General
=========================================================================

• Transient attacks of acute arthritis initiated by crystallization of urates and neutrophils, followed by chronic gouty arthritis with tophi in joints and urate nephropathy
• Causes 2-5% of chronic joint disease

Sites
=========================================================================

• 50% have initial attack in first metatarsophalangeal joint; also ankles, heels, knees, wrists, fingers, elbows

Pathophysiology
=========================================================================

• Gout is due to hyperuricemia (present in 10% of population, although only half develop gout) and deposition of monosodium urate crystals in joints and viscera and uric acid kidney stones
• Need serum urate > 7 mg/dl for deposition (saturation threshold for urate at 98.6 F)
• Uric acid/urate is product of metabolic breakdown of purine nucleotides
• Two pathways for purine synthesis: de novo (creates purines) and salvage pathway (HGPRT)
• HGPRT deficiency causes increased synthesis via de novo pathway, leading to hyperuricemia (The Medical Biochemistry Page)
• Primary gout (90%): idiopathic (85%) with overproduction of uric acid (may have normal excretion) or known enzyme defects (partial hypoxanthine-guanine phosphoribosyl transferase deficiency [HGPRT])
• Secondary gout (10%): increased nucleic acid turnover due to leukemia/lymphoma, chronic renal disease, HGPRT deficiency
• Lesch-Nyan syndrome: rare; men with HGPRT deficiency causing hyperuricemia, severe neurologic deficits with mental retardation, self-mutilation, gouty arthritis (chart; OMIM 300322)
• Arthritis: synovial fluid is poorer solvent for sodium urate than plasma, so with hyperuricemia, urates in joint fluid crystallize, particularly in ankle due to lower temperature; crystals develop in synovial lining cells, stimulate formation of antibodies, which accelerates formation of new crystals; release of crystals attracts neutrophils and complement, generates C3a, C5a, attracts more neutrophils, releases free radicals, releases lysosomal enzymes which eventually causes acute arthritis that last days to weeks without treatment; repeated attacks of acute arthritis cause chronic arthritis and formation of tophi in synovial membranes and periarticular tissue, which eventually damages joints

Clinical features
=========================================================================

• Males more commonly affected
• In women, onset occurs at very late age (Clin Rheumatol 2010;29:575)
• Risk factors for gout with hyperuricemia are age > 30 years, familial history of gout, alcohol use, obesity, thiazide administration, lead
• Aspirate: grossly white-gray and granular; strongly negative birefringent needle-shaped crystals under polarized light; foreign body giant cells

Case reports
=========================================================================

• 55 year old man with 10 year history of pain in ankle joints followed by involvement of first metatarsophalangeal joint (Indian J Med Sci 2004;58:349)
• 59 year old Chinese man with 30 year history of psoriasis vulgaris, 13 year history of polyarthralgia and 5 year history of painful mass on foot (Eur J Dermatol 2009;19:184)
• 66 year old obese woman suffering from a systemic polyarthritis for 3 years (J Orthop Surg (Hong Kong) 2005;13:203)
• 73 year old man with elbow pain (Arch Pathol Lab Med 2002;126:621)

Clinical images
=========================================================================

Milky effusion associated with gout

Various images

Various images

Fingers

Chalky white appeareance

Gross description
=========================================================================

• Chalky white appearance of gouty deposits

Gross images
=========================================================================

White deposits

Micro description
=========================================================================

• Early - edematous synovium with acute and chronic inflammatory infiltrate
• Late - tophi (large aggregates of urate crystals, granulomatous inflammation, hyperplastic fibrotic synovium); gout crystals are long, slender, needle shaped, but difficult to visualize with routine staining because they are dissolved during formalin processing (crystals are water soluble); easier to identify on scrape or with alcohol fixation
• With chronic disease, urate deposits may be present in soft tissue, ligaments, skin
• Gouty deposits may be surrounded by fibrous tissue and be rimmed by histiocytes and giant cells

Micro images
=========================================================================

1. Xray
2. Diff-Quick
3. Pap smear
4. Polarized light
5. H&E

Uric acid crystals

Needle shaped monosodium crystals

Sodium urate crystals - polarized light

Typical granuloma

 

Big toe

Differential diagnosis
=========================================================================

• Crystal deposition: deposition of calcium pyrophosphate, calcium phosphate, talc, methyl methacrylate (prosthetic joints)

This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).