Behçet's disease

PURPOSE OF REVIEW: To summarize recent scientific developments in the epidemiology, genetics, pathogenesis and treatment of Beh?et's disease. RECENT FINDINGS: Important genetic and immunologic studies were performed. Tumor necrosis factor-alpha-1031C allele was associated with disease susceptibility. Polymorphisms in interleukin-10, IL-8 and CD28 genes were also associated with Beh?et's disease. Association with endothelial nitric oxide synthase gene polymorphism was confirmed but was ethnic related. Significant T helper type 1 immune reaction was reconfirmed in recent studies, especially during active phases, but T helper type 2 reaction may also play a role. Interleukin-12B heterozygosity is associated with Beh?et's disease susceptibility and plays an important role in mediating T helper type 1 antistreptococcal immune response. Selenium binding protein may be a target antigen in Beh?et's uveitis. Pathergy reaction is most frequently positive in the forearm; multiple needle pricks increase positive rate. Experience with anti-tumour necrosis factor therapy for various manifestations is increasing. Cyclosporin A treatment may be associated with new onset of neuro-Beh?et. There is a high prevalence of headaches with moderate or severe disability. Cardiac manifestations include left ventricular dysfunction and coronary flow abnormalities. Anti-Saccharomyces cerevisiae antibodies may be especially common in intestinal Beh?et's disease and are also increased in healthy relatives of patients. SUMMARY: Considerable progress has been made, particularly in understanding the immunologic and genetic basis of the disease. The importance of novel serological markers and autoantigens merits further investigations.     

Behçet's disease

Beh?et's disease (BD) is a chronic, relapsing multisystem vasculitis with predominant involvement of the oral and genital mucosa. It has a worldwide distribution, but the prevalence is highest in Central Asia and the Far East (along the ancient 'Silk Route'). Genetic, environmental, immunological and haemostatic factors play a role in the aetiopathogenesis. The International Study Group for BD proposed criteria for the diagnosis of this condition, the essential feature being recurrent oral ulceration. Genital ulcers and skin manifestations are common, while ocular changes are the most important cause of morbidity. Almost any organ in the body can be involved, and systemic involvement may portend a poorer prognosis. There is no pathognomonic test for BD and the diagnosis is made on clinical findings. Treatment of BD would require multidisciplinary cooperation, and early referral to an ophthalmologist is advisable to prevent ocular morbidity. Topical and systemic agents (colchicine, dapsone and thalidomide) are useful in controlling exacerbation of the oral and genital ulcers. Severe disease may require immunosuppressive agents and, more recently, biological agents have been used successfully. It tends to follow an unpredictable course, and the eventual prognosis depends on the systemic involvement.     

Behçet's disease

Beh?et's disease (BD) is a systemic disorder characterized by recurrent attacks of acute inflammation. Major symptoms are oral aphthous ulcers, uveitis, skin lesions, and genital ulcerations. Involvement of vessels, gastrointestinal (GI) tract, and central nervous system (CNS) is less frequent but is associated with a poor prognosis. Pulmonary complications of BD include aneurysms of the aorta, great vessels, or pulmonary arteries; arterial or venous thrombosis; pulmonary parenchymal changes; pleurisy, and intracardiac thrombosis. Hemoptysis caused by pulmonary artery aneurysms may lead to lethal hemorrhage. Recent advances in therapeutic strategies have improved the prognosis. In this review, the salient clinical and histopathological features of BD and treatment strategies are discussed.     

Behçet's disease

Beh?et'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 Beh?et'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.     

Intestinal permeability in Behçet's syndrome

OBJECTIVE—To measure the intestinal permeability in patients with Behçet''s syndrome (BS) and to compare the results with those obtained from healthy and diseased controls.
METHOD—The study group comprised 34 patients with BS without known gastrointestinal disease. Ten patients with ankylosing spondylitis (AS), 6 with inflammatory bowel diseases (IBD), 17 with systemic lupus erythematosus (SLE), and 15 healthy subjects (HC) constituted the controls. All patients received 100 µCi (3.7 MBq) of chromium-51 EDTA (⁵¹Cr-EDTA) as a radioactive tracer after a 72 hour abstinence from all drugs. The percentage of the isotope excreted in a 24 hour urinary specimen was the measure of permeability.
RESULTS—The percentage (SD) rate of excretion of ⁵¹Cr-EDTA was 4.6 (2.6) in BS, 6 (2.4) in AS, 5.2 (1.9) in IBD, 5.56 (1.78) in SLE, and 2.3 (1) in healthy controls. (Analysis of variance: f=6.4, p=0.0002. BS v HC, AS v HC, SLE v HC significant.)
CONCLUSION—The intestinal permeability in BS was significantly more than that seen among the healthy controls. Similar results in all the diseased controls cast doubt on its specificity.

