Gout: Causes, Symptoms, Diagnosis, and Treatment

Gout: Causes, Symptoms, Diagnosis, and Treatment

Gout is a form of inflammatory arthritis caused by the deposition of urate crystals in the joints and other tissues, resulting from high levels of uric acid in the blood. When the uric acid concentration in extracellular fluid exceeds the solubility limit of urate, monosodium urate crystals precipitate in tissues, causing inflammation and pain.

Causes:

• Increased uric acid (AU) production in blood:

• Due to increased endogenous purine synthesis: Deficiency of HPRT enzyme, increased activity of PRPP enzyme.

• Due to increased nucleotide degradation.

• Due to excessive consumption of purine-rich foods.

• Decreased AU excretion via kidneys:

• Kidney failure.

• Lead-induced nephropathy.

• Use of medications that can increase AU, such as cyclosporine, pyrazinamide, ethambutol.

Classification:

• Primary gout: Due to genetics or diet.

• Secondary gout: Due to kidney failure, acute leukemia, certain medications (diuretics, anti-tuberculosis drugs, corticosteroids), excessive cell breakdown (chronic myeloid leukemia, hemolytic anemia, psoriasis), risk factors (total hip arthroplasty, obesity, metabolic syndrome, hyperinsulinemia, insulin resistance, alcohol consumption).

Diagnosis:

• Bennet and Wood diagnostic criteria (1968):

• AU crystals found in joint fluid or tophi.

• Or at least 2 of the following criteria:

• History of at least 2 episodes of sudden, severe joint swelling and pain, resolving completely within 2 weeks.

• History or current episode of swelling and pain in the great toe joint with similar characteristics as above.

• Presence of tophi.

• Good response to colchicine (reduced inflammation and pain within 48 hours) in the past or present.

• Diagnosis of chronic gout: When the following symptoms are present:

• Tophi.

• Chronic arthritis due to urate deposits.

• Gout-related kidney disease: kidney failure, kidney stones.

Symptoms:

• Acute gout attack: Starts suddenly, severe pain, redness, swelling, warmth, joint stiffness, commonly occurring in the great toe joint.

• Chronic gout:

• Tophi: Painless, hard, round, varying in size. Skin covering tophi is usually normal, thin, and may show the white color of urate crystals. Common locations: earlobes, olecranon, edges of affected joints, feet, hands, wrists, within tendons (especially Achilles tendon). Tophi may become acutely inflamed or discharge a chalky material.

• Chronic arthritis due to gout: Due to urate deposition around soft tissues adjacent to joints, around cartilage, around bones, causing mechanical joint pain, progressing subacutely, primarily affecting joints affected during acute gout attacks. X-rays may show cavities, defects, and femoral head necrosis associated with gout.

• Kidney disease due to urate deposition: Urate stones, interstitial nephritis, kidney failure.

Staging of Chronic Gout Severity according to ACR 2012:

• Mild: Stable disease, tophi in one joint.

• Moderate: Stable disease, tophi in 2-4 joints.

• Severe: Multiple tophi, complications.

Laboratory investigations:

• Blood AU test:

• Male > 420 U/l.

• Female > 360 U/l.

• 24-hour urinary AU:

• Increased AU excretion (> 600 mg/24h): AU-lowering medications that increase excretion should not be used.

• Decreased excretion (< 600 mg/24h).

• Joint fluid analysis:

• High cell count, inflammatory fluid (> 50k white blood cells/mm3), predominantly neutrophils.

• MSU crystals found: Diagnosis of gout. Crystals are needle-shaped, located inside or outside cells. Under polarized microscopy, crystals polarize strongly, exhibiting birefringence.

• Kidney function tests.

• Inflammation tests: ESR elevated, CRP elevated.

• X-ray: Almost normal.

• Comorbidities: Metabolic syndrome.

• Digital polarized microscopy.

• Ultrasound and energy Doppler ultrasound.

• Dual energy CT.

• MRI.

• Arthroscopy.

Differential diagnosis:

• Infective arthritis: Joint fluid culture, may be combined with gout.

• Rheumatoid arthritis: Gender, age, characteristics of acute inflammatory episodes, tophi, blood AU, X-ray.

Treatment:

• Treatment of acute gout attack:

• Colchicine: 1 mg/day, taken at night, maintained for 15 days. Rapid pain relief within 48 hours.

• Nonsteroidal anti-inflammatory drugs (NSAIDs): Etoricoxib, meloxicam, diclofenac.

• Corticosteroids: Topical (diprospan, hydrocortisone) or systemic doses.

• Treatment to prevent gout recurrence:

• Goal: AU < 360 (with tophi) or AU < 300 (without tophi).

• Medications:

• Uricosuric agents.

• Colchicine, low-dose NSAIDs, prednisolone.

• Diet: Limit purine-rich foods.

• Treatment to prevent lowering of blood uric acid:

• Goal: Reduce blood AU below the solubility limit (male < 6.0 mg/dL, female < 5.5 mg/dL).

• Indications:

• Presence of tophi.

• Stage 2 kidney failure.

• Kidney stones.

• Chronic arthritis due to gout.

• 2 acute gout attacks/year.

• Patients under 40 years old, AU > 480 ml/l and with accompanying diseases.

• Drug choice:

• Xanthine oxidase inhibitor group: Allopurinol, febuxostat.

• AU-increasing group: Probenecid.

• Dosage: Adjust dosage based on AU and kidney function.

• Side effects: HLA B 5801 screening should be performed before allopurinol treatment to avoid allergies and death.

• Combination therapy: Multiple medications can be combined for better treatment effectiveness.

Resistant gout:

• Biologics.

Notes:

• Adjust colchicine dosage according to kidney function.

• Combine medications appropriately based on disease severity.

• Adhere to a suitable diet.

• Monitor medication side effects closely.

Conclusion:

Gout is a chronic disease that can be controlled with early and appropriate treatment. You should follow your doctor’s instructions for the best treatment outcomes.