Gout:
When Crystals Set a Joint on Fire

What gout is

Uric acid is a normal waste product formed when the body breaks down purines — substances found in our own cells and in many foods. It is mostly cleared by the kidneys, with some removed through the gut. When production outpaces removal, the level in the blood rises (hyperuricaemia). Above roughly 6.8 mg/dL, uric acid can no longer stay fully dissolved in body fluids, and over months to years it can crystallise as monosodium urate in and around joints, tendons and other tissues.

Those crystals can sit quietly for a long time. A flare happens when the immune system suddenly reacts to them: white blood cells engulf the crystals and trigger an intense inflammatory signal (involving a molecule called interleukin-1β), producing the pain, heat and swelling that define an attack. As the review by Dalbeth and colleagues in The Lancet emphasises, gout may look like a series of separate attacks, but it is a chronic disease — the crystal deposits remain between flares unless the uric acid level is brought down.

Not everyone with high uric acid develops gout; many people with hyperuricaemia never have a flare. But the higher and longer the level stays raised, the greater the chance.

How common it is and who gets it

Gout is common worldwide and becoming more so. The Global Burden of Disease 2021 analysis estimated that about 56 million people had gout in 2020, with prevalence around three times higher in men than in women and rising with age; the number of people affected is projected to grow substantially by 2050, mainly because populations are ageing. High body-mass index was the largest identified contributor to disability from gout.

Factors associated with gout include:

• Male sex and older age; in women, risk rises after menopause
• Family history and genetic variation in the kidney and gut transporters that handle uric acid
• Higher body weight, high blood pressure, diabetes and chronic kidney disease
• Some medicines, particularly certain diuretics ("water tablets") and low-dose aspirin
• Alcohol — especially beer and spirits — and sugar-sweetened drinks
• Diets high in meat and seafood; in a large prospective study of over 47,000 men, Choi and colleagues found higher meat and seafood intake was associated with more gout, whereas purine-rich vegetables were not, and dairy intake was associated with less

Symptoms

• Sudden, severe pain in one joint, often starting overnight and peaking within about 24 hours
• Redness, heat and marked swelling; the skin may look shiny and the joint extremely tender to touch
• The base of the big toe is the classic site, but the midfoot, ankle, knee, wrist, fingers and elbow (including the olecranon bursa) can be affected
• Flares usually settle within one to two weeks, even untreated, with symptom-free periods in between at first
• Over years of uncontrolled gout, flares can become more frequent, involve several joints, and leave firm, chalky lumps called tophi under the skin, with gradual joint damage

How it is diagnosed

The most definitive test is joint aspiration: a small sample of fluid is drawn from the swollen joint with a needle and examined under a polarising microscope for urate crystals. This also allows the fluid to be checked for infection, which matters because a septic (infected) joint can look very similar and needs urgent, different treatment.

When aspiration is not practical, gout is often diagnosed from the typical pattern combined with other tests:

• Blood uric acid (serum urate) — supportive, but it can fall to normal during a flare, so a normal result does not exclude gout; it is often rechecked a few weeks later
• Ultrasound — can show urate deposits on the cartilage surface (the "double contour" sign) and tophi
• Dual-energy CT (DECT) — a specialised CT technique that can colour-code urate deposits; availability varies
• X-rays — often normal early on, but in long-standing gout can show characteristic "punched-out" erosions
• Blood tests for kidney function, glucose and lipids — because gout often travels with kidney and cardiovascular risk factors

Conditions that can look similar

Condition	Distinguishing feature
Septic arthritis	Joint infection, often with fever and feeling unwell; joint fluid shows bacteria — a medical emergency
Cellulitis	Skin infection; redness spreads beyond the joint and the joint itself moves more freely
Calcium pyrophosphate (CPPD, "pseudogout")	A different crystal; typically affects the knee or wrist of older adults
Hallux rigidus	Gradual stiffness and a bony bump on top of the big toe joint, without sudden red-hot attacks
Injury (sprain or fracture)	A clear episode of trauma; pain follows the injury rather than appearing overnight

