What are the possible diagnosis and next steps for a 56-year-old male with a history of gout, currently taking Febuxostat (febuxostat), presenting with intermittent sharp pains in the left leg, left back shoulder, and upper back, radiating to the popliteal fossa and lower back, with pain on rotation, dorsiflexion, and plantar flexion under the left medial malleolus and heel, and clicking in the left posterior glenohumeral joint?

Differential Diagnosis and Management Approach

This patient's presentation is most consistent with two distinct musculoskeletal conditions occurring simultaneously: acute gout flare in the left foot/ankle and adhesive capsulitis (frozen shoulder) or rotator cuff pathology in the left shoulder, rather than a single systemic process.

Primary Diagnostic Considerations

Left Foot/Ankle Pain - Likely Acute Gout Flare

The clinical presentation strongly suggests an acute gout attack in the left foot, given the patient's established gout history on febuxostat, intermittent sharp pain pattern, morning predominance, and pain on rotation/dorsiflexion/plantar flexion of the ankle and medial malleolus area. 1

Key diagnostic features supporting gout:

• History of gout with current urate-lowering therapy (febuxostat) - patients on ULT can still experience breakthrough flares, particularly if serum urate targets are not achieved 1
• Intermittent episodes over 1 year - recurrent pattern is highly suggestive of gout 1, 2
• Morning predominance with 2-hour duration - acute gout characteristically reaches maximum intensity within 6-24 hours 2
• Pain radiating to popliteal fossa and lower back - suggests inflammatory process affecting multiple sites 1
• Male gender, age 56, cardiovascular risk factors - classic demographic for gout 1, 2

Left Shoulder Pain - Likely Adhesive Capsulitis or Rotator Cuff Pathology

The shoulder symptoms (clicking, pain on all planes of motion, posterior glenohumeral tenderness) suggest a separate mechanical shoulder disorder rather than gouty arthritis:

• Clicking sensation - more consistent with rotator cuff pathology or labral issues than crystal arthropathy 2
• Pain on all planes of rotation, abduction, adduction - suggests capsular or rotator cuff involvement 2
• No mention of acute inflammatory signs (erythema, warmth, rapid onset) - makes acute gout less likely in shoulder 1

Immediate Next Steps

1. Confirm Gout Diagnosis in Foot/Ankle

Joint aspiration with synovial fluid analysis for monosodium urate (MSU) crystals using polarized light microscopy is the gold standard and should be performed if technically feasible, particularly since this represents a change in disease pattern. 1, 2

• Aspiration is strongly recommended when the clinical presentation is atypical or when septic arthritis cannot be excluded 1, 2
• MSU crystals appear as needle-shaped, negatively birefringent crystals with sensitivity/specificity approaching 100% 2
• Always perform Gram stain and culture even if crystals are identified, as gout and septic arthritis can coexist 2

If joint aspiration is not feasible (technically difficult in ankle/foot), proceed with ultrasound imaging as the first-line alternative diagnostic modality: 2

• Ultrasound should always include the first metatarsophalangeal joint bilaterally, even if asymptomatic 2
• Look for "double contour sign" (74% sensitivity, 88% specificity) or tophi 1, 2
• Ultrasound can also assess for active inflammation 2

2. Laboratory Evaluation

Obtain serum uric acid level immediately - though hyperuricemia alone does not diagnose gout, and normal levels do not exclude it during an acute flare 1, 2

Check inflammatory markers (ESR, CRP) and complete blood count - to assess inflammation severity and rule out infection 1

Assess renal function (creatinine, eGFR) - critical for medication dosing and to evaluate if febuxostat dose is adequate 1

Screen for associated comorbidities: 1, 2

• Fasting glucose or HbA1c (diabetes screening)
• Lipid panel (dyslipidemia)
• Blood pressure documentation (hypertension)
• Review current medications for gout-triggering agents (diuretics, low-dose aspirin) 1

3. Evaluate Febuxostat Efficacy

This patient is experiencing gout flares despite being on febuxostat, which indicates either inadequate dosing or non-adherence: 1

