Conditions that Rheumatoid Factor:
RHEUMATOID ARTHRITIS Rheumatic dz: RA, SLE, and Sjogren's syndrome
Chronic bacterial infections: SBE, Leprosy, Tb, and
Chronic inflammatory disease with symptomatic large
and small joint distribution.
Viral dz: Rubella, CMV, EBV, influenza, HBV and
Main events contributing to the pathogenesis of Parasitic dz
rheumatoid arthritis: Chronic inflammatory dz: Sarcoidosis, periodontal dz,
Influx of inflammatory cells including neutrophils, pulmonary interstitial dz and liver dz
lymphocytes, plasma cells, and macrophages into Mixed cryoglobulinemia
synovium Hypergammaglobulinemic purpura
Activation and hyperplasia, respectively. Of the
resident inflammatory cells and synoviocytes Other Labs:
Destruction of cartilage and bone by the synovial ESR: in nearly all pts with active dz.
pannus. Anemia: Normochromic, normocytic. Decreased
Cytokines are involved in one way or another in all three production.
events. These include but are not limited to, Il 2, 6, Diagnosis:
8, TNF, Vascular Endothelial Growth Factor and Presence of 4 or more of these criteria must be present
many others. In another group of chronic for >6 weeks are required for a “definite” diagnosis
inflammatory joint diseases collectively called of RA.
spondyloarthropathies (including psoriatic arthritis, 1) Morning stiffness
ankylosing spondylitis and Reiter’s syndrome), the 2) Arthritis of three or more joint areas
inflammation is usually centered at the sites of 3) Arthritis of hand joints: PIP, MCP or wrist.
insertions of ligaments onto bones (entheses). In 4) Symmetrical soft tissue swelling.
inflammatory arthritis, the synovium is the primary 5) Rheumatoid nodules
site of involvement; the articular cartilage and bone 6) Serum rheumatoid factor
are secondarily involved. 7) Radiographic changes: erosions and/or periarticular
Compared to OA, RA is considerably more destructive osteopenia in hand or wrist joints
to the joints with much less repair. Thus, ankylosis
is frequent while osteophytes are rare. Also, the Prognosis:
inflammation involves periarticular soft tissues, i.e., Course is variable and individual.
joint capsule, tendons, and ligaments and the Rate of progression toward joint destruction and
clinical indicators of an inflammatory process are disability is proportional to:
much more evident compared to osteoarthritis. intensity of inflammatory and proliferative reactions
Compared to OA, Amyloidosis is not frequent and when w/in the joints
it occurs is mostly due to fibrosis and not bony persistence of dz over time.
ankylosis. Most important prognostic factors for destructive
Clinical Presentation: rheumatoid dz:
History: Ask min of AM stiffness and relationship to Strongly (+) RF
activity and stress. Presence of rheumatoid nodules
RA pain and stiffness improved with mild Extra-articular manifestations of rheumatoid dz
activity but stressing joints remains painful. such as pericarditis, pleuritis, scleritis, and
OA pain and stiffness worse with activity. vasculitis.
Articular Manifestations: Current treatment strategies are to be very aggressive
Generalized stiffness esp after inactivity. very early in the dz. Bony erosions and joint space
Symmetric arthritis: characteristic involvement of PIP narrowing occurs and progresses most rapidly
and MCP. DIP are rarely involved. during the first 2 years of the dz.
Synovitis of wrist: Carpal tunnel syndrome
Grip strength and ROM: by pain or tightness of joint ADJUNCTIVE TREATMENT
capsule because of inflammation, joint deformities, These drugs help to relieve the pain caused by
subluxation, fibrosis, and contractures. inflammation in the joints, but do not change the
Joint effusions natural course of RA. Are useful in the short term,
Baker’s cyst: hypertrophy of gastroc bursa. but the goal is to control the dz and not make these
Extra-articular Manifestations: NSAIDS
Constitutional symptoms: weakness, easy fatigability,
Used for pain control as an initial therapeutic goal.
anorexia, and weight loss.
Without such control patients may become
Rheumatoid nodules: Extensor surfaces and over
discouraged and noncompliant.
pressure points. # of nodules does not correlate
NSAIDS may be supplemented with acetaminophen for
w/severity of dz.
Rheumatoid vasculitis: Can affect any organ. Occurs in
When NSAID medications are used continuously, the
pts w/severe dz and circulating RF. In the skin addition of misoprostol or other GI agents is
can get palpable purpura, & vasculitic ulcers
indicated for most.
Eyes: Scleritis (deeper layers and more serious) and
episcleritis (mild and transient). Usually in pts Corticosteroids
w/long standing dz and nodules. Used in low dose oral form for bridging control while
Labs: waiting for DMARD’s to take effect.
Rheumatoid Factor: Should be ordered if physical
findings document synovitis compatible with RA. DISEASE MODIFYING Tx
IgM antibody to the Fc portion of IgG. (+) is not Definition: Tx that changes the natural course of RA.
necessary for diagnosis, but RF is found in ~ 75% These drugs do not exert anti-inflammatory effects,
titers correlate w/systemic dz and more severe dz so NSAIDS must be continued while being used.
Need to relate results to pretest probability of RA. Benefits are delayed for weeks to months.
Should not be used as screening test in pts with Methotrexate:
Gold standard for efficacy and documented reduction in
Effects w/in 4 weeks and plateau at ~ 6 mo. ~ 80% will
experience moderate to excellent symptomatic
benefit from Tx, but remission is rare.
Persistent activity supplemented with Anti-TNF drugs
(Etanercept [Embrel], Infliximab [Remicaide]) or
Soluble TNF-alpha Receptor-Fc Fusion Protein:
Etanercept (Embrel): Inhibits binding of TNF- to its
receptor. Also used in pts w/poor response to MTX.
Possible future role in early RA.
Infliximab (Remicaide): Chimeric mouse/human anti-
TNF monoclonal antibody. Lead to in pain,
swelling, and tenderness of joints. Approved for pts
that have inadequate response to MTX alone.
Leflunomide: Indication in pts with poor response to
MTX or instead of MTX when MTX poorly
tolerated. Inhibits pyrimidine synthesis pathway
that is in low numbers in activated T and B cells
inhibition of T and B cells.
Cyclosporine: Second line drug after MTX found
unacceptable. Inhibits activation of CD4 T-cells.
Some improvement w/in 3 to 6 weeks after
Minocycline: Used in mild RA. Tetracycline Abx
demonstrated to superior to placebo. Efficacy may
be less than that of HDC and/or oral gold.
Sulfasalazine: Used for milder dz. Within 4 to 12
weeks, most pts experience some improvement.
Hydroxychloroquine: Used in mild RA with no poor
prognostic factors. Response to therapy is delayed
for 3 to 6 mo w/plateau at ~ 9 mo.
Gold Compounds: Efficacy questionable. Short-term
efficacy comparable to MTX, but long-term gold
loses its effectiveness over time. Subset of patients
(young women with early dz) experience significant
dz control and/or remission with gold therapy.