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Behçet's disease

https://doi.org/10.1016/j.berh.2004.02.008Get rights and content

Abstract

Behçet's disease is a systemic vasculitis characterized by recurrent oral and genital ulcers, and ocular inflammation, and which may involve the joints, skin, central nervous system and gastrointestinal tract. It is most common in those of Mediterranean and Eastern origin, although it also affects Caucasians. The aetiology of the disease remains unknown, but the most widely held hypothesis of disease pathogenesis is that of a profound inflammatory response triggered by an infectious agent in a genetically susceptible host. Supporting this is the consistent association of disease susceptibility with polymorphisms in the human leukocyte antigen complex, particularly HLA-B*51.

The diagnosis is a clinical one, and although there is no single laboratory test specific for the diagnosis of Behçet's disease, the 1990 classification criteria perform well in a clinical context. Whereas many favoured treatments for single or multisystem disease still lack a sound evidential base, cyclosporin and azathioprine perform well in clinical trials, and evidence is accumulating for the efficacy of anti-tumour necrosis factor therapy in particular clinical situations.

This review will focus on recent developments in the understanding of disease pathogenesis and clinical diagnosis, and review the evidence base for both established and new agents in the therapeutic strategy.

Section snippets

Epidemiology and pathogenesis

The geographical distribution of Behçet's disease is distinctive: it is most prevalent along the Silk Road, an ancient trading route between the Mediterranean and East Asia, where it is a major cause of morbidity.2 In Turkey, the country with the highest incidence of the disease, the prevalence is estimated to be between 110 and 420 per 100 0002., 3., whereas that in Japan is 13–20 per 100 000, and the prevalence in the UK and USA is estimated at 1–2 per 100 000.4 It is unknown among

Pathology

The common histopathological lesion underlying the clinical manifestations of Behçet's disease is vasculitis, involving particularly the venules. Lesions are characterized by perivascular lymphocytic and monocytic cellular infiltration, with or without fibrin deposition in the vessel wall and surrounding tissue necrosis.59 Significant neutrophil infiltration is also seen, particularly in early lesions including those of the pathergy reaction.60

Active systemic disease is associated with many

Recurrent aphthous ulceration

Recurrent aphthous ulceration is the sine qua non of Behçet's disease. Oral ulcers are usually the earliest sign of disease and may precede the onset of systemic symptoms by many years. Oral ulcers are similar to common mouth ulcers in appearance and localization, although they may be more extensive and painful, evolving quickly from a flat ulcer to a large sore. Lesions may occur singly or in crops, and subside without scarring. The most common sites of oral ulceration are the tongue, lips and

Pregnancy

Pregnancy is often stated to be associated with disease remission, but its influence is variable, and in 20% of patients pregnancy is associated with disease exacerbation.89 No increase in the complications of pregnancy have been observed.90 Transient neonatal Behçet's disease in the infants of affected mothers has, however, been described, suggesting that disease may be mediated by a placental transfer of maternal antibody.174., 175.

Children

Behçet's disease is uncommon in children. It affects both

Disease definition

There is no specific test for Behçet's disease, and the diagnosis is based upon clinical criteria. A number of classifications have been formulated, each with its own list of clinical features.93., 94., 95., 96. In1990, these were amalgamated into the International Study Group Classification criteria (Table 1).97 These have now been widely adopted, and although intended for the definition of patients participating in research programmes rather than for the diagnosis of individual patients, they

Treatment

Although the number of randomized controlled trials in Behçet's disease is increasing, treatment remains predominantly empirical, and considerable differences exist in practical approaches to treatment. The primary goals of management are symptom control, early suppression of inflammation and prevention of end-organ damage, the treatment options being anti-inflammatory agents and immunosuppressants. Drugs are frequently used in combination in order to maximize efficacy while minimizing side

Topical treatment

Oral ulceration can often be treated by the topical application of corticosteroids, using creams or mouthwashes (5 mg prednisolone in 20 ml water, four times daily102), or by direct application through a conventional corticosteroid inhaler. Similarly, genital ulceration often responds to topical corticosteroid therapy, although long-term use may be complicated by skin atrophy. Topical sucralfate suspension is an alternative topical therapy for aphthous ulceration.103 Topical mydriatic agents

Prognosis

Behçet's disease is characterized by relapses and remission, and its clinical course is highly variable. Overall, the disease is more severe in Mediterranean and Eastern cohorts than in Western populations, and it is generally more severe in males than females. A recently published, 20-year outcome study of 387 Turkish patients revealed an overall mortality of 9.8% in Behçet's disease.70 This is higher than previously reported76 and probably reflects the long duration of follow-up and the

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