[The 507th case: hemolytic anemia, parvovirus B19, and multiple organ dysfunction].

A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and parvovirus B19 nucleic acid was positive in blood plasma. The patient was diagnosed with cold agglutinin syndrome and multiple organ dysfunction including respiratory failure and hepatitis. In the conflict between viral infection and the treatment of cold agglutinin syndrome, we provided supportive treatment, complement inhibitors to control hemolysis, and antiviral therapy. After timely glucocorticoid and immunosuppressant therapy, the patient had achieved a good response.

Viral myocarditis in combination with genetic cardiomyopathy as a cause of sudden death. An autopsy series.

Sudden cardiac death (SCD) is a major public health issue worldwide. In the young (< 40 years of age), genetic cardiomyopathies and viral myocarditis, sometimes in combination, are the most frequent, but underestimated, causes of SCD. Molecular autopsy is essential for prevention. Several studies have shown an association between genetic cardiomyopathies and viral myocarditis, which is probably underestimated due to insufficient post-mortem investigations. We report on four autopsy cases illustrating the pathogenesis of these combined pathologies. In two cases, a genetic hypertrophic cardiomyopathy was diagnosed in combination with Herpes Virus Type 6 (HHV6) and/or Parvovirus-B19 (PVB19) in the heart. In the third case, autopsy revealed a dilated cardiomyopathy and virological analyses revealed acute myocarditis caused by three viruses: PVB19, HHV6 and Epstein-Barr virus. Genetic analyses revealed a mutation in the gene coding for desmin. The fourth case illustrated a channelopathy and a PVB19/HHV6 coinfection. Our four cases illustrate the highly probable deleterious role of cardiotropic viruses in the occurrence of SCD in subjects with genetic cardiomyopathies. We discuss the pathogenetic link between viral myocarditis and genetic cardiomyopathy. Molecular autopsy is essential in prevention of these SCD, and a close collaboration between cardiologists, pathologists, microbiologists and geneticians is mandatory.

Effect of the Functional VP1 Unique Region of Human Parvovirus B19 in Causing Skin Fibrosis of Systemic Sclerosis.

Human parvovirus B19 (B19V) is a single-stranded non-enveloped DNA virus of the family Parvoviridae that has been associated with various autoimmune disorders. Systemic sclerosis (SSc) is an autoimmune connective tissue disorder with high mortality and has been linked to B19V infection. However, the precise mechanism underlying the B19V contribution to the development of SSc remains uncertain. This study investigated the impacts of the functional B19V-VP1 unique region (VP1u) in macrophages and bleomycin (BLE)-induced SSc mice. Cell experimental data showed that significantly decreased viability and migration of both B19V-VP1u-treated U937 and THP-1 macrophages are detected in the presence of celastrol. Significantly increased MMP9 activity and elevated NF-kB, MMP9, IL-6, TNF-α, and IL-1ß expressions were detected in both B19V-VP1u-treated U937 and THP-1 macrophages. Conversely, celastrol revealed an inhibitory effect on these molecules. Notably, celastrol intervened in this pathogenic process by suppressing the sPLA2 activity of B19V-VP1u and subsequently reducing the inflammatory response. Notably, the administration of B19V-VP1u exacerbated BLE-induced skin fibrosis in mice, with augmented expressions of TGF-ß, IL-6, IL-17A, IL-18, and TNF-α, ultimately leading to α-SMA and collagen I deposits in the dermal regions of BLE-induced SSc mice. Altogether, this study sheds light on parvovirus B19 VP1u linked to scleroderma and aggravated dermal fibrosis.

[Hemophagocytic Syndrome Secondary to Human Parvovirus B19 Infection in an Acquired Immunodeficiency Syndrome Patient:Report of One Case].

The acquired immunodeficiency syndrome patients with compromised immunity are prone to hemophagocytic syndrome secondary to opportunistic infections.This paper reports a rare case of hemophagocytic syndrome secondary to human parvovirus B19 infection in an acquired immunodeficiency syndrome patient,and analyzes the clinical characteristics,aiming to improve the diagnosis and treatment of the disease and prevent missed diagnosis and misdiagnosis.

