gout Flashcards
what is Juvenile idiopathic arthritis
treatment
Formerly known as juvenile rheumatoid arthritis affects ~12,000 children:
Affects children under age of 16: autoimmune disease, one of the most common rheumatic diseases of childhood.
Joint and limb pains are common in children but arthritis is rare.
Treatment: NSAIDs to relieve pain and stiffness.
Many children do not require cDMARDs but cDMARDs like methotrexate is effective
Corticosteroids may be required for systemic disease (used with caution in children).
bDMARDs (e.g. biologics like TNF inhibitors adalimumab and etanercept):
Multiple NICE technology appraisals: choice considers age / treatment history/funding.
Stop if no response, time depends on bDMARD (12 weeks typically).
tsDMARDs (e.g. Janus Kinase inhibitor, tofacitinib)
Considered if cannot take TNF inhibitor or has not responded
what are the Crystal deposition diseases
Gout: monosodium urate monohydrate (MSU/MSUM) crystal deposition.
Pseudogout: calcium pyrophosphate dihydrate (CPPD) crystal deposition.
Gout and pseudogout symptoms include inflamed and painful joints.
Gout is the most common inflammatory arthritis characterised by deposition of monosodium urate crystals in joints and surrounding tissues. Between 1 in 40 people in the UK have gout; i.e. ~1.5 million people (2018).
what is gout
who is it more common in
and the risk factors
Abnormality in either uric acid metabolism (excess) and/or excretion (hyperuricaemia), resulting in deposition of uric acid crystals, which cause intermittent attacks of acute joint pain:
Great toe is most commonly affected (~75% cases); can affect other joints.
Can result in tophi (white nodules) in skin and around joints (commonly in ears, fingers, Achilles tendon, etc). Tophi occur in ~50% of people with untreated gout after 10 years (late complication).
More common in men than women (5-10:1):
‘Typical’ gout sufferer is a ~50 year old overweight male (women: post-menopause).
Risk factors family history (33%), obesity, excess alcohol intake, high purine diet, diuretics, acute infection, ketosis, surgery
Gout & causes Hyperuricaemia
Single most important risk factor for gout is sustained hyperuricaemia (due to a genetic predisposition).
Hyperuricaemia caused by (a) overproduction of uric acid or, most commonly, (b) renal underexcretion of uric acid, is the underlying cause of gout:
70% of urate is excreted by the kidneys and 30% by the GI tract.
Causes of hyperuricaemia:
Impaired renal excretion:
Idiopathic (unknown cause, spontaneous) primary gout, chronic renal disease, drug therapy (i.e. diuretics, low-dose aspirin, ciclosporin), hypertension, increased lactic acid production (intense exercise, alcohol, starvation), hyperparathyroidism, hypothyroidism, etc.
Increased production of uric acid:
Increased purine turnover (i.e. myeloproliferative disorders, lymphoproliferative disorders i.e. leukaemia, other cancers, psoriasis), increased de novo purine synthesis (biochemical abnormalities).
what is the diagnosis of gout
Serum uric acid levels:
Usually measured 4–6 weeks after acute gout attack.
Pathological hyperuricaemia is defined as serum uric acid concentration (408 μmol/L) above which monosodium urate crystals form (in vitro):
May be normal in acute attacks, but never in lower half of normal range.
Hyperuricaemia alone is not sufficient for diagnosis because most people with hyperuricaemia do not have gout.
Demonstration of monosodium urate crystals in synovial fluid:
Definitive diagnosis of gout is made by the demonstration of these crystals in synovial fluid (joint aspiration): rarely done in primary care.
Physical examination (joint pain and swelling, tophi), ultrasound, X-ray.
gout management:pharmacological treatments
Acute gout attack
1st line
Recommend NSAIDs (usually high dose), or colchicine* (when NSAIDs are contraindicated). Consider use of proton pump inhibitor.
Do not respond to, cannot
tolerate, or contraindicated for the above
Consider corticosteroid treatment
In patients where monotherapy is insufficient for treating acute
flares, combination of NSAIDs with either:
Intra-articular corticosteroid, or
Oral steroid, or colchicine
Refer to rheumatologist.
Consider Canakinumab (recomb. monoclonal antibody, anti-IL-1) if NSAIDs, colchicine or steroids are ineffective or unsuitable
naproxen
drug class
moa
indiacation and dose
cautions and contra-indications
Drug class: Non-steroidal anti-inflammatory drug (NSAID).
Mechanism of action: Irreversibly binds to cyclooxygenase (COX) enzymes in platelets, inactivating COX and preventing the production of prostaglandins (which normally promote the inflammatory response).
Indication and dose: acute gout; oral: initial dose of 750mg, then 250mg every 8 hours until attack has passed.
Cautions and contra-indications:
Avoid if patient has history of hypersensitivity to aspirin and other NSAIDS.
Avoid in patients with active GI ulceration or bleeding.
Use with caution if patient has asthma.
Use with caution with drugs that increase bleeding risk.
