Optimal Treatment Approaches to Intestinal Behçet's Disease Complicated by Myelodysplastic Syndrome: The KASID and KSBD Multicenter Study.

PURPOSE: Studies on intestinal Behçet's disease (BD) complicated by myelodysplastic syndrome (MDS) are rare, and no established therapeutic guidelines exist. This study aimed to evaluate the clinical presentation and outcomes of patients with intestinal BD complicated by MDS (intestinal BD-MDS) and suggest a treatment strategy. MATERIALS AND METHODS: Data from patients with intestinal BD-MDS from four referral centers in Korea who were diagnosed between December 2000 and December 2022 were retrospectively analyzed. Clinical features and prognosis of intestinal BD-MDS compared with age-, sex-matched intestinal BD without MDS were investigated. RESULTS: Thirty-five patients with intestinal BD-MDS were included, and 24 (70.6%) had trisomy 8. Among the 35 patients, 23 (65.7%) were female, and the median age at diagnosis for intestinal BD was 46.0 years (range, 37.0-56.0 years). Medical treatments only benefited eight of the 32 patients, and half of the patients underwent surgery due to complications. Compared to 70 matched patients with intestinal BD alone, patients with intestinal BD-MDS underwent surgery more frequently (51.4% vs. 24.3%; p=0.010), showed a poorer response to medical and/or surgical treatment (75.0% vs. 11.4%; p<0.001), and had a higher mortality (28.6% vs. 0%; p<0.001). Seven out of 35 patients with intestinal BD-MDS underwent hematopoietic stem cell transplantation (HSCT), and four out of the seven patients had a poor response to medical treatment prior to HSCT, resulting in complete remission of both diseases. CONCLUSION: Patients with intestinal BD-MDS frequently have refractory diseases with high mortalities. HSCT can be an effective treatment modality for medically refractory patients with intestinal BD-MDS.

Allogeneic hematopoietic stem cell transplantation for juvenile myelomonocytic leukemia with intestinal Behçet's disease: A case report.

Behçet's disease (BD) is a rare condition that is seldom associated with hematological malignancies. In this case report, we present the unique case of a 7-year-old girl diagnosed with juvenile myelomonocytic leukemia (JMML) and intestinal BD. The patient received allogeneic hematopoietic stem cell transplantation (allo-HSCT), which resulted in complete remission of both JMML and BD. Our findings suggest that allo-HSCT may be a feasible treatment option for JMML patients with coexisting BD, and holds promise for achieving remission of both illnesses. However, further clinical investigations are needed to validate these findings.

Impact of age at diagnosis on long-term prognosis in patients with intestinal Behçet's disease.

BACKGROUND AND AIM: Although age at disease onset is considered to be a significant factor in the prognosis of Crohn's disease, little is known about its influence on the long-term prognosis of those with intestinal Behçet's disease (BD). This study aimed to evaluate the long-term clinical outcomes of patients with intestinal BD according to age of disease onset. METHODS: Patients diagnosed with intestinal BD at < 18, 18-60, and > 60 years of age were classified into early-onset, adult-onset, and late-onset groups, respectively. The influence of disease onset time on clinical prognosis, including specific medical requirements, BD-related intestinal surgery, hospitalization, and emergency room visits, was compared using the log-rank test in a large cohort of patients with intestinal BD. RESULTS: Among 780 patients, 21 (2.7%), 672 (86.2%), and 87 (11.1%) comprised the early-onset, adult-onset, and late-onset groups, respectively. Patients in the early-onset group were more likely to require immunosuppressants than those in the adult-onset group (P = 0.048). Nine (42.9%), 158 (23.5%), and 18 (20.7%) patients in the early-onset, adult-onset, and late-onset groups, respectively, underwent intestinal resection. The early-onset group exhibited a higher risk for intestinal resection than the late-onset (P = 0.043) and adult-onset (P = 0.030) groups. The late-onset group exhibited a higher risk for BD-related hospitalization than the adult-onset group (P = 0.023). CONCLUSIONS: Age at diagnosis affected the clinical course of intestinal BD, including intestinal surgery, hospitalization, and specific medical requirements. Different treatment strategies should be established according to age at diagnosis.

Evaluation of the Psychoeducation Program Given to Behcet's Patients in the Context of the Roy Adaptation Model.

