Human parvovirus B19 infection mimicking systemic lupus erythematosus

Abstract

Although several recent reports have discussed the similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE), the relationship between these conditions has not been established owing to the small number of patients investigated. In 1998–1999, an outbreak of Erythema infectiosum occurred close to our hospital, enabling us to investigate the clinical, hematological, and serological findings, including serum complement and antinuclear antibodies (ANA), in 22 patients with acute HPV-B19 infection. The principal symptoms included rash (86.3%), edema (59%), arthralgia (45.4%) and fever (31.8%). Lymphadenopathy was seen in three of the 22 cases. The laboratory findings showed high incidences of leukopenia (50%), hypocomplementemia (95%), and ANA (64.7%). At the time of disease onset, patients with acute HPV-B19 infection presented with features which were similar to those of SLE. The possibility of HPV-B19 infection should therefore be considered in patients presenting with SLE-like features.     

Seroprevalence of parvovirus B19 in fibromyalgia syndrome

This study was aimed to evaluate the seroprevalence of parvovirus B19 in patients with fibromyalgia syndrome (FS). Seventy-five patients with FS (44.3 ± 8.3) and 75 healthy controls (44.2 ± 8.1) were evaluated. Serum anti-B19 IgM and IgG antibodies were measured by ELISA technique. Patients were questioned about duration of symptoms, characteristic features of FS, and symptoms related with viral infection preceding the onset of FS. No significant difference was found regarding the prevalence of anti-B19 IgM antibodies between the groups (p = 0.494). Seropositivity of anti-B19 IgG of the patients was significantly higher than control group (81.3% vs. 64% respectively, p = 0.027). No statistically significant differences were found regarding to the clinical features between fibromyalgia patients with IgG antibody compared to those without IgG antibody. Parvovirus B19 IgG seropositivity was found to be significantly higher in patients with FS. Parvovirus B19 infection might have a role in the etiopathogenesis of FS or might act as a triggering factor.     

Human parvovirus B19 infection mimicking systemic lupus erythematosus

Although several recent reports have discussed the similarities between human parvovirus B19 (HPV-B19) infection and systemic lupus erythematosus (SLE), the relationship between these conditions has not been established owing to the small number of patients investigated. In 1998–1999, an outbreak of Erythema infectiosum occurred close to our hospital, enabling us to investigate the clinical, hematological, and serological findings, including serum complement and antinuclear antibodies (ANA), in 22 patients with acute HPV-B19 infection. The principal symptoms included rash (86.3%), edema (59%), arthralgia (45.4%) and fever (31.8%). Lymphadenopathy was seen in three of the 22 cases. The laboratory findings showed high incidences of leukopenia (50%), hypocomplementemia (95%), and ANA (64.7%). At the time of disease onset, patients with acute HPV-B19 infection presented with features which were similar to those of SLE. The possibility of HPV-B19 infection should therefore be considered in patients presenting with SLE-like features. Received: January 18, 2001 / Accepted: April 19, 2001     

Human parvovirus B19 infection in bone marrow transplantation patients

We report the results of a survey of parvovirus B19 infection carried out with the aim to evaluate the frequency and the role of this infection in bone marrow transplant (BMT) recipients, as it is known that B19 virus can persist in clinical circumstances of immunodeficiency. Fifty-one patients subjected to BMT in the Bone Marrow Transplantation Center of Florence were enrolled in this study. Immunological and virological indications of B19 infection were tested weekly during the stay in hospital. A high rate of seroconversion or B19 antibody rise was observed, but, in absence of B19 IgM or B19 DNA presence, this result seems to be attributable to a passive immunization, rather than to a recent viral infection. In these 51 patients, as well as in 59 others not included in this study, clinical manifestations imputable to B19 infection have never been observed. It is possible that the isolation measures and the intravenous immunoglobulins (IVIG) administration may contribute in preventing B19 infection in the BMT recipients at least until the hospital discharge. © 1993 Wiley-Liss, Inc.     