• High-quality evidence shows that urate-lowering therapy does not reduce acute gout attacks in the first 6 months, but patients achieving lower urate levels after 1 year have fewer flares 1
• The target serum urate level is <6.0 mg/dL (360 μmol/L) - if not achieved, febuxostat dose should be titrated up 1, 3, 4
• Febuxostat can be dosed up to 120 mg daily (80 mg and 120 mg are more effective than allopurinol 300 mg) 3, 4

4. Shoulder Evaluation

Plain radiographs of the left shoulder (AP, lateral, axillary views) - to rule out structural abnormalities, calcific tendinitis, or arthritis 2

If radiographs are unrevealing and symptoms persist, consider shoulder ultrasound or MRI - to evaluate rotator cuff integrity and assess for adhesive capsulitis 2

Physical examination maneuvers - perform specific tests for rotator cuff pathology (empty can test, Hawkins-Kennedy test) and assess for true range of motion limitation suggesting adhesive capsulitis 2

Acute Treatment Plan

For Presumed Gout Flare in Foot/Ankle

Initiate anti-inflammatory therapy immediately with one of the following (strong recommendation, high-quality evidence): 1

First-line: Corticosteroids (preferred due to safety profile and cost):

• Prednisone 30-40 mg daily for 5-7 days, then taper 1
• Corticosteroids should be considered first-line in patients without contraindications (diabetes, infection risk) 1

Alternative: NSAIDs (if no contraindications):

• Naproxen 500 mg twice daily or indomethacin 50 mg three times daily 1
• Avoid in patients with renal impairment, GI bleeding history, or cardiovascular disease 1

Alternative: Colchicine:

• Low-dose colchicine 0.6 mg twice daily (or 1.2 mg once daily) is as effective as higher doses with fewer adverse effects 1
• Reduce dose in renal impairment 1

Critical: Do NOT discontinue febuxostat during acute flare - continuing ULT during flares prevents prolonged elevation of serum urate 1

For Shoulder Pain

Conservative management initially:

• NSAIDs (if not contraindicated and not already using for gout)
• Physical therapy referral for range of motion exercises
• Consider subacromial corticosteroid injection if rotator cuff pathology or bursitis confirmed

Long-Term Management Adjustments

Optimize Urate-Lowering Therapy

If serum uric acid is not at target (<6.0 mg/dL), increase febuxostat dose: 1, 3, 4

• Current dose unknown, but can titrate from 40 mg to 80 mg to 120 mg daily 1
• Febuxostat 80 mg and 120 mg achieve target urate levels in 53-62% of patients compared to 21% with allopurinol 300 mg 3

Add prophylactic anti-inflammatory therapy if not already prescribed: 1

• Low-dose colchicine 0.6 mg daily or NSAIDs effectively reduce acute gout flares in patients on ULT (strong recommendation, high-quality evidence) 1
• Continue prophylaxis for at least 3-6 months, with ongoing evaluation 1
• Moderate-quality evidence supports continuing prophylaxis beyond 8 weeks 1

Address Modifiable Risk Factors

Systematic assessment and management of gout-associated comorbidities is recommended: 1, 2

• Weight reduction if overweight/obese (RR 3.81 for gout) 2
• Blood pressure control (RR 3.93 for gout with hypertension) 2
• Review and modify medications: consider alternatives to diuretics if possible (RR 1.72) 2
• Reduce alcohol intake, particularly beer and spirits 1
• Dietary counseling: reduce red meat, shellfish, and high-fructose beverages 1

Common Pitfalls to Avoid

Do not diagnose gout based on hyperuricemia alone - up to 80% of patients with hyperuricemia never develop gout 1, 2

Do not assume a single systemic diagnosis - this patient has two anatomically distinct problems with different pathophysiologies 2

Do not stop febuxostat during an acute flare - this can prolong the attack and delay urate lowering 1

Do not fail to provide prophylaxis when optimizing ULT - early mobilization flares are common when initiating or adjusting urate-lowering therapy 1, 4

Do not assume adequate urate control without checking serum uric acid levels - clinical flares indicate either inadequate dosing or non-adherence 1

Do not overlook septic arthritis - if fever, systemic symptoms, or severe monoarticular inflammation is present, joint aspiration with Gram stain and culture is mandatory 1, 2