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)

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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 TNFα, β, INFɣ Tissue Superoxide, NO IL1 Genetic background Antigen (HSP) Macrophage (APC) Super Ag B51 T cell ( ɣδ ) PMN Vessel wall CAM, IL8 AECA B cell Hyperhomocysteinemia, antiphospholipid Ab, decrease protein C, S, antithrombin ΙΙΙ Factor V Leiden mutation thrombosis

Pathogenesis of aneurisms Unclear Suggested: Exogenous factor Mononuclear cells Functional impairment Genetic background Obliterative endarteritis of vasa vasorum, endothelial cell swelling, perivascular infiltration Destruction of media, arterial wall thickening Aneurysm formation

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 HLA B5: 53% in Iran HLA B51: 47% in Iran, ITR-ICBD: 49% 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) Sensitivity: 91%, specificity:96%

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 2 3 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)

* arterial thrombosis: cytotoxic + prednisolon Treatment 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)

Morbidity: Mortality: most common: ocular blindness Low Related to pulmonary, CNS, bowel perforation