Expression of p53 and Ki-67 antigen in bone marrow giant proerythroblasts associated with human parvovirus B19 infection

Giant proerythroblasts are hallmarks of human parvovirus B19 infection. We attempted to characterize these cells in 5 patients with parvovirus B19-induced pure red cell aplasia using immunostaining of paraffin-embedded bone marrow sections with antibodies against erythroid-lineage-specific proteins, viral capsid antigen VP-1, and apoptosis- and cell-cycle-related proteins. Giant proerythroblasts are immunohistochemically consistent with early erythroid precursors of cells in the differentiation stage of CD34-, cytoplasmic spectrin+, glycophorin A-, and band-3-. VP-1 was expressed in the nucleus and cytoplasm of small- to medium-sized spectrin+ erythroid cells but not in giant proerythroblasts. The giant proerythroblasts displayed nuclear staining for p53 (41%+/-16%) and Ki-67 antigen (100%+/-0%) and cytoplasmic staining for Bax (65%+/-11%) and procaspase-3 (78%+/-10%), whereas they were not stained for p21Wafl/Cip1, active form of caspase-3, or terminal deoxynucleotidyltransferase-mediated deoxyuridine nick-end labeling (TUNEL). Antiapoptotic proteins, Bcl-2 and Mcl-1, were not expressed in the giant cells, and Bcl-x was infrequently expressed in these cells (11%+/-4%). These immunohistochemical findings suggest that giant proerythroblasts are proliferating erythroid precursors with accumulation of nonfunctional p53.     

Emerging lupus-like manifestations in acute parvovirus B19 infection

We encountered an adult patient with acute parvovirus B19 infection who presented with transient lupus-like symptoms (i.e., polyarthritis, fever, myalgia, pancytopenia, hypocomplementemia, and nephritis). Our case is characterized by the demonstration of acute nephritis as a complication of this infection, making it difficult to distinguish between a viral infection and the first episode of systemic lupus erythematosus.     

Acute parvovirus B19 infection mimicking chronic fatigue syndrome

A Japanese woman developed prolonged fatigue, neck and shoulder pain, headache, pyrexia, insomnia, anorexia, lymphadenopathy, and diarrhea for two months. She had experienced various stressors before these symptoms developed. Serological test demonstrated that she had acute parvovirus B19 infection. Major depressive disorder was also diagnosed by a psychiatrist. Her symptoms disappeared after administration of selective serotonin reuptake inhibitors and oriental herbs, although human parvovirus B19 viral genome has been present in her serum for nine months. These findings suggest that parvovirus B19 causes clinical features similar to those of chronic fatigue syndrome in cases who have prior life stressors.     

Lupus-like presentation of parvovirus B19 infection

OBJECTIVES: To describe 2 cases of parvovirus B19 (B19) infection mimicking systemic lupus erythematosus (SLE) and to identify all cases of SLE imitated by and/or associated with B19 in the medical literature. METHODS: A computer-assisted (PubMed) search of the medical literature from 1975 to 2003 was performed using the following key words: parvovirus, B19, SLE, lupus, antibodies, auto-immunity. RESULTS: Thirty-eight patients were identified: 35 women, 3 men; mean age = 28.8 years. Clinical manifestations were as follows: fever (24 patients); articular involvement (36 patients); cutaneous lesions (28 patients); lymphadenopathy (9 patients); hepato- and/or splenomegaly (6 patients); serositis (6 patients); renal involvement (4 patients); cerebral impairment (10 patients). Cytopenia was observed in 23 cases. Antinuclear antibodies were detected in 34 patients, anti-double-stranded DNA antibodies in 20 patients, anti-Sm antibodies in 4 patients, antinuclear ribonucleoprotein antibodies in 5 patients, anti-Ro-SSA antibodies in 4 patients, anti-La-SSB antibodies in 4 patients, and anticardiolipin and/or anti-beta2-glycoprotein I antibodies in 8 patients. Hypocomplementemia was found in 15 of 26 patients. In 19 cases, the B19 infection had a self-limiting course. In 6 cases, B19 infection occurred in a context of previously established SLE, simulating SLE exacerbation. In 6 observations, symptoms persisted several months after the viral infection. In 7 cases, the exact relationship between SLE and B19 could not be determined. CONCLUSIONS: B19 infection may present a clinical and serological tableau making it difficult to distinguish between a viral infection and the first episode of SLE. Although B19 may modulate the clinical and biological features of rheumatic disease, studies in large series do not support a causative role for B19 in the pathogenesis of SLE.     

