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[Systemic manifestations of Parvovirus B19 infections].

PURPOSE: Parvovirus B19 (B19) causes many clinical disorders, of which the most common are erythema infectiosum, aplastic crisis complicating chronic hemolytic anemia, and hydrops fetalis. In young adults, the skin eruption caused by B19 is accompanied by polyarthritis and polyarthralgia in 60% of the cases. Rheumatoid factors and other antibodies including antinuclear antibodies, anti-ADN, and antiphospholipids can be produced in the wake of B19 infection. CURRENT KNOWLEDGE AND KEY POINTS: These features may simulate systemic diseases as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) (lupus-like eruption over the cheeks, cytopenia, etc.) or vasculitis (purpura, renal involvement). In addition, there have been a few reports of SLE, vasculitis and other connective tissue diseases developing shortly after a B19 infection associated with virus clearance suggesting that B19 can act as a trigger of systemic disease. However, studies in large series indicate that in fact B19 is probably an extremely rare cause of RA, SLE or vasculitis. FUTURE PROSPECTS AND PROJECTS: In fundamental studies B19 interacts with inflammatory cells by regulation of cytokines. More recently, two studies suggest that viral infection due to B19 may affect the course of SLE, leading to specific biological subsets. These preliminary findings require confirmation to elucidate the significance of the presence of B19 in systemic disease.

Adolescent↗

Childhood exanthems. Old and new.

Exanthems are a common cause of rashes in children. Several recent developments have sparked a renewed interest in this group of diseases, including the identification of parvovirus B19 and human herpesvirus 6 as the causative agents of erythema infectiosum and roseola infantum. The resurgence of measles as a childhood exanthem has caused a re-examination of current immunization practices. The most common and clinically significant exanthems are discussed, with an emphasis on new findings, origins, clinical manifestations, differential diagnosis, and management.

Adolescent↗

Acute parvovirus B19 infection associated with myocarditis in an immunocompetent adult.

Inflammatory heart disease is causally linked with progressive left ventricular dysfunction and congestive heart failure. In childhood, infection with parvovirus B19 (PVB19) is usually benign, causing erythema infectiosum. However, severe fetal PVB19 infection may be associated with hydrops fetalis and fetal death caused by myocarditis. Here we report a PVB19-induced myocarditis in a previously healthy 37-year-old patient admitted to the hospital because of chest pain and dyspnea due to left ventricular dysfunction. Four weeks after the onset of symptoms, we found lymphocytic infiltrates and PVB19 genome in left ventricular endomyocardial biopsy specimens. Consistently, acute PVB19 infection was indicated serologically by elevated IgM titers and the presence of PVB19 genome in peripheral blood lymphocytes. In conclusion, PVB19 infection may be complicated by acute myocarditis in immunocompetent adults. Because PVB19 myocarditis may progress to chronic dilated cardiomyopathy, early diagnosis by endomyocardial biopsy is important to initiate anti-inflammatory treatment.

Acute Disease↗

Parvovirus B19 infection in Hong Kong.

Human parvovirus B19 is a small DNA virus that can cause a number of diseases, notably erythema infectiosum in children, and aplastic crisis in patients with chronic haemolytic disorders. With the availability of serological tests for parvovirus infection, much is known about the prevalence of this virus in the Western population. However, there have not been any data on the epidemiological pattern of parvovirus B19 infection in Hong Kong and its surrounding region. In this report we have studied the sero-prevalence of parvovirus B19 in Hong Kong in 1983 and 1993, and were able to show a low incidence of parvovirus infection in the intervening 10 years, leading to a shift in the prevalence rate of parvovirus infection in the general population. From 1991 to 1996, of 276 patients presenting with illness which might have been caused by B19, only 2.5% were positive for IgM and 19.6% for IgG anti-B19. The prevalence of IgG anti-B19 among patients with thalassaemia major requiring frequent blood transfusion in 1995 was similar to those in the same age group in the general population, substantiating the observation that B19 infection was not common in Hong Kong in recent years.

