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PubMed2000

Raynaud's phenomenon as a manifestation of parvovirus B19 infection: case reports and review of parvovirus B19 rheumatic and vasculitic syndromes.

Infection with human parvovirus B19 is manifested as erythema infectiosum, transient aplastic crisis, or hydrops fetalis. Rheumatic manifestations include arthropathy and various vasculitic syndromes. Isolated Raynaud's phenomenon due to parvovirus B19 has never been described. We report on 2 previously healthy sisters with new-onset Raynaud's phenomenon accompanied by severe generalized polyarthralgia. A full workup was negative, except serology for parvovirus B19, which was positive. All symptoms gradually subsided within 3-5 months, and no recurrence has been noted during the 3 years since onset. We review all the studies in the English-language literature on parvovirus B19-induced rheumatic and vasculitic syndromes. We hypothesize that the pathogenesis of Raynaud's phenomenon in our patients involved immune-mediated endothelial damage leading to platelet activation and vasoconstriction. We recommend that in cases of unexplained Raynaud's phenomenon, serology for parvovirus B19 be included in the evaluation.

Adolescent↗

PubMed1995

Human parvovirus B19 infection: immunohistochemical and electron microscopic studies of skin lesions.

Erythema infectiosum is known to be caused by human parvovirus B19 and shows characteristic clinical skin manifestations in children, although adult cases of human parvovirus B19 infection do not always show such characteristic features. Recently, we experienced an epidemic adult cases of human parvovirus B19 infection and examined the erythematous skin lesion by immunohistochemistry and electron microscopy to clarify the pathogenesis of the skin manifestations. Light microscopic examination showed slightly irregular-shaped vessels in the dermis. By immunohistochemistry, using anti-human parvovirus B19 monoclonal antibody, positive reactions were found in endothelial cells. No immunoglobulins were found, but C3 deposits were present in the perivascular areas. By electron microscopy, virus particles were found in the cytoplasm of endothelial cells. An inflammatory reaction due to the direct human parvovirus B19 infection in dermal vessels seems to be an important factor in the pathogenesis of the skin manifestations.

Adult↗

PubMed1996

[Severe parvovirus B19 infection in an immunocompetent child with hemophilia A].

BACKGROUND: B19 parvovirus is a widespread virus whose typical manifestations in immunocompetent children are erythema infectiosum, acute erythroblastopenia and fetal anemia. CASE REPORT: An 11 year-old immunocompetent patient with hemophilia A was referred for an hemorrhagic syndrome. Forty days after a pasteurized coagulation factor concentrates treatment, and after 12 days of treatment with solvent/detergent factor VIII concentrates, he developed fever, consciousness disorders, pancytopenia, liver cytolysis and probably minor haemophagocytic syndrome, associated with human parvovirus B19 infection. His clinical state returned to normal within 15 days. A retrospective study revealed that the patient had received every day for 12 days, one parvovirus B19 polymerase chain reaction positive batch before the occurrence of symptoms. CONCLUSION: This case highlights the possibility of severe parvovirus B19 infection transmitted by clotting factors prepared from large pools of plasma. The use of recombinant factors would allow to reduce human virus contamination, even if immune risk has to be more accurately assessed.

Anticoagulants↗

PubMed2003

Parvovirus B19 infection and autoimmune disease.

Human parvovirus B19 infections may cause a widespread benign and self-limiting disease in children and adults, known as erythema infectiosum or fifth disease. A variety of further manifestations are associated with the infection such as arthralgias, arthritis, leukopenia and thrombocytopenia, anemia and vasculitis, spontaneous abortion and hydrops fetalis in pregnant women. Both in children and adults parvovirus B19 infections have been frequently implicated as a cause or trigger of various forms of autoimmune diseases affecting joints, connective tissue and large and small vessels. In addition, autoimmune neutropenia, thrombocytopenia and hemolytic anemia are known as sequelae of B19 infection. The molecular basis of the autoimmune phenomena and resultant pathogenesis is unclear. The involvement of molecular mimicry between cellular and viral proteins, the induction of enhanced cytokine production via the viral transactivator protein NS1 and the phospholipase A2-like activity of the capsid protein VP1 may contribute to the induction of autoimmune reactions. All the known data and the potential mechanisms involved in the pathogenesis will be discussed in this review.

Autoimmune Diseases↗

PubMed2000

[A case of Guillain-Barré syndrome (GBS) following human parvovirus B19 infection].

