Autologous Hematopoietic Stem Cell Transplantation for Behçet's Disease: A Retrospective Survey of Patients Treated in Europe, on Behalf of the Autoimmune Diseases Working Party of the European Society for Blood and Marrow Transplantation.

Background: Behçet's Disease (BD) is an autoimmune disease mostly presenting with recurrent oral and genital aphthosis, and uveitis. Patients are rarely refractory to immunosuppressive treatments. Autologous hematopoietic stem cell transplantation (aHSCT) is a standard of care in other autoimmune diseases. Some patients with BD have been treated with aHSCT based on compassionate use. Objectives: Evaluate the outcome of aHSCT in adult patients with BD treated in member centers of the European Society for Blood and Marrow Transplantation (EBMT). Methods: Adults who received aHSCT primarily for BD were identified retrospectively in the EBMT registry and/or in published literature. Data were extracted from either medical records of the patient or from publications. Results: Eight out of 9 cases reported to the registry and extracted data of 2 further patients from literature were analyzed. Four were female, median age at onset of BD was 24y (range 9-50). Median age at aHSCT was 32y (27-51). Patients had received median 4 (2-11) previous lines of therapy (89% corticosteroids, 50% methotrexate, anti-TNFα therapy or cyclophosphamide). All patients had active disease before mobilization. Conditioning regimen was heterogeneous. Median follow-up was 48 months (range 6-240). No treatment-related mortality was reported. This procedure induced complete remission (CR) in 80%, partial remission in 10% and lack of response in 10% of the patients. Relapse rate was 30% (2 relapses in patients in CR and 1 relapse in the patient in PR) with panuveitis (n=1), aphthosis (n=2) and arthralgia (n=1). Six patients were in CR. No late complications were reported. Conclusion: aHSCT has an acceptable safety profile and represents a feasible and relatively effective procedure in severe and conventional treatment-resistant cases of BD and has the potential to stabilize BD in patients with life-threatening involvements.

Significant Decline in the Incidence of Behçet's Disease in South Korea: A Nationwide Population-Based Study (2004-2017).

OBJECTIVE: Long-term population-based data on change in the incidence of Behçet's disease (BD) are scarce, although a possible decline has been reported. The present study was undertaken to investigate the incidence, survival, and mortality of BD patients from 2004 to 2017 in the Republic of Korea. METHODS: We analyzed a registry of rare intractable diseases and a claims database from the Health Insurance and Review Agency with information on BD patients between 2004 and 2017 using uniform diagnostic criteria. The study period was divided into 3 time periods: 2004-2006, 2007-2010, and 2011-2017. RESULTS: The annual incidence of BD decreased from 8.15 per 100,000 in 2004 to 1.51 in 2017, an 81.5% decrease. The annual percentage change was 6.32% for female patients and 6.15% for male patients. The decrease in BD incidence was greater for women and middle-aged people. The 3-year survival rate of BD patients during the 2011-2017 period was lower than that of BD patients in 2004-2006 and 2007-2010, although there was no statistical difference. The standardized mortality rates increased significantly in the 2011-2017 period compared to the first 2 periods. CONCLUSION: BD incidence decreased from 2004 to 2017 in the Republic of Korea. This decline in incidence might be attributable to changes in environmental factors, including a reduction in the burden of infectious diseases in the past decades and improvement in oral health during childhood. The unprecedented decline in the incidence of BD in the Republic of Korea without major changes in genetic background suggests that environmental factors are very important to the development of BD.

Surgical Experience of Behcet's Disease Involving the Peripheral Artery.