Adolescent↗

Establishment of a porcine parvovirus (PPV) DNA standard and evaluation of a new lightcycler nested-PCR assay for detection of PPV.

Porcine parvovirus (PPV) is a major causative agent in a syndrome of reproductive failure in swine. In validation (viral clearance) studies, PPV is a model of non-enveloped viruses and is widely used instead of human parvovirus B19, which causes a variety of illnesses including erythema infectiosum (fifth disease) in children and hydrops fetalis in pregnant women. To improve the sensitivity of current PCR-based assays for detection of PPV and to standardize the quantification of PPV, we have developed a lightcycler (LC) nested-PCR (nPCR) assay and constructed a PPV DNA standard evaluated in the LC nPCR assay. The PPV DNA standard, a plasmid termed pPPV, encodes a 3.3 kb PPV NADL-2 genome fragment. One genome copy equivalent (gce) of PPV equals 6.7 attograms of pPPV. The LC nPCR assay is a simple and specific method developed for detection of PPV strains but not any other viruses including members of Parvoviridae. The first 25-cycle PCR with outer primers chose by comparative analysis of 12 primers in 21 different combinations and a second 45-cycle PCR with inner primers amplify 286 and 251 bp fragments of PPV genome, respectively, for 40 min with a sensitivity of approximately 100 gce per assay (ml). By using the LC nPCR assay for analysis of PPV samples with known infectivity, we found that one 50% tissue culture infectious dose (TCID(50)) equals 1.93 +/- 0.24 log(10) gce.

Animals↗

[Parvovirus (serum-parvovirus-like-virus) and Aurillac antigen. A study of 18 cases].

Two cases of parvovirus viraemia were observed in 1972 by screening of blood donors for HBs Ag by counter-electrophoresis. This virus was named "Aurillac" from the town in which the first case originated. In London, a virus found in the same circumstances in 1975, was found identical to the Aurillac Ag. The authors named it "serum parvovirus-like virus" (SPLV) or parvovirus B 19. Since 1972, 16 additional cases have been observed in Paris. Among these 18 cases, 11 were blood donors, 4 were hospital staff and 3 were patients. Second serum samples were available for 13 of the 18 cases. Seroconversion has been detected in all except one, a patient with lymphosarcoma. Antibody could be observed within few days. Anti-Aurillac antibody was found by CEP in 25,3% of blood donors. Examination of antigen positive sera by immune electron microscopy using a late serum sample showed aggregates of spherical particles measuring 20 nm in diameter. The antigen banded in caesium chloride at a density of 1.38. Ten of the 15 healthy adults could be interviewed: 7 appeared symptomless, 1 had a fever up to 39 degrees C for one day, 2 had erythema (as well as 3 subjects who had been in contact with these 2 persons). These cases are discussed and compared to the British literature showing that this virus could provoke the fifth disease or erythema infectiosum and aplastic crisis in chronic hemolytic syndromes. This virus could contaminate clotting factors.

Adolescent↗

Rheumatic manifestations of parvovirus B19 infection.

Human parvovirus B19 is an emerging DNA virus. B19 infection is common and widespread. Major manifestations of B19 infection are transient aplastic crisis, erythema infectiosum, hydrops fetalis, acute and chronic rheumatoid-like arthropathy, and, in the immunocompromised host, chronic or recurrent bone marrow suppression. A number of less common manifestations of B19 infection include various rash illnesses, neuropathies, and acute fulminant liver failure. Of rheumatologic interest, B19 infection must be differentiated from early presentation of more classic erosive rheumatoid arthritis and, in some cases, systemic lupus erythematosus. It is unlikely that B19 plays a role in classic erosive rheumatoid arthritis, but understanding pathogenesis of B19 arthropathy may provide insights into the mechanisms by which rheumatoid arthritis develops. Evidence for persistence of B19 infection suggests that human parvovirus B19 infection may serve as a model for the study of virus-host interactions and the role of viruses in the pathogenesis of rheumatic diseases.

