Behçet's disease and activities of daily living.

OBJECTIVES: No large-scale registration study has comprehensively evaluated the activities of daily living (ADL) in patients with Behçet's disease. METHODS: The Japanese government provided us with a dataset of confirmed or suspected Behçet's disease cases derived from ongoing national registration. ADL were categorized and analysed into four categories in patients who satisfied the International Criteria for Behçet's Disease. RESULTS: Data from 2960 patients (men 38.9%, women 61.1%; median age 39 years) were assessed. While 1767 patients (59.7%) had normal ADL, the others had impaired ADL comprising limited but not assisted [n = 1058 (35.7%)], partially assisted [n = 116 (3.9%)] and fully assisted [n = 19 (0.6%)]. Logistic regression analysis showed that chronic ocular lesions [odds ratio (OR) 1.85 (95% CI 1.46, 2.35), P < 0.001], paralysis [OR 2.51 (95% CI 1.58, 3.97), P < 0.001], psychosis [OR 3.16 (95% CI 2.02, 4.95), P < 0.001] and arthritis [OR 1.69 (95% CI 1.44, 1.99), P < 0.001] led to the risk of impaired ADL. Chronic ocular lesions [OR 3.61 (95% CI 2.27, 5.72), P < 0.001], paralysis [OR 3.43 (95% CI 1.87, 6.30), P < 0.001] and psychosis [OR 3.60 (95% CI 2.00, 6.50), P < 0.001] were related to the requirement of physical assistance (partially or fully assisted), although arthritis [OR 1.39 (95% CI 0.93, 2.06), P = 0.108] was not a significant factor in this model. CONCLUSION: Ocular lesions, neurological manifestations and arthritis affected ADL. Patients with ocular lesions or neurological manifestations more frequently required physical assistance.

Validity and reliability of a checklist for patients with Behçet's disease based on the International Classification of Functioning, Disability and Health.

In 2020, we reported the "BD-checklist 92" for patients with Behçet's disease (BD) based on the International Classification of Functioning, Disability and Health. The purpose of the present study was to evaluate the validity and reliability of this checklist. Questionnaires using the "BD-checklist 92" and the 36-item Short Form Survey (SF-36) were sent to ten affiliated institutions. In total, 174 patients answered the questionnaire (response rate, 32.7%). Criterion validity was evaluated using the correlation coefficient between the number of problem categories extracted from the "BD-checklist 92" and the scores of the eight subscales and two components of the SF-36. Construct validity was assessed based on the number of problem categories extracted as an external criterion for the number of manifestations experienced and specific lesions. The comparison was performed using the Mann-Whitney U test. Cronbach's alpha coefficient was used to evaluate reliability. The number of problem categories in the "Body functions and structures", "Activities and participation", and "Environmental factors" components correlated significantly with all dimensions of the SF-36 questionnaire (P < 0.05 each). Construct validity showed that the number of manifestations experienced in all components (P < 0.001 each) and specific lesions in "Body functions and structures" and "All categories" (P = 0.002 and 0.050, respectively) contributed to an increased number of problems associated with BD. Cronbach's alpha coefficient for the "BD-checklist 92" was 0.926. This study confirmed the validity and reliability of the "BD-checklist 92".

Sexual dysfunction and depression in Behçet's disease in comparison to healthy controls.

