Recomendaciones SER sobre el tratamiento del síndrome de Behçet refractario / SER recommendations on treatment of refractory Behçet's syndrome

Objetivo: Elaborar recomendaciones multidisciplinares, basadas en la evidencia disponible y el consenso de expertos, para el manejo terapéutico de los pacientes con síndrome de Behçet refractario (difícil de tratar, resistente grave, recidivante grave) al tratamiento convencional. Métodos: Un panel de expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Estas preguntas fueron reformuladas en formato PICO –paciente, intervención, comparación, outcome o desenlace–. A continuación, se realizaron revisiones sistemáticas; la evaluación de la calidad de la evidencia se realizó siguiendo la metodología del grupo internacional de trabajo Grading of Recommendations, Assessment, Development, and Evaluation. Tras esto, el panel multidisciplinar formuló las recomendaciones. Resultados: Se seleccionaron 4 preguntas PICO relativas a la eficacia y seguridad de los tratamientos farmacológicos sistémicos en los pacientes con síndrome de Behçet con manifestaciones clínicas refractarias a terapia convencional, relacionadas con los fenotipos mucocutáneo y/o articular, vascular, neurológico-parenquimatoso y gastrointestinal. Se formularon un total de 7 recomendaciones estructuradas por pregunta, con base en la evidencia encontrada y el consenso de expertos. Conclusiones: El tratamiento de las manifestaciones clínicas más graves del síndrome de Behçet carece de evidencia científica sólida y no existen documentos de recomendaciones específicas para los pacientes con enfermedad refractaria a la terapia convencional. Con el fin de aportar una respuesta a esta necesidad, se presenta el primer documento de recomendaciones de la Sociedad Española de Reumatología específicas para el abordaje terapéutico de estos pacientes, que servirá de ayuda en la toma de decisiones clínica y la reducción de la variabilidad en la atención.(AU)

Objective: To develop multidisciplinary recommendations based on available evidence and expert consensus for the therapeutic management of patients with refractory Behçet's syndrome (difficult to treat, severe resistant, severe relapse) to conventional treatment. Methods: A group of experts identified clinical research questions relevant to the objective of the document. These questions were reformulated in PICO format –patient, intervention, comparison and outcome–. Systematic reviews of the evidence were conducted; the quality of the evidence was evaluated following the methodology of the international working group Grading of Recommendations, Assessment, Development, and Evaluation. After that, the multidisciplinary panel formulated the specific recommendations. Results: Four PICO questions were selected regarding the efficacy and safety of systemic pharmacological treatments in patients with Behçet's syndrome with clinical manifestations refractory to conventional therapy related to mucocutaneous and/or articular, vascular, neurological parenchymal and gastrointestinal phenotypes. A total of 7 recommendations were made, structured by question, based on the identified evidence and expert consensus. Conclusions: The treatment of most severe clinical manifestations of Behçet's syndrome lacks solid scientific evidence and, besides, there are no specific recommendation documents for patients with refractory disease. With the aim of providing a response to this need, here we present the first official recommendations of the Spanish Society of Rheumatology for the management of these patients. They are devised as a tool for assistance in clinical decision making, therapeutic homogenisation and to reduce variability in the care of these patients.(AU)

SNP-mediated binding of TBX1 to the enhancer element of IL-10 reduces the risk of Behçet's disease.

Aims: The genetic association between Behçet's disease susceptibility and IL-10 has been confirmed in multiple cohorts, but the underlying mechanism of this association remains unclear. Materials & methods: We combined public resources and laboratory experiments (electrophoretic mobility shift assays, chromatin immunoprecipitation, luciferase reporter gene and CRISPR/Cas9 genome editing) to analyze transcription factor binding and enhancer activity controlling IL-10 expression. Results & conclusion: The T allele of noncoding rs3024490 within super-enhancer elements is able to specifically bind TBX1 and, in turn, promotes the enhancer activity and increased expression of IL-10. However, a relative deficiency in TBX1 in Behçet's disease patients leads to the low expression of IL-10 and increased risk of developing Behçet's disease.

