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Dr. DePace, MD, FACC

Note: This Post is a contuinuation of the September 13, 2022 post on Vascular EDS

EDS has different types. Type IV is known as Vascular EDS. Pregnancy increases the likelihood of uterine or vascular rupture in women suffering from EDS type IV particularly during the last 3 months. The highest risk of rupture is during labor. Uterine hemorrhage can also occur postpartum. Occasionally a hysterectomy has been needed. The value of a Cesarean section carried out before the onset of labor has not been proven. Some have proposed that a medication called desmopressin be used to control bleeding during delivery.

The tendency towards hemorrhage in Type IV EDS is due to the fragility of tissue and capillaries rather than something wrong with the blood. The problem is due a defect in the protein collagen that makes fibers in arterial and venous blood vessels. This defect is what accounts for tears or dissections. This is one reason why digestive perforations can occur frequently.

Pregnant women with vascular EDS should receive treatment at special clinics. Because it is genetic, once EDS type IV is identified, Genetic counseling is recommended. The transmission is autosomal dominant, which means you only need one parent to pass on the trait, however 50% can be spontaneous with no family history.

A conservative approach in the management of EDS type IV is usually recommended. Avoid intense physical activities, violent sports, contact sports and scuba diving. Avoid drugs that interfere with platelet function or coagulation, like anticoagulants or vitamin K antagonist. Arteriograms and endoscopies are usually relatively contraindicated in GI and uterine complications unless absolutely necessary.

Surgery may, however, may be required urgently to treat potentially fatal complications, especially with very large or expanding aneurisms, or in the case of dissections and in the case of hemorrhage. Special techniques need to be used and information on the use of stents to treat vascular complications of EDS type IV is insufficient. That being said, simple arterial repairs have been successfully carried out.

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Dr. DePace, MD, FACC

Ehlers-Danlos Syndrome, Vascular Type

The vascular type of Ehlers-Danlos syndrome is predisposed to blood vessel and bowel rupture. Vascular EDS is not as common as hypermobile EDS, but important to recognize because of vascular complications.

Physical Characteristic Vascular Ehlers-Danlos Syndrome

The main presentation is hematoma (bruise or collection of blood) in a muscle. More serious and less common would be intracranial hemorrhage (bleeding in the skull).

Another serious complication, even less common, is arterial dissections (splitting of the wall of the blood vessel. Vascular EDS is not the only subtype of EDS  that presents with vascular complications. Hypermobile EDS is more common but rarely has vascular complications.

About 2% of non-vascular EDS have vascular complications.  The most common such problems include hematoma, then intracranial hemorrhage, arterial dissection, arterial aneurism,  GI bleeding, and operative hemorrhage or sporadic vascular complications.

In addition, venous complications such as varicose veins and deep vein thrombosis were reported. Referral for cardiovascular assessment and regular follow-up may be required.

Treatment for Vascular Ehlers-Danlos Syndrome

Therapeutic measures are limited to the treatment of symptoms in vascular EDS. There is only one evidence  based preventative medication called  Celiprolol, which reduces heart rate and pulsatile pressures if there is high blood pressure and can decrease continuous and pulsatile mechanical stress on collagen fiber within the arterial wall.

It should be emphasized that certain genetic determinants result in a shorter life expectancy. The goal is to delay the onset of complications.

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Dr. DePace, MD, FACC

Within the system of Classical Ehlers-Danlos Syndrome (EDS), there were initially 6 subtypes. However, with the identification of additional genetic and biochemical markers, in 2017 the classification was revised to include 13 types. We previously discussed vascular EDS  in greater detail   in the last blog. In this blog, we will discuss classical EDS.

With classical EDS, the major diagnostic criteria include skin hyperextensibility, widened atrophic scars, and joint hypermobility. It should be noted that the severity varies even among family members.

