Hasan Yazici

• Istanbul University

Background It was our impression that safety outcome trials were getting more frequent, raising ethical issues mainly related to patient autonomy. We and others had also proposed this autonomy would be best served if wording of the informed consents would be in the public domain. Methods Initially two observers and an arbiter tabulated the main ai...

Objective: Vascular involvement is an important cause of morbidity and mortality in patients with Behçet's syndrome (BS). We aimed to survey the efficacy and safety of infliximab (IFX) in BS patients with vascular involvement followed in a dedicated tertiary center. Methods: Charts of all BS patients who used IFX for vascular involvement between...

Background Behçet’s disease (BD) is a rare, and severe, multisystemic inflammatory disease characterized by recurrent oral aphthous ulcers, genital ulcers, skin lesions, and both anterior and posterior uveitis; articular, vascular, gastroenteric and neurological involvement may also occur. The multi-organ involvement and the wide spectrum of clinic...

Background The randomized controlled trial (RCT) remains a most important research as well as a tool for drug licensing. Informed consent also remains an integral component of this tool. The exact wording of this consent is not in the public domain and we had previously raised that concern and had pointed out it should [1, 2]. As we previously indi...

Background Despite attempts to lump Behçet syndrome (BS) with spondyloarthritides, controlled studies have shown that radiographic sacroiliitis is not increased in BS (BS). However, gastrointestinal involvement of Behçet syndrome (GIBS) shares common features with inflammatory bowel disease which, in turn, can be associated with spondyloarthritis....

Behçet's syndrome is a systemic vasculitis affecting arteries and veins of all sizes as well as recurrent oral, genital, and intestinal ulcers, skin lesions, predominantly posterior uveitis, and parenchymal brain lesions. These can be present in various combinations and sequences over time and diagnosis is made by recognizing the manifestations, as...

Purpose of review: A critique of the recently published classification criteria for three main types of antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis. Recent findings: An ACR and EULAR joint task force recently published classification criteria for three main types of ANCA-associated vasculitis. The criteria were based on pa...

Objective A decline in the frequency of AA amyloidosis secondary to RA and infectious diseases has been reported. We aimed to determine the change in the frequency of AA amyloidosis in our Behçet’s syndrome (BS) patients and to summarize the clinical characteristics of and outcomes for our patients, and also those identified by a systematic review....

Background Data on patients with Behçet’s syndrome (BS) complicated with AA amyloidosis is limited to case reports or case series with a small number of patients. Objectives In this study, we aimed to perform a systematic review (SR) of published reports on BS patients with AA amyloidosis. Methods PubMed and EMBASE were searched with the keywords...

Background Experience with mycophenolate in uveitis associated with Behçet’s syndrome (BS) is limited. Objectives We aimed to report the efficacy and safety of mycophenolate mofetil (MMF) and mycophenolate sodium (MPA) in the treatment of BS uveitis. Methods All patients with panuveitis or posterior uveitis who used mycophenolate for eye involvem...

Background Vascular involvement is the most common cause of mortality and an important cause of disability in patients with Behçet’s syndrome (BS). Cyclophosphamide has been the treatment choice for severe vascular involvement, but high frequency of adverse events such as infertility and infections cause concern. TNF inhibitors can be an alternativ...

Background Behçet syndrome (BS) is a unique vasculitis that can affect arteries and veins of all sizes. Thrombosis is an important component of vascular involvement in BS. Although several studies were conducted to highlight the mechanism of thromboinflammation in BS, it is still not fully understood. Objectives We performed a systematic review an...

Background Infliximab (IFX) is an effective therapeutic option in the management of severe and refractory manifestations of Behçet’s syndrome (BS). Objectives We aimed to evaluate long term drug survival of IFX in a large cohort of BS patients. Methods We reviewed the charts of BS patients who received IFX between 2004 and June 2021 and noted dem...

Objective An unmet need exists for reliable, validated, and widely‐accepted outcome measures for randomized clinical trials in Behçet's syndrome. The Outcome Measures in Rheumatology (OMERACT) Behçet's Syndrome Working Group, a large, multidisciplinary group of experts in Behçet's syndrome and patients with Behçet's syndrome, had an objective of de...

Objectives Infliximab (IFX) is being increasingly used for the treatment of severe manifestations of Behçet syndrome (BS). However, emergence of new manifestations has also been occasionally reported during IFX treatment. We aimed to assess the frequency of new manifestations in our BS patients treated with IFX. Methods A chart review was conducte...

