LECTURE 4 (Rheumatoid Arthritis) Flashcards

1
Q

What is Rheumatoid Arthritis?

A

An autoimmune disorder that involves inflammation of the joints (especially the hands & wrists)

ADDITIONAL INFO: more common in women & usual age of onset is 40-60)

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2
Q

What is the pathophysiology of Rheumatoid Arthritis?

A

Inflammation of the Synovium due to an unknown trigger leading to an overproduction of cytokines-especially TNF and IL-6

Synovium inflammation -> Synovial hypertrophy -> thickens into a PANNUS (synovium infiltrated with inflammatory cells + granulation tissue) -> increase in synovial fluid -> pannus can erode into cartilage and bone

Explanation: Synovium = A thin layer of tissue that lines joints and tendon sheaths + secretes hyaluronic acid to lubricate the joint space

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3
Q

What type of Hypersensitivity reaction is Rheumatoid arthritis?

A

Antibody-mediated/Type III Hypersensitivity

Explanation: There are antibodies produced in Rheumatoid Arthritis against proteins in the body which can circulate and deposit in joints and other tissues

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4
Q

What differentiates Rheumatoid arthritis from Osteoarthritis?

A
  • There is symmetric joint inflammation in RA
  • Joint stiffness goes away within one hour in Osteoarthritis (RA is >1 hour)
  • Stiffness improves with use in RA
  • No fever in Osteoarthritis (fever in RA)

Explanation: Because it is an autoimmune condition it begins straight away with SYMMETRIC joint inflammation instead of just on one side

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5
Q

What is distinguishable in Rheumatoid Arthritis?

A
  • Symmetric joint inflammation
  • Gradual onset
  • Pain, stiffness and swelling in affected joints
  • “Morning stiffness” lasting for more than one hour after rising
  • May have systemic symptoms indicating inflammation (fever)
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6
Q

Where in the body does Rheumatoid arthritis usually affect?

A

MCP and PIP joints of the hands (often tender to touch)

Explanation: DIP joints are spared contrasting to Osteoarthritis which affects all the joints of the hands

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7
Q

What happens if Rheumatoid Arthritis is left untreated?

A
  • Bones can erode/deviate and become deformed
  • Ulnar deviation (swelling of MCP joints in the wrist causes wrist to deviate towards little finger[ulnar side])
  • Swan neck deformity (hyperextended PIP joint + flexed DIP)
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8
Q

What are the joints that can be affected by Rheumatoid Arthritis?

A
  • Wrists
  • Elbows
  • Knees
  • Hips
  • Toes
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9
Q

What are the systemic symptoms of Rheumatoid Arthritis?

A
  • Baker’s cyst (popliteal cyst)
  • Serositis (inflammation of serosa) [pleuritis + pericarditis]
  • Rheumatoid nodules (subcutaneous nodules)
  • Eyes [Episcleritis, Scleritis, Uveitis]
  • Secondary Sjoren’s Syndrome
  • Osteoporosis
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10
Q

What is Baker’s cyst (popliteal cyst)?

A

A cyst that occurs at the back of the knee at the popliteal fossa

There is a synovium-lined sac at the back of the knee that can become swollen + is continuous with the joint space -> can present with pain and swelling (Baker’s cyst) -> If the cyst ruptures, it will give the patient pain travelling down their leg (symptom similar to DVT)

Clinical relevance: Patients present to the ER with leg pain thinking they have a DVT -> Doppler ultrasound is -ve because pain is due to Rheumatoid Arthritis not a blood clot

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11
Q

What is Serositis?

A

Inflammation of the serosa (most commonly Pleuritis and Pericarditis)

  • Pleuritis (inflammation of pleura of lungs) = presents as pain during inspiration + can progress to cause a pleural effusion (accumulation of fluid in pleural cavity )
  • Pericarditis (inflammation of pericardium around the heart) = symptoms of pericarditis + can progress to become a pericardial effusion (accumulation of fluid around heart) + can lead to pericardium disease
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12
Q

What are Subcutaneous nodules?

A

Palpable nodules in the subcutaneous tissues of the skin that occur in patients that are RF positive (RF+). It can occur anywhere but is most common on the elbow.

PATHOPHYSIOLOGY:
- Central necrosis surrounded by macrophages/lymphocytes

TREATMENT:
- Usually no specific treatment apart from treating Rheumatoid Arthritis in general
- May require surgery if very large

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13
Q

What is Episcleritis?

A

Inflammation of the Episclera of the eye (surface layer of the eye) which will lead to a red eye that is painful but without discharge

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14
Q

What is Scleritis?