BACKGROUND: Behcet's disease with arterial involvement shows rapid poor progression compared with Behcet's disease without arterial involvement, such that it may be thought of as a different disease. With arterial involvement, high rates of postoperative recurrence and anastomotic complications are observed. METHODS: The medical records of 1,361 patients diagnosed with Behcet's disease who visited our hospital from January 2007 to December 2019 were reviewed. Overall, 118 patients with blood vessel involvement were considered. Those with only vein involvement, intracerebral arterial involvement, and coronary arterial involvement were excluded. The 8 patients who underwent surgical treatments and the 9 patients who underwent conservative treatments were included and reported in this study. RESULTS: The mean age and mean follow-up duration of the 17 patients with peripheral arterial involvement were 49.82 ± 13.24 years and 89.85 ± 52.70 months, respectively. In all cases where the operations were performed, the first operation was an emergency operation for rupture of the aneurysm, impending sign of rupturing, or acute ischemia. Eight patients received a total of 18 operations. The average number of operations per patient and the reoperation rate were 2.25 ± 0.89 times and 75%, respectively. The 5-year and 10-year survival rates of the patients who underwent surgery were 75.0% and 30.0%, respectively. When arterial involvement occurs in the form of an aneurysm, the hazard ratio for death is 9.644 (P = 0.040, confidence interval 1.11-83.74). CONCLUSIONS: When the artery invades in the form of an aneurysm, the mortality rate is higher regardless of surgery. The main cause of mortality is complications that occur in the anastomosis sites after the operation. Postoperative short-term and regular imaging of the anastomosis area can be beneficial to detect such complications early to decrease the frequency of emergency surgeries, which will help reduce mortality.

Epidemiology, morbidity and mortality in Behçet's disease: a cohort study using The Health Improvement Network (THIN).

OBJECTIVES: The epidemiology of Behçet's disease (BD) has not been well characterized in the UK. Evidence on the risk of cardiovascular disease, thromboembolic disease and mortality in patients with BD compared with the general population is scarce. METHODS: We used a large UK primary care database to investigate the epidemiology of BD. A retrospective matched cohort study was used to assess the following outcomes: risk of cardiovascular, thromboembolic disease and mortality. Controls were selected at a 1:4 ratio (age and gender matched). Cox proportional hazard models were used to derive adjusted hazard ratios (aHR). RESULTS: The prevalence of BD was 14.61 (95% CI 13.35-15.88) per 100 000 population in 2017. A total of 1281 patients with BD were compared with 5124 age- and gender-matched controls. There was significantly increased risk of ischaemic heart disease [aHR 3.09 (1.28-7.44)], venous thrombosis [aHR 4.80 (2.42-9.54)] and mortality [aHR 1.40 (1.07-1.84)] in patients with BD compared with corresponding controls. Patients with BD were at higher risk of pulmonary embolism compared with corresponding controls at baseline [adjusted odds ratio 4.64 (2.66-8.09), P < 0.0001]. The majority of patients with pulmonary embolism and a diagnosis of BD had pulmonary embolism preceding the diagnosis of BD, not after (87.5%; n = 28/32). CONCLUSION: BD has a higher prevalence than previously thought. Physicians should be aware of the increased risk of developing ischaemic heart disease, stroke/transient ischaemic attack and deep venous thrombosis in patients with BD at an earlier age compared with the general population. Risk of embolism in patients with BD might vary across the disease course.

Coronary involvement in behçet's disease: what are its risks and prognosis? (rare cases and literature review)

