The European League Against Rheumatism (EULAR) has released updated guidelines for the management of Behçet syndrome (BS) in light of recent data on new treatment modalities, according to guidelines published online in the Annals of the Rheumatic Diseases.
The updated recommendations include 5 new overarching principles for managing BS as well as a new recommendation regarding the surgical management of vascular involvement. The recommendations for the management of mucocutaneous, joint, eye, vascular, neurological, and gastrointestinal involvement of BS have been modified.
These updated guidelines aim to help clinicians who care for patients with BS and to help standardize treatment. However, the guidelines also highlight areas of clinical research that have shortcomings.
The 5 overarching principles and recommendations for BS are as follows:
- Patients with BS typically have a relapsing and remitting course of illness. The goal of treatment is to suppress inflammatory exacerbations and recurrences to help prevent the patient from developing irreversible organ damage.
- For optimal patient care, clinicians need to take a multidisciplinary approach.
- Clinicians must tailor treatment according to the patient’s age, gender, type or severity of organ involvement, and patient preferences.
- Patients with BS who have ocular, vascular, neurological, and gastrointestinal involvement may have poor prognoses.
- In many patients, disease manifestations may improve over time.
Recommendations for BS with mucocutaneous involvement
- Oral and genital ulcers should be treated with topical measures such as steroids. To prevent recurrent mucocutaneous lesions, especially when the dominant lesion is erythema nodosum or a genital ulcer, colchicine should be tried first. Treat papulopustular or acne-like lesions with topical or systemic measures as used for acne vulgaris.
- Treatment of leg ulcers should be coordinated with the help of a dermatologist and vascular surgeon.
- In select cases, drugs like azathioprine, thalidomide, interferon-alpha, tumor necrosis factor (TNF)-alpha inhibitors or apremilast should be considered.
Recommendations for BS with eye involvement
- To manage uveitis, clinicians need to collaborate closely with ophthalmologists to induce and maintain remission. Patients with BS and inflammatory eye disease that affects the posterior segment should be treated with a regimen such as azathioprine, cyclosporine-A, interferon-alpha, or monoclonal anti-TNF antibodies. Only systemic glucocorticoids in combination with azathioprine or other systemic immunosuppressives should be used.
- If a patient presents with an initial or recurrent episodes of acute, sight-threatening uveitis, they should be treated with high-dose glucocorticoids, infliximab, or interferon-alpha. Intravitreal glucocorticoid injection is a treatment option in patients with unilateral exacerbation in addition to systemic treatment.
Recommendations for BS with isolated anterior uveitis
- Consider treating patients with poor prognostic factors such as young age, male gender, and early disease onset with systemic immunosuppressives.
Recommendations for BS with acute deep vein thrombosis
- Acute deep vein thrombosis in BS can be managed with glucocorticoids and immunosuppressives such as azathioprine, cyclophosphamide, or cyclosporine-A.
Recommendations for BS refractory venous thrombosis
- Consider monoclonal anti-TNF antibodies in patients with refractory BS. If the patient has a low risk for bleeding and coexistent pulmonary artery aneurysms are ruled out, clinicians can add anticoagulants to their treatment regimen.
Recommendations for BS with arterial involvement
- Clinicians should manage pulmonary artery aneurysms with high-dose glucocorticoids and cyclophosphamide. In refractory cases, consider monoclonal anti-TNF antibodies. Embolization should be used over open surgery in patients who have or are at high risk for major bleeding.
- Treat aortic and peripheral artery aneurysms with cyclophosphamide and corticosteroids before intervention to repair. If the patient is symptomatic, surgery or stenting should not be delayed.
Recommendations for BS with gastrointestinal involvement
- Confirm gastrointestinal involvement with endoscopy or imaging to rule out nonsteroidal anti-inflammatory (NSAID) ulcers, inflammatory bowel disease, and infections such as tuberculosis.
