eMedicine Specialties > Pediatrics: General Medicine > Hematology

Transient Erythroblastopenia of Childhood

Lennox H Huang, MD, Associate Chair (Clinical), Assistant Professor, Department of Pediatrics, McMaster University School of Medicine; Interim Chief of Pediatrics, McMaster Children's Hospital
Carol Portwine, MD, PhD, FRCP, FAAP, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology, McMaster University; Robin Miller, MD, Assistant Professor, Department of Pediatrics, Rainbow Babies and Children's Hospital, Division of Hematology-Oncology, Case Western Reserve School of Medicine, University Hospitals of Cleveland

Updated: Sep 4, 2009

Introduction

Background

Transient erythroblastopenia of childhood (TEC) is a slowly developing anemia that occurs in early childhood and is characterized by a gradual onset of pallor. As the name suggests, all patients with transient erythroblastopenia of childhood recover completely without sequelae.

Pathophysiology

The etiology of transient erythroblastopenia of childhood is unknown. However, researchers have proposed numerous viral and immunologic mechanisms. At least 2 separate case reports have noted pure red cell aplasia with concomitant human parvovirus B19 infection.^1,2 However, a prospective case series of 10 patients failed to identify a single viral causative agent for transient erythroblastopenia of childhood.³

In vitro studies using serum and immunoglobulin G (IgG) from some patients with transient erythroblastopenia of childhood demonstrated erythroid colony suppression, suggesting an immunologic etiology. Transient erythroblastopenia of childhood is not caused by a lack of erythropoietin. Bone marrow from patients with transient erythroblastopenia of childhood exhibits an absence of red cell precursors.

A recent case report of half siblings with transient erythroblastopenia of childhood and the accompanying literature review suggests that predisposition to transient erythroblastopenia of childhood may be autosomal dominant in nature.⁴

Frequency

United States

Attempts to determine frequency of transient erythroblastopenia of childhood are limited by an unknown number of asymptomatic undiagnosed cases.

Mortality/Morbidity

Morbidity relates to the severity of the anemia and diagnostic workup. Children with transient erythroblastopenia of childhood have reportedly presented with high-output shock secondary to profound anemia.⁵  Patients with atypical transient erythroblastopenia of childhood may require invasive tests such as bone marrow aspiration or biopsy. Association of transient neurologic deficits may lead the physician to pursue CNS imaging studies or a neurologic consultation.

Sex

The male-to-female ratio is 1.4:1.

Age

The median age of presentation is 18-26 months; however, the disorder may occur in infants younger than 6 months and in children as old as 10 years. In contrast, Diamond-Blackfan anemia tends to present in child younger than 1 year, whereas human parvovirus B19–associated erythroblastopenia typically presents at an older age.

Clinical

History

• Most individuals with transient erythroblastopenia of childhood (TEC) present with gradually increasing pallor and no other symptoms despite the severity of the anemia. 
• Occasionally, parents report increased fatigue or decreased energy levels in children with transient erythroblastopenia of childhood. 
• Some isolated incidents of transient neurologic events and breath-holding spells have been reported in association with transient erythroblastopenia of childhood. 
• Other differential considerations (eg, aplastic crises, hyperhemolytic crises, sequestrations) typically present more acutely than transient erythroblastopenia of childhood. Fatigue and pallor develop over the course of days and are often associated with nonspecific viral symptoms, such as fever, malaise, lethargy, abdominal pain, or upper respiratory symptoms. Jaundice may also be a presenting symptom, especially in the context of a preexisting hemoglobinopathy such as sickle cell disease or hereditary spherocytosis.
• Family history may reveal siblings with a history of anemia.

Physical

• Upon physical examination, patients are usually healthy except for findings commonly associated with anemia, such as skin and mucosal pallor, tachycardia, and, often, a cardiac flow murmur. 
• By contrast, the most common congenital anomalies associated with Diamond-Blackfan anemia include short stature, low birth weight, developmental delay, thumb malformations, craniofacial anomalies, and urogenital abnormalities. Examining for physical anomalies is important because they are found in as many as 70% of patients with Diamond-Blackfan anemia. 
• A complete neurologic examination is necessary because of case-report associations.
• In patients with symptoms such as splenomegaly and icterus, consider other diagnoses such as a hemolytic-associated anemia or sequestration-associated anemia. A characteristic "slapped cheek" rash is often associated with parvovirus B19 infection and aplastic anemia.

Causes

• The cause of transient erythroblastopenia of childhood is unknown. Viral and immunologic mechanisms may be involved.
• Reports of seasonal clusters of incidents of transient erythroblastopenia of childhood, although suggestive of a viral etiology, are not statistically significant.
• Only a handful of familial transient erythroblastopenia of childhood cases have been reported, and no apparent genetic link has been elucidated.