Use with caution in elderly (i.e. use gastroprotective treatment).
Increases risk of thrombotic events.
what is colchicine
use
side effects
An alkaloid extracted from autumn crocus.
Prevents migration of neutrophils/phagocytes into gouty joints:
Binds to tubulin resulting in depolymerisation of microtubules and reduced cell motility.
Also, it prevents release of inflammatory mediators by preventing/limiting the phagocytosis of urate crystals.
Given orally, well tolerated:
Acute gout attack (flares): 0.5mg, 2–4 times a day until symptoms relieved (e.g. pain is relieved), maximum 6mg per course.
People with moderate renal impairment: lower starting dose, or longer duration between doses is recommended.
Course not to be repeated within 3 days.
Avoid eating grapefruit or drinking grapefruit juice.
Side effects: largely GI disturbances (such as nausea, diarrhoea, vomiting, abdominal pain, etc), rhabdomyolysis (muscle damage).
what is the prevention of gout (NON-PHARMACOLOGICAL)
Key aim in the treatment of gout is to reduce the plasma uric acid levels in order to prevent the recurrence of acute gouty attacks.
Withdraw (if possible) diuretics and salicylates (e.g. do not use aspirin):
Lifestyle changes:
Lose weight.
Stop smoking.
Reduce alcohol consumption.
Do drink lots of water (unless otherwise advised).
Dietary changes:
Reduce total calorie and cholesterol intake.
Avoid purine-rich foods (i.e. Offal, red meat, certain fish e.g. anchovies, sardines, shellfish, pulses such as lentils, peas and spinach).
gout: prevention/prophylaxis (PHARMALOGICal)
Urate lowering therapy (ULT) should be discussed and started as early as possible.
ULT is recommended for those with:
Recurrent attacks (>two a year).
Tophi.
Urate arthropathy (e.g. X-ray shows joint erosion), or
renal impairment.
EULAR suggests an initial target of 360 μmol/L.
Drugs that reduce serum uric acid levels are used to prevent gout attacks:
Xanthine oxidase inhibitors (more commonly used): Allopurinol (first line therapy) and febuxostat (second line therapy) decrease uric acid production.
Uricosuric agents: (sulfinpyrazone) increases excretion of uric acid in urine.
Allopurinol, febuxostat and sulfinpyrazone should not be started during an acute attack; usually started 1–2 weeks after the attack has subsided:
Initiation of treatment may precipitate an acute attack so colchicine or NSAIDs should be used as prophylaxis and continued for up to 6 months (or more).
allopurinol
drug class
moa
indication/dose
caution and contra-indications
Drug class: xanthine oxidase inhibitor.
Mechanism of action: analogue of hypoxanthine; a competitive inhibitor of xanthine oxidase, which decreases the conversion of naturally occurring hypoxanthine into uric acid.
Indication and dose: Prophylaxis of gout, oral: initial dose of 100mg daily (preferably after food), for maintenance, dose adjusted according to plasma or urinary uric acid concentration (100 mg increments every four weeks, maximum 900 mg/day; depends on if mild/severe condition).
Cautions and contra-indications:
Withdraw therapy immediately if get a rash (if mild, can retry with caution).
May precipitate an acute attack of gout (revisit previous slide).
gout: uricosuric agents
use
Increase uric acid excretion by direct action on renal tubule.
Second line therapy: consider for patients when allopurinol is contraindicated or not tolerated, or where target serum uric acid cannot be reached.
Contraindicated in patients with renal stones.
Ineffective in patients with renal insufficiency.
what is pseudogout
who is it most common for
why it happens?
RECAP: pseudogout is a type of inflammatory arthritis characterized by sudden attacks of pain and swelling in the joints (less common than gout).
Most common in elderly people (over 80 years of age).
Often runs in families (genetic?).
Acute attacks are less severe than gout and often resemble osteoarthritis (OA):
In pseudogout, larger joints (knee, wrist) are more commonly involved.
Resembles/confused with OA due to chondrocalcinosis (calcification build up in cartilage of joints).
Not known why calcium pyrophosphate dihydrate (CPPD) crystals are deposited in articular cartilage and periarticular tissues.
May occur secondary to other diseases (i.e. OA, hyperparathyroidism, hypothyroidism and haemochromatosis, hypercalcaemia, etc).
Pseudogout: diagnosis
Physical examination (joint pain and swelling, tophi; latter is not common).
Diagnosed is confirmed through presence of small ‘brick-shaped’ crystals in synovium; can also consider ultrasound, CT scans, MRI.
Blood tests may show raised white blood cell count, mineral imbalance, e.g. low levels of magnesium.
With X-ray may see crystals and calcification of articular cartilage (chondrocalcinosis).
Pseudogout: treatment
Treatment is rest, joint aspiration (relieve pressure), NSAIDs and colchicine:
Local corticosteroid injections can sometimes be useful.
Pseudogout does not require uric acid lowering meds like allopurinol!
Chronic form of disease may lead to joint erosion so need specialist treatment (often DMARDs).
