Behcet disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Behcet disease is a relapsing inflammatory disorder of mucosa, skin, eyes, vessels, nervous system, joints and gastrointestinal tract. Recurrent oral aphthae are almost universal but common in the population, so diagnostic value comes from the multisystem combination. Genital ulcers often scar. Erythema-nodosum-like lesions, papulopustules and pathergy support the phenotype. Disease activity varies between organs and over time.

Take a chronological history of ulcers, vision, thrombosis, headache, focal neurology, abdominal symptoms, joints and skin and review ancestry and family history without restricting diagnosis by ethnicity. Examine oral and genital sites with consent, skin, eyes, veins and neurology. Baseline FBC, inflammatory, renal, liver and urine tests assess consequences and treatment but are nonspecific. Biopsy mainly excludes infection, IBD and malignancy.

Ocular disease is a treatment emergency. Anterior uveitis may be visible as a painful photophobic red eye, while posterior uveitis and retinal vasculitis cause floaters or visual loss and require systemic immunosuppression. Vascular thrombosis results from inflamed vessel walls rather than an ordinary thrombophilia. Immunosuppression is central; anticoagulation is debated and potentially dangerous when an occult pulmonary aneurysm can bleed.

Treatment follows the organ. Topical steroid and analgesia help mucosal lesions; colchicine treats genital lesions, erythema nodosum and arthritis; azathioprine or biologics prevent major relapse. Severe ocular, neurological, arterial or gastrointestinal disease uses glucocorticoid plus an early steroid-sparing agent. A specialist centre coordinates ophthalmology, rheumatology, neurology, vascular, respiratory and gastroenterology decisions.

Key points

Behcet disease is a clinical diagnosis: recurrent painful oral ulcers plus genital ulcers or scars, eye inflammation, characteristic skin lesions, vascular, neurological or gastrointestinal disease forms the pattern.
No single blood or genetic test confirms Behcet disease; HLA-B51 supports population susceptibility but has insufficient diagnostic specificity.
Document oral and genital lesions with consent, frequency, scarring and negative infection tests; ask directly because lesions may have healed before review.
Use the 2014 International Criteria to organise evidence, but exclude HSV, syphilis, HIV, inflammatory bowel disease, reactive disease, lupus and malignancy.
Any visual symptom needs same-day ophthalmology; topical drops alone are inadequate for posterior uveitis or retinal vasculitis.
Colchicine is first-line for recurrent genital ulcers and erythema nodosum and can help arthritis; topical corticosteroid treats individual mucosal ulcers.
Azathioprine, ciclosporin, interferon-alpha or anti-TNF therapy is selected for ocular or systemic disease; avoid ciclosporin in neurological involvement.
Inflammatory venous thrombosis is treated primarily with immunosuppression; anticoagulation is individualised only after excluding pulmonary-artery aneurysm and assessing bleeding risk.
Pulmonary-artery aneurysm with haemoptysis requires high-dose glucocorticoid plus cyclophosphamide or anti-TNF and interventional planning, not routine anticoagulation alone.
Coordinate contraception and pregnancy: colchicine and azathioprine may be compatible, while methotrexate, mycophenolate and cyclophosphamide require avoidance or specialist cessation.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Genetic susceptibility

HLA-B51 and multiple innate and adaptive immune variants increase risk, particularly along the historic Silk Road, but no genetic result is diagnostic.

Microbial and environmental interaction

Oral and gut microbial exposures may trigger exaggerated neutrophil and T-cell responses in susceptible people; Behcet disease is not contagious.

Variable geographic phenotype

Ancestry, sex and geography influence prevalence and severity, while UK patients of any background can develop the full multisystem disease.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Neutrophilic inflammation
Hyperreactive neutrophils and Th1 or Th17 pathways injure mucosa, skin and vessels, producing sterile ulcers and inflammatory lesions.
2
Pan-vascular involvement
Inflammation affects arteries and veins of any size, causing thrombosis through endothelial injury and aneurysm through destructive arteritis.
3
Ocular tissue injury
Recurrent anterior or posterior uveitis and occlusive retinal vasculitis damage macula, optic nerve and retinal circulation.
4
Relapsing organ-specific inflammation
Mucosal, eye, vascular, neural and gut domains relapse asynchronously, so one normal marker or healed ulcer cannot define global remission.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Recurrent mucosal disease

Painful oral aphthae recur several times yearly, while deep genital ulcers heal with scars and strongly support systemic Behcet disease.

Ocular inflammationRed flag

Photophobia, floaters, blurred vision or field change may indicate anterior or posterior uveitis and occlusive retinal vasculitis.

Inflammatory venous thrombosis

Young-onset recurrent DVT, vena-caval, hepatic or cerebral venous thrombosis with vessel-wall inflammation supports Behcet vasculopathy.

Arterial aneurysmRed flag

Haemoptysis or focal arterial pain can indicate pulmonary or systemic aneurysm and carries rupture risk.

