Doctors Revision

Gout Therapy: Acute Attacks, Colchicine, NSAIDs, Allopurinol, Febuxostat & Uricosurics

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Emergency safety: A hot, swollen, exquisitely painful joint may be septic arthritis, not gout. If there is fever, systemic toxicity, immunosuppression, prosthetic joint, skin breach, unusual joint involvement or diagnostic uncertainty, aspirate the joint and arrange urgent treatment. Do not let a serum urate result or a previous gout label delay antibiotics and drainage when infection is possible.

Gout therapy: complete pharmacology of acute attacks, urate lowering and prevention

Gout is an inflammatory crystal arthritis caused by deposition of monosodium urate crystals in joints, peri-articular tissues and sometimes the kidneys or skin. Hyperuricaemia reflects excess urate production, reduced renal/gastrointestinal excretion, or both. Drug treatment has two different targets:

Acute flare treatment

Rapidly suppress inflammation and pain using an NSAID, colchicine or a glucocorticoid. Choose one according to kidney function, gastrointestinal and cardiovascular risk, interactions, joint number and time since onset.

Long-term urate-lowering therapy (ULT)

Lower serum urate below the saturation target, dissolve crystals and prevent flares, tophi, erosions and uric-acid stones. Main agents are allopurinol, febuxostat and selected uricosurics; pegloticase is reserved for refractory disease.

Prevention and comorbidity care

Use anti-inflammatory prophylaxis when ULT is started, address obesity, alcohol, hypertension, kidney disease and medicine triggers, and monitor serum urate to a target.

Important distinction: colchicine, NSAIDs and corticosteroids treat the inflammation of a flare but do not remove urate. Allopurinol, febuxostat, probenecid and other ULTs prevent future attacks but do not give immediate analgesia.

Learning objectives

  • Explain urate production, excretion, crystal deposition and the stages of gout.
  • Differentiate acute-flare medicines from chronic urate-lowering medicines.
  • Give safe adult doses for NSAIDs, colchicine, glucocorticoids, allopurinol, febuxostat, probenecid, pegloticase and selected specialist agents.
  • Recognise contraindications, interactions, renal/hepatic dose issues and life-threatening toxicities.
  • Apply treat-to-target prescribing, flare prophylaxis, lifestyle measures and emergency joint-assessment principles.

1. Pathophysiology and clinical stages

Uric acid production and excretion

Uric acid is the end product of human purine metabolism. Adenine and guanine from endogenous cell turnover and dietary nucleoproteins are converted through hypoxanthine and xanthine; xanthine oxidase catalyses the final steps to uric acid. Humans lack functional urate oxidase, so uric acid is the terminal product.

  • Approximately two-thirds of daily urate elimination occurs through the kidneys (the reference deck gives roughly 300–600 mg/day).
  • The gastrointestinal tract contributes roughly one-third (about 100–300 mg/day) through intestinal secretion and bacterial metabolism.
  • At physiological pH, urate is mainly monosodium urate; when its concentration exceeds solubility, needle-shaped crystals form.
  • Crystals activate the NLRP3 inflammasome, interleukin-1β, neutrophils and other inflammatory pathways, producing the abrupt pain and swelling of a flare.

Causes and risk factors

Mechanism Examples Clinical implication
Reduced renal excretion Chronic kidney disease, dehydration, hypertension, insulin resistance and older age. Allopurinol is usually preferred; uricosurics may be ineffective or unsafe.
Drug-related retention Thiazide and loop diuretics, low-dose aspirin at some doses, cyclosporin, tacrolimus, pyrazinamide, ethambutol and niacin. Review the indication; do not stop cardioprotective aspirin without medical advice.
Overproduction High cell turnover, myeloproliferative disease, tumour lysis, some inherited enzyme disorders and high purine load. Consider xanthine-oxidase inhibition or uricolysis; treat the underlying illness.
Diet and lifestyle Beer and spirits, sugary fructose drinks, obesity, dehydration and large purine-rich meals. Dietary changes support but do not replace ULT when indicated.

