Hematologic Manifestations of Parvovirus B19 Infection.

Parvovirus B19 virus infection is widespread among humans because of its highly infectious and obstinate nature, with up to 80% of the population testing positive for IgG antibodies against the virus. Pronormoblasts observed in biopsy are the hallmarks of PVB19 infection. In addition, PVB19 affects the skin, heart, brain, joints, and liver and can be diagnosed through antibody detection or DNA detection via PCR. Due to its capsid proteins' high affinity for bone marrow receptors, its main presentation is the suppression of bone marrow functions. It has been shown to affect patients with hemolytic anemia and patients with hematological malignancies, presenting with pure red cell aplasia. The main available effective treatment option is IV immunoglobulins; however, the risk of recurrence remains high after treatment.

[A case of anti-SRP antibody-positive immune-mediated necrotizing myopathy triggered by human parvovirus B19 infection].

We have reported a case of a 44-year-old woman with anti-signal recognition particle (SRP) antibody-positive immune-mediated necrotizing myopathy triggered by human parvovirus B19 (PVB19) infection. She was admitted to the hospital because of lower leg edema and muscle weakness after erythema infectiosum. Magnetic resonance imaging of the lower extremities revealed high signals in the proximal muscles and subcutaneous edema on STIR. Muscle biopsy showed myofiber regenerative changes and variation in fiber size. A myositis-specific autoantibody profile indicated a positive result for anti-SRP antibodies. We diagnosed the patient with immune-mediated necrotizing myopathy (IMNM). Muscle strength and subcutaneous edema improved gradually in 3 months following immunotherapy. This is the first case report of an IMNM associated with PVB19 infection.

Effects of antibodies against human parvovirus B19 on angiogenic signaling.

Human parvovirus B19 (B19V) infection has symptoms similar to those of anti­phospholipid syndrome (APS). Antibodies against B19V­VP1 unique region (VP1u) exhibit activity similar to that of anti­phospholipid antibodies (aPLs) by inducing vascular endothelial cell adhesion factors and APS­like syndrome. Previous studies have identified an effect of aPLs on angiogenesis. However, little is understood regarding the effect of anti­B19V­VP1u antibodies on angiogenesis. The present study investigated the effects of anti­B19V­VP1u antibodies on the expression of adhesion molecules and angiogenic signaling using an aPL­induced human umbilical vein endothelial cell (HUVEC) model, and trypan blue staining and western blotting. The effect of B19V­VP1u antibodies on vascular endothelial growth factor (VEGF) expression in A549 cells, another well­known model used to study angiogenesis, was also examined. Significantly higher intracellular adhesion molecule 1 expression was observed following treatments with 10% fetal calf serum (FCS), aPL immunoglobulin G (IgG), B19V­VP1u IgG or B19V­NS1 IgG, compared with in the normal human (NH) IgG­treated cells. Conversely, significantly higher vascular cellular adhesion molecule 1 was only detected in HUVECs treated with B19V­VP1u IgG. Significantly increased integrin ß1 was detected in HUVECs treated with aPL IgG or B19V­VP1u IgG, whereas no difference in integrin ß1 was observed in those treated with 10% FCS, NH IgG or B19V­NS1 IgG. No difference in AKT­mTOR­S6 ribosomal protein (S6RP) signaling was observed in HUVECs treated with B19­VP1u IgG or B19V­NS1 IgG, compared with NH IgG­treated cells. Significantly higher human inducible factor­1α was detected in HUVECs treated with 10% FCS, aPL IgG, B19V­VP1u IgG or B19V­NS1 IgG, compared with in NH IgG­treated cells. However, there was no difference in the level of VEGF observed among HUVECs treated with NH IgG, B19V­VP1u IgG or B19V­NS1 IgG. Notably, no difference in VEGF level was observed in A549 cells treated with NH IgG, aPL IgG, B19V­VP1u IgG or B19V­NS1 IgG. These findings suggest that anti­B19V­VP1u antibodies may serve a role in activating adhesion molecules, but not in AKT­mTOR­S6RP signaling.

