Plasma therapy in atypical haemolytic uremic syndrome: lessons from a family with a factor H mutation

Whilst randomised control trials are undoubtedly the best way to demonstrate whether plasma exchange or infusion alone is the best first-line treatment for patients with atypical haemolytic uremic syndrome (aHUS), individual case reports can provide valuable information. To that effect, we have had the unique opportunity to follow over a 10-year period three sisters with aHUS associated with a factor H mutation (CFH). Two of the sisters are monozygotic twins. A similar natural evolution and response to treatment would be expected for the three patients, as they all presented with the same at-risk polymorphisms for CFH and CD46 and no identifiable mutation in either CD46 or CFI. Our report of different modalities of treatment of the initial episode and of three transplantations and relapses in the transplant in two of them, strongly suggest that intensive plasma exchange, both acutely and prophylactically, can maintain the long-term function of both native kidneys and allografts. In our experience, the success of plasma therapy is dependent on the use of plasma exchange as opposed to plasma infusion alone, the prolongation of daily plasma exchange after normalisation of haematological parameters followed by prophylactic plasma exchange, the use of prophylactic plasma exchange prior to transplantation and the use of prophylactic plasma exchange at least once a week posttransplant with immediate intensification of treatment if there are any signs of recurrence

Prophylactic plasma exchange in CD46-associated atypical haemolytic uremic syndrome

Patients with atypical haemolytic uremic syndrome (aHUS) with a mutation in the gene encoding membrane cofactor protein (CD46) are known to have a better prognosis than those with mutations in factor H (CFH) or factor I (CFI), but a small number of the former still proceed to end-stage renal failure. Plasma therapy (PE) is the recommended approach to treat both acute episodes and prevent recurrences in aHUS, but studies have yet to show PE efficacy in aHUS associated with a CD46 mutation. The factors determining failure to treatment are not clear and may be related to the mutation involved or to insufficient treatment. Our experience of PE in a family of three sisters with CFH-associated aHUS suggests that intensive and prophylactic PE allows renal function to be maintained in both native kidneys and allografts. The success of this strategy has led us to use it in all cases of aHUS. Here, we describe the effect of this strategy in a child with aHUS and a CD46 mutation. The initial episode was treated with daily PE, resulting in the recovery of renal function. However, over the next 4 years, there was a progressive decline in renal function to end-stage renal failure, with evidence of an on-going thrombotic microangiopathy despite continuous prophylactic PE. Prophylactic PE does not influence the natural course of aHUS and CD46 mutation

Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics

Item does not contain fulltextBACKGROUND: Mutations in complement factor H (CFH), factor I (CFI), factor B (CFB), thrombomodulin (THBD), C3 and membrane cofactor protein (MCP), and autoantibodies against factor H (alphaFH) with or without a homozygous deletion in CFH-related protein 1 and 3 (CFHR1/3) predispose development of atypical hemolytic uremic syndrome (aHUS). METHODS: Different mutations in genes encoding complement proteins in 45 pediatric aHUS patients were retrospectively linked with clinical features, treatment, and outcome. RESULTS: In 47% of the study participants, potentially pathogenic genetic anomalies were found (5xCFH, 4xMCP, and 4xC3, 3xCFI, 2xCFB, 6xalphaFH, of which five had CFHR1/3); four patients carried combined genetic defects or a mutation, together with alphaFH. In the majority (87%), disease onset was preceeded by a triggering event; in 25% of cases diarrhea was the presenting symptom. More than 50% had normal serum C3 levels at presentation. Relapses were seen in half of the patients, and there was renal graft failure in all except one case following transplant. CONCLUSIONS: Performing adequate DNA analysis is essential for treatment and positive outcome in children with aHUS. The impact of intensive initial therapy and renal replacement therapy, as well as the high risk of recurrence of aHUS in renal transplant, warrants further understanding of the pathogenesis, which will lead to better treatment options.01 augustus 201