Neuro-Behcet pattern

Brainstem syndrome, meningoencephalitis, myelitis or raised intracranial pressure from venous sinus thrombosis requires urgent MRI-based assessment.

Red flags requiring action

A painful photophobic eye, floaters or reduced vision requires same-day slit-lamp and retinal assessment because posterior uveitis can rapidly blind.
Haemoptysis, chest pain or pulmonary-artery aneurysm requires emergency respiratory and vascular imaging before anticoagulation.
Severe headache, papilloedema, focal deficit, confusion or seizure suggests cerebral venous thrombosis or neuro-Behcet disease.
Painful swollen limb, vena-caval obstruction or Budd-Chiari syndrome reflects inflammatory thrombosis and needs combined immune and vascular care.
Deep ileocaecal ulceration can bleed or perforate and requires urgent gastroenterology and surgery.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Clinical criteria and lesion documentationFirst step
Why
Establish recurrence and combine mucosal, ocular, skin, vascular and neurological evidence.
Interpretation and limitations
Classification supports consistency but no single score replaces specialist diagnosis or exclusion of mimics.
02
Ophthalmic slit-lamp and retinal imaging
Why
Identify anterior cells, vitritis, retinal vasculitis, macular oedema and structural damage.
Interpretation and limitations
OCT and fluorescein angiography quantify posterior activity; visual symptoms require same-day examination, not screening bloods.
03
MRI brain and MR venography
Why
Distinguish parenchymal neuro-Behcet from cerebral venous thrombosis and alternative neurological disease.
Interpretation and limitations
Brainstem lesions support parenchymal disease; venous imaging is essential when headache and raised intracranial pressure dominate.
04
CT pulmonary angiography or vascular imaging
Why
Detect pulmonary aneurysm, arterial inflammation and venous thrombosis before anticoagulation decisions.
Interpretation and limitations
Aneurysm can coexist with thrombosis; catheter or surgical intervention is planned after multidisciplinary imaging review.
05
Infection, IBD and biopsy assessment
Why
Exclude HSV, syphilis, HIV, Crohn disease, cancer and other ulcerating or inflammatory disorders.
Interpretation and limitations
Test lesions and exposures selectively; biopsy is nonspecific for Behcet but valuable when infection or malignancy is plausible.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Recurrent aphthous ulceration

Common isolated oral aphthae lack genital scars, uveitis, inflammatory thrombosis and other objective systemic or vascular inflammatory features.

Inflammatory bowel disease

Crohn disease causes oral and ileocaecal ulceration, perianal disease and arthritis; histology and distribution help distinguish or identify overlap.

Infection and sexual disease

HSV, syphilis, HIV and other infections can cause genital or oral ulceration and must be tested from exposure and lesion phenotype.

Reactive and other inflammatory disease

Reactive arthritis, SLE, complex aphthosis, Sweet syndrome, sarcoidosis and autoinflammatory syndromes can reproduce individual Behcet features.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01First-line diagnosisBuild the recurrent multisystem patternFirst stepFirst lineRecurrent oral ulcers coexist with genital, ocular, skin, vascular, neural or gut features.

1Document episode frequency, photographs, scars and objective specialist findings and screen sexual, medicine, bowel and inflammatory mimics.
2Obtain baseline blood and organ tests and urgently image or refer any eye, neurological, vascular or abdominal red flag.
3Apply criteria as support, then agree an organ-by-organ diagnosis, damage record and rapid-access plan with a Behcet-experienced team.

02Mucocutaneous treatmentUse local care then colchicineOral or genital ulcers, erythema nodosum or arthritis recurs without major-organ involvement.

1Use topical corticosteroid early on ulcers, oral hygiene, analgesia and test infection when lesion morphology or exposure warrants.
2Start colchicine and monitor lesion frequency, joint and skin response, blood count, renal and liver tolerance.
3For refractory burden consider azathioprine, apremilast or anti-TNF through specialist shared decision rather than chronic systemic steroid.

03Eye or neurological escalationProtect vision and brainEscalationPosterior uveitis, retinal vasculitis or parenchymal neuro-Behcet threatens function.

1Give high-dose systemic glucocorticoid and obtain same-day ophthalmic or neurological imaging and infection assessment.
2Add azathioprine and an anti-TNF agent or interferon-alpha for sight-threatening posterior disease; use expert immunosuppression for parenchymal neural disease.
3Avoid ciclosporin when neurological involvement is present and taper steroid only against direct eye or MRI and neurological response.

04Vascular emergencyTreat vessel inflammation before routine anticoagulationMajor venous thrombosis, pulmonary aneurysm or arterial occlusion occurs.

1Image arterial and venous territories, explicitly excluding pulmonary aneurysm before any anticoagulant decision and assess haemorrhage and organ ischaemia.
2Use high-dose glucocorticoid with cyclophosphamide or anti-TNF for severe arterial or major venous disease and involve interventional teams.
3Individualise anticoagulation for selected venous thrombosis only after aneurysm and bleeding review and continue imaging until vessel inflammation and anatomy stabilise.

