Gout is a common inflammatory arthritis typically affecting adult males, characterised by monosodium urate crystal deposition often in the first metatarsophalangeal joint, negatively birefringent crystals and punched-out juxta-articular erosions with overhanging edges and deposition of radiodense tophi.
Description
Gout is a crystal-induced inflammatory arthropathy characterised by monosodium urate (MSU) monohydrate crystals deposition in the joints, which results in recurrent attacks of arthralgia and swelling. It is caused by hyperuricaemia, a condition in which there are excessively high levels of uric acid in the blood. The excess uric acid forms crystals in the joints, causing acute bouts of pain and long-term joint damage if left untreated.
Pathogenesis
Gout pathogenesis revolves around the metabolism of purines and the subsequent formation and deposition of monosodium urate crystals in and around joints. Hyperuricaemia (plasma urate > 6.8 mg/dL), the primary risk factor for gout, may be due to overproduction or underexcretion of uric acid. The deposition of these crystals in the joints can trigger an intense inflammatory response, leading to the characteristic symptoms of gout.
- Primary uric acid overproduction accounts for 90% of gout.
- <10% of patients have a lack of hypoxanthine guanine phosphoribosyltransferase (HGPRT) which can lead to uric acid overproduction (partial deficiency or the rarer Lesch-Nyhan syndrome)
- Secondary forms of gout account for 10% of cases – chronic kidney disease, drugs (diuretics, ethanol, cytotoxics), endocrinopathies.
The distinctive patterns of gout are;
- Acute arthritis – Characterised by a dense neutrophilic infiltrate that permeates the synovium and synovial fluid.
- Chronic tophaceous arthritis – Due to chronic uncontrolled hyperuricaemia. Urate encrusts the articular surface forming visible deposits in the synovium, which becomes hyperplastic, fibrotic, and thickened by inflammatory cells. The resulting pannus destroys the underlying cartilage and leads to juxta-articular bone erosions. In severe cases, it causes fibrous or bony ankylosis resulting in loss of joint function.
- Accumulation of tophi in extraarticular sites – Pathognomonic hallmark of gout, formed by large aggregations of urate crystals surrounded by an intense inflammatory reaction of foreign-body giant cells.
- Urate (gouty) nephropathy – Urate crystals or tophi in the renal medullary interstitium or tubule causing uric acid nephrolithiasis and pyelonephritis.
Epidemiology, Risk Factors & Association
- Gout is more common in men and postmenopausal women.
- Strong male predilection of 20:1 in younger and middle-aged adults
- Prevalence increases with age (2-7% in men over the age of 65).
- Whites are more commonly affected than African Americans.
- Gout is also seen relatively frequently in young Polynesian males.
- Risk factors include dietary & lifestyle factors such as:
- High intake of Purine-rich foods (urate synthesis is the end product of purine catabolism) – e.g. red meat, seafood, spinach, and asparagus.
- High alcohol consumption, especially beer
- Obesity, hypertension
- Conditions often associated with gout include metabolic syndrome, kidney disease, and cardiovascular disease.
- Duration of hyperuricaemia – gout usually appears after 20 – 30 years of hyperuricaemia
- Genetic predisposition, including X-linked HGPRT abnormalities and primary gout, which has a multigenic pattern of inheritance
- Drugs that reduce urate excretion – e.g. thiazides
Clinical Features
- Asymptomatic hyperuricaemia
- Acute gouty arthritis – Typically first presents with sudden-onset monoarticular erythematous, warm, swollen and painful joint classically affecting the first metatarsophalangeal joint (podagra). Occasionally it is associated with a mild fever, with constitutional symptoms uncommon.
- Intercritical period – Symptom-free interval.
- Chronic tophacaeous gout – Typically non-tender yellow-white crystal which may occur anywhere in the body, including within the joint and periarticular locations such as tendons, ligaments, and bursae (particularly the olecranon bursa of the elbow). Less frequently they occur in soft tissues (earlobes, fingertips) or kidneys. Superficial tophi can ulcerate through the overlying skin.
- Gouty nephropathy – Presents with ureteral colic secondary to calculi.
Pathological Features
Microscopy
- Synovial fluid analysis: Needle-shaped, negatively birefringent monosodium urate crystals under polarised light.
Biochemistry
- Elevated serum uric acid level (>6.8 mg/dL)
- Uricosuria and an acid urine pH lead to radiolucent uric acid calculus formation with ureteral colic
- Normal during acute attacks.
Serology
- Inflammatory markers like ESR and CRP can be raised during an acute attack.
Radiological Features
General Features
- Early in the disease, X-rays are typically normal.
