Rheumatoid Arthritis and the Spine

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease that causes heat, redness, swelling, pain and destruction of synovial joints.  Synovium is the tissue that lines joints, ligaments, and tendons.  The immune system causes a transformation of synovium into an inflammatory tissue.  RA characteristically affects small joints of the feet and hands. In the spine, RA affects the cervical region, or neck, almost exclusively.  RA can modify the anatomy of the cervical spine causing excessive motion or subluxation.  At its most severe, destruction of components of the cervical spine can result in compression of the spinal cord causing neurologic dysfunction like paralysis.

Symptoms

The symptoms of RA in the cervical spine include neck pain, headaches, and arm pain.  The atlanto-axial joint, where the two top vertebrae meet, is especially prone to damage, resulting in instability.  That means that when bending the neck, the head will move forward while the spine moves backward causing a compression of the spinal cord.

Neck movement frequently precipitates aching neck pain.  Disease at the top of the spine results in pain that radiates over the back of the skull and moves toward the forehead with increasing disease.  Other complaints include loss of consciousness, incontinence, dizziness, and loss of sensation.  If one of the vertebral arteries is compromised, visual changes, dizziness, and gait abnormalities may occur.

Symptoms associated with instability in lower portions of the cervical spine cause pain over the lateral aspects of the neck, collarbones, and shoulder blades. Nerves supplying the arms may be affected.  Confusion with peripheral nerve compression, like carpal tunnel syndrome, is frequent in this circumstance.

Diagnosis

RA is a clinical diagnosis based on the medical history of joint pain, distribution of joint involvement, and characteristic laboratory abnormalities. Blood test abnormalities include an increase in rheumatoid factor and anti-cyclic citrullinated protein antibodies.  In the setting of hand and foot arthritis, the finding of neck pain associated with radiographic characteristic abnormalities including subluxations, cervical spine joint erosions without bone thickening, and disc space narrowing without bone spurs is most appropriately attributed to RA.

Treatment

The treatment for control of generalized RA includes a regimen of non-pharmacologic therapy consisting of patient education and physical therapy. Soft cervical collars offer comfort but do not protect against progressive spine slippage. Hard collars can limit anterior subluxations but do not allow reduction of slippage bending backwards.  Pharmacologic therapy includes nonsteroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biologics.

Medication

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs, a class of drugs that includes aspirin, can decrease pain, fever, and inflammation.  NSAIDs are anti-inflammatory and pain-relieving when given in larger doses long term.  In RA, NSAIDs decrease joint stiffness and pain but are often inadequate by themselves to control disease symptoms and improve function.

NSAIDs, work by blocking an enzyme in the body named cyclooxygenase  -2 (COX-2),  COX -2 produces prostaglandins.  Prostaglandins are associated with heat, swelling, and pain associated with tissue injury.  In addition to blocking COX-2, most NSAIDs block cyclooxygenase -1 (COX-1).  The prostaglandins made by COX-1 help preserve the stomach, lining, regulate kidney function, and maintain normal blood pressure.  Nonselective NSAIDS BLOCK BOTH cox-1 and 2.  By blocking COX1 and 2 the risk of gastrointestinal bleeding and esophageal reflux are increased.  A COX-2 inhibitor, Celecoxib may inhibit COX-2 without affecting COX-1 enzyme decreasing the risk of gastrointestinal toxicities.

NSAIDs fall into a number of different chemical groups.  An individual may respond to one and not anther.  Any single NSAID may help about 66% of the people who try it.  Some individuals have to try 3 or more NSAIDs before finding the one that works.

NSAIDs can be taken by mouth, or used topically as a gel or patch.  The downside of topical use is that they may need frequent application up to 4 times a day to be effective.  Even though the dose is lower, topical therapies are associated with toxicities similar to the oral form of the NSAID.

Disease-Modifying Anti-rheumatic Drugs (DMARDs)

DMARDs are a group of medications that help calm the overactive immune system and inflammatory activities in the body.  DMARDs work more slowly than NSAIDs but have the additional benefit of modifying the progression of disease.  These drugs have greater benefit in RA, including a beneficial effect on cervical spine disease.  There are two categories of DMARDs: biologic (created to be similar to proteins found in the body) and non biologic.

