoid factor, antinuclear antibody, erythrocyte sedimentation rate, and other diagnostic tests), are utilized in evaluating the patient  (see Reference 1 online). Disease presentation in elderly-onset RA (i.e., >60 years) may be different from that of young-onset RA.^1,2 For example, in a 60-year-old-plus senior with new-onset RA, rheumatoid factor may be negative and there may be an absence of rheumatoid nodules as compared with the opposite in a 60-year-old-plus senior who has been previously diagnosed with RA.⁸ 

Swelling of the joints is apparent by palpation or visible inspection.² Joint deformities of the hand occur with chronic inflammation, and trigger finger (flexor digital tenosynovitis) commonly occurs in patients with RA.^1,3 The knee may be affected, causing gait instability, and joint pain from foot and ankle involvement often makes walking difficult.² 

Dermatologic and Other Extra-Articular Manifestations

The dermatologic and other extra-articular manifestations of RA, such as pulmonary complications (e.g., pleural effusions), cardiac involvement (e.g., myocarditis), neuropathy, and ocular signs, underscore the systemic nature of this condition.^1,5,7 

Rheumatoid Nodules

Rheumatoid nodules, subcutaneous bony lumps located over or near the joints, are the most commonly known skin sign of RA.^5,9 They are not an early sign of the disease, but develop in approximately 20% to 30% of patients.^1,9 Nodules occur most often in patients with a potentially severe course of RA and may be an additional indication in support of aggressive therapy.⁹ Methotrexate (MTX) may be the cause of rheumatoid nodules in some patients.⁹ Usual sites include the extensor surfaces of the elbows, forearms, and hands where pressure and chronic irritation occur; they may also appear on the feet or other pressure-point sites.² Rheumatoid nodules can develop in the lung or pleural lining and rarely in the meninges.² While generally harmless, they may be painful and a central necrosis can develop.^3,9 When interfering with normal body function, surgery is indicated.⁹ 

Vasculitis, Skin Lesions, and Other Conditions

Small-vessel vasculitis may cause infarcts near the ends of the fingers or toes, especially around the nail beds, that are typically of little consequence; other vasculitis-related complications can be more serious.² While a senior with RA may be vulnerable to the common causes of lower extremity ulcers (e.g., venous stasis and pressure), a skin breakdown secondary to vasculitis can also be the cause of ulcers and may not be distinguished from stasis ulcers.^5,7 Vasculitis ulcers do not respond to regular stasis ulcer therapy and require aggressive treatment of the inflammatory process.² Vasculitis usually occurs in patients with long-standing RA; when larger vessels are involved, infarcts may cause irreversible motor deficits and visceral involvement.² Other dermatologic conditions in seniors have been associated with RA, including autoimmune bullous (i.e., blistering) dermatosis; Raynaud's phenomenon; palmar hyperhidrosis; and pyoderma gangrenosum.⁵ 

Treatment

A comprehensive approach to treatment balances the nonpharmacologic measures, pharmacologic modalities, and surgery. Controlling inflammation is the key to slowing or preventing the progression of disease while at the same time controlling symptoms; ideally, this is done in consultation with a rheumatologist.^2,8

Nonpharmacologic Measures

If conservative therapy fails, surgery may be warranted. Although regular rest is indicated, complete bed rest is rarely recommended.¹ In RA, the body's energy requirement increases while appetite decreases, causing gradual weight loss.⁴ A nutritious diet is usually sufficient; decreasing inflammatory prostaglandins may relieve symptoms through the replacement of omega-6 fatty acids found in meats with omega-3 fatty acids found in fish oils.¹ Seniors who are disabled by RA can benefit from occupational therapy; joint splinting; orthopedic, athletic, or molded shoes; self-help devices to assist with activities of daily living; paraffin baths to warm the digits; and exercise.^1,4 Intensive exercise, casting, or immobilization may help flexion contractures.¹ Prosthetic joints are indicated if damaged joints limit function severely.^1,3  

Highlights of Pharmacologic Therapy

Monitoring for therapeutic benefit and toxicity is required for the duration of treatment.² TABLE 1 outlines the specific agents in the pharmacologic categories discussed below. While beyond the scope of this article, a comprehensive discussion about the pharmacologic management of RA may be found in References 1 (online), 2, 10, and individual manufacturer's guidelines for each agent.^1,2,10

Disease-modifying antirheumatic drugs (DMARDs) are indicated in almost all RA patients since they appear to slow the progression of the disease.¹ DMARDs vary chemically and pharmacologically from one another and no one agent is safe and efficacious in every patient.^1,11 The ultimate goal is the prevention of erosions and progressive deformity, so DMARDs should be initiated within 3 months of diagnosis.² Use in combination with one another may be more effective than monotherapy; in some cases, a DMARD plus a biologic agent may be used to achieve a therapeutic outcome.^1,2 MTX is the most commonly prescribed DMARD in the U.S.; many rheumatologists consider it the drug of choice for managing RA.^2,8 Toxicity to MTX, or any immunosuppressive agent, is increased in the elderly.¹⁰ Penicillamine, gold compounds, and the cytotoxic, immunosuppressive, or immunomodulatory agents are used less frequently today due to toxicity and/or lack of long-term benefit, especially in the elderly, although they may have clinical value.⁸  

