Tocilizumab may not be a good option for vascular involvement due to Behçet's syndrome.

OBJECTIVES: Tocilizumab has been increasingly reported as an alternative therapeutic agent in the management of Behçet's syndrome (BS) and it has been mostly tried in BS patients with neurological and eye involvement. As therapeutic responses to each drug may vary across different types of BS involvement, we aimed to report seven patients with large vessel involvement treated with tocilizumab. METHODS: We enrolled seven BS patients with vascular involvement who were given tocilizumab at the Behçet's Disease Research Centre in Istanbul University-Cerrahpasa between 2000 and 2022. Demographic information, BS features, types of vascular involvement, previous and concomitant medications, C-reactive protein (CRP) levels, imaging modality results, and outcomes were documented from the patients' medical records. RESULTS: Within a median of 6 months after the initiation of tocilizumab, 5 patients experienced vascular relapses. These relapses included the emergence of new bilateral pulmonary artery aneurysms, a new pulmonary artery thrombus, parenchymal lung involvement, deep vein thrombosis in the lower extremity, and pseudotumor cerebri in one patient each. CRP levels were normal in 4 of the 5 patients at the time of vascular relapse. One of these 5 patients and another patient with aortitis had an exacerbation of mucocutaneous symptoms. In the last patient, venous ulcers did not respond to tocilizumab and were complicated with infection. CONCLUSIONS: Tocilizumab could potentially exacerbate vascular manifestations, similar to what is observed with mucocutaneous lesions in BS patients. Furthermore, CRP levels appear to be ineffective in monitoring these patients.

Disease and Treatment-Specific Complications of Behçet Syndrome.

PURPOSE OF REVIEW: We aimed to highlight disease-related and treatment-related complications of Behçet syndrome (BS) based on previous and recent studies and our own experience. RECENT FINDINGS: The Behçet's Disease Overall Damage Index is a newly developed instrument to assess damage in BS. Validation studies showed that damage is already present in some patients at diagnosis and continues to progress during the follow-up, mainly related to treatment complications. Nervous system and eye involvement are important causes of long-term disability. Cyclophosphamide seems to be associated with infertility and an increased risk of malignancies among BS patients, prompting the consideration of shortening the treatment duration. Flares in mucocutaneous manifestations have been reported with tocilizumab, and de novo BS manifestations with secukinumab therapy. Earlier diagnosis and treatment are essential to prevent disease-related damage in BS. Treatment-related complications seem to be the leading cause of damage during the disease course.

Behçet's syndrome: one year in review 2023.

This critical review of studies on Behçet's syndrome published during 2022 includes studies on epidemiology, patients' perspective, pathogenesis, diagnosis, clinical features and management. Studies on pathogenesis included potential biomarkers mostly related to macrophages, neutrophil and cytokine balance, new GWAS and polymorphism studies, and studies on miRNAs and long non-coding RNAs. Clinical studies showed that application of pneumococcal vaccine to the prick site increased the sensitivity and specificity of the pathergy test and the prevalence of AA amyloidosis had decreased over the years. Studies on management indicated that more data are needed to understand the effect of apremilast on BS manifestations other than oral ulcers, and new BS manifestations may develop during treatment with infliximab. Other biologics and Jak inhibitors might be an option for patients who are refractory to TNF-α inhibitors. Moreover, endovascular repair of arterial aneurysms might be an alternative to open surgery.

Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

Infliximab for vascular involvement in Behçet's syndrome.

