Dermatologic Aspects of Behcet Disease Treatment & Management
- Author: Amira M Elbendary, MBBCh, MSc; Chief Editor: William D James, MD more...
Behçet disease is a multisystem disease, and treatment requires collaboration between different specialities to prevent irreversible organ damage.
The European League Against Rheumatism (EULAR) has developed recommendations for managing patients with Behçet disease, based on best-evidence–based trials in the literature and expert opinion from physicians experienced in managing Behçet disease.
Oral and genital ulcers
The patient should dissolve the contents of a 250-mg tetracycline capsule in 5 mL of water or flavored liquid and hold the solution in his or her mouth for approximately 2 minutes before swallowing. This is repeated 4 times daily.
Topical corticosteroids are effective for oral or genital ulcerations if they are applied during the prodromal stage of ulceration.
Other useful drugs include lidocaine gel (2%), sucralfate suspension, and 5% amlexanox.
Twice-daily usage of topical 0.2% hyaluronic acid gel improved inflammation and healing periods and reduced oral ulcers.
Intralesional glucocorticoids may be used for major aphthous ulcers. Triamcinolone 5-10 mg/mL may be used.
Insufficient response may require systemic treatment. Colchicine could be used in such cases, and resistant cases may require systemic glucocorticoids. In resistant cases, azathioprine, thalidomide, and tumor necrosis factor (TNF)–alpha antagonists (infliximab or etanercept) are reported to be effective. Infliximab and etanercept have steroid-sparing effects and have decreased the frequency of attacks in patients with Behçet disease.
A patient with Behçet disease presenting with oral ulcers resistant to prednisone, azathioprine, colchicine, dapsone, and cyclosporin responded well to lenalidomide.
A case of Behçet disease resistant to prednisone, cyclosporin, azathioprine, infliximab with methotrexate, and colchicine has been successfully treated with anakinra.
There are no specific recommendations from EULAR regarding oral and genital ulcers, except for considering local corticosteroid therapy as a first-line treatment.
Acneiform lesions could be managed similarly to acne vulgaris.
In a single patient previously diagnosed with Behçet syndrome with recurrent oral aphthous ulcers, quadruple therapy (proton pump inhibitor, bismuth, tetracycline, and metronidazole), for histologically positive H pylori determined by upper gastrointestinal endoscopy, reduced the development of new ulcers and the frequency of recurrent attacks for less than 1 month. Breath testing for H pylori was negative in the first month after discontinuation of therapy.
Erythema nodosum–like lesions are reported to respond well to colchicine, and that is what EULAR recommends. In cases with a delayed response, glucocorticoids and other immunosuppressive treatments may be used to prevent the progression into ulceration
The goal of treatment in cases of ocular involvement is to suppress the inflammation and prevent recurrent attacks that eventually result in irreversible damage and visual loss.
EULAR recommendations for any Behçet disease patient with eye involvement that includes the posterior segment should include azathioprine and systemic glucocorticoids. In refractory cases, EULAR recommended the use of infliximab in combination with azathioprine or systemic glucocorticoids or interferon-alfa with or without glucocorticoids.
Intravenous methylprednisolone (1 g/day) for 3 days may be used as initial therapy in sight-threatening conditions.
FK506 (tacrolimus) has been particularly noteworthy. The Japanese FK506 study group reported that FK506 was effective in treating refractory uveitis in a dosage-dependent manner. Adverse effects were renal impairment (28.3%), neurologic symptoms (20.8%), gastrointestinal symptoms (18.9%), and hyperglycemia (13.2%). The study group also noted the need for further clinical investigations on FK506 before more widespread application.
A patient with Behçet disease with ocular involvement, dependant on corticosteroids and refractory to azathioprine, showed improvement with the addition of pentoxifylline.
