Berberine exerts an anti-inflammatory role in ocular Behcet's disease.

Behcet's disease is a multi­system inflammatory disorder, and ocular Behcet's disease (OBD) is one of the most common causes of uveitis in China. A number of studies have indicated that Th17 cells, a subset of interleukin-17 (IL-17)-producing CD4+ T­helper cells, serve important roles in the pathogenesis of OBD. Berberine (BBR) is an isoquinoline derivative alkaloid isolated from Chinese herbs, and has been used traditionally for the treatment of gastrointestinal disorders. The aim of the present study was to investigate the effect of BBR on Th17 cell proliferation and cytokine secretion, and the expression and activation of the signal transducer and activator of transcription 3 (STAT3) transcription factor in OBD in vitro. Blood samples were obtained from healthy controls and patients with active ocular Behcet's disease. Peripheral blood mononuclear cells (PBMCs) or CD4+ T cells were cultured for three days with or without BBR and in the presence of anti­CD3 and anti­CD28 antibodies. IL­17 expression in cell sample supernatants was determined by enzyme­linked immunosorbent assay, and cell viability was measured using the Cell Counting kit­8 assay. The number of CD4+IL­17+ cells and the expression level of phosphorylated (p)­STAT3 in CD4+ T cells was determined using flow cytometry analysis. The expression of IL­17 was increased in patients with active OBD following the activation of PBMCs and CD4+ T cells with anti­CD3 and anti­CD28 antibodies when compared with healthy controls. However, no significant difference in cell viability following exposure to BBR was observed in PBMCs derived from healthy controls or patients with OBD. Following incubation with BBR, the expression of IL­17 was reduced and the number of CD4+IL­17+ cells was decreased in patients with active OBD and healthy controls. Furthermore, the expression of p-STAT3 was significantly decreased in the presence of BBR in healthy controls. In conclusion, the results of the present study demonstrate that BBR may suppress the Th17 response in patients with OBD by reducing STAT3 phosphorylation. BBR may be a potential therapeutic agent for the treatment of OBD.

Overlooked Management and Risk Factors for Anemia in Patients with Intestinal Behçet's Disease in Actual Clinical Practice.

BACKGROUND/AIMS: Anemia in patients with inflammatory bowel disease significantly affects the quality of life. The aim of this study was to investigate the frequency of and risk factors for anemia and to describe the management of anemia in patients with intestinal Behçet's disease (BD) in actual clinical practice. METHODS: We included 64 patients with intestinal BD who visited the outpatient clinic of a tertiary referral center in June 2011 and had available laboratory data for the subsequent 6 months. RESULTS: Anemia was detected in 26 patients (40.6%). After 6 months, anemia was still present in 14 of these patients (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral iron supplementation was prescribed to four patients (15.4%). Of these four patients, two (50%) recovered completely within 6 months. Anemia was associated with a high Disease Activity Index for Intestinal Behçet's Disease (DAIBD, p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive for anemia in patients with intestinal BD was a higher DAIBD (≥40; odds ratio, 4.08; 95% confidence interval, 1.21 to 13.71; p=0.023). CONCLUSIONS: Although anemia is common in intestinal BD patients, its clinical importance is overlooked in daily practice. Moderate to severe disease activity is predictive of anemia.

Biotherapies in Behçet's disease.

Behçet's disease (BD) is a systemic large-vessel vasculitis characterized by a wide clinical spectrum including recurrent oral and genital ulcerations, uveitis, vascular, neurological, articular, renal and gastrointestinal manifestations. Therapeutic management of BD depends on the clinical presentation and organ involved. Although colchicine, nonsteroidal antiinflammatory agents and topical treatments with corticosteroids are often sufficient for mucocutaneous and joint involvements, more aggressive approach with immunosuppressive agents is warranted for severe manifestations such as posterior uveitis, retinal vasculitis, vascular, and neurological and gastrointestinal involvements. However, some patients still have refractory disease, relapse, sight threatening eye disease, or irreversible organ damage. Recent improvements in the understanding of the pathogenic mechanisms have led to the identification of potential targets and future biological therapies for BD. In contrast to current non-specific immunosuppressive agents, the emergence of biotherapies provides the possibility of interfering with specific pathogenic pathways. Novel targeted biotherapies might be used in the future for BD.

Study of the correlation of serum selenium level with Behcet's disease.