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 2004 and 2022 were reviewed. Primary endpoint was remission at Month 6, defined as lack of new clinical symptoms and findings associated with vascular lesion, lack of worsening of the primary vascular lesion and a new vascular lesion on imaging, and CRP < 10 mg/L. Relapse was defined as development of a new vascular lesion or recurrence of the preexisting vascular lesion. RESULTS: Among the 127 patients (102 men, mean age at IFX initiation: 35.8 ± 9.0 years) treated with IFX, 110 (87%) had received IFX for remission induction and 87 of these (79%) were already on immunosuppressives when the vascular lesion requiring IFX developed. The remission rate was 73% (93/127) at Month 6 and 63% (80/127) at Month 12. Seventeen patients experienced relapses. Remission rates were better among patients with pulmonary artery involvement and venous thrombosis compared to patients with non-pulmonary artery involvement and venous ulcers. Fourteen patients had adverse events leading to IFX discontinuation and 4 had died due to lung adenocarcinoma, sepsis, and pulmonary hypertension-related right heart failure due to pulmonary artery thrombosis (n = 2). CONCLUSION: Infliximab seems to be effective in majority of BS patients with vascular involvement, even in those who are refractory to immunosuppressives and glucocorticoids.

Apremilast Long-Term Safety Up to 5 Years from 15 Pooled Randomized, Placebo-Controlled Studies of Psoriasis, Psoriatic Arthritis, and Behçet's Syndrome.

BACKGROUND: Since US FDA approval in 2014, apremilast has consistently demonstrated a favorable benefit-risk profile in 706,585 patients (557,379 patient-years of exposure) worldwide across approved indications of plaque psoriasis, psoriatic arthritis, and Behçet's syndrome; however, long-term exposure across these indications has not been reported. OBJECTIVE: The aim of this study was to conduct a pooled analysis of apremilast data from 15 clinical studies with open-label extension phases, focusing on long-term safety. METHODS: We analyzed longer-term safety and tolerability of apremilast 30 mg twice daily across three indications for up to 5 years, focusing on adverse events of special interest, including thrombotic events, malignancies, major adverse cardiac events (MACE), serious infections, and depression. Data were pooled across 15 randomized, placebo-controlled studies and divided into placebo-controlled or all-apremilast-exposure groups. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Overall, 4183 patients were exposed to apremilast (6788 patient-years). Most TEAEs were mild to moderate in the placebo-controlled period (96.6%) and throughout all apremilast exposure (91.6%). TEAE rates of special interest were similar between treatment groups in the placebo-controlled period and remained low throughout all apremilast exposure. Exposure-adjusted incidence rates per 100 patient-years during all apremilast exposure were MACE, 0.30; thrombotic events, 0.10; malignancies, 1.0; serious infections, 1.10; serious opportunistic infections, 0.21; and depression, 1.78. Safety findings were consistent across indications and regions. No new safety signals were identified. CONCLUSIONS: The incidence of serious TEAEs and TEAEs of special interest was low despite long-term exposure, further establishing apremilast as a safe oral option for long-term use across indications with a favorable benefit-risk profile. CLINICAL TRIAL REGISTRATION: NCT00773734, NCT01194219, NCT01232283, NCT01690299, NCT01988103, NCT02425826, NCT03123471, NCT03721172, NCT01172938, NCT01212757, NCT01212770, NCT01307423, NCT01925768, NCT00866359, NCT02307513.

Behçet's disease risk-variant HLA-B51/ERAP1-Hap10 alters human CD8 T cell immunity.

OBJECTIVES: The endoplasmic reticulum aminopeptidase (ERAP1) haplotype Hap10 encodes for a variant allotype of the endoplasmic reticulum (ER)-resident peptide-trimming aminopeptidase ERAP1 with low enzymatic activity. This haplotype recessively confers the highest risk for Behçet's diseases (BD) currently known, but only in carriers of HLA-B*51, the classical risk factor for the disease. The mechanistic implications and biological consequences of this epistatic relationship are unknown. Here, we aimed to determine its biological relevance and functional impact. METHODS: We genotyped and immune phenotyped a cohort of 26 untreated Turkish BD subjects and 22 healthy donors, generated CRISPR-Cas9 ERAP1 KOs from HLA-B*51 + LCL, analysed the HLA class I-bound peptidome for peptide length differences and assessed immunogenicity of genome-edited cells in CD8 T cell co-culture systems. RESULTS: Allele frequencies of ERAP1-Hap10 were similar to previous studies. There were frequency shifts between antigen-experienced and naïve CD8 T cell populations of carriers and non-carriers of ERAP1-Hap10 in an HLA-B*51 background. ERAP1 KO cells showed peptidomes with longer peptides above 9mer and significant differences in their ability to stimulate alloreactive CD8 T cells compared with wild-type control cells. CONCLUSIONS: We demonstrate that hypoactive ERAP1 changes immunogenicity to CD8 T cells, mediated by an HLA class I peptidome with undertrimmed peptides. Naïve/effector CD8 T cell shifts in affected carriers provide evidence of the biological relevance of ERAP1-Hap10/HLA-B*51 at the cellular level and point to an HLA-B51-restricted process. Our findings suggest that variant ERAP1-Hap10 partakes in BD pathogenesis by generating HLA-B51-restricted peptides, causing a change in immunodominance of the ensuing CD8 T cell response.

