Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease that affects more women than men. Although it can occur at any age, the most common age of onset is between 30-50 years old. Traditionally, it’s been feared as the most disabling type of arthritis as it can decrease life expectancy by 3-7 years. However, although it is still a serious disease, there are many new medication available and the patient prognosis has greatly improved.

Pathophysiology of rheumatoid arthritis
Complex autoimmune and inflammatory processes causes swelling and joint damage that is associated with RA. Patients with RA lose tolerance to their own proteins due to their genes and the environment. This causes their immune systems to no longer recognize themselves and develop anti-citrullinated protein antibodies (ACPAs) against them. White blood cells accumulate in the synovium and cause swelling (ie. synovitis). RA disease progression is a complicated progress and involves both the innate and the adaptive immune system. Patients with chronic RA have joints where the synovium is thick and has many villous folds. The cells lining the synovium produces proteins which cause cartilage destruction, bone absorption, and inflammation. About 40% of RA patients develop rheumatoid nodules. A rheumatoid nodule are is a granuloma that is made up of a central necrotic area that is surrounded by macrophages, lymphocytes, fibroblasts, and plasma cells.

In summary, instead of your immune system attacking foreign bacteria/viruses, it attacks yourself, creates inflammation, and leads to symptoms associated with RA.

Signs and symptoms of rheumatoid arthritis
In early disease, patients with RA commonly have prolonged joint pain, swelling, stiffness, afternoon fatigue, and general weakness. Symptoms generally worsen quickest in the first 6 years of the disease and 80% of patients develop some permanent joint abnormality in the first 10 years. The most common joints affected by RA are your wrists, the index and middle finger joints, metatarsophalangeal joints, proximal interphalangeal joints, elbows, shoulders, kneewws, hips, and ankles.

Up to 30% of patients eventually develop subcutaneous rheumatoid nodules later on in the disease. These nodules usually occur at pressure points or areas with chronic irritation. RA can also cause leg ulcers, pericardial effusion, pulmonary fibrosis, myocarditis, pericarditis, Sjogren syndrome, episcleritis, and scleromalacia.

Treatment of rheumatoid arthritis
Lifestyle measures, medications that delay disease progression, and medication for pain are all required to manage RA. If medication therapy is unsuccessful, then patients can consider surgery to help improve motion, function, and quality of life.

Lifestyle changes for RA patients are a balance of rest and exercise. Exercise as tolerated to preserve range of motion and restore muscle mass. Bed rest is rarely recommended. There’s no evidence to suggest that any specific foods may worsen RA so a generally nutritious diet is recommended. There is some support that substituting omega-3 fatty acids, found in fish, in place of omega-6 fatty acids, found in meats, may help relieve pain and stiffness in some patients by potentially changing the bacteria in the digestive tract and decreasing inflammatory chemicals in the body. Smoking cessation is always recommended for RA patients to help increase life expectancy. Applying splints to the affected joints can help relieve severe pain or compressive neuropathies. Ice packs can help decrease swelling and pain. Athletic shoes or custom moulded shoes is recommended. Heat packs can help with stiffness and the warmth can help improve range of motion.

Drugs for rheumatoid arthritis
Disease-modifying antirheumatic drugs (DMARDs) are used to help decrease inflammation, prevent deformity, and prevent loss of joint function. DMARDs are often prescribed in combination early on in the disease. Biologic agents are also used and have been shown to slow the progression of the disease but are not used in combination with each other as they may increase the risk of infections. Non-steroidal anti-inflammatory drugs (NSAIDs) are used to help with pain but may increase cardiovascular risk. There is not a preferred or optimal combination of medication for all patients.

Disease-modifying antirheumatic drugs for rheumatoid arthritis
Almost all patients are prescribed disease-modifying antirheumatic drugs (DMARDs) which can slow the progression of RA. Depending on the medication, it can take weeks to months for the medication to have an effect. Some patients can achieve complete remission but and ⅔ of patients experience overall improvement through decreased disease activity. DMARDs are frequently used in combination as this approach is more effective than treatment with a single drug.

