Rheumatoid Arthritis Flashcards
What is rheumatoid arthritis?
A chronic, systemic, inflammatory, autoimmune disease characterised by inflammation of the synovial joints.
What causes rheumatoid arthritis?
Circulating antibodies which damage previously healthy tissue. These include cyclic citrullinated peptide (anti-CCP, specific to RA) and non-specific rheumatoid factor, an antibody which targets IgG antibody.
What is a synovial joint?
Freely movable joints in which the bones are encased in smooth cartilage and are separated by a joint cavity which contains synovial fluid (made by synovial membrane). Examples include elbow, hip, wrist, pivot (neck), ankles.
What are the risk factors for rheumatoid arthritis?
Genes e.g., HLA gene
Smoking
Gut microbiome
Hormonal factors
What are the symptoms of rheumatoid arthritis?
Long-term joint pain accompanied by swelling, heat, and stiffness of the joints, as well as occasionally systemic symptoms including fever and fatigue.
What are the main differences between presentation of RA and osteoarthritis?
Symptoms - symmetrical and of small joints vs asymmetrical and of weight-bearing joints.
Systemic symptoms - prominent vs unusual
Morning stiffness - >1 hour vs <30 mins
Worst time of day - morning vs progressive over day
Activity - lessens vs worsens
X-ray - damage and erosions of joints vs joint space narrowing (due to cartilage loss) and subchondral sclerosis (bone thickening).
Blood test - elevated anti-CCP and RF vs no changes
What is first line treatment of rheumatoid arthritis?
A DMARD (disease-modifying anti-rheumatic drug).
Name 3 DMARDs.
Methotrexate, Sulfasalazine, Leflunomide.
How is methotrexate dosed?
7.5mg once weekly.
How does MTX work?
Dihydrofolate reductase inhibitor which prevents aspects of nucleic acid synthesis, thus preventing DNA synthesis. This reduces cell division in rapidly dividing cells e.g., immune cells.
What are some common side effects of MTX?
Mucositis (pain and inflammation of GIT)
Myelosuppression (reduced blood cell production)
What can help reduce MTX side effects?
Folic acid 5mg weekly taken on a different day to MTX
What conditions is MTX contraindicated/cautioned in?
Hepatic impairment - avoid
Renal impairment - caution and reduce dose
Blood disorders
Pregnancy
What monitoring is required for MTX?
FBC
Renal function
Liver function
All baseline, then weekly until stabilised. Then every 2-3 months.
What are some key MTX interactions?
NSAIDs - increase risk of toxicity.
How does leflunomide work?
Dihydroorotate dehydrogenase inhibitor which prevents aspects of nucleic acid synthesis, thus preventing DNA synthesis. This reduces cell division in rapidly dividing cells e.g., immune cells.
What are some common side effects of leflunomide?
Abdominal pain
Hair loss
GI discomfort
Leucopenia
Weight loss
What conditions is leflunomide contraindicated/cautioned in?
Leucopenia
Thrombocytopenia
Anaemia
Pregnancy (teratogenic)
Hepatic impairment (metabolite accumulation)
What monitoring is required for leflunomide?
Prior to prescribing: pregnancy test, FBC, LFT.
Repeat FBC and LFTs every 2 weeks for 6 months, then every 8 weeks.
Ensure pregnancy prevention throughout.
Monitor BP.
What should be considered when stopping leflunomide?
Active metabolite persists for long time. If starting another DMARD or conception, give cholestyramine or activated charcoal for accelerated elimination.
How does sulfasalazine work?
Amino-salicylate which inhibits leukotriene B4 to reduce synthesis of platelet activating factor an inhibit leucocyte adhesion molecule upregulation i.e., anti-inflammatory and immunosuppressive effect.
What are some common side effects of sulfasalazine?
GI discomfort
Cough
Leucopenia
Skin reactions
Headache
Fever
What conditions is sulfasalazine contraindicated/cautioned in?
Renal and hepatic impairment - avoid
Pregnancy 3rd trimester - ensure adequate folate supplements taken by mother to prevent neonatal haemolysis.
How long do DMARDs take to work? What is the consequence of this?
DMARDs take 2-3 months to provide symptomatic relief, therefore short-term bridging with glucocorticoids (e.g., oral prednisolone) may be prescribed in the meantime.
What can be given if a person presenting with RA is waiting for a specialist appointment?
NSAID (ibuprofen, naproxen, diclofenac) or coxib (celecoxib, etoricoxib).
PPI if NSAID is taken long-term.
Name 2 types of biologics/anti-TNF alpha therapies used for RA and examples.
Interleukin-1 receptor antagonists - Anakinra.
IgG1l monoclonal antibodies - Infliximab, Adalimumab, Certolixumab.
How do anti-TNF alpha therapies work in RA?
Inhibit inflammatory cascade signaling involved in joint erosion.
How are anti-TNF alpha therapies administrated?
Anakinra - SC
MABs - IV and/or SC
What screening and monitoring do anti-TNF alpha therapies require?
Screen for latent TB and viral hepatitis as they can cause resurgence of dormant diseases.
Monitor neutrophil count before and then monthly.
Monitor FBC, LFTs, renal function, lipid profile, BP, weight. (varies on DMARD)
What parameters of DMARD monitoring indicate a referral?
WCC < 3.5 x 10^9/L
Mean cell volume >105fL
Neutrophils <1.6 x 10^9/L
Creatinine increased by >30%
cGFR <60ml/min
Eosinophilia >0.5 x 10^9/L
ALT >100 u/L
AST >100 u/L
Platelet count < 140 x 10^9/L
BP >140/90 mmHg
How would a flare up of RA present?
Worsened stiffness, pain and/or swelling in the affected joints, and general fatigue. Also, increased C-reactive protein (marker for inflammation).
How should a flare up in RA be dealt with.
- Rule out septic arthritis (characterised by systemic symptoms and single hot and swollen joint).
- Seek specialist advice. Give short-term glucocorticoids in the meantime.
- Specialist - intra-articular glucocorticoid injection e.g., methylprednisolone acetate.
- Add another DMARD if necessary.
What does DAS8 indicate?
Level of disease activity of RA.
> 5.1 = high disease activity. Requires inflixamb treatment.
3.2-5.1 = active disease
<3.2 = low disease activity
<2.1 = disease remission
Why should prednisolone and other oral steroids be weaned?
Abrupt withdrawal can cause acute adrenal insufficiency, hypotension or death. It can also lead to relapse.
Why should oral steroids such as prednisolone be avoided longterm?
Prolonged use can lead to:
Adrenal suppression
Increase risk of infection
Ulcers
Osteoporosis
How should oral prednisolone be weaned?
By 5mg every 3-5 days then stop
OR
If on higher doses, reduce down by 2.5mg every 3-4 days to 7.5mg per day then reduce more slowly e.g., by 2.5mg weekly.
What considerations should be taken when putting a patient on a course of oral steroids?
Keep course as short as possible as can cause adrenal suppression.
Wean dose before stopping as risk of adrenal insufficiency and death.
Can cause ulcer if used longer than a month. So consider giving a PPI e.g., lansoprazole 15mg od.
Basal and continuous monitoring of BP, BMI, HbA1c, potassium.
Do they have diabetes or osteoporosis, as this can be worsened.
