Vasculitis in Behçet Disease

Chapter: Vasculitis in Behçet Disease
McMaster Section Editor(s): Jonathan D. Adachi
Section Editor(s) in Interna Szczeklika: Irena Zimmermann-Górska, Jan Sznajd, Aleksandra Tuchocka-Kaczmarek
McMaster Author(s): Jocelyn Ma, Nader Khalidi
Author(s) in Interna Szczeklika: Jacek Musiał, Jan Sznajd, Andrzej Szczeklik†
† Deceased.
Additional Information

DefinitionTop

Behçet disease is an immune-mediated small-vessel vasculitis that usually affects patients aged 20 to 40 years, more frequently men than women. The course of the disease is variable, with periods of relapses and remissions.

Clinical Features and DiagnosisTop

Clinical manifestations: Recurrent oral and/or genital aphthous ulcers with concomitant cutaneous, ophthalmic, joint, gastrointestinal (GI), and/or central nervous system (CNS) inflammatory lesions. Patients may have small-vessel vasculitis, arteritis, arterial aneurysms, and venous and arterial thromboangiitis and thrombosis.

Key clinical diagnostic criteria:

1) Painful oral aphthous ulcers, recurring ≥3 times over a 12-month period and healing spontaneously within 1 to 3 weeks; these are often the presenting symptom of the disease.

2) Presence of ≥2 of the following signs and symptoms: Recurrent genital ulcers; anterior and posterior uveitis or retinal vasculitis (in >80% of patients); cutaneous lesions: erythema nodosum, acneiform eruptions, or vesicles; pathergy, that is, hyperreactive skin leading to inflammatory lesions triggered by a minor trauma (eg, a needle prick causes the appearance of a pustule within 24-48 hours).

Other symptoms: Arthritis without erosions (in 50% of patients); CNS involvement (headache, features of brainstem and corticospinal tract damage, aseptic meningitis, mood disturbances, confusion); GI symptoms (abdominal pain, diarrhea); migrating superficial phlebitis; deep vein thrombosis.

TreatmentTop

Behçet disease, like most other instances of vasculitis, is usually treated by rheumatologists. Treatment is based on severity of the disease and the specific organs involved.

1. Cutaneous lesions: First-line treatment for isolated lesions is with topical glucocorticoids.Evidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Alpsoy E, Er H, Durusoy C, Yilmaz E. The use of sucralfate suspension in the treatment of oral and genital ulceration of Behçet disease: a randomized, placebo-controlled, double-blind study. Arch Dermatol. 1999 May;135(5):529-32. PubMed PMID: 10328192. Other treatment options may include tacrolimus and antibiotics as well as colchicine (especially if there is erythema nodosum) and dapsone. In patients with severe lesions or in treatment-resistant patients, interferon alpha, methotrexate, azathioprine, and thalidomide may be used.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to potentially serious teratogenic and neuropathic adverse effects of thalidomide. Hamuryudan V, Mat C, Saip S, et al. Thalidomide in the treatment of the mucocutaneous lesions of the Behçet syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998 Mar 15;128(6):443-50. PubMed PMID: 9499327. The general concern, as with all immunosuppressive drugs, is with the potential teratogenic effect.

2. Ocular involvement: According to the European League Against Rheumatism, in inflammatory eye disease affecting the posterior segment, treatment should include azathioprine and systemic glucocorticoids.Evidence 3Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). High Quality of Evidence (high confidence that we know true effects of the intervention). Yazici H, Pazarli H, Barnes CG, et al. A controlled trial of azathioprine in Behçet's syndrome. N Engl J Med. 1990 Feb 1;322(5):281-5. PubMed PMID: 2404204. Hamuryudan V, Ozyazgan Y, Hizli N, et al. Azathioprine in Behcet's syndrome: effects on long-term prognosis. Arthritis Rheum. 1997 Apr;40(4):769-74. PubMed PMID: 9125262. If there is severe eye disease, cyclosporine (INN ciclosporin) A or infliximab may be added to the treatment regimen, or treatment with interferon alpha may be considered (with or without glucocorticoids).Evidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (low confidence that we know true effects of the intervention). For cyclosporine A, Quality of Evidence is high but strength of recommendation was lowered due to the possible adverse event of renal dysfunction. For interferon, Quality of Evidence was lowered due to the small size of the randomized controlled trial, remaining studies being open-label design, and safety concerns of depression and cytopenias. Ozyazgan Y, Yurdakul S, Yazici H, et al. Low dose cyclosporin A versus pulsed cyclophosphamide in Behçet's syndrome: a single masked trial. Br J Ophthalmol. 1992 Apr;76(4):241-3. PubMed PMID: 1390495; PubMed Central PMCID: PMC504238. Masuda K, Nakajima A, Urayama A, Nakae K, Kogure M, Inaba G. Double-masked trial of cyclosporin versus colchicine and long-term open study of cyclosporin in Behçet's disease. Lancet. 1989 May 20;1(8647):1093-6. PubMed PMID: 2566048. Alpsoy E, Durusoy C, Yilmaz E, et al. Interferon alfa-2a in the treatment of Behçet disease: a randomized placebo-controlled and double-blind study. Arch Dermatol. 2002 Apr;138(4):467-71. PubMed PMID: 11939808. Calgüneri M, Oztürk MA, Ertenli I, Kiraz S, Apraş S, Ozbalkan Z. Effects of interferon alpha treatment on the clinical course of refractory Behçet's disease: an open study. Ann Rheum Dis. 2003 May;62(5):492-3. PubMed PMID: 12695172; PubMed Central PMCID: PMC1754535.

3. Treatment of internal organ involvement: There is no well-controlled evidence to guide treatment of major vessel, GI, or CNS involvement. Treatment might include oral glucocorticoids, interferon alpha, azathioprine, cyclosporine, and cyclophosphamide.Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of studies and one randomized controlled trial that alluded to a potential risk reduction but did not directly measure it as an outcome, and due to indirectness, imprecision, and risk of bias. Hamuryudan V, Ozyazgan Y, Hizli N, et al. Azathioprine in Behcet's syndrome: effects on long-term prognosis. Arthritis Rheum. 1997 Apr;40(4):769-74. PubMed PMID: 9125262. Hamuryudan V, Er T, Seyahi E, et al. Pulmonary artery aneurysms in Behçet syndrome. Am J Med. 2004 Dec 1;117(11):867-70. PubMed PMID: 15589493. Choi IJ, Kim JS, Cha SD, et al. Long-term clinical course and prognostic factors in intestinal Behçet's disease. Dis Colon Rectum. 2000 May;43(5):692-700. PubMed PMID: 10826433. Cyclosporine A should probably be avoided in cases of CNS involvement (unless necessary due to severe ocular involvement) because of potential neurotoxicity.Evidence 6Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of studies (retrospective cohort). Kötter I, Günaydin I, Batra M, et al. CNS involvement occurs more frequently in patients with Behçet's disease under cyclosporin A (CSA) than under other medications--results of a retrospective analysis of 117 cases. Clin Rheumatol. 2006 Jul;25(4):482-6. Epub 2005 Nov 1. PubMed PMID: 16261281. Infliximab has been successfully used in treatment-resistant patients.

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