Gout

 

Epidemiology:

    • >20-30y

 

Common sites:

    • 1st MTP (50%)
    • insteps
    • ankles
    • heels
    • knees
    • wrists
    • fingers
    • elbows

 

Gross features:

    • monarticular (most)
    • visible deposits of urates may encrust articular surfaces and surrounding soft tissues
    • juxta-articular bone erosions
    • ankylosis in severe cases

 

Histologic features:

    • acute arthritis:
      • dense neutrophilic infiltrate in synovium and synovial fluid
      • edema and congestion of synovium
      • scattered lymphocytes, plasma cells, macrophages
    • monosodium urate crystals (long, slender, needle-shaped, negatively birefringent):
      • in the cytoplasm of the neutrophils
      • small clusters in the synovium
    • chronic tophaceous arthritis:
      • tophi – pathognomonic – large aggregates of urate crestals and the surrounding inflammatory reaction
        • macrophages, lymphocytes, large foreign body giant cells
        • may be found in articular cartilage, periarticular ligaments, tendons, and soft tissues
        • may have ulcerations of overlying skin if superficial
      • hyperplastic, fibrotic synovium thickened by inflammatory cells
      • destruction of underlying cartilage and juxta-articular bone erosions
    • gouty nephropathy:
      • deposition of monosodium urate crystals in the renal medullary interstitium
      • may form tophi, intratubular precipitations, or free uric acid crystals with uric acid stones
      • secondary pyelonephritis may ensue

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

    •  

 

Other features:

    • monosodium urate crystals
    • gout is a common end-point to a group of disorders that produce hyperuricemia ( > 7mg/dL)
      • primary – enzyme defects
      • secondary:
        • leukemias (increased nucleic acid turnover)
        • chronic renal disease
        • metabolism errors
    • extremities are a common site because they are cooler
    • urate nephropathy in chronic gout
    • Lesch-Nyhan syndrome:
      • X-linked
      • Complete lack of hypoxanthine guanine phosphoribosyl transferase (HGPRT) which recycles purine bases (nucleic acids)
      • Results in increased de novo synthesis of purine nucleotides
      • Causes build-up of uric acid
      • Severe neurologic deficits
    • Most are multifactorial inheritence
    • 20-30 years of hyperuricemia is required for gout to develop
    • other risk factors
      • heavy alcohol
      • obesity
      • drugs (thiazides)
      • lead toxicity

 

References:

    • Robbins 2005