Hereditary Haemorrhagic Telangiectasia (HHT-WG)

The HHT Working Group, is built upon Multidisciplinary Centres of Excellence that have been collaborating since our first international meeting in 1996.

The HHT-WG is chaired by Dr. Claire SHOVLIN, HHTIC London, Hammersmith Hospital, and Imperial College London, UK. The WG is co-chaired by Dr. Sophie DUPUIS-GIROD, HHT Center of Reference, Lyon, France in cooperation with Deputy Chair Dr. Elisabetta BUSCARINI, HHT Center, Maggiore Hospital, Crema, Italy.

These chairs, and the majority of the Working Group as well as Centers cooperating with the HHT-WG (A. KJELDSEN, H.J. MAGER, C. SABBA, L. BOTELLA, and U. GEISTHOFF) have been longstanding members of the Global Research and Medical Advisory Board (GRMAB) of the HHT Foundation International (now Cure HHT) with Hans-Jurgen MAGER the current GRMAB Vice Chair. Our HHT Centres are acknowledged as International Centers of Excellence (see International Treatment Centres) and we continue our warm collaborations with non-European HHT Colleagues.

VASCern HHT-WG cooperates with the Patient-WG, whose representative participating to the WG is Claudia CROCIONE, HHT Europe.

Milestones

1994    1st HHT Gene identified McAllister et al, 1994
1996    1st International Conference (occur biannually)
2000    HHT Diagnostic Criteria Shovlin et al, 2000
2006    Liver Consensus Statement Buscarini et al 2006
2008    Pregnancy Recommendations Shovlin et al 2008
2011    International Guidelines Faughnan et al 2011
2012    Bevacizumab trial Dupuis-Girod et al 2012
2015    11th International Conference
2016    EASL Liver Guidelines EASL 2016

While so much has been achieved, the next stages require formal acknowledgement, status and funding to ensure that European HHT patients are not left out of the current transformational changes through personalised medicine and therapeutics

Our Network Goals are to

  • continue to assist patients in their choices, by evaluating the natural history of HHT compared to the benefits and complications of diagnostic tests and treatments;
  • obtain funding for the Clinical Trials that we see as essential to provide further improvements in clinical care;
  • educate our international colleagues in the management of this challenging but highly rewarding disorder;
  • consolidate the position of HHT at the high-table of Rare Diseases, as befits its prevalence (circa 1 in 5,000, yet subject to substantial under ascertainment)

The HHT-WG is a distinct entity because in the more than 20 years that the Partners have been working together, there has been little professional need to overlap with our colleagues and friends in the Rare Vascular Anomalies Working Group (VASCA-WG).

Hereditary haemorrhagic telangiectasia (HHT) is a single, relatively common “Rare” Vascular Disease with distinct screening and management recommendations.  Abnormal vascular structures occur non randomly, and are responsible for complications: currently used treatments are symptomatic and not pathophysiological. Unlike the other ERN components, the clinical phenotype is dominated by the consequences of chronic bleeding from the abnormal vascular structures; paradoxical emboli through pulmonary arteriovenous malformations AVMs; and the wider circulatory consequences due to systemic AVMs, in turn exacerbated by anaemia and low oxygen levels.

Thus, HHT may require management from almost all specialist groupings. Small (telangiectasia) lead to nosebleeds (epistaxis), gastrointestinal bleeding and iron deficiency anaemia. Large arteriovenous malformations (AVMs) in pulmonary, hepatic, and cerebral circulations may hemorrhage; pulmonary AVMs cause preventable ischemic strokes, cerebral abscesses, and hypoxaemia; and systemic AVMs demand higher cardiac outputs aggravated by iron deficiency and/or hypoxaemia. 1 in 100 women die in pregnancy, and the SMAD4 subgroup (~2%) are also at risk of aortic rupture, juvenile polyposis and GI cancers. Paradoxically, where managed appropriately, life expectancy can be very good indeed, with likely explanations including apparent protection from certain cancers, and myocardial infarctions.