Frequency of AA amyloidosis has decreased in Behçet's syndrome: a retrospective study with long-term follow-up and a systematic review.

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. METHODS: We identified patients with amyloidosis in our BS cohort (as well as their clinical and laboratory features, treatment, and outcome) through a chart review. The primary end points were end-stage renal disease and death. The prevalence of AA amyloidosis was estimated separately for patients registered during 1976-2000 and those registered during 2001-2017, in order to determine whether there was any change in the frequency. We searched PubMed and EMBASE for reports on BS patients with AA amyloidosis. Risk of bias was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool. RESULTS: The prevalence of AA amyloidosis was 0.62% (24/3820) in the earlier cohort and declined to 0.054% (3/5590) in the recent cohort. The systematic review revealed 82 cases in 42 publications. The main features of patients were male predominance and a high frequency of vascular involvement. One-third of patients died within 6 months after diagnosis of amyloidosis. CONCLUSION: The frequency of AA amyloidosis has decreased in patients with BS, which is similar to the decrease observed for AA amyloidosis due to other inflammatory and infectious causes. However, AA amyloidosis is a rare, but potentially fatal complication of BS.

18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging Appearance of Gastrointestinal Behcet's Disease.

Behcet's syndrome (BS) is a variable vessel vasculitis with multi-organ involvement. Recurrent episodes of oral and genital ulcers, papulopustular and erythema nodosum-like skin lesions, and arthritis are relatively more frequent, whereas uveitis, venous and arterial lesions, nervous system, and gastrointestinal involvement are less common, but are severe manifestations. The frequency of gastrointestinal involvement shows important variation between countries as more common in the Far East and the United States, and much less common in Turkey and the Middle East. The main clinical signs of gastrointestinal Behcet's disease include abdominal pain, diarrhea, blood in the stool, fever, and weight loss. Ulcers seen in the terminal ileum, cecum, and ascending colon are common endoscopic findings. Herein, we presented the positron emission tomography/magnetic resonance imaging findings of gastrointestinal involvement in BS.

Screening for latent tuberculosis before starting TNF-alpha inhibitors in a population with high BCG vaccination rates.

It is assumed that in candidates for TNF-alpha inhibitor (TNFi) treatment, tuberculin skin test (TST) may be unreliable, since BCG vaccination causes false positive and drugs cause false negative results, favoring the use of Quantiferon or T-spot assays. However, these tests may not be readily available in all parts of the world. We aimed to determine the reliability of TST with respect to BCG vaccination and drugs in candidates for TNFi treatment, and how isoniazid is tolerated, assuming that the use of TST would result in increased isoniazid use. We included 1031 adult patients who were prescribed a TNFi for the first time. We analysed the association of BCG and drugs with TST and Quantiferon results, the determinants of a positive TST, and evaluated the tolerability of isoniazid. BCG vaccination and male sex were associated with positive TST (OR 3.56, 95% CI 1.98-6.41 and OR 2.54, 95% CI 1.75-3.68, respectively), while prednisolone and azathioprine were associated with negative TST (OR 0.63, 95% CI 0.43-0.91 and OR 0.40, 95% CI 0.11-0.76). Isoniazid was prescribed to 684 (66.3%) patients and had to be discontinued in 12.2% of these before 9 months, most commonly due to hepatotoxicity (44%). One patient developed tuberculosis despite isoniazid use. BCG vaccination may be associated with false positive TST, despite a long time since vaccination in candidates for TNFi treatment. Prednisolone and azathioprine use were associated with negative TST. Despite the high frequency of isoniazid use associated with using TST instead of QTF, isoniazid was generally well tolerated.

