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.

IV. PATHOPHYSIOLOGY

This young boy presented with fever, failure to thrive, fatigue, and bruising. His primary diagnosis was found to be standard risk acute lymphoblastic leukemia (ALL). ALL commonly presents in this way. The presence of all these symptoms may be attributed directly to his ALL as well as to complications that occur secondary to ALL.

ALL causes pancytopenia due to replacing the marrow’s normal hematopoietic cells with leukemic blasts. These cells grow independently of normal growth regulation and crowd the marrow. Eventually, this results in tri-lineage pancytopenia of normal cells. Leukocytes and platelets are the cells with the shortest lifespan outside the marrow, and abnormalities of these cell lines are commonly seen. Infection and bleeding are frequently the primary presenting symptom. A decrease in erythrocytes also occurs as it did in this patient, but often to a less severe extent than in the cell lines that are shorter lived.

It is common for ALL to be associated with fever on diagnosis. Fever in these patients is commonly grouped as one of the following:
  • Fever due to infection
  • Cytokine-mediated fever secondary to the leukemia itself

As normal leukocytes are lost, active barriers to infection deteriorate. Low-grade inflammation of the mucosa can generate cytokines that induce fever. Granulocytes typically respond to these lesions and initiate the healing process. Absent adequate granulocyte numbers, these mucositis lesions are frequently the cause of fever.

Fatigue and failure to thrive are due to a more complex interplay of factors. First, the leukemic clone represents a sizeable metabolic demand on the child. At diagnosis, there may be hundreds of billions of leukemic cells draining nutrients away from the host. To the degree that it is present, anemia may also factor into the fatigue and failure to thrive.

A final common presentation is that of bone pain. As leukemic cells grow in the marrow and increase the number of cells in the space allotted for the marrow, pressure is created in the bone, which is painful.

Have a question or comment about the ASH Teaching Cases? Please e-mail webmaster@hematology.org.