Recommendations for BS with refractory or severe gastrointestinal involvement
- If a patient has perforation, major bleeding, or obstruction, clinicians should seek urgent surgical consultation. Consider glucocorticoids in patients with acute exacerbations, used alongside disease-modifying agents such as 5-aminosalicylic acid (5-ASA) or azathioprine. In severe or refractory cases, clinicians should consider monoclonal anti-TNF antibodies and/or thalidomide.
Recommendations for BS with nervous system involvement
- Treat acute attacks of parenchymal involvement with high-dose glucocorticoids followed by slow tapering in addition to immunosuppressives like azathioprine. Avoid treating patients with cyclosporine. Consider treating patients with monoclonal anti-TNF antibodies in severe cases as first-line or refractory treatment.
- Treat the first episode of cerebral venous thrombosis with high-dose glucocorticoids followed by tapering. Clinicians may add anticoagulants for a short time. Patients should be screened for vascular disease at an extracranial site.
Recommendations for BS with joint involvement
- The initial treatment in patients with BS and acute arthritis should be colchicine. Treat acute monoarticular disease with intra-articular glucocorticoids. Consider azathioprine, interferon-alpha, or TNF-alpha inhibitors in recurrent and chronic cases.
The researchers used a Delphi approach to determine 52 research questions, and EULAR standardized operating procedures were used as the framework. A systemic literature search was prepared, using the recommendations given in Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols and registered in International Prospective Register of Systematic Reviews before starting the systematic literature search. To update or add to the previous recommendations, the researchers used thorough discussion followed by voting.
In addition to the recommendations, the researchers identified questions that need to be answered by future research in order to improve the management of patients with BS.
The overall research agenda should include the following:
- Controlled trials that assess the benefit of concomitant immunosuppressive use with TNFis
- Controlled trials that assess the efficacy of treatment modalities for outcomes such as fatigue
For eye involvement, the researchers proposed the following research agenda:
- Head-to-head trial that compares interferon-alpha with TNFis
- Controlled trials with interleukin-1 (IL-1) and IL-6 blockers
- Controlled trials that assess the comparative efficacy and safety of different TNFis
- Determine how long TNFis or interferon-alpha should be continued after remission
- Define remission in order to decide whether to switch to maintenance therapy or consider treatment discontinuation for eye involvement
- Controlled trials that determine whether glucocorticoids reduce the efficacy of interferon-alpha
For vascular involvement, the researchers proposed the following research agenda:
- Controlled trials that assess the efficacy and safety of anticoagulation for preventing relapses of venous thrombosis, post-thrombotic syndrome, and recurrent arterial occlusive events
- Observational studies that identify individual differences that guide the choice of surgical intervention
- Determine the optimal dose and duration of immunosuppressives after surgical intervention for peripheral artery aneurysms
- Determine optimal treatment in postoperative recurrent anastomotic aneurysms
- Determine optimal management in intracardiac thrombosis
For nervous system involvement, the researchers proposed the following research agenda:
- Controlled studies that determine the optimal management of initial, refractory, and recurrent parenchymal nervous system involvement and cerebral venous thrombosis
- Determine the role of magnetic resonance imaging (MRI) and other laboratory tests for treatment decisions and follow-up in patients with nervous system involvement
For gastrointestinal system involvement, the researchers proposed the following research agenda:
- Controlled studies that determine the optimal management of initial, refractory, and recurrent gastrointestinal system involvement
- Determine the role, optimal dose, and duration of corticosteroids in acute relapses and whether they increase the risk for perforation
- Determine whether a control colonoscopy is needed in patients with clinical remission and the optimal timing for control colonoscopy
The task force that developed the new guidelines included experts from different specialties, including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine, and vascular surgery. The task force also included a methodologist, a health professional, 2 patients, and 2 fellows.
Hatemi G, Christensen R, Bang D, et al. 2018 update of the EULAR recommendations for the management of Behçet’s syndrome [published online April 6, 2018]. Ann Rheum Dis. doi:10.1136/ annrheumdis-2018-213225