CPT2: Rheumatoid Arthritis Flashcards
What is rheumatoid arthritis?
A chronic, systemic, autoimmune disease that affects the joints, connective tissues, muscles, tendons and fibrous tissue. It is a chronic disabling condition often causing pain and deformity.
Onset and prevalence of RA?
It tends to strike during the most productive years of adulthood, between the ages of 20 and 40,
The prevalence varies between 0.3% and 1% and is more common in women in developed countries.
Within 10 years of onset, at least 50% of patients in developed countries are unable to hold down a full-time job.
Causes of rheumatoid arthritis
An autoimmune condition – caused by the immune system attacking healthy body tissue. It is not known what triggers this.
Possible risk factors:
- Genes
- Hormones (Oestrogen?)
- Smoking
Symptoms of rheumatoid arthritis
Main symptoms are joint pain, swelling and stiffness.
Symptoms can occur in any joints in the body, but typically the small joints in the hands and feet are the first to be affected.
As systemic disease more general effects can occur e.g. tiredness, sweating, loss of apepitie, weightloss, high temperature, lack of energy. Symptoms differ in different patients and can worsen/ improve.
1. Pain:
- Usually throbbing and aching.
- Often worse in the morning and after a period of inactivity.
2. Swelling:
- Joints swell and become hot and tender to touch.
- In some people, swellings develop under the skin around affected joints (rheumatoid nodules).
3. Stiffness:
- Often worse in the morning or after a period of inactivity.
- Morning stiffness is also a symptom of osteoarthritis (OA) – however in OA it usually resolves within 30
How is diagnosis confirmed?
- Suspected in anyone with persistent synovitis.
- Based on symptoms mentioned previously and characteristics of symptoms (e.g. stiffness worse in the morning/after inactivity).
- Family history.
- Automimmune diseases
- Other non-specific symptoms.
Refer to specialist if:
- Suspected synovitis with undetermined cause
- Affects small joints of hands/ feet
- Affects more than one joint
- If delay of 3 months or longer between onset of symptoms and seeking medical advice
What is the pathophysiology?
In active synovitis the synovial membrane thickens with increasing synovial cells. The membrane becomes odematous and enriched with new blood vessel formation. There is increased production of synovial fluid and the joint capsule swells along with these changes.
Circulatin inflammatory cells infiltrate the joint tissue. There is irritation and swelling of join lining, degradation and bone errosion
https://www.youtube.com/watch?v=2IIiGfO5Mm4
Due to changes in genetic make-up an immune response to the body commenses. This leads to inflammatory mediators infiltrating into the join tissue/ Cytokines relased cause synovial prolifferation, angionenesis, osteocyte activation and other mediators cause bone irritation and eroision
What investigations are carried out?
No specific diagnostic test for RA.
The following tests can speed up diagnosis and are useful as a baseline measure before starting treatment:
- Full blood count (FBC) including C-reactive protein (CRP)/Erythrocyte sedimentation rate (ESR)
- Urea and electrolytes (U&Es)
- Can affect renal function
- Liver function tests (LFTs)
- Rheumatoid factor (RF)
- Protein produced by immune system that attacks healthy tissue - 50% people with RA have this. 5% without RA have this!
- Anti-cyclic citrullinated peptide antibody (Anti-CCP)
- AB produced by body. Not all have this
- X-ray or MRI scan
If have RH and Anti-CCP then more severe
Goals of treatment for RA
- Symptom relief.
- Prevention or slowing of joint damage.
- Preserving and improving functional ability.
- Achieving and maintaining disease remission
What pharmacological treatments is there?
- Disease-modifying antirheumatic drugs (DMARDs).
- Corticosteroids.
- Biologic agents.
- Pain control – as per WHO pain ladder.
What is the first line treatment?
DMARDs
What are DMARDs available?
Describe treatment with them
- Offered first line for adults with newly diagnosed active RA.
- First line treatment is monotherapy with methotrexate, leflunomide, or sulfasalazine.
- Choice dependent on balance between toxicity and efficacy
- ADR can limit use especially if: blood disorder, infection, hepatic/ renal impairment, conconsument med may interact
- May take 2-6 months to have full effect - can consider short-term ‘bridging’ treatment with a corticosteroid.
- If treatment target has not been achieved after 3 months, a second DMARD may be added. Triple therapy is an option if a further 3 months pass and target is still not achieved.
Methotrexate:
- Mechanism
- Dose
- Contraindications
- side effects
- Mode of action: an anti-metabolite which acts primarily by competitively inhibiting the enzyme dihydrofolate reductase. It also has immunosuppressant properties. Folic acid 5mg once a week given 72 hours after methotrexate each week.
- Dose: usual starting dose is 7.5mg oral once a week, adjusted according to response up to a maximum of 20mg per week. See MHRA drug safety update September 2020: https://www.gov.uk/drug-safety-update/methotrexate-once-weekly-for-autoimmune-diseases-new-measures-to-reduce-risk-of-fatal-overdose-due-to-inadvertent-daily-instead-of-weekly-dosing
- Contraindications: pregnancy/breastfeeding, significant renal/hepatic impairment, blood dyscrasias, stomatitis, alcoholism, severe acute/chronic infections.
- Side-effects: renal/hepatic/pulmonary toxicity, blood dyscrasias, infections.
Methotrexate
- Drug interactions
- Monitoring
- Counselling
- What to do if toxicity occurs
- Important interactions:
- NSAIDs
- Concomitant use of some NSAIDs and high-dose methotrexate has been reported to increase and prolong the serum methotrexate concentration in serum and to increase gastrointestinal and haematological toxicity.
- co-trimoxazole/trimethoprim
- alcohol.
- liver damage
- NSAIDs
- Monitoring: FBC, U&Es and LFTs before treatment, weekly until therapy is stabilised, then every 2-3 months throughout treatment.
- Counselling:
- Report any signs of infection, respiratory, liver or blood toxicity immediately.
- Take only once a week and take folic acid at least 72 hours after methotrexate.
- Attend for regular blood tests.
- Contraception advice.
- Avoid live vaccines.
- Toxicity management: admit to hospital and may require treatment with folinic acid.
Leflunomide:
Mechanism
Dose
Contraindications
- Mode of action: A771726, the active metabolite of leflunomide, inhibits the human enzyme dihydroorotate dehydrogenase (DHODH) and exhibits anti-proliferative activity.
- Dose: 100mg daily for 3 days then 10-20mg once daily depending on severity of disease.
- Contraindications: renal/hepatic impairment, pregnancy/breastfeeding (up to 2 years after stopping treatment), serious infections, active/latent TB (test for TB prior)
- Washout procedure: see product SPC – required if toxicity (particularly liver toxicity) occurs due to extremely long half-life of leflunomide.
Sulfasalazine:
- Mechanism
- Dose
- Monitoring
Sulfasalazine:
- Mode of action: exerts immunomodulatory effects, antibacterial effects, effects on the arachidonic acid cascade, and alteration of activity of certain enzymes, which causes a net result of suppressing the inflammatory activity of RA.
- Dose: initially 500mg daily, increased by 500mg weekly until a daily dose of 2-3g is reached.
- Monitoring: FBC and LFTs should be monitored before starting treatment and every second week throughout the first 3 months of therapy, monthly for the following 3 months then once every 3 months thereafter.
