Ilene Claudius
Childhood leukemia, the most common childhood malignancy, will be covered in detail in this chapter. Most complications can be extrapolated to other malignancies as well.
Please refer to Chapters 137, Hemophilias and von Willebrand Disease, and 141, Emergent Complications of Malignancy, for more information on those entities.
CHILDHOOD LEUKEMIA
EPIDEMIOLOGY
Acute lymphoblastic leukemia (ALL) accounts for three-fourths of pediatric leukemia.
Peak incidence is 3 to 5 years of age.
Five-year survival is 75% to 80%.
PATHOPHYSIOLOGY
Certain chromosomal abnormalities (eg, Philadelphia translocation), radiation exposure, and chemotherapy treatment for prior malignancy are risk factors for leukemia.
CLINICAL FEATURES
Leukemia can present with symptoms of direct infiltration of bone marrow and suppression of cell lines, including pallor, fatigue, easy bruising, fever, or bone pain.
Two-thirds of patients have hepatomegaly or splenomegaly at diagnosis.
Several findings are classically associated with particular subtypes of acute myelogenous leukemia (AML), including gingival hyperplasia and subcutaneous masses (chloromas).
DIAGNOSIS AND DIFFERENTIAL
CBC often shows abnormalities of two or more cell lines, although can be normal early in the course.
Obtain electrolytes, creatinine, uric acid, phosphate, and calcium to assess for tumor lysis; a disseminated intravascular coagulation (DIC) panel, liver function tests (LFTs), and lactate dehydrogenase (LDH); blood and urine cultures if febrile; and a type and screen if anemic.
Obtain CXR to assess for mediastinal mass.
Viral syndromes and rheumatologic diseases can present similarly.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Anemia: For hemorrhage or significant symptoms, transfuse 10 mL/kg irradiated, leukodepleted packed red blood cells (PRBCs) (caution in hyperviscosity syndrome). In the absence of these indications, transfusions are done non-emergently for Hb <8 grams/dL.
Thrombocytopenia: For bleeding with platelets <50,000 to 100,000/mL3 or procedure with platelets <50,000/mL3, give 10 mL/kg or 0.1 random donor unit/kg of platelets. In the absence of these indications, platelets are given non-emergently when <10,000/mL3.
Infection: In newly presenting patients or known patients returning with neutropenia (absolute neutrophil count <1000/mL3), antibiotics with coverage for pseudomonas (eg, cefepime 50 milligrams/kg) should be given empirically with addition of gentamycin (2.5 milligrams/kg) and vancomycin (15 milligrams/kg) for patients who are ill appearing or suspected to have gram-positive infections. Attention should be paid to the possibility of typhlitis, inflammation of the terminal ileum, and anaerobic coverage added if suspected (see Table 87-1).
Tumor lysis syndrome describes the release of intracel-lular potassium, phosphate, and uric acid and the subsequent decline in calcium. It occurs with cell lysis, which can precede the initiation of chemotherapy in patients with a high WBC count. Hyperkalemia is managed in the standard fashion, and uric acid elevations can be emergently managed with IV fluids and rasburicase.
Hyperleukocytosis can cause microvascular obstruction with injury particularly to the lungs or CNS. Patients with symptoms or asymptomatic patients with WBC counts >200,000/mL3 should be aggressively hydrated. If hydration is ineffective, the patient will require emergent leukapheresis.
TABLE 87-1 Management of Neutropenic Fever
LYMPHOMA
Hodgkin’s lymphoma is a lymphoid neoplasm that typically presents as non-tender, non-erythematous cervical or supraclavicular lymph nodes in adolescence. About one-third of patients have systemic symptoms (“B-symptoms”) such as fever, weight loss, or night sweats.
Non-Hodgkin’s lymphoma (NHL) occurs in older children, particularly those with immunosuppression, and can occur anywhere in the body. The location typically drives the presenting manifestations.
Initial workup of lymphoma requires a CXR to assess for mediastinal mass, CBC for bone marrow involvement, electrolytes, uric acid, phosphate, and creati-nine to assess for tumor lysis syndrome (more likely with NHL).
ED care is supportive, with steroids being reserved for situations where a mass causes life- or limb-threatening compression.
CENTRAL NERVOUS SYSTEM TUMORS
Brain tumors are the most common solid tumors in pediatrics, and most present with signs of increased intracranial pressure. Sleep-related headache is the strongest predictor, with vomiting, ataxia, cranial nerve palsies, and vague neurologic symptoms being common in older children and bulging fontanel, increasing head circumference, and sunsetting (upward gaze paresis) being common in infants. The notable exception is primary brain stem tumors (eg, brain stem glioma), which may present initially with cranial nerve findings without signs of increased intracranial pressure.