The incidence, clinical characteristics, and outcome of COVID-19 in a prospectively followed cohort of patients with Behçet's syndrome.

Initial case series of small number of patients at the beginning of the pandemic reported a rather guarded prognosis for Behçet's syndrome (BS) patients infected with SARS-CoV-2. In this prospective study, we describe the incidence, clinical characteristics, disease course, management, and outcome in a large cohort of BS patients with laboratory-confirmed infection of SARS-CoV-2. We defined a cohort of 1047 registered BS patients who were aged between 16 and 60 years and seen routinely before the pandemic at the multidisciplinary outpatient clinic. We followed prospectively this cohort from beginning of April 2020 until the end of April 2021. During 13 months of follow-up, of the 1047 (599 M/448 F) patients, 592 (56.5%) were tested for SARS-CoV-2 PCR at least once and 215 (20.5%; 95% CI 0.18-0.23) were tested positive. We observed 2 peaks which took place in December 2020 and April 2021. Of the 215 PCR positive patients, complete information was available in 214. Of these 214, 14 (6.5%) were asymptomatic for COVID-19. In the remaining, the most common symptoms were anosmia, fatigue, fever, arthralgia, and headache. A total of 40 (18.7%) had lung involvement, 25 (11.7%) were hospitalized, 1 was admitted to the intensive care unit while none died. Favipiravir was the most prescribed drug (74.3%), followed by colchicine (40.2%), and hydroxychloroquine (20.1%) in the treatment of COVID-19. After COVID-19, 5 patients (2.3%) were given supplemental O2 and 31 (14.5%) antiaggregant or anticoagulants. During COVID-19, of the 214 PCR positive patients, 116 (54.2%) decreased the dose of their immunosuppressives or stopped taking completely; 36 (16.8%) experienced a BS flare which was mostly oral ulcers (10.3%). None of the patients reported a thrombotic event. A total of 93 (43.5%) patients reported BS flares after a median 45 days of COVID-19 infection and this was found to be significantly associated with immunosuppressive drug discontinuation. Multiple regression analysis adjusted for age and gender indicated that smoking and using interferon-alpha decreased the likelihood of getting COVID-19. The incidence and severity of COVID-19 did not differ between those who were using colchicine or not. The cumulative incidence of COVID-19 in this prospectively followed cohort of BS patients was almost two folds of that estimated for the general population living in Istanbul, Turkey, however, the clinical outcome of COVID-19 was not severe and there was no mortality. The protective effect of smoking and interferon deserves further investigation. On the other hand, colchicine did not have any positive or negative effect against COVID-19. Significant number of patients flared after COVID-19, however, this was significantly associated with immunosuppressive discontinuation during the infection. Contrary to our previous observations, COVID-19 did not seem to exacerbate thrombotic events during or after the infection.

One year in review 2021: Behçet's syndrome.

This review aims to provide a critical digest of the recent studies that enhance our understanding of Behçet's syndrome by evaluating time trends, differences in disease course between men and women, and between patients with an early and late disease onset, progress in disease assessment, novel findings on immunopathogenesis and genetics, clinical features and differential diagnosis of eye, vascular, nervous system and gastrointestinal system involvement, and new data on treatment modalities including TNF-alpha, IL-17 and IL-6 inhibitors, tofacitinib, and apremilast, as well as surgical interventions.

Aortic involvement in relapsing polychondritis: case-based review.

