Behcet s disease new concepts in vascular involvements

1. Dr. Onur GÖKSEL
Istanbul University, Istanbul Medical Faculty
Department of Cardiovascular Surgery

2. Behçet’s disease is an inflammatory disorder
characterized with recurrent oral and genital ulcers,
uveitis, skin and vascular lesions and extends from
Eastern Asia to the Mediterranean Basin along the
ancient Silk Road

3. HULUSİ BEHÇET(1889-1948)

4. Behcet’s: Epidemiology
Disease prevalence and expression vary
geographically
Mediterranean Basin
Turkiye has the highest prevalence: 80 to 370 cases
per 100,000 population.

5. Behcet’s: Epidemiology
Prevalence in Japan, Korea, China, Iran, and Saudi
Arabia ranges from 13.5 to 20 cases per 100,000
The prevalence is much lower in Western countries.
Prevalence of 0.33 per 100,000 in the United States.

6. Behcet’s: Pathophysiology
The underlying cause of Behcet's disease is unknown.
As with other autoimmune diseases, the disorder may
represent aberrant immune activity triggered by
exposure to an agent, perhaps infectious, in patients
with a genetic predisposition to develop the disease.

7. Behcet’s: Pathophysiology
The prevalence of the HLA-B51 allele is high among
patients with Behçet's disease who are of Middle
Eastern or Far Eastern ancestry (up to 81 percent of
Asian patients have the allele)
Not among white patients who live in Western
countries (13 percent).
Studies suggest a possible pathogenic role of certain
bacterial/viral antigens that have cross-reactivity with
human peptides.

8. Behcet’s: Pathophysiology
Endothelial activation in vasculo-Behcet's
Hyperfunction of neutrophils noted within active
lesions
Recurrent lesions
Inflammatory obliteration of the vasa vasorum and
consequent transmural necrosis may develop a
pseudoanurysm or rupture an arterial wall.

9. Behcet’s: Pathophysiology
Matrix metalloproteinase proteins (MMP) which play
an important role in tissue remodeling and
destruction of extracellular matrix components are
thought to have significant role in aneurysm
formation.
MMP-9 & MMP-2 markers of vascular involvement
(Pays et al)(Pays et al)
Surgery has been reported to yield poor results
and a focal repair procedure often results in early
to late complications

10. Clinical Manifestations: Vascular
The involvement of large vessels may be observed in
1.8–39.4 % of patients with BD.
The vascular involvements of BD occur in the veins
more frequently than the arteries.
Vascular involvement of BD is characterized by
aneurysm and pseudoaneurysm formation in arteries
and thrombotic occlusion in arteries and veins.

11. Hamza classification of vascular involvement in
Behçet Dİsease
Type Vascular involvement
I Venous thrombosis
II Arterial thrombosis
III Arterial aneurysm
IV Arterial thrombosis and aneurysm
V Venous thrombosis and arterial lesion

12. Arterial
Occlusive or aneurysmal lesions
The most severe complication is
aneurysm formation and rupture.
Abdominal aorta is the commonest site of
aneurysm and approximately 60% of
reported arterial lesions associated with
BD is an aneurysm.
Ao>PA>FA

13. Aneurysm
Aortic aneurysms show rapid progression to rupture,
and as a result, huge retroperitoneal hematoma or
hemoperitoneum.
Aortic aneurysms are often a pseudoaneurysm
Posterior or lateral walls of normally sized aorta and
then extend into the adjacent retroperitoneal space

14. Aneurysm
Occurrence of PAA along with deep vein thrombosis
is defined as Hughes-Stovin syndrome (HSS), which
may be a variant of BD.
Patients with HSS have a poor prognosis.
The occurrence of intracranial aneurysm in BD is very
rare

15. Treatment
Vascular Disease
There are no controlled data on, or evidence of
benefit from uncontrolled experience with
anticoagulants, antiplatelet or antifibrinolytic agents
in the management of deep vein thrombosis or for the
use of anticoagulation for the arterial lesions of BD.

