Basics
Description
An acquired, self-limited suppression of red cell production in an otherwise healthy child
Epidemiology
- Mean age at diagnosis is 26 months.
- <10% are >3 years of age at diagnosis.
- Slight male predominance (male/female 5.1:3.1)
- No seasonal predominance
Risk Factors
Genetics
- There is no simple genetic pattern.
- Familial transient erythroblastopenia of childhood has been reported (rarely), suggesting a combination of environmental factors and genetic propensity.
General Prevention
There is no known way to prevent transient erythroblastopenia of childhood.
Etiology
- Unknown
- Possible viral causes include parvovirus B19 and human herpesvirus 6 (HHV-6), but this remains hypothetical.
- A serum inhibitor, such as an IgG directed at the committed erythroid stem cell progenitor, has also been proposed but not yet proven.
Diagnosis
History
- Pallor
- Typically slow in onset and therefore often missed by parents
- Often noted by an adult who sees the child less frequently
- Activity level
- Often preserved because of slow onset of anemia
- An extremely anemic child may be irritable, sleepy, and/or lethargic.
- History of fever, easy bruisability, or frequent/severe infections (especially bacterial): should alert the clinician to consider other diagnoses such as leukemia and bone marrow failure syndromes
Physical Exam
- Child is generally well appearing and not chronically ill.
- Pallor
- Tachycardia secondary to anemia
- Usually no organomegaly, ecchymosis, petechiae, or jaundice
Diagnostic Tests & Interpretation
Diagnostic Procedures/Other
- CBC
- Low hemoglobin, normal mean corpuscular volume, normal RBC morphology
- Total WBC count/morphology and platelet count should be normal; if not, consider leukemias.
- Absolute neutrophil count may be decreased (rarely <500/ ¼L), but morphology must be normal.
- Red cell distribution width may be elevated during recovery.
- Reticulocyte count
- Low to zero during anemic phase
- Should be high during recovery
- Chemistry/blood bank:
- Bilirubin, lactate dehydrogenase, ferritin, iron levels, and direct and indirect Coombs testing should be normal to rule out iron deficiency anemia and immune hemolysis.
- Parvovirus titers, parvovirus polymerase chain reaction (PCR) testing
- Immunoglobulin (Ig) levels in some cases
- Hemoglobin electrophoresis with quantitative fetal hemoglobin
- Should be normal in transient erythroblastopenia of childhood
- Fetal Hgb elevated in Diamond-Blackfan anemia
- Chest radiograph: to determine degree of cardiomegaly
- Bone marrow aspiration
- Not mandatory to make diagnosis
- May be necessary to rule in transient erythroblastopenia of childhood and rule out other diagnoses such as Diamond-Blackfan and the leukemias
- Presence or absence of early RBC precursors may help predict time to recovery.
- Maturation of megakaryocytes and the myeloid cell line must be normal, especially if neutropenia is present.
Differential Diagnosis
- Environmental: iron deficiency anemia
- Metabolic: hypothyroidism
- Diamond-Blackfan anemia (this diagnosis usually made within 1st year of life)
- Neoplasm
- Leukemia
- Myelodysplastic syndromes
- Miscellaneous
- Renal disease
- Anemia of chronic disease
- Blood loss (usually GI)
Treatment
Medication
- No role for prednisone, iron supplements, anabolic steroids, or other immunosuppressive agents
- Short-term folic acid may be indicated during reticulocytosis.
Additional Therapies
General Measures
- Initial inpatient observation for complications of severe anemia; daily CBC at least initially to gauge rate of fall of hemoglobin/rise of reticulocyte count and to estimate time to recovery
- Packed RBC transfusion
- If there is evidence of cardiovascular compromise
- If a transfusion is needed, transfuse slowly to prevent fluid overload. A good rule of thumb is to transfuse the same number of mL/kg as the patient 's hemoglobin over 3 " 4 hours. Should a 2nd transfusion be needed, attempt to use a 2nd aliquot of the same unit to decrease donor exposure.
- Normal activity and diet for age, as tolerated
- Instruct family on signs and symptoms of severe anemia.
Ongoing Care
Follow-up Recommendations
- Clinic visits weekly to monitor hemoglobin and reticulocytes. These visits may need to be more frequent in the beginning of the illness and less frequent as recovery becomes evident.
- Elevation of reticulocyte count is the first sign of recovery.
Prognosis
- All children recover usually within 1 " 2 months from diagnosis (may take up to 8 " 12 months for full recovery).
- Prognosis is excellent.
- Recurrence is rare.
Complications
- Cardiovascular compromise secondary to severe anemia is often less than expected given the level of anemia. High-output CHF is unusual.
- Neurologic symptoms including confusion and transient hemiparesis have been reported but are rare.
- A significant number of patients also have neutropenia (absolute neutrophil count ≤1,500/ ¼L) during either the acute or recovery phase of the illness.
Alert
- Isolation is necessary because of possible teratogenicity of parvovirus 19 and contagion within the hospital.
- Transient erythroblastopenia of childhood must be an isolated normocytic, normochromic anemia. If the other cell lines are affected (except for mild neutropenia) or if the anemia is macrocytic, consider bone marrow failure syndromes.
- Iron therapy has no place in the treatment of transient erythroblastopenia of childhood. Be sure to check RBC indices and reticulocyte count prior to instituting iron therapy for anemia.
Additional Reading
- Bhambhani K, Inoue S, Sarnaik SA. Seasonal clustering of transient erythroblastopenia of childhood. Am J Child Dis. 1988;142(2):175 " 177. [View Abstract]
- Shaw J, Meeder R. Transient erythroblastopenia of childhood in siblings: case report and review of the literature. J Pediatr Hematol Oncol. 2007;29(9):659 " 660. [View Abstract]
- Skeppner G, Kreuger A, Elinder G. Transient erythroblastopenia of childhood: prospective study of 10 patients with special reference to viral infections. J Pediatr Hematol Oncol. 2002;24(4):294 " 298. [View Abstract]
Codes
ICD09
- 284.81 Red cell aplasia (acquired)(adult)(with thymoma)
ICD10
- D60.1 Transient acquired pure red cell aplasia
SNOMED
- 234375006 Transient erythroblastopenia of childhood (disorder)
FAQ
- Q: Can other children in a family get this illness?
- A: The cause(s) of this illness in otherwise normal children is unknown. It is very rare for other family members to be affected. It is appropriate to reassure parents regarding this issue.
- Q: Are transfusions always necessary?
- A: No. Only in cases of heart failure is a transfusion necessary. Most often, children can be managed with watchful waiting.
- Q: How can transient erythroblastopenia of childhood be distinguished from Diamond-Blackfan syndrome?
- A: Children with Diamond-Blackfan syndrome are usually <1 year old and can have elevated hemoglobin F levels. If a bone marrow aspirate is obtained during the recovery phase of transient erythroblastopenia of childhood, the diagnosis will be clear. Often, however, only time will tell. Children with transient erythroblastopenia of childhood always recover; those with Diamond-Blackfan syndrome do not.
- Q: Is transient erythroblastopenia of childhood a precursor to leukemia?
- A: No. However, if recovery does not occur in a timely manner, or if neutropenia worsens, a bone marrow aspirate may be indicated if not previously completed.