Part Four: Inflammatory DX - Rheumatoid Arthritis RA Flashcards
Exam 4 (Final)
Rheumatoid Arthritis (RA): What kind of disease is this considered?
Autoimmune & inflammatory
Chronic, systemic
Rheumatoid Arthritis (RA):
Is Chronic, systemic:
What symptoms exist?
Fever, malaise, rash, lymph node or spleen enlargement
Joint swelling, tenderness
Rheumatoid Arthritis (RA):
What is there destruction of?
Destruction of synovial joints
Rheumatoid Arthritis (RA):
Destruction of synovial joints:
What does it line?
Why does destruction occur?
What else does it lead to?
lines the joint cavity
Immune system targets the synovium
Synovitis
Rheumatoid Arthritis (RA):
Destruction of synovial joints:
Synovitis- What does this lead to?
Membrane thickened/swollen
Rheumatoid Arthritis (RA):
What forms?
Pannus forms
Rheumatoid Arthritis (RA):
Pannus forms: What is this?
Abnormal tissue growth in synovium
Rheumatoid Arthritis (RA):
Pannus forms: What does this consist of?
Consists of inflamed synovial cells, immune cells, and blood vessels
Rheumatoid Arthritis (RA):
Pannus forms: What does it contribute to and how?
Invades & damages nearby cartilage and bone, contributing to joint erosion and deformity
Rheumatoid Arthritis (RA)
Predisposing Factors
Age (Young & middle aged)
Environmental factors
Females
Postpartum
Patho of RA:
How does it start (What gets activated?)
Synovial fibroblasts (SF) that line joint cavity get activated
Patho of RA
When synovial fibroblasts (SF) that line joint cavity get activated, what happens?
Immune system mounts an attack
Patho of RA
What happens to synovial fibroblasts (SF)?
Synovial fibroblasts (SF) proliferate & produce inflammatory cytokines & PGs
Patho of RA
Synovial fibroblasts (SF) proliferate & produce inflammatory cytokines & PGs
What do the cytokines do?
Cytokines: Pro-inflammatory (TNF-α, IL-1, and IL-6) drive the inflammatory process.
Patho of RA:
What does the enflamed synovium (pannus) do?
The inflamed synovium (pannus) grows over the cartilage and bone, releasing enzymes that degrade cartilage and bone.
Patho of RA:
What does the SFs do?
SFs attack articular cartilage –> more release of inflamm enzymes –> spreads to joint capsule, ligaments, tendons
Patho of RA
What do activated T-cells do?
Activated T cells produce pro-inflammatory cytokines
Patho of RA
What do B-cells do?
B cells produce autoantibodies which form immune complexes that further drive inflammation.
Pannus formation (thickened synovium)
Granulation tissue from the synovium spreads over the articular cartilage, releasing enzymes and inflammatory mediators that destroy the cartilage.
Slide 5: I don’t understand
Clinical Manifestations:
How are joints?
Red, swollen, warm and painful joint
Symmetrical
Insidious onset
Multiple joints (small joints in hands, wrists, feet, larger joints like knees, shoulders, hips)
Clinical Manifestations:
Red, swollen, warm and painful joint
Symmetrical
Insidious onset
Multiple joints (small joints in hands, wrists, feet, larger joints like knees, shoulders, hips)
What leads to this?
Abnormal immune response, causing inflammation of the synovial membrane with vasodilation, increased permeability
Clinical Manifestations:
Red, swollen, warm and painful joint
Symmetrical
Insidious onset
Multiple joints (small joints in hands, wrists, feet, larger joints like knees, shoulders, hips)
What time of day is this most common?
Sx most intense in the AM
Clinical manifestations:
How are muscles?
Atrophy of muscles
Clinical manifestations:
Atrophy of muscles: Why does this occur?
Disuse of muscles and stretching of tendons and ligaments related to acute inflammation
Clinical manifestations:
What happens to bones? why?
Misalignment of bones
Due to eroded cartilage and muscle imbalance
Clinical manifestations:
Other than muscle atrophy, what happens to muscles?
Why does this occur?
Muscle spasm
Inflammation and pain
Clinical manifestations:
What happens to mobility? What else?
Why does this occur?
Deformity and impaired mobility
Contractures and deformity
Clinical manifestations:
What other symptoms occur? Why?
Fatigue, anorexia, mild fever, generalized lymphadenopathy, and generalized aching (systemic)
From the immune factors
Clinical manifestations:
Rheumatoid nodules – What are they?
Rheumatoid nodules – inflammatory tissue, consisting mainly of immune cells (macrophages, lymphocytes, fibroblasts).
They may also contain deposits of fibrin.
Eval & Management
How to diagnose?
Assessment
Labs:
Synovial fluid analysis Joint X-rays, MRI, ultrasounds
Eval & Management
Diagnose: What kind of labs are needed?
Serum rheumatoid factor test
Serum anticyclic citrullinated peptide antibodies test (ACPA) –
specific marker
ESR – erythrocyte sedimentation rate
Serum C-reactive protein
Serum antinuclear antibody
Eval & Management:
What is treatment?
Early aggressive pharmacotherapy
Surgical repair
Non-pharm
Eval & Management:
Early aggressive pharmacotherapy: Is there a cure?
⍉ cure
Eval & Management:
Early aggressive pharmacotherapy:
What does this do?
