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

CHAPTER 10. PALLOR

STEPHEN LUDWIG

BRANDON C. KU

DEFINITION

The complaint of pallor indicates a perceived decrease in rubor in the skin and mucous membranes of a child, which is associated with decreased oxyhemoglobin delivery to the skin or mucous membranes. Potential causes include decreased blood flow, which may be regional (e.g., thrombosis) or systemic (e.g., shock), and normal blood flow with decreased oxygen-carrying capacity (e.g., anemia).

In most cases, the finding of pallor demands that anemia first be considered as this is the most common cause. Exceptions include children who have a constitutional cause of pallor due to their fair complexion and lack of exposure to sunlight. However, most children with pallor should be considered to have low hemoglobin, which should be measured. Ordinarily, a complete blood count with differential count, red blood cell (RBC) indices, and reticulocyte count guide the clinician in differentiating the many causes of anemia and in determining unusual situations in which pallor is not related to anemia. In addition, a peripheral smear with examination of RBC morphology may further guide the clinician in determining the etiology of anemia.

CAUSE AND FREQUENCY

Pallor may be divided into causes involving normal hemoglobin (Table 10-1) and those involving a low hemoglobin level. The etiology of anemia may be separated into causes due to decreased RBC production, increased RBC destruction, or acute blood loss. Causes due to decreased RBC production are generally associated with low reticulocyte count while causes due to increased RBC destruction or acute blood loss are generally associated with increased reticulocyte count. Anemia may also be considered in relation to mechanism, such as trauma, toxin, metabolic tumor, congenital, or mixed etiology (Table 10-2), or in relation to RBC morphology (Table 10-3).

TABLE 10-1. Pallor with anemia.

Decreased erythrocyte or hemoglobin production

Nutritional deficiencies

Iron deficiency

Folic acid and vitamin B₁₂ deficiency or associated metabolic abnormalities

Aplastic or hypoplastic anemias

Diamond-Blackfan anemia

Fanconi anemia

Aplastic anemia^a

Transient erythroblastopenia of childhood

Malignancy: leukemia, lymphoma, neuroblastoma^a

Anemia of chronic disease

Abnormal heme and hemoglobin synthesis

Lead poisoning^a

Sideroblastic anemias

Thalassemias

Increased Erythrocyte Destruction

Erythrocyte membrane defects: hereditary spherocytosis, elliptocytosis, stomatocytosis, pyknocytosis, paroxysmal nocturnal hemoglobinuria

Erythrocyte enzyme defects

Defects of hexose monophosphate shunt: G6PD deficiency most common

Defects of Embden-Meyerhof pathway: pyruvate kinase deficiency most common

Hemoglobinopathies

Sickle cell syndrome^a

Unstable hemoglobins

Immune hemolytic anemia

Autoimmune hemolytic anemia (e.g., Evans syndrome)

Isoimmune hemolytic anemia

Infection

Viral: mononucleosis, influenza, coxsackie, measles, varicella, cytomegalovirus

Bacterial: Escherichia coli, Pneumococcus, Streptococcus, thyphoid fever, Mycoplasma

Drugs: antibiotics, methyldopa

Inflammatory and collagen vascular disease

Malignancy^a

Microangiopathic anemias

Disseminated intravascular coagulation^a

Hemolytic uremic syndrome^a

Thrombotic thrombocytopenic purpura

Cavernous hemangioma

Blood Loss

Severe trauma^a

Anatomic lesions

Meckel diverticulum

Peptic ulcer

Idiopathic pulmonary hemosiderosis^a

^aCan present as life-threatening emergencies

TABLE 10-2. Etiology of anemia by mechanism (common causes of pallor).

TABLE 10-3. Etiology of anemia by red blood cell morphology.

Microcytic Anemia

Iron deficiency

Lead poisoning

Thalassemias

Hemoglobinopathies

Sideroblastic anemia

Normocytic Anemia

Low reticulocyte count

Anemia of chronic disease

Transient erythoblastopenia of childhood

Diamond-Blackfan anemia

Infection

Myelosuppression from medication side effect

Renal disease

Leukemia

Marrow infiltration

Aplastic anemia

Elevated reticulocyte count

Blood loss

Pulmonary hemosiderosis

Goodpasture syndrome

Immune hemolytic anemia

Hemoglobinopathies

Hereditary spherocytosis and elliptocytosis

G6PD deficiency

Pyruvate kinase deficiency

Hemolytic-uremic syndrome

Thrombotic thrombocytopenic purpura

Kasabach-Merritt syndrome (hemangioma thrombocytopenia syndrome)

Macrocytic Anemia

Low reticulocyte count

Folate or vitamin B₁₂ deficiency

Aplastic anemia

Diamond-Blackfan anemia

Transient erythroblastopenia of childhood

Elevated reticulocyte count

Hemolytic anemia and high reticulocyte count

Autoimmune hemolytic anemia

Secondary folate deficiency in hemolytic anemia

QUESTIONS TO ASK AND WHY

• Is there hemodynamic instability or need for emergent intervention?

—The most important question to ask is whether a child’s pallor is secondary to severe anemia with hemodynamic compromise that requires emergent intervention and stabilization with fluid resuscitation until transfusion of packed RBCs. This question also helps to determine whether severe anemia is secondary to acute external hemorrhage that may require immediate surgical intervention. One can also elucidate if a child’s pallor is secondary to decreased blood flow from acute thrombosis or systemic shock further guiding therapy.

• What are the child’s dietary habits?

—Because the most common cause of pallor is iron deficiency anemia, important clarifying questions pertain to diet. Diets containing large quantities of cow’s milk may raise concern for iron deficiency due to lack of iron intake and loss of appetite for iron-rich foods.

aCan present as life-threatening emergencies

• Is there a family history of anemia, splenectomy, or gallbladder surgery?

—Many RBC membrane disorders are inherited. Some disorders, such as hereditary spherocytosis and elliptocytosis, frequently necessitate splenectomy due to RBC sequestration. Inherited diseases causing hemolysis, such as sickle cell disease, may be recognized in some families by a history of gallbladder surgery for gallstones.

• Are there signs of systemic illness, fatigue, growth failure, weight loss, or lymphadenopathy?

—The presence of these signs or symptoms should raise concern for malignancy.

• Was there exposure to certain medications or toxins?

—Questions regarding exposure to toxins or medications should be asked as these may cause anemia by hemolysis (e.g., sulfonamide or nitrofurantoin exposure in a patient with glucose- 6-phosphate dehydrogenase [G6PD deficiency]) or by suppressing bone marrow production of RBCs (e.g., trimethoprim/sulfamethoxazole).

• Did pallor develop quickly or gradually?

— Information about the progression of anemia provides clues about the cause. Gradual onset suggests iron deficiency while acute onset with jaundice suggests hemolysis. In cases of gradual development of pallor, additional questions should focus on sources of iron loss or blood loss, such as history of heavy menstruation, blood in stool or melena, or multiple blood draws for diagnostic testing.

SUGGESTED READINGS

1. Poncz, M. Pallor. In: Schwartz MW, ed. Pediatric Primary Care: A Problem-Oriented Approach. 2nd ed. Chicago, London, Boca Raton, Littleton, MA: Year Book Medical Publishers; 1987.

2. Segel GB, Hirsh MG, Feig SA. Managing anemia in pediatric office practice: Part I. Pediatr Rev. 2002;23:75-84.

3. Shah S. Pallor. In: Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2010.

4. Bizzaro M, Colson E, Ehrenkranz R. Differential diagnosis and management of anemia in the newborn. Pediatr Clin North Am. 2004;51:1087-1107.