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      Upper limb artery segmental occlusions due to chronic use of ergotamine combined with itraconazole, treated by thrombolysis

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          Abstract

          Background

          The ergotamine tartrate associated with certain categories of drugs can lead to critical ischemia of the extremities. Discontinuation of taking ergotamine is usually sufficient for the total regression of ischemia, but in some cases it could be necessary thrombolytic and anticoagulant therapy to avoid amputation.

          Case report

          A woman of 62 years presented with a severe pain left forearm appeared 10 days ago, with a worsening trend. The same symptoms appeared after 5 days also in the right forearm. Physical examination showed the right arm slightly hypothermic, with radial reduced pulse in presence of reduced sensitivity. The left arm was frankly hypothermic, pulse less on radial and with an ulnar humeral reduced pulse, associated to a decreased sensitivity and motility.

          Clinical history shows a chronic headache for which the patient took a daily basis for years Cafergot suppository (equivalent to 3.2 mg of ergotamine).

          From about ten days had begun therapy with itraconazole for vaginal candidiasis. The Color-Doppler ultrasound shown arterial thrombosis of the upper limbs (humeral and radial bilateral), with minimal residual flow to the right and no signal on the humeral and radial left artery.

          Results

          Angiography revealed progressive reduction in size of the axillary artery and right humeral artery stenosis with right segmental occlusions and multiple hypertrophic collateral circulations at the elbow joint. At the level of the right forearm was recognizable only the radial artery, decreased in size. Does not recognize the ulnar, interosseous artery was thin. To the left showed progressive reduction in size of the distal subclavian and humeral artery, determined by multiple segmental steno-occlusion with collateral vessels serving only a thin hypotrophic interosseous artery.

          Arteriographic findings were compatible with systemic drug-induced disease. The immediate implementation of thrombolysis, continued for 26 hours, with heparin in continuous intravenous infusion and subsequent anticoagulant therapy allowed the gradual disappearance of the symptoms with the reappearance of peripheral pulses.

          Conclusion

          Angiography showed regression of vasospasm and the resumption of flow in distal vessels. The patient had regained sensitivity and motility in the upper limbs and bilaterally radial and ulnar were present.

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          Most cited references12

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          Ergotism associated with HIV antiviral protease inhibitor therapy.

          Ergotism is a rare condition of acute vasospasm found classically in young and middle-aged women taking ergot alkaloid agents to treat migraine headache. We report the case of a young man with human immunodeficiency virus (HIV) positivity and describe the drug interaction between protease inhibitors and ergot alkaloid agents, which most likely predisposed to development of ergot toxicity. The HIV-positive population receiving antiviral therapy may be an under-recognized group at risk for ergotism through decreased hepatic metabolism of ergot preparations.
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            Ergotamine abuse: results of ergotamine discontinuation, with special reference to the plasma concentrations.

            Twenty-three patients suffering from continuous headache linked with habitual daily use of ergotamine tartrate were studied. Their headaches were classified clinically, and possible side effects of ergotamine medication, plasma levels of ergotamine, and occurrence of withdrawal symptoms after discontinuation of drug abuse were recorded. Seventeen of the patients were clinically diagnosed as suffering from "ergotamine headache", and seven of them complained of coldness in the extremities. Plasma ergotamine levels were measured by using a radioimmunoassay. In almost half of the patients the 1 h plasma levels after the daily dose were below the detection limit of the procedure (0.12 ng/ml). The duration and severity of the withdrawal symptoms did not correlate with the doses and plasma levels of ergotamine. In only 4 of the 21 patients who were followed up for 3 to 6 months did headache symptoms not improve after ergotamine withdrawal. The results indicate that even small (0.5-1.0 mg/day) doses of ergotamine tartrate taken regularly may cause continuous headache symptoms and withdrawal symptoms after discontinuation.
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              Erythromycin-associated ergotamine intoxication: arteriographic and electrophysiologic analysis of a rare cause of severe ischemia of the lower extremities and associated ischemic neuropathy.

              Vasospasm associated with ergotamine is a well-known phenomenon. In this case report we present a rare drug interaction between erythromycin and ergotamine at normal doses causing lower extremity ischemia in a 36-year-old woman. Nitroprusside proved to be the treatment of choice. The response was dramatic and took place in a matter of hours in this patient. Ischemic monomelic neuropathy is a recently described entity in which axonal necrosis is caused by a loss of distal extremity blood flow. The association between erythromycin and ergotamine may be a dangerous pharmacologic combination; drugs that have a hepatic cycle with ergotamine derivatives must be used with caution.
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                Author and article information

                Journal
                Thromb J
                Thrombosis Journal
                BioMed Central
                1477-9560
                2011
                30 August 2011
                : 9
                : 13
                Affiliations
                [1 ]Surgical Clinic, University of Brescia, 25123, Brescia, Italy
                [2 ]Radiologic clinic, University of Brescia, 25123, Brescia, Italy
                Article
                1477-9560-9-13
                10.1186/1477-9560-9-13
                3180257
                21878097
                712a6a0c-63ba-4c24-835a-4c7b5d8e074e
                Copyright ©2011 Cervi et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 January 2011
                : 30 August 2011
                Categories
                Case Report

                Cardiovascular Medicine
                itraconazole,fibrinolysis,ergotamine,upper limb ischemia
                Cardiovascular Medicine
                itraconazole, fibrinolysis, ergotamine, upper limb ischemia

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