CT and MRI are appropriate studies in the emergency department.
Seizures, if present, are treated in the standard fashion. Dexamethasone should typically be given to reduce vasogenic edema unless CNS lymphoma is likely (dose: 1 milligram/year of life to a maximum of 10 milligrams).
NEUROBLASTOMA
Neuroblastoma is a primitive ganglion tumor that can occur in the adrenal, abdomen, chest, or neck.
Typically, neuroblastoma presents as a painless mass, but can cause compressive symptoms as well. If retrobulbar, raccoon eyes and proptosis can occur and, if located in the superior cervical ganglion, can cause Horner’s syndrome and tracheal compression. Paraneoplastic symptoms include hypertension, watery diarrhea, and opsoclonus-myoclonus syndrome (rapid, multidirectional eye movements and jerking of the extremities).
Chest radiographs should be obtained to assess for mediastinal mass and CBC to assess for bone marrow infiltration. CT can assist in diagnosis and staging.
WILMS TUMOR
Wilms tumor, or nephroblastoma, arises from embryonal renal cells, typically in children <10 years of age.
Typically, children present with a painless mass, but may have hematuria, hypertension, or signs of compression of abdominal organs.
Abdominal CT and chest radiograph can assist in diagnosis and staging. Recommended laboratories include CBC, liver and coagulation profiles, serum chemistries, and urinalysis.
RETINOBLASTOMA
Retinoblastoma is a white-gray intraocular malignancy arising from the retina caused by an inherited or spontaneous mutation inactivating the RB1 tumor suppressor gene. It is typically diagnosed prior to age 2 years.
Patients frequently have leukocoria (see Fig. 87-1), or loss of the normal red reflex due to the gray-white intraocular tumor mass. Other possible presentations include strabismus, unilateral fixed pupil, or a painful, red eye (possibly associated with glaucoma). One-quarter of lesions are bilateral.
Diagnosis is by CT scan and ophthalmology consultation.
FIG. 87-1. Leukocoria in retinoblastoma. An 18-month-old child presenting with white pupil. (Reproduced with permission from Shah BR, Lucchesi M: Atlas of Pediatric Emergency Medicine, © 2006, McGraw-Hill, New York.)
BONE AND TISSUE SARCOMAS
Rhabdomyosarcoma presents as a painless tissue mass, and can be further elucidated on CT scan.
Osteosarcoma is a bony tumor that primarily affects adolescents. Common sites are proximal humerus and distal femur, with tumors in the pelvis or mandible occurring rarely. Patients experience a dull ache in the affected area, particularly at night, and may have a palpable mass on examination. Systemic symptoms are rare, and typically indicate metastatic disease.
Ewing sarcoma is also a painful bony tumor. It presents in the long bones (femur, tibia, humerus) or axial skeleton (pelvis, ribs, or spine). Presentation can be insidious, with weeks of localized pain, or as a mass and discomfort first noted after a minor trauma.
Radiograph demonstrates a destructive moth-eaten tumor displacing the native cortex outward and creating and onion-peel appearance (see Fig. 87-2).
FIG. 87-2. Ewing sarcoma of the fibula.
ANEMIA
EPIDEMIOLOGY
Iron deficiency anemia from ingestion of cow’s milk is common from 6 months to 3 years. Beyond that, or without an appropriate clinical history, gastrointestinal bleeding should be considered.
PATHOPHYSIOLOGY
Iron deficiency anemia in infants and toddlers is frequently secondary to excessive milk intake (>32 ounces/d) causing poor dietary intake of iron and blood loss through colitis.
Autoimmune hemolytic anemia due to the production of autoantibodies is typically primary in infants and small children, and in adolescents, secondary to malignancy, rheumatologic disease, or HIV.
CLINICAL FEATURES
Children with anemia can present with pallor and fatigue. Occasionally, severe anemia can present with congestive heart failure.
DIAGNOSIS AND DIFFERENTIAL
A CBC, reticulocyte count, and peripheral smear should be obtained. In severe cases, type and screen maybe necessary. If hemolysis is suspected, a peripheral smear, bilirubin, and LDH may be helpful. If iron deficiency anemia is suspected outside of the toddler age group, a stool hemocult should be obtained.