A

Inflammation of the Sclera of the eye which is often bilateral, results in dark, red eyes and deep ocular pain on eye movement

Explanation: Eye muscles insert into sclera of the eye so during scleritis it hurts to move your eyes

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15
Q

What is Uveitis?

A

Inflammation of the Uvea of your eye (vascular layer of eye). Symptoms are different depending on Anterior or Posterior Uveitis.

Posterior Uveitis = floaters + vision loss
Anterior Uveitis = symptoms similar to scleritis + episcleritis

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16
Q

What is Sjoren’s syndrome?

A

An autoimmune disease that involves damage to the salivary and lacrimal glands resulting in dry eyes and dry mouth (Sicca symptoms)

ADDITIONAL INFO: commonly associated with Rheumatoid arthritis + Lupus

17
Q

What is the correlation between Osteoporosis and Rheumatoid Arthritis?

A

Osteoporosis is accelerated by Rheumatoid Arthritis and is often worsened by steroid treatment (RA patients require steroid treatment) [BAD COMBINATION!!!!]

ADDITIONAL INFO: Increases risk of major fracture + hip fracture

18
Q

Which antibody tests can be used to diagnose Rheumatoid Arthritis?

A
  • Rheumatoid Factor (80% of RA patients are RF+)
  • Antibodies to CITRULLINATED PEPTIDES (ACPA)
    [more specific test for RA]
  • Elevated CRP and ESR
  • Strong association with HLA-DR4
19
Q

Describe the Rheumatoid Factor antibody

A

An antibody against the Fc portion of IgG antibody (RF antibody attacks the IgG antibody)

ADDITIONAL INFO:
- RF+ -> “seropositive” rheumatoid arthritis
- Poor specificity
- Positive in endocarditis, Hep B and Hep C
- Positive in Sjoren’s syndrome

20
Q

Describe Citrullinated peptides (ACPA)

A

Peptides that have had citrulline added to them

Explanation: Citrulline is a “non-standard amino acid” that is not encoded by the genome but can be added via POST-TRANSLATIONAL MODIFICATION -> there is more incorporation into proteins where there is INFLAMMATION -> Anti-citrulline peptide antibodies can occur which is elevated in patients with Rheumatoid arthritis

21
Q

What is the treatment for Rheumatoid Arthritis?

A
  • NSAIDs
  • Steroids
  • Disease-modifying antirheumatic drugs (DMARDs)
    [protects joints from destruction]
22
Q

Which drugs are Disease-modifying antirheumatic drugs (DMARDs)?

A
  • Methotrexate
  • Azathioprine
  • Cyclosporine
  • Hydroxychloroprine
  • Sulfasalazine
  • Leflunomide
  • TNF-a inhibitors (antibodies against TNF-alpha)
23
Q

What is the MOA of Sulfasalazine?

A

Sulfasalazine is split into Sulfapyridine + 5-aminosalicylic acid (5-ASA)

24
Q

What is the MOA of Leflunomide?

A
  • Used in Rheumatoid arthritis and Psoriatic arthritis
  • Inhibits dihydroorotate dehydrogenase (converts dihydroorotic acid to orotic acid in pyridine synthesis)
  • Inhibits pyrimidine synthesis -> inhibits DNA and RNA synthesis -> major impact on rapidly dividing cells including cells of the immune system -> IMMUNOSUPPRESSANT

SIDE EFFECTS:
- Diarrhoea
- Abnormal LFTs
- Decreased WBCs

25
Q

What is the MOA of Infliximab?

A
  • Used in Rheumatoid Arthritis and Crohn’s disease
  • Antibody against TNF-alpha

RISKS:
- It can cause the reactivation of Tuberculosis
[PPD screening is done prior to treatment]
- Risk of other infections e.g bacterial pneumonia, Herpes zoster

26
Q

What are some other TNF-alpha inhibitors?

A
  • Adalimumab (monoclonal antibody TNF-alpha)
  • Golimumab (monoclonal antibody TNF-alpha)
  • Etanercept (looks like the TNF receptor -> functions as a “decoy receptor” -> binds TNF)
27
Q

What are the Long term complications of Rheumatoid Arthritis?

A
  • Osteoporosis
  • Increased risk of coronary disease (inflammation can lead to plaque build-up in the walls) -> leading cause of mortality
  • Amyloidosis (Amyloid deposits in kidneys + soft tissues) -> causes secondary amyloidosis
28
Q

What is Felty syndrome?

A

A rare complication of Rheumatoid Arthritis that manifests as a triad of Rheumatoid Arthritis, Splenomegaly and Neutropenia

CAUSES:
- When a patient has severe RA for many years
[joint deformity + extra-articular disease]

TREATMENT:
- No specific treatment (usually gets better with general rheumatoid arthritis treatment)