Lay abstract Behçet's disease is a prominant cause of blindness. Previous reports show that genetic factors are linked with this disease, although the exact genetic mechanism is unclear. Many of these genetic factors are involved in the control of the immune response, including a large family of proteins known as cytokines. Some of the cytokines are proinflammatory while others can dampen the inflammatory response. An example of the latter is the IL-10 cytokine. We found that individuals carrying a specific site in the noncoding region of the IL-10 gene had a higher risk of Behçet's disease than other noncarriers. This study was designed to further investigate the biological mechanisms explaining the role of the specific site in the development of Behçet's disease. The results show that this specific site affects the binding of an important transcription factor, TBX1, which reduces IL-10 production. The dysregulated control of IL-10 explains why individuals with this genetic trait are more susceptible to developing Behçet's disease.

Inflammatory status might direct ILC and NK cells to IL-17 expressing ILC3 and NK subsets in Behcet's disease.

Innate lymphoid cells (ILCs) are lymphoid cells that have important effector and regulatory functions in innate immunity and tissue remodeling. Uncontrolled activation and proliferation of ILCs can contribute to inflammatory autoimmune diseases. Behcet's disease (BD) is a complex systemic inflammatory disorder of unknown etiology. It has been shown that natural killer (NK) cells may play an immunoregulatory role in BD, however the role of ILCs is unknown. In this study, the levels and functions of ILCs and NK cell subsets in BD patients were investigated. Cell surface and cytotoxic granules (perforin and granzyme) expression of NK cells and ILCs were evaluated and labeled according to whole blood lysing protocol in peripheral blood samples obtained from the patients and healthy subjects. Cytokine levels of NK cells were investigated in stimulated peripheral blood mononuclear cells. All data were analyzed by flow cytometry. Total ILC and ILC3+ cells were increased in active BD patients compared to inactive BD patients and healthy subjects. There was no significant difference between the patients and healthy subjects regarding NK cell surface and intracellular molecule expression. Although, an increase in IFN-γ and IL-17, and a decrease in IL-4 levels were observed in CD56dim NK cell subset of BD patients. Recent studies showed increased neutrophilic infiltration and IL-17 secreting Th17 cells in BD patients. It is known that ILC3+cells are similar to Th17 subset regarding their cytokine profile and transcription factor expression patterns. Results of current study may suggest that inflammatory microenvironment in BD patients might direct ILC cells to differentiate into ILC3+ subset, and IL-17 released by NK cells might have a role in neutrophilic infiltration.

Interrelationship of Stress, Environment, and Herpes Simplex Virus Type-1 on Behçet's Disease: Using a Mouse Model.

The purpose of this study was to investigate effects of stress and environment factors on the induction of Behçet's disease (BD) using HSV-1 infected mouse model. BD is a chronic multisystemic inflammatory disease of unknown etiology. Environmental factors, immune dysfunction, and herpes simplex virus type-1 (HSV) infection might be triggers of BD. To investigate effects of environmental factors on the incidence of BD, HSV was inoculated into mice. Mice were then maintained in conventional facility or SPF facility to compare BD incidence rates. The incidence of BD was also tracked by adding stressors such as substance P (anxiety stress), 4°C (cold stress), xanthine sodium salt (oxidative stress), or 77 dB noise (noise stress). To clarify immune mechanisms involved in the difference in BD incidence caused by various stresses, dendritic cell activation markers were analyzed using flow cytometry. The combination of conventional environment, noise stress, and HSV had the highest rate of BD (38.1%) among all groups. However, HSV inoculated group in a SPF environment had the lowest incidence (2.2%). Frequencies of dendritic cell activation markers such as CD40, CD83, CD80, and CD86 were expressed differently under various stresses. Noise stress increased frequencies of CD83 positive cells. Noise stress also upregulated transcription factors T-bet and ROR-γt. Different gut microbiota compositions were observed between SPF and conventional environment by 16S rRNA sequence analysis. Environment and stress influenced the incidence of HSV-induced BD. Microbial diversity due to environmental differences might be one explanation for regional differences in the incidence of BD.

