Overview and Risk Factors

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 destruction of the articular cartilage, bone erosions, and significant deformity, disability, and morbidity in 10 to 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 the small joints, 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, mild anemia, and elevation of the inflammatory markers erythrocyte sedimentation rate and C-reactive protein (CRP).

Risk Factors

RA affects about 1% of the adult population in the United States. Prevalence varies widely among ethnic and regional groups. For example, far less than 1% of rural Africans are affected, compared with 5% of Pima Indians. Other risk factors include:

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

Gender. RA is 2 to 3 times more common in women than in men.

Genetics. The HLA-DRB1 gene contains a short disease-conferring sequence.

Diagnosis and Treatment

Diagnosis

The diagnosis of rheumatoid arthritis is largely clinical; no single laboratory or imaging study is definitive. The American Rheumatism Association has established 7 clinical signs, 4 of which must be present for diagnosis:

• Morning stiffness in/around joints, lasting at least 1 hour before maximal improvement.
• Soft tissue swelling and pain of three or more joint areas lasting at least 6 weeks.
• Swelling of the proximal interphalangeal, metacarpophalangeal, or wrist joints lasting at least 6 weeks.
• Symmetric swelling (arthritis) lasting at least 6 weeks.
• Rheumatoid nodules.
• Positive rheumatoid factor (found in about 85% of patients).
• Radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints.

Treatment

Treatment of rheumatoid arthritis generally includes physical therapy, dietary intervention (see Nutritional Considerations), anti-inflammatory medication, and disease-modifying agents.

Extra-articular manifestations are treated according to the specific syndrome (eg, 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, are important for preserving joint function and preventing contractures and muscle atrophy.

Heat and hydrotherapy, relaxation techniques, and passive and active joint exercises are also helpful.

Pharmacologic Therapy

Anti-inflammatory medications are first-line treatments. Steroids are more effective than NSAIDs for pain relief and suppression of inflammation; however, they should be used carefully, as patients are at significant risk for bone loss, among other complications. When steroids are used, dietary supplementation with 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.

Disease-modifying antirheumatic drugs (DMARDs) are a mainstay of rheumatoid arthritis therapy and may prevent joint damage, preserve joint integrity and function, reduce health costs, and maintain economic productivity.¹ These drugs include hydroxychloroquine, sulfasalazine, methotrexate, leflunomide, gold salts, D-penicillamine, azathioprine, and cyclosporine. Many DMARDs have potentially serious side effects and require close monitoring.

Newer agents that have proven beneficial for rheumatoid arthritis include anti-tumor necrosis factor α± (TNF-α±) agents (etanercept, infliximab, adalimumab), and interleukin-1 receptor antagonists (anakinra). Other biological agents targeting key cellular constituents of the immune system or cytokines are expected to be approved in the near future.

Nutritional Considerations

Rheumatoid arthritis may sometimes be ameliorated with proper diet. 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:

Vegetarian Diets

A body of evidence indicates that patients who follow vegan or vegetarian diets may experience significant improvement in rheumatoid arthritis symptoms. Improvement in laboratory values (rheumatoid factor, CRP) is a frequent finding on these diets, and correlates with a reduction in antibodies to food antigens.^2,3 Conversely, higher intakes of meat^4,5 and elevated serum cholesterol concentrations⁶ are associated with increased risk of developing this disease. Patients with RA are known to be at higher risk for cardiovascular disease and have higher serum levels of oxidized low-density lipoprotein (LDL).⁷

Eliminating Diet Triggers

Clinical tests have shown that consumption of allergenic foods increases pro-inflammatory chemicals (cytokines) that are considered a hallmark of RA.⁸ Studies have shown that eliminating certain foods brings symptomatic improvement.^9,10 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 one at a time, every 2 days. Patients should keep a food diary and add these foods in generous amounts to observe which 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 to 2 weeks, and reintroduced to see if the same reaction occurs. If no symptoms are experienced, that food can be kept in the diet.

Antioxidants

Poor antioxidant status may be a risk factor for RA.¹¹ Studies have shown that a higher intake of certain carotenoids found in fruits and vegetables may protect against developing RA.^12,13 Foods containing beta-cryptoxanthin (eg, citrus fruits) and zeaxanthin (eg, 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.¹⁴ Lower serum levels of vitamin E and selenium were also found to predict the development of rheumatoid arthritis.¹⁵

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.  This effect was strengthened by omega-3 fatty acid supplementation,¹⁶ Studies have also found a lower incidence of arthritis in Mediterranean countries, which may be attributable to olive oil intake4,¹⁷ possibly because this fat negates the production of pro-inflammatory chemicals that affect RA patients. Supplementing with gamma-linolenic acid (GLA) was found to be an effective strategy for reducing the symptoms of RA,¹⁸ 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.^19,20 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.²¹ Folate supplementation is recommended to prevent methotrexate-induced toxicity, folate deficiency, and hyperhomocysteinemia.²²

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 therapy consultation: To recommend an individualized exercise program.