Abstract Objective: In our clinic, we aimed to investigate the effect of preoperative risk factors and postoperative complications on reoperation and mortality in cases with Behçet's disease which presents very rare coronary artery involvement. Methods: Thirteen patients with Behçet's Disease who had undergone coronary artery bypass grafting in our center between 2003 and 2015 were analyzed. We evaluated the clinical and laboratory findings, complications and mortality rates of our patients in light of the literature. Results: The mean age was 38.5 (30-55; 3 women). The mean time from onset of Behçet's disease to coronary artery disease was 4,7 (3-11) years. Fifty-four percent of the patients were asymptomatic. Coronary artery disease of these was exposed while peripheral vascular surgery was planned due to complications of Behçet's disease. Symptomatic patients presented angina pectoris (31%), acute coronary syndrome (8%) and arrhythmia (8%). In coronary pathology of patients, distal type obstruction (31%), aneurysm and pseudoaneurysm (31%), proximal segment thrombus (15%), chronic type stenosis and occlusions (31%) were present. Early mortality (15%) was due to acute myocardial infarction while the late mortality (15%) was due to cerebral and gastrointestinal bleeding. Reoperation was due to bleeding in one case on the 1st postoperative day and due to acute pulmonary embolism in another case in the 3rdpostoperative year. Conclusion: In Behçet's disease, coronary artery bypass grafting is a procedure with high mortality, especially in the acute period. The on-pump surgery technique in these cases can be safely performed for multiple bypasses and in patients above 40 years old.

The Clinical Features and Risk Factors of Parenchymal Neuro-Behcet's Disease.

To investigate the clinical features of parenchymal neuro-Behcet's disease (p-NBD), we retrospectively reviewed the medical records of 1009 BD patients admitted to Peking Union Medical College Hospital from 2000 to 2016. Forty-two patients (25 males and 17 females) with p-NBD and eighty-four age- and sex-matched BD patients without neurological involvement who were served as controls were enrolled. Neurological onset was concomitant with the onset of BD in six cases (14.3%). Pyramidal signs (50.0%) and headache (33.3%) were the most common manifestations. On MRI, the lesions were mainly in the midline structures and hyperintense in the T2-weighted image. The most common lesion was the brainstem (54.8%). Spinal cord involvement was observed in five cases, four of which with cervical cord involvement. Multifocal lesions were observed in 13 patients. Ocular involvement was more prevalent in p-NBD (35.7%) (P = 0.041, OR = 2.36, 95% CI = 1.03-5.44) compared with controls. All patients received corticosteroids and immunosuppressants, mainly cyclophosphamide (39/42). Six patients with severe/refractory condition received biological agents and achieved response measured by decreased Rankin score (P = 0.002). With a median follow-up of 28 months, 22 patients (61.1%) achieved clinical improvements, while 10 (27.8%) relapsed and 4 died (mortality rate 11.1%). p-NBD is a rare yet disabling and life-threatening complication of BD. Ocular involvement is a risk factor for p-NBD. Promptly aggressive treatment is essential for improving prognosis, and biological agents might be a promising approach for severe/refractory p-NBD.

Coronary Involvement in Behçet's Disease: what are its Risks and Prognosis? (Rare Cases and Literature Review).

OBJECTIVE: In our clinic, we aimed to investigate the effect of preoperative risk factors and postoperative complications on reoperation and mortality in cases with Behçet's disease which presents very rare coronary artery involvement. METHODS: Thirteen patients with Behçet's Disease who had undergone coronary artery bypass grafting in our center between 2003 and 2015 were analyzed. We evaluated the clinical and laboratory findings, complications and mortality rates of our patients in light of the literature. RESULTS: The mean age was 38.5 (30-55; 3 women). The mean time from onset of Behçet's disease to coronary artery disease was 4,7 (3-11) years. Fifty-four percent of the patients were asymptomatic. Coronary artery disease of these was exposed while peripheral vascular surgery was planned due to complications of Behçet's disease. Symptomatic patients presented angina pectoris (31%), acute coronary syndrome (8%) and arrhythmia (8%). In coronary pathology of patients, distal type obstruction (31%), aneurysm and pseudoaneurysm (31%), proximal segment thrombus (15%), chronic type stenosis and occlusions (31%) were present. Early mortality (15%) was due to acute myocardial infarction while the late mortality (15%) was due to cerebral and gastrointestinal bleeding. Reoperation was due to bleeding in one case on the 1st postoperative day and due to acute pulmonary embolism in another case in the 3rdpostoperative year. CONCLUSION: In Behçet's disease, coronary artery bypass grafting is a procedure with high mortality, especially in the acute period. The on-pump surgery technique in these cases can be safely performed for multiple bypasses and in patients above 40 years old.

