Vascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck Mass: a Case Report and Review of Literature
Vascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck Mass: a Case Report and Review of Literature
Bharat Maraj 0
Emily Harding-Theobald 0
Fatima Karaki 0
0 Department of Medicine, University of California, San Francisco Medical Center , San Francisco, CA , USA
Ehlers-Danlos syndrome refers to a spectrum of connective tissue disorders typically caused by mutations in genes responsible for the synthesis of collagen. Patients w i t h E h l e r s - D a n l o s s y n d r o m e o f t e n e x h i b i t hyperflexibility of joints, increased skin elasticity, and tissue fragility. Vascular Ehlers-Danlos (vEDS) is a subtype of Ehlers-Danlos syndrome with a predilection to involve blood vessels. As such, it often manifests as vascular aneurysms and vessel rupture leading to hemorrhage. There are few reports describing primary prevention of aneurysms in the setting of undiagnosed, suspected vEDS. We present a case of a 30-year-old woman who presents with a pulsatile neck mass found to have multiple arterial aneurysms on imaging, hyperflexibility, and characteristic facial features consistent with vEDS. As described in this case, management of a suspected connective tissue disorder is a multidisciplinary approach including vascular surgery, medical therapy, and genetic testing to confirm the diagnosis. We review literature regarding the care of patients with vascular Ehlers-Danlos as it might pertain to hospitalized patients.
vascular; Ehlers-danlos; aneurysm
Ehlers-Danlos syndrome is a heterogeneous group of rare
connective tissue disorders that often manifest with increased
skin elasticity, joint hypermobility, and tissue fragility.
Vascular Ehlers-Danlos syndrome (vEDS) accounts for fewer than
5% of all Ehlers-Danlos cases 1. It is associated with an
autosomal dominant mutation in COL3A1, responsible for
the synthesis of type III collagen 2–4. Type III collagen
composes connective tissue found within all organs. It provides
tensile strength for organs that must resist permanent dilation
from fluctuations in pressure. Consequently, vEDS typically
presents as rapidly progressive arterial aneurysms, arterial
rupture, bowel perforation, and uterine fragility 5–7. Suspicion
often arises when incidental findings are identified on routine
imaging studies 6. Definitive diagnosis requires identification
of a heterozygous COL3A1 pathogenic genotype. We report
the case of a young woman who was diagnosed with a rapidly
enlarging arterial pseudoaneurysm, ultimately found to have
vEDS, managed with open ligation of her external carotid
A 30-year-old woman with a history of bilateral varicose veins
was admitted from otolaryngology clinic with a 3-week
history of a painful, rapidly growing right neck mass. The patient
was previously diagnosed with parotitis at an outside hospital
but the neck mass continued to grow despite completion of a
two-week course of cephalexin. She denied trauma or injury to
her neck, jaw, or face. She denied fevers, chills, weight loss,
visual changes, and arthralgias. The patient had a medical
history of persistent bilateral varicose veins despite
uncomplicated endovenous ablation 1 year prior to admission. She also
had a remote history of colonic perforation secondary to a
lowspeed motor vehicle accident which required laparotomy and
repair. She did note a history of easy bruising throughout her
life. She had no family history of bleeding diathesis or
connective tissue disease. On admission, her vitals were within
normal limits. Her physical exam was significant for a 3-cm
diameter pulsatile mass with surrounding edema of the right
neck and mandible. There was a violaceous, reticular rash
overlying the mass (Fig. 1a). Skin elasticity was normal. Her
face had large eyes, a thin nose, thin lips and a small chin. She
had bilateral severe varicose veins without lower extremity
edema (Fig. 1b). Distal interphalangeal joints and shoulders
were hyperextensible with multiple movements (Fig. 1d, e).
Metaca rpophalangea l joints hyperextended > 90° ,
hyperflexion of wrists approached 140°, and her knees
achieved hyperextension > 15°. Cardiovascular, pulmonary,
abdominal, and neurologic examinations were unremarkable.
Complete blood count, electrolytes, serum creatinine, liver
function tests, and international normalized ratio were within
normal limits. Blood cultures were negative. Erythrocyte
sedimentation rate and C-reactive protein were not elevated.
Antinuclear antibody, rheumatoid factor, anti-neutrophil
cytoplasmic antibody, and complement levels were unremarkable.
Computer tomography angiography (CTA) of the neck
revealed a 2.7-cm aneurysm arising from the proximal right
internal maxillary artery (Fig. 2) as well as a 4-mm aneurysm
in the proximal right internal carotid artery. Brain CTA
showed a 3-mm aneurysm of the left middle cerebral artery.
Chest, abdomen, and pelvis CTA did not reveal any other
aneurysms. Transthoracic echocardiography did not show
mitral valve prolapse or other abnormalities.
