Journals | Policy | Permission

This journal has moved to cii.elmerpub.com Please go to the new site to make submissions

Clinical Infection & Immunity

Case Report

Volume 5, Number 1, March 2020, pages 1-3

Human Parvovirus B19 Infection Induced Severe Aplastic Anemia in an Immunocompetent Adult Without Hematological Disease

The human parvovirus B19 belongs to the genus Erythroparvovirus and presents with a wide spectrum of clinical findings in immunocompetent patients. Most cases of this infection are asymptomatic or present with flu-like symptoms. There are two classic syndromes associated with the parvovirus B19 infection. In children, it manifests mainly as erythema infectiosum (fifth disease), while joint symptoms are the most common manifestations in adults (particularly women). However, both syndromes may be seen in both children and adults [1].

The parvovirus B19 infection has also been associated with fetal death [2], glomerulopathies [3], acute hepatitis [4], rheumatoid arthritis, type 1 diabetes mellitus and idiopathic thrombocytopenic purpura [5, 6] and necrotizing vasculitis disorders [7].

On the other hand, parvovirus B19 is associated with some hematological complications. In the immunocompromised patients, it frequently leads to pure red-cell aplasia, resulting in chronic or recurrent anemia with reticulocytopenia [8]. In patients with chronic hemolytic anemias, transient aplastic anemia is a common finding [9].

Two cases were reported before with severe aplastic anemia due to acute parvovirus B19 infection in individuals without the underlying disease [10, 11].

In this article, we report the 3rd case of parvovirus B19 induced aplastic anemia in an immunocompetent and hematologically normal adult patient. Besides it is a very rare entity, we are emphasizing the importance of considering parvovirus B19 of one of the causes of the sudden and severe aplastic anemia in such patients.

A 28-year-old woman, mother of two school age kids, presented with generalized body weakness, arthralgia and myalgia of 3 days duration. On physical examination, she had fever (38.4 °C) and conjunctival pallor, without icteric sclera, and the rest was unremarkable.

Laboratory results showed white blood cells of 1,200/µL, hemoglobin (Hb) of 9 g/dL, platelets of 142,000/µL and mean corpuscular volume of 80.4 fL. Vitamin B12 level, Folate and Iron studies were within the normal range. The Hemoglobin electrophoresis test was negative. Serum viral panel was positive for parvovirus B19 immunoglobulin M (IgM) that confirmed with a polymerase chain reaction test. Serology was negative for influenza A/B and human immunodeficiency virus (HIV). Urinalysis was negative. Blood and urine cultures were negative. The chest X-ray was normal. Bone marrow core and aspiration was done; the flow cytometry showed no immunophenotypic evidence of hematolymphoid neoplasm, the morphology showed hypocellular bone marrow with maturation arrest at the proerythroblast stage with intranuclear inclusions and no blast, immunohistochemistry showed normal cell percentage distribution (blast 2%), and lastly the immunohistochemistry for parvovirus B19 virus was positive for scattered virus cell (Figs. 1-3)

Click for large image

Figure 1. CD71 highlights few scattered erythroid precursors (red arrow).

Click for large image

Figure 2. Hypocellular bone marrow.

Click for large image

Figure 3. Aspirate shows a giant proerythroblast with an intranuclear inclusion (red arrow).

The patient was admitted to the hospital for 4 days, one dose of granulocyte-colony stimulating factor was given, and the patient was monitored very closely.

The patient condition improved and then discharged with an outpatient follow-up visiting schedule. After 1 month, the patient was seen in the hospital clinic and was free from any complaints and the complete blood count improved significantly.

Aplastic anemia refers to the syndrome of hematopoietic failure from injury leading to diminished or absent hematopoietic precursors in the bone marrow and pancytopenia [12]. It may occur suddenly, or it can occur slowly and get worse over long time. The etiologies that have been implicated are drugs, irradiation and preceding viral infections such as non-A, non-B, non-C hepatitis, Epstein-Barr virus, cytomegalovirus, HIV and rubella. Two cases of severe aplastic anemia due to acute parvovirus B19 infection in individuals without the underlying disease have also been reported [10, 11], so in here, we report the third case of aplastic anemia caused by parvovirus B19 infection in a patient with no hemoglobinopathies or immunosuppression diseases.

The only known host cell of parvovirus B19 is the human erythroid progenitor cell. The virus has a recognized tropism for erythroblasts (red blood cell precursors) which directly translates into reticulocytopenia in peripheral blood. This pathogen has an affinity for erythroid progenitor cell lines by binding to the surface glycoprotein Gb4 erythroblasts (VP2). In contrast, granulocytopenia and thrombocytopenia, which can occur with acute parvovirus B19 infection, are also probably a result of the cytotoxic effect of the NS1 protein of the virus [8]. The NS1 protein causes cell death by lysis or apoptosis. The second hypothesis is based on the immunological damage to the individual cell lines in the bone by the action of cytokines induced by the infection. The result of this mechanism could be the onset of hemophagocytic syndrome, pancytopenia with marrow hypoplasia and aplasia. Achieving remission after use of immunosuppressive therapy may confirm this mechanism [11, 13-15].