The clinical diagnosis of HHT is based on the Curaçao criteria  Shovlin et al, 2000. Molecular diagnosis is available for the ALK1, ENG, and SMAD4 genes and mutations are found in over 90% of patients with a definite clinical diagnosis.

The PubMed List*  of 296 HHT publications from the Working Group Members is provided.

Bases for the estimated incidence and prevalence numbers: 500 Million inhabitants within European union with about 6 million newborns annually.

sub-thematic areas of expertise Rare or complex disease(s) or condition(s) or highly specialized interventions Code/ICD/ Orphacode / Group of Codes Incidence (Number of cases / year)

(in the EU)

Prevalence

 (in the EU)

HHT Pulmonary arteriovenous malformations Pulmonary AVMs ICD10: IX, I28.0 2346 195,460

(1 in 2,600)

HHT Recurrent, severe epistaxis in HHT ICD10:XVIII: R04.0 300 25 000
HHT Iron deficiency anaemia and  HHT ICD10:IV: D50.0 660 55 000
HHT Juvenile polyposis and HHT (SMAD4) IICD10: II: D12.6 29 2 400
HHT SMAD4

Aortopathy

ICD10: IX: I71 4 300
HHT HHT hepatic arterio-venous malformations IX; Q27.3 324 27 000

 

All HCP in the HHT-WG are covering this sub-thematic area of expertise.

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UNITED KINGDOM

Chair

Dr. Claire SHOVLIN
HHT Centre and Service
Hammersmith Hospital, Imperial College Healthcare NHS Trust
London, UK

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FRANCE

Co-chair

Dr. Sophie DUPUIS-GIROD
CRMR Rendu-Osler Disease – HHT Center of Reference
CHU de Lyon HCL, GH Est-Hôpital Femme Mère Enfant
Lyon, France

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ITALY

Deputy co-chair

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DENMARK

allemagne

GERMANY

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ITALY

Patient Member

Claudia CROCIONE
HHT Europe
Associazione Italiana Teleangectasia Emorragica – HHT ONLUS

Dr. Fabio PAGELLA
HHT Center, Department of Otorhinolaryngology
Fondazione IRCCS Policlinico San Matteo, University of Pavia
Pavia, Italy

Pr. Carlo SABBÀ
Center for Hereditary Haemorrhagic Telangiectasia
Azienda Ospedaliero-Universitaria Consorziale di Bari Policlinico-Giovanni XXIII
Bari, Italy

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NETHERLANDS

Dr. Hans-Jurgen MAGER
Department of Pulmonology
Dutch HHT expertise center
St. Antonius Hospital
Nieuwegein, The Netherlands

EN

Centers cooperating with HHT-WG

The HCPs member applicants are having functional cooperation with other Centers:

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SPAIN

Our HHT-WG Goals are to

  • continue to assist patients in their choices, by evaluating the natural history of HHT compared to the benefits and complications of diagnostic tests and treatments;
  • obtain funding for the Clinical Trials that we see as essential to provide further improvements in clinical care;
  • educate our international colleagues in the management of this challenging but highly rewarding disorder;
  • consolidate the position of HHT at the high-table of Rare Diseases, as befits its prevalence (circa 1 in 5,000, yet subject to substantial under ascertainment)

The goal of HHT-WG is to provide guidance to enable wise choices of investigations to maximise patient health, safety, and psychological balance, mindful of off-target consequences such as radiation exposure and unintended life-style impacts.

Guidance will be wise, distinguishing baseline, essential screening studies for all patients, from investigations that would be superfluous except in specific settings of clinical need, or research protocols.

Our goal is to add to the Guidance already generated by WG Members (see list), and we are implementing a 3 part plan to realise in an efficient and timely manner.

