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Rheumatoid Arthritis

Pathology || Signs and Symptoms || Complications || Diagnosis || Treatment || Overview || Related Articles || References and Resources || Comment || Search

Pathology





Rheumatoid arthritis is an autoimmune condition in which the body literally attacks itself. The parts of the body most affected in rheumatoid arthritis are the joints. Specifically, the body forms antibodies against antigens of the synovium. The synovium is a cellular coating that lines the joint space. It normally secretes lubricants and helps ensure the integrity of the joint space itself. However, in rheumatoid arthritis auto-antibodies bind to specific proteins in the synovial lining causing inflammation. The inflammatory process gets out of control damaging not only the synovium, but also adjacent structures like cartilage and bone. After years of inflammatory changes the joints involved become deformed.

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Signs and Symptoms

Clinically, rheumatoid arthritis typically begins as vague non-specific symmetric joint pain. In its earliest form it an be difficult to diagnose. Patients will often complain of other non-specific symptoms like fatigue, low grade fevers, and weight loss. The inflammatory response typically begins in the hands and feet. In the hands the metacarpophalangeal joints (MCP) and proximal interphalangeal joints (PIP) are most commonly involved. Interestingly, the distal interphalangeal joint (DIP) is not involved (these joints are more commonly involved in osteoarthritis).

Ulnar Deviation
After years of wear and tear several deformities occur. The two commonly seen ones are Boutonniere and Swan Neck deformities of the fingers. In addition, ulnar deviation of the hand can occur (notice how the fingers deviate in the X-ray to the left). Damage to joints in the cervical spine can lead to neck instability and possibly spinal cord injury.

Symptoms of rheumatoid arthritis may wax and wane, or disappear entirely for periods of time. Unfortunately, they almost always return. Eventually the wrists, ankles, elbows, and knees become involved. The disease is considered progressive.

Interestingly, nearly three fourths of women with rheumatoid arthritis who become pregnant have significant improvement in their symptoms during the second trimester.

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Complications

Unfortunately, rheumatoid arthritis does not solely affect the joints. Inflammatory reactions can also occur in other parts of the body.

Inflammation of the eye (specifically the episclerae) can lead to red and painful eyes. Painful inflammatory nodules, known as rheumatoid nodules, can occur underneath the skin. Interestingly, these nodules can also occur in other parts of the body such as the lung.

Effusions (ie: collections of fluid) can also occur around the heart (a pericardial effusion) or lung (a pleural effusion). Many patients with rheumatoid arthritis are also anemic.

Patients are also at increased risk for coronary artery disease. Inflammation of blood vessels (ie: rheumatoid vasculitis) can cause damage to the skin, fingers, toes, nerves, and bowel. Ultimately, many body systems other than the joints can be involved. Many of which can have devastating consequences.

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Diagnosis

Diagnosis of rheumatoid arthritis is generally delayed because of its insidious and non-specific onset. Diagnosis is made off of clinical symptoms, physical exam observations, and supporting laboratory data. Several criteria (developed by the American College of Rheumatology) are used to help support the diagnosis. They include:

(1) Morning joint stiffness (> than 1 hour for 6 weeks) that improves with activity.
(2) Greater than or equal to 3 joints involved.
(3) Symmetric (ie: occurring in the same joint on both sides of the body).
(4) Involvement of typical hand joints (MCP and PIP joints).
(5) Rheumatoid nodules.
(6) Rheumatoid factor in blood tests.
(7) Radiographic evidence of rheumatoid changes.

If you have four or more of the following, the diagnosis of rheumatoid arthritis is very likely. A blood test that looks for antibodies directed against cyclic citrullinated peptide is about 90% specific for rheumatoid arthritis. Anti cyclic citrullinated peptide antibodies also have prognostic significance.

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Treatment

Treatment for rheumatoid arthritis involves several different categories of medications. The first class is the non-steroidal anti-inflammatory medications (NSAIDs). The most well known NSAID is ibuprofen although there are many others. NSAIDs improve symptoms and help control the inflammatory response, but do little to slow the disease progression. Steroids like prednisone are also commonly prescribed to help control symptoms and acute flairs, but like NSAIDs do little to control the progression of the disease.

The second category of medications, known as DMARDS, or "disease modifying anti-rheumatic drugs" are designed to slow the course of the disease. These medications dampen the immune system and therefore slow the inflammatory process.

All patients who have been diagnosed with rheumatoid arthritis, and have active disease should be on at least one DMARD. For mild disease one of the following medications may be used: methotrexate, sulfasalazine, leflunomide, or hydroxychloroquine. Hydroxychloroquine should only be used in patients with mild non-erosive disease; it is also useful in pregnant patients as is sulfasalazine.

Individuals with moderate disease (ie: evidence of erosive arthritis) are usually started on methotrexate plus one other DMARD (ie: sulfasalazine, leflunomide, or hydroxychloroquine). If methotrexate is used in combination with leflunomide close monitoring of liver function is necessary. Patients using methotrexate should also be started on folate supplementation (1 mg/day).

Treatment Options:
- NSAIDs
- Steroids
- DMARDS
- Biologics

In people with severe disease a third category of medications known as "biologics" may be indicated. They include the three anti-tumor necrosis factors etanercept, infliximab, and adalimumab; the Il-1 receptor antagonist anakinra; the CTLA4 immunoglobulin abatacept; and the anti-CD20 medication rituximab.

Most patients with severe disease should be on a DMARD (usually methotrexate) plus an anti-tumor necrosis factor like etanercept. People who don't respond to etanercept may be given infliximab or adalimumab. If they fail to respond to one of the other two anti-TNFs, another biologic such as rituximab or anakinra may be necessary.

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Overview

Rheumatoid arthritis causes symmetric auto-immune destruction of joint spaces. It commonly starts in the hands and feet. Other organ systems may be involved as well. Diagnosis is based off of clinical symptoms, physical exam findings, and blood tests. Treatment is with NSAIDs, steroids, and disease modifying anti-rheumatic medications (DMARDS).

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Related Articles

- Systemic lupus erythematosus

- Pericardial effusion

- Coronary artery disease

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References and Resources

(1) Nishimura K, Sugiyama D, Kogata Y, et al. Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis. Ann Intern Med. 2007 Jun 5;146(11):797-808.

(2) Saag KG, Teng GG, Patkar NM, et al. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008 Jun 15;59(6):762-84.

(3) Haraoui B. Assessment and management of rheumatoid arthritis. J Rheumatol Suppl. 2009 Jun;82:2-10.

(4) Kumar V, Abbas AK, Fausto N. Robbins and Cotran Pathologic Basis of Disease. Seventh Edition. Philadelphia: Elsevier Saunders, 2004.

(5) Bickley LS, Szilagyi PG. Bates' Guide to Physical Examination and History Taking. Ninth Edition. New York: Lippincott Williams and Wilkins, 2007.

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