Myocarditis and inflammatory cardiomyopathy: current evidence and future directions.

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology. Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases. Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis. At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear. The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders. As a consequence, treatment strategies are not well established. In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis. Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field. The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed. This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.

Treatment strategies and outcome of parvovirus b19 infection in kidney transplant recipients: a case series and literature review of 128 patients.

Abstract Background There is no specific antiviral treatment for parvovirus B19 (PVB19) infection. Objective The objective of this study was to study the treatment and outcome of PVB19 infection in kidney transplant recipients (KTR) at our institution, and cases published in the medical literature. Methods We conducted a retrospective review of PVB19 infection in KTR at an academic medical center over a 16-year period and summarized the data on its treatment and outcome in 120 KTR in the medical literature. Results In our cohort of eight patients, the median time to the onset of PVB19 disease was 7.2 weeks after transplantation. All patients had severe aregenerative anemia (mean hemoglobin (Hb) of 6.2 ± 1.0 g/dl); all were treated with a reduction in their immunosuppressive regimen and the administration of single-dose intravenous immunoglobulin (IVIG) (mean total dosage of 0.87 ± 0.38 g/kg). The median time to anemia improvement (Hb >10 g/dl) was 3-week post-treatment. No recurrences were documented during follow-up (median 25 months). Among 128 patients (including our cohort of 8 and 120 reported in literature), therapeutic strategies included: 43% IVIG alone, 39% IVIG and reduced immunosuppression, 9% reduction of immunosuppression, and 9% conservative therapy. Clinical relapses were observed in 35% of 71 reported cases. Conclusions In KTR, decreasing immunosuppression and the administration of low-dose immunoglobulin seem to be not worse than the standard dose in PVB19 infection.

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.

Not the Usual Viral Suspects: Parvovirus B19, West Nile Virus, and Human T-Cell Lymphotrophic Virus Infections After Kidney Transplantation.

Kidney transplant recipients are at increased risk of developing clinical disease due to uncommon opportunistic viral pathogens. Refractory anemia is classically associated with parvovirus B19 infection. West Nile virus has the propensity to cause fever and neurologic symptoms, while spastic paresis and lymphoma can be triggered by human T cell lymphotrophic virus. In this review article, the epidemiology, clinical manifestations, diagnosis and treatment of less common viruses are discussed in the setting of kidney transplantation.

Stem cell transplantation in 6 children with parvovirus B19- induced severe aplastic anaemia or myelodysplastic syndrome.

Parvovirus B19 (PVB19) induced severe aplastic anaemia (SAA) or myelodysplastic syndrome (MDS) is rare, and haematopoietic stem cell transplantation (HSCT) in this condition has not been reported so far. 6 children with SAA (n=4) or MDS (n=2) caused by acute PVB19 infection underwent HSCT under the protection of intravenous immunoglobulines. The 4 children with SAA received matched HLA bone marrow from a sibling (n=3) or peripheral unrelated blood stem cells (n=1). 1 patient had delayed erythrocyte engraftment, whereas 3 patients had an uneventful transplantation course. HSCT in one of the 2 children with MDS was complicated by poor graft function, the other patient engrafted without complications. In conclusion, HSCT in children with PVB19 induced SAA or MDS is feasible, even though some patients may develop delayed engraftment or prolonged poor graft function.

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.

Erythema infectiosum.

BACKGROUND: Erythema infectiosum (fifth disease) is a common benign pediatric condition caused by B19 parvovirus. It can be identified clinically by a "slapped cheek" appearance that is often followed by reticulated exanthem on the trunk and extremities. OBJECTIVE: This review article provides a concise overview of erythema infectiosum. METHODS: The article is divided into the followings sections: background, epidemiologic characteristics, clinical description, diagnosis, differential diagnosis, laboratory diagnosis, prognosis, and management. RESULTS: Erythema infectiosum is found to cause a fairly prominent classic rash and generalized symptoms. CONCLUSION: Although erythema infectiosum has many distinctive symptoms, the prognosis is excellent because the condition in children is usually self-limited.

Persistent human parvovirus B19 infection in children under maintenance chemotherapy for acute lymphocytic leukemia.

