Outcome and prognosis of isolated carotid vasculitis.

OBJECTIVE: To assess the prognosis and outcome of patients with isolated carotid vasculitis. METHODS: We performed a retrospective multicenter study of 36 patients (median age at diagnosis was 37 [IQR 27-45] years and 11 [31 %] patients were men) with initial presentation as isolated carotid vasculitis. Study endpoints included vascular complications, relapses, and progression to large vessel vasculitis (i.e. Giant cell arteritis or Takayasu). RESULTS: The most frequent involvement was the left internal carotid artery (39 %), and 81 % had stenosis. After a median follow-up of 32 months [IQR 12-96], 21 (58 %) patients had a vascular event, including 31 % of new onset vascular lesions and 25 % of stroke/transient ischemic attack. Patients with stroke had less carotidynia at diagnosis (33 % vs 74 %, p = 0.046), higher significant carotid stenosis (i.e. > 50 %) (89 % vs. 30 %, p = 0.026) and higher severe carotid stenosis (i.e. >70 %) (67 % vs 19 %, p = 0.012), compared to those without stroke. Twenty (52 %) patients experienced relapses. High CRP at diagnosis was associated with relapses (p = 0.022). At the end of follow-up, 21 (58 %) patients were classified as having Takayasu arteritis, 13 (36 %) as isolated carotid vasculitis, and two (6 %) as giant cell arteritis. CONCLUSION: Carotid vasculitis may occur as a topographically limited lesion and is associated with significant rate of vascular complications.

Behçet's disease uveitis.

Uveitis in Behçet's disease (BD) is frequent (40% of cases) and is a major cause of morbidity. The age of onset of uveitis is between 20 and 30 years. Ocular involvement includes anterior, posterior or panuveitis. It is non-granulomatous. Uveitis may be the first sign of the disease in 20% of cases or it may appear 2 or 3 years after the first symptoms. Panuveitis is the most common presentation and is more commonly found in men. Bilateralisation usually occurs on average 2 years after the first symptoms. The estimated risk of blindness at 5 years is 10-15%. BD uveitis has several ophthalmological features that distinguish it from other uveitis. The main goals in the management of patients are the rapid resolution of intraocular inflammation, prevention of recurrent attacks, achievement of complete remission, and preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update previous article by our team on pathogenesis, diagnostic approaches, identification of factors associated with relapse and the therapeutic strategy of BD uveitis.

Human pegivirus identified in severe myelitis and optic neuritis in immunocompromised patients: A pathogenic role for a forgotten virus?

The role of Human pegivirus (HPgV) in patients with encephalitis has been recently questioned. We present cases of 4 patients with similar clinical, biological, and radiological characteristics, including a past history of transplantation with long-term immunosuppression and a progressive course of severe and predominantly myelitis, associated in 3 cases with optic neuropathy causing blindness. Extensive workup was negative but analysis of the CSF by use of pan-microorganism DNA- and RNA-based shotgun metagenomics was positive for HPgV. This case series further supports the hypothesis of HPgV CNS infection and highlights the utility of metagenomic next-generation sequencing of CSF in immunocompromised patients.

Anakinra in the Treatment of Patients with Refractory Scleritis: A Pilot Study.

PURPOSE: This study aimed to evaluate the safety and efficacy of anakinra for severe and refractory scleritis. METHODS: Ten patients with severe (i.e. at least 2 ocular relapses per year despite treatment) and refractory [i.e. at least to one disease modifying antirheumatic drugs (DMARDS)] scleritis were treated with anakinra (100 mg/day subcutaneously). Scleritis was associated with inflammatory systemic diseases in 60% of cases. The remission rate defined the primary outcome. RESULTS: Ninety percent of patients were complete responders with a mean follow-up of 19.4 months after starting anakinra. The corticosteroids daily dose decreased from 18.3 ± 4.1 mg to 4.2 ± 4.9 mg, (p < 0.05), at initiation of anakinra and at end of follow-up, respectively. Associated immunosuppressants were stopped in all cases except one. Side effects were observed in 4 patients who did not need anakinra withdrawal. CONCLUSIONS: This pilot study suggests the efficacy of anakinra in patients with refractory scleritis.

