Israel Medical Association Journal

The issue of genital ulcers (GUs) in Israeli Arab female patients with Behçet's disease (BD is important as GUs are considered a unique feature of BD and stand as diagnostic criterion for the diagnosis in the International Study Group (ISG) criteria [1] and the International Criteria for Behcet Disease (ICBD) [2]. According to the ISG, GUs can be detected by a physician or by the patient [1]. While oral ulcers are easily observable, the identification of more hidden GUs pose a significant challenge.

Since the introduction of the international study group (ISG) criteria for the diagnosis of Behçet's disease (BD) in the early 1990s by Yazici and colleagues [1] and the international criteria for BD (ICBD) by Davatchi and colleagues in 2014 [2], great progress has been achieved in the diagnosis of BD with fairly high sensitivity and specificity rates. However, a small, but very challenging and unique minority might not fulfill these criteria, at least at presentation. These patients are most challenging as they may present with life-threatening vascular or neurological manifestations. If the diagnosis BD is delayed, the risk for morbidity and even mortality might be increased. Therefore, we should aim for early diagnosis and prompt treatment.

Backgrounds: Behçet's disease (BD) is a chronic vasculitic multi-systemic disease of unknown etiology. BD is characterized by recurrent attacks of oral aphthae, genital ulcers, and uveitis. BD is a multisystemic disorder and as such it may provoke various psychiatric manifestations, including depression.

Objectives: To evaluate the association between BD and depression, adjusting for established risk factors for depression.

Methods: We executed a cross-sectional study based on the Clalit Health Services database, the largest healthcare organization in Israel, serving over 4.4 million members. For this study 873 BD patients were detected and matched with 4369 controls by age and sex.

Results: The rate of depression was higher among the BD patients compared with the control group (9.39% vs 5.49%, respectively, odds ratio [OR] 1.79, 95% confidence interval [95%CI] 1.37–2.31, P < 0.001). An association between BD and depression was also observed on multivariable analysis (OR 1.83, 95%CI 1.39–2.39, P < 0.001). When stratifying the data, according to established risk factors, the association between BD and depression was prominent in the youngest age group (18–39 years of age), low and high socioeconomical status, and non-smokers.

Conclusions: Establishing the association between BD and depression should influence the attitude and the treatment of BD patients, as this relationship requires a more holistic approach and a multidisciplinary treatment regimen for all patient needs.

Background: Behçet’s disease (BD) is an inflammatory disorder potentially leading to life- and sight-threatening complications. No laboratory marker correlating with disease activity or predicting the occurrence of disease manifestations is currently available.

Objectives: To determine an association between serum amyloid-A (SAA) levels and disease activity via the BD Current Activity Form (BDCAF), to evaluate disease activity in relation to different SAA thresholds, to examine the association between single organ involvement and the overall major organ involvement with different SAA thresholds, and to assess the influence of biologic therapy on SAA levels.

Methods: We collected 95 serum samples from 64 BD patients. Related demographic, clinical, and therapeutic data were retrospectively gathered.

Results: No association was identified between SAA levels and BD disease activity (Spearman's rho = 0.085, P = 0.411). A significant difference was found in the mean BDCAF score between patients presenting with SAA levels < 200 mg/L and those with SAA levels > 200 mg/L (P = 0.027). SAA levels > 200 mg/L were associated with major organ involvement (P = 0.008). A significant association was found between SAA levels > 150 mg/dl and ocular (P = 0.008), skin (P = 0.002), and mucosal (P = 0.012) manifestations. Patients undergoing biologic therapies displayed more frequently SAA levels < 200 mg/L vs. patients who were not undergoing biologic therapies (P = 0.012).

Conclusions: Although SAA level does not represent a biomarker for disease activity, it might be a predictor of major organ involvement and ocular disease relapse at certain thresholds in patients with BD.

Background: The evidence on the use of dexamethasone implants in the treatment of Behçet’s disease (BD)-related uveitis is limited to a few cases. 

Objectives: To evaluate the efficacy of dexamethasone implants on ocular functional, morphological, and clinical parameters in BD patients with severe refractory uveitis. 

Methods: Five eyes from five BD patients were enrolled. A single intravitreal dexamethasone injection was applied to each eye. Best corrected visual acuity (BCVA), central macular thickness (CMT) assessed with optical coherence tomography, retinal vasculitis assessed by fluorescein angiography, vitreous haze score (Nussenblatt scale), intraocular pressure (IOP), and lens status (LOCS III, Lens Opacities Classification System III) were recorded at baseline and at 1, 3, and 6 month follow-up visits.