  • Diagnostic criteria for hereditary hemorrhagic telangiectasia (RenduOslerWeber syndrome)- Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H. Am J Med Genet 2000 ( >990 citations).
  • Liver involvement in hereditary hemorrhagic telangiectasia: consensus recommendations. Buscarini E, Plauchu H, Garcia Tsao G, White RI Jr, Sabbà C, Miller F, Saurin JC, Pelage JP, Lesca G, Marion MJ, Perna A, Faughnan ME. Liver Int. 2006 (>100 citations).
  • HHT Foundation International – Guidelines Working Group. International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia. Faughnan ME, Palda VA, Garcia-Tsao G, Geisthoff UW, McDonald J, Proctor DD, Spears J, Brown DH, Buscarini E, Chesnutt MS, Cottin V, Ganguly A, Gossage JR, Guttmacher AE, Hyland RH, Kennedy SJ, Korzenik J, Mager JJ, Ozanne AP, Piccirillo JF, Picus D, Plauchu H, Porteous ME, Pyeritz RE, Ross DA, Sabba C, Swanson K,Terry P, Wallace MC, Westermann CJ, White RI, Young LH, Zarrabeitia R; J Med Genet. 2011(>350 citations)
  • European Association for Liver Studies – Clinical Practice guidelines: Vascular diseases of the liver. Garcia-Pagan, Buscarini E  Janssen, Leebeek F, Plessier, Rubbia Brandt, Senzolo, Shouten, Tripodi. J Hepatol 2016. (already cited)

For completed activities, please see the Working group’s 296 HHT-related publications to 04/16 at PubMed List

We are currently evaluating our 2016 WG Research Priorities.

This page is under development.  In the interim, please read the Working Group Member’s Guideline documents (listed in Quality and Safety section above), and our recent narrative reviews in English, French, Danish and German that are listed below:

ENGLISH:

Circulatory contributors to the phenotype in hereditary hemorrhagic telangiectasia. Shovlin CL.  Front Genet. 2015 Apr 9;6:101. doi: 10.3389/fgene.2015.00101

Clinical implications of pulmonary shunting on saline contrast echocardiography. Velthuis S, Buscarini E, Gossage JR, Snijder RJ, Mager JJ, Post MC. JAm Soc Echocardiogr. 2015 Mar;28(3):255-63

Pulmonary arteriovenous malformations. Shovlin CL. Am J Respir Crit Care Med. 2014 Dec 1;190(11):1217-28

Hereditary hemorrhagic telangiectasia: from molecular biology to patient care. Dupuis-Girod S, Bailly S, Plauchu H.  J Thromb Haemost. 2010 Jul;8(7):1447-56.

Hereditary haemorrhagic telangiectasia: pathophysiology, diagnosis and treatment. Shovlin CL.  Blood Rev. 2010 Nov;24(6):203-19.

FRENCH: 

Rendu-Osler disease: clinical and molecular update. Bailly S, Dupuis-Girod S, Plauchu H. Med Sci (Paris). 2010 Oct;26(10):855-60

DANISH:

Diagnosis and treatment of morbus Osler. Kjeldsen AD, Andersen PE, Tørring PM.  Ugeskr Laeger. 2011 Feb 14;173(7):490-5.

GERMAN: 

Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) as an example of a rare disease relevant for oto-rhino-laryngology. Geisthoff UW, Maune S, Schneider G.. Laryngorhinootologie. 2011 Apr;90(4):230-42; quiz 243-4. doi: 10.1055/s-0031-1271809.

The PubMed List of 296 HHT publications from the Working Group Members is provided, and emphasizes the importance of continued clinician education:

Using HHT-restricted search terms, between 1994-2016, the Working Group wrote or contributed 296 articles- 276 excluding individual case reports and only 20 Case Reports on particularly informative or unusual cases (a ratio of >13:1).  In contrast, the remaining literature comprised 902 articles excluding individual case reports, and 795 Case Reports, a ratio of 1.1:1.