Behçet's disease

Behçet's disease — recognition, diagnosis and GP management

By Dr HB Lo, FACRRM 8 min read

Behçet's disease is a chronic relapsing multisystem vasculitis affecting vessels of any calibre. In Australia it most commonly affects people from Turkish, Lebanese, Iranian, and other Middle Eastern backgrounds, though it can present in anyone.

Diagnosis is clinical, using the International Criteria for Behçet's Disease: recurrent oral ulcers plus any combination of genital ulcers, uveitis, skin lesions, neurological, vascular, or pathergy totalling four or more points.

Treatment is organ-tier stratified — colchicine and topical corticosteroids for mucocutaneous disease, azathioprine and biologics for ocular and systemic involvement — coordinated by rheumatology alongside the GP.

Behçet’s disease is rare in Australia but under-recognised among the communities it disproportionately affects. A GP who sees recurrent aphthous ulcers in a young adult from a Silk-Road background — Turkish, Lebanese, Iranian, Iraqi, Greek — and adds any systemic feature to the picture should pause and consider this diagnosis before attributing the ulcers to stress or minor trauma. Early recognition protects vision, prevents vascular catastrophe, and avoids the years-long diagnostic odyssey that many affected patients experience before reaching rheumatology.

A. Core clinical — the AU general-practice framework

What is Behçet’s disease?

Behçet’s disease (BD) is a chronic, relapsing, remitting variable-vessel vasculitis — meaning it can inflame arteries and veins of any calibre. It does not follow the pattern of most autoimmune diseases: standard autoantibodies (ANA, ANCA, dsDNA) are typically negative, which reassures rather than excludes the diagnosis. The inflammatory driver appears to involve innate immune dysregulation with IL-1, IL-6, IL-17, and TNF-α excess rather than antigen-specific autoantibody production.

Australian epidemiology

Australian prevalence is approximately 1–5 per 100,000 — far below Turkey (80–370 per 100,000), Iran, the Middle East, and East Asia. The Silk-Road gradient reflects HLA-B51 carriage rates: this allele is a supportive marker (not diagnostic), positive in 50–80% of Turkish patients versus 10–25% of Northern European controls. In Australian general practice, the CALD communities carrying the greatest burden are Turkish, Lebanese, Iranian, Iraqi, and some Greek-heritage families. Awareness of the diagnosis among GPs is the rate-limiting step for timely referral.

Peak onset is 20–40 years of age. Males and females are affected equally but males typically experience more severe disease — higher rates of uveitis, vascular, and neurological involvement.

Diagnostic criteria

The International Criteria for Behçet’s Disease (ICBD 2014) are the preferred tool in clinical practice, scoring:

  • Recurrent oral aphthous ulcers — 2 points
  • Recurrent genital aphthous ulcers — 2 points
  • Ocular lesions (anterior or posterior uveitis, retinal vasculitis) — 2 points
  • Skin lesions (erythema nodosum-like, papulopustular, pseudofolliculitis) — 1 point
  • Neurological involvement — 1 point
  • Vascular involvement (venous or arterial) — 1 point
  • Positive pathergy test — 1 point

A score of ≥4 is required for diagnosis. The older International Study Group 1990 criteria required recurrent oral ulcers plus two of the remaining features — still used but less sensitive outside Mediterranean populations.

History to take

  • Oral ulcers — frequency per year, whether they scar, duration, associated symptoms; onset in adolescence is common
  • Genital ulcers — scarring is characteristic and distinguishes BD from simple aphthae
  • Visual symptoms — any past episode of red eye, photophobia, floaters, visual change
  • Skin — painful nodules on shins, acne-like eruptions, pustule at previous blood-test sites (pathergy)
  • Neurological — headache, diplopia, dysarthria, ataxia, focal weakness, cognitive change
  • Vascular — limb swelling, haemoptysis (pulmonary artery aneurysm — life-threatening emergency)
  • Gastrointestinal — abdominal pain, diarrhoea, rectal bleeding
  • Ethnicity and family history — Silk-Road heritage, first-degree relatives with BD
  • Joint pain — non-erosive oligoarthritis, especially knees and ankles

Examination

Map and photograph oral ulcers. Examine external genitalia for active ulcers or scarring (with chaperone). Look for skin lesions — erythema-nodosum-like nodules, pseudofolliculitis, pustule at venepuncture site. Assess visual acuity and pupillary response; note any conjunctival injection. Perform full neurological screen including cranial nerves, gait, and cognition. Check peripheral pulses and limb circumference for venous thrombosis. The EULAR 2018 guideline recommends ophthalmology review with slit-lamp and dilated fundoscopy at every new diagnosis even without visual symptoms.

