-IBIS-1.5.0-
tx
immune system
rheumatoid arthritis
diagnoses

definition and etiology

definition: A chronic polyarthritis usually involving symmetrical presentation in the peripheral joints that can lead to destruction of the bone and cartilage resulting in characteristic deformities; systemic manifestations can also occur. The disease can appear in many forms: from a mild short-lasting oligoarthritic illness that causes little damage to a severe progressive polyarthropathy that leads to marked joint destruction. Most patients present with an intermediate course of the disease.

etiology: The etiology is idiopathic. Rheumatoid arthritis (RA) occurs in about 1% of the population, with women presenting three times as often as men. RA usually comes on between the ages of 35-50. It has a genetic association (monozygous twins have a 30% concordance of disease, while dizygous twins have only a 5% concordance). It is correlated with a class II major histocompatibility gene complex antigen HLA-DRA, especially in Caucasians and Japanese with the classic or definite expression of RA.

Juvenile onset RA (aka Still's disease), the most common cause of chronic synovitis in kids, is similar to the adult disease. There are three subtypes:

• polyarticular: Mostly seen in girls, it accounts for 40-50% of all JRA. There is no eye involvement. Usually the patient presents with multiple symmetrical joint involvement.
» 10% have a (+) RF and a (+) ANA, have the disease onset late in childhood and are usually affected quite severe
» 30% have (-) RF, (-) ANA, and experience a milder form
In either presentation, there is commonly a mild anemia and a slight leukocytosis.

• Pauciarticular: This is responsible for another 30-40% of JRA patients: it affects only a few asymmetrical joints. This group also presents in two ways:
» early onset before the age of 5; 30% of cases; patients often develop iritis, (-) RF and (+) ANA
» late onset mainly seen in boys, with frequent hip and sacroiliac problems but no iritis, and (-) RF and (-) ANA. In the latter sub-type, there is a high association with HLA-B27.

• systemic-onset: This is responsible for 20% of JRA, is found at any age, and affects boys slightly more than girls. It entails fevers; chills; a macular rash; splenomegaly; pleuritis and/or pericarditis; abdominal pain; severe anemia; and marked leukocytosis, followed by the appearance of a polyarthritis. RF and ANA tests are (-).

The prognosis for JRA is more favorable than that of adult RA, as about 75% of patients enjoy complete remissions.

It has been suggested that RA in females may be related to low estrogens, or in both sexes liver "filtering" dysfunction.

signs and symptoms

Onset may be sudden:
• Abrupt inflammation of many joints.
• Fever.
• Lymphadenopathy and splenomegaly.

In 75-80% of patients, RA usually occurs insidiously; initial systemic complaints include:
• Anorexia.
• Fatigue, generalized weakness.
• Vague musculoskeletal symptoms.
These initial symptoms may exist for months, resisting clear diagnosis. When specific symptoms begin, the joints usually involved are the proximal interphalangeal and metacarpophalangeal joints, feet, wrists, elbows, and ankles: however, any joint may be inflamed. Most commonly the joints are symmetrically affected.

Diagnostic criteria for RA as defined by JAMA (Vol. 224, p.799, April 30, 1973) and The Arthritis Foundation are as follows:
• Classic RA: Diagnosis needs 7 of the following criteria, with the symptoms of the first five lasting over 6 weeks.
» Morning stiffness > 1 hour.
» Pain on motion in at least 1 joint.
» Swelling (soft tissue: not just bony growth) in at least one joint.
» Swelling of at least one other joint.
» Symmetrical joint swelling not including terminal phalangeal joint involvement.
» Subcutaneous nodules usually distal to the elbow.
» X-ray changes typical of RA.
» Positive agglutination test: (+) RF.
» Poor mucin precipitate from synovial fluid or inflammatory synovial effusion with over 2000 WBC/mm3 and no crystals.
» At least 3 characteristic histologic changes in synovial membrane.
» Characteristic changes in nodules.

• Definite RA: Diagnosis requires 5 of the above criteria: in the first five the joint signs/symptoms must be continuous for at least 6 weeks.

• Probable RA: Diagnosis requires 3 of the above criteria: of the first five criteria, only 1 must be continuous for 6 weeks.

• Possible RA: Diagnosis requires 2 of the following criteria and the duration of the joint symptoms must be at least 3 weeks:
» Morning stiffness.
» Pain or tenderness on motion for at least 3 weeks.
» History or present joint swelling.
» Subcutaneous nodules.
» Elevated ESR or C-reactive protein.
» Iritis: Only useful for diagnosis of JRA.

other lab values seen in RA:
• mild or moderate anemia with hemoglobin rarely <10 gm/dl, usually hypochromic
• leukocytosis seen in only 25% of patients and then rarely >15,000/mm3
• in active RA: elevated ESR and C-reactive protein values are usually seen; this test is not specific for RA
• (+) ANA test
• increased ANA, (+) Coomb's test
• increased creatinine
• increased ASO titer
• increased copper in serum
• increased ceruloplasmin causes false (+) test for Bence-Jones protein
• increased platelets

As the disease progresses, characteristic joint deformities may occur: ulnar deviation of the finger at the metacarpophalangeal joint; swan-neck deformity (hyperextension of the proximal interphalangeal joint, with distal interphalangeal joint in flexion); boutonniere deformity (opposite of swan-neck changes). Extra-articular complaints arising from RA may include rheumatoid nodules, rheumatoid vasculitis, pleuropulmonary problems, neurologic symptoms, and Felty's syndrome (consisting of RA, neutropenia, osteoporosis, splenomegaly, and occasionally anemia and thrombocytopenia).

course and prognosis

The course and prognosis varies from patient to patient and is hard to specify. Conventional treatment can improve as many as 75% during the first year of their disease; however, despite full treatment, 5-10% of patients eventually become disabled. Five years after the onset of the disease, only a third of patients may have evidence of RA, though most patients experience persistent but cyclical illness activity. Remissions usually occur in the first year: sustained RA activity greater than one year indicates a serious problem. The greatest joint damage takes place during the first 6 years of the disease, and then progresses at a substantially slower rate. The median life span of the RA patient is lowered by 3-7 years. An increased mortality rate can be seen in patients with severe disease and is usually due to infections, gastrointestinal bleeding, and drug therapy.

differential diagnosis

• Other collagen-vascular disorders: SLE, polyarteritis, progressive systemic sclerosis, dermato(poly)myositis.
• Other diseases: Sarcoidosis, amyloidosis, Whipple's disease, acute rheumatic fever, gonococcal arthritis, Reiter's syndrome, psoriatic arthritis, ankylosing spondylitis, gout, Kellegren's syndrome/erosive osteoarthritis.


footnotes