Behçet syndrome is a systemic vasculitis with an unknown aetiology affecting the small and large vessels of the venous and arterial systems. The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn’s disease suggest that multiple pathological pathways are involved in Behçet syndrome. The...

There are important problems with the data analyses, interpretation, and the cited references in the recently reported retrospective cohort study of Takayasu arteritis (TAK) (1).

Background Infliximab (IFX) plays a key role in the management of severe and refractory manifestations of Behçet syndrome (BS). However we had previously shown that its sustained use may be limited due to adverse events and lack of patient compliance (1). Objectives To assess the retention rate of IFX, adverse events, causes of discontinuation and...

Background Infliximab (IFX) is increasingly used in the management of severe, relapsing or refractory manifestations of Behçet Syndrome (BS). Emergence of de novo manifestations have been reported during IFX treatment, despite efficacy for the initial manifestation that required IFX use ¹ . Objectives We aimed to survey a sizeable cohort of BS pat...

Background Vascular involvement is an important cause of morbidity and mortality in patients with Behçet syndrome (BS). TNF inhibitors have been reported to be effective for almost all serious manifestations of BS but data on vascular involvement is still limited. Objectives To survey the efficacy and safety of infliximab (IFX) in BS patients with...

Background The causes of hospitalization may provide important information on the course of diseases and treatment-related adverse effects. Objectives We aimed to determine the causes and outcome of hospitalizations among patients with Behçet Syndrome (BS) in a dedicated center. Methods We surveyed hospitalization records in our clinic between Ja...

Background Immunogenicity of tumor necrosis factor alpha inhibitors (TNFis) has been recognized as an important problem that may cause loss of efficacy and adverse events such as infusion reactions. TNFis are being increasingly used among patients with Behçet syndrome (BS) and scarce data exist on this topic. Objective We aimed to investigate the...

Background Oral ulcers, the hallmark lesion of Behçet’s syndrome (BS) can be disabling and impair eating, drinking and speaking. Despite recent advances in systemic medications for the treatment of oral ulcers, some patients do not achieve complete remission. Topical agents may help such patients by decreasing the pain and duration of oral ulcers....

Background Infliximab (IFX) has become an important treatment option for all manifestations of Behçet syndrome (BS). Adverse events, loss of efficacy, lack of patient compliance and cost may limit its sustained use in patients with BS. Objectives We aimed to evaluate the drug retention rates, causes of discontinuation and outcome after cessation o...

Background Changing the traditional p value significance level from 0.05 to 0.005 has been proposed as one remedy to the common ill understanding and use of the p values (1-2) especially leading to poor reproducibility. It was then reported that this change would decrease the number of statistically significant primary end points in randomized cont...

We still do not know the cause(s) of Behçet syndrome. Most probably several, separate disease mechanisms are involved. I like, some others, propose we call it not a disease but a syndrome, a construct with a list of strong and weak elements. I like to think that this frank admission of our ignorance of its cause(s) will be an important semantic sti...

Behçet’s syndrome is an inflammatory disorder of unknown aetiology that involves arteries and veins of all sizes. Most cases are from the countries around the Mediterranean basin, the Middle East, and East Asia, with the highest prevalence in Turkey. It typically presents in the second and third decades with recurrent oral ulcers (98% of cases), ge...

Objectives: Case reports and series suggest that Takayasu's arteritis (TAK) can co-exist with other inflammatory disorders. We conducted a formal study to look specifically at the frequency of such inflammatory disorders in a large cohort of TAK followed by a single tertiary centre. Methods: There were 238 patients registered with a diagnosis of...

The Editors, to underline the need for more clinical research in Behcet syndrome (BS), discuss, among surely many, some areas in which more work is needed. In this line, we like to draw the readers’ attention to subspecialty-based disease/classification criteria, a prospective approach to give more sound causality aspect to the gene associations we...

Behçet syndrome (BS) is a complex construct of unknown etiology(ies). As such a splitting rather than a lumping approach should be used in recognizing BS and deciphering its yet unknown disease mechanisms. So instead of a universal, we should have subspecialty-based classification/diagnostic criteria sets. Similarly, we should more aim to understan...

The expanded second edition of this important work provides an up-to-date and comprehensive overview of Behçet syndrome. New and updated chapters focus on recent advances in the areas of pathogenesis, the microbiome, genetics and epigenetics, clustering of symptoms, disease assessment and new treatment options. The book examines how these developme...

