ISSVA 2024 – Madrid

From May 7-10, 2024, ISSVA (International Society for the Study of Vascular Anomalies) organized a conference in Madrid, Spain. Approximately 800 participants attended in person, and around 200 participated online.

Prof. Dr. Francine Blei (USA), Lex, Prof. Dr. Ilona Frieden (USA)

On the first day, topics covered included vascular tumors, vascular malformations, pathology, interventional radiology, and surgery. The second day delved deeper into vascular tumors and venous malformations. On the third day, arteriovenous malformations, combined malformations, and capillary malformations were discussed. The final day focused on various studies of vascular malformations.

The ISSVA classification, which is designed to help understand the development of the biology and genetics of vascular malformations and tumors, is reviewed and updated at each conference. This classification is considered a “living” classification.

Prof. Dr. Mikka Vikkula, one of our advisors, presented an overview of vascular disorders and the genes involved.

During this conference, we had several booths representing various Patient Organizations from the ERNs (LGDA, HEVAS, Bundesverband Angeborene Gefässfehlbildungen). Our booth was well-visited, and among others, an American doctor mentioned that she uses our materials in her clinic.

Below is a brief report on this conference, highlighting a few specific sessions.

The first topic discussed was the ISSVA classification of vascular malformations. Regular revisions are necessary because, firstly, no classification is ever perfect. Secondly, new conditions are continually being described, new knowledge about their causes is being discovered, and new treatments are being developed. Classification must be simple, clinically useful, and reflect our understanding of the underlying biology.

The classification distinguishes between tumors and malformations. A malformation is described as a defect in embryological development, while a tumor is characterized by abnormal cells in a normal environment. Vascular malformations are further subdivided into “fast-flow” (arteries) and “low-flow” (small vessels).

During the ISSVA conference, a demonstration was given of a new development where all information was made available in an interactive manner.

ISSVA classification

From an interventional radiology perspective, it is recommended to treat arteriovenous malformations (AVMs) immediately rather than waiting to see how they develop.

The well-known medications sirolimus and alpelisib (often in combination with other drugs) were also discussed, though their long-term effects are still unknown.

AVMs seem to be effectively managed through embolization (blocking off a blood vessel), sometimes combined with surgical intervention. Additionally, sirolimus and alpelisib are used in these cases.

For overgrowth conditions (PROS = PIK3CA Related Overgrowth Spectrum), alpelisib has been applied, primarily for pain relief and reducing the size of the malformation. This approach is still in its early stages, and much more research is needed.

Tumors are also classified within the ISSVA system, and sirolimus has shown good results here as well. This is similarly true for lymphatic malformations.

Sirolimus also appears to be effective for venous and capillary malformations. However, further research is still required.

The role of surgery has changed with the advent of these medications. While fewer surgeries are needed, the complexity of the procedures has increased.

Dr. Sheppard is a pediatric geneticist that has a research group at the Eunice Kennedy Shriver National Institute of Child Health and Human Development and is part of the Comprehensive Vascular Anomalies Program at the Children’s Hospital of Philadelphia. During the primer day she presented background about genetics of vascular malformations. She discussed the importance of genetics, the role of genetic testing in the diagnosis and treatment of vascular malformations, types of genetic tests, sample types for testing, and the general pathways involved in multiple types of vascular malformations.

Genetics is important to define or refine a phenotypic diagnosis. A genetic cause can help to direct medical screening or treatment. Knowing the genetic cause can also provide recurrence risk information to the affected individual or their parent. The genetic change (known as a pathogenic variant) can be inherited from an affected parent or can be new in the child (known as “de novo”). The genetic pathogenic variant can be in all cells of the body (autosomal recessive or autosomal dominant conditions) or can be in only the vascular malformation (called “somatic mosaicism”). Genetic testing may need to be performed on DNA from a sample of the vascular malformation in order to detect the genetic change. Growth factor signaling is important for vascular development and maintenance. There are two signaling pathways called the PI3K (phosphoinositol-3- kinase) and RAS-MAPK (rat activated sarcoma-mitogen activated protein kinase) pathways that are commonly perturbed in vascular malformations and can be targeted with medical therapies. After providing this background information, Dr. Sheppard presented example cases based on the initial presentation of an “enlarged cheek”, pulsating vascular malformation, flat brown birthmarks, red-purple patches with overgrowth and chylothorax. In these cases, she discussed both the phenotypic and genotypic diagnoses

Patient Organizations (POs) are gaining an increasingly significant voice within ISSVA. Through a member of the ISSVA Board, POs now have greater access to the Board, ensuring that the voices of POs (read: patients) are more clearly heard.

Overall, POs are being increasingly involved and recognized, particularly by organizations like ISSVA and PEDRA. However, progress remains notably slow within the EADV (European Academy for Dermatology & Venereology).

Dr. Wayne Yakes (USA) and Lex

We also had a booth in a separate room, near one of the two entrances to the main hall, where we presented our organization through a whole series of new brochures, booklets, and a new banner. Of course, we brought a large quantity of ‘stroopwafels’ and chocolate, which were very well received!

Several doctors mentioned that they already use our materials. Thanks to the online ordering option for our informational materials, it is very easy to place orders, which we then send by mail. We developed a special card with a QR code that directly links to the order page.

Our new series of brochures and booklets clearly stood out, and almost all of the materials were taken.