Stages of gout

  • Asymptomatic hyperuricaemia: urate is elevated but there has been no gout flare or tophus. Routine pharmacologic ULT is generally not indicated; investigate causes and risk.
  • Acute gout: sudden severe monoarthritis or oligoarthritis, often at night or early morning. The first metatarsophalangeal joint (podagra), ankle, knee, midfoot, wrist, elbow and fingers may be affected. Untreated first attacks often last 3–14 days.
  • Intercritical gout: symptom-free interval between attacks. It is not cure; crystals may continue accumulating. A second attack often occurs within two years, but timing varies.
  • Chronic tophaceous gout: recurrent attacks, persistent synovitis, tophi, erosions, deformity, disability and possible uric-acid nephrolithiasis or nephropathy.

2. Diagnosis before treatment

Definitive diagnosis

Demonstration of negatively birefringent, needle-shaped monosodium urate crystals in aspirated synovial fluid is the diagnostic standard. A high serum urate supports the diagnosis but is not specific, and serum urate can be normal during a flare. A dramatic response to colchicine is not diagnostic because other inflammatory conditions may improve coincidentally.

Differentials that must not be missed

  • Septic arthritis: fever, rigors, toxic appearance, high inflammatory markers, immunosuppression or prosthetic joint; aspirate urgently and start empiric antibiotics when indicated.
  • Calcium pyrophosphate deposition (pseudogout): rhomboid, positively birefringent crystals.
  • Cellulitis, traumatic haemarthrosis, reactive arthritis, rheumatoid flare, osteomyelitis and necrotising infection.

Baseline assessment

  • Joint examination, temperature, vital signs, urate, CBC/FBC, creatinine/eGFR, electrolytes, liver tests, glucose and cardiovascular risk.
  • Review alcohol, diet, diuretics, aspirin, cytotoxic therapy, transplant medicines and family history.
  • Record tophi, kidney stones, frequency of flares, radiographic damage and functional limitation.

3. Acute gout flare: immediate management

First steps

  1. Rest and elevate the affected joint; a cool pack may reduce pain.
  2. Start anti-inflammatory treatment as early as possible, ideally at the first symptom.
  3. Choose an NSAID, colchicine or corticosteroid based on comorbidity and contraindications. Do not combine two NSAIDs.
  4. Continue an established ULT during a flare unless a clinician identifies severe toxicity; do not abruptly stop it.
  5. Use joint aspiration when septic arthritis remains possible.

3.1 NSAIDs

NSAIDs inhibit COX-1 and COX-2, reducing prostaglandin synthesis and the pain, vasodilation and oedema of crystal inflammation. They can be very effective, often taking 12–24 hours for a clear response, and many patients tolerate them better than high-dose colchicine.

NSAID Common adult acute-gout regimen Important limits
Indomethacin 50 mg orally three times daily for 2–3 days, then reduce to 25 mg three times daily and stop as the flare resolves. High GI, CNS and renal toxicity; avoid in older/high-risk patients when alternatives exist.
Naproxen 500 mg orally twice daily, or 750 mg initially followed by 250–500 mg every 8–12 hours, according to local protocol. Use the lowest effective duration; consider gastroprotection in GI-risk patients.
Diclofenac 50 mg orally two or three times daily for a short course. Higher cardiovascular risk; avoid in established cardiovascular disease where possible.
Piroxicam 20–40 mg/day initially, then 20 mg/day if used. Long half-life and high GI toxicity make it a less attractive choice.
Etoricoxib 120 mg orally once daily for up to 8 days where licensed. COX-2 cardiovascular and blood-pressure risk; avoid in uncontrolled hypertension or cardiovascular disease.

NSAID contraindications and interactions

  • Active peptic ulcer or GI bleeding, severe renal impairment, significant heart failure, uncontrolled hypertension, recent myocardial infarction/stroke, severe liver disease, NSAID hypersensitivity or aspirin-sensitive asthma.
  • Use extreme caution with anticoagulants, antiplatelets, corticosteroids, SSRIs, ACE inhibitors/ARBs plus diuretics (“triple whammy”), lithium, methotrexate and nephrotoxic medicines.
  • Adverse effects include dyspepsia, ulceration, GI haemorrhage, fluid retention, oedema, hypertension, acute kidney injury, bronchospasm, rash and cardiovascular events.
  • Consider a proton-pump inhibitor when GI risk is significant; gastroprotection does not remove renal or cardiovascular risk.

