Behcet Disease
Systemic vasculitis characterised by recurrent oral and genital ulceration, uveitis, and skin lesions. Involves both arteries and veins of all sizes. Most common along the 'Silk Road' from East Asia to the Mediterranean. Associated with HLA-B51.
Key Facts
Behcet disease is characterised by the triad of recurrent oral ulcers, genital ulcers, and uveitis HLA-B51 positive in 50-70% (especially in endemic regions); more common along the Silk Road (Turkey, Iran, Japan, China) Pathergy test: sterile needle prick → papule/pustule at 24-48 hours (positive in ~60% of Middle Eastern/Asian patients; rare in Western) Posterior uveitis/retinal vasculitis: the most serious ophthalmological manifestation; can cause blindness Venous thrombosis common (DVT, cerebral venous sinus thrombosis, Budd-Chiari); treat with immunosuppression NOT anticoagulation alone Arterial involvement: aneurysm formation (pulmonary artery aneurysms pathognomonic) Treatment: colchicine (oral ulcers, arthralgia), azathioprine (uveitis, mucocutaneous), anti-TNF (refractory), cyclophosphamide (neurological, major vessel) UK prevalence: rare (~1 per 100,000); higher in Turkish/Middle Eastern populations
Overview
Key Facts
Behcet disease is unique among vasculitides as it can affect both arteries and veins of all sizes. The variable-vessel vasculitis classification reflects this.
Epidemiology
- Highest prevalence: Turkey (~400 per 100,000), Iran, Japan
- UK prevalence: ~1 per 100,000; higher in immigrant populations from endemic areas
- Peak onset: 20-40 years; M=F (but more severe in young males)
Pathophysiology
- Neutrophilic vasculitis affecting all vessel sizes
- Pathergy: exaggerated immune response to minor trauma (aberrant neutrophil function)
- HLA-B51 associated; likely autoinflammatory rather than autoantibody-driven
- IL-17 and TNF-α are key cytokines
Clinical Presentation
Oral Ulcers (>95%)
- Recurrent (≥3 episodes/year)
- Painful, round, well-circumscribed with erythematous halo
- Affect lips, tongue, buccal mucosa, palate
- Often the first and most common manifestation
Genital Ulcers (60-80%)
- Painful; scrotum (males), vulva (females)
- May scar (unlike oral ulcers)
Eyes (50-70%)
- Posterior uveitis/panuveitis: most serious; risk of blindness
- Anterior uveitis: hypopyon (pus layer in anterior chamber) – classic but uncommon
- Retinal vasculitis: threatens vision
Skin (50-80%)
- Erythema nodosum, papulopustular lesions, pseudofolliculitis
- Pathergy positive
Vascular (25-30%)
- Venous: DVT, SVT, cerebral venous sinus thrombosis, Budd-Chiari
- Arterial: aneurysms (especially pulmonary artery – pathognomonic)
Neurological (Neuro-Behcet, 5-10%)
- Meningoencephalitis, brainstem syndrome
- Cerebral venous sinus thrombosis
- Progressive neurological disability
Other
- Arthritis: oligoarticular, non-erosive
- GI: ulceration (ileocaecal, mimics Crohn's)
Red Flags
- Posterior uveitis → urgent ophthalmology + immunosuppression
- Haemoptysis → pulmonary artery aneurysm → life-threatening
- Headache/neurological signs → neuro-Behcet or CVST
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| SLE | Oral ulcers, arthritis, ANA/dsDNA positive | Immunology |
| Crohn disease | Oral ulcers, GI ulceration, perianal disease | Colonoscopy |
| Reactive arthritis | Oral ulcers, urethritis, arthritis | Clinical |
| HSV | Oral/genital ulcers, vesicular | Viral swab/PCR |
| Syphilis | Painless chancre, rash, FTA-Abs | Syphilis serology |
Diagnosis / Investigation
Diagnosis is Clinical (ISG Criteria)
- Recurrent oral ulceration (≥3 episodes in 12 months) PLUS ≥2 of:
- Recurrent genital ulceration
- Eye lesions (uveitis, retinal vasculitis)
- Skin lesions (erythema nodosum, pseudofolliculitis)
- Positive pathergy test
Bloods
- HLA-B51: supportive (not diagnostic)
- CRP/ESR: elevated during flares
- No specific autoantibody (ANCA negative, ANA negative)
Imaging
- CT/MR angiography: pulmonary artery aneurysms, venous thrombosis
- MRI brain: neuro-Behcet (brainstem lesions)
- MR venography: cerebral venous sinus thrombosis
Other
- Pathergy test: read at 24-48 hours; sterile pustule formation (positive)
- OCT/fluorescein angiography: retinal vasculitis assessment
Management
Mucocutaneous (Oral/Genital Ulcers)
- Colchicine 500mcg BD: first-line for oral ulcers and arthralgia
- Topical steroids (triamcinolone oral paste)
- Azathioprine: for recurrent/severe mucocutaneous disease
- Apremilast 30mg BD: NICE approved for refractory oral ulcers
Uveitis
- Azathioprine: first-line for posterior uveitis/retinal vasculitis
- Anti-TNF (infliximab, adalimumab): for sight-threatening disease or refractory
- Ciclosporin: alternative
- Interferon-α: used in specialist centres
- Topical steroids + mydriatics: for anterior uveitis
Vascular
- Immunosuppression is primary treatment for thrombosis (NOT anticoagulation alone – risk of aneurysm rupture)
- Azathioprine, cyclophosphamide, or anti-TNF
- Anticoagulation: controversial; some use cautiously in combination with immunosuppression
Neuro-Behcet
- IV methylprednisolone + cyclophosphamide or infliximab
- Azathioprine maintenance
Pulmonary Artery Aneurysm
- Cyclophosphamide + corticosteroids: EMERGENCY
- Embolisation if life-threatening haemoptysis
- AVOID anticoagulation (aneurysm rupture risk)
Referral
- Suspected Behcet → rheumatology (specialist Behcet centre if available)
- Posterior uveitis → ophthalmology
- Neuro-Behcet → neurology + rheumatology
Prognosis
- Mortality: low (<5% at 10 years) with modern treatment
- Visual loss: reduced to <10% with immunosuppression (vs >25% historically)
- Pulmonary artery aneurysm: high mortality without treatment
- Neuro-Behcet: can cause significant disability; progressive form has worse prognosis
- Disease activity often diminishes with age
- Young males have the most severe disease and worst prognosis
Other Relevant Information
ISG Diagnostic Criteria
Recurrent oral ulceration (≥3/year) PLUS ≥2 of:
- Recurrent genital ulceration
- Eye lesions
- Skin lesions
- Positive pathergy test
Behcet Disease UK Specialist Centres
- London (Royal London Hospital)
- Birmingham
- Liverpool
- Leeds