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.

Ergotism with acute limb ischemia, provoked by HIV protease inhibitors interaction with ergotamine, rescued by multisite transluminal balloon angioplasty.

Acute limb ischemia induced by arterial vasospasm remains an exceptional situation, favoured by the use of arterial vasoconstrictors. The risk of these substances is largely underestimated in the general population, especially with the co-administration of strong cytochrome inhibitors like human immunodeficiency virus (HIV) protease inhibitors. A 33-year-old woman, who used to take dihydroergotamine for orthostatic hypotension, was prescribed a post-exposure HIV prophylaxis including lopinavir and ritonavir. One day later, she presented an acute bilateral limb ischemia with a sudden pain in both calves, initially while walking and then at rest with bilateral ischemic toes. Angiography confirmed diffuse arterial vasospasm of the lower limb arteries. A first-line therapy with isosorbide dinitrate and amlodipine was ineffective, with rapid clinical worsening. A combination of intra-arterial injections and intra-venous infusions of vasodilators, transluminal balloon angioplasty and bilateral 4-Compartment fasciotomies permitted rapid improvement and finally resulted in both lower limbs rescue. This case and literature review illustrate ergotism due to ergotamine overdose after taking HIV protease inhibitors. It also demonstrates the benefit of an interventional procedure besides medical therapy with vasodilators in severe arterial vasospasm. All along the lower limb arterial tree, transluminal balloon angioplasty restored the blood flow, without vasospasm recurrence. CONCLUSION: In case of ergotism with acute lower limbs ischemia, combining medical vasodilator therapy with interventional procedure can restore the arterial blood flow, thus allowing to save lower limbs.

Neuropatía úptica isquémica anterior unilateral asociada con ergotismo / Anterior unilateral ischemic optic neuropathy associated to ergotism

Case report of a patient with ergotism. ergotism is a complication of acute intoxication of chronic abuse of ergot derivates. Ergot is a fungus that grows on rye and less commonly on other grases such as wheat. Ergotism is a severe reaction to ergocontaminated food (such as rye bread). Ergot refers to a group of fungi of the genus Claviceps. It is a condition that develops of longterm ingestion of ergotamines. In excess, ergotamine can cause symptos such as hallucinations, severe gastrointestinal upset, a type-of dry gangrene and a pain-ful sensation in the extremities. Our patient is presented with anterior unilateral ischemic optic neuropathy. The studies performed and the clinical evaluatiion, are presented, and the treatment the same as the follow-up, are described in the article.

Isquemia de miembros inferiores secundaria a ergotamina. Reporte de casos y revisión de literatura / Lower limb ischaemia secondary to ergotamine. Case reports and a review of the literature

El ergotismo es en la actualidad un trastorno raro, asociado a la administración iatrogénica de ergotamina en pacientes que padecen de cefaleas migrañosas. La intensidad del vasoespasmo que presenta esta entidad clínica en la mayoría de los casos resulta en isquemia aguda de las extremidades. Presentamos 2 casos de isquemia aguda de las extremidades, en pacientes de sexo femenino, de mediana edad, con signos y síntomas que amenazaban la viabilidad de los miembros inferiores. El estudio por ultrasonido y la arteriografía (en el caso 1) confirmaron la presencia de espasmo arterial bilateral difuso. Inmediatamente se procedió a interrumpir la administración de ergotamina y se instauró terapia vasodilatadora. Los síntomas de las pacientes empezaron a mejorar a las 48-72 h de iniciado el tratamiento (AU)

Ergotism is a rare disorder associated with the iatrogenic administration of ergotamine in patients with migraine headaches. The intense vasospasm that occurs in this clinical condition results in acute limb ischaemia in the majority of cases. Two cases are presented of acute limb ischaemia in middle age female patients with signs and symptoms that threatened the viability of lower limbs. Duplex ultrasound and arteriography (in the first case) confirmed the presence of a bilateral diffuse arterial spasm. Ergotamine treatment was discontinued immediately and vasodilator therapy was administered. The patient's symptoms began to improve 48-72 h after starting therapy (AU)

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

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.

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.

Ergotism in Thailand caused by increased access to antiretroviral drugs: a global warning.

Ergotism is a toxic condition resulting from overexposure to the ergot compounds produced by various fungi of the genus Claviceps. Traditionally, such exposure was due to ingestion of infected grains, but long-term or excessive use of medications containing ergot derivatives or drug-drug interactions between these medications can result in ergotism. Ergotamine, typically used to treat migraine, has less than 5% bioavailability due to extensive first-pass metabolism by cytochrome P450 3A4 (CYP3A4). Concurrent intake of ergotamine and strong CYP3A4 inhibitors, such as the HIV protease inhibitors (PIs), can lead to clinical ergotism. A total of 13 cases of clinical ergotism in HIV-infected patients has been published since 1997 (most recently reviewed by Frohlich et al).