Differential Diagnoses

Acute Lymphoblastic Leukemia
Anemia of Prematurity
Anemia, Acute
Anemia, Chronic
Parvovirus B19 Infection

Other Problems to Be Considered

Diamond-Blackfan anemia⁶
Aplastic anemia
Drug-induced anemia
Leukemia
Hemolytic anemia: A person recovering from transient erythroblastopenia of childhood (TEC) may be confused with an individual with hemolytic anemia because, during the early recovery phase, the reticulocyte count may be elevated with a low hemoglobin level.

Workup

Laboratory Studies

The following studies are indicated in patients with suspected transient erythroblastopenia of childhood (TEC):

• CBC count
  • CBC count results demonstrate a normochromic normocytic anemia, with a red cell morphology within the reference range on the peripheral smear.
  • Mean corpuscular volume (MCV) is usually within the reference range; however, MCV may be elevated if the patient has begun to recover and has reticulocytosis.
• Hemoglobin studies
  • The hemoglobin level is usually 5-7 g/dL but may be as low as 2 g/dL.
  • Transient erythroblastopenia of childhood is frequently accompanied by clinically insignificant neutropenia that spontaneously resolves with the onset of reticulocytosis. Some series report the incidence of associated neutropenia to be as much as 64%. 
  • In contrast, Diamond-Blackfan anemia is characterized by fetal-like hematopoiesis with an increased fetal hemoglobin, I antigen, and MCV.
• Viral studies: A search for a viral etiology, such as cytomegalovirus, Epstein-Barr virus, and parvoviral immunoglobulin (Ig)G and immunoglobulin M, may be useful.
• Reticulocyte count: Initial reticulocyte count is less than 0.1%, and a spontaneous increase heralds the recovery phase.
• Iron studies: Iron studies are not indicated unless microcytosis is present. Serum iron levels may be elevated because of underuse.

Imaging Studies

• In individuals with suspected Diamond-Blackfan anemia, imaging studies may be helpful in revealing occult malformations; however, they are unnecessary for the diagnosis or treatment of transient erythroblastopenia of childhood.

Other Tests

• Bone marrow aspiration
  • Consider bone marrow studies when clinical history, physical findings, or CBC count is inconsistent with classic transient erythroblastopenia of childhood.
  • In patients with transient erythroblastopenia of childhood, findings include decreased or absent RBC precursors.
  • Evidence of marrow recovery precedes a rapid rise in hemoglobin levels; thus, bone marrow studies may help determine if a patient with transient erythroblastopenia of childhood who is severely anemic is likely to recover before requiring a blood transfusion.
    
  • In vitro studies have suggested that bone marrow cultures may have a future role in determining potential responsiveness of RBC aplasia to immunosuppressive therapy. In patients with classic presentations of transient erythroblastopenia of childhood, bone marrow cultures and immunosuppressive agents do not currently play a role.
• Enzyme levels: Red cell adenosine deaminase levels have been used to differentiate Diamond-Blackfan anemia from transient erythroblastopenia of childhood and other anemias. Enzyme levels are typically elevated in Diamond-Blackfan anemia, whereas levels found in persons with transient erythroblastopenia of childhood are normal or depressed.

Treatment

Medical Care

• Packed red cell transfusions are required in patients with severe transient erythroblastopenia of childhood (TEC) when signs of clinical decompensation are evident. Conditions in which transfusion may be necessary include hemodynamic instability, exercise intolerance, or altered mental status. 
• Refractory incidents of transient erythroblastopenia of childhood may be associated with a failure to thrive and also may require packed red cell transfusion. 
• Perform nonemergent transfusions in consultation with a pediatric hematologist.

Consultations

• Consultation with a pediatric hematologist is recommended in nonclassic presentations of transient erythroblastopenia of childhood or if the patient with transient erythroblastopenia of childhood has severe anemia that requires transfusion.

Diet

• No special dietary requirements are necessary.

Medication

• Treatment with corticosteroids and erythropoietin is unnecessary. Difficulty in distinguishing Diamond-Blackfan anemia (a corticosteroid-responsive condition) from transient erythroblastopenia of childhood (TEC) has led to corticosteroid treatment and subsequent resolution in some individuals with transient erythroblastopenia of childhood.
• Whether these isolated reports are true incidents of corticosteroid-responsive transient erythroblastopenia of childhood or whether the anemia can resolve independently of corticosteroid treatment is unclear.

Follow-up

Further Outpatient Care

• Until resolution of anemia, advise patients with transient erythroblastopenia of childhood (TEC) to undergo regular follow-up care with CBC count.

Prognosis

• All patients with transient erythroblastopenia of childhood completely recover, usually within 1-2 months. Occasionally, spontaneous recovery may occur as long as 12 months after onset.

Miscellaneous

Medicolegal Pitfalls

• Follow-up care is crucial. Failure to document improvement in the patient's anemia can result in failure to diagnose malignancy or cardiovascular collapse secondary to the anemia.
• Nonclassic presentations, such as sudden onset, atypical age, or cardiovascular insufficiency, should warrant a more thorough workup that may include a bone marrow aspiration or biopsy.

