Rheumatoid arthritis Flashcards
List some DDx for rheumatoid arthritis?
- Seronegative spondyloarthritis (PAIR mnemonic): psoriatic arthritis, ankylosing spondylitis, IBD, reactive arthritis
- Autoimmune (seropositive)- RA, Sjogren’s syndrome, SLE, Sarcoidosis, Polymyositis, scleroderma
- Crystalline arthropathies- gout (monosodium urate), pseudogout (calcium pyrophosphate)
- Infective- viral (EBV, Ross River virus), bacterial (Shigella, Chlamydia, Gonococcus, rheumatic fever/Strep), fungal
- Non-inflammatory- OA, trauma
What is the diagnostic criteria for RA?
Diagnostic criteria (American College of Rheumatology)
• Inflammatory arthritis >3 joints (MCP, PIP, wrist, elbow, knee, ankle, MIP joints
• Symptoms > 6 weeks
• Raised ESR or CRP
• Positive serum RF of ACPA (anti-CCP)
• Consistent radiograph changes- erosions, periarticular decalcification
• Excluding diseases w similar clinical presentation (psoriatic arthritis, reactive arthritis, polyarticular gout/pseudogout, SLE)
Note: RA unlikely if asymmetrical joint distribution, DIP involved or absent constitutional symptoms
What investigations would you order for RA?
Blood tests:
o FBC- anaemia of chronic disease (normocytic anaemia), leukopenia, thrombocytosis
o RF- high titres more severe, 80% specific, 80% sensitive, absent early on
o Anti-citrullinated peptide/protein antibodies (ACPA/anti-CCP)- 75% sensitive, 90% specific
o Inflammatory markers- raised ESR/CRP
o AI markers- ANA
o Infection serology- human parvovirus B19, HBV, HCV, Borelia serology (Lyme disease)
Imaging: joint x-ray (LESS mnemonic)
Joint aspirate:
Compare the x-ray findings between RA and OA?
RA: (LESS mnemonic)
L- loss of joint space (thinning articular cartilage)
E- erosions (bony erosion at joint margin)
S- soft tissue swelling (inflammed surrounding tissues) -> ruptured tendons/ligs -> deformities
S- soft bones (osteopenia) -> peri-articular osteoporosis
OA: (LOSS mnemonic) L- Loss of joint space O- Osteophytes (bone spurs) S- Subchondral sclerosis S- Subchondral cysts
What would an RA joint aspirate show?
Joint aspirate: RA
o Increased volume
o RF positive
o Microbial culture- negative (sterile)
o Cell count- increased WCC, turbid due to polymorphs and RA cells
o Complement (C3, 4)- decreased in synovial fluid as consumed
o Biochem- high protein, low glucose
Differentiate between the pathogenesis of RA and OA?
RA path: autoimmune reaction -> inflammatory cytokines and cells to induce pannus formation (proliferative granulation tissue) eroding articular cartilage and bone
• Risk: female, HLA-DR4, smoking, silica exposure, rheumatoid factor (anti-IgG antibody in 80%), anti-cyclic citrullineated peptide Ab (more specific)
OA path: mechanical- wear and tear destroys articular cartilage
-> Chondrocyte mediated degradation and inadequate repair
• Risk: age, female, obesity, joint trauma
Compare the clinical presentations of RA and OA?
RA clinical: pain, swelling, morning stiffness >1hr, improves with use, systemic symptoms (fever, malaise, weight loss), common extra-articular manifestations
• Extraarticular- rheumatoid nodules (subcut tissue and lung), interstitial lung disease, pleuritis, pericarditis, anaemia of chronic disease, neutropenia/splenomegaly (Felty Syndrome), AA amyloidosis, Sjogren’s syndrome, Scleritis, carpal tunnel syndrome
OA clinical: pain in weight bearing joints after use (e.g. end of day), improves with rest, asymmetric joint involvement, knee cartilage loss begins medially (“bowlegged”), NO systemic symptoms
What medications would you consider?
