For clinicians · General Rheumatology

Gout

gouty arthritis, urate crystal arthritis, monosodium urate crystal disease

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Bottom lineGout is the most common inflammatory arthritis, caused by monosodium urate (MSU) crystal deposition driven by hyperuricaemia. Management has two arms: treating acute flares, and a treat-to-target urate-lowering strategy that dissolves the crystal burden. The 2020 ACR guideline gives a clear, largely strong evidence base: allopurinol first-line, start low and titrate, target serum urate below 6 mg/dL, with anti-inflammatory prophylaxis during initiation. Every source-dependent specific on this page is transcribed from that guideline; see the per-recommendation strengths.

Understanding this condition

What gout is

Gout is a crystal arthropathy caused by monosodium urate deposition in and around joints, driven by chronic hyperuricaemia. Acute flares reflect the inflammatory response to MSU crystals; chronic untreated disease leads to tophi, structural joint damage, and recurrent flares. It is the most common inflammatory arthritis.[1]

Common symptoms

Acute monoarticular flares, classically first metatarsophalangeal (podagra), with rapid onset of severe pain, erythema, warmth, and swelling. Common sites also include midfoot, ankle, knee, and hands. The natural history moves from intermittent flares with intercritical periods toward more frequent polyarticular flares and, if untreated, tophaceous deposits and chronic gouty arthropathy.[1]

Who gets it

Gout is the most common inflammatory arthritis, affecting roughly 3.9 percent of US adults (about 9.2 million), with a male and older-age predominance. Risk associates with reduced renal urate excretion, diuretic use, obesity, metabolic syndrome, and dietary factors. Sex ratio and non-US prevalence to confirm from primary epidemiology.[1]

How it is diagnosed

Definitive diagnosis rests on identification of MSU crystals in joint fluid or a tophus aspirate, which is described here in kind. Serum urate supports but does not confirm the diagnosis, and may be normal during an acute flare. Ultrasound (double-contour sign) and dual-energy CT can demonstrate urate deposition. The 2015 ACR/EULAR gout classification criteria exist for research; see the classification callout. Crystal-analysis detail and the classification scoring to confirm from primary sources. For research and consistency, the 2015 ACR/EULAR classification criteria are transcribed in full in the classification callout (a three-step, score-based algorithm); they are for study enrolment, not individual diagnosis.[1, 2]

What to expect over time

Prognosis is favourable with sustained urate-lowering to target, which reduces flare frequency and dissolves crystal burden, including tophi, over time. Undertreated gout progresses to chronic tophaceous disease and joint damage. Frequent association with CKD, hypertension, and cardiovascular disease warrants attention to comorbidities.[1]

Living with and treating it

The goals of treatment

Two goals: abort and treat acute flares, and lower serum urate to target with ULT to dissolve the MSU crystal burden and prevent recurrence. See the treat-to-target box. The urate target and the strong preference for a treat-to-target over fixed-dose strategy are verified from ACR 2020 Table 3.[1]

Treatment options

Flare therapy: colchicine, NSAIDs, or glucocorticoids first-line. Urate-lowering therapy: allopurinol first-line (start low, titrate to target), with febuxostat or probenecid as alternatives and pegloticase reserved for severe refractory tophaceous disease and recommended against as first-line. Anti-inflammatory prophylaxis accompanies ULT initiation for 3 to 6 months. Lifestyle measures are conditional adjuncts. Agent-level detail is on the medication guides. All positions verified from ACR 2020 (see the guideline table).[1]

Monitoring and check-ups

Serial serum urate measurement guides ULT titration to and maintenance of the target (verified, ACR 2020 Table 3). HLA-B*5801 testing before allopurinol is conditionally recommended for patients of Southeast Asian descent and African American patients (higher allele prevalence), and against in others. Monitoring intervals and agent-specific laboratory follow-up are on the medication guides.[1]

