= metabolic disorder characterized by derangement of purine metabolism manifested by:

1. Hyperuricemia ←↑ production / ↓ excretion of uric acid exceeding physiologic saturation threshold of urate (around 380 μmol/L)
   Kelley-Seegmiller syndrome = partial hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency with onset of gout in late childhood
   DDx: Lesch-Nyhan syndrome (complete HPRT deficiency)
2. Deposition of positively birefringent monosodium urate monohydrate (MSU) crystals in synovial fluid
3. Gross deposits of sodium urate in periarticular soft tissues (synovial membranes, articular cartilage, ligaments, bursae)
4. Recurrent episodes of arthritis

Age: males >40 years; gout may occur after menopause

Cause:

1. Primary Gout (90%)
   Prevalence: 1–2% of population; M÷F = 20÷1; 5% in postmenopausal women
   ◊Most prevalent form of metabolic arthritis in older men
   Disturbance:
   • overproduction of uric acid ← inborn error of metabolism
   • inherited defect in renal urate excretion
   1. Idiopathic (99%)
      • normal urinary excretion (80–90%)
      • increased urinary excretion (10–20%)
   2. Specific enzyme / metabolic defect (1%)
      1. increased activity of PP-ribose-P synthetase
      2. partial deficiency of hypoxanthine-guanine phosphoribosyltransferase
2. Secondary Gout (10%)
   ◊ Rarely cause for radiographically apparent disease
   1. increased turnover of nucleic acids:
      1. Myeloproliferative disorders + sequelae of their treatment: polycythemia vera, leukemia, lymphoma, multiple myeloma
      2. Blood dyscrasias: chronic hemolysis
   2. increase in purine synthesis de novo ← enzyme defects:
      1. Glycogen storage disease Type I (von Gierke = glucose-6-phosphatase deficiency)
      2. Lesch-Nyhan syndrome (choreoathetosis, spasticity, mental retardation, self-mutilation of lips + fingertips) ← absence of hypo-xanthine-guanine phosphoribosyltransferase
   3. acquired defect in renal excretion of urates ← reduction in renal function:
      1. Chronic renal failure
      2. Drugs, toxins: lead poisoning
      3. Endocrinologic: myxedema, hypo- / hyperparathyroidism
      4. Vascular: myocardial infarction, hypertension

Histo: tophus (PATHOGNOMONIC LESION) composed of crystalline / amorphous urates surrounded by highly vascularized inflammatory tissue rich in histiocytes, lymphocytes, fibroblasts, foreign-body giant cells (similar to a foreign-body granuloma)

Clinical stages (phases) in chronologic order:

1. Asymptomatic hyperuricemia: cumulative crystal deposition is frequently clinically silent
2. Acute gouty arthritis
   • 10% of hyperuricemic individuals develop clinical gout
   • Gout accounts for 5% of all cases of arthritis
   • Precipitated by: trauma, surgery, alcohol, dietary indiscretion, systemic infection
   • Distribution:
     1. monoarticular (90%): lower limb joints 1^st MTP joint (= podagra), tarsal joints, ankles, knees → progression to elbows + hands
     2. polyarticular (10%): any joint may be affected
     • pain, swelling, erythema of affected joint
     
     Prognosis:
     1. usually self-limited episodes (pain resolving within a few hours / days) without treatment
     2. recurrent longer attacks of acute arthritis → chronic arthropathy+ tophus deposition + renal disease
3. Chronic tophaceous gout (30% within 5 years)
   = multiple large aggregates of urate crystals + proteinaceous matrix surrounded by intense inflammatory reaction
   Prevalence:<50% of patients experience acute attacks
   Histo: cartilage degeneration + destruction, synovial proliferation + pannus, destruction of subarticular bone + proliferation of marginal bone
   Age: 5^th–7^th decades; M÷F = 20÷1
   Distribution: symmetric polyarticular disease (resembling rheumatoid arthritis), asymmetric polyarticular disease, monoarticular disease
   Site: intraarticular, extraarticular, intraosseous
   Target areas: Achilles tendon, knee extensor mechanism, popliteal tendon
   • more severe prolonged attacks
   • may ulcerate expressing whitish chalky material
   
   Cx: tendon rupture, nerve compression / paralysis
4. Gouty nephropathy / nephrolithiasis
   1. Acute urate nephropathy
   2. Uric acid urolithiasis
   • May precede arthritis in up to 20% of cases!
   • renal hypertension
   • isosthenuria (inability to concentrate urine)
   • proteinuria
   • pyelonephritis
   
