Ehlers-Danlos syndrome (EDS) is an inherited disorder caused by mutations in the genes responsible for the structure, production, or processing of collagen, an important component of the connective tissues in the human body, or proteins that interact with collagen. EDS is a spectrum disorder where patients present with various forms, the most serious of which is vEDS, also known as vEDS type IV, which is generally caused by a mutation in the COL3A1 gene. vEDS causes abnormal fragility in blood vessels, which can give rise to aneurysms, abnormal connections between blood vessels known as arteriovenous fistulas, arterial dissections, and spontaneous vascular ruptures, all of which can be potentially life-threatening. Gastrointestinal and uterine fragility or rupture also commonly occur in vEDS patients.
Diagnosis and Incidence
Based on an analysis of diagnosed vEDS patients from the Truven MarketScan® database and U.S. population data, we project the total COL3A1-positive vEDS patient prevalence in the U.S. could be as high as 7,000 patients. vEDS is diagnosed through clinical observation, which is usually confirmed by mutational analysis of the COL3A1 gene. In the absence of a family history of the disorder, however, most vEDS patients are not diagnosed until the occurrence of an arterial aneurysm or dissection, bowel perforation, or organ rupture. In 2019, the World Health Organization issued a new International Classification of Diseases (ICD) code (Q79.63) specifically for vEDS. Expansion of the current classification enables specific identification of vEDS and allows for more accurate and effective diagnosis, patient monitoring and reimbursement. We will continue to evaluate this new classification to help further define and identify patients available for potential treatment. Previously, vEDS was classified within one broad category that included 13 subtypes of EDS. The issuance of the new vEDS ICD code is the result of efforts led by Dr. Brad Tinkle, a clinical geneticist at Peyton Manning Children’s Hospital in Indianapolis, in collaboration with Acer, the International Consortium on Ehlers-Danlos syndromes and Related Disorders, and the ICD-10-CM Coordination and Maintenance Committee.
Current Treatment Options for vEDS
Currently, there are no approved pharmacologic therapies anywhere in the world for vEDS. However, celiprolol, off label, has become the standard of care therapy for vEDS in Europe.1 Medical intervention for vEDS focuses on surgery, symptomatic treatment, genetic counseling, and prophylactic measures, such as avoiding intense physical activity, scuba diving, and violent sports. Arterial, digestive, or uterine complications in vEDS patients typically require immediate hospitalization, observation in an intensive care unit, and sometimes surgery. Pregnant women with vEDS are considered to be at risk and receive special care.
While vEDS patients are encouraged to take steps to minimize the chances of an arterial rupture or dissection, there are no pharmacologic options to reduce the likelihood of such an event, and accordingly current treatments for vEDS focus on the repair of arterial ruptures or dissection. Therefore, patients must adopt a “watch and wait” approach following any confirmed diagnosis. Unfortunately, many of these arterial events have high mortality associated with them, and thus, a pharmacologic intervention that reduces the rate of events would be clinically meaningful.