Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease marked by inflammation of the joints, sometimes with prominent extra-articular manifestations. The disease is initially characterized by inflammation of the synovial membranes (synovitis) of peripheral joints. If RA is uncontrolled, many cases ultimately lead to articular cartilage destruction, bone erosions, significant deformity, disability, shortened lifespan, and morbidity in 10-20 years from onset.

The etiology of rheumatoid arthritis is unknown but likely involves interaction of genetic and environmental factors. The typical presentation consists of a gradual onset of polyarticular symmetric arthritis of small joints and is characterized by pain, morning stiffness, and joint swelling. Among the early articular sites of disease are the metacarpophalangeal and proximal interphalangeal joints of the fingers, the metacarpophalangeal and interphalangeal joints of the thumbs, the wrists, and the metatarsophalangeal joints of the toes. Extra-articular manifestations may include dry eye syndrome (which occurs with variable severity in up to 50% of patients), pericarditis, episcleritis, scleritis, subcutaneous nodules, vasculitis, splenomegaly, fatigue, and mild anemia. The disease is associated with increased risk of lymphoma, infection, and early cardiovascular disease and death.

Risk Factors

RA affects 0.5-1% of the adult population in the US. Prevalence varies widely among ethnic and regional groups.[1] Other risk factors include:

Age. The typical age of onset is 30-55 years, although the disease may occur at any age.

Gender. RA is 2-3 times more common in women than in men.[2]

Genetics. The disease generally does not aggregate in families. Nonetheless, a multitude of genes may play a role in the development of RA. For example, the HLA-DRB1 gene contains a short disease-conferring sequence.

Cigarette smoking. Current or previous history of cigarette smoking has been shown to increase likelihood of RA in genetically susceptible populations.[3]

Diagnosis

The diagnosis of rheumatoid arthritis is largely clinical; no single laboratory or imaging study is pathognomonic. In order to even consider initial testing, a patient should present with swelling in at least 1 joint that cannot be explained by an alternative diagnosis. It is important to obtain a detailed history and perform a thorough physical examination as other illnesses may initially present with similar findings. The American College of Rheumatology in conjunction with the European League Against Rheumatism updated their diagnostic criteria in 2010 and now use a scoring system to diagnose RA.[4] Various signs, symptoms, and laboratory findings are taken into account, and a score of 6 or more out of 10 is diagnostic for RA. The individual criteria need not all be present simultaneously; therefore, the diagnosis can be established over time if additional criteria are met.

Criteria for diagnosis of RA include the following:

• Joint involvement
• Serology: rheumatoid factor and anti-cyclic citrullinated peptide
• Acute phase reactants: erythrocyte sedimentation rate and C-reactive protein
• Duration of symptoms

In “typical” cases, patients will report symmetric morning stiffness lasting for at least 1 hour, which has been present for more than 6 weeks. Pain and stiffness often affect the proximal interphalangeal, metacarpophalangeal, or wrist joints and almost never affect the distal interphalangeal joints.

Radiographic imaging should be obtained to establish a baseline to allow later comparison to assess disease progression.

If a joint effusion is present, aspiration with fluid evaluation can be beneficial if there is concern for infectious or crystal-related etiology.

Treatment

Treatment of RA generally includes physical therapy, dietary intervention (see Nutritional Considerations below), anti-inflammatory medication, and disease-modifying antirheumatic drugs (DMARDs). Occupational therapy and social work referrals may also be considered based on patient needs. Early referral to a rheumatologist is important both for further evaluation and also for starting DMARD treatment. Therapy is designed with a “treat to target” approach aiming to achieve remission. Reducing disease activity to the extent possible will slow disease progression.

Extra-articular manifestations are treated according to the specific syndrome (e.g., lubricating eye drops for dry eye syndrome).

Weight loss should be encouraged for overweight patients to decrease stress on the weight-bearing joints. Adequate rest and smoking cessation are also beneficial. Surgery is reserved for severe, debilitating disease.

Physical Therapy

Regular low-impact exercise, including aerobic exercises, judicious strength training, and range-of-motion exercises, is important for preserving joint function and preventing contractures and muscle atrophy. Water-based exercise does not appear to increase the rate of large joint damage. A reasonable prescription for exercise in RA patients may emphasize low-intensity water-based (and sometimes land-based) exercises.[5] Heat and hydrotherapy, relaxation techniques, and passive and active joint exercises are also helpful. There is evidence that yoga can reduce pain in RA patients.[6]

Pharmacologic Therapy

DMARDs are a mainstay of RA therapy and may prevent joint damage, preserve joint integrity and function, improve quality of life, prolong life, and reduce health care costs.[7] These drugs include hydroxychloroquine, sulfasalazine, methotrexate, and leflunomide. Azathioprine and cyclosporine are no longer in US guidelines but are still being used in Europe. Many DMARDs have potentially serious side effects and require close monitoring.

If a DMARD fails to achieve targeted improvement in disease activity (or is contraindicated), then treatment is often augmented by combining DMARDs or initiating a biologic or targeted immunomodulatory agent. These include antitumor necrosis factor α (TNF-α) agents (etanercept, infliximab, adalimumab, certolizumab pegol, golimumab), a selective costimulation modulator (abatacept), interleukin-6 receptor antagonists (tocilizumab, sarilumab), a B-cell depleting agent (rituximab), an interleukin-1 receptor antagonist (anakinra), and oral small molecule janus kinase inhibitors (tofacitinib, baricitinib, and upadacitinib). Use of these agents has revolutionized life for people with RA by preventing joint damage and reducing all-cause and cardiovascular disease-related mortality.[8] Other agents continue to be developed and show promise in treating RA and other autoimmune diseases.

