Acute Ischemia of Lower Extremities Caused by Ergotamine Toxicity due to Pharmacologic Interaction With Cobicistat in an HIV-Positive Patient.

Ergotism is an uncommon condition that affects patients with exposure to ergot alkaloids causing ischemia of extremities. We report the case of lower extremities ischemia caused by ergot toxicity in a human immunodeficiency virus (HIV) positive individual due to the interaction between ergot alkaloid and Cobicistat. In addition, we present a brief review of medical, and pharmacological aspects of this condition. To our knowledge, this is the second reported case describing this interaction.

ANNIVERSARY REVIEW: 50 years since the discovery of bromocriptine.

Ergotism is the long-term ergot poisoning by ingestion of rye or other grains infected with the fungus Claviceps purpurea and more recently by excessive intake of ergot drugs. It has either neuropsychiatric or vascular manifestations. In the Middle Ages, the gangrenous poisoning was known as St. Anthony's fire, after the order of the Monks of St. Anthony who were particularly skilled at treating the condition. In 1917, Prof. Arthur Stoll returned home to Switzerland from Germany, to lead the development of a new pharmaceutical department at Sandoz Chemical Company. Stoll, using the special methods of extraction learned from his work with his mentor Willstetter, started his industrial research work with ergot. He succeeded in isolating, from the ergot of rye, ergotamine as an active principle of an old popular remedy for excessive post-partum bleeding. The success of this discovery occurred in 1918 and was translated into a pharmaceutical product in 1921 under the trade name Gynergen. In subsequent work, Stoll and his team were leaders in identifying the structure of the many other alkaloids and amines produced by Claviceps purpurea This was the cultural background and scientific foundation on which bromocriptine was discovered.

Ergotismo por uso simultáneo de ergotamínico y terapia antirretroviral: Report of one case / Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy

High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results.

Activities and Effects of Ergot Alkaloids on Livestock Physiology and Production.

Consumption of feedstuffs contaminated with ergot alkaloids has a broad impact on many different physiological mechanisms that alters the homeostasis of livestock. This change in homeostasis causes an increased sensitivity in livestock to perturbations in the ambient environment, resulting in an increased sensitivity to such stressors. This ultimately results in large financial losses in the form of production losses to livestock producers around the world. This review will focus on the underlying physiological mechanisms that are affected by ergot alkaloids that lead to decreases in livestock production.

Ergotism: a change of persepective.

Clinical ergotism is a rare disorder, and clinical and therapeutic implications have continued to attract attention. The Holy Fire or St. Anthony's Fire was the primary vascular manifestation, causing burning pain and gangrene in the feet and hands related to the arterial spasm properties of ergot. The chronic use of ergotamine and migraine has also been associated with ergotism. Severe vasospasm and acute peripheral ischemia of the extremities can develop. However, in modern times, the spectrum of poisoning by alkaloids has broadened to include antiviral therapies in patients with HIV and abuse of stimulants. These changes have made taking an accurate medical history and conducting an accurate detailed differential diagnosis more essential. The purpose of this review is to highlight the importance of ergotism as a cause of peripheral vascular ischemia and analyze changes associated with this poisoning.

Ergotismo y HIV / Ergotism and HIV

El ergotismo es una complicación de la intoxicación aguda y/o el abuso crónico de los derivados del ergot. Se manifiesta por síndrome vasomotor con enfermedad vascular periférica que frecuentemente compromete extremidades. Presentamos cuatro casos de pacientes infectados con el virus de la inmunodeficiencia humana 1 (HIV-1), en tratamiento con antirretrovirales que incluyen inhibidores de la proteasa reforzados con ritonavir, y que habían recibido ergotamina como automedicación. Ellos desarrollaron síntomas de enfermedad vascular periférica y al examen físico sus pulsos estaban disminuidos o ausentes. El Doppler arterial confirmó signos de espasmo arterial difuso en dos de ellos. Se hizo diagnóstico de ergotismo secundario a la asociación de ergotamina-inhibidores de la proteasa. Los pacientes fueron tratados con la discontinuación de las drogas involucradas (inhibidores de la proteasa y ergotamina), bloqueantes cálcicos, profilaxis antitrombótica con enoxaparina, antiagregación con ácido acetil salicílico y uno ellos recibió pentoxifilina e infusión de prostaglandinas vasodilatadoras con mejoría de los síntomas. Discutimos la presentación clínica de esta interacción medicamentosa, difícil de diagnosticar correctamente sin una fuerte sospecha de su existencia.