Predictors of paravalvular aortic regurgitation after surgery for Behcet's disease-related severe aortic regurgitation.

BACKGROUND: Behcet's disease (BD)-related aortic regurgitation (AR) is known to be associated with paravalvular leakage (PVL) after successful aortic valve (AV) surgery. This study aimed to determine predictors of PVL after successful AV surgery in BD patients. We retrospectively collected data of 35 patients (42.1 ± 9.1 years, 27 men) who underwent surgery for severe BD-related AR at two tertiary centers. The diagnosis was established based on echocardiographic, surgical, and/or pathological findings in conjunction with the International Study Group criteria for BD. A total of 76 cases of AV surgery in 35 patients were analyzed. RESULTS: A median follow-up duration was 8.0 years (interquartile range, 5.4-14.3 years). PVL developed in 18 patients (51.4%) within 2 years after the first surgery. Six patients who met the diagnostic criteria for BD did not develop PVL, in whom 5 patients took immunosuppressive therapy (IST). However, 4 of 9 patients (44.4%) who did not meet the diagnostic criteria developed PVL, in whom four (44.4%) patients took IST. On multivariable analysis, postoperative IST and concomitant aortic root replacement (ARR) were two independent predictors for less PVL development (HR 0.38, 95% CI 0.17-0.89, p = 0.025 for postoperative IST; HR 0.17, 95% CI 0.08-0.36, p < 0.001 for concomitant ARR). Preoperative IST use did not determine PVL development (p = 0.75). CONCLUSIONS: Postoperative, but not preoperative, IST and concomitant ARR were independent predictors of less development of PVL. Special attention is required for early diagnosis BD-related AR, especially in patients not satisfying the current diagnostic criteria.

Behçet's disease presentations and care outcomes in a tertiary hospital in south-western Saudi Arabia.

AIM: To study the clinical presentations of Behçet's disease in patients visiting a tertiary hospital in south-western Saudi Arabia. PATIENTS AND METHODS: Forty-seven patients with Behçet's disease attending the Rheumatology Department at Asser Central Hospital, Saudi Arabia were recruited into the study. The study was conducted over a period of 5 years from January 2012 to July 2017. Medical records of the patients were reviewed to analyze the frequency of different clinical manifestations. RESULTS: The study had 26 men and 21 women. The mean age of the patients was 37.11 ± 11.9 years (range <30-60 years). Frequency of main clinical manifestations in these patients included 89.4% (42/47) oral ulcers, 80.9% (38) genital ulcers, 55.3% (26/47) ocular complications, 55.3% arthralgia (26/47), 31.9% arthritis (15/47), 36% neurological complications (17/47), 34% gastrointestinal involvement (16), 17% pulmonary complication (8/47), cutaneous lesions in the form of skin pustules were found in 31.9% of cases and erythema only in 4.3% of patients. Deep venous thrombosis was observed in 66.6% of patients. About 96% of patients showed improvement with drugs. Only 2 patients died during the study period. CONCLUSION: Behçet's disease showed higher male predominance in south-western Saudi Arabia, similar to other Middle-Eastern countries. The clinical characteristics are comparable to different studies reported from other countries. Regarding the care outcome, the majority of patients were cured using oral corticosteroids and other immunosuppressive drugs.

Surgical Treatment of Pulmonary Complications in Behçet's Syndrome.