Initial investigation

  • FBC, ESR, CRP, UEC, LFT, ferritin — baseline, monitoring
  • ANA, ENA, ANCA — to exclude mimics (SLE, ANCA vasculitis); typically negative in BD
  • Complement C3/C4 — normal in BD; low levels suggest SLE
  • HLA-B51 — supportive in uncertain CALD presentation; neither diagnostic nor negative-ruling
  • Urinalysis and ACR — should be blank in pure BD
  • Pathergy test — sterile 20 G needle prick to forearm, read at 24–48 h; positive if ≥2 mm pustule

The GP role is to perform initial bloods, arrange ophthalmology (same day if any visual symptom), and refer to rheumatology for diagnosis confirmation and immunosuppression planning. Organ-specific imaging — MRI brain plus MR venogram, CT angiogram for vascular disease, colonoscopy for gastrointestinal symptoms — is arranged by or with the specialist.

B. Evidence appraisal — what the trials show

Apremilast for refractory oral ulcers

The RELIEF trial (Hatemi, NEJM 2019) randomised 207 patients to apremilast 30 mg twice daily or placebo for 12 weeks. Apremilast significantly reduced oral ulcer number and pain; effects were sustained at 28 weeks. The PBS Authority Streamlined listing introduced in 2024 for adults with active BD oral ulcers refractory to topical therapy and/or colchicine represents a major access improvement in Australia. Colchicine — first-line and supported by the Yurdakul 2001 RCT showing efficacy for genital ulcers and erythema nodosum in women — remains initial therapy before escalation to apremilast.

Rituximab and TNF inhibitors for severe disease

For posterior uveitis and sight-threatening disease, adalimumab and infliximab are endorsed by EULAR 2018 and accessible via PBS Section 100 Authority for severe non-infectious uveitis. The evidence base for biologics in BD draws primarily from open-label studies and registries rather than large RCTs, reflecting the disease’s rarity.

Anticoagulation controversy

The cardinal principle separating BD vascular management from standard DVT management is that inflammation — not hypercoagulability — drives thrombosis. Accordingly, immunosuppression (glucocorticoid plus azathioprine, or cyclophosphamide for severe disease) is the primary intervention. Anticoagulation is used selectively in proximal venous thrombosis without concomitant aneurysm, but is absolutely contraindicated in pulmonary artery aneurysm where it causes fatal haemorrhage. CT angiography to exclude aneurysm before initiating any anticoagulation in BD vascular events is a non-negotiable GP and specialist responsibility.

C. Organ-tier management overview

Treatment is delivered across tiers matching disease severity and organ involvement.

Mucocutaneous (GP often co-manages): topical triamcinolone in Orabase for oral ulcers; high-potency topical corticosteroid for genital and skin lesions; chlorhexidine and benzydamine mouthwash. Systemic colchicine 0.5 mg twice daily is the backbone. Apremilast escalates when colchicine and topical therapy have failed. Azathioprine 1–2.5 mg/kg/day is added for severe or recurrent mucocutaneous disease as a steroid-sparing agent.

Ocular (always specialist-led): same-day ophthalmology for any visual symptom. Anterior uveitis alone uses topical steroids and cycloplegics. Posterior uveitis and retinal vasculitis require systemic glucocorticoids plus azathioprine as foundation. Refractory or sight-threatening disease uses adalimumab or infliximab. Cyclosporine is specifically avoided in neurological BD because it can precipitate or worsen parenchymal disease.

Neurological (always specialist-led): parenchymal neuro-BD — IV methylprednisolone pulse followed by oral prednisolone taper plus azathioprine or cyclophosphamide; TNF inhibitors (infliximab preferred) for refractory cases. Cerebral venous sinus thrombosis may receive anticoagulation provided no aneurysm is present.