Ergotism is a complication of acute intoxication and/or chronic abuse of ergot derivatives. It expresses itself through a vasomotor syndrome with peripheral vascular disease which frequently involves extremities. We report four cases of HIV-1 infected patients treated with antiretroviral drugs including boosted-protease inhibitors who had self-treated themselves with ergotamine. They developed peripheral vascular disease symptoms and their pulses where diminished or absent in the physical examination. Arterial Doppler confirmed diffused arterial spasm in two of them. Ergotism following ergotamine-protease inhibitors association was diagnosed. Patients were treated through the discontinuity of involved drugs (protease inhibitors and ergotamine), calcium blockers; antithrombotic prophylaxis with enoxaparine, antiaggregant therapy with acetylsalicylic acid, and one of them received pentoxifylline and vasodilator prostaglandins infusion, with amelioration of the symptoms. We discuss the clinical presentation of this drug interaction, difficult to diagnose properly without a strong suspicion of its existence.

Infarto esplénico ¿Ergotismo inducido por ritonavir? / Splenic infarction: Ergotism induced by ritonavir?

El ergotismo es una enfermedad conocida desde la antigüedad, que se caracteriza por isquemia y, en algunos casos, gangrena de las extremidades. Muchas drogas de uso corriente tienen la capacidad de interactuar con los ergotamínicos desarrollando ergotismo como efecto adverso. Un ejemplo de ello es el ritonavir, un inhibidor de la proteasa utilizado en pacientes con el virus de la inmunodeficiencia humana (HIV). Presentamos un caso de ergotismo en un varón de 39 años con infección por HIV en tratamiento con ritonavir que, después de ingerir 1 mg de tartrato de ergotamina, además de presentar manifestaciones clásicas de la enfermedad, desarrolló un infarto esplénico. Por lo tanto, consideramos importante advertir a los pacientes sobre la posible interacción farmacológica entre los ergotamínicos y otras drogas de uso frecuente y, en particular, el ritonavir en pacientes portadores de HIV.

Ergotism is a clinical condition known since old times and whose main characteristics are ischemia and even limb gangrene. Some drugs have the capacity of interacting with small amounts of ergotamine or its derivatives producing ergotism as a side effect. This is the case of ritonavir, a widely used anti-HIV drug. Here we present a case of ergotism that developed in an HIV positive 39 year old male under treatment with ritonavir, after taking 1 mg of ergotamine tartrate. His clinical picture, apart from showing the basic manifestations of the disease, was associated with splenic infarction. For this reason, we consider important to advise patients about the potential pharmacological interaction between ergotamines and others common drugs and, in particular, ritonavir in HIV positive patients.

Ergotismo secundario a la asociación ergotamina-ritonavir: A propósito de 3 casos / Ergotism secondary to ergotamine-ritonavir association: Report of three cases

Ergotism is a complication of the acute intoxication or chronic abuse of ergot derivatives. It may be manifested by a vasomotor syndrome with peripheral vascular disease frequently involving extremities. We report three patients infected with human immunodeficiency virus (HIV), in antiretroviral treatment (ART) that included a protease inhibitor as ritonavir, and had received self-medicated ergotamine. They developed symptoms of peripheral vascular disease and the physical examination showed no arterial pulses in the affected vessels. Arterial Doppler confirmed signs of diffuse arterial spasm in all of them. An arteriography was performed to the second patient and it showed obliteration of the distal sector of the ulnar and radial arteries. Ergotism secondary to ergotamine-ritonavir association was diagnosed. Patients were treated discontinuing the administration of involved drugs, arterial vasodilators and prophylactic anticoagulation, with marked improvement of symptoms.

Chronic ergot toxicity presenting with bilateral external iliac artery dissection and lower extremity rest pain.

Chronic use of ergot alkaloids has been recognized as a rare cause of lower extremity ischemia. Most patients with ergot toxicity present with symptoms of lower extremity claudication. Herein we present a woman with bilateral lower extremity rest pain and a history of chronic ergot use for migraine headaches. Arteriography demonstrated extensive pruning of the distal arterial tree along with bilateral external iliac artery dissections - a finding that is not often associated with young, normotensive patients with chronic ergot toxicity. This patient was treated with endovascular stenting of the dissections along with cessation of ergot. Her symptoms improved markedly, and follow-up arteriography 6 weeks later demonstrated resolution of the iliac dissections along with restoration of nearly normal lower extremity runoff vessels. Discontinuation of ergot-containing products and cessation of tobacco and caffeine use is the cornerstone of therapy in chronic ergot toxicity. The association of ergot toxicity and iliac dissection has not been previously described. Endovascular or surgical interventions may be considered in patients with ergot toxicity for specific indications or those whose symptoms progress despite conservative management.

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.

Manifold manifestations of ergotism.