Association of Behçet disease with psoriasis and psoriatic arthritis.

Behçet disease (BD) is a debilitating multi-systemic vasculitis with a litany of muco-cutaneous manifestations and potentially lethal complications. Meanwhile, psoriasis (PSO) is a cutaneous and systemic inflammatory disorder marked by hyperplastic epidermis and silvery scales, which may be accompanied by a distinct form of arthropathy called psoriatic arthritis (PsA). While the clinical pictures of these two are quite different, they feature some important similarities, most of which may stem from the autoinflammatory components of BD and PSO. Therefore, the aim of this study was to investigate the prospective link between BD and cutaneous and articular manifestations of psoriasis. BD, PSO, and PsA cohorts were extracted using the National Health Insurance Service of Korea database. Using χ2 tests, prevalence of PSO and PsA with respect to BD status was analysed. Relative to non-BD individuals, those with personal history of BD were nearly three times more likely to be diagnosed with PSO. The adjusted odds ratio (aOR) was 2.36 [95% confidence interval (CI), 1.91-2.93, p < 0.001]. Elevated PSO risk was more pronounced in the male BD cohort (aOR = 1.19, 95% CI 1.16-1.23, p < 0.001). In age-group sub-analysis, individuals over 65 years with PSO were one and a half times more likely to be affected with BD, relative to those under 65. The adjusted OR for the older group was 1.51 (95% CI 1.43-1.59, p < 0.001). BD individuals with "healthy" body weight were significantly less likely to be affected by PSO (aOR = 0.59, 95% CI 0.57-0.62, p < 0.001). On the other hand, there was a correlation between BMI and the risk of BD, with the "moderately obese (30-35 kg/m2)" group having an aOR of 1.24 (95% CI 1.12-1.38, p < 0.001). BD patients were also twice more likely to be associated with PsA (aOR = 2.19, 95% CI 1.42-3.38, p < 0.001). However, in contrast to the case of psoriatic disease itself, females were exposed to a greater risk of developing BD compared to the male PsA cohort (aOR = 2.02, 95% CI 1.88-2.16, p < 0.001). As with PSO, older BD patients were exposed to a significantly higher risk of developing PsA (aOR = 3.13, 95% CI 2.90-3.40, p < 0.001). Behçet disease may place an individual at a significantly increased risk of psoriasis, and still greater hazard of being affected with psoriatic arthritis. This added risk was pronounced in the male cohort, and tended to impact senile population, and this phenomenon may be related with the relatively poor prognosis of BD in males and PSO in older patients.

Acometimento vascular na doença de Behçet: o processo imunopatológico / Vascular involvement in Behçet's disease: the immunopathological process

Resumo A doença de Behçet constitui uma forma rara de vasculite sistêmica, que acomete de pequenos a grandes vasos. É caracterizada por manifestações mucocutâneas, pulmonares, cardiovasculares, gastrointestinais e neurológicas. Sua apresentação clínica é bastante ampla, variando de casos mais brandos a casos graves, com acometimento multissistêmico, caracteristicamente com exacerbações e remissões. Suas causas ainda são desconhecidas; entretanto, há evidências genéticas, ambientais e imunológicas, como a associação com o alelo HLA-B51. Todas essas, em conjunto, apontam para um processo imunopatológico anormal, com ativação de células da imunidade inata e adaptativa, como as células natural killer, neutrófilos e células T, que geram padrões de respostas e citocinas específicos capazes de gerar mediadores que podem lesionar e inflamar o sistema vascular, resultando em oclusões venosas, arteriais e/ou formação de aneurismas.

