Parvovirus B19 Serology Research Articles

#1231 Atypical uremic hemolytic syndrome diagnosis, therapeutic management, control and follow-up in pregnancy: about a case

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) is a clinical entity characterized by non immune hemolytic anemia, thrombopenia, and renal failure in which the lesions are mediated by a process of thrombotic microangiopathy, mutations in its genes that lead to uncontrolled activation. of C5 and formation of the membrane attack complex. Its correct diagnosis allows prescribing treatment based on eculizumab, a C5 inhibitor. The clinical case of a patient with aHUS is presented, who three months after diagnosis, becomes pregnant. The objective is to highlight the importance of early differential diagnosis for the early establishment of effective treatment of this pathology, as well as management during pregnancy, childbirth and the postpartum period. The pathophysiology, diagnosis and genetic study are updated, as well as the therapeutic management of aHUS. Case Reports 27 year old women with no personal or family history of interest. She went to the emergency room in the full pandemic by SARSCov2 due to choluric urine along with fever of 38, myalgias and generalized arthralgias. At that time, PCR positive SARSCov2, deterioration of renal function was noted with Creatinine of 1.8 mg/dl (previous normal), LDH 1954 u/l, Platelets 21000, Hemoglobin 14.4 g/dl without schistocytes in smear, albumin/creatinine ratios 8700 and intense hematuria. It was interpreted as thrombotic thrombocytopenic purpura receiving corticosteroids, rituximab and plasmapheresis. After 48 hours, thrombopenia persists, schistocytes appear in smears and renal function deteriorates creatinine to 2.8 mg/dl. ADAMS 13 is received at normal values, considering at this time a diagnosis of aHUS, the previous treatment is interrupted and a dose of eculizumab 900 mg is received, doses of 900 per week are scheduled for 4 weeks in the fifth week 1200 mg and from Then on biweekly dose 1200 mg of eculizumab. At the third week of treatment, renal function has already normalized, hemolysis data have disappeared, Htcro and platelets have returned to normal. Proteinuria and hematuria disappears which has been maintained up to now. Good tolerance to treatment without any incidence, presenting a positive pregnancy test at three months. During pregnancy treatment with eculizumab is maintained. We continued with the biweekly regimen with 1200 mg of eculizumab until delivery. Labor is induced at week 37 receiving a extra dose of 1200 mg in the first 24 hours of delivery and continuing with 4 doses of 1200 mg once a week. Afterwards the dose is changed to a biweekly dose without modifying it throughout lactation until it ends. The reason is to avoid complement deregulation in the context of pregnancy and therefore ensure blockade. Subsequently it is done Switch to ravulizumab when breastfeeding begins as follows: A loading dose of 2700 mg (according to the interval of patient's weight) 15 days after the last dose of eculizumab. The maintenance dose is 3300 mg every 8 weeks starting 2 weeks after the loading dose. Normal kidney function has been maintained. She presented on debut positive serology for parvovirus B19, receiving treatment with Immunoglobulins and PCR SARSCov2 was positive prescribing treatment with remdesivir. Vitus (CMV, HBV, HCV and HIV) serology was negative and autoimmune study as well as study of complement and proteinogram were negative or within normal limits. No data suggestive of a neoplastic process. Genetic study has been detected a pathogenic variant associated with aHUS. Conclusion We found a heterozygous carrier patient in genetic study, who developed aHUS during a Sars-cov2 infection, which could have been a trigger for its clinical expression. The clinical course of this case highlights how crucial it is to identify atypical hemolytic uremic syndrome. The early initiation of eculizumab improves the prognosis and quality of life, with pregnancy becoming increasingly more likely and therapy with eculizumab does not have safety problems in this regard, although pregnant patients with aHUS should be closely monitored close during pregnancy and postpartum.

