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542 Part VI: The Erythrocyte Chapter 36: Pure Red Cell Aplasia 543

disease, or another hemolytic anemia. The decrease in erythropoiesis Transient erythroblastopenia of childhood typically terminates
results in more evident pallor, fatigue on exertion or at rest, lassitude, after a few weeks, but anemia may persist occasionally for months.
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and dyspnea on exertion. Gastrointestinal complaints or headache may Transfusions may be required during that interval. Overtreatment of a
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be associated. Parvovirus infection can unmask previously undiag- self-limited illness and misdiagnosis of a more serious disease are to be
nosed underlying hemolytic anemia. Physical examination may reveal avoided.
signs of anemia, such as pallor, tachycardia, and a flow murmur. No rash For drug-associated transient failure of erythropoiesis, the sus-
or joint swelling is seen. Elevated serum bilirubin or overt icterus may pected offending drug is discontinued and the diagnosis established
be a clue to underlying hemolysis. from subsequent clinical improvement.
Transient erythroblastopenia of childhood presents as an acute
anemia in a previously well child. The syndrome has an estimated inci- ACQUIRED PURE RED CELL APLASIA
dence rate of 4 to 5 cases per 1 million children. 94–96 Transient erythrob-
lastopenia is a frequent diagnosis in children with severe anemia, 95,97 DEFINITION AND HISTORY
and is the most common cause of acquired red cell aplasia in pediatric
patients. 94,98 Most patients are 1 to 3 years old, 97,98 but transient erythrob- Acquired pure red cell aplasia is an uncommon cause of anemia
lastopenia of childhood can occur in the first year of life and through that occurs principally in older adults. The blood counts and mar-
adolescence. Rare complications include seizures and transient neuro- row appearance are indistinguishable from the picture of Diamond-
logic abnormalities. 99–101 Blackfan anemia, that is, anemia, severe reticulocytopenia, and absent
marrow erythroid precursor cells. The nosologic origins of acquired
pure red cell aplasia are obscure. Early descriptions are intermixed
LABORATORY EVALUATION with those of aplastic anemia (in retrospect, a poor term for general-
In both syndromes, anemia is the hallmark, and hemoglobin levels may ized marrow failure). Kaznelson is credited with the first case report
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be markedly depressed. Reticulocytes usually are absent from the blood, in 1922. Early distinction of the two syndromes was stimulated by the
and erythroid precursor cells are not present or markedly decreased in relationship of red cell aplasia to thymoma. Although red cell aplasia
the marrow. Red cell indices are normal. White blood cell and platelet shares with aplastic anemia an immune pathophysiology and respon-
counts are normal or elevated. Occasionally, neutropenia and thrombo- siveness to immunosuppressive therapies, the absence of involvement
cytopenia of mild or moderate degree are present (especially if splenic of neutrophils, monocytes, and platelets makes the diagnostic distinc-
function is intact, as in hereditary spherocytosis and in transient ery- tion evident. Many of the diverse clinical associations (Table 36–1) are
throblastopenia of childhood). If the episode is brief and diagnosed consistent with an immune-mediated pathophysiology. The mechanism
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during marrow recovery, patients may present with reticulocytosis, and
nucleated red blood cells may be seen on the blood film.
TABLE 36–1. Classification of Pure Red Cell Aplasia
DIFFERENTIAL DIAGNOSIS Fetal red cell aplasia (nonimmune hydrops fetalis)
The reticulocyte count readily distinguishes the cause of increasing ane-
mia in a patient with hemolytic disease as transient aplastic crisis. The Parvovirus B19 in utero
most important differential diagnosis for transient erythroblastopenia Inherited (Diamond-Blackfan anemia)
of childhood is inherited pure red cell aplasia. For the former, the age at RPS19 and other RPS mutations
presentation is older, the patient usually has no family history (but tran-
sient erythroblastopenia of childhood may be familial and can occur Acquired
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simultaneously in siblings), physical anomalies are absent, and the Transient pure red cell aplasia
syndrome resolves spontaneously. Acute B19 parvovirus infection in hemolytic disease (transient
In transient erythroblastopenia of childhood (in contrast to inher- aplastic crisis; ~100% of cases)
ited red cell aplasia), erythrocyte adenosine deaminase levels are nor-
mal, and red cells do not show “stress” patterns of fetal hemoglobin and Transient erythroblastopenia of childhood
i antigen (red cell antigen expressed primarily on feral erythrocytes) Chronic pure red cell aplasia
expression. The patient’s medical history, the red cell indices, and appro- Idiopathic
priate serum assays should allow prompt exclusion of more common
causes of anemia in children, such as iron deficiency or other nutritional Large granular lymphocytic leukemia
deficiencies. When transient erythroblastopenia is associated with neu- Chronic lymphocytic leukemia
tropenia, acute lymphoblastic leukemia and aplastic anemia may be Clonal myeloid diseases (especially 5q-syndrome)
suspected: marrow examination clarifies the diagnosis. A record of
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current medications, more important in adults, may provide the basis Persistent B19 parvovirus infection in immunodeficient host
for a tentative diagnosis of drug-induced rather than idiopathic disease. (~15% of cases)
Thymoma
THERAPY, COURSE, AND PROGNOSIS Collagen vascular diseases
Transient aplastic crisis resolves as neutralizing antibodies to B19 par- Post–stem cell transplantation
vovirus are made, usually within 1 to 2 weeks of infection. Ensuing Anti-ABO antibodies
reticulocytosis may be brisk, and the hemoglobin may transiently rise
to higher-than-normal values. White cell and platelet numbers may Drug induced
“rebound,” and some bone pain from marrow expansion may be present. Antierythropoietin antibodies
Severe anemia may require transfusion of red blood cells (Chap. 138). Pregnancy
No established role for administration of immunoglobulin exists.

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