Doxycycline-induced Sinusoidal Obstruction Syndrome: A Case Report

Abstract

Purpose: Sinusoidal obstruction syndrome (SOS), formerly known as venoocclusive disease, was first described with pyrrolizidine alkaloids, a compound found in certain herbal tea and spoiled wheat. In northern countries, chemotherapy, especially for induction of hematopoietic stem cell transplantation, is now the leading cause. Other etiologies have been reported such as high-dose abdominal radiotherapy, azathioprine and cyclophosphamide. We present here the case of a 48-year-old healthy man who was referred to our center for sudden onset of abdominal distension. The patient first noticed his symptoms just after completion of a 14-day doxycycline treatment for Q fever. At that time, his regular medication only included a benzodiazepine and tadalafil. No other risk factor for hepatopathy was retrieved except a daily alcohol intake of 55g for the last 20 years. The patient denied any natural medicine or drug use and there was no traveling history in the last year. Large hepatomegaly and ascites were confirmed on physical examination. Initial laboratory results included: ALP 340 U/L, ALT 32 U/L, AST 57 U/L, bilirubin 15 umol/L, albumin 31 g/L, INR 1.2, CRP 42. Whole traditional blood work-up for a specific cause of liver disease was negative and paracentesis showed a transudative gradient (SAAG = 17) resulting from portal hypertension. Abdominal CT scan demonstrated a 20-cm heterogeneous liver with normal caudate lobe, large ascites and a 14.5-cm spleen. Doppler ultrasound and MRI showed no suprahepatic veins obstruction. Upper endoscopy confirmed small esophageal varices and subtle hypertensive gastropathy. A percutaneous liver biopsy concluded to a venoocclusive disease caused by a drug reaction. Another pathologist from an expert liver center confirmed this diagnosis. Small dose diuretics were given to the patient, but no other specific treatment was instituted. Five months later, the patient is doing well with complete resolution of ascites and normalisation of hepatic blood work-up. Liver is no more palpable. A recent ultrasound showed regression of hepatomegaly with a persistently heterogeneous liver and resolution of splenomegaly and ascites. SOS is a very uncommon disorder secondary to toxic injury to sinusoidal endothelial cells. The patient's alcohol intake might have predisposed him to toxicity with doxycycline. This antibiotic has never been shown to cause SOS. However, no other agent could be incriminated in this case and the temporal relationship between the drug and the symptoms supports the causality. To our knowledge, this is the first case reported with doxycycline.