Medicine chapters
Behcet disease
A relapsing inflammatory vasculitis of unknown cause with recurrent mouth and genital ulcers, uveitis, skin lesions and a positive pathergy test, common along the old Silk Route and linked with HLA-B51.
- Behcet disease is a variable-vessel vasculitis of young adults, most common from Turkey and Iran to Japan and linked with HLA-B51.
- Diagnosis is clinical: recurrent oral ulcers plus two of genital ulcers, eye lesions (uveitis), skin lesions (erythema nodosum, pustules) or a positive pathergy test; there is no specific blood test.
- Colchicine for mucocutaneous and joint disease; steroids, azathioprine, ciclosporin or anti-TNF for eye, vascular and neurological disease; blindness from uveitis is the main threat.
On this page
Overview
Behcet disease is a chronic, relapsing inflammatory disorder of unknown cause. It is classed as a variable-vessel vasculitis: it can affect arteries and veins of any size.
The hallmark is recurrent painful mouth ulcers, usually with genital ulcers, eye inflammation and skin lesions. Most features come and go, but eye disease can cause blindness, and vascular and brain disease can kill.
Epidemiology and cause
- Most common along the old Silk Route: Turkey (highest prevalence), Iran, the Middle East, Central Asia and Japan; seen in Pakistan too. Rare in northern Europe and the USA.
- Usually starts in young adults (20s–30s). More severe in young men.
- Strong link with HLA-B51 in the high-prevalence regions (relative risk about 5–10); this link is weak in Western patients.
- Cause unknown: probably an abnormal immune reaction (neutrophil hyperactivity, Th1/Th17 responses) in genetically prone people, perhaps triggered by infection.
Clinical features
| System | Features |
|---|---|
| Mouth (almost all) | Recurrent aphthous ulcers: painful, round, with a yellow base and red rim; heal without scarring; at least 3 attacks a year |
| Genitals | Painful ulcers on the scrotum or vulva; deeper than oral ulcers; often leave scars |
| Eyes | Anterior uveitis (can give hypopyon), posterior uveitis, retinal vasculitis; repeated attacks → blindness |
| Skin | Erythema nodosum, pseudofolliculitis and papulopustular (acne-like) lesions; pathergy |
| Joints | Non-erosive mono- or oligoarthritis of knees, ankles, wrists, elbows; self-limiting |
| Veins | Superficial thrombophlebitis, DVT (calf pain and swelling), Budd-Chiari syndrome, vena cava thrombosis, cerebral venous sinus thrombosis |
| Arteries | Aneurysms (including pulmonary artery aneurysm: haemoptysis) and occlusions |
| Nervous system (neuro-Behcet) | Brainstem syndrome, meningoencephalitis, confusional states, pyramidal signs; venous sinus thrombosis |
| Gut | Ulcers in the ileum and caecum: pain, diarrhoea, bleeding, perforation; can mimic Crohn disease |
| Other | Fatigue, epididymitis, kidney disease (rare) |
Recurrent oral ulcers are the essential (cardinal) feature. Diagnosis without them is very unusual.
A young man with oral and genital ulcers who develops calf pain and swelling most likely has DVT from Behcet vasculitis.
The pathergy test
- Prick the forearm skin with a sterile needle.
- A papule or pustule appears at 24–48 hours.
- Highly specific for Behcet disease, though often negative in non-endemic regions. It reflects exaggerated skin reactivity to minor injury.
Behcet disease is linked with HLA-B51, while the spondyloarthritides are linked with HLA-B27.
Behcet = "Both Ends Hurt": ulcers in the mouth and genitals, plus the eye.
Diagnosis
There is no diagnostic blood test. The diagnosis is clinical.
International Study Group criteria: recurrent oral ulceration (at least 3 times in 12 months) plus any two of:
- Recurrent genital ulceration.
- Eye lesions: anterior or posterior uveitis, retinal vasculitis.
- Skin lesions: erythema nodosum, pseudofolliculitis, papulopustular lesions.
- Positive pathergy test.
A 28-year-old man has had mouth ulcers 5 times this year, one scrotal ulcer and erythema nodosum on the shins. Eye examination is normal; pathergy not done.
Oral ulcers 3 or more times in 12 months = essential criterion met
Additional criteria: genital ulcers (1) + skin lesions (1) = 2 → criteria for Behcet disease met
Investigations
- ESR and CRP raised in active disease; mild anaemia.
- No autoantibodies: ANA, RF and ANCA negative.
