Rheumatoid Arthritis: Causes, Treatment and Therapy

September 19, 2019

Rheumatoid Arthritis (RA) is a systemic, autoimmune inflammatory disorder of unknown etiology affecting multiple organ systems. Science has shown that it primarily affects the synovial lining of diarthrodial joints causing symmetric, erosive synovitis in the joints. This pathological process eventually leads to articular and bone cartilage destruction. Pannus formation (a granulation tissue that covers the joint margins) is the most important destructive element in RA.

RA affects females more than males (2:1 ratio), primarily affecting individuals anywhere from 20-60 years old. The peak age of onset is the 4th and 5th decade of life. Although the primary cause of RA is unknown, major theories have been proposed in the literature. These include environmental factors (ie: infectious agents), genetic predisposition and autoimmune processes.

RA is a clinical diagnosis based on 4 out of 6 criteria being positive (set forth by the American College of Rheumatology). These criteria include morning joint stiffness lasting more than 1 hour, arthritis of 3 or more joints, arthritis of the hand joints, symmetric arthritis, rheumatoid nodules over the extensor surfaces, Rheumatoid Factor (RF) positive blood test, or radiographic changes indicating erosive, bony decalcification or joint-space narrowing within the hand/wrist areas.  Although there is no single lab test to diagnosis RA, over 85% of RA patients are RF+. RF+ individuals generally have increased severity of the disease, but RF+ lab tests are also seen in a number of other autoimmune diseases. A more specific blood test for RA is a positive cyclic citrullinated peptide antibody (CCP).

Treatment of RA depends on the stage of disease. For mild RA, treatment includes patient education, physical/occupational therapy and NSAIDs such as ibuprofen or naproxen. Moderate RA disease is treated with conservative care as well as disease-modifying anti-rheumatic drugs (DMARD) such as methotrexate and daily oral steroids (i.e.: prednisone). Severe RA will include all of the above including the addition of biological agents such as anti-TNF alpha drugs, co-stimulation modulators or anti-B cell agents. Surgical intervention is done for rare, refractory cases. Surgical options include surgical fusion of C1 and C2 if atlanto-axial instability is present, synovectomy, arthroplasty of the hip or knee or arthrodesis of the ankle.

It is important to note that conservative treatment such as isometric exercise programs, joint protection with wrist splints/finger splints to decrease pain and inflammation, weight loss, superficial moist heat for chronic RA and slow passive range of motion of joints are very crucial to the time course of the disease. In combination, they can be very effective in preventing the progression of RA.

Many of the medications used for autoimmune, systemic diseases carry many side effects such as gastrointestinal bleeding, kidney dysfunction, liver impairments, high blood sugars, depressed immune response, etc. In fact, many of the DMARDs are toxic at higher doses, but risks/benefits are always discussed prior to initiating therapy.

In conclusion, RA is a systemic, inflammatory process affecting many small and large joints of the body. Conservative treatment is started very early and routine follow-up with a Rheumatologist is warranted to carefully observe the time course of the disease process.


  1. Turesson C, O’Fallon WM, Crowson CS, et al. Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years. Ann Rheum Dis 2003; 62:722.
  2. Turesson C, Schaid DJ, Weyand CM, et al. The impact of HLA-DRB1 genes on extra-articular disease manifestations in rheumatoid arthritis. Arthritis Res Ther 2005; 7:R1386.
  3. Turesson C, Jacobsson LT, Sturfelt G, et al. Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with severe extra-articular manifestations in rheumatoid arthritis. Ann Rheum Dis 2007; 66:59.
  4. Jimenez-Boj E, Nöbauer-Huhmann I, Hanslik-Schnabel B, et al. Bone erosions and bone marrow edema as defined by magnetic resonance imaging reflect true bone marrow inflammation in rheumatoid arthritis. Arthritis Rheum 2007; 56:1118.
  5. McDougall R, Sibley J, Haga M, Russell A. Outcome in patients with rheumatoid arthritis receiving prednisone compared to matched controls. J Rheumatol 1994; 21:1207.
  6. Sautner J, Rintelen B, Leeb BF. Rituximab as effective treatment in a case of severe subcutaneous nodulosis in rheumatoid arthritis. Rheumatology (Oxford) 2013; 52:1535.