RA Flashcards
definition
RA is a chronic progressive autoimmune disease.
It is characterized by persistent inflammation of the synovial joints as well as inflammation of extra-articular sites.
WHO IS AT RISK - and age and gender (Ray can be young)
Gender: 75% of affected are women.
Age: onset can be any age. Usually between 30 and 70.
Genetics: siblings of people with RA are 2-4 times more likely to develop RA then GP.
Viral / bacterial infection ?
Moderate to severe periodontal disease.
Smoking.
cause - (Ray got an infection)
The exact cause is Unknown
Research points to combination of genetic and environmental factors:
An infectious insult could trigger RA in genetically susceptible individuals.
Genetics:
RA: AUTOIMMUNE ROLE
STEP 1: PATHOGEN creates abnormal IgG .Possibly a virus or bacteria triggers the formation of an abnormal immunoglobulin (IgG).
STEP 2: Auto-Antibodies (rheumatoid factors - RF) form against this abnormal IgG
STEP 3: RF combines with the abnormal IgG and deposits into tissues. (joints, bld vessels, and pleura)
STEP 4: Inflammatory response results (which causes cartilage, bone, and systemic damage)
STAGES OF RA
1 - 4
RA:CLINICAL MANIFESTATION
Systemic symptoms such as: fatigue, malaise, fever
Joint pain with stiffness and edema
EXTRA-ARTICULAR MANIFESTATION OF RA
Extra-articular involvement is a marker of disease severity and is associated with premature death. Almost all systems could be affected.
EXTRA-ARTICULAR MANIFESTATION OF RA - hands (Ray has reynauds)
Raynaud’s phenomenon
LAB TESTS FOR RA - Serum RF (RF is IG)
No single lab test is conclusive
Serum RF (rheumatoid factor)
Present in 80-85%
Measures unusual antibodies of IgG/IgM
LAB TESTS FOR RA (RA is anti-cop)
Anti-CCP (cyclic citrulinated peptide): is more specific than RA with a sensitivity raging 50-70 % and specificity of 90 %.
This test is also positive in other condition such as TB, SLE (lupus) and chronic lung disease.
TREATMENT OF RA
Goal:
Eliminate or relieve pain
Prevent joint damage
Prevent loss of function
Drug therapy
Physical therapy
Occupational therapy
Patient and family education
DRUG THERAPY for RA (RA drugs missed dmark)
Usually require a combination of meds.
Pain
Anti-inflammatory medication
DMARD’s: Disease Modifying anti-rheumatic drugs (immunosuppress)
In the past pts were maintained on high doses of ASA and NSAIDS for several years until X-rays showed bone erosions and patient’s w/ increased GI Bleeds and stomach ulcers
Now a more aggressive drug approach is used early on to minimize the erosive, destructive process
PHARMACO-THERAPY
ASA and NSAIDS
Corticosteroids : as a bridge therapy
DMARD’s: Disease Modifying Anti-Rheumatic Drugs.
As a class , these drugs depress the overactive immune system.
They are classified as biologic and non-biologic.
PHARMACO-THERAPY : DMARDS
Non-biologic DMARDS: are indirect, non-specific:
biologic DMARDS: are specific in that they interfere with a specific mediator on of the immune system:
DMARDS: Methotrexate - first used as what?
Methotrexate: still the main stay of RA TX
First used as a chemo agent, was FDA approved for RA in 1975.
DMARDS: Methotrexate - toxicity (meth in BLLK)
Toxicity: of pulmonary , hepatic and hematological systems ( bone marrow depression)
Monitoring: CBC, chemistry including liver functions and serum creatinine.
DMARDS: NON-BIOLOGIC Azulfidine - what does it do and combo? (Azul is inflammed)
Azulfidine (Sulfasalazine)
Most common combo with Methotrexate
Suppresses the inflammatory system.
Cash price: 30$ per month
Leflunomide - MOA (no T cells lef)
Inhibits T cell activity
Cost $45/month
36% have a 50% reduction in sx’s
DMARDS: NON-BIOLOGIC -Plaquenil and Chloraquine - what do they do?- (think trump)
Remission-Inducing Agents
Antimalaria drug
Ability to bind and alter DNA modifying effect
DMARDS: NON-BIOLOGIC - REMISSION INDUCING AGENTS - gold salts
REMISSION INDUCING AGENTS
GOLD SALTS
For patients who do not respond to methotrexate.