The Grave Hematologic and Hepatic Effects of Hyperthyroidism

Background: Hyperthyroidism can present with a myriad of symptoms including some rare, but morbid systemic manifestations. Here we present the case of a patient who presented with thyrotoxicosis, pancytopenia and cholestatic liver disease. Clinical Case: A 37 year-old Hispanic female with no significant past medical history presented with weight loss, fatigue, jaundice and irregular menstrual cycles ongoing for 10 months. Upon presentation, vitals were notable for mild tachycardia. She had significant jaundice and a visibly enlarged thyroid gland, while no thyroid eye disease was noted. The patient was found to have a hemoglobin level of 6.5 g/dL (12.0 - 16.0 g/dL), white blood cell level of 2.3 K/uL (4.5 - 11.0 K/uL) and platelet count of 82 K/uL (150 - 400 K/uL). Alkaline phosphatase was elevated to 214 U/L (34.0 - 104.0 U/L) and total bilirubin was 8.7 mg/dl (0.2 - 1.2 mg/dL) with direct bilirubin of 5.4 mg/dL (0.0 - 0.2 mg/dL). Thyroid panel revealed an undetectable TSH and a free T4 of 5.58 ng/dL (0.61 - 1.18 ng/dL). Hematological work-up was negative for malignancy but did note severe iron deficiency. Hepatitis B and C virus, parvovirus B19 serology, magnetic resonance cholangiopancreatography, and autoimmune disease work-up all returned normal. Thyroid uptake scan showed diffuse uptake without nodular disease and a 24-hour uptake of 57% (normal 7-32%). Thyroid stimulating antibodies were positive at 115 IU/L (0.00-0.55 IU/L). Since all other work up was negative, it was concluded that her pancytopenia and cholestatic pattern of liver injury were likely due to hyperthyroidism with plan to do a bone marrow biopsy if she does not have improvement in blood cell counts. Patient was treated with radioactive iodine (RAI) ablation. A week after treatment she had further elevation in total bilirubin, whereas her blood counts had improved. It was decided to initiate methimazole with close monitoring of her liver function tests. Two months after treatment, her thyroid function improved and she was eventually transitioned to levothyroxine for post-ablative hypothyroidism. Bilirubin improved to normal range and her pancytopenia resolved without additional intervention. She had complete resolution of jaundice and started having regular menses 2 months after her RAI treatment. Conclusion: The etiology of pancytopenia has been thought to be multifactorial with consumption of nutrients (including iron, manifesting as iron deficiency anemia), stimulation of erythropoiesis and sequestration of blood cells due to splenomegaly. Thyroid associated hepatic dysfunction has been proposed to be secondary to relative hypoxia in the perivenular regions and the direct toxic effect of thyroid hormone on hepatic tissue. In patients with concurrent hepatic disease and thyrotoxicosis, it is reasonable to consider treatment with thionamides with close monitoring, if other etiologies for hepatic disease are ruled out.

Parvovirus B19 infection in sickle cell disease: An analysis from the Centers for Disease Control haemoglobinopathy blood surveillance project.

In the multicentre Haemoglobinopathy Blood Surveillance Project, to evaluate the seroprevalence of parvovirus B19 and DNA viral load in sickle cell disease (SCD). Although the epidemiology of parvovirus B19 seropositivity in SCD has been well documented, there are few studies that have assessed possible persistent parvovirus DNAemia and associated risk factors including blood transfusion. A qualitative analysis of parvovirus B19 serology using ELISA and quantitative parvovirus B19 DNA by RT-PCR was performed in patients with SCD. Of 322 patients, 113 (35%) were parvovirus IgG positive and 119 (37%) were IgM positive at enrolment. The prevalence of IgG positivity increased with age. 71/322 (22%) were parvovirus DNA positive at enrolment with a mean viral load of 15 227 ± 55 227 SD. (range 72-329 238 IU/mL). Patients who were positive for parvovirus B19 DNA received a significantly higher red blood cell transfusion volume in the prior year compared to patients who were negative (mean RBC volume = 8310 mL vs 5435 mL, respectively; P = .0073). Seventy-seven patients had follow-up testing approximately 1 year after enrolment and 11/28 (39%) patients had persistently positive IgM. Further studies are needed to better understand the natural history of parvovirus B19 infection in SCD especially in relation to RBC transfusion as a risk factor, as well as disease outcome and severity.

Hemophagocytic Lymphohistiocytosis Associated With a Parvovirus B19 Infection During Pregnancy

Hemophagocytic lymphohistiocytosis is potentially fatal. Prompt diagnosis and initiation of treatment are critical for ensuring the best possible prognosis. We present a case of parvovirus B19 infection related to hemophagocytic lymphohistiocytosis during pregnancy. The patient experienced fever and pancytopenia. A bone marrow biopsy demonstrated hemophagocytosis and a giant proerythroblasts, which is characteristic of a parvovirus B19 infection. Viral serology for parvovirus B19 was positive. Prompt treatment was started because of the high level of certainty of viral-associated hemophagocytic lymphohistiocytosis, and the patient was successfully treated with prednisolone administration. She delivered a healthy newborn without any complications. Hemophagocytic lymphohistiocytosis should be considered when encountering unexplained cytopenia and fever. Prednisolone was an effective treatment.

