Guidelines for Diagnosis of Gout in Primary Care: An Updated Approach

Overview

This guideline provides updated recommendations for the diagnosis and management of gout, specifically tailored for primary care settings. It aims to equip healthcare professionals with the necessary tools and knowledge for effective diagnosis, acute flare management, long-term care strategies, and appropriate referral pathways for patients with gout. This guideline supersedes previous recommendations (TA164 and ESNM23), incorporating the latest evidence and best practices in gout care.

Target Audience

This guideline is designed for:

• Healthcare professionals delivering NHS-commissioned services, particularly in primary care.
• Commissioners of health and social care services involved in resource allocation and service planning.
• Individuals affected by gout, their families, and caregivers seeking reliable information.
• The general public interested in understanding gout and its management.

Recommendations

Central to these guidelines is the principle of patient-centered care. Individuals have the right to actively participate in discussions and make informed decisions about their health management, aligning with NICE’s principles on shared decision-making. These guidelines are intended to support healthcare professionals in applying evidence-based practices while considering individual patient circumstances and preferences.

1.1. Diagnosis and Assessment

Symptoms and Signs Indicative of Gout

1.1.1. Initial Suspicion: Clinicians should suspect gout in patients presenting with the following hallmark signs and symptoms:

• Rapid Onset Severe Pain: Characterized by an abrupt and intense onset of pain, frequently occurring overnight. This pain is often accompanied by significant redness and swelling, typically affecting one or both first metatarsophalangeal (MTP) joints (the joint at the base of the big toe).
• Tophi: The presence of tophi, which are visible deposits of urate crystals in soft tissues, is a strong indicator of established gout.

1.1.2. Consideration in Other Joints: Gout should also be considered in patients experiencing rapid onset severe pain, redness, or swelling in joints beyond the first MTP joint. Common sites include the midfoot, ankle, knee, hand, wrist, and elbow.

1.1.3. Differential Diagnosis: In patients presenting with a painful, red, and swollen joint, it is crucial to differentiate gout from other conditions such as:

• Septic Arthritis: A bacterial infection within the joint, requiring urgent intervention.
• Calcium Pyrophosphate Crystal Deposition (CPPD): Also known as pseudogout, this condition shares similar symptoms with gout but involves a different type of crystal.
• Inflammatory Arthritis: Including rheumatoid arthritis, psoriatic arthritis, and other inflammatory joint conditions.

1.1.4. Immediate Referral for Suspected Septic Arthritis: If septic arthritis is suspected based on clinical assessment, immediate referral via the local care pathway is mandatory to ensure prompt and effective treatment.

1.1.5. Chronic Gouty Arthritis: Consider chronic gouty arthritis in individuals presenting with persistent inflammatory joint pain. This form of gout develops over time and can lead to joint damage and deformity if left unmanaged.

1.1.6. Comprehensive Assessment: For all patients with suspected gout, a thorough medical history and physical examination are essential. This assessment should focus on characterizing the specific symptoms and signs (as outlined in recommendations 1.1.1 and 1.1.2) to guide diagnostic and management strategies.

Image alt text: Clinical presentation of gout affecting the first metatarsophalangeal joint, demonstrating redness and swelling.

Diagnostic Confirmation

1.1.7. Serum Urate Measurement: In individuals exhibiting symptoms and signs suggestive of gout (recommendations 1.1.1 and 1.1.2), measure serum urate levels to support clinical diagnosis. A serum urate level of 360 micromol/litre (6 mg/dl) or greater is considered elevated. If the initial serum urate level is below 360 micromol/litre during an acute flare, and clinical suspicion for gout remains high, repeat the measurement at least 2 weeks after the flare has subsided to obtain a more accurate baseline.

1.1.8. Joint Aspiration and Synovial Fluid Microscopy: If the diagnosis of gout is still uncertain after serum urate testing, consider joint aspiration and microscopic analysis of synovial fluid. This procedure allows for the definitive identification of urate crystals within the joint fluid, confirming the diagnosis.

1.1.9. Imaging Modalities: In cases where joint aspiration is not feasible or the diagnosis remains unclear, consider imaging of the affected joints. Options include X-ray, ultrasound, or dual-energy CT (DECT). These imaging techniques can help visualize urate crystal deposits and assess for joint damage, further aiding in diagnosis.

1.2. Information and Support for Patients

1.2.1. Tailored Patient Education: Provide comprehensive and personalized information to patients diagnosed with gout, as well as their family members or caregivers as appropriate. This should be delivered at the time of diagnosis and reinforced during subsequent follow-up appointments. Key information should include:

• Symptoms and Signs: Clearly explain the characteristic symptoms and signs of gout, helping patients recognize and understand their condition.