Key medicines and prescribing safety4 treatments · regimens, roles and cautions

An unlicensed UK topical corticosteroid formulation that can reduce pain and duration when applied early to individual aphthous ulcers.

Topical triamcinolone oral paste

Where specialist local supply is available, apply a small amount of triamcinolone acetonide 0.1% dental paste to each dried oral ulcer two to four times daily after meals and at bedtime for up to seven days.

Explain unlicensed supply and consider a locally approved corticosteroid lozenge, mouthwash or spray instead. Avoid untreated oral infection and prolonged use; candidiasis, irritation and mucosal thinning can occur. It cannot control major-organ disease.

Off-label but guideline-supported first systemic treatment for recurrent genital ulcers, erythema-nodosum-like lesions and arthritis.

Colchicine

Start 500 micrograms orally twice daily and increase only if needed and tolerated, commonly to a maximum 1.5 mg/day under specialist review.

Reduce or avoid in renal or hepatic impairment and with strong CYP3A4 or P-gp inhibitors; monitor diarrhoea, cytopenia and neuromyopathy. It is compatible with pregnancy under BSR guidance.

Specialist steroid-sparing prevention of ocular, mucocutaneous, joint and selected systemic relapses; Behcet treatment is off-label.

Azathioprine

Start 25–50 mg orally daily after TPMT assessment and increase toward 2–2.5 mg/kg/day under blood and liver monitoring.

Monitor FBC, liver and renal function, infection, pancreatitis and allopurinol or febuxostat interaction. BSR supports doses no greater than 2 mg/kg/day during pregnancy.

Rapid TNF inhibition for major refractory or sight-threatening Behcet disease.

Infliximab

For severe ocular, vascular, neurological or gastrointestinal disease, a common off-label regimen is 5 mg/kg intravenously at weeks 0, 2 and 6 then every eight weeks, adjusted by specialist response.

Screen TB, hepatitis and infection, update vaccines and monitor infusion reactions, heart failure, demyelination and paradoxical inflammation. It may continue during pregnancy if needed; if low flare risk it can stop by 20 weeks for normal infant vaccination, while later exposure means deferring infant live vaccines until six months.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Blindness

Recurrent posterior uveitis, macular oedema and occlusive retinal vasculitis cause cumulative irreversible visual loss without rapid steroid-sparing control.

Thrombosis and aneurysm

Deep venous, caval, cerebral and hepatic thrombosis coexist with pulmonary or systemic arterial aneurysm and rupture risk.

Neurological disability

Brainstem, hemispheric, spinal or meningoencephalitic inflammation and venous sinus thrombosis cause fixed neurological injury and raised intracranial pressure.

Gastrointestinal perforation and treatment harm

Deep bowel ulcers can bleed or perforate, while prolonged immunosuppression causes infection, cytopenia, infertility, metabolic and reproductive toxicity.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Record oral and genital ulcer frequency, days with pain, scarring, skin and joint burden using the same measures across visits.
Ophthalmology follows acuity, cells, OCT and angiographic retinal activity at intervals matched to posterior disease and treatment.
Monitor neurological examination and MRI or venography, vascular symptoms and repeat aneurysm or thrombosis imaging according to lesion risk.
Follow FBC, renal and liver tests, infection, TB, hepatitis and pregnancy safety for colchicine, azathioprine and biologics.
Review steroid exposure, bone, glucose, pressure, vaccination, pain, sexual health, mood and participation.
Give explicit emergency advice for new visual change, haemoptysis, severe headache, neurological deficit, limb swelling and abdominal pain.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Oral ulcers are necessary but nonspecific

Diagnostic confidence comes from recurrence plus scarring genital, ocular, vascular, neural or characteristic skin disease.

Thrombosis is inflammatory

Behcet clots adhere to inflamed vessel walls and embolise less often than ordinary DVT, making immune control central.

Aneurysm changes anticoagulation

An occult pulmonary-artery aneurysm can rupture catastrophically, so vascular imaging precedes routine anticoagulant decisions.

CRP does not measure the eye

Posterior uveitis can be active with modest systemic markers; direct retinal examination and imaging guide treatment.

Ciclosporin has a neurological caveat

Although effective for ocular disease, it is avoided when neuro-Behcet is present because neurological outcomes may worsen.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing Behcet disease from common oral aphthae alone.
02
Waiting for HLA-B51 before making or rejecting the diagnosis.
03
Treating posterior uveitis only with topical drops.
04
Anticoagulating a venous thrombosis before excluding pulmonary-artery aneurysm.
05
Using ciclosporin in a patient with neurological Behcet disease.
06
Leaving recurrent steroid bursts without colchicine or steroid-sparing disease control.