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

CASE 10-2

Twelve-Month-Old Girl

MAYA A. JONES

HISTORY OF PRESENT ILLNESS

A 12-month-old Caucasian girl presented to the emergency department with pallor. On the day of arrival, the grandparents had arrived from Florida and were alarmed at her appearance (Figure 10-1) prompting a visit to the emergency department. The child had last been seen by her grandparents a few months prior and at that time she appeared well. The parents conceded that she did appear more pale than usual. There was no fever, rash, vomiting, or diarrhea and her activity level was normal. She had no jaundice and had not traveled recently, although the parents had visited Puerto Rico 2 weeks ago.

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FIGURE 10-1. Photograph of the child showing marked pallor.

MEDICAL HISTORY

The birth history was unremarkable. She had a febrile illness at 6 months of age but did not require hospitalization. Evaluation at that time included a complete blood count (see Diagnostic Studies) and a blood culture positive for Staphylococcus epidermidis, which was felt to be a contaminant. Her immunizations were up-to-date. She was breast fed until 6 months of age after which she began drinking whole milk. She was a finicky eater but had been growing well. There were no pets in the home and her development was normal.

PHYSICAL EXAMINATION

T 36.1°C; HR 145 bpm; RR 38/min; BP 97/53 mmHg; SpO2 99% in room air

The girl was pale but alert and playful. The conjunctivae were also pale but without injection or discharge. There was no lymphadenopathy and her neck was supple. A 2/6 systolic murmur was heard at the left upper sternal border without radiation. The lungs were clear to auscultation. On abdomen examination, there was no splenomegaly or hepatomegaly and there were no rash or petechiae on skin.

DIAGNOSTIC STUDIES

At 6 months of age, the complete blood count revealed the following: WBCs, 15 200/mm3 (71% segmented neutrophils, 25% lymphocytes, and 4% monocytes); hemoglobin, 11.2 g/dL; 365 000 platelets/mm3, with an MCV of 78 fL and an RDW was 17.3.

Her current studies revealed the following: WBCs, 8300/mm3 (58% segmented neutrophils, 31% lymphocytes, and 11% monocytes); hemoglobin, 3.4 g/dL; and 410 000 platelets/mm3 with an MCV 59 fL and an RDW of 15.1. The reticulocyte count was 1.4%. Stool was hemoccult negative.

COURSE OF ILLNESS

The history, examination (Figure 10-1), and laboratory findings suggested a diagnosis that was subsequently confirmed.

DISCUSSION CASE 10-2

DIFFERENTIAL DIAGNOSIS

Table 10-5 lists the differential diagnosis of micro-cytic anemia in children. Causes of iron deficiency include poor bioavailability, decreased iron absorption, blood loss, insufficient intake, and disruption of enteric mucosa or loss of functional bowel. Alkaline gastric pH reduces the solubility of inorganic iron, impeding absorption. Chronic use of acid pump blockers, vagotomy (for severe gastroesophageal reflux), and impaired gastric parietal cell function in pernicious anemia may compromise iron absorption. Iron absorption may also be disrupted after surgical bowel resection often following volvulus or intussusception. Iron deficiency in such cases develops slowly and may not become evident for several years. Blood loss is a leading cause of iron deficiency. Common causes of gastrointestinal blood loss in children include Meckel diverticulum, cow milk protein allergy, and parasitic infestation; however, blood loss from hematuria or pulmonary hemorrhage can also occur. In this case, the dietary history suggested a likely cause.

TABLE 10-5. Evaluation of microcytic anemia.

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DIAGNOSIS

On examination the child was extremely pale (Figure 10-1). The combination of a hypochromic microcytic anemia and paucity of dietary iron implicated iron deficiency as a cause of this child’s pallor. Subsequent tests, including iron level, ferritin, and total iron-binding capacity, supported this diagnosis. The child received a packed red blood cell transfusion followed by daily iron supplements. Studies performed 1 month later revealed a hemoglobin level of 9.7 g/dL. This case illustrates the importance of the red cell distribution width as a marker of iron deficiency that precedes anemia.

