Gout (Monosodium Urate Crystal–Induced Inflammatory Arthritis)

Also known as: Gouty arthritis, Acute gout, Acute gouty arthritis, Chronic tophaceous gout, Tophaceous gout, Urate crystal arthritis, Podagra

Last updated: December 18, 2024

Gout (Monosodium Urate Crystal–Induced Inflammatory Arthritis) is an inflammatory arthritis linked to monosodium urate crystals depositing in and around joints when serum urate stays high. It can cause abrupt flares of intense joint pain, swelling, warmth, and redness, often starting in one joint such as the big toe. Treatments may include anti-inflammatory drugs (NSAIDs, colchicine, or corticosteroids). With long-term urate reduction, flares may decrease and tophi may shrink.

Key Facts

•Gout represent an inflammatory arthritis caused by deposition of monosodium urate crystals within and around joints when serum urate levels are persistently elevated
•Sudden onset severe joint pain that peak within hours and occurs at rest, involving the first MTP joint (podagra)
•Diagnosed through history, physical exam, and imaging
•First-line treatment includes exercise, weight management, and activity modification

What It Is

Gout may represent an inflammatory arthritis caused by deposition of monosodium urate crystals within and around joints when serum urate levels are persistently elevated. Crystal deposition can activate the innate immune system (often via inflammasome signaling), which may lead to abrupt episodes of intense synovitis with pain, swelling, warmth, and erythema. Flares typically involve a single joint early in the disease course, commonly the first metatarsophalangeal joint, and can later become polyarticular. Over time, ongoing hyperuricemia can contribute to tophi formation and chronic joint damage, and urate crystal deposition may also occur in the kidneys.

Affected Anatomy

This condition affects several structures in and around the joint:

•Synovial membrane of the first metatarsophalangeal (MTP) joint
•Articular cartilage of the first MTP joint (metatarsal head and proximal phalanx base)
•Joint capsule and periarticular soft tissues of the midfoot (tarsometatarsal region)
•Synovium and articular cartilage of the tibiofemoral knee joint
•Olecranon bursa and peri-bursal soft tissue at the elbow (tophi-prone site)
•Auricular helix and pinna subcutaneous tissue (tophi-prone site)
•Renal collecting system and renal interstitium (urate crystal deposition and uric acid stone–related structures)
•Tendon sheaths and peri-tendinous tissues (tophi and inflammatory tenosynovitis in some cases)

Common Symptoms

Symptoms can vary in intensity and may change over time. Common experiences include:

•Sudden onset severe joint pain that can peak within hours and may occur at rest, often involving the first MTP joint (podagra)
•Marked joint swelling with warmth and erythema that can resemble cellulitis, typically localized to the affected joint
•Tenderness to light touch, where even minimal contact (such as bed sheets) may be painful
•Reduced range of motion and functional limitation during flares, which can involve difficulty walking when the foot is affected
•Fever or malaise that can occur during intense inflammatory episodes, particularly with larger-joint involvement
•Recurrent episodic flares with symptom-free intervals early on, which can become more frequent or polyarticular over time
•Tophi presenting as firm subcutaneous nodules (often on the ear, olecranon region, fingers, or toes) that may ulcerate in advanced disease
•Chronic joint discomfort or stiffness between flares in longstanding disease, which can reflect chronic synovitis or structural damage

Causes and Risk Factors

Multiple factors can contribute to the development of this condition:

Causes

•Hyperuricemia due to reduced renal urate excretion, which can be influenced by kidney function, medications, and genetic factors affecting urate transport
•Hyperuricemia due to increased urate production, which can occur with high cell turnover states and some hematologic conditions
•Dietary patterns that can raise serum urate (often purine-rich meats/seafood and high-fructose beverages), which may contribute to crystal formation in susceptible individuals
•Alcohol exposure (commonly beer and spirits) that can increase urate levels and may precipitate flares through metabolic and renal effects
•Medication-associated hyperuricemia, including diuretics and other agents that can reduce urate excretion or alter urate handling
•Physiologic stressors that can precipitate flares in predisposed individuals, including surgery, trauma, acute illness, dehydration, or rapid changes in serum urate

Risk Factors

•Male sex and increasing age, with gout typically more common in men and postmenopausal women
•Family history and genetic variants affecting urate transport (such as renal urate transporter pathways), which can increase susceptibility
•Chronic kidney disease or reduced kidney function, which can impair urate excretion
•Obesity and metabolic syndrome features (including insulin resistance), which can correlate with higher serum urate
•Hypertension and cardiovascular disease, which can be associated with hyperuricemia and medication exposures
•Dietary patterns high in purines or fructose-sweetened beverages, which can increase urate burden in some individuals
•Alcohol use (often beer and spirits), which can raise urate levels and may trigger flares
•Medication exposures that can elevate urate (commonly thiazide or loop diuretics; also some immunosuppressants), which can increase flare risk

How It's Diagnosed

Diagnosis typically involves a combination of clinical assessment and imaging studies:

