Anette Drøhse Kjeldsen

Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome).

Hereditary Hemorrhagic Telangiectasia (HHT) is easily recognized in individuals displaying the classical triad of epistaxis, telangiectasia, and a suitable family history, but the disease is more difficult to diagnosis in many patients. Serious consequences may result if visceral arteriovenous malformations, particularly in the pulmonary circulation, are unrecognized and left untreated. In spite of the identification of two of the disease-causing genes (endoglin and ALK-1), only a clinical diagnosis of HHT can be provided for the majority of individuals. On behalf of the Scientific Advisory Board of the HHT Foundation International, Inc., we present consensus clinical diagnostic criteria. The four criteria (epistaxes, telangiectasia, visceral lesions and an appropriate family history) are carefully delineated. The HHT diagnosis is definite if three criteria are present. A diagnosis of HHT cannot be established in patients with only two criteria, but should be recorded as possible or suspected to maintain a high index of clinical suspicion. If fewer than two criteria are present, HHT is unlikely, although children of affected individuals should be considered at risk in view of age-related penetration in this disorder. These criteria may be refined as molecular diagnostic tests become available in the next few years.

Hereditary haemorrhagic telangiectasia: a population-based study of prevalence and mortality in Danish patients

Introduction. Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by telangiectatic lesions. The disease manifestations are variable and include epistaxis, gastrointestinal bleeding, pulmonary arteriovenous malformations and cerebral arteriovenous malformations. Early death due to these complications has been described.

Gastrointestinal bleeding in patients with hereditary hemorrhagic telangiectasia

OBJECTIVE:Gastrointestinal bleeding occurs in a number of patients with hereditary hemorrhagic telangiectasia (HHT) and may lead to a high transfusion need. The aim of this study was to estimate the occurrence and severity of gastrointestinal bleeding in a geographically well defined HHT population.METHODS:All HHT families in the county of Fyn, Denmark, (470,000 population) have been identified. Probands and their first degree relatives, and all descendants from probands for whom one parent had HHT were eligible for inclusion in the study. A total of 77 patients with HHT were identified; of these, 76 patients (mean age: 52 yr) were evaluated and interviewed with regard to gastrointestinal bleeding, that is, a history of either hematemesis or melena. Patients charts were reviewed.RESULTS:A total of 25 HHT patients (33%) had a history of either hematemesis or melena. Of these, 12 (48%) had received blood transfusions. Seven patients had severe bleeding (that is, ≥6 units of blood within 6 months before inclusion in the study). Endoscopy had been performed in 16 of the 25 (64%) patients. Telangiectatic lesions were documented in nine at upper endoscopy and in one at sigmoidoscopy. Telangiectatic lesions were observed in all patients with severe bleeding, but in two patients epistaxis is likely to have contributed to the anemia. Among 51 HHT patients without a history of gastrointestinal bleeding, only five (10%) had previously received blood transfusions; however, none fulfilled the definition of severe bleeding. In the HHT population 29 patients were ≥60 yr old, but all patients with severe bleeding were ≥60 yr.CONCLUSIONS:A history of gastrointestinal bleeding is common in patients with HHT (33%). This study documents that 25% of HHT patients ≥60 yr suffer from severe gastrointestinal bleeding.

Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT)

Abstract. Kjeldsen AD, Oxhøj H, Andersen PE, Green A, Vase P (Odense University and Odense University Hospital, Odense; University of Aarhus, Aarhus; and the Department of Otorhinolaryngology, Svendborg, Denmark). Prevalence of pulmonary arteriovenous malformations (PAVMs) and occurrence of neurological symptoms in patients with hereditary haemorrhagic telangiectasia (HHT). J Intern Med 2000; 248: 255–262.

Clinical symptoms according to genotype amongst patients with hereditary haemorrhagic telangiectasia

Background.  Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease, characterized by a wide variety of clinical manifestations, including epistaxis, gastrointestinal (GI) bleeding, pulmonary arteriovenous malformations (PAVMs) and neurological symptoms. HHT is a genetically heterogeneous disorder involving at least two loci; HHT1 mapping to chromosome 9q34.1 (ENG) and HHT2 mapping to chromosome 12q31 (ALK‐1).