INCIDENCE AND EPIDEMIOLOGY

In developed countries, routine iron fortification of formulas and cereals led to a significant decrease in early childhood anemia. However, iron deficiency remains a leading cause of anemia. Currently, the prevalence of iron deficiency is approximately 7% and one-third of these children develop anemia. Children living below the poverty level are at greatest risk. Anemia is only one manifestation of iron deficiency. Even in the absence of anemia, children with iron deficiency may have neurocognitive and behavioral problems. Only some of these problems are reversible with iron supplementation, highlighting the importance of prevention.

CLINICAL PRESENTATION

The clinical examination in children with mild iron deficiency is usually normal. With moderate or severe iron deficiency the findings may be similar to other causes of anemia including fatigue and pallor. If the anemia develops gradually, as in the child presented here, immediate family members may not notice changes in pigmentation. Other findings may include pica, the compulsive consumption of nonnutritive substances such as soil or ice. Longstanding iron deficiency may lead to angular stomatitis, glossitis, and softening of the fingernails leading to concave deformities descriptively termed “spooning (koilonychia).”

DIAGNOSTIC APPROACH

Complete blood count. In children, an elevated red cell distribution width is usually the earliest hematologic finding in iron deficiency. As the deficiency progresses, other hematologic parameters are affected (Table 10-5).

Peripheral blood smear. Peripheral blood smear in early disease may reveal anisocytosis. Red blood cells become microcytic and hypochromic as the iron deficiency progresses. With severe iron deficiency, red blood cells may be deformed and misshapen and demonstrate poikilocytosis.

Other studies. In the absence of a concurrent inflammatory disease state, the ferritin level decreases, reflecting diminished total tissue iron stores. With continued iron deficiency, reticuloendothelial macrophage iron stores become depleted and serum iron levels decrease. At this point, the total iron-binding capacity increases without a change in hemoglobin levels. When the transferrin saturation decreases to approximately 10%, the availability of iron becomes the rate-limiting step for hemoglobin synthesis. This leads to the accumulation of heme precursors called free erythrocyte protoporphyrins. Ultimately, the red blood cells become smaller as their hemoglobin content decreases.

TREATMENT

Treatment of iron deficiency depends on its etiology. For children with suspected dietary deficiency, treatment is supplemental iron. In children with anemia, an initial therapeutic trial often eliminates the need for expensive laboratory testing in determining the diagnosis. The reticulocyte count usually increases within several days and the hemoglobin increases within 3 weeks. Patients should be treated until the hemoglobin reaches the normal range and then continued for at least one additional month to replete the iron stores. Failure of the hemoglobin level to rise within 1 month indicates either poor compliance with iron therapy or incorrect diagnosis. The use of iron-fortified foods can reduce the likelihood of iron deficiency anemia.

SUGGESTED READINGS

1. Oski FA. Iron deficiency in infancy and childhood. N Engl J Med. 1993;329:190-193.

2. Segel GB, Hirsh MG, Feig SA. Managing anemia in pediatric office practice: part I. Pediatr Rev. 2002;23:75-83.

3. Andrews NC. Disorders of iron metabolism and sideroblastic anemia. In: Nathan DG, Orkin SH, Ginsburg D, Look AT, eds. Nathan and Oski’s Hematology of Infancy and Childhood. 6th ed. Philadelphia: Saunders; 2003:456-497.

4. Lozoff B, Jimenez E, Wolf AW. Long-term developmental outcome of infants with iron deficiency. N Engl J Med. 1991;325:687-694.

5. Aslan D, Altay C. Incidence of high erythrocyte count in infants and young children with iron deficiency anemia: re-evaluation of an old parameter. J Pediatr Hematol Oncol. 2003;25:303-306.

6. Centers for Disease Control and Prevention. Iron deficiency-United States, 1999-2000. MMWR. 2002;51: 897-899.

7. Athe R, Vardhana Rao MV, Nair KM. Impact of iron-fortified foods on Hb concentration in children (<10 years): a systematic review and meta-analysis of randomized controlled trials. Public Health Nutr. 2013 [Epub ahead of print, PMID 23388159].