Chapter 3- Rheumatoid Arthritis Flashcards
(91 cards)
1
Q
Define Rheumatoid arthritis
A
a chronic inflammatory polyarthritis of unknown etiology that targets the synovial tissue of moveable joints.
2
Q
define the epidemiology of R.A.
A
more common in Women.
Costs are associated to disability.
peek age 55
3
Q
What are the suspected causes of R.A.?
What increases the risk of developing R.A?
A
multifactorial: genetics, environmental, immunologic, hormonal and infectious diseases.
Other: Smoking, decrease risk d/t BC pills
4
Q
What are the genetic factors resulting in an increased risk for R.A?
A
- presence of HLDA-DR4 antigen believed to be associated to R.A.
- Link to metalloproteinase-3 gene
- R.F rheumatoid factor - genetic link.
5
Q
Describe the Synovial joint
A
bones are held together by fibrous capsule lined with synovium.
provides nutrients to the avascular cartilage and produces hyaluronic acid (joint lube).
produces collages and fibrocetin used for the synovial matrix
6
Q
Why does R.A. affect the synovial joint?
A
unknown cause
7
Q
Describe the Synovial matrix
A
2 layers. 1st layer (synovial intimal layer) 1-3 cells thick: macrophage cell (type A) and fibroblast type cells (Type B).Both increase with Rheumatoid synovitis.
2nd layer subintimal area has the blood vessels. Becomes infiltrated with cells that differentiate into osteoclasts > which promotes angiogenesis > which leads to inflammation.
8
Q
What happens to the synovial cavity with R.A?
A
its normally a potential space that allows free movement, but then it becomes filled with a large amount of neutrophil fluid due to inflammation. This decreases the free space available for movement
9
Q
How are the immunologic elements T-cells, macrophages/fibroblasts and B-cells are involved in the development of R.A.?
[T-cells slide]
A
T-cells are a keyPerson in the inflammatory process. HLA-DRA, acts on APCs then They release cytokines (TNF-a, and IL-$j) which drive inflammatory process.
10
Q
How are the immunologic elements T-cells, macrophages/fibroblasts and B-cells are involved in the development of R.A.?
[B-cells slide]
A
B-cells are activated with the T-cells and cytokines. These cells then differentiate and produce additional plasma cells which results in antibodies (ie: RF and ACPAs).
In the synovial cavity, the B-cells produce more T-cells and more cytokines.
This results in ++ inflammation/fluid. Think of a continuous chain process.
11
Q
How are the immunologic elements T-cells, macrophages/fibroblasts and B-cells involved in the development of R.A.?
[Effector cell activation]
A
after T and B cells kick started the inflammation process > the macrophages and fibroblasts go on to act independently in the synovial lining to perpetuate the inflammatory process.»_space; they produce many cells.
12
Q
What do macrophages in the synovial produce?
A
cytokines: TNF- alpha, IL-1, IL-7, IL-8, and GM-CSF. prostaglandins leukotrienes nitricocide pro-inflammatory mediators > others
13
Q
What do Synovial fibroblast secrete?
A
cytokines including IL-6, IL-8, and GM-CSF
proteases
collagenases
14
Q
What manifests the progressive process of chronic synovitis?
A
- hypertrophy of lining cells
- neo-angiogenesis
- new blood vessels supporting hyperthrophied synovium, and influx of fluid, lymphocytes, and PMNs into synovial cavity d/t ++ plasma. > this activates other inflammatory cytokines and fluid in cavity
- panus formation- inflammation fo synovial issue > microvascular injury > profound proliferation + hypertrophy of synovial tissue called panus.
15
Q
What are cytokines?
A
T-lymphocytes are present and when activated they stimulate the production of pro-inflammatory cytokines.
- mediators of cell-to-cell communication
16
Q
What happens to cytokins with R.A. ?
A
Theres an imbalance of pro-inflammatory and anti-inflammatory cytokines, with pro-inflammatory cytokines dominating.
17
Q
How do TNF-a and IL-1 play a role in developing RA?
A
they stimulate synoviocytes to produce substances that degrade tissues and activate other inflammatory mediators.
Trigger: IL-6, IL-8, and GM-CSF, prostaglandins, osteoclasts, and metalloproteinases, cartilage/pannus junction.
18
Q
What do prostaglandins do?
A
increase sensitive pain and contribute to the destruction of cartilage.
19
Q
What do Osteoclasts do?
A
cause bone resorption and destruction
20
Q
What do MMPs do?