• Causes of Gout: Detail the underlying causes of gout, including the role of hyperuricemia (elevated serum urate levels) and urate crystal formation.

• Disease Progression: Emphasize that gout is a progressive condition if left untreated, with continued high urate levels leading to further crystal deposition and joint damage.

• Individual Risk Factors: Discuss any specific risk factors relevant to the patient, such as genetic predisposition, excess body weight or obesity, current medications, and co-existing conditions like chronic kidney disease (CKD) or hypertension.

• Flare Management: Provide clear guidance on how to manage acute gout flares, including available treatment options and self-management strategies.

• Long-term Management with ULT: Explain that gout is a chronic condition requiring long-term management, typically involving urate-lowering therapy (ULT) to dissolve urate crystals, prevent future flares, reduce tophi, and protect against long-term joint damage.

• Resources and Support Networks: Direct patients to reliable sources of additional information and support, such as local support groups, online forums, and national charities dedicated to arthritis and gout.

  Refer to section 1.4 for detailed recommendations on diet and lifestyle modifications.

1.2.2. Adherence to NICE Guidelines: Follow NICE guidelines for patient experience in adult NHS services and shared decision-making to ensure patient-centered communication and engagement in care planning.

1.3. Managing Gout Flares

Acute Flare Treatment

1.3.1. First-line Pharmacological Treatment: For the initial treatment of an acute gout flare, offer one of the following first-line options: a non-steroidal anti-inflammatory drug (NSAID), colchicine, or a short course of oral corticosteroids. The choice should be individualized, considering the patient’s comorbidities, current medications, and personal preferences.

1.3.2. Proton Pump Inhibitor (PPI) Co-prescription: For patients prescribed an NSAID for gout flare treatment, consider adding a proton pump inhibitor (PPI) to reduce the risk of gastrointestinal side effects, particularly in those at higher risk.

1.3.3. Intra-articular or Intramuscular Corticosteroids: If NSAIDs and colchicine are contraindicated, poorly tolerated, or ineffective, consider intra-articular or intramuscular corticosteroid injections to manage a gout flare. These localized treatments can be particularly beneficial for monoarticular flares.

1.3.4. Limited Role for Interleukin-1 (IL-1) Inhibitors: Do not routinely offer interleukin-1 (IL-1) inhibitors for gout flare treatment unless NSAIDs, colchicine, and corticosteroids are contraindicated, not tolerated, or ineffective. Prior to prescribing an IL-1 inhibitor, referral to a rheumatology service is recommended for specialist assessment and guidance.

1.3.5. Adjunctive Cold Therapy: Advise patients that applying ice packs to the affected joint (cold therapy) in conjunction with prescribed medications can provide additional pain relief and symptom management during a gout flare.

Image alt text: Gout flare affecting multiple joints in the hand, illustrating the redness and swelling characteristic of acute gout.

Follow-up Care Post-Flare

1.3.6. Post-Flare Follow-up Appointment: Consider scheduling a follow-up appointment after a gout flare has resolved. This appointment serves several critical purposes:

• Serum Urate Level Measurement: Assess the serum urate level to guide long-term management strategies, particularly regarding the need for urate-lowering therapy (ULT).

• Gout Education and Self-Management: Reinforce patient education about gout, focusing on self-management techniques and strategies to reduce the risk of future flares.

• Comorbidity and Lifestyle Assessment: Evaluate lifestyle factors and comorbidities, including cardiovascular risk factors and chronic kidney disease (CKD), which can influence gout management.

• Medication Review and ULT Discussion: Review current medications and engage in a shared decision-making discussion about the risks and benefits of long-term ULT, especially for patients with recurrent flares or risk factors for progressive gout.

  Refer to NICE guidelines on medicines adherence, chronic kidney disease, cardiovascular disease, and shared decision-making for additional guidance.

1.4. Diet and Lifestyle Recommendations

1.4.1. Balanced Diet Approach: Counsel patients with gout that current evidence does not support any specific diet for preventing flares or lowering serum urate levels. Instead, advise adherence to a healthy, balanced diet consistent with general healthy eating guidelines.

1.4.2. Weight Management and Alcohol Consumption: Advise patients that excess body weight or obesity, as well as excessive alcohol consumption, can exacerbate gout flares and symptoms. Emphasize the importance of weight management and moderation in alcohol intake as part of overall gout management.

Refer to NICE guidelines on preventing excess weight gain and obesity management for further information.