Slowed progression, delayed joint destruction
Symptomatic relief
Eval & Management:
Early aggressive pharmacotherapy:
RA is treated with three classes of drugs: What are they?
- NSAIDs for pain,
- glucocorticoids (may delay disease progression),
- disease-modifying antirheumatic drugs (DMARDs)
Eval & Management:
Early aggressive pharmacotherapy:
Glucocorticoids: What do they do?
(may delay disease progression),
Eval & Management:
Early aggressive pharmacotherapy:
NSAIDs: What are they for?
NSAIDs for pain
Eval & Management:
Non-pharm treatment?
ARTHUR
Assistive devices
Rest & pacing activities
Therapeutic activities –
Heat/cold application
Use splints, braces for support & alignment to prevent deformities
Relaxation techniques
Eval & Management:
Non-pharm treatment?
ARTHUR
A = Assistive devices ~
walkers, rails
Eval & Management:
Non-pharm treatment?
ARTHUR
Therapeutic activities –
balanced exercise & rest
PT & OT ~ massage, warm baths
Eval & Management:
Non-pharm treatment?
ARTHUR
Heat/cold application:
What is heat for? What does it do
What is cold for? What does it do?
Heat=vasodilation=decrease pain
Cold=vasoconstriction=dec pain, swelling
Eval & Management:
Non-pharm treatment?
ARTHUR
Use splints, braces for what?
for support & alignment to prevent deformities
DMARDs: Disease-Modifying Antirheumatic Drugs
What is the aim of these drugs?
Aim: reduce joint destruction & slow disease progression
DMARDs: Disease-Modifying Antirheumatic Drugs
What are the two groups? What are they based on?
Nonbiologic (traditional) vs Biological (recombinant DNA)
based on molecular size & how produced
What is the most rapid acting and first choice DMARD?
Methotrexate
RA
DMARDs:
Methotrexate- MOA
How does it treat disease progression?
Slows disease progression (not just sx relief!!!)
Interferes with rapid growth/cell division
RA
DMARDs:
Methotrexate- MOA
What does it do with B and T lymphocyte activity?
Immunosuppression of B&T lymphocyte activity
RA
DMARDs:
Methotrexate- MOA
What does it interfere with?
Interferes with rapid growth/cell division
RA
DMARDs:
Methotrexate
How long does it take therapeutic effects to occur?
Therapeutic effect: 3 to 6 weeks
RA
DMARDs:
Methotrexate
What are adverse effects?
Hepatic fibrosis
Bone marrow
suppression
GI ulceration
pneumonitis
CVD, infection, lymphomas
RA
DMARDs:
Methotrexate
What are fatal toxicities that can occur?
Fatal toxicities of bone marrow, liver, lungs, kidneys, skin reactions, hemorrhagic enteritis, GI perforation
RA
DMARDs:
Methotrexate
What is necessary when taking this med?
Supplemental folic acid necessary
RA
DMARDs:
Methotrexate
What tests are needed when taking this med?
Periodic liver, kidney function tests, CBC, Platelet
RA
DMARDs:
Methotrexate
How is life expectancy effected?
Reduced life expectancy: CVD, cancers
DMARDs II: Major Biologic DMARDs
What are they?
Tumor necrosis factor (TNF) inhibitors
DMARDs II: Major Biologic DMARDs
Tumor necrosis factor (TNF) inhibitors:
What are TNF ?
TNF is an inflammatory response mediator & responsible for joint injury
DMARDs II: Major Biologic DMARDs
In RA, what does TNF bind to?
In RA – TNF binds with synovial cells –
DMARDs II: Major Biologic DMARDs
In RA – TNF binds with synovial cells – what does this lead to? (What is stimulated)
stimulates inflammatory mediators, promotes infiltration of neutrophils & macrophages –> inflammation & joint destruction
DMARDs II: Major Biologic DMARDs
TNF inhibitors- What do they do?
Binds tightly to TNF & makes it inactive, preventing it from interacting with natural receptors on human cells in the synovium
DMARDs II: Major Biologic DMARDs
TNF:
Some interfere with B&T lymphocytes
What does this put someone at increased risk of?
Increased risk of serious infection
DMARDs II: Major Biologic DMARDs
TNF- What do some of them interfere with?
Some interfere with B&T lymphocytes
DMARDs II: Major Biologic DMARDs
TNF inhibitors: How is it administered? What can it be combined with?
Weekly subQ injections
Can be combined with methotrexate
DMARDs II: Major Biologic DMARDs
TNF inhibitors: Work by neutralizing TNF
Drugs include?
Etanercept [Enbrel]**
Adalimumab [Humira]
Certolizumab pegol [Cimzia]
Golimumab [Simponi]
Infliximab [Remicade]
- end in ‘mab’
Adverse effects of Etanercept
Injection site reactions
Serious infections
Severe allergic reactions
Heart failure
Cancer/Hematologic disorders
Liver injury
CNS demyelinating disorders
Adverse effects of Etanercept
Serious infections include? What may need to be done if infection occurs?
Fungal, TB, opportunistic
Reactivation of HBV
Increased risk with DM, HIV, immunosuppressant drugs
May need to d/c if infection develops
Adverse effects of Etanercept
Serious infections include: Fungal, TB, opportunistic
TNF plays crucial role in immune response to infection, especially TB
