Behçet's disease

Clinicopathologically, Beh?et's disease is characterized by neutrophil and platlet hyperfunction. Lesions are formed presumably because neutrophils infiltrating the affected tissue release active oxygen and lysosomal enzymes in large amounts. The mechanisms of neutrophil hyperfunction was obscure, but in recent years attention has focused on the effects of cytokines released by mononuclear cells. As more has been learned about the etiopathogenesis of Beh?et's disease, novel anti-inflammatory drugs, immunosuppressants, anti-thrombotic agents, and anticoagulants have helped to achieve remarkable progress of treatment. Particularly notable is the effect on severe uveitis of cyclosporine, which is more effective than colchicine and conventional immunosuppressants. Low dose weekly methotrexate therapy might have a beneficial effect in the treatment of patients with neuro-Beh?et's disease.     

Behçet's disease

Questions from patients about analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topic addressed in this issue is Beh?et's disease (BD), a chronic inflammatory, vascular, and/or autoimmune disease affecting the entire body, and discussion of symptoms, course of disease, treatments, prognosis, and quality of life.     

Headache in Behçet's disease

The aim of this study was to investigate the characteristics of headache in patients with Beh?et's disease (BD) seeking neurological consultation. Consecutive patients with BD seen within 1 year at the neuro-Beh?et's out-patient clinic were studied using an electronic database according to the classification criteria of the International Headache Society. During a 12-month period 118 BD patients were admitted, and 98 had headaches. Migraine was the most common type of primary headache diagnosed in 45 patients (46.4%) in the whole headache group, followed by tension-type headache (TTH) in 26 cases (26.8%). Thirty-seven patients had secondary headaches mainly due to cerebral venous thrombosis or parenchymal neurological involvement of BD. Of these patients, 15 had both primary and secondary headaches. The primary headaches of 13 patients were exacerbated with systemic BD flare-ups, and four patients had migraine attacks triggered only by systemic BD activation which showed a good response to the treatment of systemic inflammation. The majority of the headaches of patients with BD do not indicate any neurological involvement; they are usually due to migraine or TTH. In a minority of patients, migraine associated with systemic inflammation of BD is notable.     

Increased serum ferritin levels in active Behçet's disease

There is no routine test to evaluate the activity of Behçet's disease (BD). Ferritin as a serum predictor of iron storage is an important acute phase reactant. In this study, we assessed serum ferritin levels in patients with active BD and compared them with those of patients with inactive BD. We aimed to show the relationship between ferritin and BD. The patients with BD were subdivided into two groups according to disease activity: active (24 patients; 18 men and 6 women, average age 36.5 ± 4.9 [28–45] years), and inactive (20 patients; 16 men and 4 women, average age 37.2 ± 5.2 [30–49] years). Twenty healthy volunteers (15 men and 5 women; average age 38.2 ± 4.6 [30–47] years) served as controls. Patients with active BD had significantly higher serum ferritin levels (p=0.0001) than the inactive and control groups. Ferritin levels in patients with inactive BD did not differ significantly from healthy control subjects (p=0.687). We concluded that in patients with active BD, serum ferritin levels are increased and do not reflect serum iron levels.     

Prevalence of headache in patients with Behçet's disease without overt neurological involvement

The aims of the present study were to evaluate the prevalence of headache and the frequency of different headache syndromes in patients with Beh?et's Disease (BD) without neurological involvement and to investigate the relationship with other clinical, and behavioural variables. Twenty-seven BD patients and 27 control subjects underwent a validated semistructured questionnaire based on the International Headache Society criteria. Levels of anxiety and depression, disease activity, and current medication were collected. Headache occurred in 88.9% of BD patients. There was no difference in the prevalence of the different headache syndromes between BD patients and controls. Only migraine without aura (MwA) was significantly more frequent in BD patients than controls (44.4% vs. 11.1%, respectively, P= 0.013). No relationship was found between MwA and clinical, and behavioural variables. Among headache syndromes, MwA showed the highest frequency in BD. A vascular or neuronal subclinical dysfunction could justify this association. A careful interview for migraine might be included in the diagnostic work-up of BD.     

Lipid peroxidation and erythrocyte antioxidant enzymes in patients with Behçet's disease

In spite of unknown etiology, it is now accepted that reactive oxygen species (ROS) produced by neutrophils may be related to the pathogenesis of Beh?et's Disease (BD). The objective was to investigate whether increased production of ROS may affect erythrocyte oxidant/antioxidant system in patients with BD. The levels of malondialdehyde (MDA), one of the end products of lipid peroxidation, in plasma and erythrocyte, and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), antioxidant enzymes, in erythrocyte, also C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in 22 patients in active stage of the disease and also in 30 healthy controls. Increased CRP, ESR, and MDA levels in plasma and erythrocyte and increased SOD but decreased GSH-Px activities in erythrocytes were observed in the patients, when compared to the controls. In addition, significantly positive correlations between plasma and erythrocyte MDA levels, and erythrocyte MDA-CRP, MDA-ESR, MDA-SOD, SOD-ESR and SOD-CRP levels, but negative correlation between plasma MDA and erythrocyte GSH-Px, were found in BD patients. It may be suggested that increased production of ROS in BD, as reflected by higher plasma and erythrocyte MDA levels, may impair erythrocyte membrane integrity and also may lead to the alterations in the erythrocyte antioxidant defense system, as reflected by higher SOD and lower GSH-Px activities in erythrocytes.     