At prescribed doses, methotrexate has antiinflammatory effects within 3 to 4 weeks of starting therapy. However,it should be used with caution in patients with kidney or liver dysfunction and can cause liver fibrosis, bone marrow suppression, nausea, stomatitis, or pneumonitis. To avoid side effects, patients frequently take daily supplemental folic acid. Discontinuation of methotrexate can cause severe relapse of arthritis.

Leflunomide is considered to be as effective as methotrexate and it is less likely to cause bone marrow suppression, liver dysfunction, or pneumonitis. Leflunomide can cause diarrhea, neuropathy, alopecia, and skin reactions although alopecia and diarrhea generally occur at the beginning of treatment and resolve over time.

Benefits of sulfasalazine can be seen in 3 months of treatment but may cause bone marrow suppression, gastro side effects, neutropenia, hepatitis, and hemolysis. To help with some of these side effects, most prescribers recommend enteric-coated tablets. Another possible side effect of sulfasalazine treatment is neutropenia. Therefore, patients using this medication should have regular liver tests every 6 months and whenever the dose is changed.

Hydroxychloroquine is used to manage mild RA. It can cause myopathy, corneal opacity, retinal degeneration, and dermatitis. Patients using hydroxychloroquine should get regular eye exams (every 12 months). It may take a long time for hydroxychloroquine to modify RA and if no improvements are seen in 9 months, then therapy should be discontinued.

Systemic corticosteroids can decrease inflammation quicker and to a greater degree than other DMARDs but they do not prevent joint destruction and their benefits decrease over time. Long term use of corticosteroids can cause weight gain, diabetes, osteoporosis, hypertension, and cataracts. Due to these side effects, use of corticosteroids are only used in a limited time, until DMARDs take effect.

Azathioprine and Cyclosporine
Azathioprine and cyclosporine are more toxic than DMARDs but offer similar efficacy. In general, they are only used for patients who are unresponsive to DMARD therapy and to help decrease the need for corticosteroids. Lowest effective dose should be used for both medication to prevent side effects such as bone marrow suppression, liver toxicity, hypertension, and kidney dysfunction.

Biologic Agents
Rituxan (rituximab), Orencia (abatacept), and Kineret (anakinra) are used to target B cells or C cells. These medications are generally not combined with each other. Rituxan can be given every 6 months, Orencia every 4 weeks, and Kineret is given daily making it the last popular option.

TNF-alpha antagonists
Humira (adalimumab), Enbrel (etanercept), Simponi (golimumab), Cimzia (certolizumab), and Remicade (infliximab), are used to slow disease progression and greatly reduce inflammation. Many patients feel like their symptoms have improved even after the first injection. These injections are commonly given with methotrexate to prevent the formation of drug-neutralizing antibodies.

Other biologic agents used for management of RA include Kevzara (sarilumab), Actemra (tocilizumab), and Xeljanz (tofacitinib).

NSAIDs for rheumatoid arthritis
NSAIDs are used to help with pain and inflammation but they do not treat the underlying disease which is why they are usually used in conjunction with disease modifying drugs. Compared to other NSAIDs, Celebrex (celecoxib) causes less gastrointestinal upset making it a commonly chosen option. Most NSAIDs should be avoided in patients with a history of dyspepsia or peptic ulcer disease. Other common side effects of NSAIDs include headache, edema, confusion, decreased platelet function, or worsened hypertension. NSAIDs increase cardiovascular risk and can cause renal complications. To avoid these side effects, it is recommended to use the minimum effective dose. Most guidelines recommend using 1 NSAID at a time due to potential side effects. High doses of aspirin is not recommended for managing RA pain because it is likely to cause toxicity. It may take up to 2 weeks to experience the maximum effects from a NSAID so if dose adjustments are required, it should be done on a 2 week interval.

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