Non HCV-Related Mixed Cryoglobulinemic Vasculitis With Biopsy-Proven Renal Involvement: The Effects of Rituximab.

In the countries where HCV infection is still endemic, about 90% of subjects with mixed cryoglobulinemia had previously been infected with HCV and about 80% are RNA positive. Remarkable results in severe HCV-related cryoglobulinemic vasculitis have been obtained with Rituximab. Details of the clinical characteristics and effective treatment of non HCV-related cryogloulinemic syndromes are presently lacking.

A Prospective Study on Long-Term Clinical Outcomes of Patients With Lupus Nephritis Treated With an Intensified B-Cell Depletion Protocol Without Maintenance Therapy.

Background: We aimed to investigate the safety and efficacy of an intensified B-cell depletion induction therapy (IBCDT) without immunosuppressive maintenance regimen compared with standard of care in biopsy-proven lupus nephritis (LN).

Methods: Thirty patients were administered an IBCDT (4 weekly rituximab [RTX] 375 mg/m and 2 more doses after 1 and 2 months; 2 infusions of 10 mg/kg cyclophosphamide [CYC], 3 methylprednisolone pulses), followed by oral prednisone (tapered to 5 mg/d by the third month). No immunosuppressive maintenance therapy was given.

An agent-to-agent real life comparison study of tocilizumab versus abatacept in giant cell arteritis.

Objectives: The present study aimed at evaluating the efficacy of abatacept (ABA) compared to tocilizumab (TCZ), assumed as a gold standard biologic treatment in the management of patients with giant cell arteritis (GCA).

Methods: Thirty-three biospy-proven GCA consecutive patients were prospectively collected. Odd patients (from 1 to 33) were assigned to TCZ, given either intravenously (IV 8 mg/kg/month), #8 cases, or subcutaneously (SC 162 mg/week) #9, based on patient's preference.

Pathogenic variants in EP300 and ANKRD11 in patients with phenotypes overlapping Cornelia de Lange syndrome.

Cornelia de Lange syndrome (CdLS), Rubinstein-Taybi syndrome (RSTS), and KBG syndrome are three distinct developmental human disorders. Variants in seven genes belonging to the cohesin pathway, NIPBL, SMC1A, SMC3, HDAC8, RAD21, ANKRD11, and BRD4, were identified in about 80% of patients with CdLS, suggesting that additional causative genes remain to be discovered. Two genes, CREBBP and EP300, have been associated with RSTS, whereas KBG results from variants in ANKRD11.

Outcome of patients with severe AL amyloidosis and biopsy-proven renal involvement ineligible for bone marrow transplantation.

Introduction: AL amyloidosis is caused by a clone of plasma cell. Due to the impact of the disease on patient survival, careful evaluation of organ involvement is essential and treatment should be tailored to single patient's risk.

Aim: We analyzed the clinical, laboratory and histological characteristics of 21 elderly patients (pts) (mean age 74.

The "4 plus 2" rituximab protocol makes maintenance treatment unneeded in patients with refractory ANCA-associated vasculitis: A 10 years observation study.

Background: ANCA associated vasculitides (AAV) often present with a chronic relapsing course. Relapse leads to increased immunosuppressive exposure and consequent toxicity. While two randomized controlled trials have shown rituximab (RTX) to be the most effective induction treatment in patients with relapsing disease, the optimal treatment duration and RTX dose remain debated.

High-Dose Rituximab Ineffective for Focal Segmental Glomerulosclerosis: A Long-Term Observation Study.

Background: A beneficial effect of rituximab (RTX) on focal segmental glomerulosclerosis (FSGS) in pediatric patients or in transplant recipients has been reported in isolated cases. However, the use of RTX in adult patients with idiopathic FSGS needs further investigation.

Methods: Eight patients who had biopsy-proven FSGS (63.

Improved (4 Plus 2) Rituximab Protocol for Severe Cases of Mixed Cryoglobulinemia: A 6-Year Observational Study.

Background: In a prospective, single-center open study, we evaluated the very long-term effects of rituximab (RTX) administered to patients with severe mixed cryoglobulinemia (MC).

Methods: RTX was administered to 31 patients with MC (type II in 29 cases and type III in 2) with diffuse membranoproliferative glomerulonephritis (16 cases), peripheral neuropathy (26) and large skin ulcers (7). All but 4 patients had serum anti-hepatitis C virus antibodies.

