In an 80‑year‑old man with type 2 diabetes mellitus, hypertension, chronic osteoarthritis, and taking furosemide (Lasix) 40 mg daily, dapagliflozin, and other antihypertensive agents, what is the most likely cause of his sudden left knee pain and how should it be managed?

Sudden Left Knee Pain in an 80-Year-Old Diabetic on Dapagliflozin and Furosemide

The most likely cause of sudden left knee pain in this patient is acute gout precipitated by the combination of furosemide and dapagliflozin, both of which increase serum uric acid levels through different mechanisms.

Most Likely Diagnosis: Acute Gout

Why Gout is the Primary Concern

• Loop diuretics like furosemide are well-established precipitants of gout through uric acid retention mechanisms, and thiazide/thiazide-like diuretics are specifically noted as potentially problematic in patients with a history of gout 1
• Dapagliflozin independently increases serum uric acid through its osmotic diuretic effect and altered renal handling of urate, though paradoxically some studies show modest uric acid reduction 2, 3
• The combination of two diuretic mechanisms (loop diuretic plus SGLT2 inhibitor) creates additive risk for volume depletion and uric acid crystallization 4
• Diabetes and hypertension are independent risk factors for hyperuricemia and gout, and this 80-year-old patient has both conditions 1

Alternative Diagnoses to Consider

• Septic arthritis must be ruled out urgently given diabetes increases infection risk, and dapagliflozin is associated with increased genitourinary infections 2, 3
• Pseudogout (calcium pyrophosphate deposition) is common in elderly patients with osteoarthritis and can present identically to gout 1
• Acute exacerbation of osteoarthritis is possible but less likely to present as "sudden" pain
• Diabetic neuropathic arthropathy (Charcot joint) typically presents more insidiously

Immediate Diagnostic Workup

Essential First Steps

• Arthrocentesis of the left knee joint is mandatory to differentiate gout (monosodium urate crystals, negatively birefringent) from pseudogout (calcium pyrophosphate crystals, positively birefringent) and to rule out septic arthritis (Gram stain, culture, WBC count >50,000 suggests infection) 1
• Serum uric acid level should be checked, though normal levels do not exclude acute gout during an attack 1
• Complete metabolic panel to assess renal function (BUN, creatinine) and electrolytes, as both furosemide and dapagliflozin affect kidney function and electrolyte balance 5, 6
• CBC with differential to assess for leukocytosis suggesting infection 6
• Plain radiographs of the left knee to evaluate for joint effusion, fracture, or chronic changes of gout/pseudogout 1

Critical Monitoring Parameters

• Check potassium and creatinine within 24-48 hours given the combination of furosemide and dapagliflozin, as SGLT2 inhibitors can cause volume depletion and acute kidney injury, especially when combined with loop diuretics 5, 6, 4
• Blood pressure monitoring is essential as dapagliflozin reduces systolic BP by 7-10 mmHg, and combined with furosemide may cause symptomatic hypotension 7, 8

Management Algorithm

If Gout is Confirmed (Most Likely Scenario)

Acute Treatment:

• Colchicine 0.6 mg once or twice daily is preferred in elderly patients with renal impairment over NSAIDs, which are contraindicated 1
• NSAIDs are absolutely contraindicated in this patient because they destabilize blood pressure control in diabetic hypertensive patients, cause sodium retention and edema, and worsen renal function, particularly when combined with ACE inhibitors or ARBs 1
• Intra-articular corticosteroid injection (after infection is ruled out) or short course of oral prednisone 30-40 mg daily for 5 days is an alternative if colchicine is not tolerated 1

Medication Adjustments:

• Do NOT discontinue furosemide abruptly if the patient has volume overload or heart failure, as this could precipitate decompensation 5, 4
• Consider reducing furosemide dose to the minimum effective dose (e.g., 20 mg daily) once acute gout is controlled, as lower doses may reduce hyperuricemia risk 5
• Continue dapagliflozin as it provides cardiovascular and renal protection in diabetic patients, and the benefits outweigh the modest uric acid effects 1, 3
• Initiate allopurinol 100 mg daily (reduced dose for age and renal function) for long-term uric acid control after the acute attack resolves (typically 2-4 weeks), as thiazide/loop diuretics may necessitate urate-lowering therapy 1

If Septic Arthritis Cannot Be Excluded

Urgent Management:

• Admit for IV antibiotics (vancomycin plus ceftriaxone to cover MRSA and gram-negative organisms) pending culture results if synovial fluid WBC >50,000 or Gram stain is positive 6
• Orthopedic consultation for possible surgical drainage if septic arthritis is confirmed 6
• Hold dapagliflozin temporarily during acute infection as SGLT2 inhibitors may theoretically worsen glycemic control during severe illness and increase DKA risk 2, 3

If Pseudogout is Diagnosed

• Treatment is identical to gout (colchicine, corticosteroids, avoid NSAIDs) 1
• No specific medication adjustments needed for furosemide or dapagliflozin, as pseudogout is not precipitated by these agents 1

Critical Medication Considerations

Dapagliflozin-Specific Issues

• Dapagliflozin should be continued unless the patient develops severe volume depletion, acute kidney injury (creatinine increase >30% from baseline), or eGFR falls below 45 mL/min/1.73m² 2, 3
• The combination of dapagliflozin and furosemide is generally safe and may provide additive diuretic benefit in heart failure patients without significantly affecting potassium or renal function 4
• Monitor for genital and urinary tract infections as dapagliflozin increases risk, and these could theoretically seed a septic joint 2, 3

Blood Pressure Management

• Dapagliflozin reduces systolic BP by 7-10 mmHg through multiple mechanisms including volume reduction, suppression of angiotensin II, and increased atrial natriuretic peptide 7, 8
• This BP reduction is beneficial in hypertensive diabetic patients and does not require discontinuation of antihypertensive medications unless symptomatic hypotension occurs 8
• The combination with furosemide may cause excessive BP lowering, so monitor for orthostatic hypotension (measure BP supine and standing) 1, 5

Common Pitfalls to Avoid

• Do not use NSAIDs for pain control in this diabetic, hypertensive patient on ACE inhibitors or ARBs, as NSAIDs destabilize BP control, cause fluid retention, and worsen renal function 1
• Do not assume normal serum uric acid excludes gout during an acute attack, as uric acid levels often drop during acute inflammation 1
• Do not discontinue dapagliflozin reflexively for acute illness unless there is severe volume depletion or AKI, as it provides important cardiovascular and renal protection in diabetic patients 1, 3
• Do not start allopurinol during an acute gout attack, as this can paradoxically worsen and prolong the attack; wait 2-4 weeks after resolution 1
• Do not forget to check for septic arthritis in diabetic patients with acute monoarthritis, as the consequences of missing this diagnosis are catastrophic 6