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.

Clinical Presentation of Parvovirus B19 Infection in Adults Living with HIV/AIDS: A Case Series.

Parvovirus B19 (B19V) infection varies clinically depending on the host's immune status. Due to red blood cell precursors tropism, B19V can cause chronic anemia and transient aplastic crisis in patients with immunosuppression or chronic hemolysis. We report three rare cases of Brazilian adults living with human immunodeficiency virus (HIV) with B19V infection. All cases presented severe anemia and required red blood cell transfusions. The first patient had low CD4+ counts and was treated with intravenous immunoglobulin (IVIG). As he remained poorly adherent to antiretroviral therapy (ART), B19V detection persisted. The second patient had sudden pancytopenia despite being on ART with an undetectable HIV viral load. He had historically low CD4+ counts, fully responded to IVIG, and had undiagnosed hereditary spherocytosis. The third individual was recently diagnosed with HIV and tuberculosis (TB). One month after ART initiation, he was hospitalized with anemia aggravation and cholestatic hepatitis. An analysis of his serum revealed B19V DNA and anti-B19V IgG, corroborating bone marrow findings and a persistent B19V infection. The symptoms resolved and B19V became undetectable. In all cases, real time PCR was essential for diagnosing B19V. Our findings showed that adherence to ART was crucial to B19V clearance in HIV-patients and highlighted the importance of the early recognition of B19V disease in unexplained cytopenias.

Case Report: Parvovirus B19 infection complicated by hemophagocytic lymphohistiocytosis in a heart-lung transplant patient.

Immunosuppressed patients can contract parvovirus B19, and some may experience hemophagocytic lymphohistiocytosis (HLH). Herein, we describe the first report of hemophagocytic lymphohistiocytosis in a heart-lung transplant patient with concomitant parvovirus B19 infection. The patient was treated with intravenous immune globulin (IVIG) and the features of HLH were remission. This instance emphasizes the significance of parvovirus B19 monitoring in transplant patients with anemia; if HLH complicates the situation, IVIG may be an adequate remedy. Finally, a summary of the development in diagnosing and managing parvovirus B19 infection complicated by HLH is provided.

Thiamine responsive megaloblastic anaemia complicated with acute Parvovirus infection: A case report.

Thiamine responsive megaloblastic anaemia syndrome also known as Rogers syndrome is a very rare autosomal recessive disorder. The hallmark of the disease is the presence of the classic triad of anaemia, diabetes mellitus, and sensorineural deafness. We report the case of a 14-year-old boy who presented to us with severe megaloblastic anaemia, diabetes mellitus, and sensorineural deafness. The anaemia was further complicated by acute parvovirus infection. He was put on high doses of thiamine (vitamin B1) which led to an improvement.

Prevalence of parvovirus B19 antibodies in pregnant women in northern Benin.

OBJECTIVES: Parvovirus B19 (B19V) infection in pregnancy is generally asymptomatic, but in about 3% it can cause complications, including miscarriage, severe foetal anaemia and foetal hydrops. The seroprevalence in pregnancy ranges from 20% to 82% in Africa, but there are no data for Benin. We therefore retrospectively assessed the seroprevalence of B19V in pregnant women attending the Saint Jean de Dieu Hospital in Tanguiéta, a rural district of Atacora, in northern Benin. METHODS: We searched for anti-B19V immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in 227 sequential sera from as many women (mean age 26.3 years, range: 16-41) of whom 30 were in the first trimester, 66 in the second and 131 in the third. Samples that tested positive for IgM were analysed with an immunoblot test and the viral genome (DNA-B19V) was searched for using a polymerase chain reaction. RESULTS: Of the 227 women, 153 (67.4%) were positive for IgG anti-B19V, 7 (3.1%) for IgM and 73 (32.2%) were non-immune. Six IgM-positive women were also IgG positive. The difference in IgG seroprevalence between trimesters or ages was not statistically significant. Of the seven IgM-positive samples, three were confirmed positive by immunoblot (of which two were DNA-B19V positive), three were indeterminate (DNA-B19V negative) and one was negative (DNA-B19V negative). Of the three women with confirmed positive IgM, two were in the third trimester and one in the second trimester of pregnancy. CONCLUSIONS: The seroprevalence of anti-B19V IgG among pregnant women in Benin is high and in line with those reported in some African countries. IgM seroprevalence is also similar to that described in some African countries in non-epidemic periods. The low viral load observed depicts non-acute infections, but it is difficult to establish the precise time of the infection, especially for women tested in the second or third trimester of pregnancy, when the observed viremia could be a sign of an acute infection that occurred in the previous trimester. Consequently, clinical follow-up and further investigations to highlight possible foetal consequences are indicated.

