Behçet's disease

For health professionals

A vasculitis that can hit any vessel, a mouth-ulcer problem that can end in blindness or a ruptured pulmonary artery, and about 300 times commoner in Istanbul than among German-born Berliners. No blood test, no single drug, plenty of open questions. Organ by organ, with the trials.

At a glance

Definition and classification

• Chapel Hill 2012: classed as a variable-vessel vasculitis (with Cogan's syndrome): it can affect vessels of any size and type.
• ISG 1990 (International Study Group, Lancet): recurrent oral ulcers at least 3 times in 12 months, plus 2 of:
  • recurrent genital ulcers (aphthous ulcers or scars)
  • eye lesions (anterior or posterior uveitis, or vitreous cells on slit lamp)
  • skin lesions (erythema nodosum-like, papulopustular or acneiform nodules)
  • positive pathergy test, read at 24–48 hours
  Sensitivity 92%, specificity 97% (914 patients, 12 centres, 7 countries).
• ICBD 2014 (27 countries, 2,556 patients, 1,163 mimic controls):
  • 2 points each: eye lesions, oral aphthosis, genital aphthosis.
  • 1 point each: skin lesions, CNS involvement, vascular manifestations, positive pathergy (optional).
  • ≥4 points classifies as Behçet's. Validation set: 94.8% sensitive, 90.5% specific, vs ISG 85.0% and 96.0%.
• Catch: both are classification criteria used for diagnosis, and oral ulcers are absent in 1–10% of patients.

History

• 5th century BC, Hippocrates: Epidemics III describes an endemic illness with mouth ulcers, genital ulcers and eye inflammation. Likely the first description, about 2,300 years before the eponym.
• 1772, Janin (France): a man with recurrent hypopyon iritis.
• 1930–1931, Benediktos Adamantiades (1875–1962), a Greek ophthalmologist: presented in Athens a 20-year-old man with oral and genital ulcers, leg thrombophlebitis, arthritis and recurrent iritis, published in French in 1931. He thought the eye disease was the new entity. Greek authors still argue for "Adamantiades–Behçet" on grounds of fairness.
• 1937, Hulusi Behçet (1889–1948), professor of dermatology at Istanbul University: two patients (a man of 40, a woman of 34) with recurrent oral ulcers, genital ulcers and iritis, in Dermatologische Wochenschrift. He proposed one systemic disease and blamed a virus. By 1940 he called it the "triple symptom complex".
• 1941, Jensen (Denmark) first used "Behçet's syndrome" and adopted pathergy as a criterion. A 1947 Geneva congress endorsed "Morbus Behçet".
• Plot twist: Adamantiades himself used the term "Behçet syndrome" in a 1949 paper.

Pathophysiology

Genetics

• HLA-B51: pooled OR 5.78 (78 studies, 4,800 patients, 16,289 controls). Carried by 40–80% of Turkish, European and Asian patients, but as few as 13% of white Western patients, and 10–15% of healthy people. Explains about 20% of genetic susceptibility.
• Familial clustering: 1–18% of patients (Turks 18.2%, Koreans 15.4%, Europeans 1%).
• GWAS: IL23R–IL12RB2 and IL10 (2010). A Turkish GWAS (1,209 cases, 1,278 controls; Nat Genet 2013) added ERAP1, CCR1, KLRC4 and STAT4.
• ERAP1 epistasis: the ERAP1 risk variant raises risk only in HLA-B51 carriers. The same variant protects against ankylosing spondylitis and psoriasis in their own HLA contexts.
• Peptide trimming: ERAP1 trims peptides before HLA class I loading. Over 20% of HLA-B*51:01 peptides are an unconventional (non-Pro/Ala2) subset; silencing ERAP1 doubles it to about 40% (Chen, Mol Cell Proteomics 2020).

