Term
RA Pathology and Clinical Manifestations
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Definition
Initially, the synovium becomes grossly edematous, thickened, and hyperplastic. There is also a dense perivascular inflammatory infiltrate composed of lymphoid follicles (mostly CD4+ helper T cells), plasma cells, and macrophages filling the synovial stroma.
There is also increased vascularity that results from vasodilation, angiogenesis, and pannus formation.
A pannus is a fibrocellular mass of synovium and synovial stroma, consisting of inflammatory cells, granulomatous tissue, and fibroblasts,
that causes erosion of underlying cartilage.
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Term
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Definition
Stages of RA
Early rheumatoid arthritis (RA) is characterized by symmetric swelling of the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints. Typical fusiform or spindle-shaped enlargement of the PIP joints is usually seen, accompanied by tenderness and limited range of motion.
Later on, massive diffuse swelling is seen, together with deformities such as the boutonnière, the swan neck, and the unstable PIP joint that is caused by synovitis in that joint.
Long-standing RA is characterized by severe deformities resulting from joint destruction. Ulnar deviation and MCP joint subluxation are typical deformities, as are rheumatoid nodules.
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Term
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Definition
one view of the disease process is that inflammatory joint symptoms are the main determinant of disability early in the disease, while joint destruction dominates in late disease. |
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Term
Joint Erosions Occur Early in RA |
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Definition
·Up to 93% of patients with
<2 years of RA may have radiographic abnormalities
·Erosions can be
detected by MRI within
4 months of RA onset
·Rate of progression is significantly more rapid in the first year than in the second and third years
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Term
Rheumatoid Arthritis:
Treatment Principles |
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Definition
·Establish the diagnosis early
·Determine where the patient stands in the spectrum of disease
·Start disease modifying drug therapy early
·Use the safest treatment plan that matches the aggressiveness of the disease
·Monitor for adverse effects
·Monitor disease activity, revise Rx as needed
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Term
Goals of DMARD Therapy for RA |
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Definition
·Primary Aim: Prevent or retard joint erosion and destruction
·NSAIDs do not reduce progression of structural joint damage.
·Structural damage continues even though signs and symptoms may be improved by NSAIDs.
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Term
Rheumatoid Arthritis:
Drug Treatment Options |
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Definition
·NSAIDs
–Symptomatic relief, improved function
–No change in disease progression
·Low-dose prednisone (<10 mg qd)-Controversial
–May substitute for NSAID
–Used as bridge therapy
–If used long term, consider prophylactic treatment for osteoporosis
·Intra-articular steroids
–Useful for flares or persistent joints
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Term
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Definition
·Methotrexate (MTX)
·Leflunomide
·Sulfasalazine
·Hydroxychloroquine
·Cyclosporine
·Parenteral/oral gold
·Azathioprine
·D-penicillamine
·Minocycline*
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Term
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Definition
-Inhibits purine DNA synthesis via dihydrofolate reductase (use concomitant administration of folic acid); Increases adenosine which downregulates inflammatory pathways; Good long-term efficacy and tolerability
- use Mod. to Severe RA
-adverse side effects : Stomatitis, marrow suppression, hepatic fibrosis, pneumonitis
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Term
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Definition
Inhibits pyrimidine DNA synthesis via dehydrooroate dehydrogenase; Decreases radiographic progression; Improves physical function
-Use for Mod to severe RA
Side Effects: Diarrhea, alopecia, liver enzymes, marrow suppression
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Term
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Definition
-Suppresses various leukocyte and lymphocyte functions;Increases adenosine; Reduces activation ofNFkB transcription factor
-Use for Mild to Mod. RA
-Side Effects:Nausea/diarrhea; hepatitis; marrow suppression
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Term
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Definition
-Interferes with antigen processing
-Use for Mild to early RA
Side Effects: Nausea; retinal toxicity; blurred vision
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Term
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Definition
Inhibition of Cytokines
-Cytokines exert their damaging effects by binding to specific receptors, and there are several potential approaches that can be employed to block these effects.
-Cytokines can be neutralized through the use of antibodies or soluble receptors. With this approach, the cytokine never reaches the receptor on the cell of interest. This avenue for the treatment of RA has been taken with soluble TNF-a receptor fusion proteins, soluble IL receptors, monoclonal antibodies against TNF-a, and monoclonal antibodies against IL-6.
-Receptor antagonists or antibodies can bind to cytokine receptors on cells and prevent cytokines from binding. This blocks their actions on the cell in question. This approach to the treatment of RA has been taken with recombinant IL-1Ra and an antibody against the IL-6 receptor.
Administration of anti-inflammatory cytokines can inhibit expression of inflammatory cytokines. This approach has been taken with IL-4 and IL-10.
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Term
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Definition
·Abatacept is fusion protein of extra- cellular domain of human cytotoxic T-lymphocyte antigen 4 (CTLA4 linked to modified Fc portion of human IgG1.
·Abatacept binds APC CD80/86 and prevents interaction of CD28 with CD80/86.
·Thus, the costimulatory signal necessary for full activation of T lymphocytes is inhibited.
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Term
B-CELL DEPLETION
Rituximab |
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Definition
·Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen on B-lymphocytes.
·Has been used in treatment of lymphoma, rheumatoid arthritis, and systemic lupus erythematosus (experimental).
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Term
ACR20/50/70 Response Criteria |
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Definition
·- 20%/50%/70% improvement in
–Swollen joint count
–Tender joint count
–At least three of the following:
•Patient’s global assessment of
disease activity
•Physician’s global assessment of
disease activity
•Patient’s assessment of pain
•Acute-phase reactant (ESR, CRP)
•Disability (HAQ)
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Term
Safety Issues With Biologic DMARDs
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Definition
-There are a number of safety issues with the use of biologic DMARDs in RA, including serious infections, opportunistic infections such as tuberculosis (TB), malignancies, demyelination, hematologic abnormalities, administration reactions, congestive heart failure, and autoantibodies and lupus.
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