Here are the updates for the diagnosis, management and treatment of gout according to the top 3 guidelines in rheumatology namely, APLAR ACR and EULAR. 

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What causes gout?

Gout is chronic debilitating arthropathy that is due to monosodium urate crystal deposition. It is a common clinical condition faced by family physicians/primary care physicians. The approach to diagnosis & management is incongruous among various doctors. The condition is a chronic arthropathy caused by monosodium urate crystal deposition, characterised by intermittent arthritis and often accompanied by multiple comorbidities. It is a relatively common condition that requires a multidisciplinary approach to treatment.

Gout management has various controversies and non-coherent treatment approaches. Guidelines make it easier and more evidence-based; especially for primary care physicians.

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Diagnosis of gout

As per the European League association of Rheumatology 2018:

1. Patients with the following clinical scenario should be suspected and evaluated for gout -
   • The monoarticular episode involving 1st MTP joint/foot/ankle joint
   • History of a similar episode in the past
   • Rapidly progressing pain/ swelling/ erythema
   • Male gender patient with cardiovascular disease with hyperuricemia
2. In all patients with suspected gout search for monosodium urate crystals in synovial fluid/tophus aspirate because the demonstration of crystals will make a definitive diagnosis.
3. Never make the diagnosis of gout only based on hyperuricemia alone.
4. In patients with crystal, the demonstration is not possible, alternative imaging modalities can help in making diagnoses like:

Conventional radiography- is a long period of time is required for the following conventional radiography changes to be apparent:

• Bone erosion with overhanging edges
• Sclerotic rim
• Bony proliferation
• Joint space narrowing (late feature)
• Soft tissue mass

Musculoskeletal ultrasound - Have great potential with reliable specificity of double contour sign.

Dual-energy computed tomography(DECT) - Promising therapy with high sensitivity (78-87%) & specificity (85-95%).

5. Always search for the following risk factors for chronic hyperuricemia

• Chronic kidney disease
• Overweight
• Medications (Diuretics, low dose aspirin, cyclosporine)
• Alcohol
• Dietary habits (Non-diet soda/high fructose corn syrup, meat, shellfish/seafood)

6. Look for the following comorbidities:

• Obesity
• Renal impairment
• Hypertension
• Diabetes
• Dyslipidemia(Tryglyceridemia)
• Ischaemic heart disease

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Management guidelines

(Review of Asian Pacific League association of Rheumatology(APLAR) 2021, American College of Rheumatology(ACR) 2020 & European League association of rheumatology (EULAR) 2016 recommendation for gout management)

Overarching principle- (EULAR 2016 & APLAR 2021 guidelines for gout management)

1. Recognition of gout & its complications - a multidisciplinary collaborative approach
2. Patient education regarding disease, management & shared decision making between the patient & the phyiscian.
3. Gout management should be a holistic approach including urate-lowering therapy, lifestyle management, treating comorbidities etc.
4. Acute gout treatment should include early anti-inflammatory medications and treatment should aim to prevent organ damage.

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Treatment recommendations

Asymptomatic hyperuricemia- APLAR 2021 recommends against urate-lowering therapy in patients with asymptomatic hyperuricemia alone or associated with hypertension, or cardiovascular disease. And it also suggests inadequate evidence of urate-lowering therapy in preventing chronic kidney disease progression.

Management of acute gout- Should be managed with anti-inflammatory medications; therapeutic options available are Colchicine, NSAIDs, Glucocorticoids, Adrenocorticotrophic Hormone (ACTH), and Interleukin-1(IL-1) antagonist.

