Rheumatoid Arthritis Flashcards
Patients with Arthritis usually also have what…?
Normochromic and Normocytic anaemia: reduced numbers of normal-sized erythrocytes with normal Hb content associated with chronic disease
Raised inflammatory markers (ESR and CRP)
What is Rheuatoid Arthritis and who does it afffect?
Common systemic autoimmune disorder affecting 1% of UK population
Pre-menopause, women 3 times more like to be affected than men (1:1 after menopause)
Can present at any age but peak prevalence between 30-50 years
Gradual onset of symptoms most common
The cause of rheumatoid arthritis is unknown but describe the proposed mechanism
Generalised non-specific inflammatory response, localised tissue damage and release of neo-autoantigens leading to activation of synovial T cells (initiating event)
B-cells activated and produce autoantibodies and rheumatoid factors which form immune complexes, bind to complement, and stimulate neutrophils to produce pro-inflammatory cytokines (IL-1 and TNF-alpha) and chemokines
Describe the immune response in RA?
(1) Non-specific inflammation
(2) Synovial T cell activation
(3) B cell activation, auto-
antigen antibodies and rheumatoid factors
(4) Production of pro-inflammatory cytokines (IL-1 and TNF-alpha) & chemokines
Chronic inflammation is maintained by rheumatoid factors and continuous stimulation of macrophages by pro-inflammatory cytokines and chemokines
What is RA characterised by?
Chronic synovitis - inflammation of the synovial lining of joints, tendons sheaths or bursae
Describe the pathology of RA?
New synovial blood vessels, induced by angiogenic cytokines, and endothelial cell activation expedites leucocyte extravasion into the synovium
Synovium proliferates, growing out over cartilage surface, and forms a pannus.
Pannus destroys articular cartilage and subchondral bone, producing bony erosions
Subcutaneous rheumatoid nodules form
What are some of the symptoms of RA? (5)
Swelling of small joints Morning stiffness Joint capsules are weakened leading to instability Joint effusions Muscle Wasting
What are the Periarticular features of RA? (4)
Bursitis
Tenosynovitis
Muscle wasting
Subcutaneous nodules (20% cases)
What are the Extra-articular features of RA? (5)
Fever
Fatigue
Anaemia
Sjörgens syndrome (dry eyes and mouth due to destruction of epithelial exocrine glands)
Carpal tunnel syndrome (pressure on median nerve)
what are the diagnostic features of RA?
- Blood count
Anaemia (normochromic and normocytic)
Thrombocytosis (over production of platelets)
Raised ESR (Erythrocyte sedimentation rate) & CRP (C-reactive protein) - both in response to inflammation - Serum Autoantibodies
Rheumatoid factor present in 70-80% RA cases (but not only in RA)
Antinuclear factor present in 30% RA cases
Anti-citrulline-containing peptide (CCP) in 50-60% early RA cases and in erosive disease - Radiology
Soft tissue swelling, erosion at joint - Sterile synovial fluid with high neutrophil count
As there is no available cure, what management options are there for RA?
- NSAIDs
- DMARDs (Disease modifying anti-rheumatic drugs)
- Corticosteroids
Give examples of Disease modifying anti-rheumatic drugs? (6)
Penicillamine
Gold salts
Antimalarials (chloroquine, hydrochloroquine)
Sulfasalazine
Methotrexate
Cytokine inhibitors (adalimumab, anakinra, etanercept, infliximab)
How do NSAIDs work for RA?
Relieve pain ONLY. do not slow progression
Pain relief takes about 1 week
Anti-inflammatory effect takes up to 3 weeks
Start with low dose of least gastric toxic NSAID (i.e. ibuprofen 200-400mg tbs)
Gastric protection is recommended (PPIs etc)
When would corticosteroids be used in RA patients?
Disease flares, pulse with high dose corticosteroids until other drugs take effect
If patient shows no response to other drug therapies
Intra-articular injections to relieve symptoms in 1-2 joints
Limit number of injections into each joint to no more than 3 per year
When should DMARDs be used?
Only under consultant supervision
Started early in disease (3-6months)
Used in combination with methotrexate. Or alone if combination can not be tolerated
What is the first choice of DMARDs monotherapy for RA?
Sulfasalazine - effective in 70% of patients after 1 year
What dose regime of Sulfasalazine is required for RA?
Initially 500mg daily by mouth, increased by 500mg at intervals of 1 week to max of 2-3g daily in divided doses
What are some side effects of Sulfasalazine?
GI disturbances, malaise and headache, rashes, blood disorders (in first 3-6 months)
What needs to be monitored with Sulfasalazine and when?
Blood counts and liver function tests required initially and then monthly for first 3-6 months
What supplement is usually given with Sulfasalazine?
Folic acid to counteract impaired folic acid absorption
Antimalarials can be used as treatment as they can be better tolerated than gold or penicillin but why should they be used with caution?
may cause ocular toxicity/progressive loss of vision on long term treatment
Risk of ocular toxicity increases with abnormal liver or kidney function, after cumulative dose of 800g, or in patients >70 years
Which antimalarials can be used?
Hydroxychloroquine is used to treat moderate active RA
Chloroquine is less commonly used and should only be used if all other drugs have failed
What monitoring is recommended for hydroxychloroquine use?
Pre-treatment assess renal and liver function, ask about visual impairment and get optometrist assessment if present, record visual acuity.
If no abnormality, initiate treatment
During treatment, assess visual symptoms and acuity annually, refer to ophalmologist if changes/blurring of vision (discontinue treatment)
What dose of Hydroxychloroquine is used for RA?
400mg daily in divided doses, then 200-400mg daily for maintenance
What cautions and side effects of hydroxychloroquine?
VERY TOXIC in over dose - max dose of 6.5mg/kg daily (but not exceeding 400mg)
Side effects:
Common - GI disturbances, headache
Less common: ocular toxicity, hair loss, discolouration of hair, skin/nails
What is the mechanism of action of methotrexate?
A “folic acid antagonist”, inhibits dihydrofolate reductase, reducing availability of tetrahydrofolic acid (required for purine production and DNA synthesis), which suppresses cell division in immune cells, suppressing cell-mediated immunity.
How long until a response is seen with methotrexate?
4-6 weeks
What monitoring is required with Methotrexate?
Careful monitoring is required to detect/prevent occurrence of serious adverse effects such as blood disorders (some fatal), renal impairment, liver cirrhosis, pulmonary fibrosis
FBC, renal and liver function tests prior to, repeated weekly until therapy is stabilised and then every 2-3 months thereafter
Which drug class does methotrexate belong to?
An anti-metabolite drug; used at low dose as a disease modifying anti-rheumatic drug (DMARD)
What dose is recommended of methotrexate for moderate to severe RA?
Moderate to severe RA, by mouth, adult over 18yrs, 7.5mg once weekly, adjusted according to response to max. weekly dose of 20mg)
What dose is recommended of methotrexate for severe active RA?
Severe active RA, by SC, IM or IV injection, adult over 18yrs, 7.5mg once weekly, adjusted by 2.5mg according to response to max. weekly dose of 25mg
Which OTC medications should patients avoid with methotrexate?
Aspirin or Ibuprofen
How is Penicillamine thought to work
Reduction in joint swelling and nodules, ESR rate and RhF titre decrease
effective in 60% of patients within 8-12 weeks
70% within 6 months
What dose of Penicillamine should be used?
Start with 125-250mg daily orally with food, increasing after 4-6 weeks to 500-750mg daily (Max dose 1.5g daily (1g in elderly))