1.5. Long-Term Management of Gout

Urate-Lowering Therapy (ULT) Strategies

1.5.1. Indications for ULT: Offer urate-lowering therapy (ULT), employing a treat-to-target strategy (see 1.5.2), to patients with gout who present with any of the following:

• Frequent or Troublesome Flares: Defined as two or more flares per year, or flares that significantly impact quality of life.
• Chronic Kidney Disease (CKD) Stages 3-5: Glomerular filtration rate (GFR) categories G3 to G5.
• Diuretic Therapy: Ongoing use of diuretic medications, which can elevate serum urate levels.
• Tophi: Presence of tophi, indicating significant urate crystal burden.
• Chronic Gouty Arthritis: Established chronic inflammatory joint disease due to gout.

1.5.2. Consideration of ULT for Other Patients: Discuss the option of ULT, using a treat-to-target approach, with patients who have experienced a first or subsequent gout flare but do not fall into the categories listed in recommendation 1.5.1. Individual patient circumstances and preferences should guide this discussion (see 1.5.4 for timing of ULT initiation).

1.5.3. Long-term Nature of ULT: Ensure patients understand that ULT is typically a lifelong treatment and should be continued even after the target serum urate level is achieved to maintain long-term control of gout.

1.5.4. Timing of ULT Initiation: Initiate ULT at least 2 to 4 weeks after a gout flare has fully resolved. In patients with more frequent flares, ULT may be started during an ongoing flare, but with appropriate preventative measures for flare exacerbation (see section on preventing flares when starting or titrating ULT).

Treat-to-Target Strategy for ULT

1.5.5. Gradual Dose Titration: Initiate ULT at a low dose and gradually increase the dose based on monthly serum urate level monitoring. Dose adjustments should be made as tolerated by the patient, with the goal of reaching and maintaining the target serum urate level.

Target Serum Urate Level

1.5.6. Primary Target: Aim for a target serum urate level below 360 micromol/litre (6 mg/dl) for most patients with gout.

1.5.7. Lower Target in Specific Cases: Consider a lower target serum urate level, below 300 micromol/litre (5 mg/dl), for patients with:

• Tophi or Chronic Gouty Arthritis: To facilitate faster tophus dissolution and improvement in chronic joint disease.
• Ongoing Frequent Flares: Despite achieving a serum urate level below 360 micromol/litre (6 mg/dl), indicating a need for more aggressive urate lowering.

First-line and Second-line Urate-Lowering Therapies

1.5.8. First-line ULT Options: Offer either allopurinol or febuxostat as first-line ULT when initiating treat-to-target therapy. The choice should be made in consideration of the patient’s comorbidities and preferences.

1.5.9. Allopurinol in Cardiovascular Disease: For patients with gout and major cardiovascular disease (e.g., previous myocardial infarction, stroke, unstable angina), allopurinol is recommended as the first-line ULT due to cardiovascular safety considerations associated with febuxostat in this population.

1.5.10. Second-line ULT Considerations: If the target serum urate level is not achieved with first-line ULT, or if first-line treatment is not tolerated, consider switching to the other first-line agent (allopurinol or febuxostat) as second-line treatment. Again, consider comorbidities and patient preferences when making this decision. Refer to recommendation 1.5.5 for treat-to-target strategy guidance.

Preventing Gout Flares During ULT Initiation and Titration

1.5.11. Discuss Flare Prevention: Engage in a detailed discussion with patients about the benefits and risks of using medications to prevent gout flares when starting or titrating ULT. Emphasize that flares can occur as urate levels are lowered initially.

1.5.12. Colchicine for Flare Prophylaxis: For patients who opt for flare prevention during ULT initiation or titration, offer colchicine while the target serum urate level is being achieved. If colchicine is contraindicated, not tolerated, or ineffective, consider a low-dose NSAID or low-dose oral corticosteroid as alternatives.

1.5.13. PPI with NSAID or Corticosteroid Prophylaxis: Consider adding a proton pump inhibitor (PPI) for patients taking an NSAID or corticosteroid to prevent gout flares during ULT initiation or titration, particularly those with risk factors for gastrointestinal adverse events.

1.5.14. Limited Role for IL-1 Inhibitors in Flare Prevention: Do not routinely offer IL-1 inhibitors for preventing flares during ULT initiation or titration unless colchicine, NSAIDs, and corticosteroids are contraindicated, not tolerated, or ineffective. Referral to a rheumatology service is recommended before considering an IL-1 inhibitor in this setting.

