Familial Behçet’s disease

Behçet’s disease (BD) is a multisystemic vasculitis syndrome characterized by a course of remissions and exacerbations of unpredictable frequency and duration. The disease has a worldwide distribution, but the majority of cases cluster along the ancient Silk Road, which extends from eastern Asia to the Mediterranean basin. The etiopathogenesis of BD is still unknown, but familial aggregation and peculiar geographical distribution have been regarded as evidence supporting genetic influence on the pathogenesis of BD. In this article, we describe a patient with BD, who had four members of his family associated with BD.     

Diagnosis and management of intestinal Behçet’s disease

Behçet’s disease (BD) is a chronic relapsing disease with multiple organ system involvement characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. Little clinical evidence is available regarding the management of patients with intestinal BD, despite recognition that the presence of intestinal lesions is a poor prognostic factor, causing perforation and massive bleeding. Many recent case reports have suggested that anti-tumor necrosis factor alpha (TNF)α monoclonal antibodies (mAbs) are effective in patients with intestinal BD. Adalimumab, a fully human anti-TNFα mAb, has been approved in Japan for the treatment of intestinal BD. Here, we review the pathogenesis, diagnosis and management of intestinal BD, including evidence of the efficacy of anti-TNFα mAbs.     

Etanercept therapy in Behçet’s disease

Study objective

The goal of the present study was to investigate patient outcome when using the TNF receptor fusion protein etanercept in addition to conventional immunosuppressive drugs in ameliorating disease intensity and reducing relapses in refractory Behçet’s disease (BD).

Patients and methods

A single center, prospective study was conducted over 1 year. A total of 15 patients with the established diagnosis of BS were enrolled (mean age: 36.5?±?6.75 years, mean disease duration: 3.86?±?1.30 years). Clinical features were classified as refractory if the patients failed to achieve the desired response within 6 months of immunosuppressive and oral glucocorticoid therapy or flare of lesions developed while on the maximum tolerable doses of these drugs. The study included 2 patients who were on previous infliximab therapy for refractory disease. Inflammatory biomarkers (ESR and CRP) were investigated.

Results

Baseline clinical features in the study prior to inclusion showed recurrent oro-genital ulcers were observed in 100?% of patients, the pathergy test was positive in 17.6?%, ocular involvement was observed in 86.7?%, and acne lesions were recorded in 73.3?%. The following values were also recorded: mean ESR 22?±?16.97 mm/h, mean CRP level 6.87?±?4.44 mg/l, mean visual analog score 5.46?±?1.55, and mean patient global score 5.13?±?1.30. At the beginning of the study, all patients were on oral prednisolone (mean dose: 20.16?±?11.81 mg/day), azathioprine (mean dose: 126.66?±?25.81 mg/day), and oral colchicine (mean dose: 1.08?±?0.10 mg/day), then etanercept was added at a regular weekly dose of 50 mg subcutaneously for 1 year. By 8 weeks, 100?% of the patients achieve the primary endpoint, which included clinical resolution of refractory mucocutaneous, joint, and active ocular lesions with normalization of the acute phase symptoms.

Conclusion

Patients with refractory BD who received a 12-month treatment with etanercept in addition to conventional immunosuppressive therapy achieved a good therapeutic response with successful reduction of oral prednisolone to a mean dose of 6.66?±?2.24 mg/day. No serious infections or drug-related adverse events reported.     

Cardiovascular involvement in Behçet’s disease

Behçet’s disease is a chronic relapsing systemic vasculitis that can involve almost every organ and systems in the body with extremely different diverse manifestations. Cardiovascular involvement is one of these manifestations, the involvement of which might present in various patterns in itself. Cardiovascular involvement is relatively uncommon in Behçet’s disease; however, Behçet’s disease is relatively rather common in certain parts of the world. Therefore, especially in these locations recognizing such miscellaneous presentations are of critical importance, since cardiovascular involvements exceed other presentation in mortality and morbidity rates. Based on these facts, in this review, we summarized the cardiovascular involvements and its different manifestations in Behçet’s disease.     

Endothelial functions in Behçet’s disease

Behçets disease (BD) is a systemic vasculitis, capable of involving all types of vessels. Endothelial dysfunction (ED) has been previously documented in BD. The aim of the study was to see whether ED was more prominent in Behçets patients with vascular involvement (VI) than in those without. The study population consisted of 65 patients with BD, 27 of whom had VI, and 30 healthy controls. High-resolution ultrasound was used to measure endothelium-dependent vasodilatation (EDVD) of brachial artery. Overall, regardless of VI, EDVD was significantly impaired in patients with BD compared with controls (11.4±6.3 vs 20.4±9.1%,P=0.001); however, EDVD was similar in BD patients with and without VI (9.7±6.3% vs 12.6±6.1%, P=0.07). Patients with BD had significantly-higher plasma homocysteine levels than controls (13±6 mol/L vs 9±3 mol/L, P=0.001). Plasma homocysteine levels were significantly higher in the subgroup with VI than in those without (15±7 mol/L vs 12±4 mol/L, P=0.03); however, we found no positive/significant correlation between plasma homocysteine levels and EDVD. ED is a constant feature of BD, regardless of VI. Etiology of ED in BD is probably multifactorial, including high homocysteine levels. As both ED and elevated homocysteine levels may represent an early atherosclerotic process, a more structured approach to risk factor assessment is needed in BD.     