Immune mechanism

• MHC-I-opathy (McGonagle 2015): Behçet's shares an HLA class I plus ERAP1 basis with spondyloarthritis and psoriasis. Proposed sequence: barrier dysfunction or mechanical stress, innate activation, then CD8⁺ T-cell responses with prominent neutrophilic inflammation. HLA-B51 tracks eye and mucocutaneous disease, not gut disease.
• Neutrophils: hyperactive neutrophils and neutrophil extracellular traps (NETs) drive endothelial damage and thrombosis. Thrombophilia screens give inconsistent results: it's inflammation-induced thrombosis, not a clotting disorder (Bettiol 2023).
• IL-23/Th17: Th1 and Th17 responses are skewed and IL23R is a risk locus. Yet IL-17 blockade failed in uveitis while IL-12/23 blockade helped ulcers (see trials), so the axis is not simple.
• Microbes: antibodies to Streptococcus sanguinis are more frequent in patients; no single causal organism. Gut microbiome: lower diversity, less Roseburia (4.97% vs 10.45%) and lower butyrate production vs household controls (Consolandi 2015, n=22 vs 16).

Epidemiology

Global

• The Silk Road: highest along the old trade route from the Mediterranean to Japan. One hypothesis: HLA-B51 spread with nomadic and Turkish tribes.
• Prevalence per 100,000: Turkey 20–602 across studies (Istanbul 420); northern Jordan 664; Israel 50–185; Iran 16.7–100; Japan 7–13.5; Italy 4.1–15.9; China 2.6; USA 0.33–5.2; Germany 0.9–2.3. A pooled estimate is 10.3.
• Migrants carry the risk part-way: Berlin: Lebanese 101.3, Turkish 77.3, Germans 1.4. Rotterdam: Turkish 71, Moroccan 39, Dutch 1. Migrants' rates sit below their home countries', so environment matters.
• Sex: roughly equal overall, but male-predominant in the Middle East (M:F 3.4 in Saudi Arabia, 2.1 in Tunisia) and female-predominant in Japan (0.74) and the USA (0.3). Men get more severe disease everywhere.
• Age: onset usually in the 20s and 30s (mean 24.5–43 by country); rare after 50. Juvenile onset (≤16) is 5–8% of cases.
• Delay: oral ulcers precede diagnosis by about 7 years on average.

Australia

• No Australian prevalence data found. One review describes Behçet's uveitis as "quite rare in Australia" and pathergy as rarely positive here.
• Practical relevance: risk follows ancestry, so think of it in patients with Turkish, Middle Eastern, Mediterranean, Central or East Asian heritage.

Causes and risk factors

• Genetic: HLA-B51 (about 6-fold risk), ERAP1 in B51 carriers, IL23R, IL10, family history (about 6% have an affected first- or second-degree relative).
• Environmental clues: lower rates in migrants than in their home countries; lower socioeconomic status; poor oral hygiene linked with oral ulcers; streptococcal antigens; gut dysbiosis. None proven causal.
• Severity markers: male sex, young age at onset.

Preventable factors

• No intervention prevents Behçet's.
• What is preventable is organ damage:
  • Eye: onset and the worst damage cluster in the first few years. Azathioprine prevented new eye disease in a placebo-controlled trial.
  • Neuro: avoid ciclosporin (see treatment).
  • Bleeding: exclude pulmonary artery aneurysm before anticoagulating.

Clinical features by system

Mucocutaneous

• Oral ulcers: 92–100%. Minor (3–6 mm, heal without a scar) in about 75–80%, herpetiform about 20%, major (>10 mm, scarring) about 5% in one series. Major ulcers are commoner than in simple aphthous stomatitis.
• Oral ulcers alone don't mean Behçet's, but in one cohort 52.2% of 67 patients with recurrent aphthous stomatitis developed it after a mean of 7.7 years.
• Genital ulcers: 57–93%. About 90% of male ulcers are scrotal; labia in women. Scarring follows 89% of large and 49% of small ulcers, so look for scars.
• Skin: papulopustular lesions 25–96%, erythema nodosum-like lesions 15–78%, superficial thrombophlebitis.
• Pathergy: a sterile needle prick gives a papule ≥2 mm or pustule at 24–48 hours. Positivity: Turkey up to 84% (historical), Japan 44%, UK 30%, Denmark 7.7%.

