Case Presentation: A 64-year-old female presented to the hospital with 2 days of nausea, vomiting, and diarrhea. She had no recent sick contacts, travel history, or antibiotic use. Her medical history was notable for Hereditary Hemorrhagic Telangiectasia (HHT) complicated by epistaxis refractory to medical and surgical interventions, bleeding gastric ulcers, pulmonary hypertension, and hepatic arteriovenous malformations (AVMs). She didn’t smoke cigarettes and socially consumed alcohol. Her medications included oral iron sulfate and thalidomide, and her family history was significant for HHT in her mother. At the emergency department, she had large volume hematemesis. Her blood pressure was 77/38 mmHg, heart rate was 93 beats per minute, temperature was 98F, and oxygen saturation was 100% on room air. On examination, she was lethargic, had conjunctival pallor, abdominal distension with generalized tenderness to palpation, and melena and hematochezia on rectal exam. Her labs were significant for a hemoglobin of 5.0 g/dL, platelet count of 103 k/µL, prothrombin time of 15.4 seconds, and fibrinogen of 149 mg/dL. She underwent endotracheal intubation, was transferred to the intensive care unit, and was administered norepinephrine and saline infusions, packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate. Emergent esophagogastroduodenoscopy and Computed Tomography Angiography (CTA) were done, though didn’t localize a source of bleeding. Overnight, she became unarousable and developed right gaze deviation and cortical posturing. CT head was initially unremarkable, though repeat imaging roughly 24 hours later showed diffuse cerebral edema and impending transtentorial herniation. Her ammonia level, which was 120 µmol/L on admission, was rechecked once signs of herniation arose, and was found to be 259 µmol/L. She was then started on rectal lactulose, sodium benzoate/sodium phenylacetate, and L-arginine. Over the next several days her ammonia level normalized, and the cerebral edema and herniation improved. Ultimately, she remained in a persistent vegetative state and was transitioned to hospice.
Discussion: HHT is an autosomal dominant vascular disease characterized by the formation of cutaneous and visceral telangiectasias and AVMs. While epistaxis is common, multiple organs may be involved including the skin, lungs, gastrointestinal tract (GI), and brain. This case highlights a unique and unreported manifestation of HHT and illustrates the risk of cerebral herniation in these patients. Portosystemic encephalopathy due to hyperammonemia is rarely reported in HHT and has been attributed to the presence of hepatic AVMs. This patient’s refractory upper GI bleed resulted in hyperammonemia, and due to the hepatic AVMs, her liver couldn’t convert the excess ammonia to urea via the urea cycle. The use of L-arginine and sodium benzoate/sodium phenylacetate reduced her serum ammonia by upregulating the urea cycle. However, her hyperammonemic state had already resulted in elevated intracranial pressure and subsequent herniation.
Conclusions: Patients with refractory upper GI bleeds and impaired hepatic function or hepatic AVMs can develop hyperammonemia, which can subsequently precipitate increased intracranial pressure and herniation. Thus, clinicians should be aware of this potential complication in HHT patients presenting with GI bleeds and epistaxis.