Critical limb ischemia

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Critical limb ischemia (CLI), also referred to as Limb threat, is an advanced stage of peripheral artery disease. It includes ischemic rest pain, arterial insufficiency ulcers, and gangrene. The latter two conditions are jointly referred to as tissue loss, reflecting the development of surface damage to the limb tissue due to the most severe stage of ischemia. CLI has a negative prognosis within a year after the initial diagnosis, with 1-year amputation rates of approximately 12% and mortality of 50% at 5 years and 70% at 10 years.[1]

CLI was conceived to identify patients at high-risk for major amputation, but the increasing prevalence of diabetes mellitus has led to a broader conception of limb threat that includes the risk of amputation associated with severely infected and non-healing wounds.[2]


Critical limb ischemia is further subdivided into rest pain and tissue loss:

Rest pain[edit]

Rest pain is a continuous burning pain of the lower leg or feet. It begins, or is aggravated, after reclining or elevating the limb and is relieved by sitting or standing. It is more severe than intermittent claudication, which is also a pain in the legs from arterial insufficiency.

Tissue loss[edit]

Tissue loss is the development of arterial insufficiency ulcers or gangrene due to peripheral artery disease.


Treatment mirrors that of other symptoms of peripheral artery disease, and includes modifying risk factors, revascularization via vascular bypass or angioplasty, and in the case of tissue loss, wound debridement.


In 2011 pCMV-vegf165 was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[3][4]


  1. ^ Varu, VN; Hogg, ME; Kibbe, MR (January 2010). "Critical limb ischemia.". Journal of vascular surgery 51 (1): 230–41. doi:10.1016/j.jvs.2009.08.073. PMID 20117502. 
  2. ^ Mills JL, Sr; Conte, MS; Armstrong, DG; Pomposelli, FB; Schanzer, A; Sidawy, AN; Andros, G; Society for Vascular Surgery Lower Extremity Guidelines, Committee (January 2014). "The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System: risk stratification based on wound, ischemia, and foot infection (WIfI).". Journal of vascular surgery 59 (1): 220–34.e1–2. doi:10.1016/j.jvs.2013.08.003. PMID 24126108. 
  3. ^ "Gene Therapy for PAD Approved". 6 December 2011. Retrieved 5 August 2015. 
  4. ^ Deev, R.; Bozo, I.; Mzhavanadze, N.; Voronov, D.; Gavrilenko, A.; Chervyakov, Yu.; Staroverov, I.; Kalinin, R.; Shvalb, P.; Isaev, A. (13 March 2015). "pCMV-vegf165 Intramuscular Gene Transfer is an Effective Method of Treatment for Patients With Chronic Lower Limb Ischemia". Journal of cardiovascular pharmacology and therapeutics. doi:10.1177/1074248415574336. Retrieved 5 August 2015. 

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