Eye

• About 50% overall: up to 70% of young men, about 30% of women and older patients. About 20% present with eye disease first.
• Pattern: non-granulomatous panuveitis with occlusive (necrotising) retinal vasculitis of arteries and veins; branch retinal vein occlusion; a shifting hypopyon in about 25% of anterior uveitis.
• Outcome: up to 25% have severe visual loss (<6/60). Prognosis is improving with earlier immunosuppression.

Vascular

• 5–40% (up to 50% in some series), mostly young men. Venous far more than arterial.
• DVT up to 13%. Also vena cava, cerebral sinus, portal vein and right-heart thrombus.
• Budd–Chiari: <5%; mortality 18–47% over 4–9 years.
• Pulmonary artery aneurysm: <5% but the commonest arterial lesion. Mortality 26–50%, the highest of any manifestation.
• Other aneurysms: abdominal aorta is the commonest site (60%). Arterial disease tends to appear 5–10 years after onset.

Neuro-Behçet

• 3–30% (about 5% in one review). Median onset 6 years after first symptoms; it was the first manifestation in 29% of one Turkish cohort.
• Parenchymal (>80%): brainstem in about 50%, classically midbrain and pons; spinal cord up to 10%. CSF raised protein or pleocytosis in about two-thirds (neutrophilic or mixed in 54%); normal in about a third.
• Non-parenchymal (about 20%): cerebral venous thrombosis, almost always superior sagittal or transverse sinus.
• Course (parenchymal): 44% single attack, 28% secondary progressive, 10% primary progressive. Paresis at onset (OR 6.47) and brainstem lesions (OR 8.41) predict poor outcome.

Gastrointestinal

• Endoscopic disease 3.2–37% in Japan and Korea vs about 1–5% in Turkey.
• Ileocaecal: few (≤5), deep, round or oval ulcers >1 cm. Diffuse or multisegment disease is rare (2–4%).
• Perforation, fistula and bleeding: surgery in up to a third; 5-year operation rate 32%.

Joints

• 39–70%. Knee 33%, ankle 24%, wrist 14%. Monoarticular 66%, acute (under 6–8 weeks) 89%, non-erosive.

Diagnosis and differentials

• No confirmatory test. HLA-B51 is neither necessary nor sufficient. Pathergy supports but is often negative outside endemic regions.
• Before anticoagulating a venous clot, exclude pulmonary artery aneurysm (EULAR).
• Suspected GI disease: confirm with endoscopy or imaging and exclude NSAID ulcers, IBD and TB (EULAR).
• Differentials:
  • Recurrent aphthous stomatitis: the common mimic.
  • HSV: oral and genital herpes.
  • Coeliac disease: aphthous-like ulcers in 22.7% of children with coeliac disease vs 7.1% of controls (OR about 4.3); 71.7% improved on a gluten-free diet.
  • Crohn's disease: shares ileocaecal ulcers, oral ulcers and erythema nodosum. Granulomas (15–36% of Crohn's) occur occasionally in Behçet's, so histology often doesn't settle it. ASCA doesn't help.
  • MAGIC syndrome (mouth and genital ulcers with inflamed cartilage): meets criteria for both Behçet's and relapsing polychondritis.
  • A20 haploinsufficiency (TNFAIP3): early-onset, Behçet-like disease with high-penetrance dominant inheritance (six families, Nat Genet 2016). Think of it in childhood onset or strong family history.
  • Others: Sweet's syndrome, SLE, reactive arthritis, syphilis, erythema multiforme, pyoderma gangrenosum, Lipschütz ulcers.

Current treatment

EULAR 2018. Most recommendations rest on level III–IV evidence.

Principles

• Control flares fast to prevent irreversible organ damage.
• Multidisciplinary care; tailor to age, sex, organ and patient preference.
• Eye, vascular, neuro and GI disease carry the worst prognosis. Many features ease with time, so treatment can be tapered. One review suggests tapering immunosuppressants after 2–5 years of remission.

