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.

Infliximab for vascular involvement in Behçet's syndrome.

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

2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria sets for three types of antineutrophilic cytoplasmic antibody-associated vasculitis.

PURPOSE OF REVIEW: A critique of the recently published classification criteria for three main types of antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis. RECENT FINDINGS: An ACR and EULAR joint task force recently published classification criteria for three main types of ANCA-associated vasculitis. The criteria were based on patient histories and findings in nearly 7000 patients from 136 sites in 32 countries. As such the study represented hitherto the most intensive attempt to prepare classification criteria vasculitis. We propose, this truly intensive effort was, unfortunately, unsuccessful. There were two main mishaps. The first one was that the proposed criteria were not validated in an independent cohort. This is curious in that the sponsors, ACR and EULAR, require such independent cohorts for validation. The second mishap is that the concept that disease classification criteria need to be 100% sensitive and specific for a diagnosis is unrealistic. Moreover, all-purpose disease classification criteria are not respectful to scientific research and to the probabilistic nature of the art and the science of medicine. SUMMARY: The new ACR/EULAR ANCA-associated vasculitis guidelines have not been validated in independent cohorts. We propose replacing the term disease criteria with disease guidelines.

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

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

Core Set of Domains for Outcome Measures in Behçet's Syndrome.

OBJECTIVE: An unmet need exists for reliable, validated, and widely-accepted outcome measures for randomized clinical trials in Behçet's syndrome. The Outcome Measures in Rheumatology (OMERACT) Behçet's Syndrome Working Group, a large, multidisciplinary group of experts in Behçet's syndrome and patients with Behçet's syndrome, had an objective of developing a core set of data-driven outcome measures for use in all clinical trials of Behçet's syndrome. METHODS: The core domain set was developed through a comprehensive, iterative, multistage project that included a systematic review, a focus group meeting and qualitative patient interviews, a survey among experts in Behçet's syndrome, a Delphi exercise involving both patients and physician experts in Behçet's syndrome, and use of the data, insight, and feedback generated by these processes to develop a final core domain set. RESULTS: All steps were completed and domains were delineated across the organ systems involved in this disease. Since trials in Behçet's syndrome often focus on specific manifestations and not on the disease in its entirety, the final proposed core set includes 5 domains mandatory for study in all trials in Behçet's syndrome (disease activity, new organ involvement, quality of life, adverse events, and death) with additional subdomains mandatory for study of specific organ-systems. The final core set was endorsed at the 2018 OMERACT meeting. CONCLUSION: The core set of domains in Behçet's syndrome provides the foundation through which the international research community, including clinical investigators, patients, the biopharmaceutical industry, and government regulatory bodies can harmonize the study of this complex disease, compare findings across studies, and advance development of effective therapies.

Emergence of new manifestations during infliximab treatment in Behçet's syndrome.

OBJECTIVES: Infliximab (IFX) is increasingly being used for the treatment of severe manifestations of Behçet's syndrome (BS). However, emergence of new manifestations has also been occasionally reported during IFX treatment. We aimed to assess the frequency of new manifestations in our BS patients treated with IFX. METHODS: A chart review was conducted to identify all BS patients treated with IFX in our clinic between 2004 and 2020. Demographic data, indications for IFX initiation, concomitant treatments and outcomes were recorded. A new manifestation was defined as the emergence of a new organ involvement or mucocutaneous manifestation developing for the first time during IFX treatment or within 12 weeks after the last infusion of IFX. RESULTS: Among our 282 patients who used IFX, 19 (7%) patients had developed a total of 23 new manifestations during a mean follow-up of 20.0 (15.3) months. Patients with vascular involvement were more likely to develop a new manifestation (12/19, 63%). Initial manifestations that required IFX were in remission at the time of new manifestation in 14/19 patients. IFX treatment was intensified (n = 6) and/or glucocorticoids, immunosuppressives or colchicine was added to IFX (n = 21). IFX was switched to another agent for the remaining manifestations (n = 8). These treatment modifications led to remission in 17/19 patients. CONCLUSION: New manifestations developed during IFX treatment in 7% of our patients with BS. They could be managed by intensifying IFX treatment or adding other agents in the majority of these manifestations.

Behçet syndrome.

Behçet syndrome is a systemic vasculitis with an unknown aetiology affecting the small and large vessels of the venous and arterial systems. The presence of symptom clusters, regional differences in disease expression and similarities with, for example, Crohn's disease suggest that multiple pathological pathways are involved in Behçet syndrome. These disease features also make formulating disease criteria difficult. Genetic studies have identified HLA-B*51 as a genetic risk factor. However, the low prevalence of HLA-B*51 in many patients with bona fide disease, especially in non-endemic regions, suggests that other factors must also be operative in Behçet syndrome. Despite lacking a clear aetiological mechanism and definition, management of manifestations that include major vascular disease, eye disease and central nervous system involvement has improved with the help of new technology. Furthermore, even with our incomplete understanding of disease mechanisms, the prognoses of patients with Behçet syndrome, including those with eye disease, continue to improve. New treatment options and a better understanding of the underlying pathogenesis for various manifestations of this condition are required to further improve the management of the disease, which will improve patient quality of life.