A 4-year observation in lupus nephritis patients treated with an intensified B-lymphocyte depletion without immunosuppressive maintenance treatment-Clinical response compared to literature and immunological re-assessment.

Background: B cells (BC) play a critical role in systemic lupus erythematosus (SLE). BC depletion therapy still remains an attractive option, despite the disappointing results of randomized controlled trials (RTCs).

Methods: Twelve patients with SLE [3 males, mean age 43.

Canakinumab as rescue therapy in familial Mediterranean fever refractory to conventional treatment.

Familial Mediterranean fever is an autosomal recessive autoinflammatory disorder mainly affecting Mediterranean populations, which is associated with mutations of the MEFV gene that encodes pyrin. Functional studies suggest that pyrin is implicated in the maturation and secretion of interleukin-1 (IL-1). The IL-1 receptor antagonist or anti-IL-1 monoclonal antibody may therefore represent a rational approach for the treatment of the rare patients who are refractory to conventional therapy.

A multidrug, antiproteinuric approach to alport syndrome: a ten-year cohort study.

Background/aims: Combined ACE inhibitor, angiotensin-receptor-blocker, non-dihydropyridine calcium-channel-blocker, and statin therapy (Remission Clinic) reduced proteinuria and halted progression in non-diabetic nephropathies, but their efficacy in Alport syndrome (AS) nephropathy is unknown.

Methods: From February 2004 to September 2007, we included nine albuminuric AS adults with creatinine clearance >20 ml/min/1.73 m(2) in a single-center, open-label, prospective, off-on-off academic study.

Long term follow-up to evaluate the efficacy of miglustat treatment in Italian patients with Niemann-Pick disease type C.

Background: Twenty-five patients with Niemann Pick disease type C (age range: 7 months to 44 years) were enrolled in an Italian independent multicenter trial and treated with miglustat for periods from 48 to 96 months.

Methods: Based on the age at onset of neurological manifestations patients' phenotypes were classified as: adult (n = 6), juvenile (n = 9), late infantile (n = 6), early infantile (n = 2). Two patients had an exclusively visceral phenotype.

Mycophenolate mofetil as steroid-sparing treatment for elderly patients with giant cell arteritis: report of three cases.

Background And Aims: Glucocorticoids have never been studied in a placebo-controlled manner in giant cell arteritis (GCA), but their effectiveness is well established. However, evidence for the efficacy of immunosuppressant drugs as steroid-sparing agents in this disease is highly desirable, especially in elderly patients. We report the use of mycophenolate mofetil (MMF) as a steroid-sparing agent in three patients (mean age 78 years) with GCA, at high risk of longterm high dose glucocorticoids because of type II diabetes mellitus, obesity, hypertension or osteoporosis.

Apheresis as rescue therapy in a severe case of sudden hearing loss.

A 23-year-old man complained of progressive left ear hearing loss and tinnitus and was unsuccessfully treated with steroids and mannitol. Four months later he presented with sudden, severe, asymmetrical, bilateral sensorineural hearing loss. The results of the laboratory workup were normal except for antinuclear autoantibodies.

Long-term effects of rituximab added to cyclophosphamide in refractory patients with vasculitis.

Background: Current therapies have changed systemic vasculitis from a disease with a high rate of mortality to a chronic curable condition. A limited percentage of patients either remains refractory to conventional treatment or experiences dose-limiting side effects.

Methods: 11 patients (4 affected by idiopathic systemic microscopic polyangiitis, 5 by Wegener's granulomatosis, and 2 by Churg-Strauss syndrome) intolerant or refractory to conventional therapies including cyclophosphamide were enrolled.

Intensive short-term treatment with rituximab, cyclophosphamide and methylprednisolone pulses induces remission in severe cases of SLE with nephritis and avoids further immunosuppressive maintenance therapy.

Background: B cells play a central role in systemic lupus erythematosus (SLE). Rituximab is expected to induce apoptosis of all the CD20-positive B cells. A proportion of patients are refractory or intolerant to standard immunosuppression.

Effects of anti-CD20 monoclonal antibody as a rescue treatment for ANCA-associated idiopathic systemic vasculitis with or without overt renal involvement.

