Prognosis and long-term outcomes in type I cryoglobulinemia: A multicenter study of 168 patients.

Type I cryoglobulinemia (CG) accounts for 10%-15% of all cryoglobulinemias and are exclusively seen in clonal proliferative hematologic conditions. In this multicenter nationwide cohort study, we analyzed the prognosis and long-term outcomes of 168 patients with type I CG (93 (55.4%) IgM and 75 [44.6%] IgG). Five- and 10-year event-free survivals (EFS) were 26.5% (95% CI 18.2%-38.4%) and 20.8% (95% CI 13.1%-33.1%), respectively. In multivariable analysis, factors associated with poorer EFS were renal involvement (HR: 2.42, 95% CI 1.41-4.17, p = .001) and IgG type I CG (HR: 1.96, 95% CI 1.13-3.33, p = 0.016), regardless of underlying hematological disorders. IgG type I CG patients had higher cumulative incidence of relapse (94.6% [95% CI 57.8%-99.4%] vs. 56.6% [95% CI 36.6%-72.4%], p = .0002) and death at 10 years (35.8% [19.8%-64.6%] vs. 71.3% [54.0%-94.2%], p = .01) as compared to IgM CG, respectively. Overall, complete response of type I CG at 6 months was 38.7%, with no significant difference between Igs isotypes. In conclusion, renal involvement and IgG CG were identified as independent poor prognostic factors of type I CG.

Rituximab plus belimumab in non-infectious refractory cryoglobulinemia vasculitis: A pilot study.

OBJECTIVE: To report the efficacy of rituximab plus belimumab in patients with refractory cryoglobulinemia vasculitis (CV). METHODS: Belimumab was administered intravenously at a dose of 10 mg/kg on days 0, 14, 28 and then every month in association with rituximab in 4 patients with refractory CV. Demographic, clinical and laboratory characteristics, treatment modalities and outcomes were recorded. RESULTS: All patients had type II IgM Kappa cryoglobulinemia, which was associated with primary Sjögren syndrome (n = 1), hepatitis C virus infection (n = 1), and essential (n = 2). Main manifestations of CV included purpura (n = 4), arthralgia and peripheral neuropathy (n = 3), and glomerulonephritis and skin ulcers (n = 1). In all cases, CV was refractory and/or relapse following rituximab. Intravenous belimumab infusion along with rituximab resulted in rapid clinical response in the four patients. Osteitis and recurrent urinary tract infections occurred in two patients. CONCLUSION: Belimumab along with rituximab showed promising results in refractory patients with CV.

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. 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. Bilateralization 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, the prevention of recurrent attacks, the achievement of complete remission, and the preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update to a previous article by our team on pathogenesis, diagnostic approaches, and the therapeutic strategy of BD uveitis.

Perspectives for immunotherapy in noninfectious immune mediated uveitis.

Introduction: Noninfectious uveitis (NIU) is one of the leading causes of blindness worldwide. In adult patients, anterior NIU is usually managed with topical corticosteroids. In intermediate, posterior uveitis. and panuveitis, systemic corticosteroids are used especially in case of bilaterality or association with systemic disease. Biotherapies are recommended in case of inefficacy or intolerance to corticosteroids or conventional immunosuppressive drugs. Anti-TNF-α agents are by far the most widely used biotherapies. In case of failure or poor tolerance to anti-TNF-α, new targeted therapies can be proposed.Areas covered: We present and discuss an updated overview on biologics and biotherapies in NIU.Expert opinion: In case of dependency to systemic or intravitreal steroids, sight-threatening disease, and/or failure of conventional immunosuppressive drugs, anti-TNF-α are used as first-line biologics to achieve quiescence of inflammation. Anti-interleukin-6 is another option that may be proposed as first-line biologic or in case of poor efficacy of anti-TNF-α. Interferon can be directly proposed in specific indications (e.g. refractory macular edema, sight-threatening Behçet's uveitis). In the rare cases that remain unresponsive to traditional biotherapies, novel molecules, such as Janus-associated-kinase and anti-phosphodiesterase-4-inhibitors can be used. Therapeutic response must always be evaluated by clinical and appropriate ancillary investigations.

Management of Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS), is an acquired autoimmune disorder characterised by thrombosis, pregnancy morbidity, and the presence of antiphospholipid antibodies (aPL). Although venous thromboembolism is the most common manifestation, thrombotic events in APS may also occur in virtually any vascular bed, with cerebral circulation being the arterial territory most commonly affected. As APS is a heterogeneous condition, its management should be tailored with a patient-centred approach based on individual risk assessment, which includes the aPL profile, concomitant auto-immune diseases, and traditional cardiovascular risk factors. Although literature data are conflicting regarding primary prophylaxis, there is some evidence indicating that antiplatelet agents may reduce the risk of a first thrombotic event in individuals with a high-risk profile. In patients with thrombotic APS, current evidence-based guidelines recommend lifelong vitamin K antagonists (VKAs), preferably warfarin. The optimal intensity of anticoagulation following arterial thrombosis remains controversial. Arterial thrombosis should be treated either with high-intensity warfarin at a target INR > 3.0, or low-dose aspirin (LDA) combined with moderate-intensity warfarin (INR 2.0-3.0). It is recommended to avoid direct oral anticoagulants (DOACs) in patients with high-risk APS, mainly those with triple-positive PL and previous arterial events. They would only be used exceptionally in selected patients with low-risk venous thromboembolism (VTE). In low-risk VTE patients currently treated with a DOAC due to warfarin intolerance or a previous unstable International Normalized Ratio on warfarin, the decision of continuing DOACs would be taken in carefully selected patients. In women with obstetric APS, the combination therapy with LDA plus heparin remains the conventional strategy.

Risk Factors and Prevention of Pneumocystis jirovecii Pneumonia in Patients With Autoimmune and Inflammatory Diseases.

Patients with autoimmune and/or inflammatory diseases (AIIDs) are prone to serious infectious complications such as Pneumocystis jirovecii pneumonia (PJP). In non-HIV patients, the prognosis is poorer, and diagnostic tests are of lower sensitivity. Given the low incidence of PJP in AIIDs, with the exception of granulomatosis with polyangiitis, and the non-negligible side effects of chemoprophylaxis, routine prescription of primary prophylaxis is still debated. Absolute peripheral lymphopenia, high doses of corticosteroids, combination with other immunosuppressive agents, and concomitant lung disease are strong predictors for the development of PJP and thus should warrant primary prophylaxis. Trimethoprim-sulfamethoxazole is considered first-line therapy and is the most extensively used drug for PJP prophylaxis. Nevertheless, it may expose patients to side effects. Effective alternative drugs such as atovaquone or aerosolized pentamidine could be used when trimethoprim-sulfamethoxazole is not tolerated or contraindicated. No standard guidelines are available to guide PJP prophylaxis in patients with AIIDs. This review covers the epidemiology, risk factors, and prevention of pneumocystis in the context of AIIDs.