A
destroy bone, cartilage and dissolve ligaments and tendons.
21
Q
What do GM-CSF do?
A
promotes the matruations of monocytes to macrophages that, in turn, produce more cytokines.
22
Q
what does IL-6 and IL-8 do?
A
IL-8 produced by the synovium in the joint cavity where it recruits neutrophils into the synovial fluid.
IL-6 also suppresses the production of albumin by the liver, alters lipids metabolism and is a factor in the elevation of markers of inlammation, (CRP, and ESR).
23
Q
What Cytokines produce the sxs of RA including fever, muscle wasting and loss of appetite.
A
IL-1, IL-6, and TNF-alpha
24
Q
What are some differential diagnoses of Rheumatoid arthritis?
A
Acute vital arthritis, bacterial endocarditis Scarvoidosis Reiter's syndrome Polymyositis Sjogren's syndrome Amyloidosis Rheumatic fever Polymyalgia Rheymatica Systemic lupus erythmatosus systemic sclerosis polyarticular gout Vasculitis IBS Psoriatic arthritis Acute relapsing symmetric synovitis tuberculous arthritis Gouty arthritis Reactive arthritis Chronic fatigue syndrome
25
What are the typical sxs of RA
pain,
stiffness,
swelling of the diarthrodial joints (muscle atrophy common)
*morning stiffness is result of accumulated fluid in joints d/t no activity.
* small joints affected first then larger.
*joints are additive not migratory.
*Sxs can be sudden
* joint pain starts Axsx.
26
What are the most comonly affected joints?
1. proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints > hands
2. Metatarsophalangeal (MTP) joints of the feet
3. wrists and elbows
4. shoulders
5. ankles and knees
27
What are the joints that are less affected, or affected later in the disease?
```
Hips
Temporomandibular joints (TMJ) of the jaw
Atlantoaxial joint of the cervical spine,
symphysis pubis
manubriosternal joint
cricoarytenoid joint
sternoclavicular joints
ossicles of the ears.
```
28
How do you diagnosis RA?
using an algorithm - a +ve diagnosis is typically a score of >6 to 10.
using ACR or ACR-EULAR definitions: Letters A-D:
A- joint involvement (score 0,1,2,3,5)
B- Serology (score 0,2,3)
C- Acute-phase reactants (score 0,1)
D- duration of sxs (score 0-1)
29
How are people clinically diagnosed?
initial assessment: complete exam, blood chemistry, CBC with platelets, RF, ACPA, ANA, CRP, and ESR. Urinalysis, radiographs of affected joints.
Client's GP usually notes sxs, limitations in activity, monitor effectiveness of tx.
Tx starts right away
Monitoring every 6 months the following:
1. duration of morning stiffness
2. presence of inflamed joints; changes?
3. mechanical changes (motion, strength, ROM, etc)
4. Signs of active synovitis (swelling, effusion)
5. pain and tenderness with movement
6. presence of heat or redness-
7. presence of Rheumatoid nodules
8. systemic manifestations
30
What formula can be used to quantify and serially measure the disease and response to treatment?
1. disease activity Score
2. Ritchie Index
3. Thompson Index- evaluates a limited number of affected joints and uses a weighted score to estimate "burden of synovitis"
31
How does the Patient play roles in the management of his disease?
Providing information and check-ins. Confirm if tx is affective. Are there adverse sxs?,
Possibly complete a questionnaire.
Note: depression is frequently observed in pt with R.A. and may affect overall morbidity. Beck depression index is used to evaluate depression.
32
What are the 3 most commonly used laboratory tests to diagnosis and monitor the disease activity.
1. RF - limited usefulness
2. Anti-CCP antibody for ACPAs - specific to R.A. ^ levels = work disease, note that specificity is 98%
3. CRP (and ESR): most common of acute phase reactants. ^ levels are associated with progression of joint erosions. Fluctuate during disease. This method is used to differ RA from OA.
*AMCV antibodies recognize a form of citrullinated vimentin found in R.A. This has a lower sensitivity and is used in when theres an -ve Anti-CCP test. Not currently used for prognosis but undergoing studies.
33
What are seropositive patients?
+ve RF associated with HLA-DR4 molecules.
Rheumatoid nodules and vasculitis,
They have an increased risk of systemic involvement and worse prognosis
34
+ve RF can bee seen in other pt with other rhumatic diseases. Explain.
Can be found in 4% of pt, and increased to 25% in elder population.