Human parvovirus B19 (HPV-B19) infection is recently known to produce variable clinical manifestations, but neurological disorder associated with this infection is uncommon. We reported a case of GBS associated with transient lupus-like status following HPV-B19 infection. This is the first report describing an adult case of GBS following HPV-B19 infection. A healthy female, aged 33, developed erythema infectiosum simultaneously with her 5-year-old daughter. On the same day, she noticed leg fatigue, which worsened in the following days. On the day 11th, she became unable to walk. Mild pancytopenia, liver injury, proteinuria, hypocomplementemia, and increased anti-nuclear antibody (ANA) were revealed at a hospital. Polymerase chain reaction detected HPV-B19 DNA in the serum. On the day 17th, she was admitted to our hospital because of moderate generalized weakness and mild sensory disturbance, which were symmetrical and distal-dominant. The deep tendon reflexes were absent. Analysis of cerebrospinal fluid showed albuminocytologic dissociation. Other laboratory data were normal except positive ANA. Enzyme-linked immunosorbent assay (ELISA) showed high titer of the serum IgM antibody to GM1 and GD1b. Serum anti HPV-B19 IgM and IgG tested by ELISA were also positive. She improved gradually after 2 courses of double filtrated plasma pheresis.

Adult↗

PubMed1994

Immunochemiluminescent Southern blot assay for polymerase chain reaction detection of human parvovirus B19 DNA.

Human parvovirus B19 is not only an acute self-limited infection causing erythema infectiosum, transient aplastic crisis, foetal hydrops and arthritis but can also be a chronic infection causing chronic anaemia and associated with chronic neuropathy and vasculitis. Serologic studies have proven to be the most sensitive way to detect acute infection in the immunologically normal patient while polymerase chain reaction (PCR) assays for B19 DNA are the most sensitive way to detect chronic infection. The ability to detect B19 in clinical specimens can be further increased with a second amplification step using nested primers. However, nested PCR is both time consuming and enhances the risk of false-positive results due to contaminating DNA. In this study, we developed a sensitive immunochemiluminescent Southern blot assay for detecting PCR amplified B19 DNA with a digoxigenin labelled primer. The sensitivity and specificity of this assay were comparable to nested PCR and at least 100-fold more sensitive than a single PCR amplification.

Blotting, Southern↗

PubMed2001

Fatal parvovirus myocarditis in a 5-year-old girl.

Infection with parvovirus B19 is common in children and typically causes mild illness. We report here the case of a 5-year-old girl who died suddenly, 2 weeks after the clinical diagnosis of a parvoviral infection (erythema infectiosum). Microscopic examination of the heart showed severe myocarditis with extensive T-cell and macrophage infiltration. Cultures, serology, and molecular analyses of serum for enteroviridae, adenovirus, influenza, varicella zoster, cytomegalovirus, and herpes simplex viruses were negative. Quantitative polymerase chain reaction (PCR) analysis for parvovirus B19 in peripheral blood, however, showed active infection (91,000 genomes/mL serum; 2.4 genomes/mononuclear cell). Despite the presence of myocarditis, immunostaining for parvoviral surface antigens was negative in the heart. Quantitative PCR analysis of paraffin sections showed that myocardial parvoviral content was significantly less than that of the normal appearing kidney and within the range predicted simply by tissue blood content. Thus, parvovirus B19 infection can be complicated by fatal myocarditis. Because the virus does not appear to have infected the heart, per se, we speculate that myocarditis arose from immunological cross-reaction to epitopes shared between the virus and the myocardium. HUM PATHOL 32:342-345.

Antigens, Viral↗

PubMed2000

Parvovirus B19 infection associated with the production of anti-neutrophil cytoplasmic antibody (ANCA) and anticardiolipin antibody (aCL).

We described four patients who had clinical diagnosis of erythema infectiosum and presented with skin rash, polyarthralgia, polyarthritis, and mild fever. Anti-parvovirus B19 IgM and IgG antibodies were found in all four patients and parvovirus B19 DNA was detected in three of the four patients by polymerase chain reaction (PCR) in sera using standard methods. Anticardiolipin antibody (aCL) was positive in three of the four patients included three with anti-beta2 glycoprotein I (beta2GPI). The immunoglobulin isotype of aCL was found to be IgM. Anti-neutrophil cytoplasmic antibody (ANCA) included three p-ANCA and one c-ANCA was detected in all four patients by indirect immunofluoresence (IIF). Both anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) antibodies were found in two patients whom had polyarthritis for more than 6 months. These data indicate parvovirus B19 may be linked to the induction of an autoimmune response.