Mucocutaneous and joints

• Topical steroids for ulcers. Colchicine first to prevent recurrence, especially erythema nodosum and genital ulcers. Acneiform lesions are treated as acne.
• Colchicine RCT (n=116, 1–2 mg a day, 2 years): fewer genital ulcers and erythema nodosum in women; less arthritis in both sexes (Yurdakul 2001).
• Selected cases: azathioprine, thalidomide, interferon-α, TNF inhibitors or apremilast.
• Apremilast (RELIEF, NEJM 2019): n=207, 30 mg twice a day. Oral ulcer AUC over 12 weeks 129.5 vs 222.1 on placebo. Ulcer-free at week 12: 53% vs 22.3%. Commonest adverse events: diarrhoea, nausea, headache.
• Australia: apremilast (Otezla) is TGA-registered for adults with Behçet's oral ulcers who are candidates for systemic therapy. It is not PBS-listed (healthdirect); PBAC submissions found cover psoriasis only.
• Joints: colchicine first; intra-articular steroid for monoarthritis; azathioprine, interferon-α or TNF inhibitors for recurrent or chronic arthritis.

Eye

• Posterior segment disease: azathioprine or ciclosporin (level IB), or interferon-α or a monoclonal anti-TNF (IIA). Systemic steroids only alongside an immunosuppressant.
• Sight-threatening uveitis: high-dose steroids plus infliximab or interferon-α. Intravitreal steroid can be added for a unilateral flare. Adalimumab appears "an effective alternative" (discussion text, not a formal recommendation).
• Isolated anterior uveitis: consider systemic treatment if young, male and early onset.
• Azathioprine RCT (Yazici, NEJM 1990; 73 Turkish men, 2.5 mg/kg a day, 2 years): new eye disease 1 vs 8 patients; hypopyon uveitis episodes 1 vs 15.

Vascular

• Acute DVT: steroids plus an immunosuppressant (azathioprine, cyclophosphamide or ciclosporin). Refractory: monoclonal anti-TNF.
• Anticoagulation: may be added if bleeding risk is low and pulmonary artery aneurysm is excluded. Not recommended against, but controlled data are lacking.
• Pulmonary artery aneurysm: high-dose steroids plus cyclophosphamide; anti-TNF if refractory. Prefer embolisation to open surgery.
• Aortic and peripheral aneurysms: cyclophosphamide and steroids before repair, but don't delay surgery if symptomatic.

Gastrointestinal

• Steroids for flares plus 5-ASA or azathioprine. Severe or refractory: monoclonal anti-TNF and/or thalidomide.
• Urgent surgical review for perforation, major bleeding or obstruction.

Neuro-Behçet

• Parenchymal: high-dose steroids with a slow taper, plus azathioprine. Anti-TNF first line if severe, or if refractory.
• Avoid ciclosporin, even when neuro disease is inactive. New neuro disease in 6 of 21 treatment episodes on ciclosporin vs 0 of 175 on other drugs (Kötter 2006). A Japanese cohort of 317 eye patients raised the same neurotoxicity signal (Kotake 1999).
• Cerebral venous thrombosis: high-dose steroids; short-term anticoagulation may be added. Screen for vascular disease elsewhere.

Infliximab or interferon-α?

• BIO-BEHÇET'S (UK RCT, n=79, 2024): no difference in disease activity at 12 weeks. More switched off interferon (11/37 vs 3/37), with more adverse events on interferon. Underpowered after slow recruitment.

Emerging treatments and trials

• Ustekinumab (IL-12/23; French open-label cohort, n=30, colchicine-resistant oral ulcers): ulcer-free 60% at week 12 and 88.9% at week 24.
• Secukinumab (IL-17A; SHIELD, n=118, uveitis): primary endpoint missed; only a steroid-sparing signal.
• Tofacitinib (JAK1/3):
  • Pilot (n=13, refractory, ARD 2020): helped all 5 vascular patients; most GI patients were unchanged or worse (per a later letter).
  • Retrospective uveitis series (n=13): 76.9% treatment success; steroids stopped in 10.
• IL-1 inhibitors (anakinra, canakinumab; 19 patients, 31 eyes): uveitis flares fell from 200 to 49 per 100 patient-years.
• Tocilizumab: small reports in refractory vascular disease only.
• MAMBA: a registered RCT of diet-based microbiome modulation.