Vascular: immunosuppression first; cyclophosphamide plus high-dose glucocorticoids for pulmonary artery aneurysm or major arterial disease. Anticoagulation is never initiated without imaging to exclude aneurysm.

Gastrointestinal: mesalazine, azathioprine, glucocorticoids for active colitis; TNF inhibitors for moderate to severe or refractory intestinal BD.

D. Australian operations

MBS items: standard GP consultations (items 23, 36, 44); telehealth where appropriate; GPCCMP preparation item 965 and review item 967 for the multidisciplinary chronic disease framework; Mental Health Treatment Plan items 2715/2717 for adjustment to chronic illness, steroid mood effects, or fear of vision loss; specialist referral items 105/106; FBC (65070), ESR/CRP (66500), UEC/LFT (66509), ferritin (66587), ANA/ENA (71089/71091), ANCA (71097), complement (71112), HLA-B51 (73320 range), QuantiFERON-TB Gold (69471) before biologics, HBV/HCV/HIV screen (69445/69481/69384) before immunosuppression; TPMT genotyping before azathioprine.

PBS items: colchicine (PBS for gout; off-label widely accepted for BD mucocutaneous disease); apremilast Authority Streamlined 2024 for BD oral ulcers; azathioprine Authority Streamlined; prednisolone General Schedule; adalimumab/infliximab Section 100 Authority for severe uveitis and related conditions; cyclophosphamide Authority.

Therapeutic Guidelines (eTG) Rheumatology provides the AU primary-tier drug dosing and monitoring framework. The Australian Rheumatology Association has patient resources and a practitioner directory for shared-care coordination. TIS National interpreter service (131 450) should be engaged for CALD patients; the MBS bulk-billing incentive item 10990 applies to interpreter-assisted consultations.

Pre-biologic screening: QuantiFERON-TB Gold, HBV/HCV/HIV serology, VZV serology, and vaccination catch-up (non-live) are standard before starting any biologic. Live vaccines (Zostavax, MMR, varicella, yellow fever) are contraindicated on biologics or high-dose corticosteroids — use Shingrix (recombinant zoster) instead per ATAGI guidance. Bone protection with DXA, calcium, vitamin D, and bisphosphonate is relevant for patients on prolonged corticosteroids.

GPCCMP eligibility: BD qualifies as a chronic multidisciplinary condition; the plan supports referrals to dietitian (Mediterranean diet, steroid nutrition), exercise physiology (deconditioning, steroid myopathy), psychology (chronic illness adjustment), dental (aphthous hygiene, pre-biologic clearance), and podiatry if vascular complications develop.

E. Special populations

Pregnancy: methotrexate, cyclophosphamide, and mycophenolate are teratogenic — switch to azathioprine and discuss TNF inhibitors with rheumatology at least three months before planned conception. Colchicine at low dose has reasonable safety data. Document folate supplementation ≥0.5 mg/day if methotrexate or methotrexate-equivalent drugs were used prior.

Paediatric and adolescent onset: rare but well described. Requires paediatric rheumatology input and multidisciplinary school support.

Older adults: BP-associated dementia and Parkinson’s disease occur at three-fold higher rates in patients with BD-related uveitis; neurological review should have a low threshold in older patients. Falls risk increases on corticosteroids and in those with visual impairment.

CALD considerations: language and cultural barriers can delay both diagnosis and adherence. Engage TIS National (131 450), bilingual health practitioners where available, and community networks such as Behçet’s Australia and Arthritis Australia for peer support. First-degree relatives have a 1–18% risk in endemic populations, warranting family awareness.

When to escalate

Same day: any visual symptom — eye redness, blurred vision, floaters, photophobia; suspected neuro-BD; haemoptysis suggesting pulmonary aneurysm; major DVT or PE; gastrointestinal perforation signs.

Within 1–2 weeks: new BD diagnosis for rheumatology confirmation and immunosuppression planning; pregnancy planning on current disease-modifying therapy; flare on existing treatment; new organ involvement.

Ongoing shared care: 1–3 monthly GP review during active disease, 3–6 monthly when stable, coordinating with rheumatology and organ-specific specialists. Annual ophthalmology review even when asymptomatic, as BD uveitis can be clinically silent.

