Vedat Hamuryudan

The long-term mortality and morbidity of Behçet syndrome: a 2-decade outcome survey of 387 patients followed at a dedicated center.

We surveyed the 20-year outcome of a cohort of patients with Behçet syndrome with emphasis on both mortality and morbidity. During 1999 and 2000, we collected outcome information on 387/428 (90.4%) of a cohort of patients (262 male, 125 female) who had registered in a dedicated outpatient clinic between July 1977 and December 1983. In 245/345 (71.0%) patients, outcome information was based on a formal hospital reevaluation, and in the remaining patients, on detailed telephone interviews.Forty-two patients (9.8%) (39 male, 3 female) had died, mainly due to major vessel disease and neurologic involvement. Mortality, as measured by standardized mortality ratios (SMR), was specifically increased among young males, among whom morbidity was also the highest. However, the SMR tended to decrease significantly with the passage of time. The same was also true for all mucocutaneous and articular manifestations. Both the onset of eye disease and its greatest damage were also usually within the first few years of disease onset. These suggest that the “disease burden” of Behçet syndrome is usually confined to the early years of its course, and in many patients the syndrome “burns out.” However, central nervous system involvement and major vessel disease are exceptions. They can have their onset late (5–10 yr) during the disease course. As reflected in the mortality figures, the disease was less severe among the females for almost each disease manifestation. There were no female patients with arterial aneurysms.Severely impaired vision did not always mean an eventual loss of useful vision, and those patients with a late onset of eye disease had a better visual prognosis.

Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative

Objectives: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. Methods: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. Results: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. Conclusions: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

A double-blind trial of colchicine in Behçet's syndrome.

OBJECTIVE Colchicine is a widely used treatment for Behçets syndrome, even though in a previous 6-month controlled study, it was shown to be effective only in controlling erythema nodosum and arthralgias. We reassessed the effect of colchicine in Behçets syndrome in a study conducted among a larger group of patients for 2 years. METHODS We randomized 116 patients with Behçets syndrome (60 male/56 female), who had active mucocutaneous disease without eye or major organ involvement, to receive either placebo or colchicine (1-2 mg/day, adjusted to body weight) in a double-blind trial for 2 years. The primary outcome measure was the sustained absence of any lesions during treatment (complete response). The secondary outcome measure was the difference in the number of mucocutaneous lesions or arthritic joints between the active drug and placebo arms. Women and men were analyzed separately. RESULTS Eighty-four patients (72%; 45 male, 39 female) completed the 24-month study. Kaplan-Meier analyses showed significantly more complete responses in the colchicine treatment group in terms of reduced occurrence of genital ulcers (P = 0.004), erythema nodosum (P = 0.004), and arthritis (P = 0.033) among the women, and reduced occurrence of arthritis (P = 0.012) among the men. The mean numbers of genital ulcers (P = 0.001), erythema nodosum lesions (P = 0.002), and arthritic joints (P = 0.014) among the women were less in the colchicine group, and the mean number of arthritic joints (P = 0.026) among the men was less in the colchicine group. Adverse effects were similar in both groups. CONCLUSION Colchicine may be useful for treating some of the manifestations of Behçets syndrome, especially among women. This might be a reflection of less severe disease among the women.

Behçet's disease : diagnostic and prognostic aspects of neurological involvement

Abstract This study was conducted to describe clinical and prognostic aspects of neurological involvement in Behçets disease (BD). Patients referred for neurological evaluation fulfilled the criteria of the International Study Group for Behçets Disease. We analyzed disability and survival by the Kaplan-Meier method, using Kurtzkes Extended Disability Status Scale (modified for BD) and the prognostic effect of demographic and clinical factors by Cox regression analysis. We studied 164 patients; of the 107 diagnostic neuroimaging studies: 72.1% showed parenchymal involvement, 11.7% venous sinus thrombosis (VST) and the others were normal. CSF studies were performed in 47 patients; all with inflammatory CSF findings (n=18) had parenchymal involvement. An isolated increase in pressure was compatible with either VST or normal imaging. The final diagnoses were VST (12.2%), neuro-Behçets syndrome (NBS) (75.6%), isolated optic neuritis (0.6%), psycho-Behçets syndrome (0.6%), and indefinite (11%). VST and NBS were never diagnosed together. Ten years from onset of BD 45.1% (all NBS) reached a disability level of EDSS 6 or higher, and 95.7±2.1% of the patients were still alive. Having accompanying cerebellar symptoms at onset or a progressive course is unfavorable. Onset with headache or a diagnosis of VST is favorable. Two major neurological diagnoses in BD are NBS and VST. These are distinct in clinical, radiological, and prognostic aspects, hence suggesting a difference in pathogenesis.