Left ventricular assist device in a five-year-old child: A bridge to recovery in a case of viral myocarditis

IntroductionViral myocarditis can lead to heart failure that is refractory to medication. In these cases, a ventricular assist device is a good therapeutic option that can be used as a bridge to transplantation or recovery. We describe the first case in Portugal of recovery with ventricular assistance after severe myocarditis. Case reportA five-year-old boy with no previous cardiac disease presented with severe viral myocarditis, refractory to medical treatment, with positive serology for parvovirus B19 and Ebstein-Barr virus. A Berlin Heart Excor® was implanted 15 days after diagnosis. A biopsy at the time of implantation showed subendocardial fibrosis. After 40 days of assistance ventricular function recovered and the device was explanted. The patient was discharged from hospital 15 days later. DiscussionSurvival of children with ventricular assistance has improved significantly because of earlier implantation and coagulation monitoring. The presence of subendocardial fibrosis in the context of myocarditis is not a mandatory indication for transplantation.

Assistência ventricular esquerda numa criança de 5 anos – ponte para recuperação num caso de miocardite viral

IntroductionViral myocarditis can lead to heart failure that is refractory to medication. In these cases, a ventricular assist device is a good therapeutic option that can be used as a bridge to transplantation or recovery. We describe the first case in Portugal of recovery with ventricular assistance after severe myocarditis. Case reportA five-year-old boy with no previous cardiac disease presented with severe viral myocarditis, refractory to medical treatment, with positive serology for parvovirus B19 and Ebstein-Barr virus. A Berlin Heart Excor® was implanted 15 days after diagnosis. A biopsy at the time of implantation showed subendocardial fibrosis. After 40 days of assistance ventricular function recovered and the device was explanted. The patient was discharged from hospital 15 days later. DiscussionSurvival of children with ventricular assistance has improved significantly because of earlier implantation and coagulation monitoring. The presence of subendocardial fibrosis in the context of myocarditis is not a mandatory indication for transplantation.

549 Management of Twenty-Five Pediatric Patients with Hereditary Angioedema (Hae) Undergoing Home Treatment—A Clinical Surveillance Program

BackgroundHereditary angioedema (HAE) is a rare disorder characterized by C1 esterase inhibitor (C1-INH) deficiency. Clinically, HAE is characterized by relapsing episodes of edema at various body sites followed by disease-free intervals of variable duration. Episodes of upper airway obstruction (usually laryngeal edema) are potentially life-threatening and many patients died by asphyxiation in the families. In literature Longhurst et al, Buygun et al and Levi et al showed improvement of quality of life in patients with hereditary angioedema due to home treatment with C1-inhibitor-concentrate.MethodsWe investigated in a cohort study the integration of a clinical surveillance program into home treatment of pediatric patients suffering from hereditary angioedema. Parameters investigated were overall coping of the pediatric patient with home treatment, documentation of efficacy/safety of C1-INH concentrate (Berinertâ P, CSL Behring, Marburg), regular control of laboratory parameters (C1-inhibitor (INH) activity, C1-INH antigen, C4, hepatitis A, -B, -C-, HIV-1/2-, and parvovirus B19 serology) and quality of life parameters (hospitalization, absence from school).ResultsTwenty-five pediatric HAE patients (6 male, 19 female) have so far been investigated. Twenty-one patients suffer from HAE type I, 4 patients from HAE type II. Median age is 13.7 years (range: 2.8–17.4 years), first diagnosis of HAE took place at the median age of 5 years (range: 0.1–15.9 years) and first manifestation of HAE at the median age of 3.9 years (range: 0.3–11.7 years). Plasma C4 complement was reduced in nearly all patients (median: 2.4 mg/dL; range: <1.4–10 mg/dL) except one patient. All patients coped well with home treatment, compliance was excellent, clinical findings during regular medical control remained in the normal range and all parameters confirmed an improved quality of life, e.g., patients had not been hospitalized nor had they been absent from school. There were no adverse drug reactions due to administration of C1-INH concentrate.ConclusionsHome treatment might be also a valuable option for pediatric HAE patients not affecting compliance negatively and providing a significant positive impact on health-related quality of life.