Relapsing polychondritis is a systemic inflammatory disease that mainly affects ears, nose, eyes, joints, and large airway. Relapsing polychondritis may also affect cardiac valves and large vessels with the aorta being most frequently involved. We conducted a systematic literature review to delineate the clinical characteristics, treatment, and outcome of relapsing polychondritis patients with aortic involvement including thoracic and abdominal aorta, aortic valve, and coronary arteries. 113 patients reported in 85 manuscripts were retrieved through the systematic literature search and references of the selected manuscripts. With the addition of a patient from our center, a total of 114 patients were included in the analyses. Aortic vessel involvement was the predominant type of involvement that was identified in 93 (82%) patients, while aortic valve involvement was identified in 41 patients (36%). The median age at aortic involvement was 37 years [IQR: 30-53] with a delay of 5 years [IQR: 1-8] between first relapsing polychondritis symptom and aortic involvement. Nineteen percent of the patients were asymptomatic at the time of aortic involvement diagnosis. The initial treatment was immunosuppressives in 41 patients (56%) and surgery in 28 patients (38%). The mortality ratio was 27% in a 24 month follow-up [IQR: 7.5-54 months]. Aortic dissection or rupture was the most frequent causes of mortality. Concomitant coronary artery involvement suggested a worse outcome. Aortic involvement in relapsing polychondritis is a mortal complication despite medical and surgical treatments. It may be asymptomatic in 19% of the patients which warrants the importance of screening.

How to treat myelodysplastic syndrome with clinical features resembling Behçet syndrome: a case-based systematic review.

The association between myelodysplastic syndrome (MDS) and Behçet syndrome (BS) is recognized for over 25 years. High frequency of trisomy 8 and intestinal ulcers are striking features of this association. There are no recommendations for how these patients should be treated. A systematic literature review was performed in PubMed using the keyword combination "(((((intestinal) OR gastrointestinal) OR ulcer) OR Behcet*)) AND ((myelodysplastic syndrome) OR MDS)" in March 2019. Our aim was to gain insight regarding clinical responses to individual treatment modalities. A recent case was also presented and included in the analysis. Data from 41 articles reporting on a total of 53 patients carried adequate information to assess treatment responses. Glucocorticoids provided benefit in 23 of 43 patients. Azacitidine, decitabine, thalidomide, and cyclosporine contributed to a clinical improvement in 4/6, 2/3, 3/4, and 5/8 patients respectively. Hematopoietic stem cell transplantation was successful in 9 of 13 patients. With the use of TNF inhibitors, azathioprine, and mesalamine derivatives, clinical improvement was observed in 3/11, 0/4, and 6/18 patients respectively. Patients with MDS and BS-like features who are resistant to glucocorticoids have so far benefited more from treatment approaches directed at MDS, rather than the immunosuppressive agents used for BS.

Immunogenicity of Infliximab Among Patients With Behçet Syndrome: A Controlled Study.

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 prevalence of anti-infliximab (IFX) antibodies in patients with Behçet syndrome together with suitable controls. Methods: We collected serum samples from 66 consecutive Behçet syndrome patients (51 M, 15 F, mean age 37 ± 9 years) who were treated with IFX. Additionally, similarly treated 27 rheumatoid arthritis, 53 ankylosing spondylitis, 25 Crohn's disease patients, and 31 healthy subjects were included as controls. Samples were collected just before an infusion, stored at -80°C until analysis, and serum IFX trough levels and anti-IFX antibodies were measured by ELISA. We used a cut-off value of 1 µg/ml for serum IFX trough level, extrapolating from rheumatoid arthritis studies. Results: Anti-IFX antibodies were detected in four (6%) Behçet syndrome, five (18.5%) rheumatoid arthritis, three (12%) Crohn's disease, and one (2%) ankylosing spondylitis patient. The median serum IFX trough level was significantly lower in patients with anti-IFX antibodies compared to those without antibodies [2.32 (IQR: 0.6-3.6) vs. 3.35 (IQR: 1.63-5.6); p = 0.019]. The serum IFX trough level was lower than the cut-off value in 6/13 (46%) patients with anti-IFX antibodies and in 25/158 (16%) patients without anti-IFX antibodies (p = 0.015). Among the four Behçet syndrome patients with anti-IFX antibodies, two experienced relapses and two had infusion reactions. Conclusions: Immunogenicity does not seem to be a frequent problem in Behçet syndrome patients treated with IFX, but may be associated with relapses and infusion reactions, when present.

