Chronic Splenomegaly in a 10-Year-Old Boy

Rebecca Winderman, MD; Natalie Banniettis, MD; Simon S. Rabinowitz, MD, PhD


April 23, 2018


This child was a recent immigrant from Guinea, where malaria is endemic. Despite negative smears for malaria, a high index of suspicion prompted molecular testing (polymerase chain reaction [PCR]), which was positive for Plasmodium falciparum. P falciparum is responsible for more than 85% of endemic malaria species in Guinea. This child was diagnosed with hyperreactive malarial syndrome (HMS), also known as tropical splenomegaly syndrome. HMS is the leading cause of massive splenomegaly in malaria-endemic countries.[1] The incidence ranges from 0.5% to 80% of the adult population in endemic countries. The pathogenesis is unknown but has been postulated to result from chronic antigenic stimulation due to long-term exposure to the malaria parasite in the blood. This parasite is initially obtained via a bite from an infected mosquito. The highest prevalence is in Papua New Guinea (≤80%), with an estimated 3-year fatality rate of 36%.[2]

The patient in this case presented with long-standing splenomegaly, anemia, a slightly elevated IgG level, and a history of residing in a highly endemic area, making the diagnosis of HMS most likely.

Sickle cell disease is associated with splenomegaly that can evolve into splenic sequestration. However, this child had normal hemoglobin electrophoresis findings and had long-standing splenomegaly. By his age, a patient with sickle cell disease would have likely had infarction of the organ rather than stable enlargement.

Leukemia, lymphoma, or other less commonly encountered primary or metastatic pediatric malignancies may present with splenomegaly and an elevated erythrocyte sedimentation rate. However, in this case, the patient's history of a long-standing, chronic process without any clinical progression made this possibility unlikely. Furthermore, the imaging and blood tests did not suggest a heterogeneous organ or reveal any malignant cells.

Several storage diseases can present with splenomegaly. The mucopolysaccharidoses are a group of disorders that involve a defect in lysosomal enzymes, which degrade mucopolysaccharides. Patients initially develop normally, with the onset of abnormalities later in infancy or childhood. These patients often have multiorgan involvement, including neurologic, cardiovascular, pulmonary, ophthalmologic, hearing, and musculoskeletal findings. Diagnosis is initially made by measuring urine glycosaminoglycans, which were negative in this case.

Other common examples of rarely encountered lipid storage diseases include Gaucher disease or Fabry disease. Affected individuals usually have autosomal recessive inheritance of an enzyme mutation that prevents complete metabolism of a naturally occurring precursor. Abnormal metabolites then accumulate in the reticuloendothelial system, yielding enlargement of the spleen and liver. Oftentimes central nervous system or other organ system involvement is present; however, splenomegaly can be isolated. Definitive diagnosis is made by testing for the individual enzyme that is affected. If the patient in this case did not have a positive PCR result for malaria, peripheral blood leukocytes would have been obtained to measure glucocerebrosidase activity as a test for Gaucher disease.

Gaucher disease can present with splenomegaly, usually in the setting of concurrent hepatomegaly, pancytopenia (particularly anemia and thrombocytopenia), and bone involvement. Patients with Gaucher disease often have failure to thrive. In the case of Gaucher type 2 and 3, individuals have neurologic involvement. Although this patient had significant splenomegaly, he did not have the typical pancytopenia or hepatomegaly associated with Gaucher disease and had normal enzyme activity. Furthermore, Gaucher disease type 2 and 3 involves neurologic dysfunction, which the patient did not have.


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