Theoretical frontiers

Hypotheses, not recommendations.

Causes: theories

• It's the peptide, not just the HLA: ERAP1 activity reshapes the HLA-B*51:01 peptide repertoire (unconventional subset 20% → 40% with knockdown). The disease-driving peptide, if there is one, is unknown. Test: immunopeptidomics of patient tissue (oral mucosa, retina) by ERAP1 genotype.
• One HLA class I disease family: the MHC-I-opathy model links Behçet's, spondyloarthritis and psoriasis through barrier sites and mechanical stress. Pathergy is a needle-sized proof of concept. Test: compare entheseal, skin and gut immune signatures across all three.
• Butyrate deficit: lower butyrate production may weaken regulatory T cells. Cross-sectional, n=22. Test: does dysbiosis precede flares in prospective sampling?
• NETs as the clot-maker: neutrophil extracellular traps may explain why immunosuppression, not anticoagulation, prevents venous relapse. Test: NET markers as predictors of thrombosis.
• Monogenic windows: A20 haploinsufficiency gives a Behçet-like picture through unchecked NF-κB. Test: sequence TNFAIP3 and other NF-κB regulators in early-onset and familial cases.
• The migrant gradient: Turkish migrants in Germany have rates well below Turkey but far above native Germans. Test: compare microbiome and oral health between migrants and their home populations.

Prevention: theoretical options

• Risk-stratified early immunosuppression: azathioprine prevented new eye disease in young men. Test: a trial of pre-emptive treatment in high-risk (young, male, HLA-B51) patients without eye disease, with blindness as the endpoint.
• Diet: a pilot of a butyrate-rich diet improved redox status and fibrin lysis. Test: MAMBA's results, then flare and thrombosis endpoints.
• ERAP1 drugs cut both ways: ERAP1 inhibitors exist (GRWD5769 in a cancer trial; GRWD0715 aimed at axial spondyloarthritis). The ERAP1 variant that protects against ankylosing spondylitis raises Behçet's risk in B51 carriers, so an ERAP1 inhibitor might worsen Behçet's. Test: Behçet's-relevant peptide profiling before any trial.

Treatment: theoretical options

• The IL-23 vs IL-17 puzzle: IL-23 blockade helped ulcers; IL-17A blockade failed in uveitis. Different organs may run on different cytokines. Test: an organ-stratified RCT of IL-23 blockade in eye disease.
• JAK inhibitors by organ: early signals in eye and vascular disease, not gut. Test: randomised trials with organ-specific endpoints and thrombosis safety monitoring.
• IL-1 for the eye: a large drop in flares, but uncontrolled. Test: head-to-head vs anti-TNF.
• Biomarkers we don't have: femoral vein wall thickness (proposed diagnostic marker), faecal calprotectin for gut disease, urinary metabolomics to predict infliximab response, HLA-B51 for neuro relapse (OR 3.5). None is validated. Test: prospective cohorts with these as pre-specified predictors.

Gaps and open questions

Labelled hypotheses, not recommendations.

• No diagnostic test. Classification criteria are doing a diagnostic job, and pathergy positivity is falling (61.5% for onset before 1977 vs 41% after 1998), which may erode criteria accuracy.
• Anticoagulation for venous thrombosis is unresolved: EULAR found insufficient controlled data either way.
• Head-to-head data are thin: one underpowered infliximab vs interferon trial; no trial against adalimumab.
• Hypothesis: Behçet's is several diseases. HLA-B51 tracks eye and skin disease but not gut disease; GI disease is commoner in East Asia; the sex ratio flips by region.
• Australian gaps: no prevalence data, no local guideline found, and no PBS-subsidised apremilast.
• Hypothesis: "burnout" is real but uneven. Mucocutaneous disease and mortality fall with time, but neuro and arterial disease can start 5–10 years in. When to stop treatment is unknown.

