LECTURE 4 (Rheumatoid Arthritis) Flashcards
What is Rheumatoid Arthritis?
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)
What is the pathophysiology of Rheumatoid Arthritis?
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
What type of Hypersensitivity reaction is Rheumatoid arthritis?
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
What differentiates Rheumatoid arthritis from Osteoarthritis?
- 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
What is distinguishable in Rheumatoid Arthritis?
- 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)
Where in the body does Rheumatoid arthritis usually affect?
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
What happens if Rheumatoid Arthritis is left untreated?
- 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)
What are the joints that can be affected by Rheumatoid Arthritis?
- Wrists
- Elbows
- Knees
- Hips
- Toes
What are the systemic symptoms of Rheumatoid Arthritis?
- Baker’s cyst (popliteal cyst)
- Serositis (inflammation of serosa) [pleuritis + pericarditis]
- Rheumatoid nodules (subcutaneous nodules)
- Eyes [Episcleritis, Scleritis, Uveitis]
- Secondary Sjoren’s Syndrome
- Osteoporosis
What is Baker’s cyst (popliteal cyst)?
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
What is Serositis?
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
What are Subcutaneous nodules?
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
What is Episcleritis?
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
What is Scleritis?
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
What is Uveitis?
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
What is Sjoren’s syndrome?
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
What is the correlation between Osteoporosis and Rheumatoid Arthritis?
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
Which antibody tests can be used to diagnose Rheumatoid Arthritis?
- 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
Describe the Rheumatoid Factor antibody
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
Describe Citrullinated peptides (ACPA)
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
What is the treatment for Rheumatoid Arthritis?
- NSAIDs
- Steroids
- Disease-modifying antirheumatic drugs (DMARDs)
[protects joints from destruction]
Which drugs are Disease-modifying antirheumatic drugs (DMARDs)?
- Methotrexate
- Azathioprine
- Cyclosporine
- Hydroxychloroprine
- Sulfasalazine
- Leflunomide
- TNF-a inhibitors (antibodies against TNF-alpha)
What is the MOA of Sulfasalazine?
Sulfasalazine is split into Sulfapyridine + 5-aminosalicylic acid (5-ASA)
What is the MOA of Leflunomide?
- 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
What is the MOA of Infliximab?
- 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
What are some other TNF-alpha inhibitors?
- Adalimumab (monoclonal antibody TNF-alpha)
- Golimumab (monoclonal antibody TNF-alpha)
- Etanercept (looks like the TNF receptor -> functions as a “decoy receptor” -> binds TNF)
What are the Long term complications of Rheumatoid Arthritis?
- 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
What is Felty syndrome?
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)
