Table 1

Updated European League Against Rheumatism recommendations for the management of Behçet’s syndrome, with levels of evidence, grade of recommendations, voting rates and level of agreement

Overarching principles and recommendationsLevel of evidence*Strength of recommendation †Level of agreement
Overarching principles
  • BS is a condition that typically runs a relapsing and remitting course and the goal of treatment is to promptly suppress inflammatory exacerbations and recurrences to prevent irreversible organ damage.

  • A multidisciplinary approach is necessary for optimal care.

  • Treatment should be individualised according to age, gender, type and severity of organ involvement and patient’s preferences.

  • Ocular, vascular, neurological and gastrointestinal involvement may be associated with a poor prognosis.

  • Disease manifestations may ameliorate over time in many patients.

1. Mucocutaneous involvementTopical measures such as steroids should be used for the treatment of oral and genital ulcers. Colchicine should be tried first for the prevention of recurrent mucocutaneous lesions especially when the dominant lesion is erythema nodosum or genital ulcer (IB). Papulopustular or acne-like lesions are treated with topical or systemic measures as used in acne vulgaris (IV).IB/IVA/D9.4±0.8
Leg ulcers in BS might be caused by venous stasis or obliterative vasculitis. Treatment should be planned with the help of a dermatologist and vascular surgeon.IVD
Drugs such as azathioprine, thalidomide, interferon-alpha, TNF-alpha inhibitors or apremilast should be considered in selected cases.IBA
2. Eye involvementManagement of uveitis of BS requires close collaboration with ophthalmologists with the ultimate aim of inducing and maintaining remission. Any patient with BS and inflammatory eye disease affecting the posterior segment should be on a treatment regime such as azathioprine (IB), cyclosporine-A (IB), interferon-alpha (IIA) or monoclonal anti-TNF antibodies (IIA). Systemic glucocorticoids should be used only in combination with azathioprine or other systemic immunosuppressives (IIA).IB/IIAA/B9.5±0.6
Patients presenting with an initial or recurrent episode of acute sight-threatening uveitis should be treated with high-dose glucocorticoids, infliximab or interferon-alpha. Intravitreal glucocorticoid injection is an option in patients with unilateral exacerbation as an adjunct to systemic treatment.IIAB9.4±0.7
3. Isolated anterior uveitisSystemic immunosuppressives could be considered for those with poor prognostic factors such as young age, male sex and early disease onset.IVD9.0±0.8
4.Acute deep vein thrombosisFor the management of acute deep vein thrombosis in BS, glucocorticoids and immunosuppressives such as azathioprine, cyclophosphamide or cyclosporine-A are recommended.IIIC9.3±0.8
5. Refractory venous thrombosisMonoclonal anti-TNF antibodies could be considered in refractory patients. Anticoagulants may be added, provided the risk of bleeding in general is low and coexistent pulmonary artery aneurysms are ruled out.IIIC8.7±0.8
6. Arterial involvementFor the management of pulmonary artery aneurysms, high-dose glucocorticoids and cyclophosphamide are recommended. Monoclonal anti-TNF antibodies should be considered in refractory cases. For patients who have or who are at high risk of major bleeding, embolisation should be preferred to open surgery.IIIC9.2±0.9
For both aortic and peripheral artery aneurysms, medical treatment with cyclophosphamide and corticosteroids is necessary before intervention to repair. Surgery or stenting should not be delayed if the patient is symptomatic.IIIC9.0±1.0
7. Gastrointestinal involvementGastrointestinal involvement of BS should be confirmed by endoscopy and/or imaging. NSAID ulcers, inflammatory bowel disease and infections such as tuberculosis should be ruled out.IIIC9.2±0.9
8. Refractory/severe gastrointestinal involvementUrgent surgical consultation is necessary in cases of perforation, major bleeding and obstruction. Glucocorticoids should be considered during acute exacerbations together with disease-modifying agents such as 5-ASA or azathioprine. For severe and/or refractory patients, monoclonal anti-TNF antibodies and/or thalidomide should be considered.IIIC8.8±0.9
9. Nervous system involvementAcute attacks of parenchymal involvement should be treated with high-dose glucocorticoids followed by slow tapering, together with immunosuppressives such as azathioprine. Cyclosporine should be avoided. Monoclonal anti-TNF antibodies should be considered in severe disease as first-line or in refractory patients.IIIC9.1±1.2
The first episode of cerebral venous thrombosis should be treated with high-dose glucocorticoids followed by tapering. Anticoagulants may be added for a short duration. Screening is needed for vascular disease at an extracranial site.IIIC9.0±0.8
10. Joint involvementColchicine should be the initial treatment in BS patients with acute arthritis. Acute monoarticular disease can be treated with intra-articular glucocorticoids. Azathioprine, interferon-alpha or TNF-alpha inhibitors should be considered in recurrent and chronic cases.IBA9.0±1.0
  • *Level of evidence indicates evidence from: IA, meta-analysis of RCTs; IB, at least one RCT; IIA, at least one controlled study without randomisation; IIB, at least one type of quasi-experimental study; III, descriptive studies, such as comparative studies, correlation studies or case–control studies; IV, expert committee reports or opinions and/or clinical experience of respected authorities.

  • †Strength of recommendation is based on evidence: A, category I evidence; B, category II evidence or extrapolated recommendations from category I evidence; C, category III evidence or extrapolated recommendation from category I or II evidence; D, category IV evidence or extrapolated recommendation from category II or III evidence.

  • 5-ASA, 5-aminosalicylic acid; BS, Behçet’s syndrome; NA, not applicable; NSAID, non-steroidal anti-inflammatory drug; RCT, randomised controlled trial; TNF-alpha , tumour necrosis factor-alpha.