What is lower extremity vasculitis?

Lower Extremity Vasculitis

Lower extremity vasculitis is an inflammatory process affecting blood vessel walls in the legs, leading to vessel damage, compromise, or destruction, resulting in hemorrhagic and ischemic events that can cause significant morbidity and mortality if left untreated.

Definition and Classification

Lower extremity vasculitis is part of a broader spectrum of vasculitic disorders characterized by inflammation and damage to blood vessels. Vasculitis can be classified based on:

1. Vessel size affected:

   • Large vessels (aorta and major branches)
   • Medium vessels (main visceral arteries)
   • Small vessels (arterioles, venules, capillaries)

2. Primary vs. Secondary:

   • Primary: idiopathic vasculitis without clear underlying cause
   • Secondary: associated with underlying conditions such as:
     • Connective tissue diseases
     • Infections
     • Adverse drug reactions
     • Malignancies

3. Histopathologic patterns:

   • Lymphocytic
   • Leukocytoclastic
   • Granulomatous

Common Types Affecting Lower Extremities

• Buerger's disease (Thromboangiitis obliterans): A nonatherosclerotic inflammatory vasculitis that most commonly involves small and medium-sized distal arteries of the feet. Almost always associated with tobacco smoking, predominantly occurring in patients between 25-45 years with an incidence of 12.6 per 100,000 in North America 1. Presents with progressively worsening superficial thrombophlebitis, intermittent claudication, paresthesias, rest pain, and ulceration. Imaging typically shows "corkscrew" collateral vessels.

• Giant cell arteritis (Takayasu's disease): Affects large vessels including the aorta and its first and second-order branches 1.

• Polyarteritis nodosa: Classically targets medium-sized vessels (conduit muscular arteries and branches) 1.

• Rheumatoid vasculitis: Occurs in approximately 2-5% of patients with longstanding, severe rheumatoid arthritis. Presents as peripheral vascular lesions including purpura, cutaneous ulceration, and gangrene of the distal extremities 2.

• Livedoid vasculitis/vasculopathy: Most commonly affects women and is generally localized on lower extremities. May be associated with autoimmune diseases, capillary obstruction with cryoglobulins, or antiphospholipid syndrome 3.

Clinical Presentation

Lower extremity vasculitis typically manifests as:

• Skin manifestations:

  • Palpable purpura (most common)
  • Infiltrated erythema
  • Nodular erythema
  • Livedo racemosa (reticular pattern)
  • Deep ulcers
  • Digital gangrene 4

• Vascular symptoms:

  • Claudication (pain with walking)
  • Rest pain
  • Paresthesias
  • Swelling
  • Poorly healing wounds

• Systemic symptoms (may be present depending on type):

  • Fever
  • Weight loss
  • Fatigue
  • Arthralgia/arthritis

Diagnostic Approach

1. Clinical examination:

   • Comprehensive pulse examination with numerical grading (0-3)
   • Blood pressure measurement in both arms
   • Auscultation of femoral arteries for bruits
   • Thorough lower extremity examination including color and temperature of skin, presence of hair loss or trophic changes, integrity of skin, presence of ulcerations 5

2. Laboratory tests:

   • Complete blood count
   • Inflammatory markers (ESR, CRP)
   • Renal and liver function tests
   • Urinalysis for proteinuria and hematuria
   • Autoimmune markers (ANA, ANCA, RF)
   • Cryoglobulins
   • Antiphospholipid antibodies 5, 4

3. Imaging studies:

   • Ankle-brachial index (ABI) to assess for arterial insufficiency
   • Duplex ultrasound to evaluate vascular patency and flow
   • CT angiography or MR angiography for detailed vascular assessment 5

4. Biopsy:

   • Skin biopsy extending to subcutis from the most tender, reddish, or purpuric lesional skin
   • Direct immunofluorescence to distinguish IgA-associated vasculitis from IgG/IgM-associated vasculitis 4

Differential Diagnosis

Lower extremity vasculitis must be distinguished from:

• Atherosclerotic peripheral arterial disease
• Deep vein thrombosis
• Thrombotic disorders (e.g., antiphospholipid syndrome)
• Embolic disease
• Fibromuscular dysplasia
• Physiological entrapment syndromes
• Cystic adventitial disease 1

Management

Treatment depends on the specific type of vasculitis, its severity, and organ involvement:

1. General measures:

   • Leg elevation
   • Avoidance of prolonged standing
   • Smoking cessation (particularly crucial for Buerger's disease) 4

2. Pharmacological treatment:

   • Mild disease: NSAIDs, colchicine, dapsone
   • Moderate to severe disease: Systemic corticosteroids
   • Severe or refractory disease: Immunosuppressants (azathioprine, methotrexate, cyclophosphamide)
   • Very severe or life-threatening disease: Combination of corticosteroids and cyclophosphamide
   • Refractory cases: Consider plasmapheresis, intravenous immunoglobulin, or biologic therapies (TNF-α inhibitors, rituximab) 4

3. Management of complications:

   • Antiplatelet therapy for thrombotic risk
   • Antibiotics for infected ulcerations
   • Wound care for ulcerations
   • Pain management 5, 3

Prognosis

The prognosis varies significantly depending on the specific type of vasculitis, extent of organ involvement, and timeliness of treatment. Without appropriate treatment, vasculitis can lead to:

• Chronic non-healing ulcers
• Tissue loss and gangrene
• Limb amputation
• Increased risk of cardiovascular events
• Increased mortality 6, 7

Key Pitfalls to Avoid

1. Delayed diagnosis: Vasculitis can mimic other conditions, leading to delayed treatment and worse outcomes.

2. Inadequate biopsy: Obtaining a biopsy of insufficient depth or from a non-representative area can lead to false-negative results.

3. Failure to distinguish vasculitis from pseudovasculitis: Thrombotic disorders like antiphospholipid syndrome can mimic vasculitis clinically.

4. Underestimating cardiovascular risk: Patients with vasculitis have increased risk of cardiovascular events and require appropriate risk factor management.

5. Focusing only on leg symptoms: Vasculitis is often a systemic disease requiring comprehensive evaluation and management 5, 4.