Investigation and outcome of fetal anaemia in fetal parvovirus infection in pregnancy

BackgroundParvovirus infection may affect 1–5% of pregnant women. Clinical impact of maternal infection on the fetus is diverse (uncomplicated pregnancy, fetal anaemia, hydrops or intrauterine death). In mothers with proven...

Parvovirus B19 in Solid Organ Transplant Recipients

Parvovirus B19 is a common, ubiquitous human pathogen.It is a small, single-stranded linear, nonenveloped DNAvirus classified into three different genotypes (genotype1, Au and Wi strains; genotype 2, LaLi and A6 strains; andgenotype 3, V9 strains). Its worldwide genetic variability islow, and there is no clear correlation between genotypeand distinctive clinical manifestation. Parvovirus B19 repli-cates most efficiently and preferentially in human erythro-cyte precursors; thus, the virus is classified as a memberof the Erythrovirus genus of the Parvoviridae family. Mostpeople are infected between the ages of 5 and 15 years;by adulthood, up to 80% are seropositive (1). Infection ap-pears to confer lifelong immunity to immunocompetenthosts, but reinfection is possible in a minority of cases(2). It has been hypothesized that Parvovirus B19 can per-sist in the bone marrow and other tissues (3), support-ing possible reactivation rather than reinfection in certainseropositive patients. Parvovirus B19 infection can be ei-ther symptomatic or asymptomatic, depending on the age,hematologic and immunologic status of the host. Whilemostpatientsrecollectonlynonspecificflu-likesymptoms,distinctive clinical entities have been associated with Par-vovirus B19 infection in both immunocompetent hosts (4)and solid organ transplant (SOT) recipients (5). The mostcommonclinicalmanifestationsofParvovirusB19aresum-marizedinTable1.Although large, prospective surveillance studies are lack-ing, earlier studies reported an incidence of Parvovirus B19disease of

Acute splenic sequestration in children with sickle cell anemia

Since this topic is related to medical emergency, it is very important for all of us who work in general pediatrics. Other strengths of the study are the facts that it presents national data and, more importantly, what occurs in the context of the Brazilian public health services. I believe it is crucial to consider such aspect that has an overwhelming influence on good medical practice.I also would like to emphasize the fact that, at emergency rooms, the diagnosis of acute splenic sequestration (ASS) is not always established based on the classic definition presented in the article – “sudden increase in the splenic volume, associated with a drop of at least 2 g/dL in hemoglobin concentration and reticulocytosis.” Some of the factors contributing to that are: 1) relatives not always take to the emergency department the child’s clinical and baseline hematologic data reports provided by hematology referral centers; 2) lack of computerized medical record available to all medical care units, what could solve the previously mentioned problem; and 3) the fact that sometimes it is not possible to perform reticulocyte count at many emergency department laboratories. With regard to the item 3 specifically, the results shown in Table 1 of the above mentioned article suggest that this was also a difficulty in the cases reported by Rezende et al.: hemoglobin concentration was measured in 80% (138/173) of the ASS cases, whereas reticulocyte count was performed only in 14% (24/173) of them.In face of these limitations, the diagnosis of ASS is established based on clinical parameters such as significant splenomegaly, pallor and hemodynamic instability, in addition to very low hemoglobin levels. The following consequences arise from that:- Severe cases of ASS will not be underdiagnosed and will receive appropriate treatment at the emergency department. At discharge, patients will be sent to the referral center, in order to define the follow-up management.- These extreme criteria are not sufficient to diagnose mild cases of ASS. Within the age group with the highest risk for ASS, splenomegaly, anemia and reticulocytosis are typical findings of underlying disease, even if there are no complications. If the child’s clinical and baseline hematologic data are not available for the emergency department pediatrician, a mild case of ASS might be misdiagnosed as possible exacerbation of typical findings, triggered by infection, an event which these patients are more prone to. Even though it may not compromise the emergency care, in such situation, underdiagnosis certainly results in inappropriate follow-up of the patient, who will not receive the best care – attentive follow-up, periodic transfusion program or indication of splenectomy. - There might be a diagnostic confusion between ASS and red cell aplasia if reticulocyte count is not performed at the emergency department before blood transfusion. This might cause under or overestimation of the actual frequency of ASS.I would like to know if some data were analyzed in this population and not presented in the study:- Were caregiver’s educational level and family’s town of residence (and access to the health care facility) associated with the case-fatality of ASS?- Did pneumococcal vaccine protect patients against ASS?- Was parvovirus B19 serology performed in any of these reported cases?- And finally, a question not related to the main topic of the study: is the Neonatal Screening Program of Minas Gerais able to offer any kind of counseling to the relatives of children diagnosed with sickle cell trait regarding occasional reproductive risks for the person in adulthood?I congratulate the authors for the published data, and it will certainly contribute to encourage debate and increase knowledge about this topic.

