Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 10-6

Two-Year-Old Boy

STEPHEN LUDWIG

BRANDON C. KU

HISTORY OF PRESENT ILLNESS

The patient was a 2-year-old boy who was in his usual state of good health until the day of admission when he visited his grandmother who felt his “color was off.” She had not seen him for 4 weeks. The mother took his temperature, which was normal. He did not have fever, vomiting, or diarrhea and his activity level had not changed. At the grandmother’s insistence, he was taken to the hospital for evaluation. He had not received any medications recently. He had an upper respiratory infection approximately 6 weeks ago, which resolved without intervention.

MEDICAL HISTORY

The infant was born at term by spontaneous vaginal delivery after an uncomplicated pregnancy. The birth weight was 3400 g. He had not required any hospitalizations or undergone any surgical procedures. He reportedly had a “rash” with amoxicillin approximately 1 year ago during treatment of an otitis media. He had received the appropriate immunizations for his age. He had traveled to Lake George in New York State 2 months ago. His developmental history was normal. There were no siblings. The family history was unremarkable.

PHYSICAL EXAMINATION

T 38.0°C; HR 120 bpm; RR 25/min; BP 113/54 mmHg; SpO2 98% in room air

In general, the child was alert and in no acute distress. However, he was extremely pale. The conjunctivae were anicteric. The tympanic membranes were normal in appearance. The lungs were clear to auscultation. There were no murmurs on cardiac examination. Distal pulses were strong. The abdomen was soft without hepatomegaly or splenomegaly. The palmar creases were remarkable for the loss of pigmentation.

DIAGNOSTIC STUDIES

The complete blood count revealed the following: WBCs 8400/mm3; hemoglobin, 7.2 g/dL; platelets, 326 000/mm3; MCV, 81 fL; Red cell distribution width, 12.4; Reticulocyte count was 0.2%. Serum electrolytes, blood urea nitrogen, glucose, transaminases, albumin, and lactate dehydrogenase were all normal. Direct Coombs test was negative. Parvovirus IgM and IgG were also negative.

COURSE OF ILLNESS

The child was noted to be pale by his grandmother when he went to see her for a visit. This history speaks of the insidious onset of this child’s pallor. His mother who lived with him day by day did not notice the change. The child had been well except for a mild viral illness. He had no other symptoms. There was no family history of anemia and no previous complete blood counts that suggested any problem. His examination was normal except for the pallor and when laboratory studies were obtained he had a normocytic normochromic anemia and a reticulocyte count of virtually zero. None of the other cell lines was abnormal. The findings indicated a need for a bone marrow aspirate and analysis that confirmed the diagnosis (Figure 10-5).

Image

FIGURE 10-5. Bone marrow aspirate.

DISCUSSION CASE 10-6

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of acquired red cell aplasia includes transient erythroblastopenia of childhood (TEC), anemia associated with parvovirus B19, drug and chemical involved, and idiopathic. The condition may also be confused with congenital red cell aplasia (Diamond-Blackfan) but the age of onset of TEC is usually older and there are no associated anomalies. Also, TEC is a normocytic anemia while Diamond-Blackfan anemia is usually macrocytic.

DIAGNOSIS

The bone marrow aspirate revealed numerous young (nucleated) red blood cells all in the same stage of maturation (Figure 10-5). This finding combined with the normal MCV and low reticulocyte count suggested the diagnosis of transient erythroblastopenia of childhood on the verge of recovery. It is one of the most common acquired red cell aplasias.

INCIDENCE AND EPIDEMIOLOGY OF TRANSIENT ERYTHROBLASTOPENIA (TEC)

Transient erythroblastopenia (TEC) is a condition that occurs in previously well children. The age of diagnosis is usually around 2 years with a typical range of 1 - 3 years. There is often a history of a preceding upper respiratory tract infection or other viral illness but no single agent has been identified. Parvovirus infection is usually not an etio-logic agent in this diagnosis.

CLINICAL MANIFESTATION OF TRANSIENT ERYTHROBLASTOPENIA

The presenting signs and symptoms are usually pallor and fatigue. Sometimes tachycardia and feelings of palpitations prompts a visit to the physician’s office and subsequent detection. There are no other common significant manifestations but there have been sporadic cases of TEC associated with neurologic conditions including papilledema and transient hemiplegia. One recent report links TEC and breath holding.

DIAGNOSTIC APPROACHES

The suspicion for TEC comes with a patient of the appropriate age who has insidious onset of anemia and no reticulocyte response.

Complete blood count. The median hemoglobin value at presentation is 5-6 g/dL but varies significantly depending on whether the diagnosis occurs early or late in the course of disease. Reticulocyte counts are less than 1% except for those children on the cusp of recovery. White blood cell and platelet counts are typically normal, though exceptions are possible. The MCV in TEC is usually normal while the MCV in Diamond-Blackfan anemia is usually elevated. Other features also help distinguish between TEC and Diamond-Blackfan anemia (Table 10-7).

TABLE 10-7. Features of transient erythroblastopenia of childhood and Diamond-Blackfan anemia.

Image

Bone marrow aspirate. During the illness, the bone marrow reveals significant erythroblastopenia with maturation arrest. During the recovery phase, patients with TEC produce a cohort of “fetal-like” erythrocytes that evolve into normal red blood cells. All marrow red blood cells are at the same stage of maturation.

Other studies. Interpretation of MCV, fetal hemoglobin, and i antigen depends on stage of illness. During the recovery phase the MCV, fetal hemoglobin, and i antigen may all be elevated. Ultimately, the distinction is often made when the patient with TEC begins recovery.

TREATMENT

Treatment is supportive. A blood transfusion may be needed for hemodynamic instability. Resolution typically occurs within 1-3 months after diagnosis. Approximately 5%-10% of children have begun to recover by the time medical care is sought. There are no other associated hematologic problems. The prognosis is excellent.

SUGGESTED READINGS

1. Skeppner G, Kreuger A, Elinder G. Transient erythroblastopenia of childhood: prospective study of 10 patients with special reference to viral infections. J Pediatr Hem/Onc. 2002;24:294-298.

2. Chan GC, Kanwar VS, Williams J. Transient erythroblastopenia of childhood associated with transient neurologic deficit: report of a case and review of the literature. J Paediatr Child Health. 1998;34:299-301.

3. Tam DA, Rash FC. Breath-holding spells in a patient with transient erythroblastopenia of childhood. J Pediatr. 1997;130:651-653.

4. Shaw J, Meeder R. Transient erythroblastopenia of childhood in siblings: a case report and review of the literature. J Pediatr Hematol Oncol. 2007;29:659-660.