Flares and how they are treated

First-line flare therapy is colchicine, NSAIDs, or glucocorticoids (oral, IA, or IM), strongly recommended over IL-1 inhibitors or ACTH; low-dose colchicine is preferred over high-dose (high certainty). IL-1 inhibition is a conditional option when standard agents are contraindicated or poorly tolerated. Topical ice is a conditional adjuvant. ULT may be started during a flare (conditional). All verified from ACR 2020 Table 6.[1]

Living well with gout

Adherence to ULT is the dominant driver of outcome and is historically poor. Conditional lifestyle recommendations (all low or very low certainty) include limiting alcohol, purine intake, and high-fructose corn syrup, and weight loss if overweight or obese; adding vitamin C is conditionally recommended against. These are adjuncts to, not replacements for, pharmacologic urate lowering.[1]

Related conditions to watch for

Gout clusters with CKD, hypertension, metabolic syndrome, and cardiovascular disease. ACR 2020 conditionally recommends switching hydrochlorothiazide to an alternative antihypertensive where feasible and preferring losartan, conditionally recommends against stopping low-dose aspirin taken for appropriate indications, and conditionally recommends against adding or switching to fenofibrate. All very low certainty.[1]

What to expect at your appointment

Initial assessment: flare history, comorbidities and culprit medications, examination for active joints and tophi, serum urate and renal function, and joint aspiration or imaging where indicated. Shared plan centred on ULT to target plus flare management. ACR 2020 conditionally supports augmented treat-to-target protocols delivered by nonphysician providers; care may be delivered through physician-led, nurse-led, NP or PA, pharmacist-led, or ACPAC-trained extended-role practitioner models, presented non-exclusively.[1]

C2015 ACR/EULAR gout classification criteria (research); crystal identification is the clinical reference standard. Reference standard for clinical diagnosis: identification of MSU crystals in synovial fluid or a tophus; the criteria explicitly are not intended for individual diagnosis, and aspiration remains essential in practice. The 2015 ACR/EULAR classification criteria (transcribed below) apply in three steps. Entry criterion: at least one episode of swelling, pain, or tenderness in a peripheral joint or bursa. Sufficient criterion: MSU crystals in a symptomatic joint or bursa or in a tophus classifies as gout with no further scoring. If the sufficient criterion is not met, apply the Step 3 score below; a total of 8 or more (maximum 23) classifies as gout. Two categories SUBTRACT: serum urate under 4 mg/dL subtracts 4, and MSU-negative synovial fluid subtracts 2 (each reflects lower probability of gout). The reference serum-urate category, 4 to under 6 mg/dL, and any not-done imaging or fluid, score 0. Reported performance: sensitivity 0.92, specificity 0.89 (AUC 0.95); a clinical-only version without crystal or imaging data gives sensitivity 0.85, specificity 0.78.

Step 3 score (apply only if the sufficient criterion is not met) · classify if score 8 or more of a possible 23

Domain and categoryPoints
Pattern of joint or bursa involvement during symptomatic episodes (ever)
Ankle or midfoot, as part of a mono- or oligoarticular episode, without first MTP involvement1
First MTP (big toe) joint, as part of a mono- or oligoarticular episode2
Characteristics of episodes (ever): erythema over the joint; cannot bear touch or pressure; great difficulty walking or using the joint
One characteristic1
Two characteristics2
Three characteristics3
Time course of episodes (ever): a typical episode has 2 or more of, time to maximal pain under 24 hours, resolution within 14 days, complete resolution between episodes
One typical episode1
Recurrent typical episodes2
Clinical evidence of a tophus (draining or chalk-like subcutaneous nodule, often with overlying vascularity, in typical locations)
Present4
Serum urate, off urate-lowering therapy, highest value (measured by uricase method)
Under 4 mg/dL (under 0.24 mmol/L)-4
6 to under 8 mg/dL (0.36 to under 0.48 mmol/L)2
8 to under 10 mg/dL (0.48 to under 0.60 mmol/L)3
10 mg/dL or more (0.60 mmol/L or more)4
Synovial fluid of a symptomatic joint or bursa, assessed by a trained observer
MSU negative-2
Imaging evidence of urate deposition (ultrasound double-contour sign or urate on dual-energy CT) in a symptomatic joint or bursa
Present (either method)4
Imaging evidence of gout-related joint damage (at least one erosion on X-ray of the hands or feet)
Present4