Behçet's disease (BD) can affect the genital system and is more common in Middle Eastern countries and Asia but also occurs in Caucasian people. Aim of this study was to evaluate the prevalence of sexual dysfunction (SD) and depression in patients with BD compared to a healthy control group (HCG). In addition, differences with regard to depression and patients' origin were evaluated. This prospective, monocentric study included 106 consecutive patients from our specialized BD outpatient clinic. Patients were asked to fill out the paper based standardized and validated questionnaires International Index of Erectile Function (IIEF), the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI). In addition, 206 healthy controls were asked to fill out the questionnaires. 106 patients with BD were evaluated and 206 participants in the HCG. The mean age in BD group was 40.5 years as compared to 44.4 years in the HCG. Half of the patients had Middle Eastern and half Caucasian origin. SD was found in 24.5% of all subjects. Only 6.9% of male patients showed signs of SD, while half of the women's group was suffering from SD. The prevalence for SD was significantly higher in women with Middle Eastern ethnic origin compared to women with Caucasian origin (75 vs. 33.3%, p = 0.024). Erectile Dysfunction occurred in 55% of all male patients which was not statistical different from the HCG. Genital ulcers affected 73.6% of all patients. Depression was found in 36.7% of all subjects as compared to 6.25% in the HCG (p < 0.001). Both, SD and depression correlated positively in males (p = 0.017) and females (p = 0.013). SD and depression are very common problems in BD and should be addressed by the treating physician. Both manifestations are intensifying each other. Depression especially is more prevalent compared to the healthy population.

Epidemiological, clinical, and therapeutic characteristics of Behçet's disease: a monocentric study in Tunisia.

INTRODUCTION: to describe the epidemiological, clinical, therapeutic and evolving characteristics of Behçet´s disease and identify prognostic factors. METHODS: we have realized a retrospective, single-center study, conducted over a period of 26 years and including 130 patients presenting Behçet´s disease and hospitalized in an Internal Medicine Department. RESULTS: the mean age of the Behçet´s disease at onset was 30.3 ±8.8 years and that at diagnosis was 34.6 ±9.4 years. The sex ratio (male/female) was 2.5. The mean delay of diagnosis was 53.5 months. Oral aphthosis was constant. The frequency of the manifestations was: genital aphtosis 71.5%, pseudofolliculitis 84.6%, erythema nodosum 11.5%, positive pathergy test 50%, ocular disease 36.9%, venous thrombosis 30%, arterial disease 4.6%, joint damage 30.8%, neurological disease 19.2% and digestive disease 0.8%. The male gender was significantly associated with ocular involvement (p =0.02), venous disease (p =0.01) and occurrence of relapses (p =0.01). The mean follow up was 68.5 ± 77.3 months. The poor survival prognostic factors were male gender, ocular involvement, venous disease, cardiovascular disease, a duration of follow up ≤12 months and a diagnostic delay ≤ 24 months. Conclusion: improving the prognosis of Behçet´s disease requires a shortening of the time to diagnosis, multidisciplinary collaboration, intensive treatment of functional threats, regular monitoring, and patient adherence.

Optical coherence tomography angiography findings in patients with ocular and non-ocular Behcet disease / Achados de angiografia por tomografia de coerência óptica em pacientes com doença de Behçet com e sem acometimento ocular

ABSTRACT Purposes: To evaluate the optical coherence tomography angiography findings in patients with Behçet disease with and without ocular involvement. Methods: A total of 40 patients with Behçet disease and 30 healthy controls were enrolled in the study. Retinal vessel density in the superficial capillary plexus and deep capillary plexus, foveal avascular zone area and perimeter, acirculatory index, foveal density, and nonflow area in the superficial retina were automatically measured using the optical coherence tomography angiography software AngioVue and compared between the groups. Results: The mean parafoveal and perifoveal vessel densities in the superficial capillary plexus and deep capillary plexus and foveal density were significantly lower in the eyes with Behçet uveitis compared to the eyes without Behçet uveitis and eyes of the healthy controls. In the eyes with Behçet uveitis, logMAR visual acuity showed a moderate correlation with parafoveal and perifoveal vessel densities and foveal density (r=-0.43, p=0.006; r=-0.62, p<0.001; r=-0.42, p=0.008; respectively). Conclusion: Behçet disease with posterior uveitis was associated with significant perifoveal and parafoveal vascular decrements in the superficial and deep retina.(AU)

