Approach Considerations
The goals of therapy in Behçet disease are to suppress inflammation and reduce the frequency and severity of recurrences. To be effective, treatment must be started early. The sites and extent of involvement and the severity of disease determine the choice of medication.
The treatment approach depends on the individual patient, severity of disease, and major organ involvement. The European League Against Rheumatism (EULAR) recommendations for the management of Behçet disease, which were developed in 2008 and updated in 2018, aid in the management of different aspects of Behçet disease. [50, 51] Recommendations related to the eye, skin/mucosa, and arthritic disease are mainly evidence based, but recommendations on vascular, neurologic, and gastrointestinal involvement are based largely on expert opinion and uncontrolled evidence from open trials and observational studies. [50, 51]
As disease activity subsides, taper medications to the lowest dose that effectively controls disease activity. Inpatient care is based on individual organ-system involvement. Individualize the transfer situation for each patient based on the specifics of organ-system involvement.
Medical Care
For oral and genital ulcerations, topical steroids or sucralfate solution are first-line therapy for mild isolated ulcerations. Colchicine has also been used to prevent mucocutaneous relapse. [52, 53] For severe mucocutaneous lesions, systemic corticosteroids, azathioprine, pentoxifylline, dapsone, interferon-alfa, colchicine, and thalidomide have demonstrated benefit. Apremilast is a second-line treatment for oral ulcers associated with Behςet disease. [54]
For ocular disease, azathioprine is widely accepted as the initial agent. For severe eye disease (significant drop in visual acuity, retinal vasculitis, or macular involvement), either cyclosporine or infliximab may be used in combination with azathioprine and corticosteroids. [55, 56, 50, 57] An expert panel has recommended considering infliximab and adalimumab as first-line immunomodulatory agents for the treatment of ocular manifestations. [58]
Interferon-alfa, alone or in combination with corticosteroids, can be a second choice in severe ocular Behçet disease. [59, 60] It is used primarily in Europe. A retrospective study of a large case series from Germany reported long-lasting remission and improved visual prognosis in patients with severe ocular Behçet disease treated with alpha interferon. [59]
For gastrointestinal lesions, treatment alternatives based on expert opinion are aminosalicylate (5-ASA) derivatives (eg, sulfasalazine or mesalamine), systemic corticosteroids, azathioprine, tumor necrosis factor–α (TNF-α) antagonists, and thalidomide.
Arthritis may respond to prednisone, local corticosteroid injections, nonsteroidal anti-inflammatory drugs (NSAIDs), and colchicine. Interferon-alfa, azathioprine, and TNF-α blockers may be tried in rare cases of patients with resistant, prolonged, and disabling attacks.
Cutaneous disease with erythema nodosum is a special circumstance and may be treated with colchicine or dapsone.
Central nervous system (CNS) disease is usually treated with systemic corticosteroids, interferon-alfa, azathioprine, cyclophosphamide, [61] methotrexate, and TNF-α antagonists. [47]
Treatment of major-vessel disease with thrombotic events is with systemic anticoagulation in addition to corticosteroids, azathioprine, cyclophosphamide, or cyclosporine. Pulmonary arterial aneurysms are treated with cyclophosphamide and corticosteroids.
TNF-α antagonists are increasingly used and have become standard treatment of Behçet disease that is inadequately controlled by standard immunosuppressive regimens. [62, 63] Infliximab has been most widely studied, but adalimumab has proved successful in cases refractory to both conventional therapy and infliximab. [64] Etanercept is the only TNF inhibitor with data from a short-term randomized controlled study demonstrating efficacy in suppressing most of the mucocutaneous manifestations of Behçet disease. [65]
In a multicenter study of the use of TNF-α antagonists (mainly infliximab and adalimumab) for treatment of severe and/or refractory Behçet's disease in 124 patients, clinical response rates with particular organ involvement were as follows [66] :
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Ocular - 96.3%
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Mucocutaneous - 88%
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Joint - 70%
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GI - 77.8%
-
CNS - 92.3%
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Cardiovascular - 66.7%
Infliximab was reported to successfully treat a case of Behçet disease in pregnancy. [67] Other therapies with data from case reports or small pilot studies include the following, among others:
An open-label multicenter study compared the efficacy of infliximab versus adalimumab as a first‐line treatment in 177 patients with refractory uveitis due to Behçet disease. After 1 year of therapy, both treatment groups showed improvement. However, the patients receiving adalimumab had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for infliximab; P = 0.06), improvement in vitritis (93.33% versus 78.95% for infliximab; P = 0.04), and best‐corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for infliximab; P = 0.001). [72]
Apremilast, an oral phosphodiesterase-4 inhibitor initially approved for the treatment of psoriasis and psoriatic arthritis, was approved for treatment of oral ulcers associated with Behςet disease in 2019. In a phase III trial, patients taking apremilast had significantly fewer oral ulcers than individuals receiving a placebo (129.5 vs 222.1 respectively). However, 79% of those taking apremilast experienced adverse events, which included diarrhea, nausea, headache, upper respiratory tract infection, and viral upper respiratory tract infection. Although improvements were also observed in overall disease activity and patient-reported outcomes, the trial was not designed to determine whether apremilast would improve mucocutaneous manifestations other than oral ulcers. [73]
The role of anti–interleukin-17 in Behçet disease is not known. However, two small retrospective studies suggest improvement in mucocutaneous and articular symptoms with secukinumab. [74, 75]
Surgical Care
GI presentations that require surgical intervention include the following:
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Intestinal stenosis
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Lesions unresponsive to medical therapy
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Fistula formation
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Perforation
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Severe bleeding
Surgery may also be considered in the following circumstances:
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Pulmonary aneurysms and areas that incur ischemic damage due to vasculitis or thrombosis may require resection
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Ventricular aneurysms, coronary thrombosis, and endocardial fibrosis are occasionally amenable to surgery
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Glaucoma, cataracts, and retinal detachment occasionally warrant surgical intervention
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Neurosurgery may be required to correct some CNS aneurysms and clots
Consultations
Consultations with the following specialists based on clinical need:
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Rheumatologist
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Urologist for genital and urologic lesions
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Neurologist for CNS involvement
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Ophthalmologist for ocular disease
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Gastroenterologist for intestinal disease
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Dermatologist for possible help with recurrent skin lesions
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Surgeon, when indicated
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Nephrologist for proteinuria or hematuria
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Pulmonologist or cardiologist in rare cases of intracardiac or pulmonary thrombosis and aneurysms
Diet and Activity
No general dietary recommendations exist for Behçet disease. Patients with severe bowel involvement are advised to follow the same GI recommendations given to patients with inflammatory bowel disease. These patients often require total parenteral nutrition.
Activity is suggested as tolerated and may be limited owing to systemic symptoms or arthritis.
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Oral aphthous ulcers secondary to Behçet disease.
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Behçet disease. T2-weighted magnetic resonance images show brainstem involvement with meningoencephalitis in an 11-year-old girl with neurologic Behçet disease.
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Histology of Behçet disease ulcers revealing neutrophilic infiltrate and vasculitis.
Tables
Sign/Symptom |
Points |
Genital aphthosis |
2 |
Oral aphthosis |
2 |
Skin lesions |
2 |
Neurologic manifestations |
1 |
Vascular manifestations |
1 |
Positive pathergy test (optional) |
1 |