In iron deficiency anemia, there is isolated low hemoglobin with a decreased reticulocyte count and mean corpuscular volume (MCV). Involvement of additional cell lines should prompt investigation for a hematologic malignancy.
In autoimmune hemolytic anemia, the low hemoglobin is accompanied by a high MCV and an elevated indirect bilirubin. A direct Coomb’s test is positive, and a peripheral smear will show spherocytes and schistocytes.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Children with anemia from nontraumatic causes rarely require transfusion in the ED.
Transfusion can be considered for a symptomatic patient with Hb <6 to 8 milligrams/dL. Typically, the dose is based on the pre-transfusion hemoglobin, and is given over 3 to 4 hours. Patients with Hb <4 grams/dL receive 3 mL/kg, Hb 4 to 6 grams/dL receive 5 mL/kg, and Hb >6 grams/dL receive 10 mL/kg of PRBCs. Transfusion of patients with autoimmune hemolytic anemia is not without risk and should be performed after consultation with a hematologist.
Corticosteroids are appropriate treatment for patients with autoimmune hemolytic anemia.
Patients with iron deficiency anemia can typically be discharged from the emergency department. If the etiology is thought to be over-ingestion of cow’s milk, reduction of intake to <24 ounces/day is recommended. They should be started on iron therapy at a dose 1 to 2 milligrams/kg/dose of elemental iron three times daily.
THROMBOCYTOPENIA
EPIDEMIOLOGY
Idiopathic thrombocytopenic purpura (ITP) occurs as an isolated disorder in the preschool-aged child, and is often a feature of systemic infections (HIV, hepatitis) or rheumatologic disorders in the adolescent.
PATHOPHYSIOLOGY
ITP is an autoimmune disorder in which macrophages of the reticuloendothelial system destroy antibody-coated platelets.
CLINICAL FEATURES
Patients present with signs of thrombocytopenia such as diffuse petechiae, bruising, and bleeding (mainly epistaxis and mucus membrane) days to weeks after a viral upper respiratory infection. Systemic symptoms should not occur.
DIAGNOSIS AND DIFFERENTIAL
CBC will reveal significant thrombocytopenia without abnormalities in the other cell lines. Platelet volume is large. Blood type should also be sent if anti-Rh immunoglobulin is planned therapy.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
The three primary treatments for ITP are prednisone 1 to 2 milligrams/kg/d, IVIG 1 gram/kg, and anti-Rh immunoglobulin (WinRho®). Steroids should not be given unless the possibility of hematologic malignancy has been excluded. Anti-Rh immunoglobulin will typically cause some hemolysis, lowering the patient’s hemoglobin by 1 gram/dL in the days following treatment. However, several cases of severe and fatal intravascular hemolysis have been reported, and this should only be given in conjunction with a hematologist comfortable with the contraindications to anti-Rh immunoglobulin.
Although platelet transfusions are not usually effective, for life-threatening bleeds, a transfusion of two to three times the normal dose of platelets can be useful. Methylprednisolone (30 milligrams/kg) and IVIG (1 gram/kg) should be given as well.
Admission decisions should be made in conjunction with pediatric hematology.
NEUTROPENIA
EPIDEMIOLOGY
Multiple disorders can cause an isolated transient neutropenia in children, including benign transient neutropenia from viral infections or medications, autoimmune neutropenia, and cyclic neutropenia. More serious forms are chronic and persistent, such as congenital agranulocytosis or chemotherapy induced.
PATHOPHYSIOLOGY
Absolute neutrophil counts below 1000/mL3 increase the risk for bacterial infection; however, this is rarely true in the transient types of neutropenia.
CLINICAL FEATURES
Neutropenia may be asymptomatic and incidentally noted on a CBC obtained for other reasons or may be associated with systemic infections and fever.
DIAGNOSIS AND DIFFERENTIAL
CBC and blood cultures should be sent for a febrile patient in whom neutropenia is suspected.
Children with neutropenia who are ill appearing should be presumed to have a significant infection.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
Patients with benign forms of neutropenia and evidence of infection can typically be discharged home, although consultation with the patient’s hematologist and a single dose of ceftriaxone (50 milligrams/kg IV/IM) may be considered.
Ill-appearing patients and those with a fever and a more serious persistent type of neutropenia should be admitted on broad-spectrum antibiotics, such as cefepime (50 milligrams/kg IV).
For further reading in Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 136, “Oncology and Hematology Emergencies in Children,” by Rick Place, Anne Marie T. Lagoc, Thomas A. Mayer, and Christopher J. Lawlor.