Carvedilol-Induced Liver Injury, a Rare Cause of Mixed Hepatitis: A Clinical Case.

INTRODUCTION: Drug-induced liver injury is an increasingly prevalent consequence of the diversification of available therapeutic weapons, mostly idiosyncratic and with several possible mechanisms and patterns of specific damage for each drug. Carvedilol, a widely used non-selective alpha and beta blocker leads, in very rare cases, to injury of the bile ducts by toxic metabolites, resulting in a mixed-pattern hepatitis with possible progression to chronic cholestatic syndrome and cirrhosis. The authors report the second known case of this important toxicity. CLINICAL CASE: An 83-year-old woman was admitted to the Internal Medicine ward for etiological clarification of a mixed-pattern hepatitis. Clinical history was unremarkable and structural, infectious, and autoimmune causes were excluded by blood tests and imaging exams, ultimately leading to the diagnosis of toxic hepatitis that was further confirmed by liver biopsy with morphologic findings of mixed-pattern liver injury. Carvedilol, started 6 months before, was deemed the causal agent since it was the only drug with a clinically, temporally, analytically, and histologically compatible pattern. The withdrawal of the drug resulted in slow reversal of the referred abnormalities. CONCLUSION: In very rare cases, carvedilol can cause important liver toxicity as a chronic cholestatic syndrome which can evolve to cirrhosis. It should be taken in consideration as causal agent in similar cases and stopped immediately upon suspicion, as the timely withdrawal results in reversion of the pathological findings.

INTRODUÇÃO: A lesão hepática induzida por drogas é uma consequáncia cada vez mais prevalente da diversificação de armas terapáuticas disponíveis. São principalmente reacções idiossincráticas, com vários mecanismos possíveis e padrões de danos específicos de cada droga. O carvedilol, bloqueador alfa e beta não seletivo amplamente utilizado, leva, em casos muito raros, a lesão dos canalículos biliares por metabólitos tóxicos, resultando numa hepatite padrão misto com possível progressão a síndrome colestática crónica e potencialmente cirrose. Os autores relatam o segundo caso conhecido desta importante toxicidade. CASO CLÍNICO: Uma mulher idosa foi admitida na enfermaria de Medicina Interna para esclarecimento etiológico de uma hepatite de padrão misto. Esta investigação que incluiu uma extensa pesquisa de antecedentes, exclusão de causas estruturais, infecciosas e auto-imunes por análises sanguíneas e exames de imagem, levou ao diagnóstico de uma hepatite tóxica, confirmada por biópsia hepática com achados morfológicos de um padrão misto de lesão hepática. O carvedilol, introduzido 6 meses antes, foi considerado o agente causal dado ser a única substância com padrão clínico, temporal, analítico e histológico compatível. A retirada do medicamento resultou na reversão lenta das referidas anormalidades. DISCUSSÃO: Em casos muito raros, o carvedilol pode causar toxicidade hepática importante sob a forma de síndrome colestástica crónica que pode evoluir até uma cirrose hepática. Deve ser tomado em consideração como potencial agente causal em casos semelhantes e retirado imediatamente após suspeita, sendo que a suspensão atempada resulta na reversão completa dos achados patológicos.

Non-Obstructive Middle Lobe Syndrome: An Unusual Cause of Recurrent Pneumonia in an Elderly Woman.

An 84-year-old woman had five episodes of pneumonia in 4 months. Despite extensive comorbidities and advanced age, her health status was good and the recurrence seemed unjustified. Exhaustive background investigation revealed 14 episodes of right-sided pneumonias during the 3 previous years and an inconclusive investigation with CT of the thorax and bronchofibroscopy, despite some fibrotic and atelectasic alterations in the right middle lobe. A new right-sided x-ray showed a wedge-shaped density extending anteriorly and inferiorly from the hilum, and CT of the thorax revealed aggravated middle lobe abnormalities with thickening of the bronchial wall and segment atelectasis, without any visible airway obstruction. After extensive work-up had excluded other causes of recurrent pneumonia and immunodeficiency, a non-obstructive middle lobe syndrome (MLS) was deemed responsible for the repeated episodes of pneumonia. MLS is characterised by chronic hypoventilation and atelectasis of the middle lobe, facilitating secretion accumulation, chronic inflammation and repeated infection. After treatment with bronchodilators and immunostimulants was initiated, the patient experienced no recurrences for several months. LEARNING POINTS: Recurrent pneumonia is common and has several possible causes. Investigation should be directed by whether or not the location of the episodes varies, suggesting a systemic condition or a local abnormality, respectively.Middle lobe syndrome (MLS) is characterised by chronic hypoventilation of the right middle lobe resulting in atelectasis and secretion accumulation, sometimes causing recurrent pneumonia, and should therefore be considered in the differential diagnosis.MLS is not unusual in children with asthma but is quite uncommon in the elderly despite age-related changes in the characteristics of airways with reduced elastic recoil and mucociliary clearance.

Triple POCUS: A New Approach to an Old Problem.

Pulmonary embolism (PE) is the most serious and life-threatening clinical presentation of venous thromboembolism, and difficult to diagnose. Triple point-of-care-ultrasonography (POCUS) of the lung, heart and leg veins is a multiorgan approach that may help to evaluate patients suspected of having PE, in combination with existing protocols and computed tomographic pulmonary angiography (CTPA). We present the case of a 26-year-old man with sudden onset of dyspnoea and swelling of the leg with a Well's score of 9. With CTPA unavailable at the time of presentation, triple POCUS showed subpleural consolidations and a venous thrombus in a popliteal vein. A diagnosis of deep vein thrombosis with PE was made and the appropriate treatment was started immediately. Although triple POCUS has less sensitivity and specificity than CTPA, it could be very useful in some clinical settings. LEARNING POINTS: In a patient with suspected pulmonary embolism, the best diagnostic strategy is to combine clinical assessment, plasma D-dimer measurement and computed tomographic pulmonary angiography (CTPA).Triple point-of-care ultrasonography of the lung, heart and leg veins may improve clinical assessment of pulmonary embolism if CTPA is unavailable or contraindicated.Point-of-care ultrasonography should be incorporated as the fifth pillar of the physical examination.