3.2 Colchicine

Colchicine is an alkaloid from Colchicum autumnale. It is not an analgesic and does not reduce serum urate. It suppresses crystal inflammation by binding tubulin, disrupting microtubules, neutrophil chemotaxis, phagocytosis and inflammasome signalling. It works best when taken at the first sign of discomfort.

Adult dose

  • Acute flare, low-dose regimen: 1.2 mg orally at the first sign, followed one hour later by 0.6 mg. Do not exceed 1.8 mg during that initial course unless a specialist protocol says otherwise.
  • Flare prophylaxis while starting ULT: 0.6 mg once or twice daily, usually for at least 3–6 months and longer if flares or tophi persist.
  • Renal or hepatic impairment, older age and interacting medicines may require a lower dose or longer interval. Do not repeat courses too soon.

Adverse effects and toxicity

  • Common, dose-dependent: diarrhoea, nausea, vomiting, abdominal cramps and anorexia.
  • Serious: bone-marrow suppression, pancytopenia, neuromyopathy, rhabdomyolysis, alopecia, multiorgan failure and death.
  • Stop and seek urgent help for persistent vomiting/diarrhoea, muscle pain or weakness, numbness, bruising, fever or reduced urine output.

Contraindications and interactions

  • Severe renal or hepatic impairment combined with a strong CYP3A4 or P-glycoprotein inhibitor is particularly dangerous.
  • Macrolides (especially clarithromycin), azole antifungals, ciclosporin, tacrolimus, verapamil, diltiazem, ritonavir and some HIV medicines can cause fatal accumulation.
  • Statins, fibrates and other myotoxic drugs increase neuromuscular toxicity; monitor for myalgia or weakness.
  • Do not use colchicine as a substitute for diagnosing septic arthritis, and never assume that severe diarrhoea means “the gout is clearing.”

3.3 Glucocorticoids

Glucocorticoids suppress inflammatory gene transcription, cytokine production, leukocyte trafficking and oedema. They are valuable when NSAIDs and colchicine are contraindicated or inadequate, and when several joints are involved.

Route Common example When useful
Oral Prednisolone 30–40 mg once daily for 5–10 days, or 0.5 mg/kg/day for about 5–10 days followed by a short taper if needed. Polyarticular flare, renal disease or inability to use NSAIDs/colchicine.
Intra-articular Triamcinolone acetonide or methylprednisolone; dose depends on joint size, commonly 10–40 mg. One or two accessible joints after aspiration and exclusion of infection.
Intramuscular/IV Methylprednisolone 40–125 mg parenterally may be used in selected severe cases; specialist/local emergency protocol controls dose. Unable to take oral medication or severe flare requiring monitored care.
  • Monitor glucose, blood pressure, mood, infection and fluid retention. Diabetes is a relative contraindication, not an automatic reason to leave a severe flare untreated.
  • Do not inject a joint until septic arthritis is reasonably excluded.
  • Adverse effects include hyperglycaemia, insomnia, dyspepsia, mood change, hypertension, infection and rebound flare after abrupt withdrawal of a prolonged course.

3.4 Combination treatment

For very severe polyarticular disease, a specialist may combine colchicine with an NSAID, or an NSAID with an intra-articular steroid, while monitoring toxicity. Do not combine systemic steroids with multiple NSAIDs casually, and never use two NSAIDs together.

4. Urate-lowering therapy: when and why to start

Indications

  • Tophaceous gout.
  • Radiographic joint damage due to gout.
  • Frequent flares, commonly two or more per year.
  • Recurrent uric-acid nephrolithiasis or selected CKD/high-risk cases after individual assessment.
  • Patients who prefer definitive prevention after recurrent attacks.

The supplied deck states that urate-lowering drugs should be delayed until an acute flare is controlled and may begin 1–2 weeks after resolution. Current ACR guidance allows starting ULT during a flare when indicated, provided effective anti-inflammatory treatment and follow-up are in place. The practical lesson is to avoid starting or changing ULT without flare prophylaxis and education, not to withhold indicated treatment indefinitely.