Adult↗

PubMed1993

[A study of epidemiology and fetal effects of human parvovirus B19 infection].

The risk of human parvovirus B19(B19) infection in pregnant women, the relationship between B19 and early spontaneous abortion, and the pathogenesis of non-immune hydrops fetalis (NIHF) due to B19 infection were studied. 1) After the period of prevalence of erythema infectiosum(EI) between 1986 and 1987, the positive rate of anti B19 IgG antibody by sandwich ELISA in the sera from subjects aged 15-34 years old was 17-26%. This indicates that about 80% of pregnant women could be at the risk of B19 infection in future EI prevalence within ten years. 2) IgM antibody assayed by capture ELISA was positive in 1.4% of the sera from pregnant women during the period of EI prevalence. 3) B19 DNA could not be detected by in situ hybridization (ISH) in any chorionic tissues from 105 early spontaneous abortuses during the period. B19 infection could not be proven as one of the causes of early spontaneous abortion. 4) B19 DNA was localized by ISH in erythroblasts but not in myocardial cells of two fetuses out of 11 NIHF. Therefore, NIHF following B19 infection could take place due to anemia following B19 infection of erythroblasts and their destruction.

Abortion, Spontaneous↗

PubMed2000

Parvovirus B19 infection and its significance in pregnancy.

Parvovirus B19 causes prolonged epidemics of erythema infectiosum, particularly in primary school-aged children. Infection causes clinically significant anaemia in individuals with high red cell turnover, including the fetus. Approximately 40% of women of childbearing age are susceptible, and annual seroconversion rates vary from 1.5% during endemic periods to 10-15% during epidemics. Infection occurs in around 50% of susceptible women exposed at home and 20-30% following occupational exposure (for example, at a primary school). Maternal infection in the first half of pregnancy is associated with 10% excess fetal loss and hydrops fetalis in 3% of cases (of which up to 60% resolve spontaneously or with appropriate management). No congenital abnormalities or long-term sequelae have been attributed to parvovirus B19 infection. The overall risk of serious adverse outcome from occupational exposure to parvovirus B19 infection during pregnancy is low (excess early fetal loss in 2-6/1,000 pregnancies and fetal death from hydrops in 2-5/10,000 pregnancies). It is not recommended that susceptible pregnant women be excluded routinely from working with children during epidemics.

Adult↗

PubMed1993

Multiple primer pairs for polymerase chain reaction (PCR) amplification of human parvovirus B19 DNA.

Human parvovirus B19 is the etiologic agent of erythema infectiosum and transient aplastic crisis in patients with hemolytic anemias and has been associated with fetal death, arthritis, and chronic anemia. Acute B19 infection is best diagnosed by detection of IgM antibodies, whereas the diagnosis of chronic infection often requires the sensitivity of PCR to demonstrate presence of virus over time. To improve our ability to detect B19 DNA by polymerase chain reaction (PCR), we evaluated 19 primers combined into 16 different primer pairs for their ability to detect temporally and geographically diverse B19 isolates. All 16 pairs reacted with all isolates tested but with different sensitivity. Sequence analysis showed few nucleotide changes compared with published sequences. These changes did not explain observed differences in sensitivity between primer pairs. The most sensitive primer pairs detected 350 to 3500 DNA copies after 35 cycles. A second amplification cycle with nested primers improved the sensitivity 100-fold. These 16 primer pairs provide the diagnostic virologist with multiple options for B19 PCR assays.

Acute Disease↗

PubMed1996

Parvovirus B19 infection.

Human parvovirus B19, discovered in 1974, is a single-stranded DNA virus which causes erythema infectiosum, arthralgia, aplastic crisis in patients with red cell defects, chronic anaemia in immunocompromised patients, and fetal hydrops. Seroprevalence in developed countries is 2-10% in children less than 5 years, 40-60% in adults more than 20 years, and 85% or more in those over 70 years. The virus may be transmitted by the respiratory route and by transfusion of infected blood and blood products. After an incubation period of six to eight days, viraemia occurs, during which reticulocyte numbers fall dramatically resulting in a temporary drop in haemoglobin of 1 g/dl in a normal person. Clearance of viraemia is dependent on development of specific antibody to the B19 structural proteins, VP1 and VP2. The red cell receptor for the virus is blood group P antigen. Diagnosis in immunocompetent persons depends on detection of specific IgM in serum. Diagnosis in immunocompromised persons depends on detection of B19 antigen or DNA in serum. There is no specific treatment for B19 infection; however, human normal immunoglobulin may be used as a source of specific antibody in chronically infected persons. A recombinant parvovirus B19 vaccine is under development.