Objectives: CYC remains an important treatment option for Behçet's syndrome (BS) patients with life-threatening manifestations. However, adverse events may occur with CYC and this has led to increased use of biologic agents in other vasculitides. We investigated short and long term adverse events associated with CYC use in BS patients. Methods:...

Objectives: Superior vena cava syndrome (SVCS) is a medical emergency which can also be seen in Behçet's syndrome (BS). Having noted that BS patients with SVCS frequently complained of sleep disturbances, snoring and sleep apnea, suggesting obstructive sleep apnea (OSA), we formally surveyed the risk for OSA among BS patients. Methods: We studie...

Objectives: The p-value is commonly misused. We hypothesised that a close cooperation with a statistician would go along with a more proper use of p-values. We considered a close cooperation present, when a statistician was a coauthor, or a formal statistical help was acknowledged in a study report. Methods: Randomised controlled trials publishe...

Objectives: Lower extremity deep vein thrombosis (LEDVT) is a serious complication of Behçet's syndrome. Management constitutes mainly of administration of immunosuppressives, but the predictors of relapse and the optimal choice of immunosuppressives remain unclear. In this prospective study, we aimed to detect the risk and predictors of relapse a...

Background The usual onset of Behçet syndrome (BS) is in the 3. decade. Older age-onset defined as fulfilling the ISG criteria after 40 years of age is rare. One study from our center had reported the severity of eye disease was not different between early onset (≤ 24 years) and late onset (≥ 25 years) group. (1). While there is ambiguity in the de...

Background Behçet’s syndrome (BS) has a heterogeneous expression involving many organ systems and is diagnosed by recognizing the coexisting manifestations. Several patients initially have few of these manifestations and do not fulfill the International Study Group (ISG) criteria. When these are major organ manifestations, failure to recognize BS a...

Background There is an unmet need for reliable, validated, and widely-accepted outcome measures for clinical trials in Behçet’s syndrome (BS). Objectives The Outcome Measures in Rheumatology Clinical Trials (OMERACT) Behçet’s Syndrome Working Group has worked to advance the creation of a data-driven Core Domain Set for use in all clinical trials....

Background Mycophenolate mofetil (MMF) has been increasingly used in various rheumatic diseases. It may also be a safe and effective treatment option for Behçet’s syndrome (BS) where oral immunosuppressives other than azathioprine and cyclosporine are not available. Objectives We aimed to report our experience with MMF in BS patients with major or...

Background Uveitis in Behçet’s syndrome (BS) follows a recurrent disease course with inflammatory exacerbations causing damage in the uvea, retina and optic nerve even with treatment. Frequent attacks and posterior involvement are considered as predictors of poor visual outcome. Objectives The aim of this study is to delineate the predictors of da...

Background While thrombosis in Behçet’s Syndrome (BS) is considered to be mainly caused by inflammation in the vessel wall, several prothrombotic factors have been studied with inconsistent results. Objectives We aimed to perform a systematic review of clinical studies investigating the thrombophilic factors in BS. Methods The online database of...

Lower extremity venous thrombosis (DVT) is the most common vascular manifestation of Behçet’s syndrome (BS). Currently, Doppler ultrasonography (USG) is the most commonly preferred imaging modality in the diagnosis and follow-up of patients with acute and chronic DVT. Magnetic resonance (MR) venography, a quick and a non-invasive imaging modality,...

Objective: Lower extremity (LE) deep venous thrombosis (DVT) is the main feature of vascular involvement in Behçet disease (BD). We thought that vein wall thickness (VWT) could be a surrogate marker for venous inflammation and hence predict future vascular involvement. We assessed VWT in proximal LE veins in BD patients without DVT, BD patients wit...

OBJECTIVES: The faecal calprotectin (FC) test is widely used as a non-invasive method for identifying intestinal inflammation. A recent study suggested FC may help to diagnose gastrointestinal involvement of Behçet's syndrome (GIBS). We aimed to determine whether FC helps to distinguish active from inactive intestinal involvement in GIBS. METHODS:...

Objective: To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS. Methods: A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing ey...

The cover image, by Yesim Ozguler et al., is based on the Original Report Assessing the possible association of anti‐TNF use with new malignancies: A neglected methodological consideration, DOI: 10.1002/pds.4579. Design Credit: Yalcin Tuzun, MD

Purpose Whether anti‐TNF agents increase, malignancy risk remains debated. The potential problems with comparing the number of observed malignancies in anti‐TNF treated cohorts to number of expected malignancies in national cancer registries could have been an important issue. National registries give expected number of malignancies per organ invol...