Biologic Agents: These agents may be effective when DMARDs fail to achieve a therapeutic response and are associated with a higher cost of therapy.² Since the most serious adverse effect associated with the anti-tumor necrosis factor (TNF) therapies is infection, especially reactivated tuberculosis (TB), skin testing using the preferred Mantoux test (i.e., containing tuberculin purified protein derivative) or chest x-ray should be performed to screen for TB.¹ Anti-TNF therapies may also predispose RA patients to an increased risk of cancer.² Some agents (e.g., anakinra) require calculation of creatinine clearance prior to initiation of therapy, especially in seniors. 

Nonsteroidal Anti-Inflamatory Drugs (NSAIDs): These agents are used as adjunctive therapy in the early phase of the disease and used as needed, with or without corticosteroids, if symptoms are not adequately controlled with DMARDs.² They provide analgesic and anti-inflammatory properties and help reduce joint stiffness.² Aspirin use for RA requires an effective dose that is often toxic and therefore is no longer recommended for this indication.¹ The use of aspirin for antiplatelet cardioprotective effect at ≤325 mg/day, however, may be used with an NSAID as an exception to the rule of using only one NSAID at a time.¹ The elderly are a high-risk population for adverse effects from NSAIDs (e.g., gastrointestinal bleeding; edema; decreased platelet adhesiveness; confusion and other CNS symptoms; myocardial infarction, stroke, new onset or worsening hypertension; and renal function compromise).^1,10  

Corticosteroids: These are used with or without NSAIDs as adjunctive therapy in the early phase of the disease for symptoms not adequately controlled with DMARDs.² In the elderly, oral prednisone (i.e., not to exceed 7.5 mg once/day, except in those with severe systemic manifestations) is recommended at the lowest dose and alternate-day dosing, if possible.^1,3,8 In seniors with poorly controlled diabetes, severe osteoporosis, or congestive heart failure, intra-articular injections of depot corticosteroids may be safer than oral corticosteroids, and may provide both local and systemic symptom relief.⁸ 

Conclusion

Pharmacists should be familiar with both the joint and extra-articular symptoms of RA. They have an opportunity to improve the quality of life of RA patients by embracing the need for appropriate and aggressive treatment of the inflammatory process, including specific and careful monitoring. 

REFERENCES

1. Beers MH, Porter RS, Jones TV, et al. The Merck Manual of Diagnosis and Therapy. 18th ed. Whitehouse Station, NJ: Merck Research Laboratories; 2006:283-289. www.merck.com/mmpe/sec04/ ch034/ch034b.html?qt=Joint disorders&alt=sh. Accessed March 24, 2009.
2. Schuna A. Rheumatoid arthritis. In DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 6th ed. New York, NY: McGraw-Hill Inc; 2005:1671-1683.
3. Beers MH, Berkow R, eds. The Merck Manual of Geriatrics. 3rd ed. Whitehouse Station, NJ: Merck & Co; 2000:499-503,536-538,1342.
4. Beers MH, Jones TV, Berkwits M, et al, eds. The Merck Manual of Health & Aging. Whitehouse Station, NJ: Merck Research Laboratories; 2004:202,524-529,811-813.
5. Zanolli MD, Jorizzo JL. Skin signs of rheumatoid arthritis. In Newcomer VD, Young EM, eds. Geriatric Dermatology: Clinical Diagnosis and Practical Therapy. New York, NY: Igaku-Shoin; 1989:437-440.
6. Jett KF, Lester PB. Musculoskeletal disorders. In Youngkin EQ, Sawin KJ, Kissinger JF, et al, eds. Pharmacotherapeutics: A Primary Care Guide. Upper Saddle River, NJ: Pearson Prentice Hall; 2005:489-523.
7. Dorland's Pocket Medical Dictionary. 28th ed. Philadelphia, PA; Saunders; 2008.
8. Yung R. Rheumatoid arthritis and other autoimmune diseases. In Hazzard WR, Blass JP, Halter JB, et al, eds. Principles of Geriatric Medicine and Gerontology. 5th ed. New York, NY: McGraw-Hill Inc; 2003:1015-1031.
9. Paget SA, Lockshin MD, Loebl S. The Hospital for Special Surgery Rheumatoid Arthritis Handbook. New York, NY: John Wiley & Sons, Inc; 2002:24,46-48.
10. Semla TP, Beizer JL, Higbee MD. Geriatric Dosage Handbook. 14th ed. Hudson, OH: Lexi-Comp, Inc; 2009.
11. Howland RD, Mycek MJ. Pharmacology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006:485-514. 

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