Rx:
Symptomatic relief:
- NSAIDs
- Corticosteroids
Disease treatment:
- DMARDs (e.g. methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide)
- Biological agents (e.g. Infliximab/anti-TNF)
Describe the MA of NSAIDs?
NSAIDs
MA: non-selective COX inhibitor -> reduced formation of prostaglandins, thromboxanes and prostacyclins from arachidonic acid
o COX2 inhibition (inducible) -> anti-inflammatory, analgesic, antipyretic
o COX1 inhibition (constitutive) -> inhibition of PGs needed for GIT mucosa (maintaining mucosal blood floq, hydrophobic surface layer and bicarb secretion) AND platelet aggregation (thromboxanes) -> bleeding and dilation of afferent renal arteriole -> reduced GFR
o Increased breakdown of arachidonic acid by 5-lipoxygenase (as not broken down by COX 1 and 2) -> greater leukotriene production -> increased vascular permeability and constriction of bronchial smooth muscle
List some SE of NSAIDs?
NSAID SE:
o GIT: dyspepsia, PUD, GI bleed, gastritis, hepatotoxicity (rare)
o Renal: AKI (afferent vasosconstriction), electrolyte imbalance (hyperkalaemia, hyponatraemia, oedema)
o CVS: bleeding, MI, stroke (reduced prostacyclin needed for endothelium, SM relaxation and vasodilation
o Resp- bronchospasm
o Haem- reduced platelet aggregation
o Anaphylaxis
o Skin rashes- Steven Johnson syndrome
Describe the MA of corticosteroids?
Corticosteroids
MA: anti-inflammatory and immunosuppressant
o Binds to intracellular glucocorticoid receptor, translocating into nucleus and effecting gene transcription
- Bocks promotor sites for proinflammaotry genes (IL1-a, IL1-b, IL2, IL6, IL8), TNF
- Recruits promotor sequences of anti-inflammatory gene products (IL-1, IL-10, a2 macroglobulin, secretory leukocyte protease inhibitor)
- Inhibition of inflammatory cytokine synthesis
- Promotes T cell apoptosis
List some SE of corticosteroids?
Corticosteroid SE:
o Derm- skin thinning, ecchymoses, acne, facial erythema
o Appearance- weight gain, Cushingoid appearance, hirsutism
o Ocular- elevated IOP/glaucoma, exopthalmos
o CVS- fluid retention, HTN, premature arteriosclerosis, arrhythmia
o GIT- gastritis, PUD, steatohepatitis, visceral perforation
o MSK- osteoporosis, avascular necrosis, myopathy
o Neuro- euphoria, dysphoria, insomnia
o Metabolic- hyperglycaemia
o Immune- risk infection
o Haem- leukocytosis
Monitor: osteoporosis (bone scan), infection, DM/glucose intolerance, cataracts or glaucoma
What is the MA of Methotrexate?
Methotrexate- DMARD 1st line
• MA: cytotoxic and immunosuppressant effects
o Cytotoxic: inhibits hidydrofolate reductase (DHFR) (aids tetrahydrofolate synthesis) -> inhibits DNA synthesis
o Immunosuppressive: inhibits purine metabolism -> adenosine accumulation
-> inhibits T cell activation, suppression of T cell expression of intracellular adhesion molecule, B cell downregulation, IL-1 inhibition
Dosing: taken once WEEKLY, with dose folic acid to minimize SE
List some SE of methotrexate?
- SE: GIT upset, oral ulcers, mild alopenica, BM suppression (thus folate supp), hepatocellular injury, pneumonitis (leads to pulmonary fibrosis)
- Monitor: FBC (anaemia), LFTs (can increase enzymes), UEC
- CI: pregnancy, MS
Describe the indication and MA of Sulfasalazine?
Indications: alternative 1st line agent, not as effective as methotrexate
MA: inflammatory
o Suppression of IL1, TNF
o Induces apoptosis of inflammatory cells
o Increases chemotactic factors