BACKGROUND: Selenium, like other trace elements and antioxidant enzymes, is known as an antioxidant and immunomodulator trace element. Due to recent evidence for selenium deficiency in Behcet's syndrome, this study is to evaluate the correlation of serum selenium level with Behcet's disease (BD). MATERIALS: This case-control study was conducted on 46 BD patients and 46 healthy controls in a rheumatology research centre. The case and control groups were both age- and race-matched. Serum selenium level was then measured by atomic absorption spectrometry Shimadzu AA-680. Average serum levels of both groups were then compared and analyzed using t-test. RESULTS: Mean serum selenium levels of patients appeared to be 66.4 ± 15.38 µg/L which was significantly lower than that in the healthy controls (86.87 ± 17.18 µg/L) (P < 0.005). Taking physician global assessment of disease activity into account, significant difference was detected between the patients with active disease (66.57 ± 15.21 µg/L) and those in the inactive state (65.83 ± .75 µg/L). Regardless of the findings mentioned above, serum selenium level was meaningfully elevated among the patients with ocular involvement (P < 0.001). CONCLUSIONS: These findings demonstrated that selenium serum level among BD patients was lower than that in healthy controls, whereas among the patients with ocular involvement it was higher than those not involved.

[NeuroBehcet disease with corpus callosum involvement]. / Neuro-Behçet avec atteinte du corps calleux.

INTRODUCTION: Behçet's disease is a multi-system vascular-inflammatory disease with possible involvement of the central nervous system. Lesions of the corpus callosum on MRI have been rarely reported in this disease. CASE REPORT: A 47-year-old woman was admitted for a sudden right hemiplegia and confusion revealing a Behcet's disease. MRI showed a pedonculo-thalamic lesion and a white matter hypersignals, which was suggestive of the disease. Besides, involvement of the corpus callosum was observed. CONCLUSION: This case demonstrates that Behcet's disease should be considered among diseases with corpus callosum involvement.

Behçet syndrome.

We present a 34-year-old man with a two-year history of aphthous stomatitis, who later developed painful, erythematous nodules on his lower extremities. A pathergy test was positive, and the diagnosis of Behçet syndrome (BS) was made. It is important for the dermatologist to recognize the wide variety of cutaneous manifestations of this disorder. A pathergy test is a simple diagnostic tool that may assist in making a diagnosis. Case reports of other unusual skin manifestations in BS also are reviewed.

Clinicopathologic features and outcomes of neuro-Behçet disease in Spain: a study of 20 patients.

BACKGROUND: To describe the clinical characteristics and evolution of a series of adult patients hospitalized for neuro-Behçet disease (NBD). METHODS: Consecutive patients admitted for NBD in a teaching hospital were retrospectively selected. Disability at discharge and during follow-up was graded with the modified Rankin Scale, and outcome classified as good or poor (grades 3-6). RESULTS: Twenty patients were included (M/F, 13/7). Mean age at NBD diagnosis was 36.3 years. Nineteen patients had other manifestations of Behçet disease (BD) before NBD developed, but only 7 met the complete diagnostic criteria for BD. Fever, headache, motor weakness, and cranial nerve palsy were each present in approximately 60% of patients. There was a low prevalence of behavioral changes (5%), seizures (5%), and sphincter incontinence (0%), and a relatively high prevalence of meningism (25%). Non-neurologic manifestations of BD were concurrently detected in 15 patients (75%). 80% had parenchymal involvement. Brain biopsies during 5 attacks showed perivascular lymphocytic infiltration with reactive astrocytosis, but no frank vasculitis. During a mean follow-up of 6.3 years per patient, 12 had at least one relapse. In total, there were 22 relapses; all but two were in the same location and were symptomatically similar in each patient. At the end of follow-up, 7 patients (35%) had a poor outcome, including 4 who died. CONCLUSION: Recording of previous manifestations of BD and a physical examination to detect concomitant systemic manifestations of BD may help establish an early diagnosis of NBD. Relapses frequently occurred in the same location. No frank vasculitis was present in brain biopsies.

[Déjerine-Roussy syndrome of an ischaemic origin in an adolescent with patent foramen ovale]. / Síndrome de Déjerine-Roussy de origen isquémico en un adolescente con foramen oval permeable.

