Chronic Ergot Toxicity: a Rare Cause of Lower Extremity Ischemia
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Chronic ergot toxicity: A rare cause of lower extremity ischemia George D. Garcia, MD,a James M. Goff, Jr, MD,b Neal C. Hadro, MD,b Sean D. O’Donnell, MD,b and Patricia S. Greatorex, MD,a Ft Bragg, NC, Washington, DC, and Bethesda, Md Chronic ergot toxicity is a rare cause of lower extremity ischemia. The cornerstone of therapy in ergot toxicity is to discontinue the use of caffeine, cigarettes, and all ergot- containing medications. Although multiple different therapies have been recommended for acute toxicity, no specific treatment is uniformly recommended in chronic toxicity. We present a case of long-term ergot use for migraine headaches in a woman who had severe chronic lower extremity claudication. This case demonstrates the unique features associated with the diagnosis and management of chronic ergot toxicity. We recommend a conservative approach consisting of observation, antiplatelet agents, and the discon- tinuance of ergots. If symptoms progress to rest pain or gangrene, surgical treatment should be considered. (J Vasc Surg 2000;31:1245-7.) The toxic effects of ergot alkaloids have been Ergotamine decreases the vasodilation of cranial recognized for more 2000 years. The Book of Parsees, arteries, especially the branches of the external written between 400 and 300 BC, warns of “. nox- carotid artery that cause migraine headache. ious grasses that cause pregnant women to drop the Ergotamine may also stimulate serotonin receptors, womb and die in childbed.”1 Outbreaks of epidem- which causes vasoconstriction.5 Contraindications to ic gangrene occurred during the Middle Ages, and the use of ergot alkaloids include hepatic or renal dis- affected patients were said to be consumed by “holy ease, peripheral vascular disease, thrombophlebitis, fire” because of the charcoal-like appearance and hyperthyroidism, Raynaud’s or Buerger’s disease, burning pain of gangrenous limbs.2 The most effec- and pregnancy.5 tive treatment was provided at the hospitals of St Despite the known indications and contraindica- Anthony. The condition became known as “St tions to the use of ergot-containing medications, Anthony’s Fire.”2 In 1676, it was discovered that acute toxicity is still reported. However, there is lit- Claviceps purpurea was the cause of epidemic gan- tle reported literature on chronic lower extremity grene. C purpurea is an ergot-producing fungus that ischemia resulting from ergot toxicity. We describe a infects grain, most often rye.3 patient with severe lower extremity claudication The major effects of ergot alkaloids are direct from chronic ergot toxicity who has responded well smooth muscle stimulation, central sympatholytic to the discontinuance of all ergot-containing prepa- activity, and peripheral alpha-adrenergic blockade.4 rations and antiplatelet therapy. CASE REPORT From the Department of Surgery, Womack Army Medical Centera and the Peripheral Vascular Surgery Service, Walter A 34-year-old Hispanic woman with a 4-year history Reed Army Medical Center, and the Department of Surgery, of progressive bilateral lower extremity claudication was Uniformed Services University of the Health Sciences.b seen by her primary care physician. The patient noted a Competition of interest: nil. marked decrease in her walking distance over the 3 The opinions contained herein do not reflect the opinions of the months before her evaluation, and at presentation she was Uniformed Services University, the Department of the Army, able to ambulate 50 to 75 ft before the onset of bilateral or the Department of Defense. calf pain. Reprint requests: James M. Goff, Jr, MD, Peripheral Vascular Her past medical history was only remarkable for Surgery Service, Department of Surgery, Walter Reed Army migraine headaches, first diagnosed when she was age 13 Medical Center, Washington, DC, 20307. Copyright © 2000 by The Society for Vascular Surgery and years, for which she had taken ergot-containing medica- International Society for Cardiovascular Surgery, North tion (Cafergot and Migri Diaxadol) almost daily. She American Chapter. denied any history of tobacco use, hypercholesterolemia, 0741-5214/2000/$12.00 + 0 24/4/105668 hypertension, diabetes mellitus, or lower extremity trau- doi:10.1067/mva.2000.105668 ma. She was without any systemic complaints. The physi- 1245 JOURNAL OF VASCULAR SURGERY 1246 Garcia et al June 2000 