Serum amyloid-A in Behçet’s disease

Serum amyloid-A (SAA) is an acute phase protein, synthesized by the liver and previously investigated as a marker of disease activity in many rheumatologic disorders. Its significance in Behçet’s disease (BD), a chronic inflammatory disorder at the crossroad between autoimmune and autoinflammatory syndromes, is still unraveled. Our aim was to assess the role of SAA levels as a potential marker of disease activity in patients with BD. According to our findings, the occurrence of oral aphthosis, neurological impairment, and ocular disease is significantly associated with SAA serum levels higher than 30, 50, and 150 mg/L, respectively. We also suggest that increased SAA levels might identify a thrombotic risk in BD with previous or concurrent vascular involvement.     

Neuro-Behçet’s disease with chorea after remission of intestinal Behçet’s disease

Neuro-Behçets disease shows various neuropsychiatric symptoms, but chorea has rarely been reported. We report a case of neuro-Behçets disease in a 67-year-old woman with depression and chorea that occurred 22 years after the onset of intestinal Behçets disease. Brain magnetic resonance imaging (MRI) using a fluid-attenuated inversion-recovery (FLAIR) sequence demonstrated lesions more clearly than did T₂-weighted MRI. Some of the lesions appeared as small ring-like foci, i.e. low-intensity spots rimmed with remarkable hyperintense signals, in the periventricular white matter and basal ganglia. A review of the literature revealed that the onset of chorea in cases of Behçets disease varied from the time of onset of Behçets disease to 31 years after onset of the disease. Psychiatric manifestations have often been associated with neuro-Behçets disease. In the present patient, treatment with prednisolone resolved the chorea, suggesting that the chorea was caused by an autoimmune mechanism. It seems likely that the long-term development of vasculitis in patients with Behçets disease results in the formation of these particular brain lesions on FLAIR MR images. Chorea should be taken into consideration as one of the manifestations of Behçets disease, even many years after remission of the disease.Abbreviations ANCA Antineutrophil cytoplasmic antibodies - FLAIR Fluid-attenuated inversion-recovery - MRI Magnetic resonance imaging     

Smoking and Behçet’s Disease

It has recently been claimed that some of the symptoms in patients with Beh?et's disease (BD) can be activated after the patient has stopped smoking. In this study we investigated the effect of smoking on the symptoms of Beh?et's disease. Fifty asymptomatic current smokers (CS) who promised to stop smoking (group 1) and 60 current non-smokers (NS) (group 2) (21 of them ex-smokers) with BD were examined at the beginning and a week later for the presence of symptoms of BD. Forty-seven of the 50 CS completed the study. Oral aphthous ulcers were observed in 31 (65.9%) of them at the end of the study period. Besides oral aphthous lesions, genital ulcers were detected in two and erythema nodosum in two other patients. Only 15 (25%) group 2 patients developed oral aphthous ulcers during the study period. The difference between the frequencies of oral aphthous lesions in these groups was significant (p=0.0002). We concluded that cessation of cigarette smoking can activate the mucocutaneous symptoms, especially oral aphthous lesions, in patients with BD.     

Behçet’s Syndrome

Behçet’s syndrome is a systemic vasculitis with an unknown etiology affecting the small and large vessels of the venous and arterial systems. At least two clusters of disease expression have been described. The first includes superficial vein thrombosis, deep vein thrombosis, and dural sinus thrombi. The second includes acne, arthritis, and enthesitis. The presence of these clusters suggests there may be more than one disease mechanism operative in this complex disorder. Recent European League Against Rheumatism guidelines are useful for the management of the disease in organ systems distinct from the vascular, neurological, and gastrointestinal systems. This is because of a lack of controlled studies evaluating such vascular, neurological, and gastrointestinal complications.     

Behçet disease

Central nervous system involvement in Beh?et disease (BD) may be either parenchymal or nonparenchymal. Abnormal cerebrospinal fluid findings and parenchymal involvement are associated with a poorer prognosis. A self-antigenic role for HLA B51 has been postulated in the pathogenesis of BD. The sibling occurrence rate is 3.6%. Familial aggregation may be more pronounced among pediatric cases compared with adult cases. The importance of inherited coagulation abnormalities in the pathogenesis of BD is not clear. Vasculitis of the vasa vasorum seems to be the major site of pathology in large vessel disease. Even among experts, no consensus exists regarding the optimal approach to treatment. Low-dose thalidomide is effective for the mucocutaneous lesions, but polyneuropathy complicates its prolonged use. Neurologic side effects of cyclosporine A should preclude its use in patients with central nervous system involvement except in unusual circumstances. The heightened inflammatory response of BD patients to simple trauma may lead to postoperative complications, but should not be regarded as a contraindication to surgery.     