Anasarca as the presenting manifestation of parvovirus B19 associated juvenile dermatomyositis

Anasarca as the presenting manifestation of juvenile dermatomyositis (JDMS) is extremely rare. We report a case of a 4-year-old boy who was initially managed for nephrotic syndrome in view of anasarca and mild hypoalbuminemia. Later, at presentation to our institute, a diagnosis of severe edematous JDMS was made in view of associated profound muscle weakness and characteristic skin changes. The child responded to aggressive immunosuppressive therapy. On further evaluation, he had evidence of acute parvovirus B19 infection. Our case illustrates anasarca as an uncommon severe manifestation of JDMS and the possible role of parvovirus B19 in the onset of this autoimmune disorder.     

MolecularphenotypesofhumanparvovirusB19inpatientswithmyocarditis Bock CT,Düchting A,Utta F,Brunner E,Sy BT,Klingel K,Lang F,Gawaz M,Felix SB,

AIM: To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy (DCM).METHODS: Endomyocardial biopsies (EMBs) from 498 B19V-positive patients with myocarditis and DCM were analyzed using molecular methods and functional experiments. EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers. Control tissues were obtained at autopsy from 34 victims of accidents, crime or suicide. Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining. Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction (PCR). For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism (RFLP)-PCR was established. B19V-genotyping was verified by direct DNA-sequencing and sequences were aligned using BLAST and BioEdit software. B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments. Transfection experiments were conducted using human endothelial cells 1. Luciferase reporter assays were performed to determine B19V-replication activity. Statistical analysis and graphical representation were calculated using SPSS and Prism5 software.RESULTS: The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy (iCMP) compared to uninflamed DCM (59.6% vs 35.3%) (P < 0.0001). The detection of B19V-mRNA replication intermediates proved that replication of B19V was present. RFLP-PCR assays showed that B19V-genotype 1 (57.4%) and B19V-genotype 2 (36.7%) were the most prevalent viral genotypes. B19V-genotype 2 was observed more frequently in EMBs with iCMP (65.0%) compared to DCM (35%) (P = 0.049). Although there was no significant difference in gender-specific B19V-loads, women were more frequently infected with B19V-genotype 2 (44.6%) than men (36.0%) (P = 0.0448). Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissue samples and was associated with higher B19V viral load compared to B19V-monoinfected tissue (P = 0.0012). The most frequent coinfecting virus was human herpes virus 6 (HHV6, 16.5%). B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs (P = 0.0033), suggesting that HHV6 had transactivated B19V. In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator.CONCLUSION: The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP. Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype.     

细小病毒B19感染与系统性红斑狼疮相关性研究

目的通过检测系统性红斑狼疮(SLE)患者血清中细小病毒B19(PVB19)特异性抗体,观察B19 IgM阳性与SLE病情及活动程度的相关性,探讨PVB19感染与SLE之间可能存在的联系。方法采用德国IBL Hamburg公司PVB19-VP2-IgM、IgG酶联免疫吸附试验(ELISA)检测试剂盒,检测51例SLE患者及20名正常人血清PVB19的特异性抗体。结果51例SLE患者中B19 IgM抗体阳性11例(22%)。而正常对照组都为阴性,差异有统计学意义(P＜0．01)。根据B19 IgM阳性/阴性对SLE患者分组后发现,B19 IgM阳性组SLE疾病活动评分(SLEDAI)显著高于阴性组(P＜0．05)；B19 IgM阳性组与阴性组临床特征相比,除丙氨酸转氨酶(ALT)或天冬氨酸转氨酶(AST)上升差异有统计学意义(P＜0．05)外,其余差异均无统计学意义(P＞0．05)。对5例B19 IgM阳性的SLE患者随访2年发现,这些患者临床症状显著改善,SLEDAI评分显著下降(P＜0．05),但自身抗体水平[抗核抗体(ANA)、抗双链DNA(dsDNA)]无显著性改变(P＞0．05),ALT或AST均恢复正常。结论PVB19感染在诱发SLE活动中起作用,但与SLE预后可能无关。     