Abstract Behçet's disease is a rare form of systemic vasculitis that affects small to large vessels. It is characterized by mucocutaneous, pulmonary, cardiovascular, gastrointestinal, and neurological manifestations. Its clinical presentation is quite wide, ranging from milder cases to severe cases, with multisystemic involvement, characteristically with exacerbations and remissions. Its etiopathogenesis is still unclear, although there is evidence of genetic, environmental, and immunological factors, such as the association with the HLA-B51 allele. In conjunction, all of these point to an abnormal immunopathological process, with activation of cells of innate and adaptive immunity, such as NK cells, neutrophils, and T cells, which generate specific response patterns and cytokines capable of generating mediators that can damage and inflame blood vessels, resulting in venous and arterial occlusions and/or aneurysm formation.

Past and Present Behçet's Disease Animal Models.

Behçet's disease (BD) is presumably an autoinflammatory disease of unknown etiology for which several animal models have been described over the years. Agents and methods used for the development of these models have ranged from the herpes simplex type one virus (hsv-1) pathogen to the use of transgenic mice. Other models have also been used to investigate a possible autoimmune component. Each model possesses its own unique set of benefits and shortcomings, with no one model fully being able to recapitulate the disease phenotype. Here, we review the proposed models and provide commentary on their effectiveness and usefulness in studying the disease.

Immune-Related Adverse Events Mimicking Behcet's Disease in a Gastric Cancer Patient Following Camrelizumab Treatment.

BACKGROUND: Anti-programmed cell death 1(anti-PD-1) antibodies are immune checkpoint inhibitors (ICIs) used as a treatment option for a number of cancers to expand lifespan. However, the toxicity caused by ICIs is often unpredictable and can be occasionally life-threatening. OBJECTIVE: To evaluate the immune-related adverse events (irAEs) induced by Camrelizumab, an anti-PD-1 antibody in a patient with gastric cancer. CASE: The patient was a 32-year-old man who was diagnosed with stage IIIA gastric adenocarcinoma (cT4aN1M0) in pre-operative evaluation. However, pancreatic invasion and peritoneal metastasis were found during surgery. He received a three-week cycle of 200 mg Camrelizumab combined with systemic chemotherapy. After the fifth administration of Camrelizumab, the patient displayed irAE mimicking Behcet's disease with oral and penile ulcers, skin and abdominal incision lesions. Camrelizumab was permanently discontinued, but systemic chemotherapy was continued. The symptoms were improved with discontinuation of Camrelizumab and administration of glucocorticoid and immunosuppressive agents for 8 weeks, but suspicious liver metastases occurred and carbohydrate antigen 19-9 showed an increasing trend in the meantime. Given the significant improvement in the patient's symptoms after discontinuation of Camrelizumab and administration of corticosteroids and immunosuppressants, we assumed that these treatments may play a role in the rehabilitation of patients. CONCLUSION: Severe irAEs occur at a low frequency when anti-PD-1 antibodies are used as monotherapy. Whether anti-PD-1 antibodies combined with systemic chemotherapy increase the incidence of irAEs is not certain.

Modulation of gut microbiota through nutritional interventions in Behçet's syndrome patients (the MAMBA study): study protocol for a randomized controlled trial.