Treat-to-target

  • Start low and titrate every few weeks using serial serum urate measurements.
  • Usual target: serum urate <6 mg/dL (360 micromol/L); a lower target may be considered for severe tophaceous disease.
  • Continue ULT long term once target is reached; stopping commonly allows urate to rise and flares to recur.
  • Prophylactic colchicine, low-dose NSAID or low-dose prednisolone is strongly recommended during initiation, usually for at least 3–6 months and longer if active disease persists.

5. Xanthine-oxidase inhibitors

5.1 Allopurinol

Allopurinol is a purine analogue that inhibits xanthine oxidase. Its active metabolite, oxypurinol (alloxanthine), is a longer-acting non-competitive inhibitor. Reduced uric-acid synthesis lowers crystal formation and gradually mobilises urate from joints, soft tissues and kidneys.

Indications

  • Preferred first-line ULT for most patients, including many with moderate-to-severe CKD when started at a low dose.
  • Recurrent flares, tophi, urate stones, erosive disease and selected secondary hyperuricaemia.
  • Tumour-lysis prevention in patients receiving cytotoxic therapy, with different timing and dosing.

Adult dosing

Patient Starting dose Titration and usual range
Normal renal function 100 mg orally once daily. Increase by 50–100 mg every 2–5 weeks according to serum urate; common maintenance 200–300 mg/day, sometimes 400–800 mg/day in divided doses under specialist supervision.
CKD or high-risk patient 50 mg/day or 50–100 mg/day depending on eGFR and local protocol. Increase slowly; renal disease is a reason to start low, not automatically to avoid allopurinol.
Prophylaxis Begin colchicine 0.6 mg once or twice daily, or an alternative anti-inflammatory, when ULT is started. Continue prophylaxis while titrating and until disease activity is controlled.

Adverse effects and contraindications

  • Nausea, vomiting, diarrhoea, headache, drowsiness, rash and abnormal liver tests.
  • Allopurinol hypersensitivity syndrome: fever, diffuse rash, facial oedema, eosinophilia, hepatitis, renal failure, mucosal involvement, Stevens–Johnson syndrome or toxic epidermal necrolysis. Stop immediately and treat as a medical emergency.
  • Do not start during asymptomatic hyperuricaemia alone. Use caution in renal disease, liver disease and prior drug rash.
  • HLA-B*58:01 testing is conditionally recommended for high-risk ancestry groups, including many Southeast Asian populations and African-American patients; local Ugandan policy and ancestry-specific evidence should guide testing.

Interactions

  • Allopurinol inhibits metabolism of azathioprine and 6-mercaptopurine. If unavoidable, their dose must be drastically reduced (often by about 75% or more) with specialist monitoring; otherwise avoid the combination.
  • Increases risk of rash with ampicillin/amoxicillin and can interact with warfarin, theophylline and some antivirals.
  • Thiazide-associated renal impairment may increase hypersensitivity risk.

Monitoring

Check baseline serum urate, CBC, chemistry, creatinine/eGFR and liver tests. Measure serum urate after each titration and periodically once stable. Educate the patient to report any rash immediately; never “push through” an unexplained rash.

5.2 Febuxostat

Febuxostat is a non-purine, selective xanthine-oxidase inhibitor. It is rapidly absorbed, highly protein bound and metabolised mainly by glucuronidation. It is useful when allopurinol is not tolerated, contraindicated or insufficiently effective, but the cardiovascular safety warning makes patient selection important.

  • Starting dose: 40 mg orally once daily.
  • After two weeks: if serum urate remains above 6 mg/dL, increase to 80 mg once daily; some countries/products allow 120 mg under specialist guidance.
  • Indication: chronic gout with inadequate response to maximally titrated allopurinol, intolerance or inability to use allopurinol.
  • Warning: patients with established cardiovascular disease had higher cardiovascular mortality in a major outcomes study; discuss alternatives and monitor chest pain, dyspnoea, neurologic symptoms and palpitations.
  • Contraindicated with: azathioprine or 6-mercaptopurine because xanthine-oxidase inhibition causes severe toxicity; avoid or specialist-adjust theophylline.
  • Adverse effects: gout flares during initiation, liver-test abnormalities, nausea, rash, arthralgia and cardiovascular events.
  • Check LFTs before and during treatment; provide flare prophylaxis.