Background: Cyclophosphamide (CYC) is thought to be the most effective treatment for antineutrophil cytoplasmatic antibody (ANCA)-associated idiopathic systemic vasculitis with severe organ or life threatening presentation. The key mechanism of action of CYC is suppression of the B lymphocyte activity. However, a considerable minority of patients either remains refractory to conventional therapy or experiences dose-limiting side effects.

Anti-neuronal antibodies in patients with HCV-related mixed cryoglobulinemia.

Mixed cryoglobulinemia (MC) is an immunological disorder characterized by immune-complex-mediated systemic vasculitis involving small vessels, which may present with renal, cutaneous, rheumatologic, and/or neurological manifestations. Until recently, the possible appearance of anti-neuronal autoantibodies in peripheral neuropathy occurring in the context of hepatitis C virus (HCV)-associated IgMk/IgG MC has not been extensively addressed. Therefore, a sample of these patients were evaluated by means of immuno-enzyme methods of anti-neuronal autoantibody detection.

Rituximab as a therapeutic tool in severe mixed cryoglobulinemia.

Type II mixed cryoglobulinemia (MC) is a systemic vasculitis, associated in most cases with hepatitis C virus (HCV) infection, sustained by proliferation of oligoclonal cells. Systemic B cell depletion and clinical remission can be achieved in non-Hodgkin lymphoma by human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (rituximab). Similar effects could be expected in type II MC.

Anti-GM1 and anti-sulfatide antibodies in patients with systemic lupus erythematosus, Sjögren's syndrome, mixed cryoglobulinemia and idiopathic systemic vasculitis.

Objectives: Over the last two decades, increasing interest has been focused on the association between autoimmune polyneuropathies and anti-neuronal autoantibodies in immune-mediated polyneuropathy. The possible appearance of these autoantibodies in systemic diseases that are not limited to the nervous system has not been fully addressed yet.

Methods: We evaluated 32 patients with systemic lupus erythematosus, 34 patients with hepatitis C virus-associated mixed IgM-k/IgG cryoglobulinemia, 19 with small vessel ANCA-associated vasculitis, and 20 patients with Sjögren's syndrome by means of an immunoenzyme method of anti-neuronal autoantibody detection.

Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial.

Background: In chronic nephropathies, inhibition of angiotensin-converting enzyme (ACE) is renoprotective, but can further renoprotection be achieved by reduction of blood pressure to lower than usual targets? We aimed to assess the effect of intensified versus conventional blood-pressure control on progression to end-stage renal disease.

Methods: We undertook a multicentre, randomised controlled trial of patients with non-diabetic proteinuric nephropathies receiving background treatment with the ACE inhibitor ramipril (2.5-5 mg/day).

Thin glomerular basement membrane disease: clinical significance of a morphological diagnosis--a collaborative study of the Italian Renal Immunopathology Group.

Background: Thin glomerular basement membrane disease (TBMD) is a nephropathy defined by diffuse thinning of the glomerular basement membrane (GBM) at electron microscopy examination, without the alterations of Alport's syndrome (ATS). It is known that many patients with TBMD have a type IV collagen disorder and that the disease occasionally may be progressive. This study investigated 51 patients with the morphological diagnosis of TBMD lacking any sign of ATS, with the aim of defining the prevalence of type IV collagen mutations and the course of the disease.

Long-term effects of anti-CD20 monoclonal antibody treatment of cryoglobulinaemic glomerulonephritis.

Background: Type II mixed cryoglobulinaemia (MC) is a systemic vasculitis, associated in most cases with hepatitis C virus (HCV) infection, and sustained by proliferation of oligoclonal cells. Systemic B-cell depletion and clinical remission can be achieved in non-Hodgkin lymphoma by a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen (Rituximab). Similar effects could be expected in type II MC.

Nail fold videocapillaroscopy in mixed cryoglobulinaemia.

Background: Nail fold videocapillaroscopy (NVC) has been extensively used to examine morphological and functional changes of microcirculation in connective tissue diseases. The nutritional circulation that depends on tissue capillaries, can be expected to be significantly impacted in mixed cryoglobulinaemia (MC).

Methods: Using NVC, we evaluated 29 patients with MC (19 women), mean age 66 years (range 40-83).