Acute monoarticular crystal arthritis from monosodium urate deposition; classically the first MTP joint.
Also known as: gout, podagra, urate arthropathy, hyperuricemia
Overview
Crystal-induced arthropathy caused by deposition of monosodium urate (MSU) crystals in joints, tendons, and soft tissues, triggered by sustained hyperuricemia. Manifests as recurrent acute monoarticular flares progressing in some patients to chronic tophaceous disease.
Epidemiology
Most common inflammatory arthritis in men. Prevalence ~4% of US adults; rises with age, obesity, metabolic syndrome, and CKD. Premenopausal women relatively protected (estrogen is uricosuric).
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Question 1MusculoskeletalMedium
A 65-year-old man with a 3-year history of gout has had three acute flares in the past 12 months despite dietary modification. He has stage 3 chronic kidney disease (eGFR 45 mL/min/1.73 m2). He is currently between flares with no active joint inflammation. Serum uric acid is 8.9 mg/dL. He takes no urate-lowering medication. Which of the following is the most appropriate initial urate-lowering therapy?
AFebuxostat 80 mg once daily
BAllopurinol 50 mg once daily
CProbenecid 500 mg twice daily
DFebuxostat 40 mg once daily
EPegloticase 8 mg every 2 weeks
Reveal answer & full explanation
Correct answer: B — Allopurinol 50 mg once daily
AFebuxostat 80 mg once daily
BAllopurinol 50 mg once daily✓
CProbenecid 500 mg twice daily
DFebuxostat 40 mg once daily
EPegloticase 8 mg every 2 weeks
Why Allopurinol 50 mg once daily is correct
Per current ACR gout guidance, urate-lowering therapy is indicated for two or more flares per year, tophi, radiographic joint damage, or gout with stage 3 or higher chronic kidney disease — this patient qualifies on flare frequency and CKD
Allopurinol is the preferred first-line urate-lowering agent, including in CKD; it is started low (50–100 mg/day) and titrated slowly to a serum urate target below 6 mg/dL
A low starting dose with slow titration reduces the risk of allopurinol hypersensitivity and of mobilization flares
Prophylactic low-dose colchicine or an NSAID is co-prescribed during the first 3–6 months of titration
Why the others are wrong
Pegloticase 8 mg every 2 weeks — a pegylated uricase that does lower urate, but it is reserved for refractory tophaceous gout after xanthine oxidase inhibitors have failed, and its anaphylaxis and infusion-reaction risk make it indefensible in a urate-lowering-naive patient (right-goal-wrong-line)
Febuxostat 80 mg once daily — an effective xanthine oxidase inhibitor but reserved as second-line after allopurinol failure or intolerance given its boxed cardiovascular-mortality warning, and 80 mg is a high starting dose; this is the right-class-wrong-first-choice trap
Probenecid 500 mg twice daily — a uricosuric whose efficacy falls with reduced renal function and is generally avoided in stage 3 CKD; it sets the trap of ignoring the renal limitation
Febuxostat 40 mg once daily — the guideline starting dose of febuxostat (40 mg/day or less), so it looks like the safe fix for the 80 mg choice, but the drug itself is second-line: allopurinol is the strongly preferred first-line urate-lowering agent, including in stage 3 CKD, and the FDA boxed cardiovascular-mortality warning reserves febuxostat for patients who cannot take allopurinol or do not respond to it (right-dose-wrong-drug)
Question 2MusculoskeletalMedium
A 55-year-old man with a history of gout presents with 1 day of severe pain, swelling, warmth, and erythema of the right first metatarsophalangeal joint. He has stage 3 chronic kidney disease (eGFR 38 mL/min/1.73 m²) and a prior hospitalization for NSAID-induced upper gastrointestinal bleeding. Arthrocentesis yields fluid with negatively birefringent, needle-shaped crystals. Which of the following is the most appropriate treatment for this acute flare?
AOrally administered oxycodone
BOrally administered allopurinol
COrally administered indomethacin
DOrally administered colchicine
EIntra-articular triamcinolone
Reveal answer & full explanation
Correct answer: E — Intra-articular triamcinolone
AOrally administered oxycodone
BOrally administered allopurinol
COrally administered indomethacin
DOrally administered colchicine
EIntra-articular triamcinolone✓
Why Intra-articular triamcinolone is correct
The negatively birefringent, needle-shaped crystals confirm an acute monosodium-urate (gout) flare in a single accessible joint.
Two comorbidities block the usual systemic options: stage 3 chronic kidney disease (eGFR 38) and a prior NSAID-induced upper GI bleed.
An intra-articular corticosteroid delivers targeted anti-inflammatory effect with minimal systemic absorption and no renal or GI toxicity — ideal for a single joint when NSAIDs and colchicine are limited. Per current ACR gout guidance, glucocorticoids (intra-articular for a single joint) are a first-line flare option.
Why the others are wrong
Orally administered indomethacin — an NSAID, contraindicated by both the reduced eGFR and the prior GI bleed; right-disease-wrong-drug trap.
Orally administered oxycodone — provides analgesia only and does nothing to suppress the crystal-induced synovitis, so the flare runs its full course; opioids are at most an adjunct, and they add sedation, constipation, and fall risk without treating the disease.
Orally administered colchicine — effective for acute gout, but renal impairment raises the risk of colchicine toxicity (myopathy, neuropathy) and calls for close monitoring and limits on repeat courses, so it is not the safest choice here; a near-miss for a learner who forgets the renal caveat.