Serum E-selectin and beta 2-microglobulin levels in Behçet's disease

Beh?et's disease is a systemic vasculitis of unknown aetiology. Endothelial cell injury plays an important role in the pathogenesis and immunopathology of systemic vasculitises, but an immunopathogenic basis is also probable in Beh?et's disease. E-selectin is an indicator of endothelial injury, and beta 2-microglobulin (beta 2M) is increased in immunological disorders. The serum concentrations of these two markers were determined in 40 patients with active Beh?et's disease and 40 healthy controls. E-selectin was determined by enzyme-linked immunosorbent assay and beta 2M was determined by the nephelometric method. The mean (+/- SD) serum concentration of E-selectin was 122.13 +/- 62.32 ng/ml and that of beta 2M was 0.31 +/- 0.05 mg/dl. Both concentrations were statistically significantly increased in patients with Beh?et's disease compared with controls. More comprehensive studies are needed to determine whether these parameters are useful indicators of the activity of Beh?et's disease.     

Treatment of recurrent perforating intestinal ulcers with thalidomide in Behçet's disease

OBJECTIVE: To report the beneficial effects of thalidomide on recurrent perforating intestinal ulcers in a patient with Beh?et's disease (BD). CASE SUMMARY: A 24-year-old Turkish woman with BD was admitted to our hospital because of severe abdominal pain and vomiting. She had been receiving colchicine 1.5 mg/day and azathioprine 150 mg/day for treatment of BD for 2 years. During emergency laparatomy, 2 perforating ulcers were detected in the anterior cecum, which were treated with debridement and primary repair. She experienced 2 more episodes of intestinal perforations during the second and fifth weeks despite intense immunosuppressive treatment with methylprednisolone and cyclophosphamide. New intestinal perforations were found in the posterolateral cecum and transverse colon during the second operation and in the terminal ileum during the third one. Thalidomide 100 mg/day was then started, and the symptoms disappeared within 2 weeks. The woman experienced no other intestinal perforation during the follow-up period of 4 months. DISCUSSION: The mode of action of thalidomide in BD is still unclear. In BD, various cytokines have been shown to be abnormally expressed and neutrophils are overactive. This is a possible mechanism of action with thalidomide reducing both tumor necrosis factor and the neutrophil migration. CONCLUSIONS: Thalidomide may be an effective alternative treatment for BD patients with recurrent and perforating intestinal ulcers despite intense immunosuppressive therapy.     

Restless legs syndrome in Behçet's disease

The prevalence of restless legs syndrome (RLS) and its association with the clinical features of Beh?et's disease (BD) has not previously been elucidated. The inflammatory character, central nervous system involvement and neuropathies of BD led to this investigation of RLS risk in BD patients. A total of 116 BD patients and 104 healthy control subjects were included; seven BD patients were excluded because of concurrent diseases, pregnancy or alcohol misuse that might cause RLS symptoms, and the remaining 109 BD patients were included in the analysis. The prevalence of RLS was significantly higher in patients with BD (32/109; 29.4%) than in controls (5/104; 4.8%). No significant differences were found between BD patients with and without RLS with regard to the clinical features of BD. RLS severity positively correlated with age in BD patients. In conclusion, BD-related RLS should be considered in symptomatic RLS secondary to rheumatological disorders and BD patients should be examined for RLS. Further studies are needed to clarify the pathogenetic mechanisms underlying BD-related RLS.     

The prevalence and characteristics of different types of headache in patients with Behçet's disease, a case-control study

Background.— Headache is one of the most common neurologic symptoms of Behçet's disease (BD) that may be due to migraine, tension‐type headache, uveitis, or direct consequence of neuro‐Behçet's disease (NBD) or other causes. Objective.— To study the prevalence and characteristics of different types of headache in patients with BD. Method.— Subjects were recruited as consecutive patients who referred to Behçet's Clinic at the Nemazee Hospital, Shiraz, Southern Iran, from March 2004 to March 2006. All patients fulfilled the International Study Group criteria for BD. Each patient was interviewed for history of BD and headache. Neurological examinations and, if necessary, ancillary investigations were performed for each patient. Control group was an age‐ and sex‐matched population. Headache entities fulfilled the International Headache Society criteria. Results.— In total, 35% (63/180) of patients had no headache. Migraine with and without aura was the cause of headache in 1.7% (3/180) and 25.6% (46/180) of patients, respectively. Tension‐type headache was found in 23.9% (43/180) of patients. In 8.3% (15/180) of patients, headache could be justified by NBD. Headache due to uveitis was observed in 3.3% (6/180) of patients and 4 patients (2.2%) had other causes of headache. Migraine was significantly more common in patients than the control group (OR: 2.9, P < .0001). Considering the effect of gender, migraine was also significantly more frequent in patients than in the control group both in females (OR: 3.1, P < .0001) and males (OR: 3.2, P = .006). Conclusion.— Migraine and tension‐type headaches are the most prevalent types of headaches in Behçet's patients. NBD must be meticulously investigated in patients with BD who presented with headache.     