RESUMO Objetivo: Avaliar achados de angiografia por tomografia de coerência óptica em pacientes com doença de Behçet com e sem acometimento ocular. Métodos: Foram incluídos 40 pacientes com doença de Behçet e 30 controles saudáveis. A densidade vascular retiniana nos plexos capilares superficial e profundo, a zona avascular foveal, o índice de circularidade, a densidade foveal e a área sem fluxo da retina superficial foram medidos automaticamente, através do software AngioVue para angiografia por tomografia de coerência óptica, e comparados entre os grupos. Resultados: A densidade vascular parafoveal e perifoveal média nos plexos capilares superficial e profundo, bem como a densidade foveal, foram significativamente menores nos olhos com uveíte de Behçet em comparação com os olhos sem uveíte de Behçet e os olhos dos controles saudáveis. Nos olhos com uveíte de Behçet, a acuidade visual logMAR mostrou correlação moderada com a densidade vascular parafoveal e perifoveal e com a densidade foveal (respectivamente, r=-0,43, p=0,006; r=-0,62, p<0,001; e r=-0,42, p = 0,008). Conclusão: A doença de Behçet com uveíte posterior foi associada a decréscimos significativos da vascularização perifoveal e parafoveal na retina superficial e profunda.(AU)

Genetic and immunologic findings in children with recurrent aphthous stomatitis with systemic inflammation.

BACKGROUND: Recurrent aphthous stomatitis with systemic signs of inflammation can be encountered in inflammatory bowel disease, Behçet's disease (BD), Systemic Lupus Erythematosus (SLE). In addition, it has been proposed that cases with very early onset in childhood can be underpinned by rare monogenic defects of immunity, which may require targeted treatments. Thus, subjects with early onset recurrent aphthous stomatitis receiving a clinical diagnosis of BD-like or SLE-like disease may deserve a further diagnostic workout, including immunologic and genetic investigations. OBJECTIVE: To investigate how an immunologic, genetic and transcriptomics assessment of interferon inflammation may improve diagnosis and care in children with recurrent aphthous stomatitis with systemic inflammation. METHODS: Subjects referred to the pediatric rheumatologist for recurrent aphthous stomatitis associated with signs of systemic inflammation from January 2015 to January 2020 were enrolled in the study and underwent analysis of peripheral lymphocyte subsets, sequencing of a 17-genes panel and measure of interferon score. RESULTS: We enrolled 15 subjects (12 females, median age at disease onset 4 years). The clinical diagnosis was BD in 8, incomplete BD in 5, BD/SLE overlap in 1, SLE in 1. Pathogenic genetic variants were detected in 3 patients, respectively 2 STAT1 gain of function variants in two patients classified as BD/SLE overlap and SLE, and 1 TNFAIP3 mutation (A20 haploinsufficiency) in patients with BD. Moreover 2 likely pathogenic variants were identified in DNASE1L3 and PTPN22, both in patients with incomplete BD. Interferon score was high in the two patients with STAT1 GOF mutations, in the patient with TNFAIP3 mutation, and in 3 genetic-negative subjects. In two patients, the treatment was modified based on genetic results. CONCLUSIONS: Although recurrent aphthous stomatitis associated with systemic inflammation may lead to a clinical diagnosis of BD or SLE, subjects with early disease onset in childhood deserve genetic investigation for rare monogenic disorders. A wider genetic panel may help disclosing the genetic background in the subset of children with increased interferon score, who tested negative in this study.

Clinical profile and evolution of patients with juvenile-onset Behçet's syndrome over a 25-year period: insights from the AIDA network.