Plastic Bronchitis of Human Bocavirus 1 Detected by Comprehensive Polymerase Chain Reaction of Mucus Casts.

Plastic bronchitis (PB) is a rare and severe respiratory disease characterized by the formation of branching mucus casts, resulting in airway obstruction. PB can be divided into two types. Type 1 PB is primarily caused by inflammatory casts that result from allergic diseases. In type 2 PB, mucinous casts are produced in association with congenital heart disease. PB is also associated with viral respiratory infections, particularly the influenza A (H1N1) pdm09 virus, which is the most common pathogen affecting pediatric patients. Herein, we report a case of severe type 1 PB caused by human bocavirus (HBoV)1 in a child. Multiplex polymerase chain reaction (PCR) of a nasopharyngeal swab revealed the presence of respiratory syncytial virus and human parainfluenza virus 3. However, no viruses other than HBoV1 were detected in mucus casts by real-time PCR. Consequently, we suggest that HBoV can cause PB in pediatric patients, and direct and comprehensive PCR of bronchial casts may be useful for identifying the etiologic agents.

Intrauterine transfusion in 103 fetuses with severe anemia caused by parvovirus infection. A multicenter retrospective study.

PURPOSE: Evaluating procedure-related complications and perinatal outcomes after intrauterine transfusion (IUT) before or after 20+0 weeks of gestation in fetuses with severe anemia due to intrauterine human parvovirus B19 infection. METHODS: A retrospective study investigating fetuses requiring IUT for fetal Parvo B19 infection in two tertiary referral centers between December 2002 and December 2021. Procedure-related complications, intrauterine fetal death (IUFD), and perinatal outcome were correlated to gestational age (GA) at first IUT, the presence of hydrops and fetal blood sampling results. RESULTS: A total of 186 IUTs were performed in 103 fetuses. The median GA at first IUT was 19+3 (13+0-31+4) weeks of gestation. IUFD occurred in 16/103 fetuses (15.5%). Overall survival was 84.5% (87/103). Hydrops (p = 0.001), lower mean hemoglobin at first IUT (p = 0.001) and low platelets (p = 0.002) were strongly associated with IUFD. There was no difference observed in fetuses transfused before or after 20+0 weeks of gestation. CONCLUSION: IUT is a successful treatment option in fetuses affected by severe anemia due to parvovirus B19 infection in specialized centers. In experienced hands, IUT before 20 weeks is not related to worse perinatal outcome.

A Case of Refractory Anemia in Patient of Chronic Kidney Disease and the Challenges in its Management.

Anemia is a common complication of chronic kidney disease (CKD) that has been classically attributed to inadequate production of endogenous erythropoietin.1 Though there are many other common causes of refractory anemia in CKD like iron deficiency, vitamin B12, and folic acid deficiency, noncompliance to dialysis and erythropoietin therapy rare causes like blood loss, bone marrow failure, infections causing aplastic crisis like CMV, parvovirus B19 should be ruled out. Parvovirus has an extreme tropism for erythroid cells and is an uncommon cause of anemia in patients with CKD on maintenance dialysis (MHD) and on erythropoietin.2 Here we are reporting a rare case of refractory anemia in a patient of CKD on MHD secondary to parvovirus-related aplastic crisis. How to cite this article: Gade K, Londhe C, Pednekar S, et al. A Case of Refractory Anemia in Patient of Chronic Kidney Disease and the Challenges in its Management. J Assoc Physicians India 2023;71(10):94-95.

