Zika Virus Associated with Microcephaly Mlakar, Jernej; Korva, Misa; Tul, Nataša ...
New England journal of medicine/The New England journal of medicine,
2016-Mar-10, Letnik:
374, Številka:
10
Journal Article
Recenzirano
Odprti dostop
A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased ...incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.
In 2010, EULAR/PRINTO/PRES proposed new classification criteria for paediatric IgA vasculitis (IgAV) that have a higher diagnostic sensitivity than the 1990 ACR criteria. These criteria have so far ...not been evaluated in adults, in whom IgAV is considered as a rare disease. Our main objective was to compare the diagnostic performance of EULAR/PRINTO/PRES and ACR classification criteria in adult IgAV.
Adult IgAV cases fulfilling the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides (ICHCCNV) definition of IgAV at a secondary/tertiary rheumatology referral centre were critically reviewed in a partially retrospective and partially prospective manner. First, we compared the diagnostic sensitivity of ACR and EULAR/PRINTO/PRES criteria in this group of patients. Second, the diagnostic specificity of ACR and EULAR/PRINTO/PRES was determined by applying these criteria to a control group of patients with other systemic vasculitides.
Between 1 January 2010 and 31 December 2014 350 new cases of systemic vasculitis were identified. IgAV was diagnosed in 129, and other systemic vasculitides in 221 (123 had large, six medium and 92 small vessel vasculitis) cases according to ICHCCNV. The diagnostic sensitivity and specificity of the IgAV EULAR/PRINTO/PRES criteria were 99.2 % (95 % CI 95.4-99.9 %) and 86.0 % (95 % CI 80.7-90.3 %), and of the ACR criteria 86.8 % (95 % CI 79.7-92.1 %) and 81.0 % (95 % CI 75.2-85.9 %), respectively with an inter-criteria agreement of 77.5 % (95 % CI: 70.8-84.1 %).
In the adult population the EULAR/PRINTO/PRES IgAV classification criteria had a higher sensitivity and specificity than the ACR criteria.
C1q nephropathy is an uncommon glomerular disease with characteristic features on immunofluorescence microscopy. In this report, clinicopathologic correlations and outcomes are presented for 72 ...patients with C1q nephropathy. The study comprised 82 kidney biopsies from 28 children and 54 adults with male preponderance (68%). Immunofluorescence microscopy showed dominant or co-dominant staining for C1q in the mesangium and occasional glomerular capillary walls. Electron-dense deposits were observed in 48 of 53 cases. Light microscopy revealed no lesions (n = 27), focal segmental glomerulosclerosis (FSGS; n = 11), proliferative glomerulonephritis (n = 20), or various other lesions (n = 14). Clinical presentations in the patients who had no lesions histology were normal urine examination (7%), asymptomatic hematuria and/or proteinuria (22%), and nephrotic syndrome (minimal change-like lesion; 63%), which frequently relapsed. All patients with FSGS presented with nephrotic syndrome. Those with proliferative glomerulonephritis usually presented with chronic kidney disease (75%) or asymptomatic urine abnormalities (20%). Of the patients with sufficient follow-up data, complete remission of the nephrotic syndrome occurred in 77% of those with a minimal change-like lesion, progression to end-stage renal disease occurred in 33% of those with FSGS, and renal disease remained stable in 57% of those with proliferative glomerulonephritis. In conclusion, this study identified two predominant clinicopathologic subsets of C1q nephropathy: (1) Podocytopathy with a minimal change-like lesion or FSGS, which typically presents with nephrotic syndrome, and (2) a typical immune complex-mediated glomerular disease that varies from no glomerular lesions to diverse forms of glomerular proliferation, which typically presents as chronic kidney disease. Clinical presentation, histology, outcomes, and presumably pathogenesis of C1q nephropathy are heterogeneous.
To evaluate the involvement of immune abnormality in patients with idiopathic premature ovarian insufficiency (POI). In addition to the known etiology, autoimmune disorders may be a pathologic ...mechanism for POI.
Our study was a prospective controlled trial. Twenty women with POI, reasons other than autoimmune excluded, were enrolled in this study. The control group consisted of 17 healthy women. In both groups, family and personal history were taken and the levels of follicle stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, prolactin, anti-Müllerian hormone, inhibin B, antithyroglobulin and antithyroid peroxidase antibodies were determined. Antiovarian antibodies and subpopulations of peripheral blood T-lymhocytes were also determined.