OBJECTIVE: To report on B19 infection management and chemotherapy schedule consequences in five children treated for acute lymphocytic leukemia (ALL). PATIENTS AND METHODS: Between May 2001 and February 2002, five patients between 4 and 12 years of age, receiving maintenance chemotherapy for ALL, presented with symptoms suggesting B19 infection (pallor, fatigue, petechiae and pancytopenia in four patients; generalized rash in two patients; acute hepatitis in one patient). Qualitative polymerase chain reaction (PCR) on peripheral blood was used for diagnosis and follow-up of infection; quantitative PCR was used for viral load measurement. Intravenous nonspecific high-dose immunoglobulin therapy was administered until PCR was negative. RESULTS: Qualitative B19 DNA was found in the peripheral blood of all patients, confirming the infection. Viral load at diagnosis ranged from 10 to 10 particles/mL blood. B19 DNA was detectable in four patients at 45, 21, 40, and 44 weeks, respectively. Chemotherapy was delayed in all patients. No clear benefit of intravenous immunoglobulin was noted. CONCLUSIONS: Infection with B19 is rarely reported in patients with ALL, but it should be suspected when unexplained pancytopenia occurs during chemotherapy. Persistent B19 infection remains a challenge in the management of patients receiving maintenance chemotherapy for ALL, as no specific therapy such as a specific immunoglobulin or vaccine exists. The role of viral load measurement needs to be established in terms of its use in follow-up and evaluation of the therapeutic response.

Parvovirus infection and its treatment.

B19 parvovirus is an important pathogen in man. Acute infection produces fifth disease (erythema infectiosum) in normal individuals, transient aplastic crisis in the patient with haemolysis, and pure red cell aplasia in the immunologically incompetent host. Fetal infection can lead to hydrops fetalis. The target cell of the virus is the marrow erythroid progenitor. The immune response to the virus is largely humoral and directed against limited numbers of epitopes. Persistent infection is due to failure to produce neutralizing antibodies. Because viral infection is prevalent in the population, therapeutic immune globulin preparations are a good source of anti-B19 antibodies. IgG administration can lead to cure of anaemia in the congenitally immunodeficient patient and to its amelioration in AIDS patients with persistent parvovirus infection.

Successful treatment of parvovirus B19 infection and red cell aplasia occurring after an allogeneic bone marrow transplant.

Chronic parvovirus B19 infection in the immunocompromised host may cause severe anaemia secondary to failure of erythropoiesis. This has been previously documented in patients with the Acquired Immune Deficiency Syndrome (AIDS), congenital immunodeficiencies and in children with acute lymphoblastic leukaemia during maintenance chemotherapy. We describe persistent parvovirus infection in a 14-year-old boy after HLA-matched sibling allogeneic bone marrow transplantation for acute lymphoblastic leukaemia in second remission.

Parvovirus B19 infection and hematopoiesis.

Parvovirus B19, the only known human pathogenic parvovirus, is highly tropic to human bone marrow and replicates only in erythroid progenitor cells. The basis of this erythroid tropism is the tissue distribution of the B19 cellular receptor, globoside (blood group P antigen). In individuals with underlying hemolytic disorders, infection with parvovirus B19 is the primary cause of transient aplastic crisis (TAC). In immunocompromised patients, persistent B19 infection may develop that manifests as pure red cell aplasia and chronic anemia. B19 infection in utero can result in fetal death, hydrops fetalis, or congenital anemia. Diagnosis is based on examination of the bone marrow and B19 virological studies. Treatment of persistent infection with immunoglobulin leads to a rapid marked resolution of the anemia.

Chronic parvovirus B19 infection and systemic necrotising vasculitis: opportunistic infection or aetiological agent?

We describe three patients who had infection with human parvovirus B19 in association with new-onset systemic necrotising vasculitis syndromes, two with features of polyarteritis nodosa and one with features of Wegener's granulomatosis. Chronic B19 infection, lasting 5 months to more than 3 years, was shown by enzyme immunoassay for IgG and IgM antibodies to B19 and polymerase chain reaction for B19 DNA in serum and tissue samples. The patients had atypical serological responses to the B19 infection, although none had a recognisable immunodeficiency disorder. Treatment with corticosteroids and cyclophosphamide did not control vasculitis. Intravenous immunoglobulin (IVIG) therapy led to rapid improvement of the systemic vascultis manifestations, clearing of the chronic parvovirus infection, and long-term remission. These observations suggest an aetiological relation between parvovirus B19 infection and systemic necrotising vasculitis in these patients and indicate a potentially curative role for IVIG in such disorders.

Fetal medicine.

Fetal therapy continues to be an exciting yet controversial field. In utero treatment of a variety of fetal conditions is discussed: parvovirus B19 infection, fetal thyroid dysfunction, fetal ovarian cysts, twin-twin transfusion syndrome, and fetal hemolytic disease. Fetal surgery continues to be controversial. Despite considerable publicity, fetal surgery appears to be rarely, if ever, truly indicated. A new area of fetal therapy, ie, antenatal transplantation of fetal liver stem cells, is discussed.