Behcet’s Syndrome N.Movaffagh MD Rheumatologist

DEFINITION Behçet’s syndrome is a multisystem disorder presenting with recurrent oral and genital ulcerations as well as ocular involvement The diagnosis is clinical and based on internationally agreed diagnostic criteria

INCIDENCE Males and females are affected equally Males often have more severe disease Blacks are very infrequently affected young males and females from the Mediterranean region, the Middle East, and the Far East, suggesting a link with the ancient Silk Route

PATHOGENESIS The disease appears to be in the crossroads of autoinflammatory and autoimmune disorders. The main pathologic lesion is : systemic perivasculitis with early neutrophil infiltration and endothelial swelling Vasculitis of vasa vasorum(pseudoaneurysms)

PATHOGENESIS TH1, TH17, cytotoxic CD8+, and γδ T cells Circulating autoantibodies against: α-enolase of endothelial cells selenium binding protein Saccharomyces cerevisiae Their pathogenic role remains unclear.

PATHOGENESIS HLA-B*51 (MHC) class I (IL) 10 locus

CLINICAL FEATURES recurrent aphthous ulcerations genital ulcers Skin involvement Eye involvement arthritis or arthralgias Superficial or deep peripheral vein thrombosis Pulmonary emboli

Arterial involvement Neurologic involvement Gastrointestinal involvement Epididymitis amyloidosis of AA type and glomerulonephritis

Diagnostic Criteria of Behcet’s Syndrome Recurrent oral ulceration plus two of the following: Recurrent genital ulceration Eye lesions Skin lesions Pathergy test

Oral aphthous ulcerations Painful shallow or deep central yellowish necrotic base singly or in crops less than 10 mm(85%) large or herpetiform lesions are less frequent ulcers persist for 1–2 weeks Subside without leaving scars

Genital ulcers less common More specific Painful Do not affect the glans penis or urethra produce scrotal scars

Skin involvement observed in 80% Folliculitis Erythema nodosum Acne-like exanthema vasculitis Sweet syndrome pyoderma gangrenosum

Erythema nodosum

pathergy test Nonspecific skin inflammatory reactivity to any scratches or intradermal saline injection a common and specific manifestation

Eye involvement in 50% of patients bilateral panuveitis with scarring is the most dreaded complication iritis, posterior uveitis retinal vessel occlusions optic neuritis Blindness usually present at the onset

Joint Involvement Nondeforming arthritis or arthralgias in 50% of patients knees and ankles

Superficial or deep peripheral vein thrombosis is seen in 30% Pulmonary emboli are rare The superior vena cava is obstructed occasionally

Arterial involvement in less than 5% Aortitis or peripheral arterial aneurysm Arterial thrombosis Pulmonary artery vasculitis (Dyspnea, cough, chest pain, hemoptysis, and infiltrates on chestX-ray)

Neurologic involvement mainly in the parenchymal form (80%) brainstem involvement ( CNS-Behcet’s syndrome) IL-6 is persistently raised in csf

Cerebral venous thrombosis is most frequently observed in the superior sagittal and transverse sinuses headache and increased intracranial pressure MRI,MRS are very sensitive

Gastrointestinal involvement more frequently in patients from Japan consists of mucosal ulcerations of the gut Resembling Crohn’s disease

Epididymitis is seen in 5% of patients amyloidosis of AA type and glomerulonephritis are uncommon

Laboratory findings Leukocytosis ESR C-reactive protein

TREATMENT life expectancy seems to be normal (Apart from the patients with CNS-Behcet’s syndrome and major vessel disease) only serious complication is blindness

TREATMENT Mucous membrane involvement: Topical glucocorticoids(mouthwash or past) Thalidomide (100 mg/d) Colchicine

Colchicine can be beneficial for the arthritis

TREATMENT Thrombophlebitis is treated with aspirin, 325 mg/d

TREATMENT Uveitis and CNS-Behcet’s syndrome : systemic glucocorticoid therapy (prednisone, 1mg/kg per day) and azathioprine (2–3 mg/kg per day)

TREATMENT sight-threatening uveitis : Cyclosporine(5 mg/kg) alone or in combination with azathioprine

TREATMENT panuveitis refractory to immunosuppresives: Anti–tumor necrosis factor

TREATMENT pulmonary or peripheral arterial aneurysms Pulse doses of cyclophosphamide

Thank you