Hyper-reactive malarial splenomegaly (HMS) is a syndrome of massive, unexplained splenomegaly occurring in a malarious region, accompanied by lassitude, fever, weight loss, hypergammaglobulinemia (especially IgM), and cryoglobulinemia. A clinical response to prolonged antimalarial prophylaxis is diagnostic,1 but the pathogenesis is unclear. In some patients, the condition will progress to splenic lymphoma with villous lymphocytes.2 Figure 1A shows a 14-year-old Ugandan girl with HMS with the spleen profile outlined by traditional therapeutic scarifications. Figure 1B demonstrates cryoglobulinemia. The left vial contains HMS plasma kept overnight at 25°C, and the right vial shows a cloudy cryoprecipitate (containing IgM, IgG, complement, and rheumatoid factor) in the same plasma kept overnight at 4°C. Figure 1C shows typical hepatic sinusoidal lymphocytosis in a liver biopsy from an HMS patient, and Figure 1D displays IgM lining the hepatic sinusoids revealed by fluorescein-tagged goat anti-IgM antibody.3
Address correspondence to John L. Ziegler, Professor of Medicine, Emeritus, University of California–San Francisco, 2340 Sutter Street, N424, San Francisco, CA 94143-0808. E-mail:
Bates I, Bedu-Addo G, Rutherford TR, Bevan DH, 1997. Circulating villous lymphocytes—a link between hyperreactive malarial splenomegaly and splenic lymphoma. Trans R Soc Trop Med Hyg 91 :171–174.