Participants in the study group exhibited hypergonadotropichypogonadism, while high levels of follicle stimulating hormone and low levels of inhibin B and anti-Müllerian hormone were observed. In 16 (80%) patients, POI was associated in their personal and familial history with another autoimmune disease. Fifty percent of patients presented highly elevated antithyroid antibodies. The lymphocyte subset, especially B cells, was significantly higher (p=0.014), and peripheral regulatory lymphocytes CD25+ high were significantly lower (p=0.015) in the study group than in the control group. Anti- ovarian antibodies were detected in 20% of patients with POI.
We presume that the presence of anti-ovarian antibodies together with abnormalities of cellular immunity may in some cases potentially represent the involvement of an autoimmune mechanism in idiopathic POI.
The aim of our study was to evaluate the prognostic value of glomerular and tubular proteinuria and tubular enzymuria as early indicators of therapeutic response to induction therapy with i.v. pulse ...cyclophosphamide (CyC) and methylprednisolone (MP) in patients with antineutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis.
An observational single-center study was conducted in 30 patients with ANCA-associated glomerulonephritis. Patients were divided into subgroups with good or poor response to CyC therapy according to clinical and laboratory parameters. The diagnosis of ANCA-associated glomerulonephritis was based on the Chapel-Hill disease definitions. Good response to induction therapy was significantly associated with higher absolute values of urine N-acetyl-beta-D-glucosaminidase (NAG) to creatinine ratio (above 14.83 microcat/mol) and urine immunoglobulin G (IgG) to albumin ratio (above 0.09) at the time of diagnosis, while albuminuria or proteinuria did not have any early predictive value. The remission of renal disease was anticipated as early as 3 months after introduction of induction therapy in patients with reduction of urine NAG to creatinine ratio below the baseline value and in patients with at least 24% rise in eGFR.
Urine IgG to albumin and urine NAG to creatinine ratio are better early predictors of treatment response in patients with ANCA-associated glomerulonephritis than proteinuria or albuminuria.
Antineutrophil cytoplasmic antibodies (ANCA) and antibodies against glomerular basement membrane (anti‐GBM) rarely coexist. Both antibodies may be associated with rapidly progressive ...glomerulonephritis and pulmonary hemorrhage. We describe the clinical, serological and histological features of our patients with dual antibodies. From 1977 to 2008, 48 patients with anti‐GBM antibody‐associated renal disease were observed. Eight out of the 30 tested patients (26.7%), all females, had positive myeloperoxidase (MPO)‐ANCA coexistent with anti‐GBM antibodies. The patients' mean age was 63.4 ± 7.8 years. Five presented with pulmonary‐renal syndrome, all but one were dialysis‐dependent on admission. They had constitutional symptoms and different organ involvement. The kidney biopsies revealed intense linear staining for immunoglobulin G and C3 along the glomerular and distal tubular basement membrane associated with irregular diffuse or focal extracapillary crescentic glomerulonephritis with necrosis of varying extent. Lesions of varying ages were characteristically expressed. Seven patients were treated with methylprednisolone and plasma exchange, four with cyclophosphamide, and one with intravenous immunoglobulin. After 28–74 months, there were three dialysis‐dependent survivors and one patient with stable chronic renal disease. Two clinical relapses with pulmonary involvement and MPO‐ANCA positivity without anti‐GBM antibodies occurred in two dialysis‐dependent patients. In summary, screening for ANCA and anti‐GBM antibodies should be undertaken in patients with clinical signs of systemic vasculitis. In dialysis‐dependent patients, the goal of treatment is to limit the damage of other involved organs and not to preserve renal function. Careful follow‐up is necessary due to the relapsing nature of the ANCA component of the disease.
