Gout — SAQ

Stem

A 54-year-old obese man with hypertension, type 2 diabetes and chronic kidney disease (eGFR 38 mL/min/1.73 m²) presents at 3 a.m. with excruciating pain in his right great toe that reached maximum intensity within 12 hours. The first metatarsophalangeal joint is red, hot, swollen and exquisitely tender — he cannot tolerate the weight of a bedsheet. He drank six beers the previous evening. He takes bendroflumethiazide for hypertension, metformin and ramipril. Temperature 37.4 degrees C. Serum urate drawn in the emergency department is 0.42 mmol/L (7.0 mg/dL).^[9]

Questions

a) What is the most likely diagnosis, and what is the single most important differential to actively exclude? (2 marks)

The most likely diagnosis is acute gouty arthritis (podagra) — explosive monoarthritis of the first metatarsophalangeal joint. The single most important differential is septic arthritis — gout and sepsis can coexist. Aspirate for crystals, Gram stain, cell count and culture. A normal serum urate during the flare does not exclude gout: in one cohort of 221 gout patients, 39.8 percent were normouricaemic during the attack.^[9][10]

b) Outline the acute management, justifying your drug choice for this patient. (3 marks)

First, aspirate the joint. The ACR strongly recommends colchicine, an NSAID or a glucocorticoid (oral, intra-articular or intramuscular) as first-line flare treatment, chosen by comorbidity.^[1] In a 416-patient randomised equivalence trial, oral prednisolone and indomethacin had similar analgesic effectiveness, with fewer minor adverse events on prednisolone in the emergency-department phase (6 vs 19 percent).^[3] In this patient:

• Avoid NSAIDs because of chronic kidney disease.
• Low-dose colchicine (AGREE 1.8 mg total over one hour) is evidence-based for early flares but must be used cautiously in CKD and with P-gp/CYP3A4 inhibitors.^[2]
• Oral or intra-articular glucocorticoid is the safest first-line class here once sepsis is excluded on the aspirate.^[1][3]

Adjuncts: ice and joint rest. Review the thiazide once the acute situation settles.^[1]

c) He has now had three attacks this year. Outline his long-term urate-lowering plan, including the drug, how it is initiated and the target. (3 marks)

He has a strong ACR indication for ULT — frequent gout flares. Allopurinol is preferred first-line, including in moderate-to-severe CKD, started at 100 mg daily or less (lower in CKD) and titrated to a serum urate below 6 mg/dL. EULAR sets below 5 mg/dL in severe gout and adjusts allopurinol according to renal function.^[1][4]

Flare prophylaxis for at least 3 to 6 months: pooled phase-III data used colchicine 0.6 mg daily or naproxen 250 mg twice daily for up to 6 months (flare rates 3 to 5 percent versus rising to 40 percent when 8-week prophylaxis stopped).^[1][5]

A small randomised trial found starting allopurinol during an acute treated flare did not prolong it.^[6] HLA-B*5801 screening is most useful where allele frequency is at least 5 percent.^[7] Obesity and genetics explain more serum-urate variance than diet; review urate-raising diuretics.^[10]

d) Name two serious complications of inadequately treated gout and one potentially fatal drug interaction of allopurinol. (2 marks)

• Complications: chronic tophaceous gout with erosive joint disease; urate nephropathy / CKD progression; cardiovascular comorbidity (CARES enrolled patients with gout and cardiovascular disease because cardiovascular risk is increased in gout).^[11][10]
• Fatal interaction: febuxostat labelling contraindicates azathioprine and 6-mercaptopurine; allopurinol with a thiopurine also causes myelosuppression and requires a substantial thiopurine dose reduction or a switch to mycophenolate.^[8]

References11ShowHide

1. [1]FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout Arthritis Rheumatol, 2020.PMID 32390306
2. [2]Terkeltaub RA, Furst DE, Bennett K, et al. High versus low dosing of oral colchicine for early acute gout flare Arthritis Rheum, 2010.PMID 20131255
3. [3]Rainer TH, Cheng CH, Janssens HJ, et al. Oral prednisolone in the treatment of acute gout Ann Intern Med, 2016.PMID 26903390
4. [4]Richette P, Doherty M, Pascual E, et al. 2016 updated EULAR evidence-based recommendations for the management of gout Ann Rheum Dis, 2017.PMID 27457514
5. [5]Wortmann RL, Macdonald PA, Hunt B, et al. Effect of prophylaxis on gout flares after the initiation of urate-lowering therapy Clin Ther, 2010.PMID 21353107
6. [6]Hill EM, Sky K, Sit M, Collamer A, Higgs J. Does starting allopurinol prolong acute treated gout? A randomized clinical trial J Clin Rheumatol, 2015.PMID 25807090
7. [7]Yu KH, Yu CY, Fang YF Diagnostic utility of HLA-B*5801 screening in severe allopurinol hypersensitivity syndrome Int J Rheum Dis, 2017.PMID 28857441
8. [8]Logan JK, Wickramaratne Senarath Yapa S, Harinstein L, et al. Drug interaction between febuxostat and thiopurine antimetabolites Pharmacotherapy, 2020.PMID 31885095
9. [9]Lee JS, Kwon OC, Oh JS, et al. Clinical features and recurrent attack in gout patients according to serum urate levels during an acute attack Korean J Intern Med, 2020.PMID 30685959
10. [10]Dalbeth N, Gosling AL, Gaffo A, Abhishek A. Gout Lancet, 2021.PMID 33798500
11. [11]White WB, Saag KG, Becker MA, et al. Cardiovascular safety of febuxostat or allopurinol in patients with gout N Engl J Med, 2018.PMID 29527974