Rheumatology, otolaryngology, interventional radiology,
and vascular surgery were consulted. The patient’s clinical
picture was thought to be most consistent with vEDS. After
multidisciplinary discussions, the patient underwent an urgent
open ligation of the maxillary and temporal artery via vascular
surgery. The surgery was uncomplicated and the patient made
a full recovery. Genetic testing was sent to confirm the
diagnosis of vEDS. She was started on carvedilol, oral
contraception, and was discharged with genetics follow-up and a CTA
head and neck planned for 3 months after discharge.
Our patient was diagnosed with the COL3A1 gene
mutation, confirming the diagnosis of vEDS. Ongoing screening of
vascular lesions was determined on an individual basis by
vascular surgery. The interval and modality depends on the
location and size of lesions. Genetics was also consulted to
discuss the risk of inheritance and pregnancy with the patient
and her family.
Diagnosis of vEDS is challenging because of variable
penetrance within families. A family history of connective tissue
disease can be absent as haploinsufficiency and biallelic
sequence variants lead to variable clinical presentations and
severity of illness 7,8. De novo mutations in the COL3A1 gene
are also a possibility as was suspected in our patient 9.
There are 5 major and 12 minor criteria that distinguish
vEDS from other forms of Ehlers-Danlos and help to establish
a clinical diagnosis 10. Of the major criteria—arterial
vasculopathy at < 40 years of age, spontaneous colon or uterine
rupture, unexplained carotid-cavernous sinus fistulization, and
family history—our patient had bowel perforation despite
minimal trauma and early-onset vasculopathy. Several minor
criteria were also present including easy bruising, thin skin
(indicated by visible veins), characteristic facial features, joint
hypermobility, and early-onset varicose veins 10–12. Typical
facial features include large eyes, small chin, lobeless ears, and
thin nose and lips. However, characteristic facial features are
often subtle and can be absent 13. Joint hypermobility can be
assessed by the Beighton score, a standardized evaluation for
generalized joint hypermobility 14. In patients with these
features, vEDS should be suspected and genetic testing should be
completed to confirm the diagnosis.
The diagnosis of vEDS is frequently delayed until after
patients present with devastating sequelae. In one study, 61%
of patients had at least one severe vascular complication prior
to the age of 40 years 15. Our patient was initially misdiagnosed
with parotitis, but she was fortunate to return to care with a
visible pulsatile mass that was treated prior to arterial rupture.
However, most vascular abnormalities—including arterial
aneurysms, dissections, and ectasias—are not visible on physical
examination and occur in visceral arteries and deep arteries of
the head and neck 16. As such, practitioners should be aware
that many patients first present with hemodynamic instability
secondary to emergent internal bleeding. Although our patient
was not bleeding, she was at high risk of rupture and urgent
treatment of her aneurysm was necessary to prevent a
The management of vascular complications in patients with
vEDS is difficult. Endovascular procedures carry a significant
risk of arterial dissection and aneurysm formation and are not
typically recommended 17. However, there are case reports of
successful endovascular procedures in affected patients 18,19.
Our patient underwent open ligation of the external carotid
artery rather than an endovascular approach in order to avoid
arterial rupture and iatrogenic arterial damage. There is little
evidence for effective medical management in vEDS. One
randomized control trial demonstrated a significant reduction
in arterial dissection and rupture with use of celiprolol, a
β1β2 receptor antagonist 20. Our patient was discharged on
carvedilol with the hope that other beta-blockers may offer a
similar protective benefit. Oral contraception was warranted to
help prevent pregnancy given the risk of uterine rupture.
Combined oral contraception was preferred because
progestin-only contraceptives have been associated with
worsening joint hypermobility 21.
Vascular Ehlers-Danlos has a relatively poor prognosis. The
average life expectancy is 48 to 50 years. Patients typically die
from acute arterial rupture leading to exsanguination 22.
Despite treatment, our patient has other aneurysms that pose a
significant risk of bleeding and will require close outpatient
follow-up. Following vascular lesions with non-invasive
imaging has been shown to be an effective tool for counseling
patients about the risks and benefits of elective surgical repair.
However, patients should also be counseled that close
monitoring does not change overall mortality, as fatal lesions are
typically rapidly expansive 23.
We describe a case of vEDS in a woman presenting with a
pulsatile neck mass. This diagnosis requires a high degree of
clinical suspicion and aggressive management to prevent
catastrophic consequences. Clinicians should be aware that the
vascular subtype can present with findings relatively
dissimilar to the classic phenotype of Ehlers-Danlos. Endovascular
approaches must be completed with caution and open ligation
should be reserved for ruptured vessels or vessels in which
rupture is imminent. Wider recognition of this unusual
diagnosis will be essential to reducing the high morbidity and
mortality associated with vEDS.
Corresponding Author: Bharat Maraj, MD; Department of Medicine
University of California, San Francisco Medical Center, San Francisco,
CA, USA (e-mail: ).
Compliance with Ethical Standards:
Conflict of interest: The authors declare that they do not have a
conflict of interest.
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