Vascular involvement and clinical criteria

in Behcet`s disease

Presented by:

Sasan Fallahi, MD

Rheumatologist, Kerman University of Medical Sciences

History

• First description: Hippocrates in 5th century before BC

• First modern: Hulusi Behcet in 1937 (a case with recurrent oral aphtous, genital aphtous, uveitis)

Epidemiology

• worldwide

• Most prevalent in silk road ( middle east, Mediterranean,…)

• Turkey: 80-370 in 100000

• Iran: 80 in 100000

• Japan: 13.6, China: 14 in 100000

• Spain: 7.5 in 100000

• Uncommon in northern Europe & USA (0.1-7.5 in 100000)

Clinical manifestations

• Major:

* mucosal

* Skin

* eye

• Minor:

* joint, CNS, GI, vascular,…

Vascular disorders

• Iran: 8.3%, Turkey: 17%, ITR-ICBD: 18%

• Any size

• Venous: more common

*superficial phlebitis, DVT, large vein thrombosis

SVC, IVC, supra-hepatic, portal vein thrombosis

cerebral venous and retina thrombosis• Arterial:

*aneurism, thrombosis

Pathophysiology of vasculitis and thrombosis

AntigenAntigen(HSP)(HSP)AntigenAntigen(HSP)(HSP)

Genetic background

B51Super Ag Macrophage

(APC)

T cell ( ɣδ )

IL1

TNFα, β, INFɣ

B cellAECAVessel

wall

thrombosis

PMN

CAM, IL8

Superoxide, NO

Tissue

Hyperhomocysteinemia, antiphospholipid Ab, decrease protein C, S, antithrombin ΙΙΙFactor V Leiden

mutation

Pathogenesis of aneurisms

• Unclear• Suggested:

ExogenouExogenoussfactorfactor

ExogenouExogenoussfactorfactor

Genetic background

MononucleMononuclear cellsar cellsMononucleMononuclear cellsar cells

Functional Functional impairmenimpairmentt

Functional Functional impairmenimpairmentt

Obliterative Obliterative endarteritis of vasa endarteritis of vasa vasorum, endothelial vasorum, endothelial cell swelling, cell swelling, perivascular infiltrationperivascular infiltration

Obliterative Obliterative endarteritis of vasa endarteritis of vasa vasorum, endothelial vasorum, endothelial cell swelling, cell swelling, perivascular infiltrationperivascular infiltration

Destruction of media, Destruction of media, arterial wall thickeningarterial wall thickeningDestruction of media, Destruction of media, arterial wall thickeningarterial wall thickening

AneurysAneurysm m formationformation

AneurysAneurysm m formationformation

Superficial thrombophlebitis

• Most frequent type• May predict visceral involvement• Increase risk of DVT• Main symptom: localized extremity pain• May occur after venipuncture• Females are affected more than males

DVT

• Males > females• More common in younger age of disease onset• Reported as an initial symptom• Critical period for development: 2-3.2 years after

diagnosis of Behcet disease• Tend to occur earlier than arterial involvement

IVC thrombosis

• 15% of large vessel involvement• Should be suspected in:

* alternating venous thrombosis in lower limbs

* Recurrent venous thrombosis in one limb

Budd-Chiari syndrome

• Characterized by hepatomegaly, RUQ pain, ascites, oedema of lower limbs

• Rarely, spontaneous remission• Mostly, at risk of slowly progressive hepatic

failure, • Not common

SVC thrombosis

• 1.4-9.8% of venous involvement• Blockage of lymphatic circulation: chylothorax

Cerebral venous thrombosis

• Main symptom: persistent headache and papilledema due to intracranial HTN, may be the presenting feature of disease

• Is not rare

Peripheral artery involvement

• Marked male predominance• Any peripheral artery: femoral, popliteal, iliac and

abdominal aorta• Infrequent in carotid artery• Venous involvement is found in most patients• Occlusion is more common than aneurysm but

both is not unusual finding• Clinical presentation: asymptomatic to pulsatile

mass, back pain, painful mass, hematoma, intermittent claudication, abdominal pain, gangrene of forefoot, …

• Rate of death: up to 60%

Pulmonary vascular involvement

• The most sever: Pulmonary artery aneurism: leading cause of death

• Almost exclusively in males• Most frequent symptom: chest pain, hemoptysis• Association with: DVT of lower limbs, vena cava

or intra-cardiac thrombosis and aneurysms in other sites

Laboratory

ESR, CRP (ESR in Iran: 40% normal)

HLA B5: 53% in Iran

HLA B51: 47% in Iran, ITR-ICBD: 49%

Pathergy: 54% in Iran, ITR-ICBD: 49%

Diagnosis & diagnostic criteria

• Clinical• Diagnosis criteria:

-Curth, 1946

-Mason & barnes, 1969

-O Duffy: 1974

-Dilsen: 1986

-japan: 1972, 1988

-ISG: 1990

-Iran: 1993

- international criteria (ITR-ICBD) (2006)

- new ICBD (2010)

Sensitivity: 91%, specificity:96%

ISG criteria(1990)

Iran criteria(1993)

• Oral aphthae 1

• Skin lesions (PF, EN) 1

• Pathergy test 1

• Genital aphthae 2

• Eye lesions 2

>= 3 score indicates Behcet disease

ITR-ICBD(International Team for the Revision of the International Criteria for Behcet’s

Disease)

• Participants: 27 countries

– Austria, Azerbaijan, China, Egypt, France, Germany, Greece, India,

Iran, Iraq, Israel, Italy, Japan, Jordan, Libya, Morocco, Pakistan,

Portugal, Russia, Saudi Arabia, Singapore, Spain, Taiwan, Thailand,

Tunisia, Turkey, USA

• Data Collection: March 2005 to June 2006

• BD patients: 2556

international criteria (ICBD)

Oral aphthosis 1

Skin lesions (PF, EN) 1

Vascular lesions 1

Pathergy test 1

Genital aphthosis 2

Eye lesions 23 or more points » Behcet’s Disease

(sensitivity: 96%, specificity: 88%, accuracy: 93.8%)

New international criteria (new ICBD)

• Oral aphthae 2

• Skin lesions (PF, EN) 1

• Vascular lesions 1

• Genital aphthae 2

• Eye lesions 2

• CNS lesions 1• Pathergy test 1 (some where)

>= 4 score: sensitivity: 94%, specificity: 90.5%

(International society for Behcet disease, 8-10 July 2010, London)

• Vascular * arterial thrombosis: cytotoxic + prednisolon * DVT: cytotoxic + prednisolon * superficial phlebitis: NSAID * large vessel thrombosis: anticoagulant + cytotoxic

+ prednisolon * Peripheral arterial aneurysm: arterioplasty +

corticosteroid + cytotoxic * Pulmonary arterial aneurysm: corticosteroid +

cytotoxic ± embolization or surgery (in life threatening haemoptysis)

Treatment

Morbidity:• most common: ocular blindness

Mortality:• Low• Related to pulmonary, CNS, bowel perforation