Gout — Viva

Q1: A patient presents with an acutely hot, swollen first MTP. Take me through your diagnostic approach and the key differential you must not miss. (2 min)

Acute monoarthritis of the first MTP is classical podagra, but the approach is to aspirate for polarised-light microscopy, cell count, Gram stain and culture. MSU crystals in synovial fluid or a tophus are sufficient for classification. The differential I must not miss is septic arthritis — crystals do not exclude coexisting sepsis. Distinguish pseudogout by rhomboid, positively birefringent CPPD crystals. A normal serum urate during the flare does not exclude gout (39.8 percent of 221 patients in one cohort were normouricaemic during the attack).^[9][10]

Q2: Walk me through the management of an acute attack — your three options and how you choose. (3 min)

The ACR strongly recommends colchicine, an NSAID or a glucocorticoid (oral, intra-articular or intramuscular) as first-line flare treatment, chosen by comorbidity.^[1] Low-dose colchicine 1.8 mg total over one hour matched high-dose 4.8 mg for 24-hour pain response in AGREE, with diarrhoea in 23.0 percent versus 76.9 percent on high-dose.^[2] Oral prednisolone and indomethacin had similar analgesic effectiveness in a 416-patient equivalence trial, with fewer early minor adverse events on prednisolone (6 vs 19 percent).^[3] Avoid NSAIDs in CKD, heart failure, active peptic ulcer and anticoagulation; caution colchicine in CKD and with P-gp/CYP3A4 inhibitors; prefer a glucocorticoid when both are unsuitable.

Q3: When do you start long-term urate-lowering therapy, and how exactly do you do it? (2 min)

The ACR strongly recommends initiating ULT for tophaceous gout, radiographic damage due to gout, or frequent gout flares. EULAR says ULT should be considered from the first presentation, with serum urate below 6 mg/dL and below 5 mg/dL in severe gout.^[1][4] Allopurinol is preferred first-line, including in moderate-to-severe CKD, started at 100 mg daily or less (lower in CKD) and titrated by serial serum urate. Give anti-inflammatory prophylaxis for at least 3 to 6 months (trial regimens: colchicine 0.6 mg daily or naproxen 250 mg twice daily).^[5] Screen HLA-B*5801 where allele frequency is at least 5 percent.^[7] Febuxostat starts under 40 mg/day; CARES found higher all-cause (HR 1.22) and cardiovascular (HR 1.34) mortality versus allopurinol in gout with cardiovascular disease.^[11]

Q4: What is the molecular mechanism of the acute gout attack, and how does that explain the drugs that work? (2 min)

Monosodium urate crystals activate the NLRP3 inflammasome, releasing IL-1 beta — the key initiator of the gout flare. That is why an interleukin-1 blocker is considered when colchicine, NSAIDs and corticosteroids are contraindicated, and why colchicine, NSAIDs and glucocorticoids remain first-line anti-inflammatories.^[10][4][1] Aggregated neutrophil extracellular traps are important in the resolution phase. Long-term urate-lowering (for example allopurinol) dissolves crystals; nurse-led gout care produces major improvements in outcomes.^[10]

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