Behçet's syndrome (BS) represents an understudied topic in pediatrics: the main aims of our study were to characterize demographic and clinical features of a cohort of BS patients with juvenile-onset managed in three tertiary referral centers in Italy, evaluate their evolution in the long-term, and detect any potential differences with BS patients having an adult-onset. Medical records of 64 juvenile-onset and 332 adult-onset BS followed-up over a 2-year period were retrospectively analyzed and compared. Mean age ± SD of first symptom-appearance was 10.92 ± 4.34 years with a female-to-male ratio of 1.06:1. Mucocutaneous signs were the most frequent initial manifestations, followed by uveitis. Throughout the disease course, genital aphthae (76.56%) and pseudofolliculitis (40.63%) prevailed among the mucocutaneous signs, while major organ involvement was represented by gastrointestinal and ocular involvement (43.75 and 34.38%, respectively). No significant differences emerged for both mucocutaneous signs and specific major organ involvement between juvenile-onset and adult BS patients. After excluding nonspecific abdominal pain, juvenile-onset BS patients were less frequently characterized by the development of major organ involvement (p = 0.027). Logistic regression detected the juvenile-onset as a variable associated with reduced risk of long-term major organ involvement (OR 0.495 [0.263-0.932], p = 0.029). In our cohort, juvenile-onset BS resembled the clinical spectrum of adult-onset patients. Pediatric patients with a full-blown disease at onset showed a more frequent mucocutaneous involvement. In addition, patients with juvenile-onset seemed to develop less frequently major organ involvement and had an overall less severe disease course.

Parafoveal Microvascular Alterations in Ocular and Non-Ocular BehÒ«et's Disease Evaluated With Optical Coherence Tomography Angiography.

Purpose: To compare quantitative optical coherence tomography angiography (OCT-A) measurements of the parafoveal microvasculature in retinal capillary plexuses among BehÒ«et uveitis (BU) patients, non-ocular BehÒ«et's disease (NOBD) patients, and healthy volunteers (HVs). Methods: Sixty-eight subjects were enrolled in this prospective observational cross-sectional study. OCT-A imaging was performed using the Heidelberg Engineering Spectralis OCT. A custom algorithm was developed to calculate the vessel density (VD) in three retinal vascular layers: deep capillary plexus, intermediate capillary plexus, and superficial vascular plexus. The foveal avascular zone (FAZ) and acircularity index were calculated for the whole retinal vascular complex. Results: We analyzed one eye from 21 BU patients (age, 51 ± 10 years), 23 NOBD patients (age, 48 ± 14 years), and 22 HVs (age, 44 ± 13 years). One-way multivariate analysis of covariance showed a statistically significant difference in VD among the three groups when combining the layers after controlling for scan quality (P < 0.001). The VD was lowest in the BU group and highest in the HV group in all layers. The FAZ area was also statistically significant different among the groups (P < 0.005), with the largest FAZ areas in BU patients and smallest FAZ areas in the HV group. However, no statistically significant difference was found for the acircularity index. Conclusions: The parafoveal microvasculature is affected not only in BU patients but also in NOBD patients. Most deviations in the retinal microcirculation in BehÒ«et patients were found in the deeper layers of the retina by using the quantitative VD measurement.

Analysis of Parafoveal Microvascular Abnormalities in Behcet's Uveitis Using Projection-Resolved Optical Coherence Tomographic Angiography.

Purpose: To assess the characteristics of parafoveal microvascular abnormalities in Behcet's uveitis (BDU) using projection-resolved optical coherence tomographic angiography (PR-OCTA).Methods: A retrospective study of BDU patients who underwent PR-OCTA examination between April 1, 2017 and October 31, 2018.Results: Sixty consecutive BDU patients (102 eyes) were included. Sixty-two (124 eyes) healthy subjects served as normal controls (NCs). As compared with NCs, the vessel densities (VDs) of superficial and deep retinal capillary plexuses were decreased, and the fovea avascular zone area, perimeter and acircularity index were increased in BDU eyes (all p < .001). Macular edema (p < .001) and long uveitis course (p = .033) were identified as risk factors for capillary disruptions. Consistent VD reductions were observed in the quiescent fellow eyes of BDU patients during unilateral uveitis relapse.Conclusions: BDU patients had significant OCTA changes. Macular circulatory disturbances may exist in the quiescent fellow eyes during unilateral BDU attack.

Consistency of Visual Evoked Potential in Extraocular Manifestations of Behcet Disease and Impact of Corticosteroid Treatment.