  • Anti-Tumor Necrosis Factor Inhibitors (TNFi)

Cell messengers, or cytokines, are released by cells to initiate a variety of functions.  An inflammatory cytokine, TNF is associated with the clinical manifestations of RA.  TNF is associated with fatigue, joint swelling, stiffness, and pain.  A decrease in the production of TNF or removal from the blood stream can result in a decrease in disease-associated complaints.  However, the total removal of TNF can be associated with an increased risk of infection.  The goal of therapy is to obtain a physiologic level of TNF.  ANTI-TNF biologic therapies available for the treatment of RA include;

  • Enbrel® (etarnercept)
  • Humira® (adalimumab)
  • Simponi® (golimumab)
  • Cimzia® (certolizumab)
  • Remicade® (infliximab).

The use of specific DMARDs in individuals is mainly based on personal preference related to injections versus infusion and frequency of dosing.

Side effects associated with the use of TNF inhibitors include the activation of latent tuberculosis and increased risk of viral and bacterial infections.  If infections occur, the infection is treated and the TNF therapy stopped until the infection is resolved.  A small increased risk of certain cancers has also been reported and is undergoing active evaluation.

  • Non-biologic DMARDs
  • Orencia® (abatacept) Activation of lymphocytes requires a sequence of signals. Immune response that results in RA is diminished if these secondary signals are blocked.  Orencia® is a fusion protein that inhibits antigen-presenting cells from delivering co-stimulatory signals that activate T cells.  Orencia® is administered by monthly infusions or subcutaneous injections.
  • Actemra® (Tocolizumab) is a humanized monoclonal antibody directed against IL-6 receptors, blocking the effect of Interleukin -6 (IL-6), a cytokine that mediates a portion of the destructive immune response in RA. Inhibition of IL-6 is associated with decreased inflammatory complaints and joint destruction in RA.  Actemra® is administered by monthly infusions or subcutaneous injections.
  • Xeljanz® (tofacitinib) Janus kinases (Jak) are a series of enzymes that activate lymphocytes resulting in inflammatory responses. Xeljanz®  is a small molecule that inhibits Jak 3 and, to a lesser degree, Jak2.  Xeljanz® is administered by mouth on a daily basis.
  • Rituxan® (rituximab) B-lymphocytes are components of the immune system contributing to the destructive changes of RA. Rituxan®  is an antibody combining mouse and human components.  The antibody is directed against the CD 20 transmembrane protein on B lymphocytes.  The attached antibody activates an immune response causing destruction of these activated B cells.  A decreased number of CD 20 lymphocytes results in diminished activity of RA.  Rituxan® is administered by infusion on a regular schedule.
  • Methotrexate
  • Leflunomide
  • Sulfasalazine
  • Hydroxychloroquine

Corticosteroids

Systemic corticosteroids are effective in controlling the inflammatory components of RA.  Corticosteroids are the most powerful and predictable remedy inducing immediate relief of joint inflammation in RA.  Corticosteroids prescribed in low doses (5 to 10 mg) have a modest effect on reducing the rate of x-ray detected joint destruction.  The side effects of corticosteroids include hypertension, diabetes, cataracts, and obesity

Surgery

RA patients with cervical subluxation with neurologic abnormalities are potential candidates for stabilization of the cervical spine.  The surgical technique utilized will correspond to the damaged portion of the cervical spine.  Usually only the component of the spine that is damaged is stabilized.  The upper portion of the spine may be wired to the skull.  Lower portions of the spine are decompressed and fused.  Getting a surgical consultation with a spine surgeon with experience in RA cervical subluxations offers a better opportunity for a successful outcome.

References:

Borenstein DG, Wiesel SW, Boden SD: Low Back and Neck Pain: Comprehensive Diagnosis and Management. 3rd Edition. Philadelphia: W. B. Saunders, 2004, pg 921

CONDITIONS OF THE GI TRACT