Viral-induced inflammation can lead to adverse pregnancy outcomes.

INTRODUCTION: Parvoviruses are DNA viruses of small size. There have been a number of reports indicating the possible effects of B19 infections during pregnancy. These effects include spontaneous abortions, stillbirth, fetal damage, and quite often, fetal anemia with hydrops fetalis.

Parvovirus B19-Associated Severe Anemia in Adult Liver Transplant Recipients: A Case Series and Review of the Literature.

Background: Parvovirus B19 (B19V) infection is a rare cause of severe anemia in liver transplant recipients. However, few studies have systematically reviewed reported cases and summarized experience in managing this disease. Objective: We described a retrospective case series of eight adult liver transplant recipients with B19V-associated severe anemia and performed a literature review of epidemiology, etiology, clinical courses, diagnosis, treatment options available, and outcomes of B19V-associated anemia in adult liver transplant recipients. Patients and Methods: We systematically reviewed articles describing adult liver transplant recipients with B19V-associated anemia from PubMed and ScienceDirect databases from database inception to May 2022. Results: Eight articles containing 23 cases were identified in addition to eight cases from our center for a total of 31 patients (mean age, 45.7 ± 9.7 years; 74.2% male). Eighty-seven percent developed transfusion-dependent anemia within two months after liver transplantation (LT). Fever and progressive anemia are among the major manifestations. Intravenous immunoglobulin (IVIG)-based therapy was given to all patients and the treatment protocols varied among different centers. Except for two cases who died of comorbidities, 17 patients obtained long-term recovery from anemia after one course of treatment and six (19%) experienced relapses that were reversed by repeated courses of IVIG therapy. Two recipients presented with IVIG-associated side effects and two developed acute cellular rejection (ACR) after reduction of immunosuppression. Conclusions: B19V infection should be suspected early as a cause of severe anemia of unknown etiology in adult liver transplant recipients. The clearance of B19V typically lags behind recovery of anemia, and inadequate clearance of virus after cessation of IVIG appears to be a potential risk of anemia recurrence. Moreover, more attention should be paid to the side effects of high-dose IVIG infusion and ACR because of reduction of immunosuppression.

Infección aguda por parvovirus B19 con afectación articular / Acute parvovirus B19 infection with articular involvement

La infección por parvovirus B19 es frecuente en la edad pediátrica. El cuadro típico ante infección aguda por parvovirus B19 en la infancia es el eritema infeccioso, también conocido como quinta enfermedad, aunque se han descrito otras alteraciones como la afectación articular. Presentamos dos casos de artralgias y artritis aparecidas en contexto de parvovirus B19, ambas con confirmación serológica y buena evolución posterior con resolución completa de la sintomatología articular (AU)

Infection by parvovirus B19 is common in the paediatric age group. The typical presentation of acute infection in children is erythema infectiosum, also known as fifth disease, although other manifestations have also been described, including arthropathy. We describe 2 cases in paediatric patients who experienced arthralgia and arthritis in the context of acute parvovirus B19 infection, both confirmed by serology and with complete resolution of articular manifestations. (AU)

Hypothesis: Low Vitamin A and D Levels Worsen Clinical Outcomes When Children with Sickle Cell Disease Encounter Parvovirus B19.

Human parvovirus B19 causes life-threatening anemia due to transient red cell aplasia (TRCA) in individuals with sickle cell disease (SCD). Children with SCD experiencing profound anemia during TRCA often require red blood cell transfusions and hospitalization. The prevalence of vitamin deficiencies in SCD is high and deficiencies are associated with respiratory and pain symptoms, but the effects of vitamins on acute infection with parvovirus B19 remain unclear. We performed a clinical study in which 20 SCD patients hospitalized with parvovirus B19 infections (Day 0) were monitored over a 120-day time course to query relationships between vitamins A and D and clinical outcomes. There were significant negative correlations between Day 0 vitamin levels and disease consequences (e.g., red blood cell transfusion requirements, inflammatory cytokines). There were significant positive correlations (i) between Day 0 vitamins and peak virus-specific antibodies in nasal wash, and (ii) between Day 0 virus-specific serum plus nasal wash antibodies and absolute reticulocyte counts. There was a significant negative correlation between Day 0 virus-specific serum antibodies and virus loads. To explain the results, we propose circular and complex mechanisms. Low baseline vitamin levels may weaken virus-specific immune responses to permit virus amplification and reticulocyte loss; consequent damage may further reduce vitamin levels and virus-specific immunity. While the complex benefits of vitamins are not fully understood, we propose that maintenance of replete vitamin A and D levels in children with SCD will serve as prophylaxis against parvovirus B19-induced TRCA complications.