PURPOSE: To study the ability of pattern reversal visual evoked potentials (VEPs) to detect subclinical visual pathway pathologic assessment in Behcet disease (BD) and correlate VEP results in BD with disease activity and response to corticosteroid treatment. METHODS: This study included 18 patients (36 eyes) with BD without recent ocular manifestations and 20 healthy controls (40 eyes). Clinical history was taken, and clinical examinations were done. Visual evoked potential recordings were performed by an electromyographic evoked machine for patients and controls. Corticosteroids were given to patients with extraocular activity, and VEP was repeated after clinical and laboratory improvement of the manifestations. RESULTS: p100 latency of VEP was prolonged in 8 patients (11 eyes) (44.4% of cases). Mean p100 latency showed statistically significant prolongations in BD group compared with the control group (106.7 ± 8.1 ms vs. 99.6 ± 1.9 ms) with P value < 0.001. There was a positive correlation between p100 latency and the disease activity score (r = 0.8673), whereas there was no correlation between p100 latency and the disease duration (r = 0.00072). Patients treated with corticosteroids showed statistically significant reduction in mean p100 latency after treatment (P < 0.001). CONCLUSIONS: Visual evoked potential may be a valuable tool for detecting subclinical neurologic affection in BD.

Multimodal Imaging Characteristics and Functional Test Findings in a Case of Acute Macular Neuroretinopathy Accompanied by Behçet Disease.

Purpose: To report a case of acute macular neuroretinopathy (AMN) in Behçet Disease.Case: A 23-year-old male presented with a complaint for central scotoma in his right eye. He had been diagnosed with Behçet Disease 3 years ago. Best-corrected visual acuity (BCVA) was 20/20. Anterior chamber and fundus examinations were unremarkable. Optical coherence tomography revealed a paracentral area of outer nuclear layer thinning. Infrared reflectance showed a well-defined, circular, hyporeflective area. Optical coherence tomography angiography revealed an area of capillary dropout in deep retinal capillary plexus corresponding to that hyporeflective lesion. Microperimetry test showed decreased macular sensitivity on the lesion area and the loss of the macular integrity. In multifocal electroretinogram, diminished amplitudes of the central cone responses were detected nasal to fixation.Conclusion: Behçet disease is a cause of occlusive retinal vasculitis. Accompanied retinal microvascular disease may be a possible risk factor of AMN suggesting ischemic etiopathogenesis for AMN.

Central sensitization and its relationship with health profile in Behçet's disease.

OBJECTIVES: In this study, we aimed to evaluate the level of central sensitization (CS) and its relationship with health profile, including neuropathic pain and sleep quality in Behçet's disease (BD). METHOD: Eighty-eight patients with BD and 60 healthy controls (HCs) were included in the study between May 2018 and February 2019. Nottingham health profile (NHP), pain DETECT, Pittsburgh sleep quality index (PSQI) questionnaires and the central sensitization inventory (CSI) were administered to all participants. To evaluate the correlations of the NHP, PSQI, and PDQ scores with the CSI score, the CSI was modified for each questionnaire. The activity of BD was determined by the Behçet's disease current activity form (BDCAF). RESULTS: CSI scores were significantly higher in patients with BD than HCs (BD: 41.2 ± 21.1 vs HCs: 20.4 ± 16.9, p < .001). Clinical CS was detected in 69.3% of patients with BD and 28.3% of HCs (p < .001). Severe or extreme CS (CSI score ≥ 50) was present in 37.5% of patients with BD and 5.0% of HCs (p < .001). There were high correlations between the modified CSI scores and the NHP, PDQ and PSQI scores in patients with BD (R = 0.804; p < .001, Rho = 0.698; p < .001, and Rho = 0.734; p < .001, respectively). There was significant correlation between CSI and BDCAF scores (Rho= 0.470, p < .001). CONCLUSION: CS is more frequent and more severe in patients with BD than in HCs. There is a strong correlation between the severity of CS and poor health profile in patients with BD.

Fragmented QRS complexes are associated with subclinical left ventricular dysfunction in patients with Behcet's disease: Four-dimensional speckle tracking echocardiography.

