Fig. 46.9. Spleen. The normal sinusoidal pattern is preserved and there is hyperplasia of the cells in the intersinusoidal tissues. These cells are mostly mature lymphocytes. H&E, original magnification x300. (From Itakura 1995).

Fig. 46.10. Liver. There is hyperplasia and hypertrophy of the Kupffer cells and occasional lymphocytes in the sinusoids. H&E, original magnification x480. (From Itakura 1995).

Epidemiology and Pathology

Children from 4 years to puberty are the most commonly affected, but no age is exempt. It is probable that the splenomegaly is due to an abnormal immune response to malaria (a malarial antigen?), possibly with an associated genetic factor. Patients with TSS have malarial antibody titers which are higher than those of their neighbors who have normal spleens. In India children may have gross splenomegaly, portal hypertension, and noncirrhotic portal fibrosis. Those with the sickle cell trait are partially protected from TSS, as they are also from malaria. There is no lymphadenopathy. There is anemia, from blood dilution as a result of increased plasma volume together with pooling in the spleen and increased destruction of red cells: when the spleen is very large, there may be intrasplenic sequestration of a third to half of the total circulating red cell mass. Hyperplasia of cells in the intersinusoidal tissues is seen (Fig. 46.9). There is increased bone marrow activity, but this does not compensate for these changes. The intrasplenic pressure is raised. Liver biopsy shows hepatic sinusoidal lymphocytosis, and possibly hyperplasia of the Kupffer cells (Fig. 46.10). Yet, except for the lowered serum albumin, liver function tests are usually normal. T-lymphocytes in the peripheral blood are elevated, IgM is high, and cold agglutinin and rheumatoid factor titers are raised, as are thyroglobulin and antinuclear factor.

None of the above explains the splenomegaly: