What is the recommended approach to evaluating a patient with retiform purpura?

Approach to Evaluation of Retiform Purpura

Retiform purpura is a dermatologic emergency requiring immediate systematic evaluation because it signals complete vascular occlusion with downstream ischemia, and the underlying causes—including calciphylaxis, warfarin necrosis, antiphospholipid syndrome, heparin-induced thrombocytopenia with thrombosis, disseminated intravascular coagulation, and vasculitis—carry mortality rates exceeding 50% if diagnosis and intervention are delayed. 1, 2, 3

Immediate Clinical Recognition

• Retiform purpura presents as branching, net-like (livedoid) purpuric lesions with irregular borders that follow the angioarchitecture of dermal vessels, distinguishing it from simple petechiae or ecchymoses. 1, 2, 3
• When retiform purpura manifests as palpable plaques, vascular inflammation (vasculitis) is present; when non-palpable, consider thrombotic or embolic occlusion. 1, 2
• Progression to necrosis, ulceration, or eschar formation indicates full-thickness ischemia and mandates urgent intervention. 1, 2, 3

Algorithmic Diagnostic Approach

Step 1: Immediate Bedside Assessment (Within Minutes)

• Assess hemodynamic stability, fever, and signs of sepsis—bacterial endocarditis, meningococcemia, and disseminated intravascular coagulation can present with retiform purpura and require emergent blood cultures and empiric antibiotics. 2, 4
• Examine for cardiac murmur (endocarditis), digital ischemia (cholesterol emboli, antiphospholipid syndrome), and livedo racemosa (vasculopathy vs. vasculitis). 2, 3
• Document medication history within the past 2 weeks, specifically warfarin initiation (warfarin necrosis), heparin exposure (heparin-induced thrombocytopenia with thrombosis), and any new antibiotics or anticoagulants. 1, 2

Step 2: Urgent Laboratory Evaluation (Within 1–2 Hours)

Core Coagulation and Hematologic Studies

• Complete blood count with peripheral smear—look for thrombocytopenia (HIT, DIC, TTP), schistocytes (TTP, DIC), and leukocytosis (sepsis, vasculitis). 5, 2
• Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, and D-dimer—prolonged PT/aPTT with low fibrinogen and elevated D-dimer confirms disseminated intravascular coagulation. 5, 2
• Platelet count—if <100 × 10⁹/L with recent heparin exposure (5–10 days), calculate 4T score immediately and send anti-PF4 antibodies for heparin-induced thrombocytopenia. 5, 6

Thrombophilia and Autoimmune Panel

• Antiphospholipid antibody panel (lupus anticoagulant, anticardiolipin IgG/IgM, anti-β2-glycoprotein I)—positive in antiphospholipid syndrome, which causes thrombosis with thrombocytopenia. 2, 3, 7
• Protein C and protein S activity levels—deficiency causes warfarin-induced skin necrosis when warfarin is initiated without heparin bridging. 1, 2, 3
• Cryoglobulins—positive in hepatitis C-associated vasculitis and cryoglobulinemic vasculitis. 2, 4

Infectious and Inflammatory Markers

• Blood cultures × 2 sets (aerobic and anaerobic) before antibiotics—mandatory in any febrile patient with retiform purpura to exclude endocarditis and septic emboli. 2, 4
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)—markedly elevated in vasculitis and infection. 2, 3
• Antinuclear antibody (ANA), anti-dsDNA, complement C3/C4—screen for systemic lupus erythematosus, which can present with retiform purpura and antiphospholipid syndrome. 3, 7

Renal and Metabolic Studies

• Serum creatinine, calcium, phosphate, and parathyroid hormone—calcium-phosphate product >70 mg²/dL² suggests calciphylaxis in dialysis-dependent or advanced chronic kidney disease patients. 1, 2, 3
• Urinalysis with microscopy—red blood cell casts indicate glomerulonephritis from systemic vasculitis. 5, 2

Step 3: Skin Biopsy (Within 4–6 Hours)

• Perform two 4-mm punch biopsies from the edge of an early lesion (not necrotic center)—one for routine histopathology (formalin) and one for direct immunofluorescence (Michel's medium or fresh frozen). 1, 2, 3
• Histopathology distinguishes vasculitis (leukocytoclastic vasculitis, fibrinoid necrosis) from thrombotic occlusion (fibrin thrombi without vessel wall inflammation) from calciphylaxis (medial calcification with intimal hyperplasia). 1, 2, 3
• Direct immunofluorescence detects IgA deposition (Henoch-Schönlein purpura), IgG/IgM/C3 (lupus vasculitis), or is negative (thrombotic disorders). 2, 3