6. Uricosuric drugs

Uricosurics increase renal urate excretion by inhibiting proximal-tubular reabsorption through urate transporters such as URAT1 and organic-anion transport systems. They work best in under-excretors with adequate renal function and can cause uric-acid stones if hydration and urine chemistry are neglected.

6.1 Probenecid

Mechanism and indications

  • Blocks URAT1 and related transport pathways, reducing proximal-tubular urate reabsorption.
  • Useful when xanthine-oxidase inhibitors are unsuitable or as add-on therapy in selected patients with persistent hyperuricaemia.
  • Also inhibits renal secretion of penicillin and some other drugs, which is a separate pharmacological use.

Adult dose

  • 250 mg orally twice daily for one week, then 500 mg twice daily.
  • If necessary, increase by 500 mg/day every four weeks according to tolerance and serum urate; common maximum is 2 g/day, although some specialist references permit higher doses.
  • Encourage liberal fluid intake and consider urine alkalinisation when stone risk is high, following local protocol.

Contraindications, adverse effects and interactions

  • History of uric-acid stones, significant renal impairment or creatinine clearance below the effective range (often <50–60 mL/min), acute nephropathy, dehydration or inability to maintain fluid intake.
  • GI upset, rash, headache, nephrolithiasis, renal colic, haematuria, hypersensitivity and rare nephrotic syndrome or aplastic anaemia.
  • Probenecid increases concentrations of penicillins, cephalosporins, methotrexate, sulfonylureas and several other renally secreted drugs.
  • High-dose salicylates antagonise its uricosuric effect. Do not stop cardioprotective aspirin without a clinician’s risk–benefit decision.

6.2 Sulfinpyrazone

Sulfinpyrazone is an older uricosuric, rarely available in current practice. The supplied deck gives a starting dose of 100–200 mg twice daily, increased over 2–3 weeks to 600 mg/day; maintenance is often 200 mg/day in divided doses, with a maximum of 800 mg/day.

  • Adverse effects include nausea, vomiting, diarrhoea, abdominal pain, GI bleeding, rash, marrow suppression, agranulocytosis, thrombocytopenia, hepatitis, renal impairment, sodium retention and acute renal failure.
  • Reduce in mild-to-moderate renal impairment and avoid in severe disease or stone history.
  • Because safer alternatives exist, use only under a specialist/local formulary protocol.

6.3 Benzbromarone

Benzbromarone blocks renal urate reabsorption and may increase intestinal urate elimination. It is not widely available in many countries because of hepatotoxicity.

  • Dose from the reference deck: 50–200 mg orally once daily.
  • Adverse effects: GI symptoms, gout flare during initiation, uric-acid stones, renal colic and potentially severe liver injury.
  • Use only where licensed, with baseline and serial liver tests and clear stopping criteria.

General uricosuric rules

  • Do not use in significant renal impairment or previous nephrolithiasis without specialist assessment.
  • Start low, hydrate, consider urine alkalinisation where indicated and continue anti-inflammatory prophylaxis.
  • Uricosurics are preventive; they do not terminate an acute flare.

7. Uricolytic enzymes

7.1 Pegloticase

Pegloticase is a PEGylated recombinant urate oxidase (uricase). It converts insoluble uric acid to soluble allantoin, which is readily excreted. It is reserved for severe chronic gout refractory to conventional ULT, especially with tophi or ongoing disability.

  • Dose: 8 mg IV infusion every two weeks in specialist care; current labels may co-administer methotrexate 15 mg orally weekly with folic/folinic acid to reduce anti-drug antibodies, depending on local protocol.
  • Premedicate with antihistamine and corticosteroid, observe during and after infusion and have anaphylaxis equipment ready.
  • Check serum urate before each infusion. A rise above 6 mg/dL on two consecutive checks suggests loss of response and high infusion-reaction risk; discontinue under specialist guidance.
  • Serious adverse effects: anaphylaxis, infusion reactions, gout flares, heart-failure exacerbation and anti-drug antibodies.
  • Stop the infusion immediately for chest tightness, wheeze, hypotension, urticaria or angio-oedema and treat as anaphylaxis.

