Acute Hepatitis with Positive Autoantibodies: A Case of Natalizumab-Induced Early-Onset Liver Injury.

BACKGROUND Natalizumab is an anti-integrin monoclonal antibody used as an alternative treatment regimen for patients with autoimmune disorders, especially multiple sclerosis and Crohn's disease. Natalizumab-induced liver injury has been rarely reported and may follow the first dose (with increases in liver enzymes usually after 6 or more days), or after multiple doses. In general, it is non-severe acute hepatitis (with a hepatocellular pattern) and autoantibodies can be positive, mainly anti-nuclear and anti-smooth muscle antibodies. CASE REPORT We are reporting the case of a 60-year-old woman diagnosed with multiple sclerosis previously treated with interferon-beta, dimethyl fumarate, and fingolimod, who presented jaundice 1 day after the first infusion of natalizumab. She had an early-onset acute hepatitis with aminotransferases levels higher than 1000 IU/L and total bilirubin almost 41 mg/dL. Anti-nuclear and anti-smooth muscle antibodies were positive and the histopathological analysis of the liver showed intrahepatic cholestasis associated with moderate necroinflammatory activity (subacute cholestatic hepatitis) and mild diffuse perisinusoidal fibrosis, which could be compatible with the hypothesis of drug-induced liver injury. The scenario of an autoimmune-like hepatitis led the medical team to start oral prednisone and she progressively improved in clinical and laboratory features. Serum levels of liver enzymes and bilirubin were normal within 3 months and there was no further increase after discontinuation of corticosteroid therapy. CONCLUSIONS Physicians should be aware of the risk of early-onset acute hepatitis in patients starting natalizumab, especially women with multiple sclerosis. Treatment with corticosteroid for a few months may be beneficial.

Lithium Intoxication as a cause of reversible dementia mimicking FDG PET features of Alzheimer's disease.

Rapidly progressive dementia (RPD) is a rare neurological disorder. Drug toxicity is among the differential diagnoses, including the use of lithium, in which an overdosage might cause cognitive dysfunction. Clinical suspicion, laboratory confirmation, and drug interruption are key points in the management of lithium intoxication. We described a 66-year-old female patient under treatment with lithium who developed an RPD associated with parkinsonian symptoms. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed an "Alzheimer-like" pattern, while cerebrospinal fluid biomarkers for the disease were negative. There was a significant clinical and radiological improvement after lithium interruption. Lithium intoxication is a potentially reversible cause of RPD, as demonstrated in this case report. Drug discontinuation should be considered even in patients with normal levels of this metal, if cognitive impairment is detected. 18F-FDG PET/CT images may show an "Alzheimer-like" image pattern in acute intoxication and are useful for monitoring these patients.

Demência rapidamente progressiva é uma condição rara, cujos diagnósticos diferenciais incluem intoxicação por drogas como lítio, podendo causar importante disfunção cognitiva. A suspeita clínica, a confirmação laboratorial e a interrupção do uso medicamentoso são elementos fundamentais em seu diagnóstico e manejo. Trata-se de paciente feminina, de 66 anos de idade, que apresentou quadro demencial após intoxicação por lítio. Tal quadro foi acompanhado de sintomas parkinsonianos, além de Tomografia por Emissão de Pósitrons com 18F-Fluodeoxiglicose (18F-FDG PET/CT) compatível com padrão "Alzheimer-like". Houve melhora objetiva de parâmetros clínicos e imaginológicos após a interrupção do uso medicamentoso. A intoxicação por lítio é uma causa potencialmente reversível de demência rapidamente progressiva. A descontinuação da droga deve ser considerada também em pacientes com níveis normais do metal no sangue se alterações cognitivas forem encontradas. Imagens 18F-FDG PET/CT podem demonstrar achados sugestivos de doença de Alzheimer na intoxicação aguda e parecem ser um método útil no seguimento.

Lithium Intoxication as a cause of reversible dementia mimicking FDG PET features of Alzheimer's disease / Intoxicação por lítio como causa de demência rapidamente progressiva: um relato de caso e revisão da literatura

ABSTRACT. Rapidly progressive dementia (RPD) is a rare neurological disorder. Drug toxicity is among the differential diagnoses, including the use of lithium, in which an overdosage might cause cognitive dysfunction. Clinical suspicion, laboratory confirmation, and drug interruption are key points in the management of lithium intoxication. We described a 66-year-old female patient under treatment with lithium who developed an RPD associated with parkinsonian symptoms. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) showed an "Alzheimer-like" pattern, while cerebrospinal fluid biomarkers for the disease were negative. There was a significant clinical and radiological improvement after lithium interruption. Lithium intoxication is a potentially reversible cause of RPD, as demonstrated in this case report. Drug discontinuation should be considered even in patients with normal levels of this metal, if cognitive impairment is detected. 18F-FDG PET/CT images may show an "Alzheimer-like" image pattern in acute intoxication and are useful for monitoring these patients.

RESUMO. Demência rapidamente progressiva é uma condição rara, cujos diagnósticos diferenciais incluem intoxicação por drogas como lítio, podendo causar importante disfunção cognitiva. A suspeita clínica, a confirmação laboratorial e a interrupção do uso medicamentoso são elementos fundamentais em seu diagnóstico e manejo. Trata-se de paciente feminina, de 66 anos de idade, que apresentou quadro demencial após intoxicação por lítio. Tal quadro foi acompanhado de sintomas parkinsonianos, além de Tomografia por Emissão de Pósitrons com 18F-Fluodeoxiglicose (18F-FDG PET/CT) compatível com padrão "Alzheimer-like". Houve melhora objetiva de parâmetros clínicos e imaginológicos após a interrupção do uso medicamentoso. A intoxicação por lítio é uma causa potencialmente reversível de demência rapidamente progressiva. A descontinuação da droga deve ser considerada também em pacientes com níveis normais do metal no sangue se alterações cognitivas forem encontradas. Imagens 18F-FDG PET/CT podem demonstrar achados sugestivos de doença de Alzheimer na intoxicação aguda e parecem ser um método útil no seguimento.