What are the treatment options for a swollen knee without a history of trauma or injury?

Swollen Knee Without Injury: Treatment Approach

For a swollen knee without trauma, begin with plain radiographs (AP, lateral, sunrise/Merchant, and tunnel views) to identify underlying causes such as osteoarthritis, chondrocalcinosis, or osteochondritis dissecans, then proceed with arthrocentesis and synovial fluid analysis to differentiate infectious, crystal-induced, and inflammatory etiologies before initiating treatment. 1, 2, 3

Initial Diagnostic Workup

Mandatory First Steps

• Obtain four-view plain radiographs (anteroposterior, lateral, sunrise/Merchant, and tunnel views) as the essential first imaging study to exclude fracture, osteoarthritis, osteochondritis dissecans, loose bodies, chondrocalcinosis, or tumor. 4, 2, 3

• Perform arthrocentesis with synovial fluid analysis to differentiate infectious arthritis, crystal-induced arthropathy (gout, CPPD), and inflammatory conditions—this is essential before any treatment decisions. 1, 3

• Assess for posterior knee swelling or palpable mass: If present, obtain compression ultrasound of the proximal deep veins immediately to rule out popliteal vein thrombosis, which requires urgent anticoagulation. 3

Clinical History Details to Elicit

• Age and chronicity: Patients ≥45 years with activity-related knee pain and less than 30 minutes of morning stiffness have 95% sensitivity for osteoarthritis. 5

• Pattern of swelling: Recurrent episodes suggest crystal arthropathy (CPPD) or chronic inflammatory conditions; persistent swelling after initial improvement may indicate Lyme arthritis requiring re-treatment. 1

• Mechanical symptoms: Locking, catching, popping, or giving way suggest meniscal pathology or loose bodies, though meniscal tears are incidental findings in the majority of patients >70 years. 4, 2

• Signs of inflammation: Presence of effusion, warmth, and erythema warrant immediate arthrocentesis to exclude septic arthritis before any corticosteroid administration. 1, 3

Treatment Algorithm Based on Underlying Diagnosis

If Osteoarthritis with Effusion (Most Common in Adults ≥45 Years)

Non-pharmacological interventions form the foundation and should be initiated immediately:

• Exercise therapy (strengthening and aerobic exercise) is first-line treatment with demonstrated efficacy in reducing pain and improving function. 4, 2

• Weight reduction if overweight—a large cohort study showed weight loss reduced the risk of knee OA progression. 4

• Patient education and self-management programs to empower patients in managing their condition. 4, 2

Pharmacological options (after non-pharmacological measures):

• Paracetamol (acetaminophen) up to 4 grams daily is the oral analgesic to try first and the preferred long-term oral analgesic, with good safety profile (adverse events 1.5%) and efficacy similar to naproxen 750 mg/day in two-year trials. 4

• Topical NSAIDs have clinical efficacy and are safe, particularly for localized knee pain. 4

• Oral NSAIDs should be considered in patients unresponsive to paracetamol; in patients with increased gastrointestinal risk, use non-selective NSAIDs with effective gastroprotective agents or selective COX-2 inhibitors. 4, 6

• Intra-articular corticosteroid injection is indicated for flare of knee pain, especially if accompanied by effusion, but only after infection has been excluded by synovial fluid analysis. 4, 1, 3

If Calcium Pyrophosphate Deposition (CPPD) Disease with Chronic Inflammatory Arthritis

First-line pharmacological treatment:

• Low-dose colchicine or NSAIDs combined with gastro-protective agents are first-line treatments for chronic CPP crystal inflammatory arthritis causing recurrent knee swelling. 1, 3

• Colchicine demonstrated an NNT of 2 for clinical response (>30% pain reduction) at 4 months in patients with knee OA and persistent CPPD inflammation. 1

Second-line options for refractory cases:

• Hydroxychloroquine is effective for chronic inflammatory arthritis with CPPD, with an NNT of 2 for clinical response (>30% reduction in swollen/tender joint count). 1

• Low-dose methotrexate showed excellent clinical response in uncontrolled trials for severe CPPD refractory to conventional treatment, with significant decreases in pain intensity, joint counts, and attack frequency. 1, 7

If Lyme Arthritis with Persistent/Recurrent Swelling

Treatment algorithm:

• Re-treatment with another 4-week course of oral antibiotics is recommended first if arthritis has improved but not completely resolved after initial antibiotic treatment. 1

• Wait several months before initiating re-treatment to allow for the anticipated slow resolution of inflammation after antibiotic therapy; use NSAIDs for symptom control during this period. 1

• Do NOT administer intra-articular corticosteroids during active infection or while awaiting response to antibiotics. 1, 3

• If arthritis persists despite intravenous therapy and synovial fluid PCR is negative, symptomatic treatment with NSAIDs, intra-articular corticosteroids, or DMARDs is appropriate. 1

When to Proceed with MRI

MRI without contrast is appropriate when:

• Radiographs show only joint effusion or are normal, AND pain persists despite 4-6 weeks of conservative treatment. 2, 3

• Clinical suspicion exists for meniscal tear, ligament injury, or occult fracture in the appropriate clinical context. 2

• Concomitant knee pathology is suspected (meniscal pathology, ACL injury, articular cartilage injury) after initial radiographic evaluation. 4

Note: MRI should never be performed before plain radiographs—approximately 20% of patients with chronic knee pain inappropriately undergo MRI without recent radiographs. 2, 3

Critical Pitfalls to Avoid

• Never administer intra-articular corticosteroids before excluding infection through arthrocentesis—this can worsen septic arthritis and lead to joint destruction. 1, 3

• Never delay compression ultrasound when posterior knee swelling is present—popliteal DVT requires immediate anticoagulation to prevent fatal pulmonary embolism. 3

• Do not withhold anticoagulation for confirmed popliteal DVT—the risk of fatal PE far outweighs bleeding risks. 3

• Avoid performing MRI before plain radiographs—this leads to unnecessary costs and may miss important radiographic findings like chondrocalcinosis or osteochondritis dissecans. 2, 3

• Do not assume mechanical symptoms indicate surgical pathology—meniscal tears are equally common in painful and asymptomatic knees in patients 45-55 years, and conservative management (exercise therapy) is first-line treatment even in the presence of mechanical symptoms. 4, 2, 5

Monitoring and Follow-up

• Patients on long-term NSAIDs should have hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia; decrease in hemoglobin of 1 gram or more was observed in 17-23% of patients on ibuprofen 1600-2400 mg daily. 6

• Patients on methotrexate should be monitored for hepatic effects, as borderline elevations of liver tests may occur in up to 15% of patients; notable elevations of ALT or AST (approximately three times the upper limit of normal) have been reported in approximately 1% of patients. 7

• Re-evaluate at 4-6 weeks if conservative management (exercise, weight loss, NSAIDs) is initiated for osteoarthritis or suspected meniscal pathology. 5