Vasospastic side effects leading to organic manifestations are rare in ergotamine therapy. To our knowledge, combinations of more than two signs of ergotism have rarely been described in the literature so far. We present a 65-year-old male patient who as a consequence of severe migraine had developed ergotamine abuse. He was admitted to our hospital after one week of increasing abdominal pain. During laparotomy, necrotic areas of the small intestine and the sigmoid colon were resected, which on histopathologic examination revealed severe hypertrophy of the smooth musculature of mesenteric arteries, resulting from chronic vasospasms. Postoperatively, the patient developed ischaemia of the limbs which was confirmed by angiography. Before death, the patient also showed ischaemic signs in the acrae and necrosis of the tongue.

Ergotismo: ¿iatrogenia o idiosincrasia? / Ergotism: Iatrogenic or idiosyncrasy?

El ergotismo continúa siendo una causa rara de insuficiencia arterial crónica y aguda en pacientes en edad productiva, que si no es detectada y tratada a tiempo puede causar daño neurológico permanente o pérdida de la extremidad y como consecuencia invalidez del paciente. En un lapso de dos años se recibieron en el servicio cuatro pacientes con diagnóstico de ergotismo, tres mujeres y un hombre, se manejaron con interrupción de la ergotamina, vasodilatadores y dos de ellos con simpatectomía lumbar; dos de los pacientes presentaron secuelas y determinar si el ergotismo es una iatrogenia causada por el uso prolongado de este medicamento

[Vascular ergotism through inhalation of grain dust]. / Vaskulärer Ergotismus durch Getreidestaubinhalation.

HISTORY AND CLINICAL FINDINGS: For 6 months a 42-year-old farmer without cardiovascular risk factors had been suffering from increasing pain in both feet and calves. Angiography two months apart had demonstrated progressive narrowing of all lower-leg arteries. Pain-free walking had become restricted to 50 m, there were no palpable pulses in the right foot and those in the left foot were markedly reduced. INVESTIGATIONS: Occlusion pressure of the right foot was 55 mm Hg. Repeat angiography showed proximal occlusion of all three lower-leg arteries. Biopsy and biochemical tests excluded degenerative and inflammatory causes of the vascular disease. DIAGNOSIS, TREATMENT AND COURSE: Enquiry of the patient discovered that he had been exposed to ergotamine-containing milling dust in the preparation of rye flour. Inhalational intake of ergotamine was proven by a high plasma ergotamine level. Attempted treatment with prostaglandin E1 (intraarterially for 16 days), doxazosin (2 mg/d) and acetylsalicylic acid 300 mg/d) had only little effect on symptoms. But complete avoidance of exposure to flour dust slowly decreased the plasma level of ergotamine within 4 months, after which all lower-leg arteries had almost completely re-opened. CONCLUSIONS: This is the first reported case proving that chronic ergotamine inhalation can cause ergotism affecting peripheral arteries. As the plasma ergotamine level fell only slowly it must be assumed that ergotamine had accumulated in a, so far unknown, body depot with slow release into the blood.

Saint Anthony's fire revisited. Vascular problems associated with migraine medication.

Ergotamine and related compounds have been used for many years in the management of migraine. This review highlights the potential for toxic effects upon the arterial system which may arise from the use of ergot medications. Data on four female patients aged from 30 to 49 years were collected retrospectively from in-patient records and out-patient follow-up between 1978 and 1990. All four patients presented with the symptoms and signs of arterial obstruction and all had been prescribed ergot preparations as treatment and prophylaxis of migraine, for periods ranging from three to 12 years. Two patients had an acute arterial obstruction that resolved completely when the migraine medication was withdrawn. Two had chronic obstructions and radiological and surgical examination gave evidence of arterial stenosis. These two patients were treated with bypass surgery. Review of the literature indicated that other authors had described similar cases but without specifying the methods of data collection. This report supports the findings of others regarding the toxic effects of ergot preparations upon the arterial system, which may take the form of chronic or acute obstruction. General practitioners and physicians should be aware of the possible complications arising from prolonged or excessive use of ergot medications.

St. Anthony's fire: successful reversal of ergotamine-induced peripheral vasospasm by hydrostatic dilatation.

A 60-year-old trauma victim developed severe ischemia of all four extremities following administration of heparin-dihydroergotamine as prophylaxis against deep venous thrombosis. Despite cessation of heparin-dihydroergotamine and infusion of intraarterial papaverine into the right femoral artery, both lower extremities progressed to frank gangrene and amputation (above-knee on the left and below-knee on the right). However, both ischemic upper extremities were salvaged following intraoperative hydrostatic dilatation with balloon catheters. Ergotism is an avoidable and potentially treatable cause of peripheral gangrene in the critically-ill patient.