Management of aneurysms in Behçet's syndrome: An analysis of 24 patients

BACKGROUND The surgical therapy of Behçet aneurysms is often unsuccessful, resulting in graft occlusions, anastomoses, and/or new aneurysms. METHODS Twenty-nine aneurysms were documented in 24 Behçets patients during a period of 19 years. All patients were male, ranging in age from 20 to 53 years (mean, 35 +/- 7.3 years). The mean duration of disease was 9 +/- 5 years. There were nine abdominal aorta, four iliac, three common femoral, five superficial femoral, four popliteal, one subclavian, one carotid, and one posterior tibial artery aneurysm. In addition, in one patient an aneurysm developed from the arterialized venous conduit that had been inserted for a common femoral artery aneurysm elsewhere. Five patients were already under immunosuppressive therapy for ocular problems at the time of diagnosis. Fifteen patients received immunosuppressive therapy after operation. We performed one abdominal aneurysmorrhaphy, two iliac artery PTFE graft interpositions, two aortobiliac bypasses (PTFE), six aortic tube graft (three PTFE, three Dacron) interpositions, one avrtofemoral bypass (PTFE), two iliofemoral bypasses (PTFE), two superficial femoral artery graft (PTFE) interpositions, and three popliteal graft interpositions (one PTFE, two vein graft). Also as an initial procedure one carotid, one subclavian, four superficial femoral, one popliteal, and one posterior tibial artery were ligated. RESULTS Nineteen patients were followed up for a mean duration of 47.3 +/- 27 months (range, 1 to 108 months). The patient with a subclavian aneurysm died of massive bleeding on postoperative day 15. Four patients were lost to follow-up. In the abdominal aortic aneurysm group one patient died of gastrointestinal bleeding 4 years after the operation. Another patient from the same group died 5 years after operation without any vascular disease. In the common femoral artery group the patient with an occluded iliofemoral graft died of an exsanguinating pulmonary artery aneurysm in the first year after operation. Overall, there were five anastomotic aneurysms. In addition, after the initial operation two iliofemoral, one aortofemoral, and one popliteal interposition graft were occluded without disabling ischemia. CONCLUSIONS Aneurysms limited to the extremities could be ligated without disabling ischemia. Abdominal aortic aneurysms could be treated with tube graft insertion, giving satisfactory results. Patients could tolerate graft occlusion without major ischemia.

Low dose cyclosporin A versus pulsed cyclophosphamide in Behcet's syndrome: a single masked trial.

A single masked trial of cyclosporin A 5 mg/kg/day versus monthly 1 g intravenous boluses of cyclophosphamide was conducted among 23 patients with Behçets syndrome and active, potentially reversible uveitis. The trial was unmasked after a mean of 12 (SD 2) months for the cyclosporin A group (n = 12) and a mean of 10 (SD 3) months for the cyclophosphamide group (n = 11). During the initial 6 months the visual acuity significantly improved (p < 0.001) in the cyclosporin A group whereas this was not observed in the cyclophosphamide group. The subsequent follow-up of patients up to 24 months suggested that the initial improvement in visual acuity with cyclosporin A was not sustained. More extensive and especially long-term studies of cyclosporin A in the uveitis of Behçets syndrome are warranted.

Gastrointestinal involvement in Behçet's syndrome: a controlled study.

OBJECTIVE: To make a retrospective and prospective analysis of the frequency of symptomatic inflammatory bowel disease in patients with Behçets syndrome (BS). METHODS: The medical records of the first 1000 patients with BS were reviewed retrospectively for past or present history of diarrhoea. The past and present history of diarrhoea was also elicited prospectively among 147 consecutive patients with BS and 78 diseased controls (42 with rheumatoid arthritis, 17 with systemic lupus erythematosus, seven with seronegative spondylarthropathy, and 12 with miscellaneous rheumatic diseases). Inflammatory mucosal changes were sought in rectal biopsy specimens from 75 patients with BS, 47 diseased controls (29 with nephrotic syndrome, eight with rheumatoid arthritis, six with familial Mediterranean fever, and four with ankylosing spondylitis), and 14 patients with ulcerative colitis. RESULTS: In chart review there were only seven Behçets patients with diarrhoea; none of them had inflammatory bowel disease. In the prospective survey there were no significant differences between the BS and control groups in the past and present history of diarrhoea. There were no significant differences in the rectal mucosal histology between patients with BS and controls, while patients with ulcerative colitis showed pronounced differences. CONCLUSION: Symptomatic inflammatory bowel disease is not common in BS patients from Turkey.

Lipid, protein, DNA oxidation and antioxidant status in rheumatoid arthritis.

