Porto-sinusoidal vascular disorder and nephrotic-range proteinuria due to venous vasculitis in Behçet's disease.

Behçet's disease (BD) is an autoinflammatory disease with multifactorial and polygenic etiology, potentially involving arteries and veins of any size resulting in variable vessel vasculitis. We report a case of an Iranian male who presented with porto-sinusoidal vascular disorder due to venous vasculitis as initial manifestation of BD. Despite immunosuppression, anticoagulation and venous recanalization, he subsequently developed severe nephrotic-range proteinuria mimicking a primary renal disease which was completely and immediately ameliorated by stenting of the vena cava. This demonstrates that the proteinuria was caused by increased intraglomerular pressure due to venous outflow obstruction as a consequence of venous vasculitis. To our knowledge, this is the first report of massive proteinuria caused by venous obstruction of the caval vein in the context of BD. Altogether, this case demonstrates the extensive spectrum of vascular disease in BD.

Long-term data on efficacy and safety of adalimumab in Behçet's disease.

INTRODUCTION: Behçet's disease (BD) is a systemic, inflammatory disorder affecting multiple organ systems, frequently treated with TNF-α blocking agents, as infliximab and adalimumab. Insights about long-term use of adalimumab are lacking. Therefore, we conducted a study into the long-term efficacy and safety of adalimumab in BD. METHODS: A retrospective cohort study from patients with BD treated with adalimumab in the Erasmus Medical Center was performed. Patients included were at least 18 years of age, diagnosed according to ISG criteria, and uninterruptedly used adalimumab for at least 36 months. RESULTS: In a population of 39 BD patients using adalimumab, 29 patients persisted treatment >36 months (range 37-206 months). Indications for treatment were uveitis (n = 15) 51.7%, mucocutaneous involvement (n = 9) 31%, arthritis (n = 2) 6.9%, intestinal disease (n = 3) 10.3%. Overall, adalimumab decreased the occurrence of flares from 0.64 to 0.17 flares per year and BCVA improved subsequently. Also, a steady decline in BDCAF is reported over the course of at least 5 years. Subsequently, 79% was able to reduce their use of immunosuppressive agents aside from adalimumab. Adverse effects were reported in, (n = 15) 51.7% of which (n = 13) 86.6% were infectious complications. Two of those required inpatient hospital care. CONCLUSION: Our study illustrates durable long-term efficacy of adalimumab treatment in patients with BD. In our patient cohort long-term adalimumab treatment is safe, with a low incidence of serious adverse events.

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.