Benedetta Guidi

Fatal Hepatitis After Long-Term Pulse Itraconazole Treatment for Onychomycosis

Objective: To report the occurrence of acute cytolytic hepatitis In a patient exposed to pulse itraconazole therapy for 24 weeks and provide a concise review of the literature on cases of itraconazole-induced hepatitis. Case Summary: A 61 -year-old woman with no apparent risk factors for liver injury developed acute hepatitis one week after the final dose of a long-term course of pulse itraconazole therapy (200 mg orally twice daily, 1 wk on, 3 wk off, for 24 wk) for onychomycosis. Monitoring of liver enzymes was not performed during the treatment period. Serologic evaluations on presentation ruled out Infectious diseases or other etiological factors. Liver function tests showed alanine aminotransferase 3330 U/L, aspartate aminotransferase 3250 U/L, and bilirubin 21 mg/dL Liver function continued to deteriorate, and the patient underwent liver transplantation 17 days after admission. Her liver displayed reduced volume and them was a mild accumulation of ascitic fluid in the retroperitoneal cavity. Histologic evaluation showed massive panlobular necrosis. Complications occurred after transplantation and a rejection crisis worsened the clinical picture until the patient died about 4 months later. Use of the Naranjo probability scale showed the relationship of itraconazole therapy and the occurrence of acute hepatitis as probable. Discussion: Itraconazole pulse therapy for onychomycosis appears to be at least as effective as and safer than a continuous treatment regimen, particularly from the perspective of potential liver damage. Only one case of severe symptomatic hepatitis occurring after pulse therapy with itraconazole for onychomycosis and requiring transplantation has been reported previously. In that case, as well as the one reported here, hepatitis symptoms occurred after completion of long-term treatment in patients who were asymptomatic both before and during therapy. Conclusions: Prolonged exposure to itraconazole, administered either continuously or intermittently, may precipitate severe and irreversible hepatotoxic events. Accordingly, careful monitoring of liver function parameters should be performed both during and after treatment when onychomycosis requires prolonged itraconazole administration, even in asymptomatic patients lacking apparent risk factors of hepatic injury.

Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome.

Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.

Emergency radiology without the radiologist: the forensic perspective

PurposeThe aim of this paper is to describe two cases from the authors’ forensic archive database in which teleradiology was related to unfavourable outcomes.Material and methodsTwo patients underwent autopsy after unexpected death following road accidents. In one case, death was caused by multiple cervical fractures following minor neck injury in the presence of diffuse idiopathic skeletal hyperostosis. In the other case, death was due to delayed isthmic aortic rupture occurring after thoracic blunt trauma in a young adult. Both conditions were diagnosed at autopsy only.ResultsIn both cases, the lethal outcome was due to the failure to obtain radiological reports of the X-rays performed in the emergency department. Radiological diagnoses could have been established by activating the teleradiology service which, according to the hospitals’ teleradiology protocols, is available on demand in cases of emergency only, as selected by the physician requesting the service.ConclusionsThese cases suggest the high risk of excluding the radiologist from the management of patients whose images are transmitted via a teleradiology system.RiassuntoObiettivoGli autori intendono descrivere due casi tratti dal proprio archivio autoptico medico-legale nei quali l’esito sfavorevole è connesso all’uso della teleradiologia.Materiali e metodiSono descritte le risultanze dell’indagine autoptica eseguita su due soggetti deceduti in maniera inattesa dopo incidente della strada. In un caso la morte è dipesa da fratture cervicali multiple determinatesi, in soggetto affetto da DISH (iperostosi scheletrica idiopatica diffusa), per un trauma minore del collo. Nel secondo caso un giovane adulto riportava una contusione del torace con “rottura in due tempi” dell’istmo aortico. Entrambe le patologie traumatiche sono state diagnosticate solo in sede di esame autoptico.RisultatiLa mancata diagnosi in vita ha tratto origine, in entrambi i casi, dalla “non refertazione” degli esami radiologici eseguiti in urgenza; la diagnosi radiologica avrebbe potuto effettuarsi mediante attivazione del sistema di teleradiologia, utilizzabile, secondo il protocollo gestionale della struttura, solo in casi urgenti, selezionati dal medico richiedente la prestazione.ConclusioniQuesti due casi suggeriscono che l’esclusione del radiologo dalla gestione dei pazienti le cui immagini sono trasmesse in teleradiologia comporta un rischio molto elevato di prestazioni inadeguate.

Transient acute liver failure complicating transurethral resection syndrome

Abstract Transurethral resection (TUR) syndrome, resulting from dilutional hyponatraemia for excessive absorption of irrigating fluid, represents the most relevant complication of transurethral resection of prostate (TURP). Ethanol is used as a tracer in the irrigant solution to monitor fluid absorption with a breathalyser. An unusual case of transient acute liver failure complicating TUR syndrome is reported. A 54-year-old male patient, without risk factors for the development of toxic hepatitis, was subjected to TURP for treatment of benign prostatic hyperplasia. Fluid absorption (2275 ml), estimated by breathalyser, exceeded maximum allowed absorption (2000 ml) only at the end of the surgical intervention. No signs of possible toxicity were evident in the few hours following the intervention. About 10 h after the end of TURP, the patient developed sweating, vomiting and diarrhoea. Laboratory analysis revealed severe hyponatraemia (116 meq/l) with signs of severe liver impairment (total bilirubin 5.8 mg/dl, alanine aminotransferase 56 500 U/l, aspartate aminotransferase 32 700 U/l), kidney failure (serum creatinine 1.93 mg/dl) and serum ethanol levels of 219 mg/dl (0.2%). The patient was treated with acetylcysteine 150 mg/kg i.v. and furosemide 50 mg i.v. Liver and renal functions improved in few days and recovered completely within 30 days. The TUR syndrome observed in this case was probably extravascular in nature, and could have been identified and prevented by measuring ethanol levels 10 min after ending the surgical procedure. The performance of such a test should be strongly recommended to all surgeons. The clinicians attributed the development of liver impairment in this case to ethanol toxicity. However, further studies are warranted to confirm whether hepatic injury can represent a possible complication of TUR syndrome when ethanol solution is used as irrigant fluid.