Recent-onset myelodysplastic syndrome mimicking acute leukemia during infection

A previously healthy 74-year-old patient without a prior history of hematological disease presented with an acute respiratory infection. Peripheral pancytopenia led us to perform a bone marrow biopsy, and the diagnosis of undifferentiated acute myelogenous leukemia (AML, 61% blasts) was made. Following antibiotic treatment and resolution of the infection, the blast count in the bone marrow fell to 2%, leaving a clinicopathologic picture consistent with myelodysplastic syndrome (MDS, French-American-British type refractory anemia), and the patient survived for a total of 16.5 months following the initial presentation with cytokine support. A preterminal blast proliferation occurred during a bacterial ear infection and rapidly responded to a withdrawal of cytokine support, antibiotic therapy, and hydroxyurea. The patient succumbed ultimately to an apparent myocardial infarct. Clinicians should consider transient acceleration of MDS in their differential diagnosis when confronted with apparent AML and acute infection.     

Bone marrow necrosis and fat embolism syndrome in sickle cell disease: Increased susceptibility of patients with non-SS genotypes and a possible association with human parvovirus B19 infection

Fat embolism syndrome (FES) due to extensive bone marrow necrosis (BMN) in sickle cell disease (SCD) is a potentially under-diagnosed complication associated with severe morbidity and mortality. We identified 58 cases reported in the world literature to date. Typically, patients presented with a seemingly uncomplicated vaso-occlusive crisis (VOC) and subsequently deteriorated rapidly with a drop in their haemoglobin and platelets, development of respiratory failure, encephalopathy and varying degrees of involvement of other systems. Overall mortality in the reported cases was 64% but differed according to the use of transfusion and was 29%, 61% and 91% for patients receiving exchange, top-up or no transfusion respectively. Patients most at risk appear to be those with a “milder” form of SCD as 81% of patients had a genotype other than HbSS and the majority had no history of significant sickle-related complications. Human parvovirus B19 (HPV B19) infection was documented in 24% of cases.     

Acute parvovirus B19 infection mimicking juvenile myelomonocytic leukemia

An 11-month-old patient with parvovirus infection mimicking juvenile myelomonocytic leukemia (JMML) is presented. The patient's history, presenting physical and laboratory features, was suggestive of JMML and consisted of fever, hepatosplenomegaly, lymphadenopathy, desquamation of the skin, anemia, leukocytosis with monocytosis and trilineage dysplastic findings of the peripheral blood and bone marrow. However, positive IgM titers for parvovirus B19 followed by seroconversion, negative cytogenetics and the benign follow-up of the patient suggested acute parvovirus infection as an etiologic factor for development of dysplastic features in the patient, and thus is recommended for consideration in the differential diagnosis of MDS. Although parvovirus B19 infection mimicking MDS has previously been shown in two patients with spherocytosis and one with subclinical immune deficiency; to our knowledge, the present report is the first describing the association of acute parvovirus B19 infection with dysplastic features mimicking myelodysplasia (MDS) in a child without a demonstrable underlying hematolymphoid disorder.     

Multiple small pulmonary emboli associated with transient antiphospholipid syndrome in human Parvovirus B19 infection

Antiphospholipid antibodies (aPL) have been reported to occur in several conditions other than antiphospholipid syndrome, including infections. We herein report the case of a 21-year-old Japanese woman with Parvovirus B19 infection, who developed multiple pulmonary emboli associated with aPL, a lupus anticoagulant and IgM anticardiolipin antibody. Eight weeks later, antiphospholipid antibodies spontaneously disappeared and normal pulmonary flow was observed. Considering the high prevalence of Parvovirus B19 infection, we should be aware of thrombosis associated with transient aPL antibodies in this infectious disease.     