PARVOVIRUS B19-INDUCED PERSISTENT PURE RED CELL APLASIA IN A CHILD WITH T-CELL IMMUNODEFICIENCY

Persistent pure red cell aplasia can be a manifestation of parvovirus B19 infection in immunocompromised hosts. Failure of the humoral immune response to clear parvovirus B19 in such patients results in persistent pure red cell aplasia. The authors describe a child who had T-cell immunodeficiency and persistent pure red cell aplasia due to parvovirus B19 infection. Interestingly, they detected human parvovirus B19 genome by polymerase chain reaction (PCR) not in the peripheral blood, but in the bone marrow specimen of the patient. In their patient, T-cell immunodeficiency may have caused impaired B-cell activation and failure of effective humoral immune response to neutralize the virus. Additionally, before the diagnosis of pure red cell aplasia, IVIG treatment given at a dosage of 400 mg/kg/day with 3-week intervals may result in sufficient neutralization of peripheral blood parvovirus B19, whereas it may not be sufficient for the neutralization of parvovirus B19 genome in bone marrow. Thus, peripheral blood parvovirus B19 serology (IgM and IgG) and PCR were negative, whereas bone marrow aspiration sample was positive for parvovirus B19 PCR in this patient. Reticulocytopenia and severe anemia may warn the physicians of parvovirus B19 infection, especially in immunocompromised children. Diagnosis may require demonstration of absence of late erythroid precursors in the bone marrow as well as serologic testing and detection of parvovirus B19 genome by PCR in the serum and/or bone marrow samples of the patient.

Massive fetal hemorrhage and fetomaternal alloimmune thrombocytopenia from human platelet antigen 5b incompatibility: an unusual association

Massive fetal hemorrhage and fetomaternal alloimmune thrombocytopenia from human platelet antigen 5b incompatibility: an unusual association

Meconium peritonitis and parvovirus B19 infection associated with hydrops fetalis

Two preterm infants with non-immune hydrops fetalis associated with meconium peritonitis are reported. The first presented with a cystic abdominal mass and the second had positive parvovirus B19 serology. The association of meconium peritonitis with hydrops fetalis was through different mechanisms in each patient.

Human Parvovirus B19 Serology and Avidity Using a Combination of Recombinant Antigens Enables a Differentiated Picture of the Current State of Infection

In order to improve serodiagnostic methods for the determination of the state of human parovirus B19 infection, a new test system, recomLine Parvovirus, based on the use of recombinant antigens, has been developed and evaluated. The test system combines the advantages of enzyme-linked immunosorbent assay (ELISA) methods with those of the Western blot technique. For the recombinant line assay, five antigens of human parvovirus B19 that were recombinantly produced in Escherichia coli were applied directly on nitrocellulose membranes: VP2, the aminoterminal and the carboxyterminal domain of VP1 (VP-N and VP-C), VP-1S another fragment of VP-N and NS1. In addition, empty virus particles isolated from eukaryotic cell cultures were also applied. The recombinant-line assay was used to detect human IgG and IgM antibodies directed against human parvovirus B19. In addition, the avidity of the IgG antibodies was investigated. The recombinant line assay was evaluated using 87 human serum samples of patients recently infected with human parvovirus B19 including 10 samples of three infection time courses and 100 serum samples of healthy blood donors. All results were compared with commercially available ELISAs. In the case of discrepancies, Western blot analysis was performed. The data revealed the recombinant line assay to be highly sensitive and specific. The individual determination of the human immune response against several recombinant antigens covering the structural proteins of human parvovirus B19 gives a deeper insight into the actual status of infection. In addition, the determination of IgG avidity against these individual recombinant antigens enables a more precise and differentiated picture of the infection event.