We described disease characteristics, management and outcome of a group of Behçet's syndrome (BS) patients who underwent pulmonary lobectomy, segmentectomy or various pleura interventions for complications due to pulmonary artery or descending aorta involvement. There were 9 patients with BS (8 M/1 F; mean age: 24.8 ±â€¯7.5 and mean disease duration: 4.3 ±â€¯3.8 years) who underwent lung surgery from 2000 to 2017. Their medical files including operation details and radiological and pathological studies were reviewed retrospectively. Lobectomy was done in 6 patients, decortications and pleura interventions in the remaining 3. The reason for the surgical procedures were giant pulmonary arterial aneurysms refractory to the medical treatment (n = 4), pneumothorax due to large cavities (n = 2), pleural effusions refractory to the medical treatment (n = 1), a bronchopleural fistula after embolization (n = 1) and bronchiectasis (n = 1). All patients received medical treatment with cyclophosphamide and corticosteroids before the surgical interventions. The histological examination in patients with pseudo-aneurysms showed destruction of medial elastic fibers, inflammatory cell infiltration of adventitial tissues and penetration into the adjacent bronchi with adherent thrombi. Two patients died: one due to Budd-Chiari syndrome 1 year after the surgery, another because of a massive hemoptysis 3 months after lobectomy. The remaining 7 patients are still alive with a median follow-up of 8 years (inter-quartile range [IQR]: 4-11). Lobectomies in BS patients with giant pulmonary aneurysms refractory to medical treatment can be done with favorable outcome. Also, complications such as large cavities causing pneumothorax, refractory pleural effusions, bronchiectasis, and embolization complications can be managed effectively with surgical interventions.

Incidence, prevalence, and mortality of Adamantiades-Behçet's disease in Korea: a nationwide, population-based study (2006-2015).

BACKGROUND: The epidemiology of Adamantiades-Behçet's disease varies among ethnic populations worldwide. Trends in the incidence of Adamantiades-Behçet's disease have not been investigated based on the Korean National Health Insurance database. OBJECTIVES: This study investigated the incidence and mortality of Adamantiades-Behçet's disease by age using nationwide population data in Korea. METHODS: A nationwide population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2006 to 2015. The incidence of Adamantiades-Behçet's disease was calculated by age, sex, calendar year and habitat. And comorbid metabolic diseases were also analysed in patients with Adamantiades-Behçet's disease. RESULTS: The annual incidence of Adamantiades-Behçet's disease per 100 000 person-years was 3.976 (2.587 for males and 5.373 for females) from 2006 to 2015. The incidence of Adamantiades-Behçet's disease peaked among people in their 40s (6.561 per 100 000 person-years). Incidence was significantly higher in subjects with comorbid metabolic conditions, such as diabetes mellitus, hypertension and dyslipidemia. The mortality rate per 1000 person-years increased with age in patients with Adamantiades-Behçet's disease. CONCLUSIONS: This study showed the incidence, prevalence and mortality of Adamantiades-Behçet's disease. Metabolic conditions increased the risk of Adamantiades-Behçet's disease among Koreans.

Atrium Advanta V12 Large Diameter Stent-Graft Applications for Infrarenal Abdominal Aortic Pseudoaneurysms (due to Behcet Disease): Safety and Efficacy.

BACKGROUND: The aim of the study was to determine the safety and effectiveness of Atrium Advanta V12 large diameter stent-graft applications for infrarenal abdominal aortic pseudoaneurysms (due to Behcet disease [BD]). METHODS: Data of Advanta V12™ (Atrium Europe B.V, Mijdrecht, the Netherlands) applied 12 female patients (mean age 30.5 ± 6.3, range 26-44) with infrarenal abdominal aortic pseudoaneurysms were analyzed retrospectively. All Advanta V12 large diameter stent grafts were implemented from right or left sided 12F femoral sheaths. Stent grafts with 12-16 mm in size and 29-61 mm in length were utilized. Technical success rate, procedure-related mortality and morbidity, and primary patency rate at 4 years were evaluated. RESULTS: Technical success rate was 100%. Neither procedure-related mortality nor morbidity was determined. The mean aortic diameter was 14.0 ± 0.8 mm for pseudoaneurysmatic abdominal aortas. The mean follow-up period was 46.5 ± 40.3 months (range 18-75). During follow-ups, only one recurrent aneurysm has evolved at the stenting site due to patients' withdrawal of immunosuppressive treatment. The advent of a new aneurysm proximal or distal to the stent-graft region or at the femoral access localization was not observed. There were no stent occlusions. Primary patency rate at 4 years was 100%. Complete aneurysm exclusion was achieved 100% at 48 months. CONCLUSIONS: The use of Advanta V12 large diameter stent grafts for infrarenal abdominal aortic pseudoaneurysms (due to BD), especially in female patients with small aortic diameter, is safe and efficient. Primary patency rate of the stent grafts at 4 years is excellent.