Prognosis and quality of life

• Istanbul 20-year cohort (Kural-Seyahi 2003; 387 patients): 42 died (9.8%), 39 of them men, mostly from major vessel and neuro disease. SMR highest in young men and fell over time. No women had arterial aneurysms.
• Paris cohort (Saadoun 2010; 817 patients, 7.7 years):
  • 5% died; 95.1% of deaths were men; mean age at death 34.8.
  • Causes: major vessel disease 43.9%, cancer 14.6%, CNS 12.2%, sepsis 12.2%.
  • SMR 2.99 at age 15–24, 2.90 at 25–34, not raised over 35.
  • Predictors: male sex (HR 4.94), arterial involvement (HR 2.51), frequent flares (HR 2.37).
• Ancestry: 15-year mortality 6% in European, 9% in North African and 19% in sub-Saharan African patients in Paris (Savey 2014).
• Organ mortality: pulmonary artery aneurysm 26–50%, Budd–Chiari 18–47%, parenchymal neuro-Behçet 11–21%.
• Eye: up to 25% severe visual loss; visual prognosis is better with late-onset eye disease.
• Quality of life: active oral ulcers carry an OR of 6.2 for impaired quality of life.

Weird trivia

• A diagnostic test that's a needle prick: blunt 20G needles gave 85% positivity vs 32.5% with sharp ones, and povidone-iodine skin prep for 4 minutes reduced positive results. Disposable needles may explain why positivity has fallen.
• From Copenhagen to Istanbul: pathergy is positive in 7.7% of Danish patients and up to 84% of Turkish patients.
• The quitting paradox: in 47 patients who stopped smoking, 65.9% developed oral ulcers vs 25% of non-smokers (Soy 2000). Not a reason to smoke: vascular disease is what kills people with Behçet's.
• Behçet blamed a virus: his 1937 paper's title called the ulcers "caused by a virus". None has been found.
• On money and mail: Turkey honoured him with a postage stamp (1980) and a silver coin (1996).
• Hypopyon that moves: the Behçet's hypopyon shifts with head position.

Guidelines

• EULAR 2018 update: management of Behçet's syndrome (Hatemi, Ann Rheum Dis 2018)
• ICBD 2014: International Criteria for Behçet's Disease (JEADV 2014)
• ISG 1990 criteria, as reproduced in Dermatology Online Journal 2004
• Chapel Hill 2012 nomenclature: variable-vessel vasculitis (Batu and Ozen, Pediatr Nephrol 2015)
• No Australian guideline found.

Key trials

• Yazici azathioprine (NEJM 1990): prevented new eye disease and hypopyon uveitis.
• Yurdakul colchicine (2001): fewer genital ulcers and erythema nodosum in women; less arthritis.
• SHIELD (secukinumab, 2013): uveitis endpoint missed.
• RELIEF (apremilast, NEJM 2019): fewer oral ulcers; the first US-approved treatment for Behçet's oral ulcers.
• Mirouse ustekinumab cohort (2019, open-label): 60% ulcer-free at 12 weeks.
• Tofacitinib pilot (2020): vascular signal, not GI.
• BIO-BEHÇET'S (infliximab vs interferon-α, 2024): no difference in activity; interferon tolerated worse.