Usefulness of routine hepatitis C virus, hepatitis B virus, and parvovirus B19 serology in the diagnosis of recent-onset inflammatory arthritides

Usefulness of routine hepatitis C virus, hepatitis B virus, and parvovirus B19 serology in the diagnosis of recent-onset inflammatory arthritides

Familial collapsing glomerulopathy: Clinical, pathological and immunogenetic features

Collapsing glomerulopathy (CG) is an aggressive form of glomerular injury frequently seen in association with HIV infection, although it is also recognized in non-HIV patients as a primary disease. Until now, the occurrence of CG in a familial pattern has not been reported. We studied five members of a family (siblings), admitted for evaluation of proteinuria and nephrotic syndrome. They had no other family history of renal disease. Blood samples for major histocompatibility complex (MHC) analysis were obtained from the five siblings, both parents and four relatives. Renal biopsy performed in four out of the five siblings revealed capillary collapse and retraction with visceral epithelial cell swelling and reabsorption droplets, consistent with CG. Two of the patients had suggestive symptoms of systemic lupus erythematosus, such as arthritis, rash, hair loss, moderate leukopenia and lymphopenia, low titers of antinuclear antibodies (ANA) and anti-SSA/Ro antibodies, but no immune complex deposition on renal biopsy. IgG serology for parvovirus B19 (PVB-19) was positive only in two siblings but polymerase chain reaction (PCR) was negative. Immunogenetic analysis showed that all patients shared the same MHC haplotype inherited from the mother. CG can present in a familial pattern. Since a similar MHC haplotype was observed in affected and non-affected members of the family, we conclude that the environment plays an important role in the development of the disease.

An epidemic of parvovirus B19 in a population of 3,596 pregnant women: a study of sociodemographic and medical risk factors.

To estimate the incidence of human parvovirus B19 among pregnant women before and during an epidemic, to elucidate possible sociodemographic and medical risk factors during pregnancy and to estimate the association between parvovirus B19 infection and negative pregnancy outcome. Prospective study among pregnant women followed from their first antenatal visit before 24 full weeks of gestation until delivery. Department of Obstetrics and Gynaecology, Odense University Hospital, Denmark, November 1992 to February 1994. 3,596 pregnant women were invited to participate. The women were examined at first antenatal visit in the period from November 1992 to February 1994 and at delivery. The last delivery was in August 1994 and samples were thus collected before and during a large parvovirus B19 epidemic in Denmark January to September 1994. A blood sample for parvovirus B19 serology was taken at enrollment and from the umbilical cord at delivery. Three questionnaires were completed during 2nd and 3rd trimesters and a registration form at delivery. In total, 3,174 (87.6%) were enrolled and 79.5% completed the study. The prevalence of B19 IgG seropositivity at the first antenatal visit before 24 full weeks of gestation was 66% . The cumulative prevalence proportion of acute parvovirus B19 infection during pregnancy among IgG negative women was found to be 10.3% (IgM seropositivity and/or IgG seroconversion). The IgG seroconversion incidence increased significantly from 1.0% to 13.5% among 932 seronegative pregnant women before and during the epidemic, respectively (P < 0.001). Independent risk factors related to increased risk of B19 infection during pregnancy, adjusted for other sociodemographic and medical factors, were: children at home (adjusted OR 2.1, 95% CI 1.3-3.2); serious medical disease (adjusted OR 3.0, 95% CI 1.0-8.5); and a stressful job (adjusted OR 1.8, 95% CI 1.0-3.3). Parvovirus B 19 IgM seropositivity was associated with events of late spontaneous abortions and stillbirths (crude OR 9.9; 95% CI 3.3-29.4). Before and during an epidemic of acute B19 infection incidences were measured among pregnant women to be 1.0% and 13.5%, respectively. Three factors, significantly increasing the risk of acute B19, were identified as: having children at home; suffering from serious medical diseases; and having a stressful job. IgM positivity for parvovirus B19 was associated with negative outcome of pregnancy.