Step 4: Imaging and Subspecialty Consultation

• Echocardiography (transthoracic or transesophageal)—obtain within 24 hours if blood cultures are positive, new murmur is present, or septic emboli are suspected. 2, 4
• Computed tomography angiography or Doppler ultrasound—if cholesterol emboli are suspected (recent vascular procedure, livedo, renal failure, eosinophilia). 2, 3
• Dermatology consultation—essential for biopsy interpretation and management of calciphylaxis, warfarin necrosis, and complex vasculitis. 1, 2, 3
• Hematology consultation—mandatory if thrombocytopenia, coagulopathy, or thrombophilia is identified. 5, 2

Etiology-Specific Management Priorities

Heparin-Induced Thrombocytopenia (HIT)

• Immediately discontinue all heparin products (including flushes) and initiate non-heparin anticoagulation (argatroban, bivalirudin, fondaparinux) without awaiting antibody results if 4T score ≥4. 5, 6
• Do not transfuse platelets unless life-threatening bleeding occurs, as platelet transfusion in HIT increases thrombosis risk. 5

Warfarin-Induced Skin Necrosis

• Stop warfarin immediately and administer intravenous vitamin K 10 mg plus fresh frozen plasma to reverse anticoagulation. 1, 2, 3
• Initiate therapeutic heparin or low-molecular-weight heparin for underlying thrombotic indication while protein C levels recover. 1, 2, 3
• Screen for protein C/S deficiency and consider long-term anticoagulation with direct oral anticoagulants or warfarin with proper heparin bridging. 1, 2, 3

Antiphospholipid Syndrome

• Begin therapeutic anticoagulation with low-molecular-weight heparin or unfractionated heparin, transitioning to warfarin (target INR 2–3) for long-term management. 2, 3, 7
• Avoid direct oral anticoagulants in triple-positive antiphospholipid syndrome (lupus anticoagulant, anticardiolipin, anti-β2-glycoprotein I), as warfarin is superior. 3, 7

Calciphylaxis

• Discontinue vitamin K antagonists, iron supplementation, and calcium-based phosphate binders. 1, 2, 3
• Initiate sodium thiosulfate 25 g intravenously three times weekly during dialysis sessions—this is the only intervention with mortality benefit. 1, 2, 3
• Aggressive wound care with non-adherent dressings and pain control; avoid debridement of non-infected eschar, as it worsens ischemia. 1, 2, 3

Disseminated Intravascular Coagulation

• Treat the underlying trigger (sepsis, malignancy, trauma) with source control, antibiotics, or chemotherapy. 5, 2
• Transfuse platelets if <20 × 10⁹/L with active bleeding; transfuse fresh frozen plasma if PT/aPTT >1.5× normal with bleeding; transfuse cryoprecipitate if fibrinogen <100 mg/dL. 5, 2

Vasculitis

• Initiate high-dose corticosteroids (methylprednisolone 1 g intravenously daily × 3 days, then prednisone 1 mg/kg/day) for medium-vessel vasculitis or systemic vasculitis with organ involvement. 2, 3
• Add cyclophosphamide or rituximab for ANCA-associated vasculitis or cryoglobulinemic vasculitis refractory to corticosteroids. 2, 4

Critical Pitfalls to Avoid

• Never assume retiform purpura is "just a rash"—it represents vascular occlusion with impending necrosis and requires the same urgency as acute limb ischemia. 1, 2, 3
• Do not delay skin biopsy waiting for laboratory results—histopathology provides the definitive diagnosis and guides therapy before antibody or culture results return. 1, 2, 3
• Never restart warfarin without heparin bridging in a patient with warfarin-induced skin necrosis, as this will precipitate recurrent thrombosis. 1, 2, 3
• Do not transfuse platelets in heparin-induced thrombocytopenia unless life-threatening bleeding is present, as this paradoxically increases thrombosis risk. 5, 6
• Avoid debridement of calciphylaxis lesions unless frank infection is present, as surgical trauma extends ischemic injury. 1, 2, 3