Current therapy for Behçet's disease

Classified among the vasculitides, the clinical spectrum of Beh?et's disease (BD) ranges from a mild mucocutaneous disease to a life-threatening systemic vasculitis, characterized by remissions and recurrences. The major morbidity is recurrent eye inflammation that may lead to blindness, but severe central nervous system, gastrointestinal, or vascular involvement may occur and might be fatal. In contradistinction to most other vasculitides, the venous system is commonly affected in BD. The treatment of BD is usually symptomatic and palliative. This includes topical steroids for orogenital ulcers, nonsteroidal antiinflammatory agents for joint involvement, and colchicine as prophylaxis against disease flares (although evidence that colchicine prevents recurrences of oral and genital ulcers is restricted to female patients). Immunosuppressives and cytotoxic agents are used for more severe involvement, and thalidomide and interferon have attracted attention in recent years.     

Headache in Behçet's syndrome

OBJECTIVE: To study the frequencies and characteristics of different headache types seen in patients with Beh?et's syndrome (BS) in a large cohort of patients. BACKGROUND: Patients with BS may present with different neurological problems, related either directly or indirectly to the disease, with headache being the most common neurological symptom seen in this syndrome, as well as independent from neurologic involvement. METHOD: This study was carried out at the multidisciplinary Beh?et outpatient clinic of the Beh?et's Syndrome Research Center. Every fifth admitted patient who had fulfilled the International Study Group for Beh?et's Disease classification criteria was recruited for this study. Each patient was interviewed by one of the examining neurologists through a semistructured questionnaire. In case of the presence of more than one headache type, the best defined one was diagnosed and evaluated. All patients received a complete neurological and physical examination. A chi(2) test was used to evaluate the differences between frequencies. One sample t-test was used to compare means. The prevalence rates of primary headaches were compared with results of the Turkish Headache Epidemiology study by using goodness-of-fit test. RESULTS: Two hundred and twenty-eight patients were studied. Headache was reported in 66.2% (151/228) of the study cohort. Primary headaches were seen in 38.6% of the patient population, which corresponds to 58% of BS patients with any type of headache. Tension-type headache (TTHA) and migraine were seen in 23.6% and 14.9% of the whole study cohort, respectively. In 5.2% of the study cohort, the headache was associated with neurological involvement and in 3.9% to uveal inflammation. A predominantly frontal, bilateral paroxysmal throbbing pain of moderate severity was reported in 18.4% of the study cohort who did not fulfill the criteria of the International Headache Society (IHS) for any of the primary headaches. It was commonly associated with exacerbations of the mucocutaneous symptoms of the syndrome. The neurological examination was normal in all of these patients. This type of headache was categorized as the nonstructural headache of Beh?et. CONCLUSION: Headache is the most common neurological symptom seen in BS, both in patients with and without neurological involvement. The results of our study reveal that headache is seen in a majority of patients with neurological involvement due to BS and in a minority with uveal inflammation. The prevalence of migraine and TTHA are close to the population in general, but a nonstructural migrainous headache, which is commonly associated with exacerbations with some of the systemic symptoms of the syndrome, is noteworthy in patients with BS. This form of headache is not specific for this disorder, but may be explained by a vascular headache triggered by the immunomediated disease activity in susceptible individuals.     

Impaired endothelium-dependent flow-mediated dilation in Behçet's disease: more prominent endothelial dysfunction in patients with vascular involvement

Brachial artery endothelial dysfunction was shown previously in a small group of Behçet's disease (BD) patients. This study aimed to compare the endothelial function in BD patients with and without vascular involvement. The study group consisted of 25 BD patients with vascular involvement, 25 BD patients without any vascular disease and 46 healthy controls. Brachial artery flow‐mediated (endothelium‐dependent) dilation (FMD), nitroglycerine‐induced dilation and carotid artery intima‐media thickness were measured. FMD was impaired in patients with BD (10.41 ± 3.85%) compared to healthy controls (14.41 ± 3.39%, p < 0.001). FMD was significantly lower in BD patients with vascular involvement (8.80 ± 3.63%) than those without any vascular disease (12.02 ± 3.43%, p = 0.003). This study reveals that endothelial dysfunction documented by brachial artery FMD is a feature of BD, and it is more prominent in patients with vascular involvement.