What this article is and is not

This is general health information based on current Australian clinical guidelines — Therapeutic Guidelines (eTG), RACGP resources, ARA guidance, and the EULAR 2018 Behçet’s recommendations. It is not personal medical advice and does not create a doctor–patient relationship. All treatment decisions require assessment by a registered medical practitioner familiar with your individual circumstances.

For Australian consumer information: HealthDirect — Behçet’s disease, Better Health Channel, and Arthritis Australia. For mental health support: Lifeline 13 11 14, Beyond Blue 1300 22 4636.

Sources cited

  1. Therapeutic Guidelines (eTG) — Rheumatology
  2. RACGP — clinical resources
  3. Australian Rheumatology Association (ARA)
  4. ATAGI — Australian Immunisation Handbook
  5. HealthDirect — Behçet’s disease
  6. Better Health Channel — Vasculitis
  7. EULAR 2018 — Hatemi G et al, management recommendations for Behçet’s syndrome (Ann Rheum Dis)
  8. ICBD 2014 — International Criteria for Behçet’s Disease (J Eur Acad Dermatol)
  9. RELIEF trial — Hatemi et al, apremilast for oral ulcers in Behçet’s disease (NEJM 2019)
  10. Yurdakul 2001 — colchicine RCT in Behçet’s disease (Arthritis Rheum)
  11. PBS — apremilast Authority listing
  12. MBS Online

Frequently asked questions

  • What are the early warning signs a GP should recognise?

    The most common first sign is recurrent painful oral aphthous ulcers occurring three or more times per year, often beginning years before systemic features appear. When any combination of genital ulcers, unexplained eye redness or blurred vision, skin nodules on the shins, joint pain, or neurological symptoms accompanies these oral ulcers — particularly in a person from a Turkish, Lebanese, Iranian, or Middle Eastern background — Behçet's disease should be actively considered and referral to rheumatology arranged without delay.

  • Why is eye involvement a same-day emergency?

    Posterior uveitis and retinal vasculitis in Behçet's disease can cause irreversible visual loss within hours if untreated. The inflammation is typically intraocular and may not produce obvious external redness. Any visual symptom — blurring, floaters, photophobia, pain, new scotoma — in a person with known or suspected Behçet's disease requires same-day review by an ophthalmologist with slit-lamp and dilated fundoscopy. The GP's same-day referral pathway is the single most important protective action.

  • Is anticoagulation used for blood clots in Behçet's disease?

    With caution and important exceptions. Behçet's disease drives venous thrombosis through vessel-wall inflammation rather than a hypercoagulable state, so the primary treatment is immunosuppression — glucocorticoids and azathioprine — rather than anticoagulation alone. Crucially, anticoagulation is absolutely contraindicated when a pulmonary artery aneurysm is present, because rupture causes fatal haemorrhage. A CT angiogram should exclude aneurysm before any anticoagulation is started in Behçet's-related venous thrombosis, as directed by the EULAR 2018 guidelines.

  • How is Behçet's disease treated in Australia?

    Treatment is organ-tier stratified and specialist-led, with the GP co-managing mucocutaneous disease and monitoring. For oral and genital ulcers: topical corticosteroids and colchicine are first-line; apremilast (Otezla) has PBS Authority Streamlined listing for refractory oral ulcers following the RELIEF trial. Posterior uveitis requires azathioprine plus systemic glucocorticoids. Refractory ocular, neurological, or intestinal disease uses adalimumab or infliximab via PBS Section 100 Authority. The GP's role includes recognition, safety-netting, immunosuppression monitoring, vaccinations, and same-day escalation.

  • Which specialists should be involved in care?

    Rheumatology is the coordinating specialty for diagnosis confirmation and systemic immunosuppression. Ophthalmology is involved at diagnosis and urgently for any visual symptom. Neurology reviews suspected neuro-Behçet's. Vascular surgery or interventional radiology manages arterial aneurysms. Gastroenterology addresses ileocaecal disease. The Australian Rheumatology Association and the GP coordinate shared care, with GPCCMP item 965/967 supporting multidisciplinary allied-health access including psychology, dietitian, and exercise physiology.

Source quality

Sources grouped by evidence tier. AU primary tier first; international where AU is silent or lagging; named-author reconstruction where guidelines have not yet caught up. How tiers work.