The physical, social, and psychological effects of Behcet's disease necessitate the person's adaptation in many areas. This study was conducted to examine the effect of psychoeducation provided to people living with Behcet's disease in the context of the Roy adaptation model on illness adjustment, dyadic adjustment, self-esteem, and psychiatric symptoms. The study was quasi-experimental. The study was with 70 patients with Behcet's disease: 35 patients were in the intervention group and the same number in the control group. The data of the study were collected using the Adaptation to Chronic Illness Scale, Dyadic Adjustment Scale, Rosenberg Self-Esteem Scale, and Brief Symptom Inventory. A seven-session psychoeducation program was provided to the intervention group. After the psychoeducation program, adaptation to illness increased significantly and psychiatric symptoms decreased significantly in the intervention group compared with the control group (P < .05).

Neurological involvement by Behçet's syndrome: clinical features, diagnosis, treatment and outcome.

Neurological involvement in Behçet's syndrome arises predominately through an inflammatory meningoencephalitis characterised by perivenular inflammation due to activation of Th-17 immunological pathways. The brainstem is involved in 50% of cases, the diencephalon and other areas of the brain in 30%, and the spinal cord in 10%. Movement disorders and epilepsy may occur. Psychiatric syndromes may arise with brain and brainstem involvement, and cognitive disorders relate to the brain disease, to circulating inflammatory factors, and to fatigue and despondency. Eighty per cent of cases begin with a relapsing disease course, of whom 70% have only one attack, and 30% have a progressive disease course either from onset or following an initially relapsing course. Venous thrombosis leading to intracranial hypertension and cerebral venous infarction is less common and caused by inflammation in affected veins and a circulating prothrombotic state. Arterial involvement is rare and relates to an arteritis affecting large-sized and medium-sized vessels within the brain leading to infarction, subarachnoid and parenchymal haemorrhage, aneurysm formation and arterial dissection. There is a newly recognised disorder of cerebral cortical hypoperfusion. Cranial neuropathy, peripheral neuropathy and myositis are rare. There has been significant progress in understanding the pathophysiology and treatment of the systemic disease, leading to improved outcomes, but there has been no randomised trial of treatment in the neurological disorder.

[An update on Behçet's syndrome]. / Neues zum Behçet-Syndrom.

Behçet's syndrome (BS, synonym: Behçet's disease, or Adamantiades-Behçet's disease, ABD) is classified as a vasculitis of variable vessel size and can manifest itself in both arterial and venous vessels. Its extensive and at the same time interindividually very different clinical picture is not uncommon a challenge, both with regard to the diagnosis of this rheumatic systemic disease, which is rather rare in our latitudes, and its therapeutic options. In addition to the four cardinal symptoms of recurrent oral aphthae, genital aphthae, skin and eye lesions, the clinical picture offers numerous other manifestations which often require interdisciplinary cooperation. In addition to the above mentioned ocular involvement, which can still lead to blindness if inadequately treated, this is especially true for intestinal and cerebral manifestations as well as for large vessel vasculitis.A final revision of the European League Against Rheumatism recommendations for the management of Behcet's syndrome (EULAR) was made in 2018, and the recommendations are now established internationally as an important treatment guide. Therapy is based on the leading organ involvement. After adalimumab received approval for the treatment of posterior ocular involvement in 2016, another agent, apremilast, became available in 2020. The drug is recommended for the treatment of recurrent oral aphthae in adult Behçet's patients requiring systemic therapy. Nevertheless, there is a further need for new drugs.This article aims to highlight recent findings in the areas of epidemiology, immunopathogenesis & genetics, clinical findings, and therapy, with an emphasis on clinical relevance.

Clinical features of Behçet's disease and prediction of the use of biologics in 488 cases: a single tertiary center study.

The objectives are to describe the demographic and clinical properties of Behçet's disease (BD) and investigate their relationship with the use of biological agents. Four hundred-eighty-eight patients, (299 (61.3%) males, 189 (38.7%) females), who fulfilled the ISG classification criteria for BD were included, retrospectively. The patient's demographics, disease onset age (DOA), clinical findings of the disease, and the drugs were determined and analyzed statistically. The means of patient age and DOA were 40.7 ± 9.9 and 30.8 ± 8.8 years, respectively. The most common initial findings were oral ulcer (OU)s (30.1%), genital ulcer (GU) (27.5%), ocular involvement (OI) (12.5%), and papulopustular lesion (PPL)s (10.1%). The most common clinical manifestations were OUs (96.9%), PPLs (70.2%), HLA-B51 (64.4%), positive pathergy reaction (26.4%), GU (58.8%), OI (44.7%), erythema nodosum (29.8%), and vascular involvement (VSI) (27.3%). Although, the frequency of GU was higher in females (p = 0.01), PPLs (p = 0.001) and VSI (p = 0.001) were higher in males. Sixty-three (8.9%) patients used a biological agent. Its frequency was higher in younger patients (< 40 years) (p = 0.006), males (p = 0.012) and patients with OI (p = 0.001). Besides, the DOA (p = 0.012) and the current age (p = 0.001) were lower in biological agent users. The possibility of using biological agent was increased in males (OR = 2.2), patients with OI (OR = 2.7) and young patients (OR = 0.9). Mucocutaneous lesions are distinctive features of BD, especially OUs precede other findings. GU was more common in females and PPLs and VSI were in males. The probability of using biologics is higher in males, patients with OI, and young patients.

