Keywords

Overview

  • Definition

    • A chronic, relapsing inflammatory disorder of unknown etiology with classic triad findings

      • Recurrent oral and genital aphthous ulcers

      • Ocular inflammation

      • Skin lesions

    • International criteria:

      • Behçet’s Research Committee of Japan

        • Complete, incomplete, suspect, possible

      • International Study Group for Behçet’s Disease Criteria

        • Oral ulcers +2 of: genital ulcers, eye lesions, skins lesions, pathergy test

    • Frequently involves CNS and GI tract as well

    • Ocular inflammation in 67–95%

      • Anterior uveitis

      • Devastating retinal vasculitis

  • Symptoms

    • Blurring

    • Scotomas

    • Redness

    • Periorbital pain

    • Photophobia

    • Tearing with rare ocular discharge

    • Diplopia (with neurologic involvement)

  • Laterality

    • Unilateral progressing to bilateral, 80%

  • Course

    • Recurrent inflammation, not typically chronic

    • Ocular flares are often severe

  • Age of onset

    • 25–35 years worldwide (range 2 months to 72 years)

  • Gender/race

    • Historically M > F, may be more even distribution

    • Most common in Eastern Mediterranean and East Asian

  • Systemic association

    • Systemic vasculitis

    • Oral and/or genital aphthous ulcers

    • Various mild to severe organ involvement including skin, heart, CNS, GI, lungs, GU, joints

Exam: Ocular

Anterior Segment

  • Acute anterior uveitis (AU):

    • Non-granulomatous

    • May progress to “shifting” hypopyon if untreated, 19–31%

  • More common:

    • Cataract

    • Posterior synechiae

    • Peripheral anterior synechiae

    • Iris atrophy

  • Less common:

    • Scleritis

    • Episcleritis

    • Filamentary keratitis

    • Neovascularization of iris

      • From posterior inflammation

      • Poor prognostic sign

Posterior Segment

  • Posterior or panuveitis

    • Vitritis with acute inflammation

  • Retinal and/or vitreous hemorrhage

  • Venous and capillary dilatation

  • Obliterative necrotizing retinal vasculitis (RV)

    • May involve arteries and veins simultaneously (also capillaries)

    • Ghost vessels, “silver-wired” vessels

    • CRVO or BRVO

    • CRAO or BRAO

    • NVE, NVD

  • CME

  • Chorioretinal scarring

  • Retinal tears and detachment

  • Papillitis, later progressive optic atrophy

  • Neovascular glaucoma

Exam: Systemic

  • Oral aphthous ulcers, required for diagnosis

  • Skin

    • Erythema nodosum

    • Hyperpigmented/hypopigmented scarring

    • Pathergy (40%)

    • Acne vulgaris or folliculitis, on thorax or face

  • Vasculitis (8–38%)

    • Any vessels (arteries, veins, capillaries), any size

    • Superficial thrombophlebitis, upper or lower extremities

  • Neurologic (3–10%, neurologic or vascular in origin)

    • Cranial nerve palsies (CN VI, CN VII, transient)

    • Papillitis, papilledema

    • Audiovestibular dysfunction

    • Venous sinus thromboses, intracranial hypertension

    • Pyramidal brainstem lesions

    • Seizures

    • Psychiatric disorders

  • Genitourinary

    • Ulcers

    • Epididymitis

    • Glomerulonephritis

    • IgA nephropathy

    • Amyloidosis

    • Renal vein thrombosis

  • Gastrointestinal

    • Diarrhea

    • Hemorrhages

    • Ulcers in esophagus, stomach, intestine; may perforate

  • Pulmonary (18%)

    • Hemoptysis, dyspnea, chest pain, fever, cough

    • Vascular lesions, pulmonary emboli

    • Aneurysmal bronchial fistula

  • Musculoskeletal

    • Arthritis – knee, sacroiliitis, ankylosing spondylitis, non-migrating

Imaging

  • OCT: CME, CNV, macular atrophy (after vascular insult)

  • FA: CME, retinal vasculitis (may see arteritis, phlebitis, and/or capillaritis), papillitis, vascular occlusion/delay, neovascularization, chorioretinitis

    • Diffuse dye leakage may be seen after inflammation subsides

  • ICG: hypocyanescent choroidal lesions

  • ERG: decreases in overall standard and pattern ERG

Laboratory and Radiographic Testing

  • No definitive serologic or laboratory testing

  • May be elevated acute phase reactant proteins: ESR, CRP, complement

  • HLA-B51 association (not diagnostic)

  • Elevated soluble CD25 may precede recurrence

Differential Diagnosis

  • HLA-B27 associated uveitis

    • Reactive arthritis

  • Sarcoidosis

  • Systemic lupus erythematosus

  • ANCA vasculitides

  • Viral retinitis

Treatment

  • Acute AU: frequent topical corticosteroid +/− cycloplegia

    • Q1h steroid and atropine 1% BID with hypopyon

  • Severe AU or posterior involvement

    • Requires aggressive and urgent therapy

    • Systemic corticosteroids, oral or intravenous (or both)

    • Initiation of immunomodulatory therapy

      • May coordinate with other specialists

  • Immunomodulatory therapy

    • Antimetabolites

      • Azathioprine or mycophenolate

    • Calcineurin inhibitors

      • Cyclosporine may supplement antimetabolite therapy

    • Biologics (especially with RV)

      • TNFα inhibitors – adalimumab, infliximab

      • CD20 inhibition – rituximab

      • Anti-IL1β – anakinra, canakinumab (used in some cases)

    • Alkylating agents

      • Chlorambucil or cyclophosphamide

  • Other therapeutic measures

    • Colchicine

    • Plasmapheresis

    • Interferon α-2a

    • Dapsone

    • Pendoxyphilline

    • Penicillin

    • Thalidomide

Referral/Co-management

  • Rheumatology

  • Cardiology

  • Neurology

  • Dermatology

  • ENT

  • Gastroenterology

  • Urology

  • Pulmonology