Fever and Petechiae in an Infant

James Harper, MD

Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE

This case was reviewed and updated in May 2011 by members of the Teaching Cases Subcommittee

Copyright of the American Society of Hematology, 2006. ISSN: 1931-6860.

VII. TEACHING POINTS

  1. Childhood ALL has its peak age incidence around 2-3 years of age, with increased incidence through 10 years of age, then declining incidence until the early 20's, where it stabilizes through the early 60's, when incidence increases.
  2. ALL is the most common malignancy in children, accounting for about 23% of cancer diagnoses under the age of 15 years.
  3. Leukemia in children is most commonly lymphoblastic and acute, in contrast to adults, where chronic leukemias and leukemias of the myeloid lineages are more common. ALL does occur in adults and tends to have a worse prognosis than in children.
  4. Common presentations of childhood ALL include fever, fatigue/malaise, bruising or bleeding, bone pain (especially periarticular and back pain) and lymphadenopathy. A high index of suspicion is always required in making this diagnosis.
  5. The differential diagnosis for ALL includes:

    Infection
      EBV
      CMV
      HIV
      Pertussis
    Immunologic
      JRA
      SLE
      Immune cytopenias
    Other malignancies
      AML
      CML
      Juvenile Chronic Myelogenous Leukemia
      Lymphoma
      Neuroblastoma
      Rhabdomyosarcoma
    Other marrow diseases
      Aplastic anemia
      Myelodysplastic syndrome
      non-immune neutropenia
    Others

  6. The differential diagnosis for fever of unknown origin includes:

    Entity Incidence
    Infection
      Respiratory
      Urinary Tract
      Bacterial Meningitis
      Tuberculosis
    52.3%
      14.5%
      3.9%
      1.8%
      1.9%
    Collagen-vascular/Inflammatory
      JRA
      SLE
      Crohn's Disease
    11.5%
      5.1%
      1.4%
      1.5%
    Malignancy
      Leukemia
      Lymphoma
    5.0%
      2.4%
      1.0%
    Undiagnosed 21.8%
    (ref: Lau, Uba, Lehrman, Infectious Disease Chapter 9, Rudolph's Fundamentals of Pediatrics Ed 3. 2002. Eds. Rudolph A, Kamei R, Overby K. Page 318, table 9-17.)

  7. Genetic analysis of the leukemic blast cells may offer prognostic assistance by detecting non-random translocations that confer either good or bad risk features to the disease.
  8. Genetic analysis of the leukemic blasts by karyotype and by Fluorescence In Situ Hybridization (FISH) may also allow for more precise measurement of residual disease after treatment. The presence of blast cells at the end of induction chemotherapy, even if only detectable by FISH, confers a poor prognosis for cure.
  9. Flow cytometry may detect DNA quantity and surface antigens that can be of prognostic significance and can be used to measure response to disease.
  10. Lymphoblasts may invade the testicles and the CNS where barriers protecting chemically sensitive normal structures may protect them from systemic chemotherapy (Sanctuary Sites).
  11. Advances in the treatment of childhood cancer have come about due to the efforts of the various cooperative research groups involved with childhood cancer. Because childhood cancer, including ALL, is relatively uncommon, all children should be offered treatment on an appropriate cooperative group research protocol in a pediatric oncology setting.

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