What is chronic limb ischemia?

Definition of Chronic Limb Ischemia

Chronic limb ischemia (CLI) is a condition characterized by chronic (≥2 weeks) ischemic rest pain, nonhealing wounds/ulcers, or gangrene in one or both legs attributable to objectively proven arterial occlusive disease. 1

Key Diagnostic Features

Clinical Presentation

• Rest pain: Burning pain in the arch or distal foot that occurs during recumbency and is relieved when the feet are in a dependent position 2
• Tissue loss: Nonhealing ulcers or gangrene 1
• Chronicity: Symptoms persisting for at least 2 weeks, distinguishing it from acute limb ischemia 1

Objective Diagnostic Criteria

• Arterial disease must be objectively proven using one or more of the following:
  • Ankle-Brachial Index (ABI) ≤ 0.4
  • Ankle systolic pressure ≤ 50 mmHg
  • Toe systolic pressure ≤ 30 mmHg
  • TcPO₂ < 30 mmHg 3, 2

Distinguishing CLI from Acute Limb Ischemia

Feature	Chronic Limb Ischemia	Acute Limb Ischemia
Onset	Gradual, ≥2 weeks	Sudden, <2 weeks
Clinical signs	Rest pain, nonhealing wounds, gangrene	Pain, pallor, pulselessness, poikilothermia (cold), paresthesias, paralysis (6 P's)
Collateral development	Present	Limited or absent
Tissue viability	Threatened but stable	Immediately threatened

Risk Factors for CLI Development and Limb Loss

• Diabetes mellitus
• Severe renal failure
• Severely decreased cardiac output
• Vasospastic diseases
• Smoking and tobacco use
• Infection (cellulitis, osteomyelitis)
• Skin breakdown or traumatic injury 1

Clinical Significance and Prognosis

CLI represents the most advanced form of peripheral arterial disease (PAD) with significant implications for morbidity, mortality, and quality of life:

• Incidence: 500-1000 per million per year, highest among older adults, smokers, and diabetics 4
• Amputation rates: 10-40% without intervention 4
• Cardiovascular risk: 3-fold higher risk of myocardial infarction, stroke, and vascular death compared to patients with intermittent claudication 4
• Quality of life: Can be worse than that of patients with terminal cancer 1

Management Considerations

The primary goals in managing CLI are:

1. Relieve ischemic pain
2. Heal ulcers
3. Prevent limb loss
4. Improve function and quality of life
5. Prolong survival 5

Treatment options include:

• Revascularization: Surgical bypass or endovascular procedures

  • Surgical bypass with vein is preferred for patients likely to survive ≥2 years or those with long segment occlusions 6
  • Endovascular therapy is preferred for patients with reduced life expectancy or elevated surgical risk 6

• Medical management:

  • Antiplatelet therapy (aspirin or clopidogrel) to reduce cardiovascular events and risk of arterial occlusion
  • Prostanoids (particularly iloprost) may help with rest pain, ulcer healing, and reducing amputation risk 5

• Primary amputation: May be considered for patients with unreconstructable disease, extensive necrosis involving weight-bearing areas, non-ambulatory status, or severe comorbidities 6

Monitoring and Follow-up

Patients with CLI or who have undergone successful treatment for CLI should be evaluated at least twice annually by a vascular specialist due to the relatively high incidence of recurrence 1.

Emerging Therapies

Research is ongoing into novel approaches including:

• Angiogenic growth factors
• Stem cell therapies
• Biomaterial approaches to stimulate angiogenesis 7, 5

CLI represents a critical public health issue due to its negative impact on quality of life and poor prognosis both in terms of limb salvage and survival 4.