Diagnosis of parvovirus is usually based on the clinical recognition of the typical presentation. In rare circumstances, laboratory confirmation is necessary. Specific laboratory diagnosis depends on identification of parvovirus B19 antibodies, viral antigens, or viral DNA. In the immunologically competent patient, determination of anti-B19 IgM is the best marker of recent or acute infection on a single serum sample. IgM antibodies develop rapidly after infection and are detectable for as long as 6 - 8 weeks. Specific IgG antibodies become detectable a few days after. Patients with B19-induced aplastic crisis may present before antibodies are detectable; however, IgM will be detectable within 1 - 2 days of presentation, and IgG will follow within days. Histologic examination is also helpful in diagnosing B19 infection in certain situations. Examination of bone marrow aspirates in anemic patients typically reveals giant pronormoblasts or “lantern cells” against a background of general erythroid hypoplasia. However, the absence of such cells does not exclude parvovirus B19 infection. Electron microscopy has proved useful and may reveal viral particles in the serum of some infected patients and cord blood or tissues of hydropic infants [13].

Specific antiviral therapy is not available to treat parvovirus B19 infection. The treatment approach of infection depends on host factors such as immune status, underlying conditions and manifestations of infection. Most cases of infection in immunocompetent hosts do not need treatment, because the symptoms are self-limiting. However, patients with the transient aplastic crisis may need supportive therapy with blood transfusions until neutralizing antibody response can clear the virus and hematopoiesis is restored. Also, the patient needs to be followed up in outpatient setting closely to make sure there is full recovery and treat the chronic anemia if happened [16].

Severe acute aplastic anemia should be considered as one of the complications of parvovirus B19 infection in an immunocompetent and hematological free disease adult patient. Patients with this presentation may need supportive therapy until hematopoiesis restores and regular follow-up checking for chronic anemia development and treat it accordingly.

Acknowledgments

None to declare.

Financial Disclosure

None to declare.

Conflict of Interest

The authors report no conflict of interest.

Informed Consent

Not applicable.

Author Contributions

HA collected the data, guided the literature search and wrote the manuscript, and is the article guarantor. RA, JA, JC and AM helped with data collection and writing the article. JN reviewed and supervised the study.

1. Moore TL. Parvovirus-associated arthritis. Curr Opin Rheumatol. 2000;12(4):289-294.
   doi pubmed
2. Syridou G, Skevaki C, Kafetzis DA. Intrauterine infection with parvovirus B19 and CMV: implications in early and late gestation fetal demise. Expert Rev Anti Infect Ther. 2005;3(4):651-661.
   doi pubmed
3. Waldman M, Kopp JB. Parvovirus B19 and the kidney. Clin J Am Soc Nephrol. 2007;3(Suppl 1):S47-56.
   doi pubmed
4. Furukawa M, Kaji K, Masuda H, Ozaki K, Asada S, Koizumi A, Kubo T, et al. Severe aplastic anemia following parvovirus B19-associated acute hepatitis. Case Reports Hepatol. 2017;2017:1359486.
   doi pubmed
5. Kerr JR. The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease. J Clin Pathol. 2016;69(4):279-291.
   doi pubmed
6. Patti G, Raju YS, Reddy SD. A case of human parvo virus B 19 infection with erythroid hypoplasia and Idiopathic thrombocytopenic purpura in an immunocompetent child: a case report. Int J Res Med Sci. 2016;5(1):346-349.
   doi
7. Durst R, Goldschmidt N, Ben Yehuda A. Parvovirus B19 infection associated with myelosuppression and cutaneous polyarteritis nodosa. Rheumatology (Oxford). 2002;41(10):1210-1212.
   doi pubmed
8. Srivastava A, Bruno E, Briddell R, Cooper R, Srivastava C, van Besien K, Hoffman R. Parvovirus B19-induced perturbation of human megakaryocytopoiesis in vitro. Blood. 1990;76(10):1997-2004.
   doi pubmed
9. Kobayashi Y, Hatta Y, Ishiwatari Y, Kanno H, Takei M. Human parvovirus B19-induced aplastic crisis in an adult patient with hereditary spherocytosis: a case report and review of the literature. BMC Res Notes. 2014;7:137.
   doi pubmed
10. Osaki M, Matsubara K, Iwasaki T, Kurata T, Nigami H, Harigaya H, Baba K. Severe aplastic anemia associated with human parvovirus B19 infection in a patient without underlying disease. Ann Hematol. 1999;78(2):83-86.
    doi pubmed
11. Rajput R, Sehgal A, Jain D, Sen R, Gupta A. Acute parvovirus b19 infection leading to severe aplastic anemia in a previously healthy adult female. Indian J Hematol Blood Transfus. 2012;28(2):123-126.
    doi pubmed
12. Moore CA, Krishnan K. Aplastic Anemia. In: StatPearls. Treasure Island (FL), 2019.
13. Adler SP, Koch WC. Human parvovirus infections. Infectious diseases of the fetus and newborn infant. (Sixth Edition) 2006; p. 867-892.
    doi
14. Macri A, Crane JS. Parvoviruses. In: StatPearls. Treasure Island (FL), 2019.
15. Pawelec K, Zdziechowicz I, Siwicka A, Matysiak M. Parvovirus B19 as a cause of transient aplastic anemia - case report. Post N Med. 2016:581-583.
16. Rogo LD, Mokhtari-Azad T, Kabir MH, Rezaei F. Human parvovirus B19: a review. Acta Virol. 2014;58(3):199-213.
    doi pubmed

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Clinical Infection and Immunity is published by Elmer Press Inc.