BACKGROUND: Behcet's disease (BD) is a chronic systemic inflammatory disease in which early detection of cardiac involvement is essential. The aim of this study was to assess the left ventricular (LV) functions in BD patients using four-dimensional (4D) speckle tracking echocardiography (STE) and to test the correlation between LV dysfunction and the presence of QRS fragmentation. METHODS: This cross-sectional study included 64 Behcet's patients and 48 healthy volunteers. The BD group was divided into two subgroups depending on the presence (fQRS+) or absence (fQRS-) of fragmented QRS (fQRS). In both groups, left ventricular global area strain (LV-GAS), global radial strain (GRS), global longitudinal strain (GLS), and global circumferential strain (GCS) were obtained with 4D echocardiography. RESULTS: GAS, GRS, GLS, and GCS values were significantly different in Behcet's patients and in healthy volunteers. GLS and GAS values were lower in the fQRS+ than in the fQRS- group (-15.8 ± 1.8 and -17.9 ± 1.6, P = .001 vs -25.0 ± 3.1 and -29.2 ± 4.2, P < .001, respectively). The duration of disease was longer in fQRS+ than in fQRS- patients (120.8 ± 67.4 vs 71.0 ± 40.5, P < .001). Multiple linear regression analysis showed that fQRS and disease duration were independent predictors of LV-GAS. CONCLUSIONS: Four-dimensional STE may be helpful for the prediction of early cardiac dysfunction in patients with BD. The presence of fQRS may be an indicator of subclinical LV dysfunction.

Clinical Manifestations and Management of Pediatric Behçet's Disease.

Behçet's disease (BD) is a chronic, vasculitic disorder affecting all sizes of vessels. The disease rarely onsets at childhood and an early diagnosis is often challenging. Oral ulceration and fever of unknown cause are common initial manifestations that might confuse other inflammatory disorders. The clinical manifestation pattern in pediatric BD is heterogeneous and varies in different genders, ethnicities, and geographic regions. There are also some differences in clinical presentations and prognosis between pediatric and adult BD. The disease also affects children at an extremely young age with mostly benign outcomes compared with that in older children. A limited number of studies reported issues about pediatric BD, let alone studies of children's treatments. Currently, the recommendation of the treatment in pediatric BD is according to the guideline of adult BD. The heterogeneity of clinical features makes the treatment more complicated. The main goal of the treatment is to control the inflammatory process and prevent recurrences. We will discourse the definition, epidemiology, clinical features, diagnosis, and treatment of pediatric BD in this review.

Herbal Medicine for Behçet's Disease: A Systematic Review and Meta-Analysis.

Patients with Behçet's disease often use complementary and alternative medicine for treating their symptoms, and herbal medicine is one of the options. This systematic review provides updated clinical evidence of the effectiveness of herbal medicine for the treatment of Behçet's disease (BD). We searched eleven electronic databases from inception to March 2020. All randomized controlled trials (RCTs) or quasi-RCTs of BD treatment with herbal medicine decoctions were included. We used the Cochrane Handbook for Systematic Reviews of Interventions to assess the risk of bias and the grading of recommendations assessment, development and evaluation (GRADE) approach to assess the certainty of evidence (CoE). Albatross plot was also used to present the direction of effect observed. Eight studies were included. The risk of bias was unclear or low. The methodological quality was low or very low. Seven RCTs showed significant effects of herbal medicine on the total response rate (Risk ratio, RR 1.26, 95% CI 1.09 to 1.45, seven studies, very low CoE). Four RCTs showed favorable effects of herbal medicine on the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level compared with drug therapy. Herbal medicine favorably affected the ESR (MD -5.56, 95% CI -9.99 to -1.12, p = 0.01, I2 = 96%, five studies, very low CoE). However, herbal medicine did not have a superior effect on CRP. Two RCTs reported that herbal medicine significantly decreased the recurrence rate after three months of follow-up (RR 0.23, 95% CI 0.09 to 0.63, two studies, low CoE). Our findings suggest that herbal medicine is effective in treating BD. However, the included studies had a poor methodological quality and some limitations. Well-designed clinical trials with large sample sizes are needed.