What to Tell the Family

Rheumatoid arthritis can be ameliorated through dietary measures and medication as needed to control symptoms. Due to the strong hereditary component of RA, family members may benefit from a similar diet. 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

1. American College of Rheumatology Ad Hoc Committee on Clinical Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum.2002;46:328.

2. McDougall J, Bruce B, Spiller G, Westerdahl J, McDougall M. Effects of a very low-fat, vegan diet in subjects with rheumatoid arthritis. J Altern Complement Med. 2002;8:71-75.

3. Hafstrom I, Ringertz B, Spangberg A, et al. A vegan diet free of gluten improves the signs and symptoms of rheumatoid arthritis: the effects on arthritis correlate with a reduction in antibodies to food antigens. Rheumatology (Oxford). 2001;40:1175-1179.

4. Pattison DJ, Symmons DP, Lunt M, et al. Dietary risk factors for the development of inflammatory polyarthritis: evidence for a role of high level of red meat consumption. Arthritis Rheum. 2004;50:3804-3812.

5. Grant WB. The role of meat in the expression of rheumatoid arthritis. Br J Nutr. 2000;84:589-595.

6. Heliovaara M, Aho K, Knekt P, Reunanen A, Aromaa A. Serum cholesterol and risk of rheumatoid arthritis in a cohort of 52,800 men and women. Br J Rheumatol. 1996;35:255-257.

7. Kim SH, Lee CK, Lee EY, et al. Serum oxidized low-density lipoproteins in rheumatoid arthritis. Rheumatol Int. 2004;24:230-233.

8. Karatay S, Erdem T, Yildirim K, et al. The effect of individualized diet challenges consisting of allergenic foods on TNF-alpha and IL-1beta levels in patients with rheumatoid arthritis. Rheumatology (Oxford). 2004;43:1429-1433.

9. van de Laar MA, Aalbers M, Bruins FG, van Dinther-Janssen AC, van der Korst JK, Meijer CJ. Food intolerance in rheumatoid arthritis. I. A double blind, controlled trial of the clinical effects of elimination of milk allergens and azo dyes. Ann Rheum Dis. 1992;51:298-302.

10. Kjeldsen-Kragh J, Haugen M, Borchgrevink CF, et al. Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis. Lancet.1991;338:899-902.

11. Heliovaara M, Knekt P, Aho K, Aaran RK, Alfthan G, Aromaa A. Serum antioxidants and risk of rheumatoid arthritis. Ann Rheum Dis. 1994;53:51-53.

12. Cerhan JR, Saag KG, Merlino LA, Mikuls TR, Criswell LA. Antioxidant micronutrients and risk of rheumatoid arthritis in a cohort of older women.
Am J Epidemiol. 2003;157:345-354.

13. Comstock GW, Burke AE, Hoffman SC, et al. Serum concentrations of alpha tocopherol, beta carotene, and retinol preceding the diagnosis of rheumatoid arthritis and systemic lupus erythematosus. Ann Rheum Dis. 1997;56:323-325.

14. Pattison DJ, Symmons DP, Lunt M, et al. Dietary beta-cryptoxanthin and
inflammatory polyarthritis: results from a population-based prospective study. Am
J Clin Nutr. 2005;82:451-455.

15. Knekt P, Heliovaara M, Aho K, Alfthan G, Marniemi J, Aromaa A. Serum selenium, serum alpha-tocopherol, and the risk of rheumatoid arthritis. Epidemiology. 2000;11:402-405.

16. Adam O, Beringer C, Kless T, et al. Anti-inflammatory effects of a low arachidonic acid diet and fish oil in patients with rheumatoid arthritis. Rheumatol Int. 2003; 3:27-36.

17. Linos A, Kaklamani VG, Kaklamani E, et al. Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables? Am J Clin Nutr. 1999;70:1077-1082.

18. Little C, Parsons T. Herbal therapy for treating rheumatoid arthritis. Cochrane Database Syst Rev. 2001;CD002948.

19. Lau CS, Morley KD, Belch JJ. Effects of fish oil supplementation on non-steroidal anti-inflammatory drug requirement in patients with mild rheumatoid arthritis--a double-blind placebo controlled study. Br J Rheumatol. 1993;32:982-989.

20. Belch JJ, Ansell D, Madhok R, O'Dowd A, Sturrock RD. Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study. Ann Rheum Dis. 1988;47:96-104.

21. Whittle SL, Hughes RA. Folate supplementation and methotrexate treatment in rheumatoid arthritis: a review. Rheumatology (Oxford). 2004;43:267-271.

22. Morgan SL, Baggott JE, Lee JY, Alarcon GS. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during long-term, low-dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J Rheumatol. 1998;25:441-446.