- HLA-B51 supports but does not prove the diagnosis.
- Slit-lamp and fundus examination (fluorescein angiography for retinal vasculitis).
- Doppler ultrasound for DVT; CT/MR angiography for aneurysms; MRI brain for neuro-Behcet (brainstem lesions); CSF shows raised cells and protein.
- Colonoscopy for gut disease.
- Exclude herpes simplex, syphilis and other causes of ulcers.
Differential diagnosis
| Condition | Distinguishing clue |
|---|---|
| Recurrent aphthous stomatitis | Mouth only; no genital, eye or skin disease |
| Herpes simplex | Grouped vesicles, positive PCR |
| Syphilis | Painless chancre; positive serology |
| Crohn disease | Granulomas on biopsy; mouth ulcers and erythema nodosum may also occur |
| Reactive arthritis | Painless mouth ulcers, urethritis, conjunctivitis, HLA-B27 |
| SLE | Painless ulcers, ANA and anti-dsDNA positive |
| Coeliac disease, iron/B12/folate deficiency | Mouth ulcers with blood test abnormalities |
Management
Treatment depends on the organs involved. Managed by a team (rheumatology, ophthalmology, dermatology).
| Problem | Treatment |
|---|---|
| Mouth and genital ulcers | Topical steroids, antiseptic or anaesthetic mouthwash; colchicine; apremilast (PDE4 inhibitor) for resistant oral ulcers |
| Erythema nodosum, arthritis | Colchicine; NSAIDs; short steroid courses |
| Eye disease (posterior uveitis, retinal vasculitis) | Systemic corticosteroids plus azathioprine or ciclosporin; anti-TNF (infliximab, adalimumab) or interferon-alpha for severe or resistant disease. Anterior uveitis: steroid eye drops |
| Venous thrombosis | Immunosuppression (steroids, azathioprine) is the main treatment, as clots come from vessel wall inflammation; anticoagulation used selectively (beware coexisting arterial aneurysms) |
| Arterial aneurysms, neuro-Behcet, gut disease | High-dose steroids with azathioprine, cyclophosphamide or anti-TNF; surgery or stenting for aneurysms |
| Resistant mucocutaneous disease | Thalidomide |
Thalidomide works for severe mouth and genital ulcers but is teratogenic (phocomelia) and causes peripheral neuropathy and drowsiness. Never give it in pregnancy.
Mouth and genital ulcers are self-limiting; the features that need urgent immunosuppression are posterior uveitis, neurological disease, arterial aneurysms and major vein thrombosis.
Prognosis
- Relapsing and remitting; tends to become milder with time.
- Worse in young men.
- Main causes of serious disability or death: blindness from uveitis, pulmonary artery aneurysm rupture, neurological disease and major vessel thrombosis.
Expect: recurrent oral ulcers as the essential criterion, genital ulcers, uveitis with hypopyon, erythema nodosum, the pathergy test (pustule at 24–48 hours), HLA-B51, high prevalence in Turkey, Iran and Japan, absence of autoantibodies, DVT and thrombophlebitis as vascular features, colchicine for mucocutaneous and joint disease, steroids with azathioprine, ciclosporin or anti-TNF for eye disease, and thalidomide toxicity.
Quick revision
- Variable-vessel vasculitis; arteries and veins.
- Turkey, Iran, Japan; HLA-B51; young adults, worse in men.
- Oral ulcers (essential) + 2 of: genital ulcers, eye lesions, skin lesions, pathergy.
- Pathergy: pustule 24–48 hours after needle prick.
- No autoantibodies; ESR/CRP raised.
- Uveitis can blind; DVT and aneurysms; neuro-Behcet in brainstem.
- Colchicine for ulcers, skin and joints; steroids + azathioprine/ciclosporin/anti-TNF for eyes and major organs.
- Thalidomide: teratogenic, neuropathy.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
What is the single essential feature of Behcet disease?
Recurrent mouth ulcers; the diagnosis needs them plus at least two other typical features.
Is there a blood test that confirms Behcet disease?
No. ESR and CRP may be raised and HLA-B51 is common, but autoantibodies are absent and the diagnosis is clinical.
What does a positive pathergy test look like?
A small papule or pustule at the site of a sterile needle prick, appearing after 24 to 48 hours.
Why are anticoagulants not the main treatment for clots in Behcet disease?
The clots arise from inflammation of the vein wall, so immunosuppression is the mainstay; anticoagulation carries a bleeding risk if arterial aneurysms are present.