References

1. Prassouli A, Papadakis V, Tsakris A, et al. Classic transient erythroblastopenia of childhood with human parvovirus B19 genome detection in the blood and bone marrow. J Pediatr Hematol Oncol. Jun 2005;27(6):333-6. [Medline].

2. Geetha D, Zachary JB, Baldado HM, et al. Pure red cell aplasia caused by Parvovirus B19 infection in solid organ transplant recipients: a case report and review of literature. Clin Transplant. Dec 2000;14(6):586-91. [Medline].

3. Skeppner G, Kreuger A, Elinder G. Transient erythroblastopenia of childhood: prospective study of 10patients with special reference to viral infections. J Pediatr Hematol Oncol. May 2002;24(4):294-8. [Medline].

4. Shaw J, Meeder R. Transient erythroblastopenia of childhood in siblings: case report and review of the literature. J Pediatr Hematol Oncol. Sep 2007;29(9):659-60. [Medline].

5. Chabali R. Transient erythroblastopenia of childhood presenting with shock and metabolic acidosis. Pediatr Emerg Care. Oct 1994;10(5):278-80. [Medline].

6. Martinez Barrio A, Eriksson O, Badhai J, et al. Targeted resequencing and analysis of the Diamond-Blackfan anemia disease locus RPS19. PLoS One. Jul 9 2009;4(7):e6172. [Medline].

7. Chan GC, Kanwar VS, Wilimas J. Transient erythroblastopenia of childhood associated with transient neurologic deficit: report of a case and review of the literature. J Paediatr Child Health. Jun 1998;34(3):299-301. [Medline].

8. Cherrick I, Karayalcin G, Lanzkowsky P. Transient erythroblastopenia of childhood. Prospective study of fifty patients. Am J Pediatr Hematol Oncol. Nov 1994;16(4):320-4. [Medline].

9. Freedman MH. 'Recurrent' erythroblastopenia of childhood. An IgM-mediated RBC aplasia. Am J Dis Child. May 1983;137(5):458-60. [Medline].

10. Gussetis ES, Peristeri J, Kitra V, et al. Clinical value of bone marrow cultures in childhood pure red cell aplasia. J Pediatr Hematol Oncol. Mar-Apr 1998;20(2):120-4. [Medline].

11. Gustavsson P, Klar J, Matsson H, et al. Familial transient erythroblastopenia of childhood is associated with thechromosome 19q13.2 region but not caused by mutations in coding sequencesof the ribosomal protein S19 (RPS19) gene. Br J Haematol. Oct 2002;119(1):261-4. [Medline].

12. Krijanovski OI, Sieff CA. Diamond-Blackfan anemia. Hematol Oncol Clin North Am. Dec 1997;11(6):1061-77. [Medline].

13. Miller R, Berman B. Transient erythroblastopenia of childhood in infants < 6 months of age. Am J Pediatr Hematol Oncol. Aug 1994;16(3):246-8. [Medline].

14. Mupanomunda OK, Alter BP. Transient erythroblastopenia of childhood (TEC) presenting as leukoerythroblastic anemia. J Pediatr Hematol Oncol. Mar-Apr 1997;19(2):165-7. [Medline].

15. Tam DA, Rash FC. Breath-holding spells in a patient with transient erythroblastopenia of childhood. J Pediatr. Apr 1997;130(4):651-3. [Medline].

16. Walters MC, Abelson HT. Interpretation of the complete blood count. Pediatr Clin North Am. Jun 1996;43(3):599-622. [Medline].

Keywords

transient erythroblastopenia of childhood, TEC, anemia, pallor, pure red cell aplasia, human parvovirus B19, Diamond-Blackfan anemia, aplastic crises, hyperhemolytic crises, hemoglobinopathy, sickle cell disease, hereditary spherocytosis, splenomegaly, icterus, hemolytic-associated anemia, sequestration-associated anemia, aplastic anemia

Contributor Information and Disclosures

Author

Lennox H Huang, MD, Associate Chair (Clinical), Assistant Professor, Department of Pediatrics, McMaster University School of Medicine; Interim Chief of Pediatrics, McMaster Children's Hospital
Lennox H Huang, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Physician Executives, Canadian Medical Association, Ontario Medical Association, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Carol Portwine, MD, PhD, FRCP, FAAP, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology, McMaster University
Carol Portwine, MD, PhD, FRCP, FAAP is a member of the following medical societies: American Academy of Pediatrics, Canadian Medical Association, Canadian Paediatric Society, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Robin Miller, MD, Assistant Professor, Department of Pediatrics, Rainbow Babies and Children's Hospital, Division of Hematology-Oncology, Case Western Reserve School of Medicine, University Hospitals of Cleveland
Disclosure: Nothing to disclose.

Medical Editor

Sharada A Sarnaik, MBBS, Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan
Sharada A Sarnaik, MBBS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

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