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We describe two cases of massive splenomegaly from an area of Ghana endemic for malaria.
A 32-year-old woman presented with lethargy and an abdominal mass which had been present for 3 years. On examination she had moderately pale conjunctivae but no jaundice or lymphadenopathy and there were no stigmata of chronic liver disease. A non-tender, massively enlarged, firm spleen was palpable 24 cm below the costal margin and there was hepatomegaly of 2 cm with no detectable ascites. Stool and urine microscopy were unremarkable. Haematological investigations revealed a normochromic, normocytic anaemia 7.5 g/dl, total lymphocyte count 12.4 × 109/l and platelet count 100 × 109/l. There were no malaria parasites in her peripheral blood and haemoglobin electrophoresis showed genotype AS. Her total IgM was 7.9 g/l, which was markedly raised compared to the local, normal mean of 3.5 g/l (+2 SD). She was treated with proguanil 100 mg daily and both her spleen size and leucocyte counts reduced. However, despite continuous antimalarial therapy, her spleen enlarged again after 3 years. Further investigations including protein electrophoresis (figure 1) were undertaken.
A 46-year-old man with a 4-year history of abdominal swelling, weight loss and night sweats was found to have generalised lymphadenopathy and splenomegaly of 17 cm. His haemoglobin was 11.4 g/dl, total leucocyte count 93.4 × 109/l and platelet count 150 × 109/l. Bone marrow aspirate showed marked infiltration with mature lymphocytes. There were no malaria parasites on the blood film and haemoglobin electrophoresis showed genotype AA. Immunoglobulin studies revealed IgG 7.6 g/l, IgA 0.9 g/l and IgM 0.07 g/l. There was no paraprotein band on protein electrophoresis. Two months later the patient was re-admitted with a 3-day history of severe diarrhoea and dehydration and died 2 hours after admission.
- What are the common causes of massive splenomegaly in malarious areas?
- Case 1: What was the initial diagnosis?
- Case 1: What does the protein electrophoresis show in the gamma region (figure 1)?
- Case 2: What is the likely diagnosis?
- Case 2: How do you explain the results of the immunoglobulin studies?
See box FB1.
Hyper-reactive malarial splenomegaly (HMS), formerly known as tropical splenomegaly syndrome.
Paraprotein band in the gamma region.
Chronic lymphocytic leukaemia.
Severe, selective IgM deficiency.
Although both these cases presented with massive splenomegaly and lymphocytosis, the sex and age of the patients, the response to antimalarial therapy (case 1) and the associated lymphadenopathy (case 2), pointed towards different diagnoses. Diagnostic criteria for HMS include splenomegaly ⩾10 cm, elevated IgM, response to antimalarial therapy, and exclusion of underlying lymphoma.1 Initially, case 1 fulfilled criteria for HMS but immunofixation and immunoselection of her paraprotein demonstrated μ-heavy chain with no associated immunoglobulin light chain (figure 2) and a diagnosis of μ-heavy chain disease was made. μ-Heavy chain disease is the least common type of heavy chain disease and was first reported in 1970.2 It is usually associated with massive splenic enlargement and lymphocytosis; bone lesions and transformation to large cell lymphoma have also been described.3 4 Several of the reported cases originated in West Africa, leading to the suggestion that a high rate of parasitic infestation and subsequent IgM response may be relevant to the aetiology.
Although chronic lymphocytic leukaemia in industrialised countries is usually associated with lymphadenopathy, splenomegaly is a common presentation in Africa (case 2).5 B-Lymphoproliferative disorders are often associated with reduced immunoglobulin levels. However, case 2 had severe selective IgM deficiency with normal IgG and IgA levels. This immunoglobulin profile has been described in adults in association with systemic lupus erythematosus, Hashimoto's disease, atopy, coeliac disease, meningococcal septicaemia and as a familial condition.6 It is not a feature of chronic lymphocytic leukaemia. In adults, selective IgM deficiency is usually detected incidentally but despite this, reports indicate a fatal outcome, usually from infection, as in this case.
These two patients illustrate that the classical list of causes of massive splenic enlargement should not be considered exclusive, and that if clinical and laboratory findings do not completely support the initial diagnosis, supplementary tests should be performed.
Case 1: μ-heavy chain disease.
Case 2: chronic lymphocytic leukaemia with selective IgM deficiency.