Medicine – Gout

Gout is an inflammatory crystal arthropathy caused by the deposition of monosodium urate crystals within joints and surrounding tissues. These crystals form when serum urate levels are persistently elevated, leading to crystal precipitation and an intense inflammatory response. Gout most commonly affects the first metatarsophalangeal joint, producing the classic presentation known as podagra, although virtually any joint can be involved.

1. Monosodium Urate Crystal Deposition

The underlying abnormality in gout is the accumulation of monosodium urate crystals within articular and periarticular tissues. Crystal deposition stimulates a strong inflammatory reaction, resulting in sudden attacks of severe pain, swelling, warmth, and erythema. Repeated attacks can eventually lead to chronic joint damage and the development of tophi.

2. Diagnosis by Joint Aspiration

The most definitive way to diagnose gout is by identifying urate crystals in synovial fluid obtained from an affected joint. Joint aspiration is particularly important when the diagnosis is uncertain or when septic arthritis must be excluded.

3. Crystal Appearance

Under polarised light microscopy, monosodium urate crystals are typically needle-shaped and strongly negatively birefringent. This finding helps distinguish gout from pseudogout, in which calcium pyrophosphate crystals are usually rhomboid-shaped and positively birefringent.

4. Typical Joint Involvement

The first metatarsophalangeal joint is the most characteristic site of gout. An acute attack often presents with sudden, intense pain, swelling, redness, and extreme tenderness, sometimes developing overnight. However, gout can also involve the ankles, knees, wrists, fingers, elbows, and other joints.

Causes of Gout

Hyperuricaemia can result from either increased urate production, decreased renal excretion, or drug-related effects. In many patients, more than one factor contributes.

1. Increased Production of Urate

Increased Purine Synthesis

Some patients overproduce urate because of increased purine synthesis. This may be idiopathic, meaning that no specific cause is identified.

A rare inherited cause is Lesch–Nyhan syndrome, an X-linked disorder of purine metabolism caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase. This leads to excessive purine breakdown and marked hyperuricaemia.

Increased Turnover of Preformed Purines

Conditions associated with rapid cell turnover can produce excessive breakdown of nucleic acids and therefore increased urate formation. These include lymphoproliferative and myeloproliferative disorders, chronic haemolytic anaemias, and other states with accelerated cell destruction.

Cytotoxic chemotherapy can also cause a sudden rise in urate because of rapid tumour cell breakdown, particularly in tumour lysis syndrome.

2. Decreased Urate Excretion

Idiopathic Reduced Excretion

In many patients with gout, the main abnormality is reduced renal excretion of urate without an identifiable secondary cause.

Chronic Renal Failure

Chronic kidney disease reduces the ability of the kidneys to eliminate urate efficiently, leading to progressive hyperuricaemia and an increased risk of gout.

Increased Organic Acids

Certain metabolic states raise the concentration of organic acids that compete with urate for renal tubular excretion. This can occur with alcohol excess, starvation, vigorous exercise, and ketoacidosis, all of which may contribute to acute attacks in susceptible individuals.

3. Drugs

Diuretics

Thiazide and loop diuretics, such as furosemide, can reduce renal urate excretion and increase the risk of hyperuricaemia and gout.

Low-Dose Salicylates

Low-dose salicylates can also reduce urate excretion and therefore contribute to hyperuricaemia. Their effect differs from that of very high salicylate doses, which may increase urate excretion.

Treatment of Gout

Acute Gout

1. NSAIDs

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat acute attacks by rapidly reducing joint inflammation and pain. Drugs such as naproxen or other appropriate NSAIDs may be used if there are no contraindications.

2. Colchicine

Colchicine is another effective treatment for acute gout. It suppresses the inflammatory response to urate crystals by interfering with neutrophil activity. It is most effective when started early in the attack.

3. Corticosteroids

Corticosteroids may be used when NSAIDs or colchicine are unsuitable. They can be given systemically or, when one or a few joints are involved, by intra-articular injection after joint infection has been excluded.

Prevention of Recurrent Gout

Allopurinol

Allopurinol is a xanthine oxidase inhibitor that reduces the formation of uric acid. It is used as long-term urate-lowering therapy to prevent recurrent attacks and reduce tophus formation.

Allopurinol is generally introduced as part of a long-term prevention strategy rather than used solely to treat the pain of an acute attack. Serum urate levels are monitored and the dose is adjusted to achieve an appropriate target.

Modern prevention may also include other urate-lowering therapies, such as febuxostat, depending on the patient’s clinical situation, kidney function, drug tolerance, and treatment response.

Key Clinical Pattern

Gout is best remembered as an acute inflammatory arthritis caused by monosodium urate crystals, which are needle-shaped and negatively birefringent. The first MTP joint is the classic site, and the major mechanisms are either excess urate production or reduced renal excretion. Acute attacks are treated with NSAIDs, colchicine, or corticosteroids, while recurrent disease is prevented with urate-lowering therapy such as allopurinol.