Behçet’s disease: Current therapeutic perspectives

Behcet's disease is a chronic relapsing systemic vasculitis of small and large vessels, of unknown etiology, characterized by recurrent oral and genital ulcers, and ocular inflammation. Other involved organs may include the joints, skin, and gastrointestinal tract, as well as the pulmonary, renal, central nervous, and the cardiovascular systems. The treatment of Behcet's disease is basically empiric, geared to control the symptoms, suppress the inflammatory process, and prevent organ damage. Thus, various anti-inflammatory and immunosuppressive agents have been used as the main therapeutic modalities, although none of them has been effective in controlling the diverse symptoms. Earlier, these drugs included colchicine, azathioprine, systemic corticosteroids, dapsone, cyclosporine A, and tacrolimus. Recently emerging studies show the effectiveness of thalidomide, interferon alpha, interferon gamma, acyclovir, low-dose weekly methotrexate, cyclophosphamide pulse therapy, and anti-tumor necrosis factor (TNF) therapy. Anti-TNF agents, such as infliximab, are emerging as being effective in rapid control of sight-threatening panuveitis and cerebral vasculitis, as well as in orogenital ulcerations, gastrointestinal disease, and skin lesions of Behcet's disease. Limited anecdotal case reports have been published with the use of the fusion protein etanercept in Behcet's disease. Hopefully, prospective clinical trials, which are now ongoing, will provide more data as to the efficacy of the anti-TNF agents, compared with the conventional immunosuppressive therapy.     

Increased sucrose permeability in Behçet’s disease

Behçets disease (BD) is a chronic, relapsing, systemic vasculitis with unknown etiology. During the progression of the disease, gastrointestinal involvement can be observed. The aim of this study was to find out the predictive value of the sucrose permeability test in detecting gastrointestinal mucosal damage in BD. Twenty-six male Behçets patients and 21 age- and sex-matched controls were enrolled in the study. Seventeen patients had active disease, while nine did not. Active disease was defined as having elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels or at least two of the diagnostic criteria in the previous month. Patients and controls were investigated with the upper gastrointestinal permeability test. Of all the patients, 25 were investigated endoscopically. The urine sucrose levels were significantly higher in patients than in the control group (P=0.0001) and in patients with active disease than those with inactive disease (P<0.0001), while urine sucrose of patients with inactive disease and the control group did not differ. The endoscopic findings were not specific to BD. Active and inactive BD had similar endoscopic findings. Increased upper gastrointestinal permeability was established in patients with BD. This increased permeability was not related to a specific gastrointestinal BD lesion. Further studies with larger series must be performed in order to determine the value of the sucrose permeability test in detecting mucosal involvement in BD.     

Neonatal Behçet’s disease without maternal history

A neonate presented with frequent vomiting since 10 days old, followed by severe diarrhea. Multiple oral ulcers and recurrent genital ulcers subsequently appeared. Colonoscopy showed multiple shallow round ulcerations in the colon. The symptoms responded well to a short course of oral prednisolone. There was a brief recurrence of vomiting, diarrhea, and oral ulcers at 2 months old. The mother has never had any symptoms of Behçet's disease to date. This is the first reported case in literature of neonatal Behçet's disease without a maternal history of Behçet's disease, which raises doubts about the assumed role of maternal antibodies in the pathogenesis of neonatal Behçet's disease. A literature review of neonatal Behçet's disease shows that oral ulcers, skin lesions, fever, and leukocytosis are common features. However, only half of the patients fulfill the classical diagnostic criteria based on adult studies. A treatment consensus for neonatal cases is also lacking.     

Pulmonary artery aneurysms in Behçet’s disease

Behçet’s disease is the most common cause of pulmonary artery aneurysms. Pulmonary artery aneurysms are rare, but they are life-threatening because of their high tendency to rupture. However, there is also a chance that the aneurysms may completely resolve with immunosuppressive therapy. A 30-year-old man was admitted with chest pain, painful oral and genital ulcers, skin rash, weakness, and intermittent hemoptysis. He had a history of Behçet’s disease for 6 years. The chest radiography showed a round opacity superior part of hilus on right. The helical thoracic computed tomography (CT) angiography demonstrated pulmonary aneurysms associated with Behçet’s disease. The patient was successfully treated with colchicine, corticosteroids, and cyclophosphamide. A discussion about pulmonary artery aneurysms associated with Behçet’s disease is provided in this case.     

Recurrent meningitis revealing a Behçet’s disease

The aim of the present study was to describe a case of Behçet’s disease revealed by a recurrent meningitis and to review literature on these two conditions. We describe the case of a 25-year-old man who presented four episodes of recurrent meningitis without any locoregional cause and developed oral and genital ulcerations few months later. Behçet’s disease is a chronic, multisystemic disorder with variable prevalence in different geographical areas. Its neurological manifestations are well recognized. Both central and peripheral nervous systems can be involved. Recurrent meningitis in Behçet’s disease is exceptional. To our knowledge, only two cases reported recurrent meningitis as initial manifestation of Behçet’s disease. This case report underscores another facet of neurological manifestations of Behçet’s disease.     

Coexisting Behçet’s Syndrome and Spondyloarthritis

A patient suffering from Beh?et's syndrome and undifferentiated spondyloarthritis developed dactylitis and psoriasis over the next three years.