What is the most likely etiology of a 72-year-old woman's right lower extremity symptoms, with erythema, ill-defined line of demarcation, and a 5 cm stage 1 wound, without fever, chills, or trauma, and a normal temperature, with a past medical history negative for diabetes and clotting disorders?

Most Likely Etiology: Cellulitis

The most likely etiology is cellulitis, a bacterial soft tissue infection characterized by erythema with an ill-defined border, which is the hallmark distinguishing feature from other causes of lower extremity erythema. 1, 2

Key Diagnostic Features Supporting Cellulitis

The clinical presentation demonstrates classic inflammatory signs of infection:

• Erythema with ill-defined demarcation is pathognomonic for cellulitis, as opposed to the sharp, well-demarcated borders seen in erysipelas 1
• Presence of ≥2 inflammatory signs (erythema, local warmth based on low-grade temperature, wound presence) meets diagnostic criteria for soft tissue infection 3, 2
• Stage 1 wound serving as portal of entry provides the necessary break in skin integrity for bacterial invasion, even without reported trauma 1
• Low-grade fever (99.3°F) indicates systemic response without meeting criteria for severe infection requiring immediate surgical consultation 1, 3

Critical Differential Considerations to Exclude

Venous Insufficiency (Phlebolymphedema)

While venous disease is the most common cause of lower extremity erythema in this age group (41.8% of cases), several features argue against this diagnosis 4:

• Venous stasis typically presents with bilateral involvement (74.5% of cases), whereas this patient has unilateral symptoms 4
• Venous dermatitis develops gradually over months to years with chronic edema, hyperpigmentation, and lipodermatosclerosis, not acutely over 5 days 1, 5
• The acute 5-day timeline is inconsistent with chronic venous disease progression 1

Deep Vein Thrombosis

DVT remains in the differential but is less likely given 6:

• Absence of severe pain, cyanosis, or pulselessness that would suggest phlegmasia cerulea dolens 6
• Normal vital signs except minimal temperature elevation 6
• However, duplex ultrasound should still be obtained to definitively exclude DVT, as cellulitis and DVT can coexist 2

Peripheral Arterial Disease

PAD is unlikely because 1:

• The patient lacks classic claudication symptoms or rest pain 1
• Erythema and warmth suggest hyperemia rather than ischemia 1
• Stage 1 wound without tissue loss is inconsistent with critical limb ischemia 1

Immediate Management Algorithm

Wound Assessment and Drainage

• Examine the wound for purulent drainage, probe depth, and assess for deeper tissue involvement to determine infection severity (Grade 2 mild vs Grade 3 moderate) 1, 3, 2
• If purulent material present, perform incision and drainage immediately as this is the most critical intervention, more important than antibiotics alone 1, 3
• Obtain wound cultures from deep tissue before initiating antibiotics 3

Antibiotic Selection

Given the systemic signs (fever) and erythema extending beyond the wound:

• Initiate empiric antibiotics covering Staphylococcus aureus and Streptococcus species 1, 3
• Consider local MRSA prevalence when choosing between anti-staphylococcal penicillin (if MRSA unlikely) versus vancomycin or linezolid (if MRSA prevalent) 3
• Start with parenteral therapy given fever and systemic signs, transitioning to oral highly bioavailable agents once improving 3
• Plan for 2-4 weeks total duration for moderate soft tissue infection with systemic signs 3

Mandatory Vascular Assessment

Despite infection being most likely, perform bedside vascular testing immediately 2:

• Palpate dorsalis pedis and posterior tibial pulses bilaterally 2
• Measure ankle-brachial index (ABI) 2
• Order duplex ultrasound if pulses diminished or ABI <0.9 to exclude concomitant DVT or arterial insufficiency 2

Critical Pitfalls to Avoid

• Do not rely on antibiotics alone if purulent material is present—drainage is mandatory and more important than antimicrobial therapy 1, 3
• Do not assume normal WBC or minimal fever excludes significant infection—inflammatory markers may be absent in up to half of patients with serious infections 7
• If no improvement within 24-48 hours, broaden coverage to include gram-negative and anaerobic organisms (piperacillin-tazobactam or carbapenem) for polymicrobial infection 1, 3
• Reassess daily for signs of necrotizing fasciitis: pain out of proportion, crepitus, bullae, rapid progression, or systemic toxicity requiring emergency surgical consultation 1, 3