Severity score for hereditary hemorrhagic telangiectasia
- PDF / 836,702 Bytes
- 6 Pages / 595.276 x 793.701 pts Page_size
- 100 Downloads / 171 Views
RESEARCH
Open Access
Severity score for hereditary hemorrhagic telangiectasia Giuseppe A Latino1,2*, Helen Kim3,4, Jeffrey Nelson3, Ludmila Pawlikowska3,4, William Young3ˆ, Marie E Faughnan2,5 and the Brain Vascular Malformation Consortium HHT Investigator Group
Abstract Background: A disease severity score in hereditary hemorrhagic telangiectasia (HHT) would be a useful tool for assessing burden of disease and for designing clinical trials. Here, we propose the first known HHT severity score, the HHT-score. Methods: Demographics and disease characteristics were collected for the first 525 HHT patients recruited to the HHT Project of the Brain Vascular Malformation Consortium (BVMC). HHT-score was calculated based on presence of: organ arteriovenous malformations (maximum 3 points); chronic bleeding (maximum 2 points); and severe organ involvement (maximum 2 points). Points were summed and patients categorized as having mild (0–2), moderate (3–4) or severe (5–7) disease. The occurrence of “any adverse outcome” was evaluated for association with HHT-score categories. Results: The frequency of “any adverse outcome” was significantly different across the three groups (49.6% in mild, 65.8% in moderate and 89.5% in severe, p < 0.001). Adjusting for age and gender, the risk of “any adverse outcome” was higher in the moderate (OR = 1.84, 95% CI: 1.15-2.95, p = 0.011) and severe groups (OR = 9.16, 95% CI: 1.99-42.09, p = 0.004) compared to the mild. Conclusions: We have taken the first steps toward creating a global measure of disease severity in HHT. While the initial results are promising, further validation of the HHT-score is still required. Keywords: Hereditary Hemorrhagic Telangiectasia (HHT), Osler-Weber-Rendu, Arteriovenous Malformation (AVM), Bleeding, Disease severity, Severity score
Background Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant condition of vascular dysplasia characterized by mucocutaneous telangiectases and organ arteriovenous malformations (AVMs) mainly affecting the lungs, liver and brain [1,2]. To date, mutations in three different genes have been identified, all coding for proteins of the TGF-β/BMP-9 signalling pathway. The two most commonly mutated genes are endoglin (ENG or HHT1) and activin A receptor type II-like 1 (ALK-1 or HHT2) [1],
* Correspondence: [email protected] ˆDeceased 1 Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada 2 Division of Respirology, Department of Medicine, St. Michael’s Hospital, University of Toronto, Toronto, Canada Full list of author information is available at the end of the article
with SMAD4 mutations reported in a small subset of patients, most of whom also have juvenile polyposis [1,3]. HHT is thought to affect at least 1 in 10000 individuals with no known ethnic predisposition [1,2,4-8]. Telangiectases and AVMs are prone to bleeding, leading to chronic epistaxis and/or gastrointestinal (GI) bleeding in most HHT patients, and a risk of
Data Loading...
