(Hyper-reactive malarial splenomegaly; Big spleen disease)
Tropical
Splenomegaly Syndrome or Big Spleen Disease is massive enlargement of the spleen resulting
from abnormal immune response to repeated attacks of malaria. It is seen among residents
of endemic areas of malaria and it is not species specific. It occurs mainly in tropical
Africa, but also in parts of Vietnam, New Guinea, India, Sri Lanka, Thailand, Indonesia,
South America and the Middle East. It must be differentiated from splenomegaly associated
with acquisition of immunity in endemic and hyperendemic areas.
Tropical Splenomegaly Syndrome is
characterised by massive splenomegaly, hepatomegaly, marked elevations in levels of serum
Ig M and malaria antibody. Hepatic sinusoidal lymphocytosis is also seen. In about 10% of
African patients, it may be associated with peripheral lymphocytosis (B cells).
The interaction of repeated malarial
infection and unknown host factors results in the production of cytotoxic Ig M
antisuppressor lymphocyte (CD8+) antibodies. This causes inhibition of suppressor T cells,
which normally regulate IgM production. This leads to uninhibited B cell production of IgM
and the formation of cryoglobulins (IgM aggregates and immune complexes). The need to
clear these macromolecular aggregates stimulates the reticuloendothelial system, resulting
in hyperplasia. This causes the progressive and massive enlargement of the spleen and
hepatomegaly.
The spleen is massively enlarged. It
shows dilated sinusoids lined with reticulum cells showing marked erythrophagocytosis and
lymphocytic infiltration of the pulp. Liver exhibits sinusoidal dilatation, infiltration
with lymphocytes and hyperplasia of the Kupffer's cells with phagocytosis of cellular
debris and red cells.
Most patients present during adult life.
Patients present with dragging pain in the upper abdomen, or sometimes may even complain
of a palpable mass. Some may experience recurrent sharp pains in the upper abdomen,
probably due to perisplenitis or splenic infarcts. Some patients may have weight loss and
cachexia. On examination, there is massive splenomegaly and hepatomegaly.
The peripheral smear shows normocytic
normochromic anemia with increased reticulocyte count. Leukopenia and thrombocytopenia may
also be seen due to hypersplenism. Malarial parasites are not found in the peripheral
blood. There is increase in the serum levels of polyclonal IgM with cryoglobulinemia,
reduced C3 and the rheumatoid factor may be positive.
The condition should be differentiated
from other causes of splenomegaly in the tropics- Kala-Azar, Schistosomiasis,
post-necrotic cirrhosis, thalassemia, leukemia, lymphoma, myelofibrosis, non-tropical
idiopathic splenomegaly, Felty's syndrome etc. In patients with splenic lymphoma, more
than 30% of circulating lymphocytes are villous and they can be differentiated from
hairy-cell leukemia by their lack of CD25, CD11C and
tartrate-resistant acid phosphate markers. Increased levels of IgM and antimalarial
antibody, hepatic sinusoidal lymphocytosis on liver biopsy and response to antimalarial
therapy (improvement in clinical condition as well as reduction in IgM and malarial
antibody titre within three months of continuous antimalarial treatment) favour a
diagnosis of tropical splenomegaly syndrome.
The disease generally runs a benign
course. However, sometimes it may be associated with severe anemia, leading to congestive
cardiac failure. These patients are also more prone for secondary bacterial infections of
the skin and respiratory tract and have an increased mortality. Portal hypertension does
not develop and the condition is reversible with antimalarial treatment. Some patients in
Ghana were found to develop splenic lymphoma with hairy lymphocytes.
The treatment of tropical splenomegaly
syndrome involves administration of antimalarial prophylaxis for prolonged periods of
time. This removes the antigenic stimulus provided by repeated malarial infection and
allows the immune system to return to normal. The choice of antimalarial depends on the
local sensitivity pattern. Chloroquine weekly or proguanil daily have been found to be
useful. These drugs may have to be continued for long periods, possibly for life. Severe
anemia may require blood transfusion. Splenectomy may do more harm than good and it may be
beneficial in only patients with splenic lymphoma. Splenic irradiation or antimitotic
therapy are not beneficial and may be even dangerous.
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