What is the differential diagnosis for purpuric (purpura) lesions over the lower extremities?

Differential Diagnosis for Purpuric Lesions Over the Lower Extremities

The differential diagnosis for purpuric lesions on the lower extremities should prioritize IgA vasculitis (Henoch-Schönlein purpura), drug-induced vasculitis, ANCA-associated vasculitis (particularly EGPA), necrotizing fasciitis with purpuric features, erythema migrans with purpuric presentation, and Stevens-Johnson syndrome/toxic epidermal necrolysis.

Primary Vasculitic Causes

IgA Vasculitis (Henoch-Schönlein Purpura)

• Most common systemic vasculitis presenting with non-thrombocytopenic palpable purpura concentrated on the lower extremities and buttocks 1, 2, 3
• Lesions appear as purpuric papules that may evolve into hemorrhagic vesicles and bullae in severe cases 2
• Often preceded by upper respiratory infection or pharyngitis within days to weeks 1
• Key diagnostic features include concentration of lesions at pressure points (visible "sock line" where compression occurs) 1
• Skin biopsy reveals leukocytoclastic vasculitis with IgA deposits in vessel walls on direct immunofluorescence 2, 4
• May present with associated arthralgia, abdominal pain, and hematuria without proteinuria 1

ANCA-Associated Vasculitis (EGPA)

• Purpura occurs in 20-53% of ANCA-positive patients and is more common in MPO-ANCA positive disease 5
• Skin tissue from purpuric lesions shows perivascular inflammation of dermal vessels with eosinophilic infiltrates 5
• Must evaluate for asthma, eosinophilia (absolute eosinophil count), chronic rhinosinusitis, peripheral neuropathy, and cardiac involvement 5
• ANCA testing (particularly MPO-ANCA) should be performed in all suspected cases 5
• Biopsy reveals eosinophil-rich vasculitis when feasible 5

Infectious Causes with Purpuric Features

Erythema Migrans (Lyme Disease)

• On lower extremities, erythema migrans lesions may be partially purpuric 5
• Lesions typically appear 7-14 days after tick bite and should be ≥5 cm in diameter for secure diagnosis 5
• Unlike tick bite hypersensitivity reactions, true erythema migrans increases in size over 1-2 days rather than resolving 5, 6
• Lesions often occur at unusual sites for bacterial cellulitis including the axilla and popliteal fossa 5, 6
• Serologic testing is too insensitive in the first 2 weeks to be diagnostically helpful; diagnosis should be clinical 5

Necrotizing Fasciitis with Purpuric Presentation

• Initial presentation mimics cellulitis but progresses with distinctive features 5, 6
• Wooden-hard feel of subcutaneous tissues extending beyond visible skin involvement is pathognomonic 5, 6
• Skin discoloration or gangrene occurs in 70% of cases 5
• Bullous lesions, skin necrosis, and ecchymoses are late findings 5
• Immediate surgical consultation is mandatory if suspected; diagnostic imaging should not delay treatment 5, 6

Drug-Induced and Severe Cutaneous Reactions

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis

• Presents with purpuric macules or flat atypical targets with epidermal detachment 5
• Widespread purpuric macules are characteristic of SJS/TEN spectrum 5
• Lesions described as dark red centers surrounded by pink rings, often confluent 5
• Involvement of palms and soles can be prominent with blistering 5
• Mucous membrane involvement (eyes, mouth, genitalia) is usually an early feature 5

Drug-Induced Leukocytoclastic Vasculitis

• Clindamycin and other antibiotics can trigger vasculitic reactions 1
• Presents as palpable purpura predominantly on lower extremities 1
• Temporal relationship to medication initiation (typically within 7-21 days) is key 1

Critical Diagnostic Algorithm

Initial Assessment

• Palpate all purpuric lesions to distinguish palpable purpura (vasculitis) from non-palpable purpura (coagulopathy or thrombocytopenia) 5
• Assess subcutaneous tissue consistency for wooden-hard feel indicating necrotizing fasciitis 5, 6
• Document lesion characteristics: size, borders, central clearing, target appearance, and distribution pattern 5
• Examine for pressure-point concentration (sock lines, waistbands) suggesting HSP 1

Essential Laboratory Evaluation

• Complete blood count with differential (eosinophil count, platelet count) 5
• Urinalysis with microscopy for hematuria and proteinuria 5, 1
• ANCA testing (MPO and PR3) in all cases 5
• Coagulation studies if non-palpable purpura present 1

Biopsy Indications

• Skin biopsy with direct immunofluorescence is recommended when feasible for definitive diagnosis 5
• Biopsy should be performed early in immunocompromised patients 5
• Specimens should be sent for routine histology, direct immunofluorescence, and culture if infection suspected 5

Common Pitfalls to Avoid

• Do not dismiss purpuric lesions as simple dermatitis without proper evaluation for systemic vasculitis 6
• Do not delay surgical consultation if necrotizing fasciitis is suspected based on wooden-hard subcutaneous tissues 5, 6
• Do not rely on serologic testing for early Lyme disease; diagnosis is clinical in the first 2 weeks 5
• Do not assume all lower extremity purpura is HSP in adults; ANCA-associated vasculitis and drug reactions are more common in this population 5, 7
• Do not proceed without documenting medication history, particularly recent antibiotic use 1
• Failure to assess for systemic involvement (renal, cardiac, gastrointestinal, neurologic) can miss life-threatening complications 5, 1, 2