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.

An unusual mimicker of a sepsis outbreak: ergot intoxication.

Methylergonovine (MEV) is a semi-synthetic ergot alkaloid used in the prevention and control of postpartum hemorrhage. This report describes 12 newborns born on the same day in a local country hospital in Turkey and developed sepsis-like symptoms and encephalopathy within the first 6 h of life due to accidental administration of MEV instead of vitamin K in the delivery room. The major features of MEV poisoning were lethargy (41.7%), seizure (75.0%), feeding intolerance (66.6%), hypoventilation (58.3%), irritability (25%), and peripheral circulatory abnormalities (58.3%). As a conclusion, clinical findings of ergot toxicity in newborns cannot be distinguished from infectious disease or neonatal encephalopathy.

[Angiospastic occlusion of the superficial femoral artery by chronic ergotamine intake]. / Vasospastischer Verschluss der Arteria femoralis superficialis nach chronischem Ergotaminkonsum.

HISTORY AND CLINICAL FINDINGS: A 42- year old women with a long history of migraine presented with burning pain of the limbs and reduced walking distance. No risk factors for peripheral arterial occlusive disease were present. Her daily medication included an ergotamine-containing-combination (2 mg ergotamine tartrate, 100 mg caffeine daily). INVESTIGATIONS: On examination both limbs were found to be cool and pulseless below the knee. The peripheral Doppler pressure indicated a bilaterally reduced ankle-brachial index. Color-coded duplex sonography showed constricted vessels and long stenosis with a decreased echo from the wall of the left and a distal occlusion of the right femoral artery without atherosclerotic changes. A diagnosis of ergotism was made and an arteriography was omitted because of the typical findings. TREATMENT AND COURSE: A detoxication treatment was initiated and optional intravenous prostaglandine E1 recommended if the condition did not improve. 23 days later the Doppler pressure and the Duplex sonography had become normal and showed spontaneous revascularization of the previously occluded right femoral artery, although collateral vessels were still detectable. CONCLUSION: Nowadays iatrogenic ergotism of the limbs is a rare diagnosis. An exact medical history and typical duplex sonographic findings confirm the diagnosis even if characteristic risk factors are missing. The first therapeutic measure in case of claudication is for ergotamine to be stopped. In case of critical ischaemia or gangrene immediate vasodilator therapy, e. g. with prostaglandine E1, is indicated.

Painful ANA-positive scleroderma-like disease with acral ulcerations: a case of chronic gangrenous ergotism.

Chronic ergotism is a rare cause of limb ischemia. In this case report, the authors present a 62-year-old woman with history of long-term use of ergotamine alkaloids for the treatment of menstrual pain, who developed a severe painful disease initially misdiagnosed as systemic sclerosis (scleroderma) for 3 decades. She presented with a combination of acral gangrene, foot ulcer, renal obstruction, mild pulmonary fibrosis, and reduced esophageal motility. Right-sided renal obstruction was evident. The condition was extremely painful and had led to muscular contractions and immobility, drug abuse, and anemia. After establishing the diagnosis of chronic gangrenous ergotism, changing drug therapy, mobilization, and treatment of chronic wounds, she showed a remarkable recovery. Eventually the foot ulcer was closed successfully using a mesh graft transplantation, and the patient was able to walk alone. Chronic ergotism is rare but has to be taken into account when presented with painful chronic digital and foot ulcers.

Presumptive gangrenous ergotism in free-living moose and a roe deer.

Presumptive gangrenous ergotism in 10 moose (Alces alces) and one roe deer (Capreolus capreolus) is reported. Three of the moose came from a municipality in southeastern Norway where the disease occurred as a cluster in 1996. The other moose represented solitary or sporadic cases diagnosed in four municipalities in northwestern Norway between 1996 and 2004. Affected moose (seven calves, three yearlings) were found between October and June, showing distal limb lesions on one to three limbs. The lesions in the moose found during October and November presented as dry gangrene, whereas moose found between December and June presented with loss of the distal part of the limbs or open lesions close to sloughing. Four of the moose also had bilateral ear lesions affecting the outer third of the pinnae. A retrospective diagnosis of ergotism (June 1981) was made in a 1-yr-old roe deer from northwestern Norway showing loss of the distal part of all four limbs.