Patient with red, tender, warm, non‑follicular patches on the legs extending beyond the lower portion—what is the differential diagnosis and recommended work‑up and treatment?

Red, Non-Follicular Patches on Legs: Differential Diagnosis and Management

The most critical first step is to determine whether this represents cellulitis, erythema nodosum, or a life-threatening necrotizing soft tissue infection—look immediately for severe pain disproportionate to findings, systemic toxicity, skin necrosis, bullae, or crepitus, which mandate emergency surgical consultation. 1

Immediate Red Flags Requiring Emergency Intervention

• Severe pain disproportionate to clinical findings suggests necrotizing fasciitis and requires immediate surgical exploration 1
• Systemic toxicity with altered mental status, fever >38°C or <36°C, heart rate >90 bpm, or hypotension indicates systemic inflammatory response syndrome requiring urgent intervention 1
• Skin necrosis, bullae, ecchymoses, or crepitus are late findings of necrotizing infection demanding immediate surgical debridement 1
• Hard, wooden feel of subcutaneous tissue extending beyond visible erythema suggests deep fascial involvement 1
• Failure to respond to initial antibiotic therapy within 48-72 hours should prompt reconsideration of necrotizing infection 1

Differential Diagnosis Framework

Most Likely Diagnoses for Red, Tender, Warm, Non-Follicular Leg Patches:

Cellulitis:

• Presents with erythema, warmth, tenderness, and edema extending beyond the area of skin involvement 1
• Look for at least 2 classic inflammatory signs: erythema, warmth, swelling, tenderness, or purulent discharge 1, 2
• Typically unilateral and spreads rapidly over hours to days 1

Erythema Nodosum:

• Raised, tender, red or violet subcutaneous nodules 1-5 cm in diameter 1
• Commonly affects anterior tibial areas (extensor surfaces) 1
• Associated with inflammatory bowel disease, sarcoidosis, streptococcal infection, or medications 1
• Firm clinical diagnosis can usually be made without biopsy 1

Necrotizing Fasciitis (if severe features present):

• May initially resemble cellulitis but progresses rapidly 1
• Distinguished by the red flags listed above 1

Alternative Diagnoses to Consider:

Drug eruption, Sweet syndrome, leukocytoclastic vasculitis, or erythema multiforme should be considered in the differential, particularly in immunocompromised patients 1

Contact dermatitis or severe seborrheic dermatitis may present with atypical distribution 1

Diagnostic Work-Up Algorithm

Step 1: Clinical Assessment

• Document presence of at least 2 inflammatory signs (erythema >0.5 cm, warmth, tenderness, swelling, purulent discharge) 1
• Measure temperature difference between affected and unaffected leg—difference ≥2°C suggests active inflammatory process 2
• Assess for systemic signs: fever, tachycardia, hypotension, altered mental status 1

Step 2: Risk Factor Identification

• Diabetes with neuropathy: Increases risk of infection and Charcot neuro-osteoarthropathy 1, 2
• Peripheral vascular disease: Absent pulses or ankle-brachial index <0.9 increases infection risk 1
• Immunosuppression: HIV, malignancy, chemotherapy, transplant recipients require broader differential 1
• Recent trauma or wound: Increases risk of necrotizing infection 1

Step 3: Laboratory Testing

• Blood cultures if systemic signs present 1
• Complete blood count looking for leukocytosis >12,000 or <4,000 cells/μL 1
• Metabolic panel to assess for acidosis, hyperglycemia, or azotemia suggesting severe infection 1
• Wound culture if purulent drainage present 1

Step 4: Imaging (When Indicated)

• Plain radiographs as first-line imaging to evaluate for gas in soft tissues, which indicates necrotizing infection 1, 2
• CT or MRI may show fascial plane edema in necrotizing fasciitis, but should not delay surgical consultation if clinical suspicion is high 1
• Avoid delaying definitive treatment while waiting for imaging if necrotizing infection suspected 1

Step 5: Tissue Diagnosis (Select Cases)

• Biopsy or aspiration should be implemented early in immunocompromised patients with atypical presentations 1
• Surgical exploration is both diagnostic and therapeutic for suspected necrotizing fasciitis—fascia appears swollen, dull gray with stringy necrosis 1

Treatment Algorithm

For Suspected Cellulitis (Most Common Scenario):

Empiric Antibiotic Therapy:

• Mild infection: Oral cephalexin or dicloxacillin targeting Staphylococcus aureus and Streptococcus pyogenes 3
• Moderate-to-severe infection: IV vancomycin if MRSA suspected, or IV ceftriaxone for streptococcal coverage 1
• Reassess at 48-72 hours for clinical improvement; if no improvement, reconsider diagnosis and broaden coverage 2

For Erythema Nodosum:

• Treat underlying condition (inflammatory bowel disease, streptococcal infection) 1
• Systemic corticosteroids are usually required for symptomatic relief 1
• Azathioprine or anti-TNF therapy (infliximab, adalimumab) for resistant or recurrent cases 1

For Necrotizing Fasciitis:

• Immediate surgical debridement is the primary therapeutic modality—return to operating room every 24-36 hours until no further debridement needed 1
• Broad-spectrum IV antibiotics: Vancomycin plus piperacillin-tazobactam or carbapenem, plus clindamycin (for toxin suppression) 1
• Add doxycycline plus ceftriaxone if water exposure suggests Vibrio or Aeromonas 1

Common Pitfalls to Avoid

• Do not wait for imaging results if necrotizing fasciitis is suspected—clinical judgment and immediate surgical consultation are paramount 1
• Do not assume cellulitis if pain is disproportionate to findings—this is the hallmark of deeper infection 1
• Do not delay antibiotics in patients with systemic signs—mortality increases with delayed treatment 1
• Do not perform biopsy for typical cellulitis—reserve for immunocompromised patients with atypical presentations 1, 4
• Do not ignore bilateral presentation—consider systemic causes like drug reaction, vasculitis, or Sweet syndrome 1

When to Escalate Care

• Immediate surgical consultation for any suspicion of necrotizing infection based on clinical red flags 1
• Infectious disease consultation for immunocompromised patients, recurrent infections, or failure to respond to initial therapy 1, 2
• Dermatology consultation if diagnosis remains uncertain after initial work-up or if biopsy shows atypical features 1