Switchbacks, microstreams, and broadband turbulence in the solar wind

Switchbacks are a striking phenomenon in near-Sun coronal hole flows, but their origins, evolution, and relation to the broadband fluctuations seen farther from the Sun are unclear. We use the near-radial lineup of Solar Orbiter and Parker Solar Probe during September 2020 when both spacecraft were in wind from the Sun's Southern polar coronal hole to investigate if switchback variability is related to large scale properties near 1 au. Using the measured solar wind speed, we map measurements from both spacecraft to the source surface and consider variations with source Carrington longitude. The patch modulation of switchback amplitudes at Parker at 20 solar radii was associated with speed variations similar to microstreams and corresponds to solar longitudinal scales of around 5°–10°. Near 1 au, this speed variation was absent, probably due to interactions between plasma at different speeds during their propagation. The alpha particle fraction, which has recently been shown to have spatial variability correlated with patches at 20 solar radii, varied on a similar scale at 1 au. The switchback modulation scale of 5°–10°, corresponding to a temporal scale of several hours at Orbiter, was present as a variation in the average deflection of the field from the Parker spiral. While limited to only one stream, these results suggest that in coronal hole flows, switchback patches are related to microstreams, perhaps associated with supergranular boundaries or plumes. Patches of switchbacks appear to evolve into large scale fluctuations, which might be one driver of the ubiquitous turbulent fluctuations in the solar wind

Vancomycin-induced Henoch-Schönlein purpura: a case report

<p>Abstract</p> <p>Introduction</p> <p>Henoch-Schönlein purpura is a small-vessel systemic vasculitis. Although its exact pathophysiology remains unknown, Henoch-Schönlein purpura has been reported in association with various medical conditions including hypersensitivity. We report the case of a patient with vancomycin-induced Henoch-Schönlein purpura.</p> <p>Case presentation</p> <p>A 42-year-old Caucasian man who had previously undergone a heart transplant was diagnosed as having an intra-abdominal abscess after he underwent a Hartmann procedure. At 15 days after initiation of antibiotic therapy including vancomycin, he developed a purpuric rash of the lower limbs, arthralgia, and macroscopic hematuria. At that time, our patient was already on hemodialysis for end-stage renal disease. Henoch-Schönlein purpura was diagnosed. After a second 15-day course of vancomycin, a second flare of Henoch-Schönlein purpura occurred. Skin biopsies showed leucocytoclastic vasculitis with IgA deposits and eosinophils in the peri-capillary inflammatory infiltrate, suggesting an allergic mechanism. After vancomycin was stopped, we did not observe any further flares. Only five cases of isolated cutaneous vasculitis, one case of lupus-like syndrome and one case of Henoch-Schönlein purpura after vancomycin treatment have been described to date in the literature.</p> <p>Conclusions</p> <p>Clinicians should be aware that systemic vasculitis can be induced by some treatments. Vancomycin is a widely prescribed antibiotic. Occurrence of rare but serious Henoch-Schönlein purpura associated with vancomycin requires its prompt discontinuation.</p

The porin and the permeating antibiotic: A selective diffusion barrier in gram-negative bacteria

Gram-negative bacteria are responsible for a large proportion of antibiotic resistant bacterial diseases. These bacteria have a complex cell envelope that comprises an outer membrane and an inner membrane that delimit the periplasm. The outer membrane contains various protein channels, called porins, which are involved in the influx of various compounds, including several classes of antibiotics. Bacterial adaptation to reduce influx through porins is an increasing problem worldwide that contributes, together with efflux systems, to the emergence and dissemination of antibiotic resistance. An exciting challenge is to decipher the genetic and molecular basis of membrane impermeability as a bacterial resistance mechanism. This Review outlines the bacterial response towards antibiotic stress on altered membrane permeability and discusses recent advances in molecular approaches that are improving our knowledge of the physico-chemical parameters that govern the translocation of antibiotics through porin channel

Pathogenesis of Henoch-Schönlein purpura nephritis

The severity of renal involvement is the major factor determining the long-term outcome of children with Henoch-Schönlein purpura (HSP) nephritis (HSPN). Approximately 40% children with HSP develop nephritis, usually within 4 to 6 weeks after the initial onset of the typical purpuric rashes. Although the pathogenetic mechanisms are still not fully delineated, several studies suggest that galactose-deficient IgA1 (Gd-IgA1) is recognized by anti-glycan antibodies, leading to the formation of the circulating immune complexes and their mesangial deposition that induce renal injury in HSPN