7.2 Rasburicase

Rasburicase is another recombinant urate oxidase. It is not routine chronic gout treatment. Its main role is rapid control of chemotherapy-induced hyperuricaemia and tumour lysis syndrome in high-risk leukaemia, lymphoma or solid-tumour patients.

  • Dose: 0.2 mg/kg by IV infusion over 30 minutes once daily for up to 5 days.
  • Emergency warning: contraindicated in G6PD deficiency because hydrogen peroxide generated during urate oxidation can cause severe haemolysis and methemoglobinaemia.
  • Suspected haemolysis presents with jaundice, dark urine, falling haemoglobin, back pain, hypoxia or cyanosis; stop the drug, give urgent supportive care and involve haematology.
  • Blood samples for uric acid must be kept cold and processed promptly because rasburicase can continue degrading urate in the tube and produce a falsely low result.

8. Drug selection by clinical situation

Patient situation Reasonable direction Avoid or use caution
Acute flare, healthy adult NSAID, colchicine or oral steroid started early. Do not combine two NSAIDs or delay treatment while waiting for urate.
CKD or renal impairment Low-dose colchicine with adjustment, oral/intra-articular steroid; allopurinol started low for long-term control. High-dose NSAID, standard colchicine repetition, probenecid without specialist review.
Peptic ulcer or anticoagulant use Colchicine or corticosteroid depending on renal/hepatic function. NSAIDs because of GI bleeding risk.
Diabetes Colchicine or carefully monitored NSAID; steroid if necessary with glucose plan. Unmonitored high-dose steroid hyperglycaemia.
Established cardiovascular disease Allopurinol is usually preferred for ULT; choose acute therapy based on individual risk. Febuxostat without a cardiovascular risk discussion; NSAIDs in high-risk patients.
Recurrent tophi or erosions Treat-to-target ULT, usually allopurinol or febuxostat, with prophylaxis; specialist escalation if refractory. Stopping ULT when symptoms improve.
Uric-acid stone history Xanthine-oxidase inhibitor, hydration and urine-directed care. Probenecid and other uricosurics unless a specialist specifically advises.
Chemotherapy tumour lysis risk Allopurinol prophylaxis or rasburicase for high-risk established hyperuricaemia. Rasburicase in G6PD deficiency.

9. Lifestyle, comorbidity and medicine review

  • Maintain hydration unless fluid restriction is required; dehydration precipitates attacks.
  • Reduce beer, spirits, sugar-sweetened/fructose drinks, large portions of red meat, organ meat and some seafood. A balanced diet is more sustainable than extreme fasting.
  • Gradual weight loss, exercise and control of blood pressure, diabetes and lipids reduce overall risk.
  • Review thiazide and loop diuretics where clinically feasible. Losartan has a modest uricosuric effect, and fenofibrate may lower urate; changing therapy must preserve cardiovascular and renal indications.
  • Do not stop low-dose aspirin prescribed for secondary cardiovascular prevention without medical advice; its cardiovascular benefit usually outweighs a modest urate effect.
  • Avoid crash diets and excessive alcohol after a flare; abrupt dietary changes can themselves change urate and precipitate attacks.

10. Monitoring and patient education

Before ULT

  • Serum urate, CBC, creatinine/eGFR, electrolytes and liver tests.
  • History of rash or allopurinol hypersensitivity, CKD, stones, cardiovascular disease, peptic ulcer, anticoagulation and medicine interactions.
  • Examine for tophi and document the baseline flare frequency and functional impact.

During titration

  • Measure serum urate every 2–5 weeks after dose changes until target is reached, then periodically.
  • Check kidney and liver function and ask about rash, fever, GI toxicity, stone symptoms and adherence.
  • Explain that early flares can increase when crystals mobilise; this is not treatment failure. Use prophylactic colchicine/NSAID/steroid and continue ULT.
  • Write the exact dose, timing, maximum dose and duration; check combination cold, pain or antibiotic medicines.

When to seek emergency care

  • Fever with a hot joint, rigors, confusion or hypotension.
  • Rash with fever or mucosal lesions while taking allopurinol or another new medicine.
  • Persistent vomiting/diarrhoea, severe weakness or muscle pain on colchicine.
  • GI bleeding, black stool, reduced urine or chest pain on NSAIDs.
  • Wheeze, hypotension or angio-oedema during pegloticase infusion.
  • Sudden severe breathlessness or chest pain suggesting pulmonary embolism or a cardiovascular event.

