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Arthritis [Rheumatoid Arthritis – RA]

Rheumatoid Arthritis (RA) is a chronic, systemic inflammatory disorder of unrecognized etiology that primarily involves the joints. RA typically affects the small joints of the hand and foot and can lead to deformity and destruction of the joints due to erosion of cartilage and bone. RA occurs worldwide; its prevalence in the developed countries varies between 0.5% and 2%. It affects women two to three times as often as men with peak onset between the ages of 30 and 55 years. The disease onset is usually insidious (weeks to months), with pain, stiffness, and swelling of multiple joints. Weight loss, low-grade fever, malaise, fatigue, and depression also may be present. Regardless of early asymmetrical involvement, most patients eventually will develop a symmetric inflammatory arthritis.

Elderly patients may first display diffuse myalgias, weight loss, stiffness, and fatigue (similar to polymyalgia rheumatica) and only later develop the typical joint swelling. A small percentage of patients will have an acute onset (days to weeks) of symptoms.

The joints most commonly involved are the metacarpophalangeal, proximal interphalangeal, metatarsophalangeal, and the wrists. Later in the course of the disease, typical deformities can develop, including ulnar deviation of the fingers with subluxation of the affected joints, swan-neck deformities (hyperextension of the proximal and flexion of the distal interphalangeal joints) and boutonnière deformities (fixed flexion of the proximal and hyperextension of the distal interphalangeal joints).

Most patients will have a prolonged course of slowly progressing, destructive disease, with alternating characteristic periods of exacerbation and improvement. A small percentage may enjoy prolonged clinical remissions (bringing the diagnosis of RA into question). A small percentage may suffer a rapidly progressive and destructive course of the disease.

Radiographic evidence of joint damage is common. Early findings include joint space-narrowing from cartilage destruction and osteopenia (loss of bone density) around the affected joints. The majority of patients with RA eventually display radiographic evidence of erosions in the small joints of the hands and feet. In some patients, erosions occur first in the ulnar styloid or metatarsophalangeal joint. It is, thus, worth evaluating both the hands (including the wrists) and the feet radiographically. The number of joint erosions increases over time and correlates with the persistence of inflammation, as evidenced by clinical measures of morning stiffness, synovial swelling, and elevation of ESR and CRP (C-reactive protein).

Active inflammation in the joints of the cervical vertebrae can lead to joint destruction and subluxation, just as in the peripheral joints. Atlantoaxial subluxation is the most common and results usually from laxity (or disruption from erosive disease) of the transverse ligament. Without the posterior stabilization from the transverse ligament, the odontoid process can compress the spinal cord, particularly with neck flexion.

Lateral views taken of the spine cervical region in flexion will demonstrate the subluxation. More than 3 to 4 mm of space between the odontoid process and the posterior arch of the atlas is abnormal. A gap of 8 to 9 mm or more (atlantoaxial subluxation) is associated with an increased frequency of cord compression. Cervical spine radiographs need to be done routinely in the preoperative evaluation of even asymptomatic RA patients, since manipulation of the neck during intubation may lead to neurologic damage.

MRI is invaluable for the assessment of cervical spine disease in RA, because it permits visualization of the cord and any potential compression. Myelopathy from cord compressions may present with pain radiating upwards, peripheral sensory changes, weakness, reflex changes, or slowly progressing spastic quadriparesis. Other signs and symptoms that suggest cervical myelopathy include a sensation of the head falling forward upon flexion of the cervical region, changes in the level of consciousness, “drop” attacks, loss of sphincter control, respiratory dysfunction, dysphagia, vertigo, convulsions, hemiplegia, dysarthria and nystagmus, and peripheral paresthesias without evidence of peripheral nerve disease or compression. Suspected myelopathy requires immediate attention and possibly intervention. Unfortunately, soft cervical collars do not adequately stabilize the affected region. A definitive therapy is the surgical stabilization of the cervical vertebrae.

