Gout: What to Know about that Big Red Toe

Background

Characteristics of acute gout: 

  • Sudden onset
  • Monoarticular (<20% polyarticular)
  • Severe pain, redness, swelling
  • Pain peaks in 12-24h, lasts days to weeks
  • +/- presence of tophi

Who’s at risk?

Source: Hainer BL, Matheson E, Wilkes RT. Diagnosis, treatment, and prevention of gout. Am Fam Physician. 2014 Dec 15;90(12):831-6.

Diagnostic Criteria

Multiple criteria exist: 

  • New York criteria
  • American Rheumatology Association criteria
  • Janssens diagnostic rule
  • Clinical Gout Diagnosis criteria
  • Monoarthritis of the first metatarsophalangeal joint
  • SUGAR (Study for Updated Gout Classification Criteria)
  • 2015 American College of Rheumatology and European League Against Rheumatism gout classification criteria 

  • Recommendation: ACP recommends that clinicians use synovial fluid analysis when clinical judgment indicates that diagnostic testing is necessary in patients with possible acute gout. (Grade: weak recommendation, low-quality evidence)
  • Clinical considerations:
    • Synovial fluid analysis is considered the reference standard for gout diagnosis, although it may be difficult to perform in primary care.
    • Synovial fluid analysis should be used in the following clinical circumstances:
      • The joint can be aspirated without substantial patient discomfort by an experienced clinician who can minimize the risk of infection.
      • A reliable and accurate source (including a polarizing microscope and a trained operator) is available to detect the presence of urate crystals.
      • The clinical situation is ambiguous, and a probability of infection exists.
    • Clinical algorithms are shown to have sensitivities and specificities >80%, although little evidence exists that they can be used to distinguish septic joints.

Clinical adjuncts for gout diagnosis: 


Treatment: Traditional

  • Acute gout: 
    • NSAIDS, colchicine, and/or oral corticosteroids
    • Maybe intraarticular steroid injections (less evidence), ice
  • Prevention: 
    • Lifestyle modifications: DASH or low-purine diet, exercise, weight loss, decrease alcohol consumption
    • Urate lowering therapy (ULT): allopurinol, probenicid, or febuxistat (increased risk of CV-related death according to CARES trial)

Treatment: What’s New?


NSAIDs vs colchicine

  • A 2019 multicenter randomized trial by Roddy et al compared the effectiveness and safety of naproxen and low-dose colchicine for treating gout flares in primary care: 
    • 200 patients received naproxen 750mg loading dose followed by 250mg q8h for 7 days
    • 199 patients received colchicine 0.5mg TID for 4 days
  • Outcomes:
    • Primary: change in worst pain intensity from baseline daily over 7 days and at week 4
    • Secondary: self-reported side effects (n/v, headache, rash, GI upset), other analgesic use
  • Results:
    • No significant difference in pain intensity over 7 days among people with gout flare between naproxen and colchicine groups
    • Naproxen caused fewer side effects (diarrhea, analgesic use)
  • Conclusions: No difference in pain intensity over 7 days between people with a gout flare randomised to either naproxen or low-dose colchicine. Naproxen caused fewer side effects supporting naproxen as first-line treatment for gout flares in primary care in the absence of contraindications.

New 2020 ACR guideline for the Management of Gout

The ACR has a ton of evidence-based recommendations for urate lowering therapy (ULT): 

  • Indications for ULT: 
    • Initiating ULT is strongly recommended for gout patients with any of the following: ≥1 subcutaneous tophi; evidence of radiographic damage (any modality) attributable to gout; OR frequent gout flares, with frequent being defined as ≥2 annually.
    • Initiating ULT is conditionally recommended for patients who have previously experienced >1 flare but have infrequent flares (<2/year).
    • Initiating ULT is conditionally recommended against in patients with gout experiencing their first gout flare. However, initiating ULT is conditionally recommended for patients with comorbid moderate-to-severe CKD (stage ≥3), serum urate concentration >9 mg/dl, or urolithiasis.
    • Initiating ULT is conditionally recommended against in patients with asymptomatic hyperuricemia.
  • Recommendations for choice of initial ULT for patients with gout: 
    • Treatment with allopurinol as the preferred first-line agent, over all other ULTs, is strongly recommended for all patients, including those with moderate-to-severe CKD (stage ≥3).
    • The choice of either allopurinol or febuxostat over probenecid is strongly recommended for patients with moderate-to-severe CKD (stage ≥3).
    • The choice of pegloticase as a first-line therapy is strongly recommended against.
    • Starting treatment with low-dose allopurinol (≤100 mg/day and lower in patients with CKD [stage ≥3]) and febuxostat (≤40 mg/day) with subsequent dose titration over starting at a higher dose is strongly recommended.
    • Starting treatment with low-dose probenecid (500 mg once to twice daily) with subsequent dose titration over starting at a higher dose is conditionally recommended.
    • Administering concomitant antiinflammatory prophylaxis therapy (e.g., colchicine, NSAIDs, prednisone/prednisolone) over no antiinflammatory prophylaxis therapy is strongly recommended.
    • Continuing concomitant antiinflammatory prophylaxis therapy for 3-6 months over <3 months, with ongoing evaluation and continued prophylaxis as needed if the patient continues to experience gout flares, is strongly recommended.
  • Timing of ULT initiation: 
    • When the decision is made that ULT is indicated while the patient is experiencing a gout flare, starting ULT during the gout flare over starting ULT after the gout flare has resolved is conditionally recommended.
    • A treat-to-target management strategy that includes ULT dose titration and subsequent dosing guided by serial serum urate (SU) measurements to achieve a target SU, over a fixed-dose ULT strategy, is strongly recommended for all patients receiving ULT.
    • Achieving and maintaining an SU target of <6 mg/dl over the use of no target is strongly recommended for all patients receiving ULT.
    • Delivery of an augmented protocol of ULT dose management by nonphysician providers to optimize the treat-to-target strategy that includes patient education, shared decision-making, and treat-to-target protocol is conditionally recommended for all patients receiving ULT.
  • Duration of ULT: 
    • Continuing ULT indefinitely over stopping ULT is conditionally recommended.

Does allopurinol slow CKD?


Take-Home Points!

  • In absence of contraindications, naproxen may be just as good as colchicine (with fewer side effects) for treatment of acute gout flares
  • Start ULT in presence of
    • Tophi
    • Radiographic damage
    • ≥2 flares/year 
    • First flare in presence of CKD (≥III), serum urate >9, or urolithiasis
  • Allopurinol is first line for ULT
    • Start low and titrate to target serum urate <6
    • Start prophylaxis with NSAIDS or colchicine when initiating ULT
  • Don’t treat asymptomatic hyperuricemia

Blog post based on Med-Peds Forum talk by Chelsea Boyd, PGY2