Brain Abscess and Stroke in Children and Adults With Hereditary Hemorrhagic Telangiectasia: Analysis of a Large National Claims Database

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disease associated with pathogenic variants in transforming growth factor-β signaling pathway–related genes, resulting in abnormal vascular development in various organs. Brain arteriovenous malformations (AVMs) may lead to intracranial hemorrhage, and brain abscess or ischemic stroke may result from right to left shunting via pulmonary AVMs. We aimed to investigate the risk for these severe complications in both adults and children with HHT. METHODS: We conducted a case-control study among participants aged 1–64 years in the MarketScan Commercial (2006–2019) and Multistate Medicaid Databases (2011–2019). We identified cases with HHT using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9/10) diagnosis codes (ICD-9-CM 448.0, ICD-10-CM I78.0). Control patients without HHT coding were frequency matched 10:1 to patients with HHT by age, duration of insurance enrollment, sex, and Medicaid status. Outcomes of interest (brain abscess, stroke, and intracranial/subarachnoid hemorrhage) were identified using the appropriate ICD-9/10 diagnosis codes. We calculated incidence and standardized rates of the various outcomes and compared rate ratios (RRs) between HHT cases and controls. RESULTS: A total of 5,796 patients with HHT, of whom 588 were children (age younger than 16 years), were matched with 57,960 controls. There was an increased incidence of brain abscesses in HHT cases compared with controls, with an RR of 35.6 (95% CI 15.4–82.5). No brain abscesses were recorded in children aged 15 years or younger. Hemorrhagic strokes/subarachnoid hemorrhages were more common in HHT cases, with an RR of 4.01 (95% CI 2.8–5.7) in adults and 60.2 (95% CI 7.2–500.4) in children. Ischemic strokes were also more common in cases, with an RR of 3.7 (95% CI, 3.0–4.5) in adults and 70.4 (95% CI 8.7–572.3) in children. DISCUSSION: We observed a much higher incidence of severe CNS vascular complications in patients with HHT, particularly in children. Although a higher incidence of brain abscesses was noted in adult patients with HHT, no brain abscesses were recorded in children, a result that may be considered when surveillance recommendations for this population are revisited.