Treating a flare

The goal during a flare is to switch off the inflammation quickly. The 2020 American College of Rheumatology (ACR) guideline and the 2016 EULAR recommendations both endorse three main options, chosen according to the person's other health conditions and medicines:

Option	Notes
Colchicine	Works best when started within the first day or so; low-dose regimens are preferred. Dose must be adjusted for kidney function and some interacting drugs
NSAIDs	Anti-inflammatory painkillers; may not be suitable with kidney disease, stomach ulcers, heart failure or blood thinners
Corticosteroids	By mouth, or as an injection into the joint when a single large joint is affected; useful when the other options are unsuitable
Interleukin-1 blockers	Reserved in guidelines for people with frequent flares who cannot take the options above; access varies by country

Resting and elevating the joint and applying ice can help comfort alongside medicine. Trials suggest the main options are broadly comparable in effect. In the AGREE trial, Terkeltaub and colleagues found a low-dose colchicine regimen relieved early flares as effectively as a high-dose regimen but with far fewer gastrointestinal side effects. In a randomised trial of 416 emergency patients in Hong Kong, Rainer and colleagues found oral prednisolone and the NSAID indomethacin relieved pain to a similar degree, with fewer minor side effects early on in the prednisolone group.

People who have had gout before are often given a "flare kit" plan by their doctor so they can start treatment at the first twinge.

Preventing flares: urate-lowering therapy

Treating flares does not remove the crystals that cause them. The long-term strategy is to lower blood uric acid enough that existing crystals slowly dissolve and new ones do not form. Both major guidelines recommend urate-lowering therapy (ULT) for people with recurrent flares, tophi or gout-related joint damage on X-ray, and the ACR guideline recommends a "treat-to-target" approach: start at a low dose, check the blood level every few weeks, and increase the dose until serum urate is below 6 mg/dL (EULAR suggests below 5 mg/dL for severe gout).

Two practical points often surprise people. First, flares can temporarily become more frequent in the early months of ULT as crystals start to dissolve, so guidelines recommend a low-dose anti-inflammatory "cover" (commonly colchicine) for at least three to six months. Second, ULT generally works only while it is taken — it is usually long-term, and stopping it tends to let uric acid, and then flares, return.

Questions have been raised about the heart safety of febuxostat. The CARES trial (White and colleagues) in people with gout and established cardiovascular disease found febuxostat was non-inferior to allopurinol for major cardiovascular events but reported higher cardiovascular and all-cause mortality. The later FAST trial (Mackenzie and colleagues) in over 6,000 older European patients with cardiovascular risk factors found no increase in cardiovascular events or deaths with febuxostat compared with allopurinol. The choice of medicine is therefore individual and should be discussed with the treating doctor.

Lifestyle measures

Lifestyle changes help, but for most people with established, recurrent gout they are a complement to medication rather than a substitute. Commonly recommended measures include limiting alcohol (particularly beer), reducing sugar-sweetened drinks, moderating large servings of meat and seafood, losing weight where appropriate, staying well hydrated, and reviewing any medicines that raise uric acid with the prescribing doctor. Because gout is linked with high blood pressure, diabetes, kidney disease and heart disease, a check of these risk factors is part of good gout care.

Is surgery ever needed?

Surgery plays only a small role in gout. Occasionally, large tophi that are infected, discharging through the skin, pressing on nerves or tendons, or limiting shoe wear are removed surgically, and joints severely damaged by long-standing gout may need reconstructive procedures. Even then, controlling uric acid with medication remains the foundation of treatment, since crystals will otherwise continue to form.

When to see a doctor

See a doctor if you have a sudden, painful, swollen joint — particularly the first time, when the diagnosis needs to be confirmed. Seek urgent medical care if a hot, swollen joint comes with fever or chills, if you feel generally unwell, or if you have a joint replacement or a weakened immune system, as infection must be ruled out. If you already have a gout diagnosis and are still getting flares, it is worth asking about urate-lowering therapy and your target uric acid level. Gout is usually managed by a rheumatologist or an internal medicine / primary care physician.