1. Sjogern's syndrome: 75-90% have +ve
2. Mixed connective tissue disease (50-60%)
3. Systemic lupus erythematosus (15-35%)
Also seen in those with Hep B and C, sarcoidosis, malignancy and primary biliary cirrhosis.
35
What are the typical CBC abnormalities associated with an RA diagnosis?
1. WBC normal, or modestly elevated.Differential should be normal
2. hemoglobin and hematocrit should be normal or mild decrease. Normocytic anemia common in chronic disease. Serum iron low, but ferritin normal. MCV normal
3. mild thrombocytosis,
36
What are some other abnormalities in blood chemistries associated with RA? (Not related to CBC reports)
1. globulins elevated (polyclonal grammopathy)
2. Lipids low in late-stage
3. HDL low d/t inflammation
4. low albumin > poor prognosis
5. serum creatinine should be normal
37
What does the urinalysis look like for an RA pt?
Should be normal,
| Proteinuria may be indication thats its another connective tissue disorder
38
Synovial fluid is tapped (arthrocentesis) when there are obvious effusions. What would a normal synovial fluid look like?
1. straw-colored
2. <2,000 WBC/mm3 with 50% polymorphonuclear lymphocytes
3. -ve when cultured
4. without crystals.
39
How are the joints assessed with a RA diagnosis?
bone erosion is primary feature of R.A. Osteopenia common too - by year 2 90% of RA pt have sig erosions and loss of joint space (if not tx)
Sharp score- bone erosion and joint space narrowing in affected joints. 0= no damage, 5= advanced disease.
MRI used to assess and detect Pannus development, bone edema, and loss of cartilage. US can detect synovitis, effusion and erosions,
40
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
(Vasculitis details)
Vasculitis: common in males, HLA-DR4 genotype, cutaneous vasculitis most common. Can have skin ulcers, nail infarcts.
41
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
(Skin manifestations)
nodules (30% pt) cause site specific damage, areas of increased pressure/repetitive trauma- biopsy can be done for diagnosis.
Skin becomes thin and atrophic allowing for easy bruising and palmar erythema
42
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
(skeletal manifestations)
Osteoporosis, osteopenia. Glucocorticoid-induced bone loss. Synovial cysts can occur around any affected joint.
43
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
( Muscle manifestations)
some muscle weakness/atrophy not tenderness
decrease use of joints results in reflex atrophy.
Use of steroids- induce myopathy.
44
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
(eye involvement)
scleritis and episcleritis (1-5% of pt)
scleritis more serious, and can cause ulcers.
Keratoconhunctitivis sicca (dry eyes) present in 15% of pt. increase risk of corneal infection
45
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
(lung disease)
associated with increase morbidity.
associated with seropositive RA and more common in males.
Nodules can occur in lungs (r/o malignancy)
common complications:
1. pleural disease
2. RA nodules seen in parenchyma
3. Caplan's syndrome
4. Interstitial lung disease
5. Small airway disease
6. Upper airway obstruction from cricoarytenoid abN
7. Bronchiectasis
* higher risk of COPD
46
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
(cardiovascular manifestations)
```
35% of patients
SOB most common sxs
most common complications:
1. CAD, atherosclerosis
2. Pericardial disease
3. granulomatous myocarditis
4. nodules causing conduction abN or valve dysfunction
5. Atrocities associated with vasculitis
6. diastolic dysfunction.
```
47
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
(neurological manifestations)
Subluxation of an unstable atlantoaxial joint with transection of the spinal cord
- C1-C2 involvement = pain and motor weakness
- mild peripheral neuropathies of the legs and feet
nerve entrapment syndromes (CTS and tarsal tunnel syndrome.
possible TIA, stroke or brain syndrome associated with vasculitis.
48
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
(kidney manifestations)
rare: glomerulonephritis, amyloidosis, vasculitis
more common to see toxicity associated with drugs (Tx)
49
What are some systemic manifestations that may arise with a history of Rheumatoid arthritis?
(Hematological Manifestations)
```
anemia
decreased bone marrow
GI bleed d/t NSAIDS
felty syndrome
neutropenia (rare)
LGL syndrome (t-cell leukaemia)
```
50
How is RA treated?
goal= decrease pain and inflammation, slow down the progression of joint erosions, restore function and achieve remission with the least amount of toxicity.
Early detection results in a better prognosis
affect of treatment is measured by achieving improvement 3/5 of these variables:
1. Pt's assessment of sxs
2. GP's assessment of sxs
3. pain
4. disability
5. acute phase reactants.