   Cx: increased incidence of calcium oxalate stones (urate crystals serve as a nidus)

Location:

1. joints: hand + foot (1^st MTP joint most commonly affected = podagra) >ankle >heel >wrist (carpometacarpal compartment especially common and severe) >finger >elbow; knee; shoulder; sacroiliac joint (15%, unilateral) [pod = Greek, foot; agra = Greek, seizing]
2. Involvement of hip + spine is rare
3. bones, tendon, bursa
4. external ear; pressure points over elbow, forearm, knee, foot

◊Radiologic features present in 45% of afflicted patients but usually not seen until 6–12 years after initial attack!

• Soft tissues
  • eccentric juxtaarticular lobulated soft-tissue masses (hand, foot, ankle, elbow, knee)
    Site: tendency for extensor tendons, eg, quadriceps, triceps, Achilles tendon
  • calcific deposits in periphery of gouty tophi in 50% (sodium urate crystals are NOT RADIOPAQUE, tophi radio-graphically visible only after calcium deposition which requires an underlying abnormality of calcium metabolism)
  • bilateral effusion of bursae olecrani (PATHOGNOMONIC), prepatellar bursa
  • aural calcification
• Joints
  • joint effusion (earliest sign)
  • periarticular soft-tissue nodules
  • preservation of joint space until late in disease (IMPORTANT CLUE):
    • cartilage destruction (late in course of disease)
  • ABSENCE of periarticular demineralization ← short duration of attacks; important DDx for rheumatoid arthritis)
  • eccentric erosions with thin sclerotic margins:
    • scalloped erosion of bases of ulnar metacarpals
  • chondrocalcinosis (5%):
    Location: menisci (fibrocartilage only)
    • Patients with gout have a predisposition for calcium pyrophosphate dihydrate deposition disease (CPPD)
    
    Cx: secondary osteoarthritis
  • round / oval well-marginated subarticular cysts (pseudotumor) up to 3 cm (containing tophus / urate crystal-rich fluid)
  
  DDx: rheumatoid arthritis (marginal erosions without sclerotic rim, periarticular demineralization)
• Bone
  • “punched-out” lytic bone lesion ± sclerosis of margin = “mouse / rat bite” erosion ← long-standing soft-tissue tophus
  • “overhanging margin” (40%) = elevated osseous spicule separating tophaceous nodule from adjacent erosion (in intra- and extraarticular locations) (HALLMARK)
  • proliferative bone changes:
    • club-shaped metatarsals, metacarpals, phalanges
    • enlargement of ulnar styloid process
    • diaphyseal thickening
  • ischemic necrosis of femoral / humeral heads
  • intraosseous calcification:
    • punctate / circular calcifications of subchondral / subligamentous regions (DDx: enchondroma)
    • bone infarction ← deposits at vascular basement membrane (DDx: bone island)
• Kidney
  • renal stones (in up to 20%):
    • pure uric acid stones (84%): radiolucent on radiographs, hyperdense on CT
    • uric acid + calcium oxalate (4%)
    • pure calcium oxalate / calcium phosphate (12%)

US:

• distended joint capsule
• intra-articular echogenic material with snowstorm appearance of multiple dotted bright foci ← urate acid crystals movable with transducer pressure
• sharply defined erosion
• positive color Doppler signals ← synovitis
• lobulated echogenic mass(es) ← tophaceous gout

MR:

• tophus (most frequently) isointense to muscle on T1WI
• low to intermediate signal intensity on T2WI
• homogeneous intense enhancement

Dx: needle-shaped negatively birefringent monosodium urate crystals in aspirated joint fluid / tophus

Rx: colchicine, allopurinol (effective treatment usually does not improve roentgenograms)

DDx:

1. CPPD (pseudogout symptomatology, polyarticular chondrocalcinosis involving hyaline and fibrocartilage + degenerative arthropathy with joint space narrowing)
2. Psoriasis (progressive joint space destruction, paravertebral ossification, sacroiliac joint involvement)
3. Rheumatoid arthritis (nonproliferative marginal bone erosions, fusiform soft-tissue swelling, symmetric distribution, early joint-space narrowing, osteopenia)
4. Septic arthritis (rapid destruction of joint space, loss of articular cortex over a continuous segment)
5. Amyloidosis (bilateral symmetric involvement, periarticular osteopenia)
6. Xanthomatosis (laboratory work-up)
7. Osteoarthritis (symmetric distribution, elderly women)