Vascular Ehlers Danlos Syndrome (vEDS) is a disorder of Type III Collagen, a crucial component of connective tissue. The disease is initiated by a mutation that causes malformation of collagen fibrils, which are a major component of ligaments, tendons, intestines, and, most importantly, blood vessels. Major blood vessels, especially large arteries like the aorta and femoral artery, become weakened and fragile due to the lack of functional collagen, and are at increased risk of rupturing, causing a life-threatening internal hemorrhage.
There is currently no curative treatment available for the disease, and treatment has largely been limited to surgical intervention to fortify, or repair, weakened organs and arteries. Since breakage of major arteries is almost always fatal due to massive internal bleeding, closely monitoring major vessels and identifying weaknesses is essential to patient survival. Vessel weaknesses generally present as aneurysms, a small budge in a blood vessel, or as dissection, in which the inner, but not the outer, wall of the aorta tears. Such vessel abnormalities can be detected via basic medical imaging techniques, like MRI, CT scan, or ultrasound; these tools are all non-invasive, which is now considered preferable because interventional methods may inadvertently further damage blood vessels (Busch et al, 2014). In many cases, such arterial abnormalities are detected accidentally during medical scans for a different condition.
Grafts and Stents
When weaknesses of the vessels are detected, they can be treated with either surgery or stents. Surgical treatment, or “open” repair is highly invasive, as the physician makes a large incision near the aneurysm, and then stops blood flow to the area (Coselli, Bozinovski, and LeMaire, 2007). Blood flow to this region can then be stopped using endovascular embolization (blockage caused by intentional blood clotting), as this is one of the few methods that do not cause excess pressure on the surrounding vessels, which might cause further breakage in vEDS patients (Nakanishi, et al 2014). For small aneurysms, it may also be possible to clamp (rather than remove) the aneurysm, which prevents blood from entering the aneurysm and thus relieves pressure, decreasing the likelihood that it will burst. In most cases, though, this is insufficient, and the surgeon will need to completely resect the aneurysm, and then cover this section with a graft, which serves as a patch to physically close the artery. Alternatively, a small vein from the leg could be used to close the aneurysm instead of a synthetic graft. This type of surgery, though, is generally considered high-risk, and may result in postoperative infection and major scarring at the site of incision.
Therefore, the second method of treatment, endovascular stent graphs, is rapidly becoming the preferred method of treatment for aneurysms and other vessel weaknesses; this treatment uses endovascular surgery with small incisions, rather than traditional open surgery with large incisions, where there is a greater risk of infection and damage to surrounding tissue. An endovascular stent is inserted near the groin and moved through the blood vessels to the location of the aneurysm, where it is inflated. The stent then serves as a tunnel through which the blood can move through; the blood thus puts pressure on the walls of the stent, rather than on the walls of the artery itself. This thus reduces the stress on the artery and drastically decreases the likelihood of future vessel rupture. This stent minimizes the likelihood of future vascular complications, and has been shown to be highly successful (Nakagowa et al, 2014).
Both methods of surgical treatment are still relatively common and effective. Fixing aneurysms is a relatively common procedure for surgeons, and is generally successful. vEDS patients, though, are high risk patients due to the weaknesses in the blood vessels, and have a much higher mortality rate; the weakened blood vessels are at increased risk of rupture or injury during surgery, sometimes resulting in a fatal hemorrhage. Both endovascular and open surgery can be used upon detection of a vessel weakness, but open surgery is likely required after the artery has burst. In many cases, the rupture of a major artery, like the aorta, is immediately fatal, and surgery is not able to save the patient.
Surgical Repair of Organ Rupture
Surgery also features prominently in the repair of other symptoms of vEDS. Sadly, organ rupture is also a relatively common procedure that requires surgical correction, in which a tear in the organ is physically stitched closed. This is extremely common in the intestines and reproductive organs, as these organs use large amounts of collagen to maintain both strength and flexibility. This is particularly problematic during pregnancy, where uterine rupture is a common symptom due to pressure from the growing fetus (Murray et al, 2014). The fetus can also damage neighboring organs, resulting in a massive hemorrhage. In cases of vessel or uterine perforation, emergency surgery is usually required in which the baby is removed via C-section and the vessel is repaired. In some cases, these problems can be fatal.
Elective Surgeries for minor symptoms
The musculoskeletal abnormalities that result in a long, thin nose and pursed lips can be fixed electively using cosmetic surgery, if desired (Byers et al, 1979). These symptoms, though, are not particularly drastic, and many choose not to undergo surgery, particularly because surgery is so high risk. Varicose veins, which are enlarged, spider-like veins, are also extremely common in these patients. While these veins do not rely heavily on collagen for strength (and thus are not at increased risk of perforation), they do rely on collagen to maintain their normal, straight shape. Endovenous surgery using lasers, though, has been shown to be useful to treat this problem (Whiteley and Holdstock, 2014). It is important to note that these musculoskeletal symptoms do not greatly affect the health of the patient, and any surgical treatment is purely elective.
Until recently, surgical intervention was the only treatment available for vEDS patients. Recently, though, Celiprolol, a medication previously prescribed for patients with high blood pressure, has shown to be effective at reducing the incidence of vascular rupture in vEDS patients over a five-year double blind clinical trial (Ong et al, 2010). Although the mechanism has not yet been proven, it is believed that Celiprolol works by upregulating the beta-androgenic receptor, which then activates a downstream transforming growth factor (TGFB), a protein that controls a wide variety of biosynthetic pathways during growth; TGFB is previously known to upregulate the production of both Type I and III collagen. The newly synthesized collagen could then be incorporated into the walls of blood vessels and organs, making them much less likely to burst. Since the rupture of these structures is often fatal, this treatment method is revolutionary for vEDS patients.
All types of treatment, though, is somewhat high-risk, as surrounding blood vessels and organs are extremely weak, and frequently accidentally damaged during surgery. Therefore, it is generally recommended that all types of surgery be minimized in vEDS patients, except in cases where the risks of not doing the surgery outweigh the risks involved with the surgery. For this reason, it is recommended that, whenever possible, physicians use non-invasive methods when attempting to diagnose and treat any medical concerns in patients with vEDS. Thus, the development of Celiprolol, a non-surgical treatment method, is seen as an exciting breakthrough in the field.