INTRODUCTION: Déjerine-Roussy syndrome, or thalamic syndrome, is characterised by transient mild hemiparesis, hemichoreoathetosis, hemihypoesthesia, hyperalgesia, allodynia and hemiataxia with astereognosia that varies in intensity, and it appears in the presence of lesions in the posterior nuclei of the thalamus. It can be produced by strategic cerebral infarction, reported in elderly patients with vascular risk factors. Patent foramen ovale has been suggested as a risk factor for ischaemic stroke in young people, especially when associated to aneurysm of the auricular septum and above all to a procoagulating status. CASE REPORT: An 18-year-old male with a family history of Behçet's disease, who presented right-side thalamic and hippocampal cerebral infarction; following an exhaustive study, patent foramen ovale with septal aneurysm was found as the only risk factor. At that time he did not satisfy criteria for Behçet's disease, and thorough systemic screening did not reveal direct or indirect signs of venous thrombosis. Percutaneous closure of the foramen was performed. CONCLUSIONS: This is the first reported case of Déjerine-Roussy syndrome as a manifestation of cryptogenic cerebral infarction associated to patent foramen ovale in an adolescent. Taken as a whole, the clinical and complementary data enable us to reconstruct the pathophysiological sequence that position foramen ovale with an associated septal 'aneurysm' as the only detectable risk factor, which, when linked to the stress of the patient and the family, triggered its early closure.

Monozygotic twins concordant for intestinal Behçet's disease.

Although Behçet's disease (BD) is a multisystem disorder of unknown causes, both genetic and environmental factors have been suggested. This is the second reported case of monozygotic twins concordant for Behçet's disease and the first such report of intestinal Behçet's disease. Patient 1 was a 17-year-old man with fever, recurrent oral aphthae, and skin eruptions. He developed hematochezia and was given corticosteroid empirically. One month after he was discharged, he again developed oral ulcerations, fever, and hematochezia. Colonoscopy was performed again, showing aphthous ulcerations in the entire colon, and deep oval ulcers with marginal elevation around the ileocecal valve, which are characteristics of intestinal Behçet's disease. He was treated with colchicine and azathioprine in combination with salazosulfapyridine (SASP) and prednisolone (PSL) and achieved remission. Patient 2 was the twin brother of patient 1. He was admitted because of oral aphthous ulcerations, fever, pustules on his face and body, and genital ulcers. Two weeks later he developed hematochezia. Colonoscopic and barium enema findings were similar to those of his brother. SASP, PSL, colchicines, and azathioprine were also required to achieve remission. Both of the patients were diagnosed with intestinal Behçet's disease. Their monozygosity was confirmed by detailed genetic typing, and HLA-B51 was negative.

Radiologic findings of Behçet syndrome involving the gastrointestinal tract.

Behçet syndrome is characterized by the histopathologic finding of nonspecific vasculitis in multiple organs. The diagnosis is usually made on the basis of the combination of clinical signs and symptoms. This disease involves the gastrointestinal tract in 10%-50% of patients, and the terminal ileum and cecum are chiefly affected. Barium study is useful in demonstrating the characteristic radiographic features of Behçet syndrome involving the gastrointestinal tract. The presence of deep, penetrating ulcers results in a high rate of complications, such as perforation, fistula, hemorrhage, and peritonitis. Furthermore, recurrence of disease adjacent to or at the surgical anastomosis is common. Computed tomography is useful in determining the extent of the lesions and in identifying cases in which complications are likely to occur. Familiarity with the various radiologic findings of Behçet syndrome involving the gastrointestinal tract helps in making an early diagnosis, as well as in establishing an appropriate treatment strategy.

Prediction of the clinical course of Behçet's colitis according to macroscopic classification by colonoscopy.

BACKGROUND AND STUDY AIMS: The lesions in Behçet's colitis show aphthoid or punched-out ulceration, but the macroscopic types of lesion found have not been defined. To predict the clinical outcome in patients with Behçet's colitis according to the colonoscopic findings, we classified the characteristic colonic ulcers, evaluated the efficacy of medical treatment on colonoscopic lesions, and calculated the operation rates and recurrence rates relative to the macroscopic types. PATIENTS AND METHODS: The medical records and colonoscopic photographs of 50 patients with Behçet's colitis were reviewed. The colonic lesions were examined by colonoscopy in patients with Behçet's disease and gastrointestinal symptoms. The colonoscopic findings were categorized into three types of ulceration: volcano-like, geographic, and aphthous. The efficacy of medical treatment was assessed by follow-up colonoscopy or double-contrast barium enema four to eight weeks after treatment, and recurrence of the lesions was evaluated during the follow-up periods. Cumulative surgery rates were obtained using the Kaplan-Meier method. RESULTS: The macroscopic classification of colonic ulcers identified 25 of 50 patients (50%) with volcano-type lesions, 11 (22%) with the geographic type, and 14 (28%) with the aphthous type. The rates of complete remission after medical treatment and surgery, respectively, were six of 25 (24%) and 13 of 25 (52%) with volcano-type ulcerations; eight of 11 (73%) and one of 11 (9%) with the geographic type; and nine of 14 (64%) and two of 14 (14%) with the aphthous type. The endoscopic and clinical recurrence rates were nine of 19 (47%) in volcano-type ulcerations, one of nine (11%) in the geographic type, and one of 11 (9%) in the aphthous type. CONCLUSION: Volcano-type ulcerations in Behçet's colitis showed a less favorable response to medical treatment, a more frequent requirement for surgery, and more frequent recurrences than the geographic and aphthous types of ulcerations.

