Transient Erythroblastopenia of Childhood (TEC)

Case

An otherwise well 18-month old male is noted on a screening CBC to have a normocytic anemia with Hb 7 g/dL and MCV 85, normal WBC and platelets.  His reticulocyte count is <1%.   

 

Background

Transient erythroblastopenia of childhood is an acquired and self-limited pure red cell aplasia first described in 1970. It is the most common cause of decreased RBC production in the pediatric population, and typically presents as a normocytic anemia with reticulocytopenia in an otherwise asymptomatic and normal child with no evidence of other causes for anemia including blood loss, hemolysis, nutritional deficiency or malignancy.

 

Epidemiology

Although it has been diagnosed in children as young as 1 month old, it usually presents in children  6 months – 6 years old, particularly between the ages of 1 and 4 years. It is more common in males than in females. The incidence of TEC is difficult to estimate since it is likely that most cases are subclinical, but it is a relatively uncommon diagnosis, with estimates of incidence ranging from 5/100,000 to 5/1,000,000.

 

Etiology

The etiology for suppression of erythropoesis in TEC remains unknown, although contributions from environmental exposures, viral illness, and genetic predisposition have been proposed. While parvovirus B19 is known to cause red cell aplasia in children with hemolytic anemia, no association has been found with TEC in multiple studies. However, multiple case series have suggested that there is an association with an antecedent viral URI or gastroenteritis 2-3 months prior to symptom onset, although there is no seasonal clustering.  There has also been one study investigating genetic markers that segregate with TEC in a small group of families in which multiple members were affected, which identified a chromosomal marker that co-segregated with TEC.  No specific mutation or affected gene was identified, and it is unclear whether this finding is relevant to sporadic TEC, which comprises the majority of cases.

 

Clinical presentation

Due to the gradual onset of the anemia, patients are often asymptomatic and the anemia is detected incidentally, but the degree of anemia can be significant enough to cause symptoms such as fatigue, tiredness, and shortness of breath, as well as the finding of pallor on exam.

  • Findings on CBC:
    • ​Normocytic anemia
      • During the recovery phase, RBCs become transiently macrocytic
    • ​Reticulocytopenia (<3%)
    • Normal WBC
      • ​ Mild neutropenia (average ANC 1.9 ± 1.2 in one case series) in 20-50%
    • ​Normal platelets

 

Differential Diagnosis

The differential diagnosis for anemia due to reduced RBC production (normocytic anemia with reticulocytopenia and without pancytopenia) in children:

  • Congenital pure red cell aplasia: Diamond-Blackfan Anemia (DBA) - click here to learn more about DBA
  • Acquired pure red cell aplasia:
    • ​TEC
    • Infectious (parvovirus, hepatitides, EBV, HIV, HHV6, echovirus)
    • Less common in children than adults:
      • ​Drug associated (AEDs, sulfonamides, isoniazid, azathioprine, procainamide)
      • Rheumatologic (SLE, JIA)
      • Autoimmune
      • Thymoma, lymphoid malignancies
    • Causes of aplastic anemia and pancytopenia must also be considered, as the involvement of multiple cell lines may not yet reflected in an initial CBC.

The most common diagnosis in an otherwise healthy child is TEC and in the setting of chronic hemolytic anemia is parvovirus B16, however the must not miss diagnosis when considering TEC is DBA, especially in children <1 year old.

 

Diamond-Blackfan Anemia and Transient Erythroblastopenia of Childhood.

 

DBA

TEC

Age at diagnosis

<1 year old (90%)

>1 year (80%)

Stature

Short

Normal

Abnormal physical exam findings

Congenital anomalies (20-50%)

-       microcephaly

-       micrognathia

-       hypertelorism

-       epicanthal folds

-       abnormal thumbs

None

Hemoglobin

1.5-10 g/dL

2.2-12.5 g/dL

MCV increased

Throughout course (100%)

During recovery phase only (90%)

Leukopenia or neutropenia

5%

20-50%

Elevated HbF fraction*

-       diagnosis

-       recovery

-       remission

 

100%

100%

85%

 

25%

100%

0%

RBC adenosine deaminase activity

Elevated

Normal

RBC i antigen*

Present

Absent

Adapted from Segel et al 2002

 

Diagnosis

On history, symptoms or personal or family history consistent with congenital hemolytic anemia, drug exposures, recent infectious illnesses and rheumatologic disorders should be assessed.  On exam, a particular focus should be on discerning whether congenital anomalies concerning for DBA are present.  

 

Initial work-up should include repeat CBC with RBC indices, reticulocyte count, differential and smear. RBC i antigen, hemoglobin electrophoresis, and RBC adenosine deaminase (eADA) activity should also be sent to help discriminate between DBA and TEC, particularly in children <1 year old. If there is no concern for hemolysis, and no congenital anomalies on exam, no macrocytosis, no elevated HbF, eADA or i antigen, the presumptive diagnosis of TEC can be made. However, it should be noted that while the absence of elevated HbF, eADA, and i antigen (characteristics of fetal RBCs), strongly supports a diagnosis of TEC over DBA, their presence can be non-pathologic in the first year of life, as well as during the recovery phase of TEC even in older children, and thus does not rule TEC out. If there is significant concern for DBA in such a scenario, diagnostic strategies that can be employed include trending of MCV (since TEC is only macrocytic during the recovery phase while DBA is persistently macrocytic) and testing for genetic mutations found in DBA.

 

The diagnosis of TEC can be confirmed with bone marrow biopsy showing isolated erythroblastopenia in an otherwise normal background, but is not necessary unless there is a concern for acute leukemia.

 

Clinical course and treatment

The anemia of TEC typically resolves spontaneously 1-2 months from presentation, and steroids have not been shown to alter the course of the disease.  Some children may require a transfusion if they are severely symptomatic from the anemia, but if they require more than one the diagnosis should be reconsidered. Recurrence is very rare.

 

References

1.     Segel GB, Hirsh MG, Feig SA. Managing anemia in a pediatric office practice:

Part 2. Pediatr Rev. 2002 Apr;23(4):111-22. Review. PubMed PMID: 11927743.

2.     Oski FA. Transient Erythroblastopenia. Pediatr Rev 1982; 4:25.

3.     van den Akker M, Dror Y, Odame I. Transient erythroblastopenia of childhood is

an underdiagnosed and self-limiting disease. Acta Paediatr. 2014

Jul;103(7):e288-94. doi: 10.1111/apa.12634. Epub 2014 Apr 29. PubMed PMID:

24635829.

4.     Cherrick I, Karayalcin G, Lanzkowsky P. Transient erythroblastopenia of

childhood. Prospective study of fifty patients. Am J Pediatr Hematol Oncol. 1994

Nov;16(4):320-4. Review. PubMed PMID: 7978049.

5.     Segel GB. Anemia. Pediatr Rev. 1988 Sep;10(3):77-88. Review. PubMed PMID:

3064057.

6.     Perkins SL. Pediatric red cell disorders and pure red cell aplasia. Am J Clin

Pathol. 2004 Dec;122 Suppl:S70-86. Review. PubMed PMID: 15690644.