•Clinical history and physical examination focusing on flare pattern, joint distribution (often first MTP), erythema/warmth, functional limitation, and assessment for tophi
•Arthrocentesis with synovial fluid analysis, where identification of needle-shaped, negatively birefringent monosodium urate crystals under polarized light microscopy can support diagnosis and can also help exclude septic arthritis
•Serum urate measurement, which can support risk assessment and long-term management context, although levels may be normal during an acute flare in some individuals
•Inflammatory markers (such as ESR and CRP), which can be elevated during flares and may help characterize inflammatory burden while remaining nonspecific
•Musculoskeletal ultrasound, which can identify features such as the double-contour sign, tophi, and effusions that may support crystal arthropathy assessment
•Dual-energy CT (DECT), which can detect and map urate crystal deposits and may be useful when aspiration is not feasible or when diagnosis is uncertain
•Plain radiography (X-ray) of affected joints, which can show erosions with overhanging edges and soft-tissue tophi in chronic disease, while often appearing normal early in the course

Treatment Options

Treatment approaches range from conservative measures to surgical interventions, often starting with the least invasive options:

Self-Care and Activity Modification

•Urate-lowering therapy (ULT) to reduce serum urate and crystal burden over time, commonly with xanthine oxidase inhibitors (such as allopurinol or febuxostat) or uricosuric therapy in selected individuals
•Lifestyle and dietary pattern modification that may lower urate burden (often weight reduction when appropriate, limiting alcohol, and reducing high-purine and high-fructose exposures), typically as an adjunct to medical therapy

Medications

•Flare prophylaxis during initiation or adjustment of ULT, often using low-dose anti-inflammatory agents for a defined span to reduce mobilization flares
•Management of contributing conditions and medication review, including addressing kidney disease, hypertension, and diuretic exposure when clinically appropriate, which can influence urate levels
•Biologic anti-inflammatory therapy targeting IL-1 signaling (such as anakinra in some settings) for refractory flares or when standard agents are not suitable, depending on local practice and patient factors

Injections and Office-Based Procedures

•Acute flare symptom control with anti-inflammatory medications such as NSAIDs, colchicine, or corticosteroids (oral, intramuscular, or intra-articular), with selection often influenced by comorbidities and contraindications
•Local therapy during flares, including joint aspiration for pain relief and diagnostic clarification, and intra-articular corticosteroid injection for accessible joints in selected cases

Surgery

•Pegloticase (intravenous uricase) for severe, refractory, tophaceous gout in selected patients, typically requiring monitoring for infusion reactions and immunogenicity
•Surgical or procedural management for complications, including tophus debulking, drainage of ulcerated tophi, or joint reconstruction/arthrodesis in advanced destructive arthropathy, in carefully selected cases

Prognosis and Recovery

The course of this condition varies between individuals:

•With effective long-term urate reduction, flare frequency can often decrease over time and tophi may shrink, although the time course can vary by baseline crystal burden and adherence factors
•Without sustained urate control, flares may become more frequent, more prolonged, and more likely to involve multiple joints, potentially progressing to chronic gouty arthritis
•Tophaceous disease can be associated with joint erosions, deformity, and functional limitation, and may require prolonged therapy spans to reduce crystal deposits
•Comorbid conditions such as chronic kidney disease, cardiovascular disease, and metabolic syndrome can complicate management and may influence outcomes
•Uric acid nephrolithiasis and urate-related kidney involvement can occur in some individuals, and prognosis may depend on overall kidney health and urate control

Joint Aspiration (Arthrocentesis)(Procedure)
Corticosteroid Injection (Joint Injection)(Procedure)
Rheumatoid Arthritis (RA)(Condition)

Frequently Asked Questions

Common symptoms include: Sudden onset severe joint pain that can peak within hours and may occur at rest, often involving the first MTP joint (podagra); Marked joint swelling with warmth and erythema that can resemble cellulitis, typically localized to the affected joint; Tenderness to light touch, where even minimal contact (such as bed sheets) may be painful; Reduced range of motion and functional limitation during flares, which can involve difficulty walking when the foot is affected; Fever or malaise that can occur during intense inflammatory episodes, particularly with larger-joint involvement.

Diagnosis typically involves: Clinical history and physical examination focusing on flare pattern, joint distribution (often first MTP), erythema/warmth, functional limitation, and assessment for tophi; Arthrocentesis with synovial fluid analysis, where identification of needle-shaped, negatively birefringent monosodium urate crystals under polarized light microscopy can support diagnosis and can also help exclude septic arthritis; Serum urate measurement, which can support risk assessment and long-term management context, although levels may be normal during an acute flare in some individuals; Inflammatory markers (such as ESR and CRP), which can be elevated during flares and may help characterize inflammatory burden while remaining nonspecific.

Treatment options range from conservative measures to surgical interventions, including: Acute flare symptom control with anti-inflammatory medications such as NSAIDs, colchicine, or corticosteroids (oral, intramuscular, or intra-articular), with selection often influenced by comorbidities and contraindications; Local therapy during flares, including joint aspiration for pain relief and diagnostic clarification, and intra-articular corticosteroid injection for accessible joints in selected cases; Urate-lowering therapy (ULT) to reduce serum urate and crystal burden over time, commonly with xanthine oxidase inhibitors (such as allopurinol or febuxostat) or uricosuric therapy in selected individuals; Flare prophylaxis during initiation or adjustment of ULT, often using low-dose anti-inflammatory agents for a defined span to reduce mobilization flares; Lifestyle and dietary pattern modification that may lower urate burden (often weight reduction when appropriate, limiting alcohol, and reducing high-purine and high-fructose exposures), typically as an adjunct to medical therapy.