Hallmark of therapy: DMARDS- more potent and more toxic than traditional treatments with NSAIDs- which only aid in pain and reducing inflammation.
51
What are cyclooxygenase inhibitors?
NSAIDS predispose pt to GI erosions and ulcers.
COX-2 have been used to lower risk of GI bleeding compared to COX inhibitors and salicylates but then the risk of developing CAD is increased.
52
What are DMARDS (Disease modifying anti-rheumatic Drugs)?
Drugs that target the pro-inflammatory process in R.A. and slow the process of joint erosions.
53
What are some examples of DMARDS?
```
Methotrexate,
selfasalazine
azathioprine
Hydroxychloroquine,
D-penicillamine
Gols
leflunomide
```
54
Which drug is the gold standard in the treatment of moderate to severe R.A.?
Methotrextate
PROS:
its a folic acid analog and immunosuppresive
inexpensive, safe
used in 60% of cases
slows down joint erosings
used concomitanley with NSAIDS, corticosteroids
CONS:
Can cause liver and lung toxicity (LFTs are monitored)
Folic acid supplements can be given to reduce side-effects.
55
What are the DMARDS drug(s) of choice for mild to moderate R.A?
```
Sulfasalazine and hydroxychloroquine
slow acting
used with steroids for initial tx.
well tolerated,
Sulfasalzine is better at preventing joint erosions.
```
slit lamp opthalmologic exams are recommended for LT use of Plaquenil
56
What are the second line DMARDS that are typically used
GOLD and D-penicillamine-
| - effective for some patients.
57
Which DMARDS drug is a pyrimidine synthesis inhibitor that affects T-cells ?
Leflunomide
Brand name: Arava.
Can be used as first-line tx, cant be used in preg F or M wanting children.
58
What are biologic modifiers?
Genetically engineered immunosuprresives, that are highly effective DMARDS that target specific factors involved in the inflamatory process.
- faster than MTX, and just as effective.
59
What is TNF-a
a pro-inflammaotry cytokine secreted by monocytes, macrophages, and T-cells that promotes the proliferation of other cells significant to R.A.
+ [] in synovial fluid.
60
Which drugs target anti-TNF-a? What are the typical adverse effects of these drugs?
etanercept, infliximab, adalimumab, and golimumab.
AE: Serious infection ( Ie TB, fungal disease), ^ risk of lymphoma, MS, hepatotoxicity, lupus, anemia.
61
Which drug is an interleukin-1 receptor antagonist? How does it work? What are the AE?
Anakinra
- works by decreasing production of prostaglandins and metalloproteinases by synovial cells.
- cant be used with TNF-A inhibitors
- AE; bacterial infection, thrombocytopenia, neutropenia, injection site reactions.
62
Which drug is an anti-CD20 antibody that binds to the CD-20 antigen located on the B-cell membrane to prevent their activation and differentiation?
Rituximab- disrupts the inflammatory process but not the production of immunoglobulines.
63
Which drug is a fusion protein that inhibits T-cell activation and the production of cutokines in the inflammatory process?
Abatacept
- reduces sxs in patients that had dailed tx by MTX and TNF-a inhibitors.
- used with Caution for px with COPD.
- intravenous
64
Which drug competes with IL-6 for binding ot the IL-6 receptor?
Tocilizumab
- one of the newest products on the market,
its a janus kinase (JAK) inhibitor and decrease the inflammation in the joint.
65
How are corticosteroids used in the treatment of RA?
tx of active synovitis.
rapidly reduces inflammattion
used as initial tx modality in low doses with MTX or DMARDS as binding therapy then is tapered off
- can prevent joint erosions
-AE: bone loss and Osteoporosis, infection , steroid-myopathy, GI ulcers, acceleration of atherosclerosis
66
whats the most commonly used corticosteroid?
prednisone/ prednisolone
67
R.A. pt have an ^ risk of osteoporosis. How are pt treated for Osteoporosis risk?
1. Vit D + Ca+ addded
2. hormone replacement therapy for pt
3. Calcitoning for Pt at ^ risk of #
4. . Bisphosphonates (Fosamax) for long-term use.
5. exercise.
68
Why is statin therapy a benefit in the tx of dyslipidemia associated with inflammation in RA?
reduction in Atherosclerotic risk factors,
| suppression in Helper T-cells and cytokinine production.
