{"doi":"10.1002/pbc.31252","title":"The ghost of parvovirus past: Idiopathic pure red cell aplasia responding to IVIG following resolved perinatal parvovirus B19 infection","abstract":"To the Editor: Pure red cell aplasia (PRCA) is characterized by anemia in the setting of reticulocytopenia and markedly decreased or absent erythroid precursors in the bone marrow. Congenital PRCA is most commonly associated with Diamond–Blackfan anemia (DBA) syndrome secondary to germline ribosomal protein (RP), GATA1, or TSR2 mutations, though mutations in ADA2 and EPO have also been implicated.1-5 In comparison, acquired PRCA can be classified as either primary (idiopathic) or secondary to drugs, autoimmunity, lymphoproliferative disorders (chronic lymphocytic leukemia, large granular lymphocytic leukemia), solid tumors (thymoma), anti-erythropoietin (EPO) antibodies, or infections.6-8 The most notable viral-induced etiology of PRCA is human parvovirus B19 (B19), a highly contagious single-stranded DNA virus that is toxic to erythroid precursors and classically associated with PRCA in immunocompromised hosts.8, 9 B19 can cause transient aplastic crisis in individuals with chronic hemolysis and nonimmune hydrops fetalis when maternally transmitted to a fetus.9-11 We report an unusual case of a 5-year-old female with no syndromic features and unremarkable family history who developed recurrent transfusion-dependent anemia. The patient was born prematurely at 29 weeks gestation, presenting with nonimmune hydrops fetalis and severe anemia (hemoglobin 6.9 g/dL), secondary to maternal transmission of B19 (positive maternal B19 qualitative polymerase chain reaction [PCR] and serology [IgM 3.9 intravenously (IV), IgG 5.2 IV]). During the first 12 weeks of life, she was treated with exchange and packed red blood cell (PRBC) transfusions only. At discharge, her hemoglobin was 14.2 g/dL with a reticulocyte percentage of 1.4%, 5 days after last PRBC transfusion. Two months later, she presented with profound anemia in the setting of continued B19 infection (hemoglobin 3.3 g/dL, absolute reticulocyte count [ARC] 0.008 × 106/mm3 [0.9%], quantitative B19 PCR >100 million DNA copies/mL, IgM 5.15 IV, IgG 0.34 IV). She received intravenous immunoglobulin (IVIG) 2 g/kg in addition to four PRBC transfusions, and was discharged with a hemoglobin of 13.1 g/dL and ARC of 0.026 × 106/mm3 (0.6%). During follow-up evaluations, quantitative B19 PCR gradually decreased over 9 months until it was undetectable, coinciding with seroconversion to negative B19 IgM and positive B19 IgG. She remained asymptomatic with normal growth and development for greater than 4 years, when without evident triggers she developed chronic anemia requiring PRBC transfusions every 3−4 weeks (hemoglobin nadir 6.5–7.5 g/dL, ARC 0.010–0.015 × 106/mm3 [∼0.2%–0.5%]), except for an 8-week period without transfusion after a single dose of IVIG 1 g/kg (Figure 1). Bone marrow evaluations during transfusion-dependence revealed loss of erythroid precursors consistent with PRCA (Figure 2A,B) without dysplasia, increased blasts, or giant proerythroblasts characteristic of B19 infection.10 Complete B19 eradication was further supported by negative PCR on both bone marrow and peripheral blood and repeat serology consistent with past infection (IgM negative, IgG positive), therefore IVIG therapy was not continued. Whole genome sequencing-based VirusScan12 did not detect viral sequences from B19, CMV, EBV, HHV-6, HHV-7, HPV, HBV, or TTV. EPO was appropriately elevated at 1433 mU/mL. There was no evidence of hemolysis (total bilirubin 0.7 mg/dL, lactate dehydrogenase [LDH] 230 U/L, haptoglobin 244 mg/dL), autoimmune disease (negative DAT, ANA, ALPS panel, and complement testing), or immunodeficiency (normal lymphocyte subsets and immunoglobulins). Genetic testing for congenital PRCA (RP genes associated with DBA as well as ADA2 and EPO)5 and red cell enzymopathies was negative. Chromosome microarray was normal and whole genome sequencing (performed under the INSIGHT-HD protocol, ClinicalTrials.gov: NCT02720679) failed to identify any pathogenic variants for hematologic disease or immunodeficie","journal":"Pediatric Blood & Cancer","year":2024,"id":483644,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.959,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1019131,"name":"Kacie Sims","orcid":null,"position":1,"is_corresponding":false},{"id":719460,"name":"Sara Lewis","orcid":"0000-0003-0364-375X","position":2,"is_corresponding":false},{"id":253325,"name":"Shaohua Lei","orcid":null,"position":3,"is_corresponding":false},{"id":1324692,"name":"Nidhi Bhatt","orcid":"0000-0002-2454-8092","position":4,"is_corresponding":false},{"id":1307372,"name":"Gabriela Gheorghe","orcid":"0000-0002-4579-8699","position":5,"is_corresponding":false},{"id":1156641,"name":"Clifford M. Takemoto","orcid":"0000-0002-2832-6884","position":6,"is_corresponding":false},{"id":653876,"name":"Marcin W. Włodarski","orcid":"0000-0001-6638-9643","position":7,"is_corresponding":false},{"id":1324691,"name":"Nathan Gray","orcid":"0009-0000-8030-9670","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-19T02:07:33.718973Z","pmid":"39129170","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}