Long term follow-up of Behçet's syndrome patients treated with cyclophosphamide.

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: We conducted a retrospective chart review of all BS patients treated with CYC between 1972 and 2006. Patients were called in and a standard form was used for collecting demographic characteristics, indication for CYC, its cumulative dose and short term adverse events, defined as those causing discontinuation of CYC, hospitalization and/or death, long term adverse events, including infertility and malignancy, and outcome. RESULTS: Of 5790 BS patients, 198 (3.4%) had used at least one dose of CYC. Main indications were vascular or neurological involvement. After a median follow-up of 17 years, 52 (26%) patients had died, 113 (57%) could be contacted, and 33 (17%) were lost to follow-up. Vascular involvement was the leading cause of death (n = 27). Seventeen (9%) patients experienced short term adverse events with haemorrhagic cystitis being the most common. After a median follow-up of 25 years (interquartile range: 15-26 years), 17 malignancies occurred in 15 (8%) patients. Infertility was experienced by 26 (30%) patients. CONCLUSION: Long term adverse events such as malignancy and infertility were major problems in our BS patients treated with CYC. These results underline the need for safer treatment modalities that are at least as effective as CYC.

One year in review 2019: Behçet's syndrome.

Several epidemiologic studies report on the prevalence of Behçet's syndrome (BS) and demographic and clinical findings in patients from different countries and ethnicities. Although these studies point out geographic differences in disease course, methodologic differences make it difficult to compare the results of these studies. Recent data suggest that neutrophil extracellular trap levels are elevated in patients with BS, and that it may be a potential therapeutic target for the reduction or prevention of BS-associated thrombotic risk. Details on the mode of functioning of ERAP have been delineated and further epigenetic data reported. Wall thickness of lower extremity veins is increased among BS patients without any apparent clinical involvement. Magnetic resonance (MR) venography and Doppler ultrasonography (USG) were comparable in the diagnosis of chronic deep vein thrombosis, while MR venography is more effective in detecting collateral formations. Results were also collected on some dietary and non-dietary factors in triggering oral ulcers, while smoking seems to have a protective role. With regards to the therapy, it has been demonstrated that endovascular interventions carry the risk of inducing pathergy phenomenon. Apremilast has been convincingly shown to be useful for oral ulcers of BS and classical immunosuppressives are effective as first line therapy in more than half of patients with uveitis. While infliximab and adalimumab seem to be equally effective in the treatment of refractory uveitis of BS, the combination of adalimumab and immunosuppressives appears to be superior to immunosuppressives alone for venous thrombosis of the extremities. In addition, tocilizumab might be an alternative to anti-TNF agents for patients with arterial involvement refractory to immunosuppressives. On the other hand, the place of IL-17 inhibition in the treatment of BS still remains questionable.

Update on the treatment of Behçet's syndrome.

Behçet's syndrome (BS) is a complex disease that shows important heterogeneity in clinical findings and physiopathology. Its treatment can be problematic as BS manifestations in different organs may respond differently to the same drug. The cornerstone of therapy for inducing remission is corticosteroids whereas immunomodulatory and immunosuppressive agents such as colchicine, azathioprine, cyclosporine-A, interferon-alpha, and cyclophosphamide are used as steroid-sparing agents and to prevent further relapses. However, a considerable number of patients continue to have mucocutaneous lesions despite therapy, and some patients require more aggressive treatment for refractory major organ involvement. Tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, are increasingly used for various refractory BS manifestations despite the lack of controlled studies. In this review, we aim to focus on both the traditional and new treatment modalities for BS, with more emphasis on recent data on newer agents.