Adult↗

PubMed1995

New pathogens, and diseases old and new. I) Afipia felis and Rochalimaea. II) Parvovirus B 19. III) herpesvirus 6.

The paper describes events that in the last fifteen years, have led to the identification of the aetiological agents of three widely known diseases: cat scratch disease, erythema infectiosum and exanthem subitum. The particular features of Afipia felis and Rochalimaea, Parvovirus B 19 and Herpesvirus 6 are presented. The paternity of new diseases (i.e. bacillary angiomatosis, bacillary peliosis hepatitis, LES-like syndrome, chronic fatigue syndrome, petechial glove and sock syndrome, etc.) has also been attributed to some of these pathogens as has the paternity of some older ones (i.e. aplastic crisis, erythroblastosis fetalis, trench fever, hepatitis, opportunistic infection, etc.). It has been argued that the same pathogen can cause different diseases depending on the immunogenic state of the subject. To date, persisting difficulties in isolating the pathogen or differentiating between latent or active infection, still in some cases raises doubts concerning the attribution of the disease to a specific agent. New immunological or molecular techniques, allowing the direct detection of in vivo replication, are still needed in order to establish a sure connection between some of these agents and some of these diseases. Progress here will both give more accurate data about the epidemiology of some diseases and allow us to apply more appropriate treatment and prevention techniques.

Bartonella henselae↗

PubMed1992

Prenatal diagnosis of intrauterine infection with parvovirus B19 by the polymerase chain reaction technique.

Human parvovirus B19 is a recently recognized cause of fetal hydrops and death. Efforts to characterize the natural history of fetal infection with this virus have been hampered by the lack of sensitive and specific tests for diagnosis in utero. Using the highly sensitive polymerase chain reaction (PCR) assay, we determined the fetal infection status in 56 pregnancies by testing amniotic fluid, fetal serum, and maternal serum for B19 DNA and antibodies. Factors associated with a high risk of B19 infection were fetal disease, exposure to persons with erythema infectiosum, or signs or symptoms of acute B19 infection. Fifteen women (27%) were B19 IgM-positive, a status suggesting recent infection; the positivity of all of the corresponding fetal specimens for B19 DNA in the PCR was indicative of fetal infection. In four of these cases, serial ultrasonographic examinations documented spontaneous resolution of fetal hydrops. Twenty-four women (43%) were IgG-positive and IgM-negative; this pattern suggested prior infection. The PCR gave positive results, consistent with recent maternal infection, in four of these cases. Seventeen women (30%) were IgG-negative and IgM-negative, a pattern suggesting no prior infection; the PCR results in four cases were indicative of a possible early maternal infection or a possible atypical immune response. The PCR is a sensitive and rapid method for the diagnosis of intrauterine infection with human parvovirus B19 and promises to facilitate studies of the natural history and treatment of this infection.

Adolescent↗

PubMed1995

[Seroprevalence of IgG antibodies against parvovirus B19 in the population of the Czech Republic].

The human parvovirus B 19 was discovered in 1975 by Cossart in England. Later (1984) evidence was provided that this virus is the etiological agent of erythema infectiosum and hydrops foetalis, and in 1985 it was provided that it is also the etiological agent of some types of arthritis or arthropaties and vasculitis. The diagnosis of the disease caused by this agent is most frequently based on evidence of specific immunoglobulins. The epidemiological and clinical impact of parvoviral infections in the Czech Republic was not known so far. Examination of sera from 562 subjects aged 0-60 years assembled in 1992 in three Czech regions revealed in children, age 0 - 4 years 9.8%, during preschool and school age 27 - 35.7% and in age groups above 15 years a 53.3 - 57.7% seroprevalence of IgG parvovirus B 19, roughly equally distributed among both sexes. The more frequent prevalence of specific immunoglobulins was proved in small groups of female workers in nurseries (66.7%), nursery schools (91.7%) and in blood transfusion stations (77.8%). The seropositivity of the general female population of matched age groups, with the exception of women aged 20 - 24 years, was 53.86%.