The aim of our retrospective study was to analyze the clinical course and outcome of patients with immunoglobulin A (IgA) nephropathy who presented with macroscopic hematuria and acute kidney injury ...(AKI). During the period from 1990 to 2005, seven out of 584 adult patients with IgA nephropathy (1.2%) fulfilled the criteria for macroscopic hematuria‐induced AKI. There was an equal gender distribution among our patients, and a rather high average age at presentation (55.7 ± 10.9 years). Four patients who were oliguric upon admission to hospital needed hemodialysis treatment. The average serum creatinine at the time of kidney biopsy was 429.8 ± 377 µmol/L (median value 378). The percutaneous kidney needle biopsies showed focal proliferative crescentic glomerulonephritis of subclass III, according to the Haas scheme, associated with prominent red blood cell tubular casts and acute tubulointerstitial nephritis. Four patients with the most prominent crescents and tubulointerstitial involvement were treated with methylprednisolone. All patients, treated and untreated, recovered their kidney function (the serum creatinine at a median follow‐up of 15 months was 111.7 ± 38 µmol/L). In conclusion, AKI in IgA nephropathy accompanied by macroscopic hematuria appears to have been a reversible condition in our series of patients. Regarding pathogenesis, the kidney biopsy study points to the important role of glomerular bleeding with consequent, widespread obstructive red blood cell tubular casts accompanied by tubular injury and interstitial nephritis.
Summary A 35-year-old white male with symptoms of paranoid schizophrenia was treated by psychiatrists for 13 years. During the final year, he developed severe dysphagia, reduced strength of the upper ...extremity muscles, and cognitive dysfunction. The patient died in his sleep. The only pathology found in coronal brain sections was ill-defined periventricular foci with prominent, firm vessels. Microscopy revealed abundant, hematoxylin and eosin–eosinophilic, periodic acid–Schiff–positive, thioflavin T–positive, and Congo red–negative deposits in the vessel walls, with hypoxic encephalopathy in the affected regions. Immunohistochemistry showed λ light chains as the main component of the deposits. Ultrastructural analysis showed amorphous electron dense material in the vessel walls. Perivascular B-cell proliferation was present in the vicinity of affected areas. Polymerase chain reaction was applied for the assessment of B-cell clonality, revealing monoclonal rearrangement of the heavy chain Ig gene. Neither in the kidney nor in any other organ were deposits detected. This is the first case report of light chain deposition disease restricted to the brain.
Hantavirus Nephropathy FERLUGA, Dusan; VIZJAK, Alenka
Journal of the American Society of Nephrology,
09/2008, Letnik:
19, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Pathogenic rodent-borne hantaviruses cause in humans generalized infections that involve the peripheral vascular bed and severely affect their permeability. We describe a 30-yr-old male patient with ...clinical symptoms characterizing five conventional phases of hemorrhagic fever with renal syndrome after an uncommonly severe hantavirus infection with the Puumala strain. Renal biopsy in this situation typically demonstrates acute hemorrhagic interstitial nephritis, particularly pronounced in the outer medulla. Hantaviruses are not cytopathic for most cells, and their interactions with endothelial cells that activate immune mechanisms play a key role in the pathogenesis of vascular dysfunction characterizing this disease.
-The 2015 outbreak of Zika virus in Brazil resulted in a 20-times increased prevalence of congenital microcephaly in stillborns and neonates and was instrumental in raising the suspicion of a causal ...association between Zika virus and microcephaly.
-To provide a comprehensive description of the neuropathologic features of congenital Zika virus infection.
-Autopsy evaluation of the brain from a fetus of 32 weeks and 6 days of gestation, with a prenatal diagnosis of microcephaly associated with polymerase chain reaction-confirmed, fetal, Zika virus infection.
-Multiple severe pathology findings were present. These included lissencephaly, except for the occipital lobes, where some pachygyria was observed. Also present was reduction and thinning of white matter, ventriculomegaly of the lateral ventricles, and coalescent calcifications in the cortical-subcortical white matter border associated with glioneuronal outbursting into the subarachnoid space above and heterotopias below. There were small, scattered calcifications in the basal ganglia, with fewer in the white matter and germinal matrix, and none in the cerebellum and brainstem. The cerebellum and pontine base were atrophic because of Wallerian degeneration or maldevelopment of descending tracts and pontocerebellar connections.
-Our findings are in agreement with neuroimaging of Zika virus-associated fetal and infant micrencephalic brains and, to some extent, with neuroimaging of other intrauterine infections causing microcephaly.
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