     

Renal microinfarction in Behçet's disease

SIR, We describe a patient with Behçet's disease andrenal cortical microinfarction whose renal impairment stabilizedfollowing anticoagulation. Behçet’ disease is achronic inflammatory vascular disorder of unknown aetiology.Vasculitis, thrombosis and infarction have been reported ina variety of organs with varying frequency. Renal involvementin Behçet's disease is uncommon and includes amyloidosis,crescentic glomerulonephritis and IgA nephropathy. In the literaturethere is only one report of acute renal infarction due to Behçet'sdisease [1]. We describe a patient with Behçet's diseasewith bilateral renal microinfarcts confirmed by computed tomography(CT) and DMSA     

Cardiovascular involvement in Behçet's disease

The incidence and nature of cardiac involvement in Beh?et's disease are not yet clearly documented. We first used transesophageal echocardiography in combination with resting and signal averaged electrocardiography to define cardiac involvement in Beh?et's patients. Transthoracic and multiplane transesophageal echocardiography, and resting and signal averaged electrocardiography were performed in 35 Beh?et's disease patients (9 women and 26 men, mean age: 38 +/- 12 years) and 30 normal subjects. Higher incidences of interatrial septum aneurysm (31% to 6%), mitral valve prolapse (25% to 3%), mitral regurgitation (40% to 6%) and aneurysmal dilatations of sinus valsalva and ascendan aorta were observed in the Beh?et's disease patients than in the normal subjects. Mean QT dispersion and mean corrected QT dispersion values were significantly greater in the patients with Beh?et's disease. Patients with interatrial septum aneurysm (and/or PFO), valvular dysfunction or proximal aorta dilatation had greater QT dispersion values than thase without these pathologies in the Beh?et's group (63 +/- 11 vs 44 +/- 19 ms, 58 +/- 23 vs 41 +/- 24 and 60 +/- 27 vs 42 +/- 23 ms respectively, P<0.05). Positive signal averaged electrocardiography parameters were detected in 18 (51%) Beh?et's disease patients compared with one (3%) in controls (P<0.001). Dilatation of the proximal aorta, interatrial septal aneurysm, mitral valve prolapse, and mitral regurgitation are the common findings of cardiac involvement in Beh?et's disease. Increased dispersion of ventricular repolarisation and positive late potentials are also detected. QT dispersion is significantly higher in patients with these cardiac abnormalities. These findings suggest that cardiac involvement in this disorder is a diffuse process which involves both cardiac structure and vascular elements.     

Arterial lesions in Behçet's disease

BACKGROUND: Arterial involvement is a rare but serious condition in the course of Beh?et's disease. We aimed to assess the results of therapeutic approaches in our patients with arterial lesions caused by Beh?et's disease. PATIENTS AND METHODS: The records of 534 patients with Beh?et's disease between 1987 and 2002 were retrospectively evaluated for the presence of arterial lesions. All patients were followed up regularly at 3 to 6 months intervals. RESULTS: Arterial lesions were diagnosed in 21 (3.9%) patients. Eight of these patients had pulmonary artery aneurysms (PAA), and the other 13 patients had non-pulmonary arterial lesions. Urgent surgical intervention was performed in three patients with PAA leading to death in all three. In addition, three other patients died due to massive haemoptysis at home despite to immunosuppressive therapy. Only two out of eight patients with PAA are still alive who were treated with cyclophophamide and corticosteroids. Thirteen operations were performed in 7 out of 13 patients having non-pulmonary arterial lesions. Although ten of the operations were primary operations, three reoperations had to be performed. A stent-graft was applied for the management of an iliac artery aneurysm in one patient. Only one patient died 8 years after the first non-pulmonary arterial involvement following a type IV thoracoabdominal aortic aneurysm repair. Five patients with arterial occlusive lesions were successfully treated by corticosteroids. CONCLUSIONS: Pulmonary artery aneurysms in Beh?et's disease patients have a poor prognosis despite any form of therapy. High dose corticosteroids alone can be successfully used for isolated non-pulmonary arterial occlusive lesions, unless disabling symptoms occur. Surgery or stent-graft insertion is indicated for non-pulmonary arterial aneurysms because these aneurysms entail high risk of complications.