Adolescent↗

PubMed1995

Antibodies to parvovirus B19 NS-1 protein in infected individuals.

Human parvovirus B19 is the aetiological agent of the common childhood disease erythema infectiosum (fifth disease). The infection is usually benign and self-limiting, but in adults cases of severe arthritis which may persist for years have been reported. Neutralizing antibodies directed against the structural proteins are usually produced shortly after the infection. The immune response against the third major protein, the non-structural protein NS-1, of parvovirus B19 has not been characterized so far. We cloned and expressed the full-length NS-1 protein and fragments thereof in Escherichia coli. The purified recombinant proteins were used to investigate the presence of antibodies to the NS-1 protein in sera from patients with parvovirus B19 infection. Specific antibodies could be detected in sera from patients suffering from severe parvovirus B19-associated arthritis using Western blot analysis and an ELISA. Sera from patients with acute or past infection without complications did not contain detectable levels of immunoglobulin to NS-1. The use of subfragments of the NS-1 protein allowed localization of the antigenic domains in the carboxy-terminal region of the protein.

Antibodies, Viral↗

PubMed1994

Resistance to parvovirus B19 infection due to lack of virus receptor (erythrocyte P antigen).

BACKGROUND: The presence of a specific cellular receptor is thought to be necessary for susceptibility to viral infection. The erythrocyte P antigen is the cellular receptor for parvovirus B19. We hypothesized that the rare persons with the p phenotype, whose erythrocytes do not have this receptor, would be naturally resistant to B19 infection, which causes erythema infectiosum. METHODS: Blood samples were collected from two populations in cross-sectional studies. We determined the P antigen phenotype of the red cells and tested plasma for anti-B19-specific antibodies. Bone marrow from donors of known P antigen phenotype was inoculated with parvovirus B19. Infectivity was measured by assays of erythroid progenitor cells, dot blot analysis, and in situ hybridization for B19 DNA, and an immunofluorescence assay for viral-capsid proteins. RESULTS: Of the 17 subjects with the p red-cell phenotype, who did not have P antigen on their erythrocytes, none (0 of 11 and 0 of 6) had serologic evidence of previous parvovirus B19 infection. In contrast, the seropositivity rates in the two control groups were 71 percent (53 of 75, P < 0.001) and 47 percent (32 of 68, P = 0.03). In vitro, bone marrow from donors with the p phenotype maintained normal erythropoiesis despite very high concentrations of virus, with no evidence of infection of erythroid progenitor cells by parvovirus B19. CONCLUSIONS: People who do not have P antigen, which is the cellular receptor for parvovirus B19, are naturally resistant to infection with this pathogen.

Adolescent↗

PubMed1995

Systemic monocyte and T-cell activation in a patient with human parvovirus B19 infection.

Infection with human parvovirus B19 induces a biphasic disease. The initial phase has been associated with viremia. During the second phase of the disease, a spectrum of clinical syndromes can manifest, including erythema infectiosum, perinatal complications, and symmetric arthropathy that resembles rheumatoid arthritis. Although investigators have suspected that some of the second-phase symptoms are related to immune complex formation, the pathogenesis of parvovirus B19-induced clinical manifestations is not understood. Herein we describe a 63-year-old woman with malaise, fever, and symmetric polyarthritis who had IgM antibodies specific for parvovirus B19. Messenger RNA (mRNA) specific for interleukin (IL) 1 beta, IL 6, and interferon-gamma (IFN-gamma) was detected by polymerase chain reaction. Transcript concentrations were semiquantified by serial dilution of cells and determination of the minimal number of cells that provided a positive signal. Concentrations of IL 1 beta and IL 6 mRNA in peripheral blood mononuclear cells collected during acute disease were increased by the factor of 32 and 8, respectively. IFN-gamma was detected at a 16-fold increased concentration. Two months later, after the patient had experienced complete recovery, production of monokines and IFN-gamma was almost normalized. These data raise the possibility that acute parvovirus B19 infection is characterized by a widespread and systemic activation of monocytes, T cells, and natural killer cells. The correlation of increased cytokine mRNA levels and clinical symptoms suggests a potential role of proinflammatory monokines and lymphokines in disease manifestations.

Acute Disease↗