Orally administered allopurinol — the gout history invites urate-lowering therapy, but allopurinol has no anti-inflammatory effect and cannot settle the crystal-induced synovitis of an active flare; when newly indicated it may be started during a flare only alongside anti-inflammatory treatment and prophylaxis, never in place of them (flare-treatment-versus-urate-lowering trap).
Additional high-yield points
Oral prednisone is a reasonable systemic alternative when several joints are involved or injection is not feasible.
Continue any existing urate-lowering therapy through the flare; when newly indicated, it may be started during the flare with anti-inflammatory prophylaxis (ACR 2020).
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Sustained serum urate above the saturation threshold (~6.8 mg/dL at 37 °C) leads to MSU crystal formation in cooler peripheral tissues. Crystals are phagocytosed by macrophages, activating the NLRP3 inflammasome and releasing IL-1β, which drives neutrophil influx and acute inflammation. Chronic deposition produces tophi and erosive arthropathy.
Clinical presentation
Symptoms
Sudden onset (often nocturnal) severe monoarticular pain peaking within 12-24 hours
Classic site: first metatarsophalangeal joint (podagra) in ~50% of first attacks
Other sites: midfoot, ankle, knee, wrist, elbow, fingers
Self-limited untreated attacks resolve in 7-14 days
Recurrent flares with eventual chronic polyarticular involvement
Tophi — firm, painless subcutaneous nodules on extensor surfaces, helix of ear, Achilles tendon, finger pulps (chronic disease)
Classic findings
Podagra: red, hot, exquisitely tender first MTP joint.
Differential diagnosis
Septic arthritis — Fever, prior bacteremia, prosthetic joint; can coexist with gout — must perform arthrocentesis with Gram stain and culture in every suspected first gout attack
Pseudogout (CPPD) — Knee or wrist most common; rhomboid positively birefringent crystals; chondrocalcinosis on radiograph
Cellulitis — Diffuse erythema without joint capsule signs; no crystals; arthrocentesis distinguishes
Rheumatoid arthritis flare — Polyarticular, symmetric; tophi may be confused with rheumatoid nodules
Trauma / fracture — Mechanism and radiographs distinguish
Diagnostic workup
Diagnostic criteria
Definitive: identification of MSU crystals in joint fluid or tophus. 2015 ACR/EULAR classification criteria available for cases where aspiration is not feasible.
Gram stain and culture on every arthrocentesis to exclude concurrent septic arthritis
Serum urate (may be NORMAL during acute attack; recheck 2-4 weeks later)
CBC, ESR/CRP often elevated
BMP, urate excretion (24-h urine urate) to classify under- vs over-excretors if planning therapy
Lipid panel and A1c — frequent comorbidities
Imaging
Plain radiographs — early attacks usually normal; chronic disease shows 'rat-bite' periarticular erosions with overhanging edges, sparing of joint space until late
No urate-lowering; treat underlying metabolic disease
Gout vs pseudogout — polarized microscopy is the definitive distinction.
Treatment
First-line
Acute flare (treat ASAP, ideally within 24 h of onset):
• NSAIDs — indomethacin, naproxen, ibuprofen at full anti-inflammatory dose × 5-7 days (avoid in CKD, HF, GI bleed)
• Colchicine 1.2 mg PO, then 0.6 mg one hour later, then 0.6 mg daily-BID (renal dose adjustment; avoid in severe CKD or with strong CYP3A4/P-gp inhibitors)
• Glucocorticoids — prednisone 30-40 mg/day × 5 days with taper, or intra-articular triamcinolone (preferred if monoarticular and septic excluded)
• IL-1 inhibitor — anakinra or canakinumab for refractory or contraindication to others
Urate-lowering therapy may be started during a flare when indicated (ACR 2020, conditional), with concurrent anti-inflammatory treatment and prophylaxis; never stop urate-lowering therapy that is already running
Complications
Chronic tophaceous gout with joint destruction and disability
Urate nephrolithiasis
Chronic urate nephropathy
Coexistent metabolic syndrome and cardiovascular disease
Drug reactions: allopurinol hypersensitivity (SJS/TEN), febuxostat CV events
Septic arthritis can coexist with gout — crystals in the fluid do not exclude infection; always send Gram stain and culture
PANCE pearls
Serum urate may be normal during an acute attack — do not use it to rule out gout.
First arthrocentesis MUST include Gram stain and culture; septic arthritis and gout coexist.
Negatively birefringent (yellow when parallel to red compensator) needle-shaped crystals = gout. Positively birefringent rhomboid crystals = pseudogout (mnemonic: 'PPP' — Positive Pseudogout, Parallel).
Allopurinol does not treat a flare, but ACR 2020 permits starting it during a flare with anti-inflammatory cover; if a patient is already on it, continue without interruption.
Always co-prescribe anti-inflammatory prophylaxis (colchicine or low-dose NSAID) for 3-6 months when starting urate-lowering therapy to prevent mobilization flares.
Colchicine binds tubulin and blocks neutrophil microtubule function (chemotaxis, phagocytosis) and NLRP3 inflammasome activation; it is anti-inflammatory only and does not lower urate. Toxicity: diarrhea; myopathy and neuropathy with CKD or CYP3A4/P-gp inhibitors.
References
ACR 2020 — 2020 American College of Rheumatology Guideline for the Management of Gout (FitzGerald et al., Arthritis Care Res 2020)
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