Diagnosis, Differential↗

Parvovirus B19 and autoimmune diseases.

Parvovirus B19 (B19) causes many clinical disorders, of which the most common are erythema infectiosum, aplastic crisis complicating chronic hemolytic anemia, and hydrops fetalis. In young adults, the skin eruption caused by B19 is accompanied with polyarthritis and polyarthralgia in 60% of the cases. The joint abnormalities predominate in the hands and feet and usually resolve within a week (range 2-21 d). Serological tests show IgM antibodies against B19, confirming the diagnosis of recent infection. Protracted polyarthritis occurs in some patients and seems associated with the DR4 histocompatibility alleles. Rheumatoid factors can be produced transiently in these patients. Other autoantibodies produced in the wake of B19 infection include anti-nuclear antibodies, anti-DNA, anti-SSA/SSB, and anti-phospholipids. Acute B19 infection can simulate early rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) (lupus-like eruption over the cheeks, cytopenia, etc.). In addition, there have been a few reports of erosive RA or SLE developing shortly after a B19 infection, with positive PCR tests for B19 DNA in synovial tissue or blood cells. Studies in large series indicate that B19 is probably an extremely rare cause of RA or SLE. Vasculitides affecting the small vessels (Henoch-Schonlein purpura, Wegener's granulomatosis), medium-sized vessels (periarteritis nodosa), and large vessels (giant cell arteritis) can occur after B19 infection. Here again, the number of clinical cases is small.

Adolescent↗

Chronic human parvovirus B19 infection in rheumatic disease of childhood and adolescence.

Parvovirus B19 causes erythema infectiosum in children, but the virus is associated with an increasing range of different diseases. About 20% of infections are associated with delayed virus elimination and viremia persisting over several months or years. These persistent B19-infections are characterised by the presence of IgG against the non-structural protein NS1. This study aimed to find further evidence for an association of parvovirus B19 persistence with VP1/2- and NS1-specific IgG-antibodies in children suffering from rheumatic diseases of childhood. Forty-eight children and adolescents with joint complaints lasting longer than 1 year including patients with juvenile systemic sclerosis and juvenile dermatomyositis showed antibodies against the viral NS1-protein. Laboratory markers of inflammation, humoral immune response against parvovirus B19 proteins and the presence of viral genomes in patients' sera as well as in 124 healthy children were investigated. Almost 50% of the patients showed laboratory signs of chronic inflammation. B19-DNA was amplified in 31% of patients' sera and 7% of the controls (P<0.0001). VP2-specific IgM was detectable in 50% of the patients' and 6% of control sera. NS1-specific immune reactions were linked to persistent B19-infection as indicated by the presence of viral genomes in the peripheral blood and of VP2-specific IgM years after disease onset. To estimate the severity of the disease and the clinical course, the number of affected and functionally impaired joints were noted and compared with the records from patients' initial visit in the hospital. Disease related complications were registered. Impairment of activities of daily living was assessed by Childhood Health Assessment Questionnaire (CHAQ)- and Munich Quality of Life Questionnaire (KINDL)-tests. During observation the clinical state of four patients worsened, 27 improved, the others remained stable. Twenty-four children were restricted in their daily activities.

Adolescent↗

Detection of human parvovirus B19 infection: a study of 212 suspected cases in the state of Rio de Janeiro, Brazil.