Background Superior vena cava syndrome (SVCS), is a medical emergency and can also be seen in Behçet’s syndrome (BS). Contrary to the severe outcome seen in malign conditions, SVCS in BS usually has a benign course, complicated rarely by hemoptysis, pleural effusion, and a chylothorax. We had noted that BS patients with SVCS frequently complained o...

Background Formal experience with leg ulcers in Behçet’s syndrome (BS) is limited. It is a rare complication that can be seen during the course of mainly pts with the post-thrombotic syndrome. They can be difficult to manage and may cause disability leading to unemployment and severe impairment in quality of life. Objectives In this observational...

Background Sensorineural hearing loss has been reported to be increased in several chronic autoimmune and non-autoimmune diseases such as systemic lupus erythematosus (SLE), progressive systemic sclerosis, rheumatoid arthritis, small vessel vasculitides, ankylosing spondylitis and Behçet’s syndrome. We had sporadically noted several degrees of sens...

Background There is some evidence that incident Behcet’s syndrome (BS) might be becoming less severe.¹ Objectives We compared clinical findings at presentation of BS patients registered in a large, long standing dedicated multidisciplinary outpatient clinic at 4 time points during a 40 years period. Methods There were 4 groups. Group 1 included p...

Background Lower extremity vein thrombosis (LEVT) is the key feature of vascular involvement in Behçet’s syndrome (BS). Vein wall thickness (VWT) is proposed to be a surrogate marker of venous disease. A pilot MR study done in 7 BS patients and controls, had demonstrated increased VWT and signal enhancement in the lower extremity veins of BS patien...

Background A decline in the frequency of AA amyloidosis secondary to rheumatoid arthritis and infectious diseases has been reported. This is probably due to more effective treatment strategies. We had previously reported that although amyloidosis occurs in less than 0.5% of BS patients, it is one of the leading causes of death.1–3 We had an impress...

Background Lower extremity deep vein thrombosis (LEDVT) is a disabling complication of Behçet’s syndrome (BS). Relapses are frequent and cause permanent disability due to post-thrombotic syndrome.¹ The management of LEDVT in Behcet’s syndrome (BS) constitutes mainly of azathioprine (AZA) and corticosteroids (CS) as first-line agents.² Interferon-α...

Background The quality of statistical analysis and reporting are wanting even in our most prestigious journals.¹ It stands to reason that active participation of biostatisticians in data analysis and reporting would improve the situation. Objectives We aimed to test the hypothesis that more close cooperation with biostatisticians would improve the...

Background Pulmonary artery involvement (PAI) is the most common form of arterial involvement in Behçet’s syndrome (BS) and is a well-known cause of mortality and morbidity. A previous survey¹ by our group had analysed the clinical characteristics and outcome of 47 pts with PAI registered between 2000–2007 and shown that: 1.the overwhelming male pr...

Background Immunogenicity of anti-TNFs has been recognised as an important problem that may cause loss of efficacy and adverse events such as infusion reactions. Anti-TNFs are being increasingly used among patients with Behçet’s syndrome (BS). Objectives We aimed to investigate the prevalence of anti-drug antibodies against infliximab (IFX) in pat...

Background Cyclophosphamide (CYC) remains an important treatment option for Behçet’s syndrome (BS) patients with life-threatening conditions such as arterial aneurysms. However, several adverse events may occur with CYC and this has led to increased use of biologic agents such as rituximab in other vasculitides. Objectives The aim of this study is...

Objectives: The aim of this systematic review was to inform the update of European League Against Rheumatism (EULAR) Recommendations for the management of Behçet's syndrome (BS), on the evidence for the treatment of skin, mucosa and joint involvement of BS. Methods: A systematic literature search, data extraction, statistical analyses and assess...

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet’s syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was...

This corrects the article DOI: 10.1038/nrrheum.2017.208.

As we try to outline above, there is more to know about the disease mechanisms in Behçet syndrome. Importantly, we currently have much better insight about how HLA-B*51, the most established risk factor for Behçet syndrome, might be operative in pathogenesis. On the other hand, the frequency of HLA-B*51 is ∼60% even in areas where Behçet syndrome i...

Obectives: Menstruation triggers several conditions such as migraine, recurrent aphthous stomatitis and acne vulgaris in healthy individuals. There is evidence that Behçet's syndrome (BS) and familial Mediterranean fever (FMF) may exacerbate during menstruation. The aim is to assess whether BS and FMF patients experience menstrual flares. Methods...