Renal and Hematological Complications in Long-Term Treatment with Granulocyte Colony-Stimulating Factor 779

The value of granulocyte colony-stimulating factor (G-CSF) in the treatment of conditions associated with bone marrow aplasia/suppression is well appreciated. However, accruing experience is bringing to light adverse side effects that appear to be associated with long-term administration of G-CSF. We report 2 siblings with severe congenital neutropenia (SCN) (Kostmann's disease) who featured G-CSF (Filgrastim) -induced major renal and hematological complications. FA, a 12yr old girl and AA, her 17yr old brother, received daily G-CSF therapy for the last 9yrs. Both patients developed persistent microscopic hematuria with normal kidney function 2 mo after starting G-CSF. However, 4 yrs later, FA showed proteinuria, macroscopic hematuria and reduced kidney function. Renal biopsy revealed membranoproliferative glomerulonephritis type I. Discontinuation of G-CSF therapy for 4 months resulted in improvement of renal function. Persistent severe neutropenia and bacterial infections required resumption of G-CSF, which has led to deterioration of renal function and partially steroid-responsive hematuria and proteinuria. AA, who continues to show microscopic hematuria, has lately developed pancytopenia, with positive Coombs test and antiplatelet antibodies. Serology for parvovirus B19 was negative. Bone-marrow aspirates revealed maturation arrest of neutrophil precursors at the promyelocyte/myelocyte stage, and also megaloblastic changes and diminution of red cell progenitors and of megakaryocytes. Myeloid dysplasia or acute myeloid leukemia were not found. Each attempt to increase G-CSF dosage failed to raise the neutrophil count but aggravated the pancytopenia, requiring blood transfusions. In contrast, discontinuation of G-CSF resulted each time in a prompt reversal of pancytopenia and in disappearance of the Coombs and antiplatelet antibodies. AA was scheduled for bone marrow transplant and received during 33 days a glycosylated G-CSF (Lenograstim) preparation without adverse hematological phenomena.

Falsch-positives mütterliches Röteln-IgM bei intrauterinem Fruchttod durch Parvovirus B19?

A 38-year-old secundiparous woman was referred at 29 weeks of gestation for fetal death with massive hydrops fetalis. At 19 weeks of gestation, the mother had experienced a rubella-like rash with positive rubella-lgM. Against the regulations, no rubella serology had been done previously. Although there is no clear clinical distinction between rubella and fifth disease and false positive rubella-lgM tests in connection with fifth disease have been described in the literature, neither sucrose gradient centrifugation of the serum for specificity control nor parvovirus B19-serology were carried out at 19 weeks of gestation. The serum was discarded, and three was no sonographic follow-up of the fetus. Parvovirus B19 was detected in the heart blood of the dead fetus by polymerase-chain-reaction (PCR). Streptococcus intermedius (milleri) in pure culture was found in placental and fetal pharyngeal swabs. The clinical course, fetal hydrops with positive B19 PCR, and positive maternal B19 IgM at 29 weeks of gestation point to fifth disease with false positive rubella IgM. Fetal death could probably have been prevented by more accurate diagnostic measures, storage of serum samples, sonographic follow-up and fetal transfusion.

Human parvovirus B19 in bone marrows from adults with acquired immunodeficiency syndrome: A comparative study using in situ hybridization and immunohistochemistry

Human parvovirus B19, which infects and lyses erythroid precursors, can cause severe anemia in patients with immunodeficiency. The incidence of parvovirus infection in adult acquired immunodeficiency syndrome (AIDS) patients is unknown. Eighty-one archival formalinfixed, paraffin-embedded (FFPE) bone marrow biopsies from 73 AIDS adults were immunostained with monoclonal R92F6 against B19 VP1 and VP2 capsid proteins using streptavidin peroxidase and streptavidin alkaline phosphatase techniques. In addition, the same tissues were hybridized in situ with a digoxigenin-labeled parvovirus B19 DNA probe. Five FFPE bone marrows, from 3 HIV-negative patients with positive immunoglobulin M (IgM) serology for parvovirus B19, and 1 parvovirus B19-infected fetal liver were positive controls. By immunoperoxidase, all tissues were negative with R92F6 except the fetal liver, which exhibited strong positivity predominantly in viral inclusions. With immunoalkaline phosphatase, all positive controls were immunoreactive with R92F6; however, the AIDS marrows were negative. With in situ hybridization (ISH), all positive controls and 7 of 81 (8.6%) of AIDS marrows were positive for B19 parvovirus DNA. We conclude that ISH is more sensitive than R92F6 immunohistochemistry in parvovirus B19 detection. A small but significant number of bone marrows from AIDS adults shows evidence of human parvovirus B19 infection.