11. Emergency clinical cases

Case 1: first hot swollen joint

A 58-year-old man has abrupt severe first-toe pain and a temperature of 38.5°C. He has diabetes and chronic kidney disease. Do not assume gout. Aspirate if possible, send Gram stain/culture and crystal analysis, obtain blood cultures if septic, and start appropriate antibiotics when infection is suspected. Once sepsis is excluded, choose a renal-safe anti-inflammatory plan.

Lesson: sepsis outranks the convenience of treating a presumed gout flare.

Case 2: recurrent gout and CKD

A patient has four flares and tophi with eGFR 35 mL/min/1.73 m². Start low-dose allopurinol and titrate to serum urate <6 mg/dL, with adjusted colchicine prophylaxis or another anti-inflammatory. Do not default to probenecid, which may be ineffective and increase stone risk in CKD.

Lesson: “renal disease” changes the starting dose and monitoring, not the need for disease modification.

Case 3: allopurinol rash

Two weeks after starting allopurinol, a patient develops fever, facial oedema and widespread rash with mucosal soreness. Stop allopurinol immediately, assess for organ involvement, admit and involve dermatology/toxicology. This may be allopurinol hypersensitivity or Stevens–Johnson syndrome.

Lesson: a rash is not a minor expected effect until serious hypersensitivity has been excluded.

Case 4: colchicine toxicity

A patient with CKD takes colchicine while receiving clarithromycin and develops profuse diarrhoea, muscle weakness and pancytopenia. Stop colchicine and interacting drugs, provide supportive care, check FBC/renal/liver tests and CK, and seek urgent toxicology advice.

Lesson: CYP3A4/P-glycoprotein interactions can make a low dose fatal.

Case 5: tumour lysis

A patient with aggressive lymphoma develops hyperuricaemia, hyperkalaemia, hyperphosphataemia and rising creatinine after chemotherapy. This is tumour lysis syndrome, not ordinary gout. Start the local TLS protocol, give intensive hydration and use rasburicase when indicated; check G6PD status and monitor electrolytes and renal function in a high-dependency setting.

Lesson: the uricolytic drugs in the gout lecture have an important oncology emergency role.

12. High-yield revision summary

  • Gout results from monosodium urate crystals caused by hyperuricaemia from overproduction, under-excretion or both.
  • A normal serum urate during a flare does not exclude gout; crystals in aspirated synovial fluid are definitive.
  • Always exclude septic arthritis before injecting a joint or treating diagnostic uncertainty as routine gout.
  • Acute flare options are NSAIDs, colchicine or glucocorticoids; start early and choose according to comorbidity.
  • Colchicine dose: 1.2 mg at first symptom, then 0.6 mg one hour later; prophylaxis 0.6 mg once or twice daily. Diarrhoea, myopathy and marrow toxicity are warning signs.
  • Allopurinol is preferred first-line ULT for most patients, including many with CKD. Start ≤100 mg/day (lower in CKD) and titrate to urate <6 mg/dL.
  • Allopurinol plus azathioprine/6-mercaptopurine can cause fatal toxicity unless the purine analogue dose is drastically reduced under specialist supervision.
  • Febuxostat starts at 40 mg daily and may rise to 80 mg after two weeks; discuss the cardiovascular mortality warning and avoid with azathioprine/6-mercaptopurine.
  • Probenecid starts 250 mg twice daily for one week, then 500 mg twice daily; it requires functioning kidneys, hydration and stone-risk assessment.
  • Pegloticase is 8 mg IV every two weeks for refractory chronic gout; monitor urate and anaphylaxis risk. Rasburicase 0.2 mg/kg IV daily for up to five days is mainly for tumour lysis and is contraindicated in G6PD deficiency.
  • Starting ULT can precipitate flares; use prophylaxis, continue ULT consistently and titrate by serial serum urate rather than symptoms alone.

Sources for further study

Educational disclaimer: Gout medicines require patient-specific decisions based on renal function, liver function, cardiovascular risk, pregnancy, infection, drug interactions and local availability. Verify the current Ugandan formulary and manufacturer information before prescribing.

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