A Meta-Analysis on the Seroprevalence of Parvovirus B19 among Patients with Sickle Cell Disease.

BACKGROUND: Parvovirus B19 (B19 V) infection had been reported to be more frequent with serious clinical outcomes in patients with sickle cell disease (SCD) than in the general population. There is a wide variation in data among the existing literature regarding the seroprevalence of B19 V in patients with SCD. These data require further summary and analyses for better accuracy. This systematic review and meta-analysis was done to estimate the seroprevalence of B19 V in patients with SCD. METHODS: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases of MEDLINE/PubMed, Virtual Health Library (VHL), ScienceDirect, Google Scholar, and OpenGrey were used for the systematic search. The random-effects model was used to estimate the pooled prevalence with the corresponding 95% confidence interval (CI) using OpenMeta Analyst software. Publication bias was estimated based on Begg's test, Egger's test, and examination of the funnel plot. Subgroup analyses and metaregression were used to explore the moderators of heterogeneity between studies. RESULTS: A total of 18 studies including 2890 patients were analyzed. The overall IgG seroprevalence of B19 V infection among patients with SCD was found to be 48.8% (95% CI 39.5%-58.0%). Evidence of publication bias was not detected. Evidence of acute viral infection detected by positive IgM antibodies among the screened SCD patients was found in 8.30% (95% CI 5.20%-11.4%) of them. There was a statistically significant association between seroprevalence of B19 V and geographical areas. CONCLUSION: There was a high prevalence of B19 V in patients with SCD. Healthcare providers need to be aware of the magnitude of B19 V infection in patients with SCD to ensure effective management. This review could provide a comprehensive view of B19 V prevalence in this susceptible population.

Aggressive large B-cell lymphoma triggered by a parvovirus B19 infection in a previously healthy child.

In absence of red blood cells disease or immune defect, parvovirus B19 (PVB-19) is usually considered as a benign condition. Here, we report the case of a 10-year-old boy, previously healthy, presenting with a PVB-19 infection revealed by a bicytopenia and a voluminous axillary adenopathy. Pathophysiology examination showed reactional lymphoid population. Nine months later and in the absence of remission, a new biopsy of the same adenopathy revealed a Hodgkin lymphoma with area of T-cell rich aggressive large B-cell lymphoma. This case suggests PVB-19 as potential trigger of this malignant childhood hemopathy. Although no definitive conclusion can be drawn, our clinical case questions the role of PVB-19 in lymphomagenesis.

Post-infectious acute glomerulonephritis with podocytopathy induced by parvovirus B19 infection.

Human parvovirus B19 infection causes a variety of glomerular diseases such as post-infectious acute glomerulonephritis and collapsing glomerulopathy. Although each of these appears independently, it has not been fully determined why parvovirus B19 provokes such a variety of different glomerular phenotypes. Here, we report a 68-year-old Japanese man who showed endocapillary proliferative glomerulonephritis admixed with podocytopathy in association with parvovirus B19 infection. The patient showed acute onset of heavy proteinuria, microscopic hematuria and kidney dysfunction with arthralgia and oliguria after close contact with a person suffering from erythema infectiosum. In the kidney biopsy specimen, glomeruli revealed diffuse and global endocapillary infiltration of inflammatory cells, with some also showing tuft collapse with aberrant vacuolation, swelling, and hyperplasia of glomerular epithelial cells. Immunofluorescence revealed dense granular C3 deposition that resembled the "starry sky pattern". Intravenous glucocorticoid pulse therapy followed by oral prednisolone and cyclosporine combination therapy resulted in considerable amelioration of the kidney dysfunction and urinary abnormalities. The present case reveals that parvovirus B19 infection can induce different glomerular phenotypes even in the same kidney structure. This finding may provide hints useful for the further elucidation of the pathogenesis of parvovirus B19-induced glomerular lesions.