[Chinese expert consensus on the clinical diagnosis and treatment of Behcet's uveitis (2023)].

Behcet's disease is a chronic and recurrent multisystemic inflammatory disease, and its etiology and pathogenesis are not completely clarified. Behcet's uveitis is one of the common types of uveitis with the highest rate of untreatable blindness among various uveitis entities in China. The blindness in patients with Behcet's uveitis is commonly caused by retinal vascular occlusion, retinal atrophy and optic nerve atrophy. Early diagnosis and treatment are essential to preserve and improve visual function in these patients. To provide general guidance and reference in the diagnosis and treatment of Behcet's uveitis, consensus opinions have been developed through an extensive investigation on this disease by the experts in the Uveitis and Ocular Immunology Group of Chinese Ophthalmologist Association and the Ocular Immunology Group of Ophthalmology Society of Chinese Medical Association.

Behçet Syndrome.

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 there are no diagnostic biomarkers or genetic tests. Treatment modalities include immunomodulatory agents, immunosuppressives and biologics, tailored according to prognostic factors, disease activity, severity, and patients' preferences.

Outcome measures in Behçet syndrome.

Disease assessment has been challenging in Behçet syndrome due to the heterogeneous disease course and multiorgan involvement with variable treatment response. There have been several recent improvements regarding outcome measures including development of a Core Set of Domains for Behçet syndrome and novel instruments for assessing specific organs and overall damage. This review focuses on the current state of outcome measures in Behçet syndrome, unmet needs, and a research agenda towards the development of standardized and validated outcome measure instruments.

Successful allogeneic hematopoietic stem cell transplantation for myelodysplastic neoplasms complicated with secondary pulmonary alveolar proteinosis and Behçet's disease harboring GATA2 mutation.

Myelodysplastic neoplasms (MDS) are defined by cytopenia and morphologic dysplasia originating from clonal hematopoiesis. They are also frequently complicated with diseases caused by immune dysfunction, such as Behçet's disease (BD) and secondary pulmonary alveolar proteinosis (sPAP). MDS with both BD and sPAP is extremely rare, and their prognosis is poor. In addition, haploinsufficiency of the hematopoietic transcription factor gene GATA2 is recognized as a cause of familial MDS and is frequently complicated by sPAP. Herein, we report a case of MDS combined with both BD and sPAP in association with GATA2 deficiency in a Japanese woman. Because she developed progressive leukopenia and macrocytic anemia during BD treatment at the age of 61, she underwent a bone-marrow examination and was diagnosed with MDS. She subsequently developed sPAP. At the age of 63, she underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Since allo-HSCT, she has maintained complete remission of MDS as well as the symptoms of BD and sPAP. Furthermore, we performed whole exome sequencing and identified the GATA2 Ala164Thr germline mutation. These findings suggest that patients with MDS, BD and sPAP should be considered for early allo-HSCT.

Behcet's Disease Mimicking Crohn's Disease: A Diagnostic Pitfall in GI Tract Biopsies.

Behcet's disease is a rare entity. It's a multi-systemic inflammatory disease of unknown etiology characterized by recurrent ulcers and vasculitis, mainly including the oral cavity, eyes, gastrointestinal tract and joints. Crohn's disease is a chronic inflammatory disorder that may affect the same organs as Behcet's disease, however more frequently the gastrointestinal tract. Distinguishing Behcet's disease from Crohn's disease can be challenging due to the overlapping clinical presentation and similar morphology features on pathology biopsy specimens. This is a case report of a 32-year-old female who first presented at the emergency department with fatigue, weight loss, arthralgia, and erythema nodosum. The patient was admitted for oral ulcers, skin rash, genital ulcers, and melena one month later. Treatment with prednisone was started at the time and further workup for Behcet's disease versus inflammatory bowel disease was started. Her esophagus biopsy shows granulomatous-like vasculitis, and her colon biopsies show overlapping features with Crohn's disease. Herein, we present a rare and interesting case in which Behcet's disease mimics inflammatory bowel disease on the gastrointestinal tract biopsies but with some unique findings and diagnostic pitfalls for gastrointestinal tract vasculitis and ulceration.