69
When would an R.A. pt undergo joint replacement therapy ?
extensive erosion
treament failure
intractable pain and funtion/mobility.
^ EST associted with eventual need for joint replacement.
70
Which joints are most often replaced with RA patients?
hip
knee
MCP joints (ankles/wrists)
* can be fused
71
What % of RA pt will:
1. be in remission
2. suffer from intermittent courses
3. Progressive diease
1. 10%
2. 30%
3. 50%
*affected by persistence of inflammatory process, pt ability to cope with diease, and actively educate themselves to reduce risk
72
What are 7 factors that have predictive value for progressive joint involvement?
1. high radiographic score
2. high RF and anti-CCP titers, elevated ESR
3. presence of the HLA-DR4 genotype
4. early or adanced are at onset
5. swollen joint count
6. extra-articular manifestations
7. prednisone
73
What are 3 non-disease factors also affecting mortality of RA pt?
1. fewer than 12 years of education
2. tobacco exposure
3. functional status
74
A patients functional status is affected by what 4 factors?
1. the cumulative structural damage of joints
2. muscle strength and tone
3. general fitness level
4. psychosocial factors
75
what is the mortality ratio of RA pt compared to the general public?
+30-300
7 years Males
3 years Females
76
What are some comorbidities affecting RA mortality?
diabetes,
HTN
Cardiovascular disease
77
How does CAD affect RA pts?
cause of 50% deaths.
F with RA at 2x higher risk of MI - d/t chronic inflammation, and hyperlipidemia.
^^ risk of thrombosis
78
How are infections an ongoing issue for RA patients?
```
^ risk of mortality
lungs, skin and joints are at higher risk for infection
due to:
1. immunosuppression
2. presence of subclinical inflammatory lung disease
3. SM
4. immobility/ disability
5. neutropenia.
```
79
How is pulmonary disease associated with mortality in RA pts?
8% of deaths d/t pulmonary manifestations
| infection is also at risk.
80
What cancers do RA patients have a higher chance of developing?
lymphoproliferative disorders
lung cancer
lymphoma and leukaemia (2x higher)
81
The American College of Rheumatology established classification criteria for fundtional impairments. Classes 1-4. Describe them.
1. able to preform ADLs and occupation tasks., and avocations
2. able to preform ADLS/occupation tasks but not avocations
3. able to preform ADLS . but limited in occupation task and avocations
4. limited to preform all ADLS, or participate in occupation and avocations.
82
How would one classify/UW a pt with mild dissease?
1. joint pain
2. no more than 5 inflamed joints
3. no extra-articular disease
4. -ve or +ve RF
5. elevated ESR or CRP
6. no eivdence of erosion or cartilage loss
83
How would one classify/UW a pt with moderate disease?
```
6-20 inflamed joints
absence of systemic disease
elevated ESR and CRP
+ve RF and ati-CCP
evidence of inflammation and osteopenia
```
84
How would one classify/UW a pt with severe dissease?
```
>20 inflammed joints
Elevated ESR and CRP
Anemia of chronic diease
hypoalbuminemia
+Ve RF
rapid progression of joint erosions
systemic disease
```
85
Juvenile RA has been reclassified as Juvenile idiopathic arthritis (JIA). Dx of JRA is by exclusion, what are 3 other subsets of JRA?
1. systemic onset JRA
2. Polyarticular onset JRA
3. Pauciarticular onset JRA
86
The etiology of JRA is linked to what?
genetic
environmental
immunologic factors
87
Define Systemic onset JRA (Still's disease)
sxs: Rash, fever, arthritis
lease common,
age 1-16
diffficult to dx, lack to abx tx is a key feat.
condition abates after 6 months-can be recurrent.
low motality rates
88
Define Polyarticular onset JRA
30-40% of cases
F > M
bimodal presentation peek at 2-5 ya, second 10-14 ya.
slow onset but progressive- if dx before 10,
>10 yo at dx can have two forms 1. seropositive with gradual onset,
89
Define Pauciarticular onset JRA:
most common >50% of cases.
<5 joints involved
F > M
< 5 yo.
sxs present for 6 weeks, joints swollen.
complication: uveitis, with perm visual damage.
possible limb discrepancy
90
How is JRA txed?
use of NSAIDS and DMARDS if more progressive.
| Hormones, and supplemental calcium can help limit osteo risk.
91
What are common complications of JRA?
linear growth abnormalities
osteoporosis
failure to thrive
AE: d/t corticosteroids