Case reports describe treatment of patients with recalcitrant disease or those in whom conventional immunosuppressive agents have failed.[112, 113, 114, 115, 116] Pediatric case responding to infliximab has been reported. Infliximab has resulted in responses after etanercept failed. Infliximab infusions of 5-10 mg/kg have been used with variable dosing schedules. Infliximab infusions, at a starting dose of 5 mg/kg, have been beneficial in Behçet disease patients with ocular involvement who were unresponsive to standard immunosuppressive therapy.
Tuberculosis was a reported adverse effect of infliximab infusion in one Behçet disease patient.
Several patients not responding to infliximab have been treated with adalimumab.
Based on the fact that vein thrombosis in Behçet disease results mainly from inflammation in the vessel wall, EULAR recommends immunosuppressive drugs such as corticosteroids, azathioprine, cyclosporine, or cyclophosphamide in the management of acute deep venous thrombosis.
As the thrombus is adherent to the vessel wall, the use of anticoagulation is controversial and is not recommended.
Thrombosis of the superior vena cava or Budd-Chiari syndrome may require a potent immunosuppressive agent such as monthly pulses of cyclophosphamide.
Arterial aneurysms are treated with immunosuppressives followed by surgery to prevent recurrence. Surgery carries a very high risk in cases of pulmonary aneurysms, and treatment with potent immunosuppressives such as high doses of glucocorticoids or monthly pulses cyclophosphamide was found to yield better outcomes.
Pericarditis has been treated with immunosuppressive agents and aspirin. Myocardial involvement has been treated with high doses of prednisone with aspirin. Cardiac inflammatory masses and thrombi may also require immunosuppressive drugs together with anticoagulant therapy. Great caution should be used when administering antithrombotic therapy, owing to the risk of bleeding from asymptomatic pulmonary aneurysms.[122, 123]
Deep penetrating ulcers are treated first with immunosuppressive drugs unless emergency surgery is indicated. Azathioprine as maintenance therapy has been reported to decrease recurrence rates. In refractory cases, TNF-alpha antagonists and thalidomide have been reported to be effective.
EULAR recommendations for patients with parenchymal involvement include corticosteroids, azathioprine, cyclophosphamide, methotrexate, TNF-alpha antagonists, and interferon-alfa. In cases of dural thrombosis, corticosteroids are recommended.
Cyclosporine is best avoided, owing to its neurotoxic effects.
The use of nonsteroidal anti-inflammatory agents yields satisfactory results. Colchicine is beneficial. Intramuscular corticosteroid depot injections have not shown satisfactory results.
Tumor necrosis factor-alpha inhibitors in severe and refractory disease
The outcomes of tumor necrosis factor-alpha inhibitor use in Behçet disease was evaluated in a multicenter study that evaluated the outcome of infliximab (62%) and adalimumab (30%) in 124 Behçet disease patients. A response was achieved in 90.4% in patients with severe/refractory mucocutaneous ulcers and ocular, gastrointestinal, central nervous system, and cardiovascular manifestations. The lowest achieved remission rate was observed in patients with cardiovascular manifestations (66.7%). No significant difference was noted when these agents were used as monotherapy or when combined with conventional immunosuppressive therapy.
Surgical therapy becomes necessary in serious conditions, including the following:
Enterocutaneous fistula formation
Spontaneous arterial aneurysm formation
Thrombotic obstruction in large-caliber vessels
Proper timing for surgical treatment is important. Delayed wound healing or inflammation at operative sites may be related to pathergy.
Consultation with the following specialists may be necessary:
Dermatologist - For evaluation of mucocutaneous lesions (ie, oral ulcer, genital ulcer, skin lesions)
Ophthalmologist - For evaluation of eye involvement
Rheumatologist or orthopedic surgeon - For evaluation of joint involvement
Neurologist or psychiatrist - For evaluation of CNS involvement
Internal medicine specialist - For evaluation of gastrointestinal, pulmonary, renal, or endocrine involvement
General surgeon - For evaluation of gastrointestinal involvement
Chest surgeon or cardiologist - For evaluation of cardiovascular involvement
Ear, nose, and throat specialist or dentist - For evaluation of oral cavity
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