What are the possible causes of unilateral lower‑leg swelling in a 60‑year‑old woman taking amlodipine 5 mg?

Causes of Unilateral Lower Limb Swelling in a 60-Year-Old Female on Amlodipine 5mg

The most likely cause is amlodipine-induced peripheral edema, which occurs as a dose-limiting side effect in patients taking calcium channel blockers, but deep vein thrombosis must be urgently excluded first due to its life-threatening potential.

Immediate Priority: Exclude Deep Vein Thrombosis

Deep vein thrombosis is the most critical diagnosis to rule out first, as it carries significant morbidity and mortality risk if untreated. 1

Clinical Features Suggesting DVT

• Unilateral extremity swelling (present in 80% of DVT cases), pain (75%), erythema (26%), heaviness distal to the thrombus, and unexplained persistent calf cramping 1, 2
• Unilateral swelling specifically indicates obstruction at the level of major veins 1, 2
• Temperature asymmetry >2°C between limbs suggests active inflammatory process requiring urgent evaluation 1, 2

Risk Factors to Assess

• Indwelling venous devices (highest risk), active malignancy, recent surgery or trauma, heart failure, advanced age (60 years qualifies), hypercoagulability, or prolonged immobilization 1
• Recent history of vascular access procedures or COVID-19 infection 3

Diagnostic Approach for DVT

Proceed directly to proximal compression ultrasound or whole-leg ultrasound without D-dimer testing if clinical suspicion is high (Wells score ≥3). 1

• If Wells score ≤1 (low probability): Begin with highly sensitive D-dimer; negative result excludes DVT 1
• If Wells score = 2 (moderate probability): Highly sensitive D-dimer is preferred initial test 1
• If Wells score ≥3 (high probability): Skip D-dimer and obtain immediate ultrasound 1
• Initiate parenteral anticoagulation immediately while awaiting results in high-risk patients 1, 2

Primary Cause: Amlodipine-Induced Peripheral Edema

Lower limb peripheral edema is explicitly recognized as a dose-limiting factor for calcium channel blockers, particularly amlodipine. 3

Mechanism and Characteristics

• Amlodipine causes peripheral edema through preferential arteriolar vasodilation without corresponding venodilation, leading to increased capillary hydrostatic pressure and fluid extravasation 4
• The FDA label lists "swelling of your legs or ankles" as one of the most common side effects 4
• Edema is more common with the 10 mg dose but can occur at 5 mg 5
• European Society of Cardiology guidelines specifically identify "lower limb peripheral oedema" as a limiting factor for dose increase in calcium channel blocker therapy 3

Clinical Pattern

• Typically bilateral but can present unilaterally, particularly early in the course 6
• Develops gradually after starting therapy or dose increase 4
• Pitting edema that worsens throughout the day and improves with leg elevation 2
• Not associated with warmth, erythema, or pain (unlike DVT or cellulitis) 1

Alternative Diagnoses to Consider

Chronic Venous Insufficiency

• Presents with aching, heaviness, cramping, throbbing, and swelling that worsens at day's end and improves with leg elevation 2
• Associated with varicose veins and symptoms worsening with prolonged standing 2
• Requires duplex ultrasound to assess venous reflux and deep venous system 2

Cellulitis

• Presents with erythema, warmth, tenderness, and unilateral red, warm, swollen leg 1
• Must be differentiated from DVT as both can present similarly 1
• Radiographic findings may show soft tissue swelling, effacement of fat planes, or gas formation 2

Heart Failure

• Causes increased capillary hydrostatic pressure leading to peripheral edema 3, 2
• Typically bilateral but can be asymmetric 2
• Associated with other signs of volume overload (dyspnea, orthopnea, elevated jugular venous pressure) 3

Lymphedema

• Excessive accumulation of protein-rich fluid in interstitial and fibro-adipose tissues 2
• Chronic, progressive course with non-pitting quality in advanced stages 2
• May be primary or secondary to surgery, radiation, or malignancy 2

Diagnostic Algorithm

1. Calculate Wells score to stratify DVT risk 1
2. If high probability (Wells ≥3): Obtain immediate compression ultrasound; start empiric anticoagulation if imaging delayed >4 hours 1
3. If low-moderate probability: Obtain D-dimer; if positive, proceed to ultrasound 1
4. If DVT excluded: Consider amlodipine as primary cause given temporal relationship and known side effect profile 3, 4
5. Assess for alternative causes: Examine for signs of venous insufficiency (varicose veins, skin changes), heart failure (jugular venous distension, pulmonary rales), or infection (warmth, erythema) 2

Management if Amlodipine-Induced Edema Confirmed

Discontinuation of amlodipine results in resolution of edema. 6

• Consider switching to an alternative antihypertensive class (ACE inhibitor, ARB, thiazide diuretic) 3
• If calcium channel blocker required, consider non-dihydropyridine (diltiazem) which has lower incidence of peripheral edema 3
• Diuretics are generally ineffective for calcium channel blocker-induced edema as the mechanism is not volume overload 3

Critical Pitfalls to Avoid

• Do not dismiss unilateral swelling as benign drug effect without excluding DVT first 1, 2
• Do not rely on absence of warmth or redness to exclude DVT—approximately one-third of DVT patients are asymptomatic 1
• Do not use D-dimer as initial test in high-probability patients—proceed directly to ultrasound 1
• Do not assume bilateral presentation is required for drug-induced edema—amlodipine can cause unilateral upper or lower extremity edema 6