Objectives: The prognosis of uveitis in Behçet's syndrome (BS) has improved over decades. Whether this is related to the use of more aggressive management strategies is not known. Methods: This is a retrospective study of BS patients who received infliximab (IFX) for refractory eye disease between 2003-2015. The patients were divided into two gr...

Objectives: Familial Mediterranean fever (FMF) is characterised by recurrent attacks of fever and serositis. It may affect the peritoneum, pleura, synovia and the skin. Usually the liver is intact in FMF. Recently, this concept was challenged by some groups which claimed that hepatitis is a feature of FMF and that non-alcoholic liver disease (NAFL...

Background Elevated fecal calprotectin (FC) levels indicate activity in Crohn's disease (CD) and ulcerative colitis and are used as non-invasive biomarkers in these diseases. Gastrointestinal involvement of Behçet's syndrome (GIBS) shows clinical and endoscopic similarities to CD. A previous study suggested that FC may help to diagnose GIBS patient...

Background Case reports and series suggest that Takayasu's arteritis (TA) can co-exist with various inflammatory disorders. Objectives We conducted a formal study to look specifically at the frequency of inflammatory disorders and symptoms in a large cohort of TA followed by a single tertiary center. Methods There were 238 patients registered wit...

Objectives Cardiovascular complications are the main causes of morbidity and mortality in the course of Takayasu arteritis (TA).In addition to the occlusive vasculitis,hypertension and accelerated atherosclerosis are possibly other factors playing role in the ethiopathogenesis of these complications.Although,strict management of traditional cardiov...

Background Papulopustular lesions (PPL) are the most common skin lesions in Behçet's syndrome (BS). Objectives To assess whether PPL are different in BS according to localization, age, sex and medications used when compared to rheumatoid arthritis patients (RA) and apparently healthy subjects (HS). Methods 209 consecutive BS patients who were rou...

Background Behcet's syndrome (BS) is a well-recognized cause of cerebral venous sinus thrombosis (CVST). Objectives We aimed to assess the outcome of a large cohort of patients with CVST due to BS attending a single dedicated center. Methods We identified 100 (81 M/19 F) patients with BS who were diagnosed as having CVST. All contacted were calle...

Background: Most patients have serious digestive complications after renal transplantation. Therefore, it is important to protect gastrointestinal function to improve the survival rate of transplant patients. Proton pump inhibitors (PPIs) such as lansoprazole and rabeprazole are widely administered to renal transplant patients with mycophenolic ac...

Background: Human leukocyte antigen (HLA) allo-immunization is caused by various events such as blood transfusions, pregnancies, or organ transplantations, which can lead to sensitization. In this retrospective study, we evaluated different sensitization models and their effects on panel-reactive antibody (PRA) profiles of renal transplantation ca...

Background: The serum levels of galactose-deficient immunoglobulin (Ig)A1 (Gd-IgA1) represent the most promising candidate biomarker for IgA nephropathy (IgAN). The aim of this study was to evaluate the serum levels of Gd-IgA1 as a novel noninvasive biomarker for post-transplant IgAN recurrence. Methods: Serum Gd-IgA1 levels of 18 patients with...

Background: Immunosuppressive regimens with tacrolimus or cyclosporine A (CsA) were compared for graft-related outcomes in conjunction with complement-binding de novo donor-specific antibodies (DSAs). Methods: Non-sensitized adult patients without rejection episodes within 3 months after transplantation were screened for the presence of de novo...

Background. Anesthetic management of patients during renal transplantation is vitally important for ensuring proper functioning of kidneys that have undergone ischemia-reperfusion damage. The goal of this prospective study was to compare the effects of 2 different inhalation agents (sevoflurane and desflurane) on grafted kidney function in renal tr...

Background: Anesthetic management of patients during renal transplantation is vitally important for ensuring proper functioning of kidneys that have undergone ischemia-reperfusion damage. The goal of this prospective study was to compare the effects of 2 different inhalation agents (sevoflurane and desflurane) on grafted kidney function in renal t...

Objective: The Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group has been working toward developing a data-driven core set of outcome measures for use in clinical trials of Beh?et's syndrome [Beh?et disease (BD)]. This paper summarizes the group's work through OMERACT 2016, discussions during the meeting, and the future research...

Although skin-mucosa lesions are common in almost all patients with Behçet syndrome (BS), clinical properties may differ from one patient to another. Within BS, there are subsets with different organ involvement and hence probably different pathological pathways. These subsets can be described as a) solo skin-mucosa disease with no major organ invo...