Transcribed and verified from the 2015 ACR/EULAR gout classification criteria (Neogi et al, Arthritis Rheumatol 2015;67(10):2557-2568, Table 2, with Table 1 definitions). These are classification criteria for research and clinical trials, explicitly not a diagnostic tool for individual patient care; crystal identification remains the clinical reference standard.

Treat to target

Treat-to-target: lower and maintain serum urate below 6 mg/dL, with ULT dose titration guided by serial serum urate, strongly recommended over a fixed-dose strategy (target below 6 mg/dL, high certainty; treat-to-target strategy, moderate certainty). A lower target may be chosen for severe tophaceous disease. ULT is continued long term (conditional recommendation to continue indefinitely).

Verified from ACR 2020 Table 3. A lower target for severe tophaceous disease is noted in the guideline discussion; exact threshold to confirm.

Track your urate level and flaresRecord your blood urate against the target and keep a simple flare diary, save and print for your visit

Treatment ladder

  1. 1

    Treat the flare

    Acute flare: colchicine, NSAIDs, or glucocorticoids (oral, IA, or IM) first-line, chosen by patient factors; low-dose colchicine preferred. IL-1 inhibition is reserved for when standard agents are contraindicated. Topical ice is a conditional adjuvant.

    Verified from ACR 2020 Table 6. Colchicine has no dedicated general drug guide yet.

  2. 2

    Start urate-lowering therapy when indicated

    Initiate ULT for tophi, radiographic damage, or frequent flares (2 or more per year), all strong; conditionally for infrequent recurrent flares. Allopurinol is the strongly preferred first-line agent for all, including CKD stage 3 or worse, started low (100 mg/day or less, lower in CKD) and titrated.

    Verified from ACR 2020 Tables 1 and 2. Allopurinol has no dedicated general drug guide yet.

  3. 3

    Prophylaxis and titrate to target

    Give concomitant anti-inflammatory prophylaxis (colchicine, NSAIDs, or low-dose glucocorticoid) for 3 to 6 months from ULT initiation, and titrate ULT by serial serum urate to a target below 6 mg/dL, maintained long term.

    Verified from ACR 2020 Tables 2 and 3.

  4. 4

    Alternatives and refractory disease

    Alternatives to allopurinol include febuxostat and probenecid (a xanthine oxidase inhibitor is preferred over probenecid in CKD stage 3 or worse). Pegloticase is reserved for severe refractory tophaceous disease and is strongly recommended against as first-line. Switching agents when not at target is guided by ACR 2020 Table 5.

    Verified from ACR 2020 Tables 2, 4, and 5. Febuxostat, probenecid, and pegloticase have no dedicated general drug guides yet.