OBJECTIVES To investigate lipid, protein, DNA oxidation and antioxidant status in blood and synovial fluid of rheumatoid arthritis (RA) patients and to determine the importance of oxidative stress parameters in reflecting disease activity. DESIGN AND METHODS 20 RA patients and 15 healthy controls were included. Lipid peroxidation (thiobarbituric acid reactive substances (TBARS), lipid hydroperoxide, and conjugated diene), protein oxidation (carbonyl and thiol), DNA oxidation (8-OHdG) and antioxidant status markers (glutathione (GSH), glutathione peroxidase (GSH Px), superoxide dismutase (CuZn SOD), and catalase) were determined in blood and synovial fluid. RESULTS TBARS (p<0.001), lipid hydroperoxide (p<0.001), conjugated diene (p<0.001), carbonyl (p<0.001) and 8-OHdG (p<0.01) levels were significantly higher; thiol (p<0.01) and GSH levels (p<0.01) and GSH Px (p<0.001) and CuZn SOD (p<0.01) activities were significantly lower in blood of RA patients. TBARS (p<0.001), lipid hydroperoxide (p<0.001), conjugated diene (p<0.01), carbonyl (p<0.001) and 8-OHdG (p<0.05) levels were significantly higher, catalase activity (p<0.001) significantly lower in synovial fluid of RA patients. CONCLUSIONS Increased lipid, protein and DNA oxidation markers and impaired antioxidant status confirm the role of oxidative stress in the pathogenesis of RA. Lipid peroxidation markers can serve as surrogate markers for disease activity.

Genetic anticipation in Behçet’s syndrome

OBJECTIVE To examine the presence of genetic anticipation in families with Behçet’s syndrome (BS). METHODS A total of 18 families with 40 affected members in two successive generations were evaluated by interviewing them for their ages at the onset of the first symptom of BS and for their ages at the time they fulfilled the diagnostic criteria. RESULTS It was noted that the age of onset of the first symptom was lower in the second generation in 14 families (p=0.01) with a mean (SD) age of 20.57 (7.47) years in the children compared with 33.29 (9.92) years in the parents (t=7.79, p<0.0001), whereas the diagnostic criteria were fulfilled at an earlier age in the children in 15 families (p=0.01) with a mean age of 21.2 (6.74) years in the children compared with 36.4 (9.55) years in the parents (t=7.41, p<0.0001). CONCLUSION Genetic anticipation was present in 15 of 18 (84%) of the families with BS in the form of earlier disease onset in the children compared with their parents.

Pulmonary Artery Involvement and Associated Lung Disease in Behçet Disease: A Series of 47 Patients

AbstractPulmonary artery aneurysms (PAAs) are well known causes of mortality and morbidity in Behçet disease (BD). However, pulmonary artery involvement in BD is not limited to PAA; the other main type of pulmonary artery involvement is pulmonary artery thrombus (PAT), with or without associated PAA. In addition, other types of lung disease like nodules and cavities in the lung parenchyma are frequently associated with pulmonary artery involvement, and can be misinterpreted as being due to infection. We surveyed the clinical, radiologic, and laboratory characteristics and outcome of 47 BD patients with pulmonary artery involvement and the associated findings, all seen and followed at a single dedicated tertiary care center.We identified 47 (41 male, 6 female) patients in whom pulmonary artery involvement was diagnosed, who were registered in the multidisciplinary clinic at Cerrahpasa Medical Faculty between January 2000 and December 2007. Mean age at diagnosis was 29 ± 8 years, and mean disease duration to the onset of pulmonary artery involvement was 3.6 ± 4.8 years. Hemoptysis was the most common presenting symptom (79%) followed by cough, fever, dyspnea, and pleuritic chest pain. Thirty-four of 47 patients (72%) presented with PAA, including 8 with associated PAT. The remaining 13 patients (28%) had isolated PAT. Patients with isolated PAT in general have clinical features similar to patients with PAA. However, hemoptysis was less frequent and voluminous in patients with isolated PAT. Most (91%) of the patients had active disease outside the lungs when they presented with pulmonary artery involvement.Forty (85%) patients had nodules and 6 (13%) had cavities when first seen. Peripheral venous thrombosis was present in 36 of 47 (77%) patients, and intracardiac thrombi in 12 of the 36 (33%) patients. Nodules, cavities, and intracardiac thrombi were mainly present in the acute stages of pulmonary artery involvement.Pulmonary artery involvement is usually multiple, and involves mostly descending branches of the pulmonary artery. Pulmonary artery involvement may disappear, but arterial stenosis or occlusions usually develop at the same location. After a mean follow-up of 7 years, 12 of 47 (26%) patients were dead; patients with larger aneurysms were more likely to die. Sixteen of 47 (34%) patients were symptom free, and the remaining 40% had mild dyspnea (13/47) and/or small bouts of hemoptysis (8/47).Pulmonary artery pressure may be elevated, and may indicate a poor prognosis. Mediastinal lymphadenopathy and mild pleural and pericardial effusions may also be observed. Corticosteroids and immunosuppressive agents are the mainstays of treatment; however, refractory cases may require embolization, lobectomy, cavitectomy, and decortication.