16. Clinical Manifestations: Vascular
Fatal complications
organ failure
Bleeding
limb ischemia
Despite immunosuppression

17. Treatment
Vascular Disease
There is no firm evidence to guide the management
of major vessel disease in BD.
 For the management of acute deep vein thrombosis
in BD, immunosuppressive agents such as
corticosteroids, azathioprine, cyclophosphamide or
cyclosporine A are recommended.

18. Treatment
Vascular Disease
Peripheral artery aneurysms carry a high rupture risk
and require repair accompanied by systemic
immunosuppressives.

28. 27-year old lady
90x67x58 mm abdominal aortic pseudoaneurysm
from distal suture line of an earlier patch
24x70 mm, tube-shaped Talent Endoluminal
Stent-Graft
Initial experience with EVAR in Behçet’s diseaseInitial experience with EVAR in Behçet’s disease
Rupture of right CIA (Ligation and cross-over
bypass with 6 mm ePTFE graft)
She is well and complication-free at her 4th year
followup.

29. Patient No. 3 open aortoenteric fistula
52-year-old lady with hypotension abdominal pain,
pulsatile mid-abdominal mass, fever, anemia (hematocrit
of 26%), leukocytosis and abdominal tenderness
Initial diagnosis: 50x 60x 55 mm infrarenal aortic
pseudoaneurysm

30. New CAT scan: a contained aortic
rupture & a fistula into 4th
segment of duodenum with a 40
mm aortic connection obstructed
with hematoma
Emergency open procedure
Small intestines firmly adhered to
rupture site
 Aortic site was replaced with a 16
mm- PTFE graft in a 45 mm-long
segment during open surgery.

31. Intestines viable and intestinal defect primarily repaired
Oral feeding on day 3
Frank hematemesis after 9 days of uneventful course in
the hospital.
An abdominal CAT scan with oral contrast showed a
residual aortoenteric fistula
Tube shaped self-expandible 18 x 70 mm Talent
Endoluminal Stent-Graft (World Medical Manufacturing,
Sunrise, Fla) via right femoral artery

32. She is symptom-free at 3 years

34. 30-year-old diabetic male w/ rupturedruptured 60x55
mm-infrarenal aortic aneurysm
Emergency laparatomy with aneurysm repair
with 18 mm- polytetrafluoroethylene tube graft
On day 7, persistant abdominal pain and
gradual hematocrit drop
CAT scan: a hematoma around the proximal
suture line.
A tube shaped self-expandible 18 x 70 mm
Talent Endoluminal Stent-Graft
At the time of the intervention, hematocrit was
as low as 18% and did not further drop after
EVAR and control CAT scan eliminated a
possible leak.
Unfavorable general status
He expired on day 28 with multiorgan failure.
Active Behçet’s disease with other classic
systemic manifestations.

35. A focal surgical repair often results in late
complications requiring a re-intervention as in our
first patient
Endovascular repair may be a better option for aortic
pseudoaneurysms being less invasive with avoidance
from aortic anastomoses
Emergency or contaminated settings (aorto-enteric
fistulae) open surgery may be required.
In our experience, treatment of such lesions with
patch-repair results in recurrence

37. Kwon et al. EJVES 2008Kwon et al. EJVES 2008

38. Small Aneurysm <40 mm

40. Importance of close scrutiny for vascular lesions in
Behcet’s disease can not be overstated
Follow-up with a CAT scan as frequent as every six
months in spite of adequate suppression of the active
Behçet’s disease has been suggested

41. Experience on a limited number of patients and
presentation of complicated cases at most of the time
may hinder the true outcome of EVAR in these
situations.
More specific conclusions on issues particularly as
aortoenteric fistulae are to be reached with growing
experience.

42. Strategy?

43. Timing?!?

44. No ordinary lesion?

45. Cooperation-coordination!

46. Investigational Tx
No doubt is about the future role of biologic agents
and targeted agents against proinflammatory
cytokines such as IL-15, 17, 21, and adhesion molecules
in controlling BD.
Using biological agents targeting TNF-alpha may
improve endothelial dysfunction responsible for more
features of BD.

47. 97 published papers 1990
573 papers 2010