- Predilection for the lower limb – classically the first metatarsophalangeal joint (podagra); midfoot, ankle, and knee are also common, with small hand joints typically involved in chronic/tophaceous disease.
- Knee – patellofemoral predilection – Gout commonly involves the patellofemoral compartment and extensor mechanism (quadriceps/patellar tendons, prepatellar bursa) more than the medial/lateral tibiofemoral compartments.
- Characteristic peri-patellar findings – Intra-/peri-tendinous tophi, pre/infrapatellar bursitis, and juxta-articular overhanging edge erosions at the patella/trochlea.
- Hand and wrist distribution – Distal and proximal interphalangeal joints and intercarpal/radiocarpal joints are frequently affected in chronic/tophaceous disease; MCP joints are less commonly involved than interphalangeal joints.
- Ancillary wrist features – Tophi may deposit in the TFCC and along flexor tendons (carpal tunnel), with preserved joint spaces until late and minimal periarticular osteopenia compared with inflammatory arthritides.
XR
- Juxta-articular punched-out lytic erosions with sclerotic margins and overhanging edges
- Punched-out: Sharply defined
- Overhanging edge: Bony excrescence that extends out towards the tophus, beyond the the normal bony margin due to tophus undermining the bone.
- Joint space preservation until late in disease
- Bone density is usually normal
- Soft tissue swelling, joint effusion
- Tophi present as eccentric soft-tissue nodules within bursae or periarticular soft tissues, often showing amorphous mineralisation with subtle to dense calcification.
CT
- Can reveal tophi and bone erosions.
- Dual Energy CT: To detect uric acid in joints or radiolucent uric acid urolithiasis. Differentiates urate mineralisation and calcification. Urate crystals typically green-coloured in post-processing
US
- Gouty tophi appear as heterogeneous soft tissue masses with a mixture of hypoechoic and predominantly hyperechoic areas, sometimes producing posterior acoustic shadowing1
- Double-contour sign – represents a irregular hyperechoic line of urate crystals deposited on the hyperechoic cartilage paralleling the bone contour, usually as bright as cortex
- Snowstorm appearance – joint effusion with dependent hyperechoic punctate debris
- Acute synovitis – Synovial thickening with increased vascular flow
- Deposition of MSU crystals in the synovium generates two image signs:
- Bright stippled foci (punctiform urate deposits) – thought to be more sensitive than the double-contour sign
- Hyperechoic areas (tophi).
MR
- Signal depends on crystal density vs inflammatory/granulation tissue; calcification/crystal-rich cores are low on all sequences.
- Location patterns – Intra-/peri-tendinous and bursal tophi mirror the same signal behaviour; may show adjacent partial-thickness tendon change.
- Bone changes – Juxta-articular erosions with overhanging edges; marrow oedema is usually mild unless superinfection/osteitis.
- T1-weighted: Tophi typically iso–low to muscle; dense calcific/crystal foci are very low; adjacent marrow/oedema is low.
- T2/STIR (fluid-sensitive): Variable – from markedly low (crystal/calcific dominant) to heterogeneous intermediate–high when oedema and granulation tissue are present; perilesional oedema often conspicuous.
- PD/T2 fat-sat: Improves conspicuity of active inflammation (oedema) around a low-signal core.
- GRE/SWI: Susceptibility/blooming from calcific foci (less diffuse than PVNS/haemosiderin); useful for confirming mineralised components.
- Post-contrast – Characteristic peripheral rim and internal septal enhancement with a non-enhancing central core; associated enhancing synovitis and bursitis common.
- Pitfalls/differentials – CPPD (often more chondral calcification), rheumatoid nodules (less mineralisation), PVNS (diffuse GRE blooming); correlate with DECT or crystal analysis when uncertain.
Diagnosis
- The definitive diagnosis is made by joint aspiration showing negatively birefringent monosodium urate crystals or the presence of tophus.
- Clinical features and hyperuricaemia can support the diagnosis.
Differential Diagnoses
- Calcium pyrophosphate disease (CPPD): The most common crystalline arthropathy and the great mimicker of other arthropathies. Microscopically, positively birefringent (blue) rhomboid crystals. Hallmark radiographic finding is chondrocalcinosis.
- Septic arthritis: Can be differentiated by joint aspiration showing bacteria.
- Rheumatoid arthritis: Gout demonstrates absence of periarticular osteopaenia, absence of ligamentous laxity, absence of joint space narrowing (until late disease)
Management
- Acute attacks are managed with NSAIDs, corticosteroids, or colchicine.
- Urate-lowering therapy (e.g. allopurinol or febuxostat) is used for long-term management and prevention of gout attacks.
- Dietary modification and weight loss are also recommended.
References