Outcome of patients with arthritis and parvovirus B19 DNA in synovial membranes

To investigate the follow-up of the 17 patients during the period of 1995–2001 of the outpatient Clinic for Rheumatology at the University Hospital of Zurich with arthritis and the presence of parvovirus B19 DNA demonstrated by PCR in synovial biopsies. Seventeen patients of 163 with arthritis, which were routinely examined by needle arthroscopy during 1995–2001 with a positive parvovirus B19 DNA by PCR of synovial biopsy were reevaluated. Investigations included medical history, clinical examination and blood tests. Joint fluid was taken on patients with joint effusion. The observation period of the 17 patients (F:M = 11:6) was 2–8 years (Ø = 6.5 years). In 8 of 17 patients the arthritis could not be classified neither at entry nor during the follow up of the study. The arthritis could be diagnosed in six patients early in the onset of the disease and included three cases of lyme arthritis of the knee joint, two cases with arthritis following a gastrointestinal infection (one with Salmonella typhimurium—positive faecal test—and the other one with a culture negative agent), one patient probably had an infection-associated arthritis after a gastrointestinal infection with Entamöeba histolytica (Schirmer et al. in Rheumatol Int 18:37–38, 1998; Kasliwal in Am J Proctol Gastroenterol Colon Rectal Surg 32:12, 16, 28, 1981; Haslock and Wright in J R Coll Phys Lond 8:1554–162, 1974; Than-Saw et al. in Trop Geogr Med 44:355–358, 1992) with remission after antibiotic therapy. After a disease course of 9 months one patient could be classified as rheumatoid arthritis in the presence of anti-cyclic citrullinated antibodies but lack of rheumatoid factor. One patient with polyarthritis developed psoriasis of the skin 22 months later. From the nine patients with unclassified arthritis 4 (45%) got into complete remission with no symptoms or signs of joint inflammation after a disease course of 9–45 months, whereas 5 (55%) still demonstrate active non erosive arthritis (disease duration between 3 and 10 years). The presence of parvovirus B19 DNA in synovial tissue of patients with joint inflammation does not allow the diagnosis of parvovirus induced arthritis. If the arthritis remains unclassified and without erosions over time a virus associated aetiology may be assumed. However, no definitive diagnosis is possible even in the presence of parvovirus B19 DNA in synovial tissue.     

Transient blood plasmacytosis in parvovirus B19 infection: a report of two cases

Two patients with sickle cell disease were diagnosed with aplastic crisis caused by acute parvovirus B19 infection. One patient also developed thrombocytopenia associated with hemophagocytic histiocytosis in the bone marrow biopsy. Both patients developed transient blood plasmacytosis and hypocomplementemia soon after admission to the hospital. Transient blood plasmacytosis may be an immunological response to acute parvovirus B19 infection.     

低增生型骨髓增生异常综合征的骨髓病理观察

目的：评估骨髓活检在骨髓增生异常综合征尤其是低增生型病例时的诊断价值。方法：对比分析５３例骨髓增生异常综合征的患者的骨髓涂片与切片的诊断结果。结果：骨髓活检病理检查对于诊断骨髓增生异常综合征,尤其在低增生型骨髓增生异常综合征患者有很大帮助。结论：骨髓活检是确诊低增生型骨髓增生异常综合征的必要手段。     

骨髓增生异常综合征骨髓细胞DNA倍体和增殖活性的研究

目的：探讨DNA倍体和增殖活性在骨髓增生异常综合征（MDS）的变化和意义。方法：用流式细胞仪（FCM）DNA单参数和DNA／膜抗原双参数法分析了41例MDS患者和10例良性血液病患者的骨髓细胞DNA倍体和增殖活性。结果：10例良性血液病无一例FMC0－DNA非整倍体检出,MDSFCM－DNA非整倍体检出,MDSFCM－DNA非整倍体检出率（63．4％）明显高于对照组,MDS骨髓细胞G0／G1期百分比明显高于对照组（P＜0．05）,S＋G2／M期百分比明显低于对照组（P＜0．05）,CD71^ ,CD15^ ,CD33^ ,HLA-DR^ 免疫标志阳性细胞多处于增殖期。结论：FCM－DNA非整倍体是MDS一个有用的诊断和预后指标,MDS造血细胞增殖分化异常。     

Pure red cell aplasia associated with parvovirus B19 infection occurring late after allogeneic bone marrow transplantation

Differential diagnosis for anemia late after allogeneic stem cell transplantation is broad. In this report, we describe a case of severe anemia secondary to pure red cell aplasia associated with human parvovirus B19 infection over 8 years after allogeneic bone marrow transplantation. Characteristics of parvovirus B19 infection and the immunosuppressed state after allogeneic stem cell transplantation are reviewed.