Persistence of Villous Immaturity in Term Deliveries Following Intrauterine Transfusion for Parvovirus B19 Infection and RhD-associated Hemolytic Disease of the Fetus and Newborn.

Common causes of fetal anemia and hydrops include parvovirus B19 infection during the first 2 trimesters of pregnancy, as well as maternal alloimmunization to RhD with subsequent hemolytic disease of the fetus and newborn (HDFN) in an RhD positive fetus. Although both of these conditions have historically caused significant fetal morbidity and mortality, the advent of intrauterine transfusion (IUT) over the last few decades has dramatically improved outcomes. Prior literature has extensively documented placental changes associated with untreated parvovirus infection and RhD HDFN in intrauterine fetal demises and preterm births; however, histopathologic changes in term placentas from term infants treated with IUT have not been reported. We present placental findings in 2 cases of parvovirus B19-associated hydrops and 2 cases of RhD HDFN-associated hydrops in term infants after IUT, highlighting unique aspects that may be diagnostically useful for the examining pathologist.

A Case Report of Parvovirus B19 Infection in a Renal Allograft.

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.

Pure red cell aplasia.

Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorders such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphocytic leukemia or large granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma and other solid tumors; or a variety of other disorders, drugs, or toxic agents. The therapeutic approach to PRCA typically involves immunosuppression, but specific pathogenic subtypes are associated with specific therapeutic approaches. Cyclosporine A, with or without concurrent corticosteroids, appears to be the single most effective immunosuppressive agent.

Diagnostic and prognostic value of molecular and serological investigation of human parvovirus B19 infection during pregnancy.

To define diagnostic and prognostic markers of parvovirus B19 (B19V) fetal infection, two groups were investigated: 1) pregnant women with specific symptoms or contacts with symptomatic households (n=37); 2) mothers with pathological ultrasound findings and the relevant fetus at the time of prenatal diagnosis (n=16). In the first group, diagnosis of B19V infection was achieved using IgM detection in 29/37 (78.3%) of patients, while B19V DNA was detected in 36/37 (97.3%) of infected women. In the second group, intrauterine infection was investigated by amniocentesis (n=5), cordocentesis (n=3) or both (n=5). Median B19V DNA load in amniotic fluid was 8.2x107 copies/ml and in fetal blood was 2x109 copies/ml. Maternal blood was positive for B19V DNA (median 3.8x104 copies/ml) in 14/16 (87.5%) women examined. At time of fetal US investigation, all mothers were B19V IgG positive and B19V IgM were detected in 10/16 (62.5%), while fetal B19V IgG and IgM were detected in 1/8 (12.5%) and 5/8 (62.5%), respectively. Phylogenetic analysis revealed that all B19V maternal and fetal strains belonged to genotype 1A. Diagnosis of maternal, fetal and neonatal B19V infection should be based on both IgM and DNA detection. Prognostic markers of congenital B19V infection need to be defined.

Atypical exanthems associated with Parvovirus B19 (B19V) infection in children and adults.

Parvovirus B19 (B19V) infection may differently manifest in various age groups. Erythema infectiosum ('fifth disease') is the most common B19V manifestations in children. Arthralgias and arthritis, with or without rash, are common manifestations of B19V infection in adults. Pruritus is usually present in adults and children. However, other cutaneous manifestations and atypical exanthems have been occasionally reported during B19V infection. To investigate the putative role of B19V infection in atypical exanthems, a total of 390 consecutive patients with atypical exanthems were analysed for B19V infection by determining B19V IgG and IgM antibodies titres in acute and convalescent phase as well as B19V DNA detection in serum by polymerase chain reaction (PCR). Atypical exanthems resulted related to B19V infection in 6 of the 120 pediatric (5%) and 14 of the 270 adult patients (5.2%). In conclusion this study reveals that atypical exanthems related to B19V infection are possible both in children and in adults, with a similar prevalence.