Safety of systemic treatments for Behçet's syndrome.

INTRODUCTION: Treatment of Behçet's syndrome (BS) is aimed at controlling all symptoms of such a complex disorder, ensuring a good quality of life and preventing life-threatening complications. A better understanding of the pathogenic role of different chemokines has improved our knowledge of BS and elicited a more specific use of therapies currently available, minimizing the burden of potential side-effects related to treatment. AREAS COVERED: This work aims to provide a detailed overview of the safety profile for current therapies available in the treatment of BS, focusing on the main side-effects, toxicity and contraindications. EXPERT OPINION: The greatest experience in the management of BS has been achieved with the employment of monoclonal anti-tumor necrosis factor antibodies which have been advocated for BS refractory manifestations. Moreover, interleukin-1 inhibitors have proven to be effective as well as safe, despite escalation of their dosage, especially to manage the most severe and difficult-to-treat ocular manifestations. However, general treatment of BS patients remains awkward as protean clinical features may respond differently to the same treatment or even worsen. Therefore, patients' safety for therapies used in BS promotes the implementation of precision medicine, which could help targeting accurately the pathogenetic mechanisms concealed behind specific clinical phenotypes.

Atypical cardiopulmonary manifestations in pediatric Behçet's disease.

BACKGROUND: Behçet's disease (BD) is a multisystem autoinflammatory disease of unknown etiology. Cardiopulmonary involvement is rare, especially in young patients, and carries high morbidity and mortality rates. AIM: Of 26 patients with pediatric BD enlisted in our center, we encountered three patients with severe atypical cardiorespiratory presentations. Our aim was to describe the manifestations and the course that led to the diagnosis of BD. RESULTS: Three adolescents presented with intracardiac thrombi and left anterior descending obstruction causing myocardial infarction, pulmonary artery aneurysm with pulmonary embolism in situ, and suspected epiglottitis. Two patients had a delayed diagnosis of BD, and all had a good response to anti-inflammatory agents. CONCLUSIONS: This study demonstrated that pediatric BD is associated with atypical cardiopulmonary manifestations which maybe life threatening. Since diagnosis maybe challenging, a high index of suspicion is needed especially in young patients, to promptly diagnose and treat these complications. Cardiopulmonary signs and symptoms, though uncommon, maybe the first manifestation and a clue to the diagnosis of this rare disease.

Evidence-based diagnosis and clinical practice guidelines for intestinal Behçet's disease 2020 edited by Intractable Diseases, the Health and Labour Sciences Research Grants.

Behçet's disease (BD) is an intractable systemic inflammatory disease characterized by four main symptoms: oral and genital ulcers and ocular and cutaneous involvement. The Japanese diagnostic criteria of BD classify intestinal BD as a specific disease type. Volcano-shaped ulcers in the ileocecum are a typical finding of intestinal BD, and punched-out ulcers can be observed in the intestine or esophagus. Tumor necrosis factor inhibitors were first approved for the treatment of intestinal BD in Japan and have been used as standard therapy. In 2007 and 2014, the Japan consensus statement for the diagnosis and management of intestinal BD was established. Recently, evidence-based JSBD (Japanese Society for BD) Clinical Practice Guidelines for BD (Japanese edition) were published, and the section on intestinal BD was planned to be published in English. Twenty-eight important clinical questions (CQs) for diagnosis (CQs 1-6), prognosis (CQ 7), monitoring and treatment goals (CQs 8-11), medical management and general statement (CQs 12-13), medical treatment (CQs 14-22), and surgical treatment (CQs 23-25) of BD and some specific situations (CQs 26-28) were selected as unified consensus by the members of committee. The statements and comments were made following a search of published scientific evidence. Subsequently, the levels of recommendation were evaluated based on clinical practice guidelines in the Medical Information Network Distribution Service. The degree of agreement was calculated using anonymous voting. We also determined algorithms for diagnostic and therapeutic approaches for intestinal BD. The present guidelines will facilitate decision making in clinical practice.