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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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
Do NOT start urate-lowering therapy during an attack, but do NOT stop it if already on it
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 — never assume monomicrobial
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).
Initiating allopurinol during a flare can prolong it — but 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.
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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