Sources

• Hatemi G et al. 2018 update of the EULAR recommendations for Behçet's syndrome. Ann Rheum Dis 2018 (PDF)
• Davatchi F et al. ICBD: a collaborative study of 27 countries. JEADV 2014
• Sanchez-Negron FA. Behçet's disease (ISG 1990 criteria). Dermatol Online J 2004
• Gönül M et al. The history and diagnosis of Behçet's disease. IntechOpen 2019
• Oguz ID et al. The epidemiology of Behçet's disease. IntechOpen 2017
• Esatoglu SN et al. Behçet's syndrome: providing integrated care. J Multidiscip Healthc 2017
• Review: genetics of Behçet's disease (Istanbul prevalence, HLA-B51 meta-analysis, familial cases). 2012
• Yildiz M et al. Pediatric Behçet's disease. Front Med 2021
• Yazici Y et al. Behçet syndrome. Nat Rev Dis Primers 2021
• Kötter I, Lötscher F. Vascular, neurologic, GI and musculoskeletal manifestations. Front Med 2021
• Bettiol A et al. Vascular Behçet syndrome: from pathogenesis to treatment. Nat Rev Rheumatol 2023
• McGonagle D et al. 'MHC-I-opathy': unified concept for spondyloarthritis and Behçet disease. Nat Rev Rheumatol 2015
• NIH: new Behçet's loci and ERAP1–HLA-B51 epistasis (Kirino, Nat Genet 2013; summary)
• Chen L et al. ERAP1-regulated HLA-B*51:01 subpeptidome. Mol Cell Proteomics 2020
• Consolandi C et al. Behçet's syndrome patients exhibit a specific microbiome signature. Autoimmun Rev 2015 (PDF)
• Zhou Q et al. A20 haploinsufficiency causes an early-onset autoinflammatory disease. Nat Genet 2016
• Nakamura K et al. Mucocutaneous manifestations of Behçet's disease. Front Med 2021 (PDF)
• Kilic A. Mucocutaneous findings in Behçet's disease. IntechOpen 2017 (PDF)
• Ergun T. Pathergy phenomenon. Front Med 2021 (PDF)
• EyeWiki (American Academy of Ophthalmology): Behçet disease
• Campisi G et al. Coeliac disease and aphthous-like ulcers in children. Dig Liver Dis 2008
• MAGIC syndrome: case report and review. Indian J Dermatol 2016
• Hatemi G et al. Trial of apremilast for oral ulcers in Behçet's syndrome. NEJM 2019;381:1918–28
• MDedge: RELIEF results (complete response rates)
• Consultant360: RELIEF ulcer AUC and adverse events
• TGA: Otezla (apremilast) registration and indications
• healthdirect: Otezla indications and PBS status
• PBAC public summary: apremilast, November 2023 (psoriasis)
• Yurdakul S et al. A double-blind trial of colchicine in Behçet's syndrome. Arthritis Rheum 2001
• Yazici H et al. A controlled trial of azathioprine in Behçet's syndrome. NEJM 1990
• Kötter I et al. CNS involvement with ciclosporin in Behçet's disease. Clin Rheumatol 2006
• Kotake S et al. CNS symptoms in Behçet patients on ciclosporin. Ophthalmology 1999
• Moots RJ et al. BIO-BEHÇET'S: infliximab vs interferon-α RCT. Efficacy Mech Eval 2024
• Mirouse A et al. Long-term outcome of ustekinumab for Behçet's disease. Arthritis Rheumatol 2019
• Dick AD et al. Secukinumab in non-infectious uveitis (SHIELD). Ophthalmology 2013
• Liu J et al. A pilot study of tofacitinib for refractory Behçet's syndrome. Ann Rheum Dis 2020
• Letter: tofacitinib in refractory Behçet's uveitis (13 patients). Ann Rheum Dis 2023
• HCPLive: IL-1 inhibitors in Behçet's uveitis (Fabiani, Clin Rheumatol 2016)
• Grey Wolf Therapeutics: ERAP1 inhibitors GRWD5769 and GRWD0715
• EMITT-1 (NCT06923761): GRWD5769 in advanced solid cancers
• Kural-Seyahi E et al. Two-decade outcome of 387 patients. Medicine 2003
• Saadoun D et al. Mortality in Behçet's disease. Arthritis Rheum 2010
• Savey L et al. Ethnicity, manifestations and mortality in Behçet's disease. Orphanet J Rare Dis 2014 (PDF)
• Soy M et al. Smoking and Behçet's disease. Clin Rheumatol 2000
• LITFL: Hulûsi Behçet (biography, 1937 paper, stamp and coin)
• LITFL: Behçet disease (history timeline, Hippocrates, Adamantiades, Jensen)
• Matiakis A et al. Adamantiades–Behçet syndrome: a Greek–Turkish medical history. 2012 (PDF)

Information only. Most Behçet's recommendations rest on low-level evidence, and drug availability differs by country. Check product information, PBS status and specialist advice before acting.

Reviewed 1 November 2026. General education for health professionals; not a substitute for local protocols.

maladywise.com/deep-dives/behcets/