Monitoring Serum Urate Level

1.5.15. Annual Serum Urate Monitoring: Consider annual monitoring of serum urate levels in patients with gout who are on long-term ULT and have achieved their target serum urate level. This ongoing monitoring helps ensure sustained urate control and early detection of any loss of efficacy or need for dose adjustment.

1.6. Referral to Specialist Services

1.6.1. Referral Criteria: Consider referral to a rheumatology service for patients with gout in the following circumstances:

• Diagnostic Uncertainty: When the diagnosis of gout remains uncertain despite initial investigations.
• Treatment Challenges: If treatment is contraindicated, not tolerated, or ineffective in achieving therapeutic goals.
• Advanced Chronic Kidney Disease: Patients with CKD stages 3b to 5 (GFR categories G3b to G5) often require specialist input for complex management.
• Organ Transplant Recipients: Individuals who have undergone organ transplantation may need specialist rheumatology care due to the complexities of immunosuppression and drug interactions.

Recommendations for Research

The guideline committee has identified key areas where further research is needed to enhance the evidence base for gout management.

Key Research Priorities

1. Pharmacological Management of Gout Flares

Research Question: In patients with gout, including those with co-existing chronic kidney disease (CKD), what is the comparative clinical and cost-effectiveness of colchicine versus corticosteroids for managing acute gout flares?

2. Preventing Gout Flares During ULT Initiation

Research Question: In patients with gout, including those with CKD, what is the comparative clinical and cost-effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) or corticosteroids for preventing gout flares when initiating or titrating urate-lowering therapy (ULT)?

3. Optimal Target Serum Urate Level

Research Question: What is the optimal and most cost-effective target serum urate level when using a treat-to-target strategy for gout, including in patients with CKD?

4. Follow-up Strategies After a Gout Flare

Research Question: What are the clinical and cost-effectiveness and patient acceptability of different follow-up approaches after a gout flare, including patient education and flare management strategies?

5. Frequency of Serum Urate Monitoring

Research Question: In patients with gout, including those with CKD, what is the most clinically and cost-effective frequency of serum urate level monitoring once the target serum urate level has been achieved and maintained?

Additional Research Areas

When to Start Urate-Lowering Therapy

Research Question: What is the comparative clinical and cost-effectiveness of initiating ULT during an acute gout flare versus starting ULT once the flare has completely resolved?

Rationale and Impact of Recommendations

Symptoms and Signs of Gout (Recommendations 1.1.1 – 1.1.6)

The recommendations on symptoms and signs are based on clinical consensus and available evidence, which, while limited, aligns with expert clinical experience. Recognizing the combination of rapid-onset severe pain, redness, and swelling in the first MTP joint as highly suggestive of gout, and considering gout in other joint presentations, are key diagnostic steps. These recommendations primarily aim to standardize diagnostic suspicion in non-specialist settings, reinforcing best practices without major practice change.

Diagnosis of Gout (Recommendations 1.1.7 – 1.1.9)

Diagnosis recommendations emphasize serum urate measurement as a primary diagnostic tool, with joint aspiration and synovial fluid analysis reserved for uncertain cases. Imaging modalities like ultrasound and DECT are acknowledged as valuable adjuncts when aspiration is not feasible or diagnosis remains unclear. These recommendations largely reflect current diagnostic pathways, aiming for clarity and reinforcement of evidence-based approaches without significant practice overhaul.

Patient Information and Support (Recommendations 1.2.1 and 1.2.2)

The strong emphasis on patient information and support is driven by evidence highlighting gaps in patient knowledge about gout causes, management, and the importance of long-term ULT. Tailoring information, addressing misconceptions, and directing patients to support resources are crucial. These recommendations aim to enhance patient empowerment and adherence to management plans, likely improving the quality of care within existing service frameworks.

Managing Gout Flares (Recommendations 1.3.1 – 1.3.5)

Flare management recommendations endorse NSAIDs, colchicine, or corticosteroids as first-line treatments, reflecting current practice and evidence showing comparable efficacy. The guideline highlights individualizing treatment based on patient profiles and comorbidities. The limited role of IL-1 inhibitors and the recommendation for adjunctive cold therapy are also based on evidence and clinical experience. These recommendations reinforce established practices with minor refinements, not expected to cause significant practice changes.

Follow-up After a Gout Flare (Recommendation 1.3.6)

The recommendation for post-flare follow-up is a significant shift from current practice in many settings. It emphasizes the importance of seizing the post-flare period to educate patients, assess comorbidities, and initiate or optimize ULT. This proactive follow-up is anticipated to improve long-term outcomes by increasing ULT uptake and adherence, potentially leading to cost savings through reduced flare frequency and gout-related complications.