Management of severe complications in Behçet's disease with TNF inhibitors.

INTRODUCTION: The efficacy of anti-TNFα agents has been recently evaluated in many studies in Behçet's disease (BD), particularly in ocular and life-threatening manifestations such as neurological and vascular disease. Areas covered: The following article aims to summarize the currently available efficacy and safety data of anti-TNFα agents in BD. Expert opinion: Most studies have shown dramatic and rapid efficacy with anti-TNFα agents on the main BD-associated issues including posterior uveitis, gastro-intestinal and neurological complications as well as major vessel disease. Experts in the field do recommend the use of anti-TNF agents (either infliximab or adalimumab) as a first-line therapy in severe posterior uveitis in BD and now use anti-TNFα treatment in BD-associated life threatening manifestations. However, data is mainly based on retrospective cohorts or open-label prospective studies. Controlled studies (versus conventional immunosuppressants such as azathioprine and cyclophosphamide) are warranted to properly evaluate their efficacy as first line therapeutic in life-threatening manifestations of BD.

Biotherapies in large vessel vasculitis.

Giant cell arteritis (GCA) and Takayasu's arteritis (TA) are large vessel vasculitis (LVV) and aortic involvement is not uncommon in Behcet's disease (BD) and relapsing polychondritis (RP). Glucocorticosteroids are the mainstay of therapy in LVV. However, a significant proportion of patients have glucocorticoid dependance, serious side effects or refractory disease to steroids and other immunosuppressive treatments such as cyclophosphamide, azathioprine, mycophenolate mofetil and methotrexate. Recent advances in the understanding of the pathogenesis have resulted in the use of biological agents in patients with LVV. Anti-tumor necrosis factor-α drugs seem effective in patients with refractory Takayasu arteritis and vascular BD but have failed to do so in giant cell arteritis. Preliminary reports on the use of the anti-IL6-receptor antibody (tocilizumab), in LVV have been encouraging. The development of new biologic targeted therapies will probably open a promising future for patients with LVV.

Th1 and Th17 cytokines drive inflammation in Takayasu arteritis.

OBJECTIVE: Takayasu arteritis (TAK) is a large-vessel vasculitis that induces damage to the aorta and its branches. Glucocorticoids remain the gold standard of therapy for TAK. The nature of the T cells driving vascular inflammation and the effects of glucocorticoids on the systemic components of TAK are not understood. The aim of this study was to analyze T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta in patients with TAK. METHODS: T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta were analyzed using Luminex analysis, flow cytometry, and immunohistochemical analysis. The study included 41 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK (17 patients with active TAK and 24 patients with disease in remission), 30 patients with giant cell arteritis and 39 patients with Behçet's disease (disease controls), and 20 age- and sex-matched healthy control subjects. RESULTS: We observed a marked increase in the expression of Th1 and Th17 cells, which correlated with TAK disease activity. The addition of serum from patients with active TAK to sorted CD4+ T cells from healthy donors in culture medium induced significant production of interferon-γ (IFNγ) and interleukin-17A (IL-17A). We demonstrated the presence of IFNγ-, IL-6-, and IL-17A-producing T cells in vascular inflammatory infiltrates in patients with TAK. Corticosteroid therapy was associated with decreased levels of circulating Th1 cytokines in corticosteroid-treated patients with TAK compared with steroid-free patients with TAK (for IL-2, mean ± SD 5,079 ± 5,300 versus 7,359 ± 3,197 pg/ml; for IFNγ, 2,592 ± 3,072 versus 8,393 ± 3,392 pg/ml; for tumor necrosis factor α, 847 ± 724 versus 1,491 ± 392 pg/ml). However, glucocorticoids had essentially no effect on the frequency of Th17 cytokines (IL-1 receptor, IL-17, and IL-23). CONCLUSION: The Th17 and Th1 pathways contribute to the systemic and vascular manifestations of TAK. Glucocorticoid treatment suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK.