Digital necrosis

Digital necrosis. An 18-year-old woman, with a history of severe anorexia nervosa of 5 years duration, who acknowledged regular use of tobacco and cannabis, was hospitalized for necrosis of the left index and thumb that had occurred shortly after left radial artery puncture for blood gas analysis. Acrocyanosis of the four limbs had been present since the onset of anorexia nervosa. Arteriography of the upper limbs showed major spasm of the left radial and cubital arteries and thromboses in the left interdigital arteries of the left index and thumb. The distal portions of the arteries were then on the left and on the right. The necrotic lesions healed after intravenous administration of ilomedine and interruption of tobacco and cannabis. Acrocyanosis of the four limbs persisted . 

B. Devulder. Digital necrosis in a patient with anorexia nervosa. Association of vasculopathy and radial artery injury Presse Med 2000 29(34) 1850-1852. 

Raynaud s phenomenon can occur, particularly in patients with chronic myelogenous leukemia (SEDA-20, 326) (31), and severe cases were complicated by digital necrosis (SEDA-20, 326) (SEDA-21, 369). 

There have been two reports of intraarterial promethazine injection that led to digital necrosis both eventually led to amputations [20" ]. 

In 24 cases of Raynaud s syndrome, interferon alfa was the causative agent in 14, interferon beta in 3, and interferon gamma in 5 (32). There was no consistent delay in onset and the duration of treatment before the occurrence of symptoms ranged from 2 weeks to more than 4 years. The most severe cases were complicated by digital artery occlusion and necrosis requiring amputation. Few patients had other ischemic symptoms, such as myocardial, ophthalmic, central nervous system, or muscular manifestations. Severe Raynaud s phenomenon was also reported in a 5-year-old girl with hepatitis C (33). 

Some local anaesthetics, lidocaine and bupivacaine, can be used in combination with adrenaline. Adrenaline is a vasoconstrictor and its use increases the speed of onset and prolongs the duration of action of the local anaesthetic. Vasoconstrictors should never be used with local anaesthetics in digits or appendages, because of the risk of vasoconstriction leading to ischaemic necrosis. See page 277 for a list of local anaesthetics and other injectable drugs that can be administered by podiatrists. 

Systemic vinblastine (velban, others) is approved for use in Kaposi s sarcoma and advanced cutaneous T-cell lymphoma. Intralesional vinblastine also is used to treat Kaposi s sarcoma. Intrale-sional bleomycin (blenoxane, others) is used for recalcitrant warts and has cytotoxic and proin-flammatory effects. Intralesional injection of bleomycin into the digits has been associated with a vasospastic response that mimics Raynaud s phenomenon, local skin necrosis, and flagellate hyperpigmentation. Intralesional bleomycin has been used for palliative treatment of squamous cell carcinoma. Systemic bleomycin has been used for Kaposi s sarcoma (see Chapter 51 for a more complete discussion of these agents). Liposomal anthracyclines [specifically doxorubicin (doxil, CAELYX)] may provide first-line monotherapy for advanced Kaposi s sarcoma. 

The authors pointed out that inadvertent intra-arterial administration of promethazine leads to ischemia and tissue necrosis. They further suggested that hand surgeons must be aware of this compUcation and consider the diagnosis of intra-arterial promethazine administration when evaluating patients with digital and hand ischemia who have recently had intravenous injection of medications. 

MAPKAP-K2 (MK-2), a direct substrate of p38 MAPKs, has been shown to play an important role in the production of pro-inflammatory cytokines, such as tumor necrosis factor-a (TNF-a), interleukin-1 a (IL-la) and IL-6. Thus inhibition of MK-2 kinase activity may potentially be useful for treatment of inflammatory diseases such as rheumatoid arthritis, psoriasis and inflammatory bowel disease. Two classes of MK-2 inhibitors based on carboline or pyrazinoindolone templates are highlighted. Extensive SAR efforts lead to compounds with single-digit nanomolar molecular potency. Further optimization of pyrazinoindolone-based inhibitors provides compounds with the sub-micromolar cellular potency. 

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