50% effective
Oral Gold (Ridaura) Side effect= GI
Haven’t been used very much since 1990s
Cost: 1,381
Penicillamine & Minocycline- type of drugs?
Remission Inducing agents
Has antimicrobial and anti-inflammatory effects
ETANERCEPT (etan is a tumor)
Binds to TNF (tumor necrotic factor) and blocks it’s effect in the synovial fluid.
$ 2,700/month
In combination with Methotrexate
39% have a 50% reduction in sx’s
15% have a 70% reduction in sx’s
Rheumatoid Arthritis Treatments continued
INFLIXIMAB (influx of TNF)
INFLIXIMAB
Neutralizes the biologic activity of TNF
Costs: 6,000/month
In combo with Methotrexate:
39% have 50% reduction in sx’s
25% have 70% reduction in sx’s
RA - stage I (sin is the first)
Stage I: Synovitis.
RA - stage II (2 pans)
Stage II: Pannus formation between the synovium and the cartilage
RA - stage III (sin in the 1st, pan takes 2nd, 3 fibers take the pan, bone takes the fiber)
Stage III: fibrous ankylosis: fibrous connective tissue replaces pannus.
RA - stage IV (4 bones take the fiber)
Stage IV: bony ankylosis: fibrous tissue calcifies.
In the late stages of the disease, there is destruction of articular cartilage, narrow joint space, erosions and subluxation.
RA - hallmark symptom
The hall mark: stiffness in joints lasting an hour or more
RA - edema? (Ray is symmetrical)
Symmetrical edema of small joints of hands and feet
RA - joints most affected? (the RA is a PIP)
The most affected joints are MCP, PIP, MTP
metacarpophalangeal (meta is first)
knuckle
proximal interphalangeal joint (PIP) (pip in the middle)
middle
Distal Interphalangeal Joint (DIP) (distal is end)
end
RA - bones
osteopenia+ osteoporosis
RA - muscles
Myositis (muscles become weak, pain)
RA - blood vessels
Vasculalitis
RA - skin - just nodules - you know this
Rheumatoid nodules ( most common on pressure points : i.e. olecranon) and skin ulcers
RA - eyes (Ray has conjunctivitis)
episcleritis, scleritis, keratoconjunctivis (dry eye).
RA - heart
pericarditis, myocarditis, CAD
RA - neurovascular (pull my RA)
PVD
RA - neuropathy
carpal tunnel syndrome
RA - blood
anemia
RA - kidneys
renal disease
RA - lymphatic
Lymphatic obstruction and lymphedema
lab tests for RA - (Ray has ESP)
ESR (erythrocyte sedimentation rate)
↑ in 85%.
Good marker of inflammation and response to tx.
lab tests for RA (Ana has RA)
ANA (Antinuclear Antibody)
Measures unusual antibodies that cause cellular death
Less often positive than RF
RA & WBC?
↑ WBC’s in synovial fluid
lab tests for RA (Ray is reactive)
CRP (C-Reactive Protein) Good indicator of inflammation and response to treatment
RA & anemia?
Moderate anemia is common
Methotrexate - biologic or nonbiologic
non-biologic
Biologic DMARDS
TNF, Interleukins, lymphocytes
methotrexate - MOA (meth messes w/ folic acid)
Inhibits metabolism of folic acid thus inhibits the synthesis of DNA and RNA
methotrexate - onset and side effects (meth doesn’t work right away)
Used in combination with other DMARDS
Onset:Onset 6 – 8 weeks
Common side effects: severe mouth ulcers, nausea, diarrhea, rash, alopecia
Cash Price: $50-80
methotrexate - precautions - screen for what?
Before being started on MTX, pts are screened for TB and hepatitis B and C
DMARDs - Plaquenil & Chloraquine - biologic or non biologic?
non-biologic
Plaquenil & Chloraquine - cost
Plaquenil cost about $1,000, Chloraquine about $100
Sulfasalazine - biologic or non?
non-biologic
Hydroxychloroquine - biologic or non?
non-biologic
leflunomide - biologic or non?
non-biologic
gold salts - biologic or non?
non-biologic
Etanercept - biologic or non? (enter biology)
biologic
Abatacept - biologic or non? (cept it’s biologic)
biologic
RA - genetics - what antigen?
An ↑ prevalence of HLA-DR4 (human leukocyte antigen) occurs in 70% of RA patients (28% in control group)
People with HLA-DR4 tend to have more severe RA