BACKGROUND: Parvovirus B19 infections are associated with different clinical manifestations that vary from symptom-less to severe. The main clinical manifestations are erythema infectiosum or fifth disease, transient aplastic crisis in individuals with hemoglobinopathies, chronic anemia in the immunocompromised, acute polyarthralgia syndrome in adults, hydrops fetalis, spontaneous abortion and stillbirth. Although the classical features of B19 and rubella infections are distinct, uncommon presentations can lead to misdiagnosis. OBJECTIVE: The goal of this study was to assess the occurrence of parvovirus B19 (B19) infection in patients with clinical signs of toxoplasmosis or rubella, both of which were not confirmed by laboratorial techniques. STUDY DESIGN: Serum samples from 214 patients were collected between January 1996 and December 1997 in the state of Rio de Janeiro, Brazil, B19 specific IgG and IgM were detected by using commercial enzyme-linked immunosorbent assays (ELISA), and viral nucleic acid was detected employing a nested polymerase chain reaction (PCR) protocol. RESULTS: Combining the results obtained by IgM ELISA and PCR, 14.5% of the samples were positive in one or both tests, with a concordance of 92.5% between the two techniques. CONCLUSIONS: Specimens collected in 16 out of 22 municipalities were positive in at least one out of the three tests employed, indicating that parvovirus B19 circulates in several regions of the state of Rio de Janeiro.

Abortion, Spontaneous↗

Acute parvovirus B19 infection in connection with a flare of systemic lupus erythematodes in a female patient.

BACKGROUND: Since its discovery parvovirus B19-infections could be linked to a growing variety of diseases. Besides the harmless exanthema erythema infectiosum perferentially observed with B19-infections in childhood a panel of rather serious and also chronic courses that may be associated with anemia, thrombocytopenia, arthritis and others have been described. OBJECTIVE: In a 26-year-old female patient an acute parvovirus B19-infection was followed by a serious episode of systemic lupus erythematosus (SLE). Here we demonstrate the clinical and serological parameters which were observed in the patient during that episode in addition to the nucleotide sequence of the virus isolate. RESULTS AND CONCLUSION: In this patient parvovirus B19 was not the initial causative agent for SLE. However the B19 infection was followed by a severe flare of SLE and therefore may be considered as an enhancer of the autoimmune disease. The amount of nucleotide variability observed in the viral genome was in the range known from other B19 isolates. An elevated degree of mutations in antigenic domains was not detectable. Therefore, we would like to emphasize the possible role of parvovirus B19 in the aetiology or the enhancement of autoimmune diseases like SLE and the necessity of an according differential diagnosis.

Adult↗

Concurrent outbreaks of influenza and parvovirus B19 in a boys' boarding school.

In the spring term of 1985 there was a protracted outbreak of upper respiratory tract febrile illness consistent with a clinical diagnosis of influenza in a boys' boarding school, which lasted from 23 January to 29 March. Although influenza virus infection was confirmed in 89% of cases in the first half of the term, 53% of the cases which occurred in the second half of the term had no evidence of infection with influenza virus. Between 5 February and 31 March 28 boys presented with skin rashes consistent with a clinical diagnosis of erythema infectiosum; 68% of these were associated with parvovirus B19. Investigation of the cases of clinical influenza with no identified respiratory pathogen revealed a 58% infection rate with B19. B19 DNA was identified in either throat swabs or acute stage bloods of nine pupils with influenza-like symptoms. Cohort studies revealed that 44% of pupils aged 15-16 years were immune before the outbreak compared with only 17% of pupils aged 11-12 years. Infection in the younger group was common and was associated with influenza-like illnesses as well as rashes. Forty-eight per cent of those who did not report any symptoms were also infected with B19.

Adolescent↗

[Exanthema as a main symptom in the febrile child].

Distinguishing in febrile children between harmless rashes and those, which require specific action, is a common problem in pediatric primary care. Major exanthematous diseases necessitating emergency hospitalization include invasive meningococcal disease and rarely gram-negative septicaemia caused by other pathogens, staphylococcal and streptococcal toxic shock syndrome, endocarditis, fever and rash in travellers returning from tropical countries and drug hypersensitivity syndrome. Therapeutic intervention is also necessary in patients with scarlet fever, rheumatic fever, varicella in postpuberal and immunocompromised individuals, in Kawasaki's disease, in Still's disease and in other non-infectious, inflammatory diseases (e.g., familial mediterranean fever). Finally, various specific measures need to be taken in reportable diseases, erythema infectiosum (parvovirus B19), primary HIV infection and in Henoch-Schölein purpura.

