RA Prelecture Flashcards
What is RA?
● Immune-mediated systemic inflammatory joint disease
○ Immune system targets synovium (and sometimes other internal organs)
causing pain, swelling, inflammation, and joint destruction
○ Hallmark: persistent symmetric synovial proliferation & tenderness of
multiple joints, particularly in the hands and feet
Epidemiology
● Prevalence
○ 1% overall, affecting 300,000 Canadians
○ ↑ with age
○ most commonly diagnosed between 25-50y
● Affects more females than males, approximately 3:1
● Health care costs ~3x higher than age & sex-matched controls
● Prognosis
○ historically poor, with progressive joint damage and deformity
■ acute &/or chronic pain
■ erosions on X-ray à deformities
■ long-term disability
○ reduced life expectancy
We are doing a better job managing it now
female patients tend
to be diagnosed at a younger age
compared to males who are often
diagnosed in their 50s 60s or even 70s
Pt lifespan remains approx 10yrs shorter
Etiology and Risk Factors
● Genetics
○ disease specific genes
■ T lymphocytes with HLA-DR4 or HLA-DR1 variation
● Host Factors
○ pregnancy
● Environmental Factors
○ smoking
○ viral infection
○ air pollution
HLA is an MHC
class II molecule that presents foreign
antigen to T cells initiating an immune
response to a foreign invader
more commonly
diagnosed in the year following a
pregnancy and patients who are pregnant
often experience an improvement in
symptoms
smoking being
the strongest known environmental risk
Factor
viral infections have also long been
suspected but never proven
air pollution
is the other one that’s difficult to
prove but incident rates tend to be
higher in communities where there is
worse air quality
Pathophysiology: Phases of Early RA
external trigger leads to autoimmune reaction in genetically susceptible individual
Rheumatoid Factor (RF)
Anti-citrullinated protein antibody (ACPA)
Chronic inflammation leads to synovial changes
○ presence of pannus: thickened, inflamed joint lining
■ invades cartilage & bone surface, leading to erosions and permanent joint
destruction (deformities)
○ influx of inflammatory cells in the synovial fluid
■ T-lymphocytes, B-lymphocytes, cytokines, etc
○ angiogenesis
■ further enables inflammatory response
Cascade of inflammation and destruction
the synovium or joint lining which is
usually just one to two layers thick
becomes infiltrated with various
inflammatory cell types due to altered
production and regulation of those
cytokines
as it gets thickened
and sort of established as an inflamed
joint lining we call pannus
eventually that pannus shoves its way
into cartilage and Bone leading to Joint
destruction
-
release of vasoactive substances like
histamine and prostaglandins and kinins
increase the permeability of the
vasculature bringing more inflammatory
mediators to the joints and leading to
the red hot swollen joints
Pathophysiology w lymphocites
Activated T-lymphocytes
Stimulate release of macrophages or
monocytes
Ø release of cytotoxins and inflammatory cytokines
Activate osteoclasts Ø degrade bone
Activate release of MMPs Ø degrade connective tissue
Stimulate B-lymphocytes
Activated B-lymphocytes
Produce autoantibodies Ø rheumatoid factor (antibody to Ig)
Ø anti-citrullinated protein antibody (ACPA)
Serve as antigen presenting cells to
T lymphocytes
Ø perpetuate the inflammatory response
Produce pro-inflammatory cytokines Ø Further stimulate fibroblasts, osteoclasts, MMPs
Ø cellular damage to synovium and bone
Pathophysiology
● Cytokines
○ imbalance leads to inflammation and joint destruction
ANTI-Inflammatory
* IL-1RA
* IL-4
* IL-10
PRO-Inflammatory
* TNFa
* IL-1
* IL-6
* IL-8
* IL-17
tnf Alpha and il-6 as
the two dominant pro-inflammatory
players
Also targeted by drug tx
RA Joint Adaption and Destruction
Normal Joint Rheumatoid Joint
swelling
within the joint capsule with
neutrophils and macrophages and B cells
and T cells and other immune cells all
present that synovial lining is thick
and you can see that that panus is
pushing its way into the bone and eating
away at the cartilage
Clinical Presentation
● Onset:
○ insidious (usually over weeks or months)
● Distribution:
○ usually initially oligoarticular, progressing to polyarthritis
○ can affect almost any joint, symmetrical in presentation
○ most common: small joints of hands & feet
● Symptoms:
○ morning stiffness (‘gelling’) for >1h
○ symmetric swelling and tenderness
■ reduced grip strength, inability to make a fist
○ reduced functional status, inability to do ADLs
○ systemic:
■ profound fatigue (afternoon), poor sleep
■ decreased energy
■ possible weight loss &/or low-grade fever
Pattern of Joints Affected
Prognosis
proximal interphalangeal joints = PIP
metacarpal phalangeal joints = MCP
Pattern of Joints Affected
metatarsal phalangeal joints = MTP
almost any joint
can be in fact affected the one
exception is the spine so patients with
rheumatoid arthritis do not have back
pain that’s associated with that
rheumatoid arthritis
Joint Deformity: due to prolonged joint inflammation
Swan Neck Deformity
Boutonnière Deformity
Associated Signs/Symptoms
Ø RA affects more than the joints; it’s a systemic disease
Anemia * normocytic or hypochromic/microcytic
* multifactorial: chronic inflammation, bone
marrow suppression (meds), blood loss
Eyes * keratoconjunctivitis sicca (dry eyes)
Nervous System * carpal tunnel syndrome, tarsal tunnel syndrome
Extra-Articular Manifestations
Rheumatoid
Nodule
Rheumatoid
Nodule
Baker’s cyst
(aka popliteal)
they’re not the same as a joint deformity they’re
often asymptomatic and don’t require
specific treatment so they are local
sort of swelling or lumps they’re
painless but they might restrict
movement when you press on them
They can occur on the the pressure points so near inflamed joints
Potential Complications
Cardiovascular
Disease
* associated with traditional & RA specific risk factors
* ~1.5 fold higher than general population
Infections * historically ~2 fold higher (URTI, those requiring hospitalization)
* herpes zoster risk ~1.5-3 fold higher
Cancer * ~2 fold higher risk of lymphoma; also lung
cancer and perhaps melanoma
Osteoporosis * 2 fold higher risk of hip/vertebral #
* surrounding affected joints > globally (steroids, inactivity)
Systemic inflamm, also increased incidince of hypertension dyslipidemia and diabetes
potentially both disease related and
treatment related so traditionally patients with rheumatoid arthritis have a higher risk of lymphoma but also lung cancer and perhaps melanomas with good treatment we’ve seen the incidence of these decrease
the bones are are weaker so surrounding affected joints but also globally and this might be related to steroid treatment
or they’ve got more severe disease that limits their
activity they’re not as able to do the things that we know help to prevent osteoporosis
Common Comorbidities
depression
asthma
GI ulcer
any solid cancer
any skin cancer
MI, stroke, lymphoma
Hep B and C
Consider Sarah:
Which signs and symptoms does Sarah have that fit
with a diagnosis of RA?
Signs Symptoms
What RA risk factors does she have?
ok
How is RA diagnosed?
● History, physical exam, lab tests (and x-rays)
● Need to ‘rule out’ other diagnoses:
○ Osteoarthritis
○ Bursitis, tendonitis
○ Infection
○ Fibromyalgia
