Impact of treatment on damage and hospitalization in elderly patients with microscopic polyangiitis and granulomatosis with polyangiitis

OBJECTIVE: Age is a risk factor for organ damage, adverse events, and mortality in microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). However, the relationship between treatment and damage, hospitalizations, and causes of death in elderly patients is largely unknown. METHODS: Consecutive patients from Sweden, England, and the Czech Republic diagnosed between 1997 and 2013 were included. Inclusion criteria were a diagnosis of MPA or GPA and age 75 years or more at diagnosis. Treatment with cyclophosphamide, rituximab, and corticosteroids the first three months was registered. Outcomes up to two years from diagnosis included vasculitis damage index (VDI), hospitalization, and cause of death. RESULTS: Treatment data was available for 167 of 202 patients. At two years, 4% had no items of damage. There was a positive association between VDI score at two years and Birmingham Vasculitis Activity Score at onset, and a negative association with treatment using cyclophosphamide or rituximab. Intravenous methylprednisolone dose was associated with treatment-related damage. During the first year, 69% of patients were readmitted to hospital. MPO-ANCA positivity and lower creatinine levels decreased the odds for readmission. The most common cause of death was infection, and this was associated with cumulative oral prednisolone dose. CONCLUSION: Immunosuppressive treatment with cyclophosphamide or rituximab in elderly patients with MPA and GPA was associated with development of less permanent organ damage and was not associated with hospitalization. However, higher doses of corticosteroids during the first three months was associated with treatment-related damage and fatal infections

Rituximab in adult minimal change disease and focal segmental glomerulosclerosis - What is known and what is still unknown?

Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations

Individual Water Sources and their Potential Effect on Human and Animal Health in Environmentally Burdened Region

The quality of water in a well that serves as an individual drinking water source, located in the Slovakian region previously burdened with mining activities, was investigated in relation to the quality of surface water in the same region. Selected microbiological and physicochemical parameters were determined in samples of ground water (well) and surface water (brook and river). Plate counts of coliform bacteria, E. coli, enterococci and bacteria cultivated at 22 °C and 37 °C were determined. Microbiological quality of samples collected from the well was generally satisfactory. Examination of the samples of surface water (river) showed a significant organic pollution indicated by fluorescence spectra. In all water samples the values of: pH, electrical conductivity, dissolved oxygen, ammonium ions, nitrites, nitrates, chlorides and chemical oxygen demand (CODMn) were below the limits set by the state legislation. In the surface water, high levels of arsenic were found. The sum of calcium and magnesium in the well water was close to or below the recommended minimum level. In this well water, the level of antimony exceeded 10-fold the maximum limit for drinking water and was of the largest concern as this well water has been used for drinking, cooking, and watering of animals and vegetables for a long period of time. This poses a risk of accumulation of this metalloid in the food chain

Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients.

Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis, 41 patients with anti-GBM disease, and 37 double-positive patients with ANCA and anti-GBM disease from four European centers. Double-positive patients shared characteristics of ANCA-associated vasculitis (AAV), such as older age distribution and longer symptom duration before diagnosis, and features of anti-GBM disease, such as severe renal disease and high frequency of lung hemorrhage at presentation. Despite having more evidence of chronic injury on renal biopsy compared to patients with anti-GBM disease, double-positive patients had a greater tendency to recover from being dialysis-dependent after treatment and had intermediate long-term renal survival compared to the single-positive patients. However, overall patient survival was similar in all three groups. Predictors of poor patient survival included advanced age, severe renal failure, and lung hemorrhage at presentation. No single-positive anti-GBM patients experienced disease relapse, whereas approximately half of surviving patients with AAV and double-positive patients had recurrent disease during a median follow-up of 4.8 years. Thus, double-positive patients have a truly hybrid disease phenotype, requiring aggressive early treatment for anti-GBM disease, and careful long-term follow-up and consideration for maintenance immunosuppression for AAV. Since double-positivity appears common, further work is required to define the underlying mechanisms of this association and define optimum treatment strategies