Certain proteins called collagen, which provide strength and structure to the extracellular matrix of tissues and organs. The genes that are associated with classical EDS are passed on with autosomal dominant inheritance, which means you only need one parent to get the gene.

Classical Type Ehlers-Danlos Syndrome Criterion

The Major criteria include:

1. Skin hyperextensibility and atrophic scarring.
2. General hypermobility (a Beighton score of 5 or more)

Minor criteria include:

1. Easy bruising
2. Soft doughy skin
3. Skin Fragility or traumatic splitting
4. Mulluscoid pseudotumors, which are fleshy lesions associated with scars at pressure points.
5. Subcutaneous spheroids, which are small round hard bodies that are mobile and commonly located on the forearms and chin.
6. Hernia or history of hernia
7. Epicanthal folds
8. Complications of joint hypermobility such as sprains, subluxation, pain, or flexible flat foot.
9. First degree relatives who meet clinical criteria.

Minimal criteria suggestive of classical EDS include skin hyperextensibility and atrophic scaring plus generalized joint hypermobility and 3 or more minor criteria.

Genetic confirmation is required for a definitive diagnosis. More than 90% of classical EDS patients labor a mutation of one of the genes that encode for type V collagen. A reduction in type V collagen is central to the pathogenesis of classical EDS.

While musculoskeletal joint hyper-mobility is present in classical EDS, the skin is the key to establishing the diagnosis of classical EDS. The skin is hyperextensible and soft with severe atrophic scarring and hemosiderin deposits, or brown areas over the shin and extensor surfaces, due to easy bruising. Poor wound healing is often seen in classical EDS.

A characteristic facial feature has been described. These are epicanthic folds, excess skin on the eyelids, a prematurely aged appearance, and scars on the forehead and chin. The absence of striae or stretch marks has also been noted in classical EDS patients.

Other problems are gastrointestinal problems, most commonly nausea, vomiting, and gastroesophageal reflux, followed by chronic constipation. Abnormalities in the cornea are also found in classical EDS with thin and steep and transparent corneas.

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Ehlers-Danlos Syndrome and Vascular / Arterial Rupture

Dr. DePace, MD, FACC

This is an excerpt from an upcoming book by Dr. Nicholas DePace about Ehlers-Danlos Syndrome (EDS)

Over fifty cases of bowel perforation have been documented in the literature. A type of Ehlers-Danlos Syndrome is vascular EDS and one case that was reported int the literature involved a 68-year-old man who presented with severe of abdominal pain. It was due to a jejunal artery aneurysm rupture, that’s the blood supply to the middle section of the small bowel. The man had they have part of the bowel removed and the two ends of the intestine put back together. The point is, that there has to be a high index of suspicion on the part of the doctor. As a patient, can assist with a detailed family history because the risk of multiple aneurysms, which are ballooning of the artery or vessel supplying oxygen to that part of the body, that may not be identified with screening that identifies inflammation or vasculitis.

The aneurisms are not restricted to the bowel and have been noted in the right hepatic, splenic, aortic, superior mesenteric, celiac and renal arteries. More alarming it most percent by the age of forty. Proper surgical management in vascular EDS patient, with its challenges, which may include hemorrhage (blood loss) and shock (loss of blood pressure and consciousness).

While the mechanism is controversial for what triggers the arterial accidents, it may involve inflammation or disruption of metabolic pathway for collagen, a protein that acts to keep the blood vessels intact. The individual with vascular EDS may not have the classic signs a skin hyper-extensibility or stretching but may just have easy bruising wrinkling or delayed wound healing.

While the details of collagen synthesis are beyond the scope of this blog, what is important is an accurate diagnosis to allow for rapid decision making by the treating physician which may require an MRI or CT scan as well as surgical intervention rather than medical treatment. A physician who is familiar with the implications of the family history becomes extremely important and preventing death due to ruptured arterial aneurysms. This may include using new treatments that increase survival in vascular EDS patients.  Please note that research in this area is ongoing