Behcet disease: an undifferentiating and complex vasculitis.

Behçet Disease is a relapsing and remitting variable vessel vasculitis characterized by recurrent mucocutaneous ulcers that can involve almost every organ system in the body. Indeed, the presence of recurrent oral or genital ulcers with other auto-inflammatory symptoms should raise suspicion for this elusive disease. It is unique among the vasculitides in that it can affect vessels of small, medium, and large size and tends to involve venous rather than arterial circulation, and its effects on the pulmonary venous circulation are particularly notable for their role in disease mortality. Classically seen in Mediterranean, Middle-Eastern, and eastern Asian countries, and relatively rare in the United States, prevalence has been increasing, prompting an increased need for internists to be aware of Behcet's clinical presentation and treatment. As early recognition and diagnosis of the disease is key to successful treatment and better prognosis, this review provides a brief summary of the current etiological theories, important clinical manifestations, and treatments including newer biologic alternatives.

Case report and analysis: Behçet's disease with lower extremity vein thrombosis and pseudoaneurysm.

Background: Behçet's disease (BD) is a unique autoimmune chronic systemic vasculitis that affects veins and arteries of all sizes. BD can lead to recurrent vascular events, especially venous thrombosis, with an incidence rate of 40%, or pseudoaneurysms formed under long-term inflammatory reaction or iatrogenic stimulation. BD-related risk factors promote endothelial dysfunction, platelet activation and overactivation of tissue factors leading to mural inflammatory thrombi. Thrombosis may be the first clinical manifestation of BD. Case presentation: A 32-year-old man complaining of progressive swelling and pain in the right lower extremity for 30 days was initially diagnosed with "venous thrombosis of the right lower extremity," using color Doppler ultrasonography. Patient underwent inferior vena cava filter placement combined with deep vein angioplasty of the right lower extremity and catheter-directed urokinase thrombolysis. Postoperative oral anticoagulant therapy was administered. However, the patient was readmitted 20 days later for pulsatile pain in the right groin. Prior medical history included 4 years of repeated oral and perineal ulcers, and 2 months of blurred vision. Abdominal computed tomography angiography (CTA) revealed rupture of the right common iliac artery (CIA) and left internal iliac artery (IIA), complicated by a pseudoaneurysm. Based on the clinical manifestations and other auxiliary examination results, the patient was re-diagnosed with "BD combined with deep venous thrombosis of the right lower extremity and an iliac artery pseudoaneurysm." Stent implantation was performed for iliac artery pseudoaneurysm after symptoms were controlled with timely immunosuppressive therapy. After endovascular treatment, the patient underwent continued immunosuppressive therapy and dynamic reexaminations of abdominal CTA, which revealed that a small amount of contrast agent at the stent in the right CIA continued to flow into the cavity of the pseudoaneurysm; in addition, the size of the pseudoaneurysm was gradually increasing. Therefore, the patient underwent a second stent implantation for iliac artery pseudoaneurysm, and the condition improved further. Conclusion: The importance of early diagnosis of BD should be recognized, and the choice of interventional and surgical procedures should be carefully evaluated, as this may trigger further damage to vascular access in BD patients with aneurysm.

Development and implementation of the AIDA International Registry for patients with Behçet's disease.

Purpose of the present paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to pediatric and adult patients with Behçet's disease (BD). The Registry is a clinical physician-driven non-population- and electronic-based instrument implemented for the retrospective and prospective collection of real-life data about demographics, clinical, therapeutic, laboratory, instrumental and socioeconomic information from BD patients; the Registry is based on the Research Electronic Data Capture (REDCap) tool, which is thought to collect standardised information for clinical real-life research, and has been realised to change over time according to future scientific acquisitions and potentially communicate with other existing and future Registries dedicated to BD. Starting from January 31st, 2021, to February 7th, 2022, 110 centres from 23 countries in 4 continents have been involved. Fifty-four of these have already obtained the approval from their local Ethics Committees. Currently, the platform counts 290 users (111 Principal Investigators, 175 Site Investigators, 2 Lead Investigators, and 2 data managers). The Registry collects baseline and follow-up data using 5993 fields organised into 16 instruments, including patient's demographics, history, clinical manifestations and symptoms, trigger/risk factors, therapies and healthcare access. The development of the AIDA International Registry for BD patients will facilitate the collection of standardised data leading to real-world evidence, enabling international multicentre collaborative research through data sharing, international consultation, dissemination of knowledge, inclusion of patients and families, and ultimately optimisation of scientific efforts and implementation of standardised care.Trial registration NCT05200715 in 21/01/2022.