BACKGROUND: Behçet's syndrome (BS) is a systemic inflammatory disorder of unknown etiology, and it is characterized by a wide range of potential clinical manifestations. Recent evidence suggests that the gut microbiota (GM) in BS has low biodiversity with a significant depletion in butyrate producers. The aim of the present project is to investigate whether a dietary intervention could ameliorate the clinical manifestations and modulate the GM of individuals with BS. METHODS: This is a randomized, open, cross-over study that involves 90 individuals with BS, who will be randomly assigned to one of three different diets for 3 months: a lacto-ovo-vegetarian diet (VD), a Mediterranean diet (MD), or a Mediterranean diet supplemented with butyrate (MD-Bt). The VD will contain inulin-resistant and resistant-starch-rich foods, eggs, and dairy in addition to plant-based food, but it will not contain meat, poultry, or fish. The MD will contain all food categories and will provide two portions per week of fish and three portions per week of fresh and processed meat. The MD-Bt will be similar to the MD but supplemented with 1.8 g/day of oral butyrate. The three different diets will be isocaloric and related to the participants' nutritional requirements. Anthropometric measurements, body composition, blood, and fecal samples will be obtained from each participant at the beginning and the end of each intervention phase. The primary outcomes will be represented by the change from baseline of the BS gastrointestinal and systemic symptoms. Changes from baseline in GM composition, short-chain fatty acid (SCFA) production, and the inflammatory and antioxidant profile will be considered as secondary outcomes. DISCUSSION: BS is a rare disease, and, actually, not all the available treatments are target therapies. A supportive treatment based on dietary and lifestyle issues, able to restore immune system homeostasis, could have a high impact on cost sustainability for the treatment of such a chronic and disabling inflammatory condition. TRIAL REGISTRATION: clinicaltrials.gov: NCT03962335. Registered on 21 May 2019.

Factors influencing the recurrence of arterial involvement after surgical repair in Behçet disease.

OBJECTIVE: Arterial involvement in Behçet disease (BD) is rare, and its surgical management is a major concern because of its high recurrence rate. This study evaluated the influence of the surgical technique, device, and immunosuppressive treatment used on the postoperative recurrence in patients with non-pulmonary arterial BD. METHODS: A single-center, retrospective study was conducted of 23 patients meeting the international criteria for BD who underwent surgery for arterial involvement between May 1996 and September 2015. Recurrence was defined as the occurrence of arterial aneurysm or thrombosis during follow-up. Perioperative medical treatment and surgical technique used were reported. RESULTS: There were 47 surgical procedures performed in 23 patients. Mean follow-up was 8.4 ± 7.5 years. Initial arterial lesions were aneurysms and thrombosis in 85% and 15% of cases, respectively. Arterial lesions were aortic and peripheral in 48% and 52% of cases. Recurrence rate was 51%. Recurrences developed within <1 year in 24% of cases and at the same anatomic site in 92% of cases. Among the 24 recurrences, 17 were false aneurysms, 6 were thrombosis, and 1 was a true aneurysm in a different arterial site. To treat the arterial lesion, direct anastomosis was performed in 6 cases; bypass using the saphenous vein, graft, or allograft was performed in 6, 27, and 5 cases, respectively; and stent graft was used in 3 cases. Vascular lesions involved the aorta in 19 cases and a peripheral artery in 28 cases. Preoperative medical treatments, including colchicine, steroids, and immunosuppressants, significantly decreased recurrence rate: 28% (7/25) vs 75% (15/20) in untreated patients (P = .002). The recurrence rate was 42.5% (17/40) in patients treated postoperatively vs 80% (4/5) in untreated patients. The nature of the device used (vein, prosthetic graft, allograft, stent graft, or direct anastomosis) did not change the risk of recurrence. When anastomoses were protected using the prosthetic sleeving technique, the recurrence rate was three times lower (P = .08). CONCLUSIONS: Relapse is a main concern after surgical repair of arterial BD. This study suggests the need for targeted perioperative medical management to reduce the risk of arterial recurrence in BD patients. To this end, a multidisciplinary approach is mandatory. The use of sleeve anastomosis is associated with a numerically lower risk of recurrence. However, further studies are needed to confirm this efficacy.

BehÒ«et's Disease, and the Role of TNF-α and TNF-α Blockers.