Neuro-Behçet's disease.

We are reporting a case of Behçet's disease without vasculitis, but with acute neutrophilic inflammation which involved the brain and other organs. The patient exhibited waxing and waning neurological deficits which were unresponsive to treatment. The neuroradiologic findings simulated those of multiple sclerosis. The neuropathological examination revealed an acute, focal, though disseminated encephalitis involving the frontal lobe, internal capsule, basal ganglia, cerebellum, and brain stem. The acute inflammation consisted of a neutrophilic and eosinophilic infiltration of the perivascular spaces and parenchyma without evidence of vasculitis, fibrinoid necrosis, or thrombosis. Cultures and special stains for microbial organisms were negative. Ultrastructural examination revealed no viral structures or other microorganisms. In situ hybridization for Epstein-Barr virus (EBV), herpes simplex virus type I (HSVI), and cytomegalovirus (CMV) was negative. In this case, the lack of inflammation in the vessel walls points out that the necrotizing lesions in neuro-Behçet's disease need not be the result of vasculitis and superimposed thrombosis, but may occur as a result of primary, acute neutrophilic inflammation.

Crohn's disease with Behçet's syndrome like appearance: a case report.

The differential diagnosis of Behçet's syndrome or Crohn's disease can be extremely difficult. In this case report we present a 32-year old female patient with Crohn's disease. The coexisting extraintestinal symptoms such as mucocutaneous apthous lesions of the mouth and vulva, the erythema nodosa of the lower extremities and recurrent arthralgias made the correct diagnosis even more difficult. The patient was treated with a combination of systemic corticosteroids and azulfidine enema, under which she recovered.

Behçet's disease. Relation of serum C-reactive protein and erythrocyte sedimentation rates to disease activity.

In a prospective study of 150 patients with Behçet's disease, significant associations were shown between CRP positivity and the presence of erythema nodosum (p less than 0.02) and acute thrombophlebitis (p less than 0.05) and between ESR and erythema nodosum (p less than 0.01), acute thrombophlebitis (p less than 0.001), and acute arthritis (p less than 0.01). Mucocutaneous, ocular, or central nervous system activities did not show significant associations with these indices of inflammation. In 50 patients in whom quantitative CRP determinations were performed, clinical disease activity was accompanied by slight to moderate increases in CRP and ESR.

Behçet's syndrome in a family with inflammatory bowel disease.

Although the gastrointestinal and systemic features of Behcet's syndrome and inflammatory bowel disease overlap to a considerable extent, they are generally viewed as two distinct diseases. We evaluated three members of a family who have inflammatory bowel lesions, two of whom met criteria for Behcet's syndrome. The propositus had classic features of both Crohn's ileocolitis and Behcet's syndrome. A daughter, who never met criteria for Behcet's syndrome, had undergone colectomy for ulcerative colitis. A second daughter had classic features of Behcet's syndrome, including recurrent episodes of colitis with distinct aphthous ulcers in the colon. The findings in this family suggest that inflammatory bowel disease and Behcet's syndrome may be closely related and part of a spectrum of disease rather than distinct disease entities.

Behçet syndrome with "aphthous colitis".

A 46-year-old man with Behçet syndrome and a long history of recurrent bouts of colitis was studied by sigmoidoscopy, barium enema x-ray film, and colon biopsy. A nonspecific colitis characterized by shallow mucosal ulcerations and submucosal mononuclear infiltration in the absence of meaningful roentgenolographic changes was seen. A histopathological comparison was made between the oral and colonic lesions. The aphthous colitis appears, therefore, to be a colonic manifestation of Behçet syndrome, differing from typical chronic nonspecific ulcerative colitis in terms of clinical course, severity, and histologic appearance. The simultaneous occurrence of Behçet syndrome and inflammatory disease of the colon was discussed in terms of the differential diagnosis of colitis.