The management of Behçet's syndrome

Beh?et syndrome (BS) is a multisystem vasculitis characterized by skin and mucosa lesions and musculoskeletal, ocular, gastrointestinal, neurological and major vessel involvement. It is seen mainly in the Mediterranean basin, Middle East and the Far East. The disease runs a more severe course among young males and the severity diminishes with age. This review describes the management of this disease, which should be individualized and varies according to site and gender.     

The management of Behçet's syndrome

Beh?et's syndrome (BS), originally described as a triad of oral aphthae, genital ulcerations and uveitis, is a systemic vasculitis that is prevalent in the Middle east, Far East and in the Mediterranean basin. It is characterized by a heightened state of inflammation although the main drive that initiates and sustains this is not yet elucidated. Suppression of this inflammatory state constitutes the major goal of treatment and therapy is tailored according to the specific manifestations observed. We now have considerable more insight on drug management of BS compared to 20 years ago. Particularly, within the recent past we have learned to use more rationally the agents that were already available to us. This is especially true for azathioprine, cyclosporin A, thalidomide and colchicine. Promising data are also being collected with alpha-interferon. With these agents, significant progress has been achieved in the management of uveitis and mucocutaneous symptoms but treatment issues related to thrombotic problems, major vessel involvement and neurological disease have not yet been resolved.     

Interferons and Behçet's disease

BACKGROUND: Beh?et's disease is a vasculitis of unknown origin. Various therapeutic agents have been proposed. Interferon alpha 2a or 2b appear to be the most promising. CURRENT KNOWLEDGE AND KEY POINTS: Numerous anecdotal reports and some short series have shown the efficacy of interferon in some cases previously resistant to conventional therapy, particularly to immunosuppressors. Posology, depending on the author, may vary from three million three times a week to 18 million three times a week. Interferon alpha is useful in cases of ocular, muco-cutaneous and articular involvement. Data is lacking for digestive, vascular and neurological manifestations. FUTURE PROSPECTS AND PROJECTS: Multicenter trials will nevertheless be required to determine the duration of therapy, risk of relapses, associated therapy and the optimal time to commence interferon treatment.     

Atherosclerosis in Behçet's Syndrome

OBJECTIVES: We had the impression and preliminary evidence that atherosclerosis was not much increased in Beh?et's syndrome (BS). Thus, we evaluated the presence of subclinical atherosclerosis in a sizeable group of patients with BS both with major organ involvement and mucocutaneous disease along with diseased and healthy controls. METHODS: We studied 239 (162 M/ 77 F; mean age: 40.7+/-7.0) patients with BS. Seventy-two (32 M/ 40 F) had only mucocutaneous and/or joint disease and 167 (130 M/ 37 F) had major organ involvement. Also 100 (24 M/ 76 F; mean age: 44.7+/-7.1) patients with rheumatoid arthritis (RA), 74 (58 M/ 16 F; mean age: 39.4+/-7.0) patients with ankylosing spondylitis (AS) and 156 (83 M/ 73 F; mean age: 39.2+/-6.6) healthy controls (HC) were studied as the control groups. We used B-mode USG to assess the frequency of plaques and intima-media thickness (IMT) in the carotid and femoral arteries. Traditional atherosclerotic risk factors were also evaluated. Men and women were analyzed separately. RESULTS: The frequency of plaques and the mean IMT in the carotid and femoral arteries were similar between patients with BS, AS and HC and also between the 2 subgroups of BS, among both men and women. Only men with RA were found to have significantly increased frequency of carotid artery plaques after adjustment for atherosclerotic risk factors. CONCLUSION: Increased atherosclerosis is not a prominent feature of BS, even among those patients with major organ involvement.     

Behçet's syndrome and micro-organisms

Beh?et's syndrome (BS) is a multi-systemic vasculitis of unknown aetiology. More than one mechanism seems to be operative in the pathogenesis of Beh?et's syndrome, including genetic and environmental factors, causing different manifestations of the syndrome. There are several clues to the role of environmental factors and especially micro-organisms in the pathogenesis. These include clinical findings such as a decrease in the frequency of a positive pathergy reaction with surgical cleaning of the skin before the procedure, the acne-arthritis association carrying similar features to acne-associated reactive arthritis, a higher rate of tonsillectomy, cold sores, late birth order, higher number of siblings, history of travel to countries with a high incidence of BS and earlier age at first sexual intercourse. Moreover, basic research on both viruses and bacteria suggests that micro-organisms may be playing a role, possibly through heat shock proteins and T-cell hypersensitivity.     

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 syndrome: disease manifestations, management, and advances in treatment

The acne lesions characteristic of Beh?et's syndrome are not sterile and are commonly observed in combination with arthritis. The two main nodular skin lesions--superficial thrombophlebitis and erythema nodosum--are equally frequent, and rather difficult to distinguish. Superficial thrombophlebitis is usually observed in combination with thrombosis in large veins, and thrombosis of the large veins usually clusters with dural sinus thrombi, which make up approximately 20% of all central nervous system (CNS) lesions of Beh?et's syndrome. The remaining CNS lesions are parenchymal, mainly located in the brainstem, and associated with a graver prognosis than dural sinus thrombi. The presence of clinical clusters indicates that there are at least two pathogenetic pathways in Beh?et's syndrome: a reactive arthritis pathway and a thrombophilia pathway. Research into the pathogenesis of Beh?et's syndrome has shown that the most consistent genetic marker of Beh?et's syndrome is HLA-B51; however, the genetic association of this true-to-form 'complex' disorder with HLA-B51 is only 20%, and a whole-genome study showed associations with 16 different loci. The severity of Beh?et's syndrome and the mortality associated with it tend to decrease with time, and there is no associated increase in incidence of atherosclerosis. Although treatment of skin-mucosa manifestations, eye disease and pulmonary artery aneurysms has improved significantly in the past decades, the treatment of CNS lesions and thrombophilia are still problematic.     

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.     

Pulmonary embolism and Behçet's disease

Pulmonary embolism is an unusual complication of Beh?et's disease. Our aim study is to analyse epidemiological, physiopathological and evolutive aspects of this condition. Among 153 patients with Beh?et's disease according to the criteria of the International Study Group for Beh?et's disease, seven (5 men and 2 women mean aged at 26.6 +/- 6 years) were diagnosed as having pulmonary embolism. This was inaugural in 3 cases; for 2 females, pulmonary embolism complicated pregnancy. Cardiac thrombosis was presented in 2 cases and pulmonary aneurysm in 2 patients. Pulmonary infarction has been noted in 4 cases. Protein C, protein S and antithrombin III levels were normal in all cases. One patient was positive for IgG anticardiolipin antibody. The hyperhomocysteinemia has been noted (17 to 30 micromol/) in 5 cases. All our patients were treated successfully by anticoagulation therapy combined with high dose prednisone, colchicine and intravenous cyclophosphamide in 6 patients. Pulmonary embolism is one of the severe and worst prognostic manifestations of the disease. Furthermore, the hyperhomocysteinemia may play an important role in the pathogenesis of such complication. Immunomodulation therapy associated to folate may be beneficial to attenuate this hyperhomocysteinemia especially, when introduced in the early stages.     

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.