[Behçet's disease]. / Morbus Behçet.

Behçet's disease Abstract. Behçet's disease (BD) represents a diagnostic and therapeutic challenge for the treating physician. The rarity of the disease and its heterogeneous clinical presentations hamper physicians in easily gaining knowledge about the disease. Moreover, the diagnosis of BD commonly relies on clinical grounds only and treatment decision are guided by relatively few data from clinical trials. In this article, some basic principles for diagnosing and managing BD are reviewed.

Allogeneic stem cell transplantation for trisomy 8-positive myelodysplastic syndrome or myelodysplastic/myeloproliferative disease with refractory Behçet's disease: Case report and the review of literature.

We had two cases of trisomy 8-positive myelodysplastic syndrome (MDS) with incomplete Behçet's disease (BD) in which the remissions of both diseases were maintained by allogeneic stem cell transplantation (allo-SCT). Among MDS with BD patients, sometimes it is difficult to control the symptoms of BD with standard therapies such as corticosteroids and tumor necrosis factor (TNF) inhibitors. Although there should be careful consideration regarding indications for transplantation, our two cases, in which refractory BD was completely controlled by allo-SCT, suggest that allo-SCT can be one of the treatment options for higher-risk MDS with BD patients.

Immunopathogenesis of Behçet's disease and treatment modalities.

INTRODUCTION: Behçet's disease (BD) is an auto-inflammatory disease, primarily characterized by recurrent painful mucocutaneous ulcerations. METHODS: A literature search was performed to write a narrative review into the pathogenesis and current treatment options of BD. RESULTS: The pathogenesis of BD remains to be elucidated, but is considered a genetically primed disease in which an external trigger causes immune activation resulting in inflammatory symptoms. GWAS data show an association between multiple genetic polymorphisms (HLA-B51, ERAP1, IL10 and IL23R-IL12RB2) and increased susceptibility to BD. Bacteria as streptococci, an unbalanced microbiome or molecular mimicry trigger the inflammation in BD. Increased production or responsiveness of pro-inflammatory components of the innate immune response (TLR, neutrophils, NK-cells or γδ T-cells) to these triggers may be a crucial step in the pathogenesis of BD. Additionally to an increased autoinflammatory response there is evidence of a dysregulated adaptive immune system, with a disturbed Th1/Th2 balance, expansion of Th17 cells and possibly a decrease in regulatory T cells, resulting in a surplus in pro-inflammatory cytokines. The inflammation causes a typical clinical phenotype including orogenital ulcerations, uveitis and skin lesions. Treatment is aimed at the aberrations found in the innate (neutrophils and γδ-T cells) and adaptive immune system (TNF-α, INF-γ, IL-1), directed at organ involvement and individualized based on patient characteristics. CONCLUSION: We presented an extensive review into the pathogenesis and treatment options of BD.

Clinical presentation and treatment outcomes of arterial involvement in Behçet's disease: a single-centre experience.

Arterial involvement, although rare, accounts for significant mortality and morbidity in patients of Behçet's disease (BD). There is paucity of data on arterial BD. The objective of this 5-year retrospective cohort study was to examine the clinical presentation, pattern of arterial involvement, and treatment outcome in Indian arterial BD patients. Data on demography, clinical presentation, radiology, instituted therapy, vascular interventions and treatment outcomes were recorded and analyzed. Ten (16.9%) out of 59 patients with BD had arterial involvement in 13 vascular territories [mean age 30 (8) years, 9 (90%) males]. Pulmonary artery was most commonly involved (46%), followed by abdominal aorta (15%), femoral artery (15%), descending thoracic aorta (8%), common iliac (8%), and dorsalis pedis artery (8%). Two patients had multi-territory involvement. The median interval between disease onset and development of arterial aneurysms was 3 years (3 months-12 years). Concomitant deep vein thrombosis was seen in 60% cases. Prednisolone and cyclophosphamide were the most common immunosuppressive therapy used; one patient who relapsed on cyclophosphamide responded to infliximab. Five surgical or endovascular interventions were performed. Four patients (40%) died due to aneurysm rupture-all had a delayed diagnosis, and three had pulmonary artery involvement, with death due to massive hemoptysis. Based on the present study, we concluded that arterial involvement in BD is seen predominantly in males and has a high mortality. Early detection and aggressive treatment with immunosuppression and surgical or endovascular interventions are essential for good outcomes.