Gout: Pathophysiology and Clinical Aspects

Rheumatoid Arthritis (RA) Extra-articular Manifestations (EAM)

• EAM are manifestations outside of the joints affected by RA
• Skin: Rheumatoid nodules, Raynaud's phenomenon, palmar erythema, leukocytoclastic vasculitis, peripheral ulcers, cutaneous vasculitis
• Pleuropulmonary: Pleuritis, pleural effusion, rheumatoid lung nodules, small airway disease, interstitial lung disease, scleritis, episcleritis, keratoconjunctivitis sicca
• Eyes: Scleritis, episcleritis, keratoconjunctivitis sicca
• Cardiovascular: Atherosclerosis, myocardial infarction, pericarditis, arrhythmias, valvular heart disease
• Neurological: Entrapment neuropathy, mononeuritis multiplex, cervical subluxation
• Musculoskeletal: Osteoporotic changes, tendon, and ligament rupture
• Renal: Glomerulonephritis, secondary amyloidosis
• Hematological: Felty's syndrome, LGL syndrome, anemia, thrombocytosis
• Vascular: Vasculitis

Gout

• Gout is characterized by transient attacks of acute arthritis, initiated by urate crystals within and around joints.
• Hyperuricemia (excessive uric acid) in tissues and body fluids is a key feature, with plasma urate levels above 6.8 mg/dL.
• Gout can be primary (caused by an enzyme defect) or secondary (resulting from other underlying diseases).

Causes of Gout

• Primary Gout (90%): Enzyme defect in uric acid metabolism, such as a deficiency in hypoxanthine guanine phosphoribosyl transferase (HGPRT).
• Secondary Gout (10%): Linked to chronic renal disease, congenital conditions, and increased nucleotide turnover (e.g., leukemia).

Gout Pathophysiology

• Purine metabolism produces uric acid
• Normal serum urate levels are around 4-6 mg/dL (240-360 μM) in humans and below 1 mg/dL (60 μM) in mice.
• Uric acid excretion occurs primarily through the kidneys (80%) and gastrointestinal tract (20%).
• Elevated levels of uric acid lead to hyperuricemia and the deposition of urate crystals.
• Urate crystals induce inflammation and joint damage.

Gout Morphology

• Acute arthritis: Dense inflammatory infiltrate in the synovium and synovial fluid. Synovium is edematous and congested. Urate crystals are long, slender, and needle-shaped.
• Chronic tophaceous arthritis: Urate crystals cover the articular surface, forming chalky deposits in the synovium. Synovium becomes hyperplastic, fibrotic, and thickened. Synovium forms a pannus that destroys the cartilage. Tophi (masses of urate crystals) appear in cartilage, ligaments, tendons, and bursae.
• Gouty nephropathy: Accumulation of urate crystals/tophi in renal medullary interstitium or tubules. Uric acid nephrolithiasis and pyelonephritis can occur.

Gout Clinical Course

• Gout is associated with male sex, obesity, metabolic syndrome, excess alcohol intake, renal failure, and age greater than 30 years.
• Stages: Asymptomatic hyperuricemia, acute arthritis (joint pain, hyperemia, warmth; often monoarticular, 50% in the first metatarsophalangeal joint), asymptomatic interval, and chronic tophaceous gout (loss of joint space).

Calcium Pyrophosphate Crystal Deposition Disease (CPPD)

• Also known as pseudogout, CPPD is characterized by calcium pyrophosphate crystal deposition.
• It primarily affects individuals over 50 years old.
• CPPD is categorized as sporadic (idiopathic), hereditary, or secondary.
• Secondary types are associated with previous joint damage, hyperparathyroidism, hemochromatosis, and diabetes.
• Crystals initially deposit in articular cartilage, menisci, and with enlargement, may rupture and seed the joint.
• Inflammation, while present, is usually milder than in gout.
• CPPD is often asymptomatic.
• Joint involvement can be monoarticular or polyarticular.

Test your knowledge on gout, its pathophysiology, and clinical features with this quiz. Discover key concepts surrounding gouty tophi, hyperuricemia, and risk factors. Ideal for medical students and healthcare professionals looking to strengthen their understanding of this condition.