1. EULAR 2016 recommends starting acute gout management as soon as possible to prevent damage. It recommends educating patients to self-medicate as early/first warning sign/symptom appears.
2. Colchicine should be the first-line agent preferred. Low dose (1.2 -1.8 mg/d) is recommended over high dose (4 - 5.8 mg/d).
3. Colchicine should be avoided in patients with renal disease, co-prescription with statins/CYP3A4 inhibitors like cyclosporine, clarithromycin etc.
4. Concomitant two anti-inflammatory medications can be prescribed in the absence of contraindication.
5. Oral/Intramuscular/Intra-articular glucocorticoids can be prescribed. (Oral prednisolone at the dose of 30-35mg/day for 3-5 days)
6. Colchicine, NSAIDs and Glucocorticoids are the preferred agents over IL-1 antagonists & ACTH.
7. IL-1 antagonists can be considered in cases of contraindication for other medications.
8. Initiation of urate-lowering therapy during or after the acute flare has insufficient evidence regarding which to follow
9. Non-pharmacological measures like topical ice application can be considered.
10. APLAR 2021 recommends the conditional use of acupuncture therapy for acute attacks.
11. APLAR 2021 suggests insufficient evidence for the usage of herbal medications

Indications of initiating Urate Lowering Therapy(ULT):

• Recurrent gout flare: ≥2 flares/year
• ≥1 Subcutaneous tophi
• Radiographic evidence of damage attributable secondary to gout
• Conditional recommendation for the patient having multiple but infrequent attacks (<2 per year)
• In patients with first gout flare with comorbid like chronic kidney disease (Stage ≥3), serum uric acid ≥9 mg/dl, urolithiasis, multiple comorbid

Urate lowering therapy:

1. All the guidelines recommend Allopurinol as the first line of urate-lowering therapy.
2. Allopurinol should be started at a low dose (100mg/day) and up titrated every (2-4) weekly to achieve target serum uric acid <6 mg/dl.
3. Urate lowering therapy should be continued indefinitely.
4. Genetic testing for HLA B*5801 is indicated in populations with high prevalence (Han Chinese, Korean, Thai descent & Subgroup of Africa-Americans). It is not recommended for all patients.
5. Other xanthine oxidase inhibitors can be considered only in the setting with any contraindication to allopurinol.
6. Febuxostat is not recommended as a first-line even in the high prevalence region of HLA B *5801.
7. Febuxostat should not be considered or switched in patients with history/new-onset cardiovascular disease (Low-evidence)
8. Both Allopurinol & Febuxostat can be considered in chronic kidney disease patients.
9. Uricosurics like probenecid do not require testing urinary uric acid level.
10. No recommendation for alkalinizing urine in patients on uricosurics
11. In refractory patients, whose target uric acid level is not achieved with the full dose of xanthine oxidase inhibitor or combination with uricosuric; Pegloticase can be considered
12. Pegloticase should not be considered as first-line therapy.

Prophylactic therapy:

1. Prophylactic therapy with anti-inflammatory medication is recommended for 3-6 months in all patients started on urate lowering therapy.
2. If no contraindication; Colchicine (0.5-1mg/day) should be the first choice for prophylaxis.
3. NSAIDs at a low dose (e.g 250 mg BD Naproxen) can be considered as the 2nd line prophylactic therapy.
4. Very low evidence for glucocorticoids as prophylactic therapy.

Lifestyle management:

• Strong agreement for limiting alcohol
• Limit high purine-rich diet
• Weight reduction strategies/interventions are recommended for lowering uric acid
• No role of vitamin C supplementation

Guidelines for concomitant medications:

1. Switch Hydrochlorthiazide to alternative anti-hypertensive.
2. Prefer uricosuric antihypertensive like Losartan wherever not contraindicated.
3. Don't stop low dose aspirin.
4. For dyslipidemia management, don’t add or switch to fenofibrate; although fenofibrate has uric lowering potential.

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Limitations 

There are certain limitations of the above-mentioned guidelines. They have not clarified regarding management strategy for hyperuricemia related to malignancies, and refractory gout. They also have not provided clear guidelines regarding the time to start urate-lowering therapy after or during acute episodes.

 

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising Rheumatologist from Bangalore.