Postmortem cardiac magnetic resonance in sudden cardiac death

Postmortem imaging is increasingly used in forensic practice as good complementary tool to conventional autopsy investigations. Over the last decade, postmortem cardiac magnetic resonance (PMCMR) imaging was introduced in forensic investigations of natural deaths related to cardiovascular diseases, which represent the most common causes of death in developed countries. Postmortem CMR application has yielded interesting results in ischemic myocardium injury investigations and in visualizing other pathological findings in the heart. This review presents the actual state of postmortem imaging for cardiovascular pathologies in cases of sudden cardiac death (SCD), taking into consideration both the advantages and limitations of PMCMR application.

Fatal hepatitis after long-term pulse itraconazole treatment for onychomycosis RID B-2113-2012

Objective: To report the occurrence of acute cytolytic hepatitis In a patient exposed to pulse itraconazole therapy for 24 weeks and provide a concise review of the literature on cases of itraconazole-induced hepatitis. Case Summary: A 61 -year-old woman with no apparent risk factors for liver injury developed acute hepatitis one week after the final dose of a long-term course of pulse itraconazole therapy (200 mg orally twice daily, 1 wk on, 3 wk off, for 24 wk) for onychomycosis. Monitoring of liver enzymes was not performed during the treatment period. Serologic evaluations on presentation ruled out Infectious diseases or other etiological factors. Liver function tests showed alanine aminotransferase 3330 U/L, aspartate aminotransferase 3250 U/L, and bilirubin 21 mg/dL Liver function continued to deteriorate, and the patient underwent liver transplantation 17 days after admission. Her liver displayed reduced volume and them was a mild accumulation of ascitic fluid in the retroperitoneal cavity. Histologic evaluation showed massive panlobular necrosis. Complications occurred after transplantation and a rejection crisis worsened the clinical picture until the patient died about 4 months later. Use of the Naranjo probability scale showed the relationship of itraconazole therapy and the occurrence of acute hepatitis as probable. Discussion: Itraconazole pulse therapy for onychomycosis appears to be at least as effective as and safer than a continuous treatment regimen, particularly from the perspective of potential liver damage. Only one case of severe symptomatic hepatitis occurring after pulse therapy with itraconazole for onychomycosis and requiring transplantation has been reported previously. In that case, as well as the one reported here, hepatitis symptoms occurred after completion of long-term treatment in patients who were asymptomatic both before and during therapy. Conclusions: Prolonged exposure to itraconazole, administered either continuously or intermittently, may precipitate severe and irreversible hepatotoxic events. Accordingly, careful monitoring of liver function parameters should be performed both during and after treatment when onychomycosis requires prolonged itraconazole administration, even in asymptomatic patients lacking apparent risk factors of hepatic injury.

Fatal hepatitis after long-term pulse itraconazole treatment for onychomycosis: a case report with review of literature

Objective: To report the occurrence of acute cytolytic hepatitis In a patient exposed to pulse itraconazole therapy for 24 weeks and provide a concise review of the literature on cases of itraconazole-induced hepatitis. Case Summary: A 61 -year-old woman with no apparent risk factors for liver injury developed acute hepatitis one week after the final dose of a long-term course of pulse itraconazole therapy (200 mg orally twice daily, 1 wk on, 3 wk off, for 24 wk) for onychomycosis. Monitoring of liver enzymes was not performed during the treatment period. Serologic evaluations on presentation ruled out Infectious diseases or other etiological factors. Liver function tests showed alanine aminotransferase 3330 U/L, aspartate aminotransferase 3250 U/L, and bilirubin 21 mg/dL Liver function continued to deteriorate, and the patient underwent liver transplantation 17 days after admission. Her liver displayed reduced volume and them was a mild accumulation of ascitic fluid in the retroperitoneal cavity. Histologic evaluation showed massive panlobular necrosis. Complications occurred after transplantation and a rejection crisis worsened the clinical picture until the patient died about 4 months later. Use of the Naranjo probability scale showed the relationship of itraconazole therapy and the occurrence of acute hepatitis as probable. Discussion: Itraconazole pulse therapy for onychomycosis appears to be at least as effective as and safer than a continuous treatment regimen, particularly from the perspective of potential liver damage. Only one case of severe symptomatic hepatitis occurring after pulse therapy with itraconazole for onychomycosis and requiring transplantation has been reported previously. In that case, as well as the one reported here, hepatitis symptoms occurred after completion of long-term treatment in patients who were asymptomatic both before and during therapy. Conclusions: Prolonged exposure to itraconazole, administered either continuously or intermittently, may precipitate severe and irreversible hepatotoxic events. Accordingly, careful monitoring of liver function parameters should be performed both during and after treatment when onychomycosis requires prolonged itraconazole administration, even in asymptomatic patients lacking apparent risk factors of hepatic injury.