Diet and Lifestyle Advice (Recommendations 1.4.1 and 1.4.2)

Diet and lifestyle recommendations advise a balanced diet approach, cautioning against specific dietary fads for gout. Emphasizing weight management and moderation in alcohol consumption reflects the evidence linking these factors to gout exacerbation. These recommendations align with current general advice, unlikely to result in practice changes.

Management of Gout with Urate-Lowering Therapies (Recommendations 1.5.1 – 1.5.4)

These recommendations advocate for broader use of ULT, particularly in patients with recurrent flares, CKD, tophi, or chronic gouty arthritis. Discussing ULT options even after a first flare aims to address undertreatment and improve long-term gout control. Starting ULT 2-4 weeks post-flare, or even during a flare in frequent flare scenarios, reflects a pragmatic approach to ULT initiation. The anticipated impact is a significant increase in ULT uptake, leading to improved patient outcomes and long-term cost-effectiveness despite initial resource implications.

Treat-to-Target Strategy (Recommendation 1.5.5)

The treat-to-target strategy is endorsed based on evidence of improved long-term flare control and cost-effectiveness. This approach, involving gradual ULT dose titration guided by serum urate monitoring, is recommended to optimize urate lowering and minimize flare risk during ULT initiation. Wider adoption of treat-to-target is expected to improve gout management and patient outcomes.

Target Serum Urate Level (Recommendations 1.5.6 and 1.5.7)

Setting a target serum urate level below 360 micromol/litre (6 mg/dl) as a primary goal, with a lower target of 300 micromol/litre (5 mg/dl) considered for severe gout, reflects a balance between efficacy and feasibility in primary care. These targets align with current practice and expert consensus, aiming to guide ULT dosing and monitoring without significant practice change.

Urate-Lowering Therapies (Recommendations 1.5.8 – 1.5.10)

Recommending both allopurinol and febuxostat as first-line ULT options, with allopurinol prioritized in cardiovascular disease, expands treatment choices. This recommendation acknowledges the evidence base and the MHRA safety guidance on febuxostat. Considering both agents as second-line options if the first-line agent fails or is not tolerated further broadens treatment strategies. This shift may lead to increased febuxostat use, but overall cost impact is expected to be minimal due to similar drug costs.

Preventing Gout Flares When Starting or Titrating ULT (Recommendations 1.5.11 – 1.5.14)

Colchicine is recommended as the primary agent for flare prophylaxis during ULT initiation and titration, reflecting current practice. NSAIDs or corticosteroids are suggested as alternatives when colchicine is unsuitable. These recommendations reinforce established flare prevention strategies during ULT initiation, with no major practice changes anticipated.

Monitoring Serum Urate Level (Recommendation 1.5.15)

Annual serum urate monitoring for patients on long-term ULT is recommended to ensure sustained urate control and medication adherence. This proactive monitoring is expected to improve long-term outcomes by preventing urate rebound and subsequent flares, potentially leading to cost savings.

Referral to Specialist Services (Recommendation 1.6.1)

Referral recommendations aim to clarify appropriate referral pathways to rheumatology services, focusing on diagnostic uncertainty, treatment complexities, advanced CKD, and organ transplant recipients. These criteria are intended to optimize specialist resource utilization for complex gout cases, potentially increasing referrals in specific patient subgroups.

Context of Gout in Primary Care

Gout is a prevalent form of arthritis in the UK, affecting 2-3% of the population, predominantly men over 30 and post-menopausal women. Primary care is the main setting for gout management. Effective diagnosis and management, including ULT, are crucial to prevent flares, joint damage, and long-term complications such as renal stones and CKD. Despite available treatments, gout remains undertreated, with low ULT uptake and suboptimal serum urate control in many patients. Improving gout diagnosis and management in primary care is essential to enhance patient quality of life and reduce the burden of this chronic condition.

Further Information and Guideline Details

For comprehensive details on related NICE guidance, development process, evidence reviews, and guideline committee information, please refer to the NICE topic page on arthritis and the evidence reviews associated with guideline NG219. Tools and resources to support guideline implementation are also available on the NICE website.

Disclaimer: These guidelines represent the views of NICE based on careful evidence review. Healthcare professionals are expected to consider these guidelines alongside individual patient needs and preferences when making clinical judgments. These guidelines are not mandatory and do not supersede professional responsibility for individualized patient care. Local commissioners and healthcare providers are responsible for enabling guideline application within the context of local and national priorities and for promoting equitable and sustainable healthcare practices.