🔍 What Is Gout?
Gout is the most common crystalline inflammatory arthritis, resulting from deposition of monosodium urate (MSU) crystals in joints and soft tissues; this typically occurs when serum uric acid exceeds ~6.8 mg/dL, exceeding crystallization thresholds OHSU+15PMC+15BioMed Central+15. The first metatarsophalangeal (MTP) joint (podagra) is affected in ~50% of cases. Gout flares are driven by innate immune activation, especially via the NLRP3 inflammasome Wikipedia+1PMC+1.
🌐 Epidemiology
- Global prevalence rose by ~22.5% from 1990 to 2020, affecting ~660 per 100,000 people (~55.8 million individuals) publichealth.jmir.org+3clinexprheumatol.org+3The Lancet+3.
- Prevalence in developed nations: 3–5% adults, increasing—e.g. 3.6% to 5.1% in the US (2011–2018) .
- Incidence ~0.1–0.3% annually; male-to-female ratio roughly 3–4:1 .
- Rising incidence in adolescents has been documented, with a 23% increase from 1990 to 2021 Frontiers.
- High-risk groups include individuals in high-SDI countries, those with obesity, renal impairment, and metabolic syndrome Frontiers+2PMC+2publichealth.jmir.org+2.
🧬 Pathophysiology
- Hyperuricemia arises from impaired renal excretion (90%) or overproduction (~10%) MDPI.
- Predisposition involves genetic variants in transporters like SLC2A9, ABCG2, and SLC22A12 clinexprheumatol.org.
- MSU crystals activate the NLRP3 inflammasome, releasing IL-1β and triggering acute inflammation MDPI+1PMC+1.
⚠️ Risk Factors
- Non-modifiable: Male sex, older age (post‑menopausal in women), family history, genetic predisposition.
- Modifiable: Obesity, hypertension, dyslipidemia, CKD, metabolic syndrome, diet (red meat, seafood, fructose, alcohol), certain medications (diuretics, low-dose aspirin, cyclosporine) .
- Environmental exposures: lead toxicity, chemotherapy, systemic disease.
🩺 Clinical Presentation & Staging
- Acute gout: Rapid onset (<12 hours) of intense monoarticular joint pain—most often 1st MTP—accompanied by swelling, erythema, and warmth Wikipedia.
- Systemic symptoms: mild fever, malaise.
- Stages of gout:
- Asymptomatic hyperuricemia
- Acute intermittent gout (flair & remission)
- Intercritical gout (no symptoms between flares)
- Chronic tophaceous gout (tophi, erosive disease)
🧪 Differential Diagnosis
Consider:
- Pseudogout (CPPD)
- Septic arthritis
- Psoriatic or reactive arthritis
- Rheumatoid arthritis
- Osteoarthritis flare
- Cellulitis, bursitis, tenosynovitis
🔬 Investigations
- Synovial fluid analysis: pathognomonic MSU crystals (needle-shaped, strong negative birefringence) OHSUPMC+15Wikipedia+15PMC+15jrd.or.kr+1verywellhealth.com+1.
- Serum uric acid: may be normal during acute attacks.
- Inflammatory markers: CRP/ESR elevated.
- Renal function & lipids: evaluate comorbidities.
- Imaging:
- US/DECT: detect tophi and crystal deposits even interictally Wikipedia.
- X-ray: chronic erosions with overhanging edges.
🧾 Management
Acute Gout
According to 2020 ACR guidelines:
- Options: NSAIDs, colchicine, or systemic corticosteroids are all viable first-line treatments PMC+2PMC+2rheumatology.org+2.
- Low-dose colchicine: 1.2 mg then 0.6 mg an hour later. Higher doses avoided due to GI toxicity Wikipedia.
- Intra-articular steroids or joint aspiration with steroid injection useful for large joints.
Chronic Management & Prophylaxis
- Target serum urate < 6 mg/dL (< 5 mg/dL with tophi) OHSU.
- Urate-lowering therapies (ULT):
- Allopurinol preferred first-line; start low (100 mg/d, adjust by renal function), titrate q2–5 weeks Agency for Care Effectiveness+2PMC+2thescottishsun.co.uk+2OHSU+1Wikipedia+1.
- Febuxostat alternative if allopurinol-intolerant.
- Uricosurics (probenecid, benzbromarone) appropriate in under-excretors.
- Pegloticase used for refractory, tophaceous gout.
- Flare prophylaxis during ULT initiation (6+ months): low-dose colchicine, NSAIDs, or prednisone OHSUAgency for Care Effectiveness.
- Lifestyle: diet modification, weight loss, alcohol reduction, hydration, treat comorbidities, and switch diuretics to uricosuric agents (e.g., losartan) .
🏥 Complications
- Tophi: collections of MSU in soft tissues leading to deformity and erosions.
- Urolithiasis: urate stones in 10–40% of patients.
- Urate nephropathy: kidney impairment.
- Cardiovascular risk: flares associated with transient CV events; gout independently linked to HTN, diabetes, CKD, and mortality .
📊 Prognosis
- ~60% experience a recurrent flare within 1 year if untreated .
- Early and sustained urate control reverses tophi and limits joint damage.
- Life expectancy modestly reduced (~13%) due to comorbidity burden.
✅ Key Takeaways
- Gout is a common, rising, systemic inflammatory disease with crystal-driven pathophysiology.
- Diagnosis requires confirmation of MSU in fluid; imaging assists in subclinical detection.
- Management encompasses acute control and chronic urate lowering, guided by 2020 ACR/NICE recommendations OHSU.
- Addressing comorbidities and risk factors is essential to optimize outcomes.