In this both narrative and systematic review, we explore the role of TNF-α in the immunopathogenesis of Behçet's disease (BD) and the effect of treatment with TNF-α blockers. BD is an auto-inflammatory disease, characterized by recurrent painful oral ulcerations. The pathogenesis of BD is not yet elucidated; it is assumed that TNF-α may play a key role. In the narrative review, we report an increased production of TNF-α, which may be stimulated via TLR-signaling, or triggered by increased levels of IL-1ß and IFN-γ. The abundance of TNF-α is found in both serum and in sites of inflammation. This increased presence of TNF-α stimulates T-cell development toward pro-inflammatory subsets, such as Th17 and Th22 cells. Treatment directed against the surplus of TNF-α is investigated in the systematic review, performed according to the PRISMA guideline. We searched the Pubmed and Cochrane database, including comparative studies only. After including 11 studies, we report a beneficial effect of treatment with TNF-α blockers on the various manifestations of BD. In conclusion, the pivotal role of TNF-α in the immunopathogenesis of BD is reflected in both the evidence of their pro-inflammatory effects in BD and in the evidence of the positive effect of treatment on the course of disease in BD.

Tumor necrosis factor (TNF)-308, -1031, and angiotensin-converting enzyme (ACE) DD/II polymorphisms' role in Behcet's disease with and without uveitis: a meta-analysis.

PURPOSE: There are conflicting results of studies investigating the association between the tumor necrosis factor (TNF) and angiotensin-converting enzyme (ACE) gene polymorphisms and Behcet's disease (BD). The aim of this meta-analysis is to assess the association between these gene polymorphisms and ocular involvement in BD. METHODS: We identified relevant studies and reviewed the full-text manuscripts of the studies in order to select those for inclusion. Heterogeneity of studies was evaluated using Cochran Q-test and I-square index. To modify the heterogeneity in the variables we used random effects model. Meta-analysis was performed using STATA. RESULTS: We analyzed TNF-1031, -308 and ACE DD/II genotype difference between BD patients with and without uveitis. Among these polymorphic genetic loci TNF-308 AA genotype has a statistically significant protective effect against BD uveitis (OR = 0.45 vs 1.23, p = .017). Such a statistically significant effect was not seen for other studied genotypes. CONCLUSION: This meta-analysis revealed a significant protective effect of TNF-308 AA genotype against ocular involvement in Behcet's disease.

Behçet Syndrome as a Construct

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 stimulus for more meaningful research.

Interleukin-27 gene variant rs153109 is associated with enhanced cytokine serum levels and susceptibility to Behçet's disease in the Iranian population.

Behcet's disease (BD) is a systemic vasculitis, characterized by recurrent oral aphthous, genital ulcers, ocular lesions, and other organ involvement. Interleukin (IL)-27 with its pro- and anti-inflammatory effects might be an important effective cytokine in this disease. The aim of this study was to investigate the association of IL-27 serum concentration and a single-nucleotide polymorphism (SNP) rs153109 (-964 A > G) with the risk and clinical features of the patients with BD. IL-27 Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the IL-27 serum levels were measured using enzyme-linked immunosorbent assay (ELISA). It is shown that AG, GG, and AG + GG genotypes, as well as G allele of rs153109, can significantly increase the risk of BD in total and in male individuals. Significantly higher frequencies of AG and GG genotypes and G allele were observed in total and male patients with an active form of BD. AG and GG genotypes were associated with joint (p = 0.046) and vascular (p = 0.02) involvement. The frequency of the G allele was higher in all patients, as well as in female patients with vascular involvement (p = 0.02). Serum cytokine analysis indicated an increased level of IL-27 in BD patients compared to healthy subjects (p = 0.038). Additionally, a higher level of IL-27 was detected in patients carrying the rs153109 GG genotype (p = 0.04) and those with renal (p = 0.009) and skin (p = 0.05) involvement. In conclusion, this study underscores the involvement of IL-27 rs153109 variants and increased serum level in BD susceptibility and pathogenesis.

Association of Interleukin-23R Gene Polymorphisms with Behcet's Disease Susceptibility: A Meta-Analysis of Case-control Studies.