The value of endografts in the surgical management of arterial lesions secondary to Behçet disease.

BACKGROUND: This study summarizes our experience in the surgical management of arterial lesions secondary to Behçet disease (BD) and assesses the value of endografts. METHODS: Data from BD patients with arterial lesions managed surgically in our center from January 1998 to December 2015 were studied retrospectively. Surgical procedures, graft selection, graft-related complications, and retreatments were analyzed. RESULTS: We recruited 33 patients (29 men and 4 women; male-to-female ratio, 7.25:1) with an average age of 36.7 years (range, 25-51 years). The arterial lesions included 27 aneurysms in 24 patients and nine stenotic or occlusive lesions in nine patients. Immunosuppressive therapy was administered routinely preoperatively and postoperatively as recommended. Altogether, 15 great saphenous veins (GSVs), 8 synthetic grafts, and 13 endografts were used in 36 primary procedures. The mean follow-up duration was 3.8 ± 2.9 years. Graft-related pseudoaneurysm was seen in three GSVs (20%) and in three synthetic grafts (38%) at the anastomosis, but not in endograft implantations (log-rank, P = .171). Graft occlusions were observed in 1 GSV (7%), 2 synthetic (25%), and 2 endografts (15%; log-rank, P = .881). Graft infection occurred in one synthetic graft (13%) and in one endograft (8%) but not in the GSVs (log-rank, P = .689). Graft-related artery rupture occurred in only one endograft (8%). Two patients died, giving a mortality rate of 6.1%. CONCLUSIONS: In the surgical management of arterial lesions secondary to BD, endografts were superior to GSV and synthetic grafts in decreasing anastomotic pseudoaneurysm. However, improvements are needed to enhance the long-term patency and reduce infections.

Outcomes of surgery for patients with Behcet's disease causing aortic pseudoaneurysm: a shift from open surgery to endovascular repair.

OBJECTIVES: Behcet's disease is a form of systematic vasculitis that affects vessels of various sizes. Aortic pseudoaneurysm is one of the most important causes of death among patients with Behcet's disease due to its high risk of rupture and associated mortality. Our study aimed to investigate the outcomes of Behcet's disease patients with aortic pseudoaneurysms undergoing open surgery and endovascular aortic repair. METHODS: From January 2003 to September 2014, ten consecutive patients undergoing surgery for aortic pseudoaneurysm met the diagnostic criteria for Behcet's disease. Endovascular repair was the preferred modality and open surgery was performed as an alternative. Systemic immunosuppressive medication was administered after Behcet's disease was definitively diagnosed. RESULTS: Eight patients initially underwent endovascular repair and two patients initially underwent open surgery. The overall success rate was 90% and the only failed case involved the use of the chimney technique to reach a suprarenal location. The median follow-up duration was 23 months. There were 7 recurrences in 5 patients. The median interval between operation and recurrence was 13 months. No significant risk factors for recurrence were identified, but a difference in recurrence between treatment and non-treatment with preoperative immunosuppressive medication preoperatively was notable. Four aneurysm-related deaths occurred within the follow-up period. The overall 1-year, 3-year and 5-year survival rates were 80%, 64% and 48%, respectively. CONCLUSIONS: Both open surgery and endovascular repair are safe and effective for treating aortic pseudoaneurysm in Behcet's disease patients. The results from our retrospective study indicated that immunosuppressive medication was essential to defer the occurrence and development of recurrent aneurysms.

