Rheumatoid Arthritis Flashcards
What is rheumatoid arthritis and its consequences?
- an autoimmune disease which results in chronic joint inflammation
- can result in; joint destruction, deformity, loss of function and extra-articular complications
Outline the pathophysiology of rheumatoid arthritis
- not well understood, genetic predisposition (multiple genes) and environmental factors (viral, bacterial, smoking) involved
- initiation (periphery): RA patients contain antibodies (ACPA) which can bind to self-proteins and cause complement activation
- propagation (synovium): infiltration of immune cells; innate eg. Dendritic and monocytes, and adaptive eg. TNF and IL6 leading to pannus formation (inflammatory tissue that invades and takes over the synovium
- Tissue damage (bone and cartilage): fibroblast activity and inflammation lead to osteoclast generation (leading to bone erosion) and mast cell mediated ROS and NO production
What are the symptoms of RA?
- pain
- stiffness (early morning, joint gelling - ok on activity but stiff with rest)
- small joints more affected that large
- symmetrical
- persistent
What are the signs which can be seen in RA?
- synovitis (swelling and tenderness of the joints)
- deformity (eg. Swan, neck, Boutonniere, z-thumb, ulnar deviation)
- rheumatoid nodules (extensor surfaces)
What differentials do you need to keep in mind when considering RA?
- polyarticular gout
- psoriatic arthritis
- osteoarthritis
- SLE/ connective tissue disorder
What investigations would you do if suspecting RA?
Lab:
- CRP/ESR
- FBC
- bone/urate
- specific immunology
Imaging:
- plain radiograph
- US/MRI (assess how active inflammation is)
What is rheumatoid factor?
- IgM antibody
- directed against Fc portion of IgG antibody
- also found in: SLE, Sjogren’s PBC, hepatitis B and C, bacterial endocarditis
What is the anti-CCP antibody?
- much more specific antibody for RA (not seen in other conditions)
- created by the alteration of the shape of citrulline in inflammatory induced cellular damage (enzyme conversion of arginine residues to citrulline)
What are the RA induced changes seen in imaging?
X-ray
- early: normal X-rays (can be used for baseline)
- first changes: peri-articular osteopenia and soft tissue swelling
- late changes: erosion, joint destruction, subluxation
US:
- thickening of synovium (hypertrophy)
- doppler flow shows degree of flow which correlates with the degree of inflammation in the synovium
What are the aims of RA treatment?
- reduce inflammation
- maintain joint function
- prevent progression
What is the initial therapy for RA and its risks?
Reduce inflammation:
- NSAIDs (eg. Ibuprofen, naproxen, diclofenac): GI toxicity, CV risk
- COX-2 inhibitors (eg. Etoricoxib): contraindicated in renal impairment and anti-coagulation, caution in elderly and CV risk
- steroids for flare ups (eg. Prednisolone, intramuscular methylprednisolone, intra-articular depomedrone)
When are DMARDs given to RA patients and examples?
- first line and within 3 months of symptom onset
- eg. Methotrexate, leflunomide, sulfalazine, hydroxychloroquine (if mild)
Describe features of methotrexate
- folate antagonist
- taken once weekly
- side effects: mucosal, GI, pneumonitis (rare)
- requires FBC/LFT monitoring
- contraindicated in pregnancy
Describe the features of sulfalazine
- immunomodulatory (folate, T and B cell antagonist)
- daily dosing (based on weight)
- side effects: GI, headache, rash
- requires FBC, US and Es and LFT monitoring
- can be used in pregnancy
Describe features of hydroxychloroquine
- blocks toll-like receptors of plasmacytoid dendritic cells reducing their activation
- taken daily (least potent DMARD)
- side effects: headache, nausea, muscle pain, rash
- requires ocular monitoring (rare side effect = retinopathy)
- can be used in pregnancy