Isolated Anemia in a 69-Year-Old Man with HIV-1: Features of Pure Red Cell Aplasia Mediated by Chronic Parvovirus-B19 Infection.

BACKGROUND Pure red cell aplasia (PRCA) is an uncommon syndrome characterized by ineffective erythropoiesis and severe anemia. Among immunodeficient patients, including those with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), persistent parvovirus-B19 can cause PRCA. We report a rare case of an Australian man with parvovirus-B19 mediated PRCA secondary to a new diagnosis of HIV-1/AIDS. The case highlights the importance of early treatment initiation with anti-retroviral drugs and pooled immunoglobulins to enable marrow recovery and long-term disease remission. CASE REPORT A 64-year-old man residing in rural Indonesia presented with severe anemia. Apart from 8 kg of unintentional weight loss, he denied any occult bleeding, diatheses, or constitutional symptoms. His bloodwork revealed a normocytic, normochromic anemia (Hb 81 g/L) with profound reticulocytopenia (9.5×109/L). Parvovirus-B19 serology and polymerase chain reaction testing confirmed active viremia. Lymphopenia and an undetectable CD4 T-lymphocyte count (<1%) were also noted; HIV-1 was subsequently diagnosed. Bone marrow sampling later confirmed features consistent with parvovirus-B19-driven PRCA secondary to HIV-1/AIDS. The patient received 1 g/kg intravenous immunoglobulin for two days and initiated anti-retroviral HIV therapy. Rapid reticulocytosis with slow incrementation of his hemoglobin were observed over one month. At three years following his diagnosis, he remains in remission. CONCLUSIONS Severe, isolated anemia in immunodeficient patients, particularly those with HIV-1/AIDS, should prompt consideration of parvovirus-B19-mediated PRCA. Depletion of CD4-T-lymphocyte populations enables the establishment of parvovirus-B19 reservoirs within erythroid progenitors, thereby hampering physiological erythropoiesis. Long-term remission can be achieved with the rapid institution of intravenous immunoglobulin and anti-retroviral HIV therapies.

Parvovirus B19-triggered hemophagocytic lymphohistiocytosis in a patient with Crohn's disease.

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life threatening condition caused by inappropriate immune activity. Infection is often the trigger, both in genetically predisposed and in sporadic cases. Although more commonly seen in the paediatric population, patients of all ages can be affected. Case presentation: A 26-year-old male patient with Crohn's disease, treated with ustekinumab, presented with high fever, epistaxis and anorexia. Laboratory results showed pancytopenia, and a high serum levels of ferritin and LDH. Colonoscopy revealed only mild signs of disease activity. CT-scan showed splenomegaly and multiple lymphadenopathies. Bone marrow aspirate was suggestive for hemophagocytosis. PCR & serology for parvovirus B19 came back positive. Treatment with ustekinumab was temporarily put on hold and supportive care was given. Viral replication decreased and he recovered completely. Conclusion: There is a known association between HLH and Crohn's disease. This is probably because they are more susceptible to infections with CMV, EBV and parvovirus B19, all known as triggers for HLH. The role of ustekinumab is unclear: did it play a role in the pathophysiological evolution of this primo-infection with parvovirus B19? On the other hand, did it contribute to the rather mild course of the disease, acting as a immunomodulator that works on interleukin-12, a cytokine that plays a role in HLH? Further study is warranted to answer these questions.