Selective embolization in the treatment of intractable epistaxis

Conclusions. In skilled hands, selective embolization is a safe procedure and represents an effective treatment for prolonged epistaxis. Embolization therapy can be repeated if necessary. Objective. Severe posterior epistaxis is a common clinical problem in an ENT department and controlling the bleeding may present difficulties. Several methods are used to control posterior epistaxis, one of the latest treatment strategies being selective embolization of the nasal arteries. The aim of this study was to describe the effect of selective embolization in 22 patients treated with a total of 30 procedures at the ENT Department of Odense University Hospital between January 1995 and March 2004. To our knowledge this is the first Nordic work in which selective embolization has been used as a treatment strategy for patients with hereditary hemorrhagic telangiectasia (HHT). Material and methods. This was a retrospective review. Post-treatment effects and complications were evaluated by means of a questionnaire and a telephone interview. Owing to the different treatment strategies used, the results were evaluated for 2 groups of patients: Group A, 9 patients with HHT; and Group B, 13 patients with causes of epistaxis other than HHT. Results. In Group A, 15 procedures were performed, 12 of which were beneficial as the duration and number of episodes of epistaxis were reduced. In Group B, 15 procedures were performed and the success rate was 87%. One patient suffered from skin necrosis at the tip of the nose. No other serious side-effects of the treatment were observed.

Mutations in endoglin and in activin receptor-like kinase 1 among Danish patients with hereditary haemorrhagic telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is a rare disorder with one per 6000–10,000 affected individuals in the general Caucasian population. HHT is genetically heterogeneous, involving at least two loci HHT1 mapping to chromosome 9q34.1 and HHT2 mapping to chromosome 12q31. The loci have been identified as endoglin (ENG) and activin receptor‐like kinase 1 (ALK1). In order to gain knowledge of the genotype distribution and prevalence in the Danish population and to establish a reproducible and sensitive molecular genetic test method, we developed a denaturating gradient gel electrophoresis protocol for mutation scanning of the two loci. Twenty‐five Danish HHT families were tested. A total of eight new as well as seven previously reported mutations were identified. A founder mutation was characterized present in seven families and possibly introduced around 350 years ago. In one individual, a presumed spontaneous mutation was characterized. The method developed proved to be very sensitive for mutation detection in both ENG and ALK1. Genetic screening in HHT families facilitates an early treatment strategy for silent HHT manifestations in first degree relatives.

Quality of life and associated factors in persons with chronic rhinosinusitis in the general population: A prospective questionnaire and clinical cross‐sectional study

The European Position Paper on Rhinosinusitis and Nasal Polyps describes methods to perform population‐based and clinical studies on chronic rhinosinusitis in a standardised way, and it also describes how to clinical investigate CRS. The aim of this cross‐sectional study was to evaluate quality of life and objective findings in persons with chronic rhinosinusitis recruited from the general population.

Mutations in the ALK‐1 gene and the phenotype of hereditary hemorrhagic telangiectasia in two large Danish families

Mutations in the ENG gene on chromosome 9 (HHT 1) and in the ALK-1 gene on chromosome 12 (HHT 2) have been reported as causes of hereditary hemorrhagic telangiectasia (HHT). HHT 1 has been correlated with a higher prevalence of pulmonary arteriovenous malformations than HHT 2. Other distinct phenotype-genotype correlations have not been described. The prevalence of HHT in the county of Fyn, Denmark, was 15.6 per 100,000 on January 1, 1995. All living patients and their first-degree relatives were invited to attend a detailed clinical examination and blood was drawn for mutation analysis. In two families mutations were identified in exon 8 of the ALK-1 gene. In family 6 we found a T1193A mutation. In this family a high prevalence of PAVM and severe GI bleeding was documented, while in family 8 with a C1120T mutation no individuals with PAVM were identified and only one patient had a history of severe GI bleeding. No mutations in the endoglin locus were found in either family.

Cerebral abscesses among Danish patients with hereditary haemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT) is a dominantly inherited disease characterized by a wide variety of clinical manifestations, including pulmonary arteriovenous malformations (PAVMs), which due to paradoxical embolization may cause cerebral abscess.