Fig 1. Pelvic arteriogram showing marked vasospasm and Fig 3. Marked vasospasm of the left superficial femoral extensive collaterals. Note the narrow left external iliac artery. artery. progressive improvement over the following 3 months, and her superficial ulcers are healed. The patient reports that she can walk 100 yd before the onset of pain. Her peripheral pulse examination now shows palpable pedal pulses and ankle-brachial indices of 0.8 bilaterally. DISCUSSION Ergot toxicity is seen most often in women in their midthirties who have migraine headache.5 The incidence of ergot intoxication is difficult to mea- sure, but it has been estimated at less than 0.01% of all users.4 It can occur after short-term small doses, after excessive doses, and after therapeutic doses over a long period of time. Most cases of ergot tox- icity have been associated with excessive doses, but serious extremity ischemia has been seen with as lit- tle as 2 mg of ergotamine.5 Although the usual dose of ergotamine is 1 mg orally or 2 mg rectally (with Fig 2. Extensive vasospasm of the right superficial femoral 100 mg of caffeine) not to exceed 10 mg in 1 week, artery. the absorption of ergot alkaloids is erratic, and exact therapeutic and toxic levels have not been estab- lished.6 There is an increased incidence of toxicity cal examination was remarkable for normal upper extrem- with suppositories because absorption is greater by ity pulses and blood pressures. The lower extremity exam- means of this route.7 The clinical signs of ergotism ination was remarkable for a weak left femoral pulse and do not correlate with blood ergotamine levels absent pedal pulses bilaterally. Ankle-brachial indices were because toxicity can occur even with undetectable 0.3 on the left and 0.45 on the right. She had marked ele- blood levels.6 vation pallor and dependent rubor of both feet. The skin Three classes of side effects can occur with ergot on her feet was atrophic, and she had superficial ulcers on the great toes of both feet. toxicity: neurologic side effects, including headache, An arteriogram was obtained that showed findings vertigo, psychosis, convulsions, and coma; alimentary consistent with vascular ergot toxicity (Figs 1-3). All side effects, including nausea, vomiting, diarrhea, and ergotamine-containing medications were discontinued, cramping abdominal pain; and finally, vascular side and aspirin was prescribed for the patient. She has had effects, including vasospasm and, rarely, thrombosis.8 JOURNAL OF VASCULAR SURGERY Volume 31, Number 6 Garcia et al 1247 The predominant vascular toxicity occurs in the 3 weeks of bilateral hand ischemia. This was success- extremities, with 60% to 70% of cases affecting the ful, presumably because of disruption of arterial lower limbs.2 However, cases of vasospasm in the smooth muscle, which prevented vasoconstriction. aorta, renal, carotid, digital, mesenteric, retinal, and coronary arteries have been reported, as well as uter- CONCLUSION ine cramping and spontaneous abortion.5 The vas- We have presented the case of a 34-year-old cular insufficiency of ergotism results from spasm woman with a 20-year history of ergot use that has and is characterized in the extremity by pallor, cool- resulted in chronic arterial insufficiency. No other ness, numbness, and intermittent claudication pro- case in the literature has documented symptoms of gressing to pain at rest. If ergot use continues, the this duration. The cornerstone of therapy in ergot affected limb may develop dry gangrene and, less toxicity is to discontinue the use of caffeine, ciga- commonly, suppurative gangrene and sepsis.4 rettes, and all ergot-containing medications. We rec- There are three arteriographic findings that can ommend a conservative approach consisting of be seen in ergotism: a generalized intense arterial observation, antiplatelet agents, and the discontinu- spasm, formation of collateral vessels, and throm- ance of ergots. If symptoms progress to rest pain or boses.8 Spasm most often begins in the superficial gangrene, surgical treatment should be considered. femoral artery and becomes more severe distally REFERENCES with smooth, tapered, “threadlike narrowings,” fol- lowed by abrupt severe spasm causing distal occlu- 1. Tanner R. St. Anthony’s fire, then and now: a case report and historical review. Can J Surg 1987;30:291-3. 5 sion. In chronic toxicity, collateral vessels form. 2. 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