Outcomes of surgery for patients with Behcet's disease causing aortic pseudoaneurysm: a shift from open surgery to endovascular repair

OBJECTIVES: Behcet’s disease is a form of systematic vasculitis that affects vessels of various sizes. Aortic pseudoaneurysm is one of the most important causes of death among patients with Behcet’s disease due to its high risk of rupture and associated mortality. Our study aimed to investigate the outcomes of Behcet’s disease patients with aortic pseudoaneurysms undergoing open surgery and endovascular aortic repair. METHODS: From January 2003 to September 2014, ten consecutive patients undergoing surgery for aortic pseudoaneurysm met the diagnostic criteria for Behcet’s disease. Endovascular repair was the preferred modality and open surgery was performed as an alternative. Systemic immunosuppressive medication was administered after Behcet’s disease was definitively diagnosed. RESULTS: Eight patients initially underwent endovascular repair and two patients initially underwent open surgery. The overall success rate was 90% and the only failed case involved the use of the chimney technique to reach a suprarenal location. The median follow-up duration was 23 months. There were 7 recurrences in 5 patients. The median interval between operation and recurrence was 13 months. No significant risk factors for recurrence were identified, but a difference in recurrence between treatment and non-treatment with preoperative immunosuppressive medication preoperatively was notable. Four aneurysm-related deaths occurred within the follow-up period. The overall 1-year, 3-year and 5-year survival rates were 80%, 64% and 48%, respectively. CONCLUSIONS: Both open surgery and endovascular repair are safe and effective for treating aortic pseudoaneurysm in Behcet’s disease patients. The results from our retrospective study indicated that immunosuppressive medication was essential to defer the occurrence and development of recurrent aneurysms.

Preoperative immunosuppressive therapy reduces paravalvular leakage after aortic valve surgery in patients with aortic regurgitation attributable to Behçet's disease.

OBJECTIVES: Severe aortic regurgitation (AR) attributable to Behçet's disease (BD) is a rare but challenging problem in light of the surgical treatment notoriously complicated with paravalvular leakage (PVL) and high mortality. This study aims to test whether immunosuppressive therapy is effective in reducing the complication of the operation and improve the prognosis. METHODS: In a retrospective cohort of 644 hospitalised BD patients who were diagnosed and followed up between January 1998 and September 2014, 18 patients (2.8%) with severe AR due to BD were identified and their medical records were analysed. RESULTS: Among the 18 patients, 15 patients underwent the valve surgery and PVL developed in 7 (47%) at a median interval of 3.5 months. In the median follow-up of 32.5 months from first operations, patients with PVL had a significantly higher incidence of repeat surgery and death (71% vs. 0%, p=0.007). They less likely received preoperative immunotherapy (14% vs. 100%, p=0.001), had a lower cumulative dosage of cyclophosphamide before first operations (2.1±5.7g vs. 13.0±6.4g, p=0.004) and a higher preoperative erythrocyte sedimentation rate (44.4±20.7mm/first hour vs. 25.0±12.1mm/first hour, p=0.04) compared with those without developing PVL. Multivariate analysis showed preoperative immuno-suppressive therapy (hazard ratio 18.58; 95% confidence interval, 2.134-161.81; p=0.008) was an independent factor associated with the absence of PVL. The 5-year PVL-free survival rates were significantly higher in patients receiving preoperative immunotherapy (p=0.0004). CONCLUSIONS: In patients with severe AR due to BD, preoperative immunosuppressive therapy, especially cyclophosphamide in conjunction with glucocorticoid, could reduce PVL after the corrective surgery and improve the outcomes.

Behçet's syndrome: a critical digest of the 2014-2015 literature.