Child↗

Acute lung injury due to parvovirus pneumonia.

OBJECTIVE: Human parvovirus B19 is responsible for the common childhood exanthematous illness, erythema infectiosum. Adults infected with B19 have been reported to develop a febrile illness associated with arthritis. Life threatening parvovirus infections in non-immunocompromised adults have not been reported to date. We report a previously healthy middle aged female who developed severe parvovirus pneumonia. The patient recovered with supportive care provided in the ICU. Parvovirus may represent an under diagnosed cause of community acquired pneumonia.

Acute Disease↗

[Association of non-immunologically-induced hydrops fetalis with Parvovirus B19 infection].

Five weeks after the onset of clinical symptoms of erythema infectiosum, a 24 year old pregnant woman, gravida I, para 0, suffered a hydrops fetalis which resulted in fetal loss. The maternal infection with the human parvovirus B19 could be confirmed serologically with ELISA and immunoblot by detecting specific IgM antibodies against B19. In an amniotic sample of the fetus Parvovirus B19 DNA could be detected by hybridisation. Fetal loss was obviously due to a parvovirus B19 infection of the mother and the fetus.

Adult↗

Human parvovirus infection in pregnancy and hydrops fetalis.

Human parvovirus is the causative agent of erythema infectiosum, a mild epidemic illness. In a recent outbreak in northeast Scotland, six women had serologic evidence of having contracted human parvovirus infection during pregnancy. Two of the women had midtrimester abortions, and both abortuses were grossly hydropic with anemia. They had similar microscopical histopathological features--a pronounced leukoerythroblastic reaction, hepatitis, excessive iron pigment in the liver, and eosinophilic changes in the hematopoietic cell nuclei. Dot hybridization with radiolabeled human parvovirus DNA probes revealed viral DNA in several tissues from both fetuses, indicating that they had been infected by the virus in utero. The remaining four women had uncomplicated pregnancies and delivered apparently healthy babies, none of whom had human parvovirus-specific IgM antibody at delivery. We conclude that this common virus may pose a serious risk to the fetus after maternal infection.

Abortion, Septic↗

Bioportfolio: lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue.

Human erythrovirus is a minute, single-stranded DNA virus causing many diseases, including erythema infectiosum, arthropathy, and fetal death. After primary infection, the viral genomes persist in solid tissues. Besides the prototype, virus type 1, two major variants (virus types 2 and 3) have been identified recently, the clinical significance and epidemiology of which are mostly unknown. We examined 523 samples of skin, synovium, tonsil, or liver (birth year range, 1913-2000), and 1,640 sera, by qualitative and quantitative molecular assays for the DNA of human erythroviruses. Virus types 1 and 2 were found in 132 (25%) and 58 (11%) tissues, respectively. DNA of virus type 1 was found in all age groups, whereas that of type 2 was strictly confined to those subjects born before 1973 (P < 0.001). Correspondingly, the sera from the past two decades contained DNA of type 1 but not type 2 or 3. Our data suggest strongly that the newly identified human erythrovirus type 2 as well as the prototype 1 circulated in Northern and Central Europe in equal frequency, more than half a century ago, whereafter type 2 disappeared from circulation. Type 3 never attained wide occurrence in this area during the past > or =70 years. The erythrovirus DNA persistence in human tissues is lifelong and represents a source of information about our past, the Bioportfolio, which, at the individual level, provides a registry of one's infectious encounters, and at the population level, a database for epidemiological and phylogenetic analyses.

Adolescent↗

Renal involvement of human parvovirus B19 in an immunocompetent host.

Human parvovirus B19, which is most commonly known to cause erythema infectiosum in children, is also known to cause infection in adults, with complications ranging from a self-limited polyarthropathy in immunocompetent patients to hydrops fetalis in pregnant women, transient aplastic crises in patients with chronic hemolytic anemias, and chronic aplastic anemia in immunocompromised hosts. We describe a previously healthy immunocompetent woman who presented with manifestations of acute parvovirus B19 infection.

Adult↗