BACKGROUND: The pathological mechanisms associated with the occurrence and development of Behcet's disease (BD) are not yet known. Two large genome-wide association surveys revealed an association between interleukin (IL)-23R single nucleotide polymorphism and BD. This study aimed to investigate the association between IL-23R gene polymorphisms and BD susceptibility. METHODS: Comprehensive literature search was performed across four online databases - PubMed, Embase, Cochrane Library, and Web of science. The included studies had to be published before May 15, 2019. The Newcastle-Ottawa scale was used to assess the quality of every included study, and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using the allele model of inheritance to evaluate the potential associations between IL-23R gene polymorphisms and BD risk. RESULTS: In all, 12 case-control studies comprising 6,926 BD patients and 10,211 controls were identified and included in this meta-analysis, in which 5 loci of IL-23R gene polymorphisms were investigated. Of these 5 loci, 2 were found to be significantly associated with BD susceptibility: rs17375018 (G vs. A, OR = 1.50, 95% CI: 1.34-1.68, P < .00001) and rs924080 (T vs. C, OR = 1.36, 95% CI: 1.29-1.43, P < .00001). Only a systematic review was conducted for rs12119179, rs11209032, and rs12141431, owing to the lack of sufficient data. CONCLUSION: This meta-analysis indicated that rs17375018 (G/A) and rs924080 (T/C) were associated with BD susceptibility. However, association of the other IL-23R polymorphisms could not be estimated owing to the lack of studies. ABBREVIATIONS: BD: Behcet's disease; SNP: single nucleotide polymorphism; HLA: human leukocyte antigen; IL: interleukin; OR: odds ratio; CI: confidence interval; HWE: Hardy-Weinberg equilibrium; UK: United Kingdom; NOS: Newcastle-Ottawa scale; GWAS: genome-wide association study; TNF-α: tumor necrosis factor-α.

Enhanced NLRP3 and DEFA1B Expression During the Active Stage of Parenchymal Neuro-Behçet's Disease.

BACKGROUND/AIM: Neurological symptoms (neuro-Behçet's disease; NBD) occur in a fraction of Behçet's disease (BD) patients and often present with parenchymal brain lesions and clinical exacerbations. Our aim was to identify genes associated with attack and remission periods of NBD. MATERIALS AND METHODS: Microarray analysis was performed using peripheral blood mononuclear cell (PBMC) samples obtained during attack and remission periods of five NBD patients. Expression levels of the most significantly up-regulated genes were measured with real-time PCR using PBMC samples of 15 NBD patients and 20 healthy controls. RESULTS: During NBD attacks, the most remarkably up-regulated genes were defensin alpha 1B (DEFA1B) and NLR family, pyrin domain containing 3 (NLRP3). Real time PCR studies showed significantly increased DEFA1B and NLRP3 expression levels during attacks. CONCLUSION: Immunological factors showing the most significant increase in expression during NBD attacks were primarily associated with innate immunity functions. DEFA1B and NLRP3 can be used as biomarkers for estimation of disease activity in NBD.

The effectiveness of adalimumab treatment for non-infectious uveitis.

Uveitis, which is a major cause of blindness worldwide, is defined as intraocular inflammation that affects the iris, ciliary body, vitreous, retina and choroid. Tumor necrosis factor-alpha (TNF-α) is a key cytokine involved in the pathogenesis of many inflammatory diseases including uveitis. Corticosteroids and immunosuppressive agents are the conventional therapy to treat non-infectious uveitis. In cases that are resistant to these therapies, anti-TNF agents are added. An anti-TNF-α agent, adalimumab, was recently approved for the treatment of refractory non-infectious uveitis. In this review, we provide an introduction to uveitis and summarize the effectiveness and safety of adalimumab in the treatment of non-infectious uveitis.

Behcet's Disease.

Behcet's disease is a rare systemic vasculitis disorder of unknown etiology characterized by recurrent attacks of acute inflammation affecting multiple parts of the body.