Several studies were published last year which focused on the epidemiology, immunopathogenesis, genetics, clinical manifestations and management of Behçet's syndrome. Recent epidemiologic studies support the earlier contention that the frequency of BS increases from North to South in Europe, BS is rare in Sub-Saharan Africa, it follows a more severe course among young men, especially if the disease onset is at a young age and that in European countries, the frequency is higher among immigrants from BS prevalent countries compared to locals living in the same environment. The relationship between HLA-B51 and Behçet's was re-emphasised and a functional role affecting cellular cytotoxicity was proposed. Innate immunity was explored and TLR7 copy number variations and nucleic acid sensors of varying inflammasome pathways were studied. Vascular relapse risk is decreased when BS patients are treated with immunosuppressives with or without anti-coagulation rather than anti-coagulation alone. Although rare in the Far East, the clinical picture of the vascular involvement was quite similar to the previously published reports. Interestingly a female predominance among those with cerebral vein thrombosis was noted. Venous claudication is a frequent and severe symptom among BS patients with lower extremity DVT. Budd-Chiari syndrome associated with BS is usually associated with IVC thrombosis. Silent cases exist and have a better prognosis. The mortality rate among the patients symptomatic for liver disease remains high. Methotrexate seems to be effective in the treatment of chronic progressive neuro-Behçet's disease. Renal involvement is an uncommon disorder in BS. Suicidal thoughts are increased among BS patients with severe organ involvement. Work-related disability in BS is high and under-appreciated. Apremilast, an inhibitor of phosphodiesterase-4, was effective in a phase 2, double blind, placebo-controlled study. Adalimumab seems to be effective in severe uveitis of BS even after failure of infliximab. New cytokine inhibitors targeting IL-1 and IL-6 appear to be effective especially for uveitis and CNS involvement refractory to anti TNF agents.

Alemtuzumab as Remission Induction Therapy in Behçet Disease: A 20-year Experience.

OBJECTIVE: To study the efficacy and safety of anti-CD52 antibody (alemtuzumab) in the treatment of refractory and relapsing Behçet disease (BD). METHODS: Thirty-two patients (22 women) with BD received 60 courses of alemtuzumab between 1994 and 2013. Three-dose regimens were used: 134 mg in 21 courses (Group 1), 95 mg in 18 courses (Group 2), and 60 mg in 21 courses (Group 3). Immunosuppressive drugs were stopped at the time of alemtuzumab, and prednisolone was reduced according to clinical response. Treatment response was assessed by clinical status, inflammatory activity, prednisolone dose, and the need for subsequent immunosuppressive drugs and disease relapse. RESULTS: After the first alemtuzumab course, 27 of 32 patients (84%) achieved partial or complete remission (CR). Fifty of 60 courses (83%) resulted in remission (66% CR) without differences in remission rates between dosing regimens. Profound lymphocyte depletion occurred after all courses. Relapse-free survival rates were 83.6% at 6 months and 52.8% at 12 months, and were higher among Group 1 patients (Group 1: 100% and 77.8%, Group 2: 81.3% and 37.5%, and Group 3: 65.0% and 37.1%, p < 0.001). Mild to moderate infusion reactions occurred after 16 courses (27%). Eight patients (25%) developed symptomatic thyroid disease. CONCLUSION: Alemtuzumab led to remission in the majority of patients with difficult-to-treat BD. Relapse was common and may be associated with lower dosing. Adverse events included infusion reactions and new autoimmunity. Achieving complete lymphocyte depletion did not affect the remission rate or duration.

What the Cardiologist Should Know About Cardiac Involvement in Behçet Disease.

Behçet disease (BD) is a chronic multisystem inflammatory vasculitis affecting mainly young adults and is characterized by a remitting-relapsing course. In North America, the prevalence is 5.2 per 100,000 population. It is believed that cardiac involvement is one of the most severe complications in patients with BD despite its sporadic occurrence, being greatly correlated with mortality.