Anti-inflammatory medications are first-line treatments for pain relief. Steroids are generally more effective than nonsteroidal anti-inflammatory drugs (NSAIDs). Oral steroids may be used for short-term treatment of RA flares or for long-term treatment of moderate or high disease activity, while intra-articular steroids may be considered for individual joint pain no more frequently than every 3 months. Long-term steroid use has gastrointestinal, cardiovascular, integumentary, endocrine, and musculoskeletal complications. The physician should consider prophylaxis against pneumocystis jirovecii with any anticipated long-term steroid use.[9] When steroids are used, dietary supplementation with adequate vitamin D and calcium should be instituted. Patients who require steroid therapy beyond 3 months may benefit from the addition of a bisphosphonate, such as alendronate.

Nutritional Considerations

Alongside DMARD therapy, rheumatoid arthritis may often be ameliorated with diet changes, and some cases of complete remission have been reported. Studies have shown both symptomatic and laboratory evidence of improvement with vegetarian diets and various elimination diets. Omega-3 fatty acids may reduce pain and inflammation in RA. The key nutritional issues in RA are summarized below:

Vegan and Vegetarian Diets

Some evidence indicates that patients who follow vegan or vegetarian diets may experience significant improvement in RA symptoms. Researchers in Norway found that a vegan diet led to reductions in pain, swelling, and morning stiffness, as well as improvements in C-reactive protein. Another study found significant improvements in RA symptoms with a 4-week vegan diet intervention.[10]

Some studies have focused on meat specifically. Although 1 study found no connection between meat and RA, others have found that higher intakes of meat and elevated serum cholesterol concentrations are associated with increased risk of developing this disease.[11],[12],[13],[14],[15] In addition, the removal of meat products from the diet has shown to improve symptoms for the long term.[10] Patients with RA are known to be at higher risk for cardiovascular disease and to have higher serum levels of oxidized low-density lipoprotein.[16]

Eliminating Diet Triggers

Clinical tests have shown that consumption of allergenic foods increases proinflammatory chemicals (cytokines) that are considered a hallmark of RA.[17] Studies have shown that eliminating certain foods brings symptomatic improvement.[10],[18] To identify trigger foods, an elimination diet can easily be instituted on an outpatient basis. The procedure is as follows:

Start with a simple baseline diet, excluding foods that are more common triggers (dairy products, corn, meats, wheat, oats and rye, eggs, citrus fruits, potatoes, tomatoes, nuts, and coffee) and including only those foods not implicated in arthritis, listed below:

• Brown rice
• Cooked or dried fruits (cherries, cranberries, pears, prunes)
• Cooked green, yellow, and orange vegetables (artichokes, asparagus, broccoli, chard, collards, lettuce, spinach, string beans, squash, sweet potatoes, tapioca, and taro)
• Plain or carbonated water
• Condiments (modest amounts of salt, maple syrup, vanilla extract)

After approximately 4 weeks on this diet, if symptoms have improved or disappeared, patients may introduce previously eliminated foods 1 at a time, every 2 days. Patients should keep a food diary and add these foods in generous amounts to observe which ones cause arthritic symptoms. Foods listed above as common triggers should be added last. A newly added food associated with increased joint pain should be removed from the diet for 1-2 weeks, and then reintroduced to see if the same reaction occurs. If no symptoms are experienced, that food can be kept in the diet.

Antioxidants

In general, fruits and vegetables seem to be protective against the development of RA.[19] Poor antioxidant status may be a risk factor for RA.[20] Studies have shown that a higher intake of certain carotenoids found in fruits and vegetables may protect against developing RA.[21],[22] Foods containing beta-cryptoxanthin (e.g., citrus fruits) and zeaxanthin (e.g., green leafy vegetables) may be particularly helpful. The European Prospective Investigation of Cancer (EPIC)–Norfolk study of more than 25,000 individuals found that those consuming the highest amounts of these carotenoids had half the risk for developing inflammatory polyarthritis, compared with those consuming the least amount.[23] Lower serum levels of vitamin E and selenium were also found to predict the development of rheumatoid arthritis.[24]

Oil Intake

A diet low in arachidonic acid, an omega-6 fatty acid found in animal products, was found to ameliorate inflammation in patients with RA.[25] This effect was strengthened by omega-3 fatty acid supplementation.[25],[26] Studies have also found a lower incidence of arthritis in Mediterranean countries, which may be attributable to olive oil intake, possibly because this fat negates the production of proinflammatory chemicals that affect RA patients.[12],[27] Supplementing with gamma-linolenic acid (GLA) was found to be an effective strategy for reducing the symptoms of RA, and supplementation with a combination of GLA and omega-3 fatty acids was found to both reduce symptoms and decrease the need for NSAIDs in RA patients.[28],[29],[30] These fatty acids appear to work by blocking production of arachidonic acid-derived inflammatory mediators, an effect that is achievable with vegan diets as well (see above).

Folic Acid

Patients with RA are often treated with methotrexate, a folate antagonist that can increase plasma homocysteine concentrations.[31] Folate supplementation is recommended to prevent methotrexate-induced toxicity, folate deficiency, and hyperhomocysteinemia.[32]

Orders

Vegetarian diet, nondairy, to be tried on a prospective basis.

Nutrition consultation: to advise patient in the above diet, consider elimination diet to evaluate for occult food allergies, and arrange follow-up to assist patient in long-term dietary modifications.

Physical and occupational therapy consultations: to recommend an individualized exercise program.

What to Tell the Family

RA can be ameliorated through dietary measures and medication as appropriate for disease severity. Diet changes can be helpful, sometimes dramatically so, and due to the hereditary component of RA, family members may benefit from similar diet changes. The patient should stay physically active through regular low-impact exercise, light strength training, and range-of-motion exercises. Exercises learned in physical therapy should be incorporated into the daily exercise routine.

References