Results: At baseline, all eyes showed marked macular edema and 4/5 had concomitant active retinal vasculitis. Mean BCVA was increased from baseline at each control visit with a mean improvement of 0.26 ± 0.18 lines at 6 months follow-up. Mean CMT decreased from baseline at each control visit with a mean improvement at 6 months follow-up of 198.80 ± 80.08 µm. At the end of the study, none of the eyes showed macular edema and the mean CMT was 276.80 ± 24.94 µm. Retinal vasculitis resolved in all eyes. One eye experienced an IOP spike during treatment that resolved spontaneously, and one eye developed a clinically significant lens opacity at 6 months follow-up. 

Conclusions: Treatment with a dexamethasone implant in BD-uveitis and inflammatory macular edema was safe and effective as an additional treatment combined with systemic immunomodulatory drugs.

 

Behçet’s disease (BD) is a systemic inflammatory disorder characterized by a protean clinical spectrum and an enigmatic pathogenesis. After being classified as an autoimmune disorder, spondyloarthritis and vasculitis, today BD is considered at the crossroad between autoimmune and auto-inflammatory syndromes. Many pathogenetic, clinical and therapeutic clues support this recent interpretation, enabling novel treatment choices such as interleukin (IL)-1 inhibition. Thus, in the last decade the IL-1 receptor antagonist anakinra and the anti-IL-1β monoclonal antibody canakinumab were increasingly administered in BD patients resistant to standard therapies, leading to interesting results and new intriguing pathogenetic implications. However, further studies are essential to both establish how the innate and acquired immune systems interact in BD patients and identify the best way of administering anti-IL-1 agents with regard to dosage, interval of administration and organ response.

Behçet's disease (BD) is a multi-systemic disorder of unknown etiology characterized by relapsing oral-genital ulcers, uveitis, and involvement of the articular, gastrointestinal, neurologic, and vascular systems. The choice of treatment is based on the severity of systemic involvement, clinical presentation and the site affected, and includes corticosteroids, azathioprine, interferon, cyclophosphamide, methotrexate or tumor necrosis factor-alpha and interleukin-1 blockers. We present a case series of four refractory BD patients successfully treated with intravenous immunoglobulins (IVIG). All patients fulfilled International Study Group criteria. The patients’ mean age was 38.75 ± 12.09 years and mean disease duration 10.25 ± 8.5 years. Human leukocyte antigen B51 was positive in two of four patients. In addition to oral aphthosis, all patients suffered from genital ulcers and cutaneous BD-related manifestations; central nervous system involvement and arthralgia were found in two patients. Peripheral nervous system, gastrointestinal and eye involvement occurred in 25% of cases. In all patients, previously treated according to EULAR recommendations without reaching satisfactory results, IVIG induced immediate and sustained response over time without incurring any side effects. We propose IVIG administration as an additional effective and safe treatment option in patients with severe and resistant BD.

Background: Arterial involvement in Behçet's syndrome is rare. Aneurysms are common among the arterial lesions, affecting various arteries but mostly the abdominal aorta. Surgical interposition graft insertion is the treatment of choice for large aneurysms. However, vasculitis in these patients is the reason for the notorious surgical complications that result in up to 50% false aneurysms in anastomotic sites. Recently, endovascular repair for abdominal aortic aneurysms has been established.

Objectives: To learn more about vascular Behçet and, specifically, to compare the results of surgical treatment and endovascular repair of AAA[1] in patients with Behçet's syndrome.

Methods: We retrieved the medical records of all 53 patients with Behçet disease admitted to Rambam Medical Center during the years 1985 and 2001 and analysed the results and follow-up of open surgery versus endovascular repair of AAA in patients with known Behçet's syndrome.

Results: Of the 53 patients with Behçet's disease 18 had vascular manifestations (34%). AAAs were encountered in 8 patients (15%) and 5 were treated. Open surgery (group 1), under general anesthesia, lasted less than 3 hours with an average aortic clamping time of 34 minutes (range 26–41 min) after which the patients were transferred to the intensive care unit for 24–48 hours. Endovascular treatment (group 2), although lasting about the same time without the need for intensive care, necessitated contrast media and fluoroscopy. The length of hospital stay was considerably shorter for patients after endovascular repair compared to open surgery (3 days vs. 6 days). Combined mortality and morbidity was higher in patients who underwent open surgery compared to endovascular repair (one death, one major amputation and three anastomotic pseudoaneurysms compared to one temporary contrast-induced nephropathy).

Conclusions: Vasculo-Behçet patients with AAA are better candidates for endovascular treatment than atherosclerotic patients. Combined morbidity (especially anastomotic pseudoaneurysms) and mortality of Behçet patients after endovascular repair is considerably lower than after open surgery.