Guideline recommendations

TopicRecommendationStrengthGuideline
ULT for tophiFor patients with one or more subcutaneous tophi, initiate ULT (strong, high certainty).[1]StrongACR 2020 (strong, high certainty)
ULT for frequent flaresFor frequent gout flares (2 or more per year), initiate ULT (strong, high certainty). Radiographic damage attributable to gout is also a strong indication (moderate certainty).[1]StrongACR 2020 (strong, high certainty)
ULT after a first flareFor a first flare, conditionally recommend against initiating ULT, except conditionally for it with CKD stage 3 or worse, serum urate above 9 mg/dL, or urolithiasis.[1]Conditional (against, with exceptions)ACR 2020 (conditional, moderate certainty)
Asymptomatic hyperuricaemiaFor asymptomatic hyperuricaemia (serum urate above 6.8 mg/dL, no prior flares or tophi), conditionally recommend against pharmacologic ULT.[1]Conditional (against)ACR 2020 (conditional, high certainty)
Allopurinol first-lineAllopurinol is the strongly preferred first-line ULT for all patients, including CKD stage 3 or worse, over all other agents.[1]StrongACR 2020 (strong, moderate certainty)
Start low and titrateStart allopurinol at 100 mg/day or less (lower in CKD) and febuxostat below 40 mg/day, with subsequent titration to target, over a higher starting dose.[1]StrongACR 2020 (strong, moderate certainty)
Treat to target serum urateTreat-to-target ULT titration guided by serial serum urate to a target below 6 mg/dL, maintained long term, over a fixed-dose strategy (target strong, high certainty).[1]StrongACR 2020 (strong; target below 6 high certainty)
Anti-inflammatory prophylaxis at ULT startConcomitant anti-inflammatory prophylaxis (colchicine, NSAIDs, or prednisone/prednisolone) at ULT initiation, continued 3 to 6 months and longer if flares persist.[1]StrongACR 2020 (strong, moderate certainty)
Flare first-line therapyFor acute flares, colchicine, NSAIDs, or glucocorticoids (oral, IA, or IM) first-line over IL-1 inhibitors or ACTH; low-dose colchicine over high-dose (high certainty).[1]StrongACR 2020 (strong)
HLA-B*5801 testing before allopurinolConditionally test HLA-B*5801 before allopurinol in patients of Southeast Asian descent (for example Han Chinese, Korean, Thai) and African American patients; conditionally against testing in others.[1]ConditionalACR 2020 (conditional, very low certainty)
Lifestyle adjunctsConditionally recommend limiting alcohol, purine intake, and high-fructose corn syrup, and weight loss if overweight or obese; conditionally against vitamin C supplementation. All low or very low certainty, as adjuncts to ULT.[1]ConditionalACR 2020 (conditional, low to very low certainty)
Comorbid antihypertensive choiceConditionally switch hydrochlorothiazide to an alternative antihypertensive where feasible and prefer losartan; conditionally against stopping low-dose aspirin taken for appropriate indications, and against adding or switching to fenofibrate.[1]ConditionalACR 2020 (conditional, very low certainty)

Key points

PointEvidence
A treat-to-target urate-lowering strategy to a serum urate below 6 mg/dL, maintained long term, is strongly recommended (high certainty). Fixed-dose strategies are inferior.[1]·
Allopurinol is strongly recommended as preferred first-line urate-lowering therapy for all patients including moderate-to-severe CKD, started at a low dose (100 mg/day or less, lower in CKD) with titration to target.[1]·
Concomitant anti-inflammatory prophylaxis (colchicine, NSAIDs, or low-dose glucocorticoid) is strongly recommended when starting ULT, continued for 3 to 6 months and longer if flares persist.[1]·
For acute flares, colchicine, NSAIDs, or glucocorticoids (oral, intraarticular, or intramuscular) are strongly recommended first-line over IL-1 inhibitors or ACTH; low-dose colchicine is preferred over high-dose.[1]·
Lifestyle measures (limiting alcohol, purine intake, and high-fructose corn syrup, and weight loss if overweight) are each conditionally recommended, of low certainty, as adjuncts, not substitutes, for ULT.[1]·

Medication guides

Plain-language guides to the medicines used for this condition. Each has a patient and a clinician view.

Key numbers

References

  1. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744-760. doi:10.1002/acr.24180 https://doi.org/10.1002/acr.24180
  2. Neogi T, Jansen TLTA, Dalbeth N, et al. 2015 Gout Classification Criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arthritis Rheumatol. 2015;67(10):2557-2568. doi:10.1002/art.39254 https://doi.org/10.1002/art.39254