Standard therapy of patients with RA includes prednisone, hydroxychloroquine, sulfasalazine, and methotrexate, either as single agents or in combination. Methotrexate has been a very popular agent in the United States. It is relatively strong and, although it has the potential for significant toxicity, is generally well tolerated. Usual doses are 15-20 mg taken weekly either orally or injected subcutaneously. Common side effects include oral ulcers, headache, nausea, and diarrhea. Monthly blood counts (monitoring potential cytopenias) as well as AST and albumin determinations (monitoring potential liver toxicity) and creatinine determinations are required. Although hypersensitivity pneumonitis can be a serious complication, it is unusual. Leflunomide has been used in Europe for transplant immunosuppression prior to its approval in the United States. Although studies vary, it is likely as effective as methotrexate, with liver toxicity as a major adverse event.

New facts:
Active synovitis and joint destruction cause a high degree of economic loss and morbidity and are associated with early mortality. There is mounting evidence that currently available Disease Modifying Anti-Rheumatic Drugs (DMARD) and anti-cytokine agents can control synovitis and may slow or even stop radiographic progression. The treatment goals are to control the signs and symptoms, restore the physical function, and prevent (or halt) the development of joint damage. With refractory disease, the treatment goals are to relieve pain, improve joint motion, limit functional loss, and incur a minimum of adverse effects.

Recently, several new agents have been approved by the FDA for the treatment of patients with RA, including etanercept, infliximab, adalimumab, and anakinra. These new medications represent a more targeted approach to RA, directed against specific components of the inflammatory process. Cytokines–particularly Tumor Necrosis Factor (TNF) and Interleukin-1 (IL-1)–play a major role in perpetuating the inflammation that causes joint destruction in RA.

Etanercept is a soluble TNF receptor, which binds the circulating TNF and makes it biologically inactive. It is effective in controlling the symptoms of RA and appears to slow the rate of radiographic progression of joint damage. It is injected twice weekly in a dose of 25 mg per injection. Side effects include injection-site erythema and flu-like symptoms.

Infliximab is an antibody directed against TNF. Because it is a chimeric antibody that combines mouse proteins with human proteins, there is concern that an RA patient may develop antibodies to the mouse protein that could render infliximab ineffective. The FDA recommends infliximab be used in combination with methotrexate to suppress such antibody formation. Infliximab is given by intravenous infusion every other month. Common side effects include infusion reactions and flu-like symptoms.

Adalimumab is also an antibody directed against TNF. It is different from infliximab because it has no mouse proteins, only human proteins. It is injected subcutaneously twice monthly. Common side effects include injection site reactions and flu-like symptoms.

Anakinra is a recombinant, non-glycosylated form of the human IL-1 receptor antagonist. It blocks the biologic activity of IL-1 through competitive inhibition of the IL-1 receptor, which is expressed in a wide variety of tissues and organs.

Heberden’s Nodes
About 1800 William Heberden, renowned for first describing angina, published a 79-word comment “What are these little hard knobs, about the size of a small pea, which are frequently seen upon the fingers, particularly a little below the top, near the joint?” he said, “(they are more) unsightly than inconvenient.” He called them “digitorum nodi.” We now call them Heberden’s nodes.

These nodes indicate osteoarthritis, a non-fatal condition that adds disability to the elderly. Everyone knows what it is but it’s hard to define. It affects joints with cartilage and synovial (joint) fluid. Cartilage continually remodels and imbibes water, acting like a coiled spring. The underlying bone is spongy too, resulting in a smooth frictionless joint.

Primary to osteoarthritis is loss of joint cartilage. Joint bone and cartilage suffer microsplits. Pits and holes appear. The damage spreads. The bone underneath spills out of the joint like molten wax. Knees, hips, back and hands are most affected. On x-ray there are joint margin excrescences called “osteophytes” (literally bony growths). Subcartilage bone becomes like ivory.

We don’t know the cause but there are well-recognized risk factors. For example heredity, obesity (it precedes the osteoarthritis), joint overuse, and weight bearing, prior injury, or congenital skeletal formations that change bone stresses.

The hands are a frequent site, with the most distal joints affected, then the mid-finger joints, then the base of the thumb.

Heberden’s nodes can develop gradually with little discomfort or begin with red tender and swollen joints, deeply aching, diffuse, poorly localized pain, often when falling asleep. There may be crackling with movement. The aching stiffness is most common in the index, fifth and middle finger in that order. Involvement is symmetrical.

DISCLAIMER: The information provided here is for general informational purposes only, and is provided as a supplement for students enrolled in Meditec’s medical career training courses. The information should NOT be used for actual diagnostic or treatment purposes or in lieu of diagnosis or treatment by a licensed physician.