November 1995, Volume 45, Issue 11

Case Reports

Severe Haemophagocytic Syndrome in Falciparum Malaria

Masood Anwar  ( Armed Forces Institute of Pathology, Rawalpindi. )
Muhammad Saleem  ( Armed Forces Institute of Pathology, Rawalpindi. )
Iftikhar Ahmad Malik  ( Armed Forces Institute of Pathology, Rawalpindi. )

Malaria is responsible for 0.5-1.2 million deaths each year1. The majority of fatal cases are due to Plasmodium falciparum infection which is known for its severity, compli­cations and drug resistance1,2. Most of the fatalities occur in children and non- immune travellers to the endemic areas1. A number of complications have been described in falciparum malaria2 but, to the best of our knowledge, haemophagocytic syndrome has not been described in this condition. We report a case of Choloroquine resistant falciparum malaria which was complicated with severe haemophagocytic syndrome.

Case Report

A young German tourist reported on 30 August, 1993 with fever, generalized weakness and yellow discolouration of eyes for seven days. He had been in Pakistan for the last 20 days and was not having chemoprophylaxis for malaria. He was non-addict and gave no history of risk factors for HIV infection. On examination, he was pale and jaundiced, temperature was ‘39.2°F. The positive findings, on systemic examination, were heap to (2’cm) splenomegaly (3 cm). His blood counts (Table) revealed mild anaemia with normal leucocyte and platelet counts. Peripheral blood smear showed numerous trophozoites and gametocytes of Plasmodium falciparum. Urine examination revealed increased urobilino­gen but no haemoglobinuria and liver function tests showed hypethilirubinemia (168 umol/L) with normal hepatic en­zymes. The screening tests for viral hepatitis and HIV infection were negative. The patient was put on standard doses of Chlomquine, to which he did not respond. Repeat blood counts on 3rd September (Table), showed a fall in Hb, leucocyte count and platelet count and malarial parasites were still present in almost the same numbers in the peripheral blood. Serum bilirubin raised further (340 umol/L). The patient was then put on standard doses of Fansidar with which his fever subsided and by 7th September the bilirubin level came down to 59.5 umol/L At this stage, however, his blood counts showed a persistent fall in Hb, TLC and platelet count although the malarial parasites had disappeared from the peripheral blood (Table): Because of pancytopenia a bone marrow aspiration biopsy was performed on 9th September. The examination of Leishman stained bone marrow smears revealed marked proliferation of mature looking histiocytes, the majority of which showed active haemophagocytosis. Almost all types of blood cells were being phagocytosed by these macrophages (Figure).

There was associated cry throid hyperplasia with normal mvelopoiesis and normal mega karyocytes. Few gametocytes and occasional tropho­zoite ofPlasmodiumfalciparum were seen in the bone marrow. One week later, his blood counts had markedly improved and no malarial parasite could be seen in the peripheral blood (Table).

Discussion

Histiocytic hyperplasia with haemophagocytosis (HHH) was first recognized by Scott and Robb-Smith in 19393 and was believed to be a malignant condition for a long time. In 1979 a similar benign and reversible condition was described in association with viral infections in immunosup­pressed patients by Risdal et al4. Since then, reactive histio­cytic hyperplasia with intense haemophagocytosis has been described in a number of benign and malignant disorders. These have been reviewed by Suster et al5. However, malaria has not been documented as a cause of HHH. Risdall et at4 proposed that this type of haemophagocy­tosis results due either to alteration in the phagocytic cells or in the ingested elements and probably represent an exaggeration of the normal function of the histiocytes. In our case a high antigen load, due to malarial parasites in a previously unexposed individual, might have resulted in an exaggerated macrophage response. It has also been suggested that in­creased production of macrophage colony stimulating factor probably could result in proliferation of histiocytes6. The marked stimulation of the immune system could also result in excessive production of phagocytosis inducing factor (PIF) by CD4÷ T-lymphocytes7 and PIF could then cause histiocytic proliferation and haemophagocytosis. These mechanisms may also have been operative in this case. Besides the Tumour Necrosing Factor (TNF), which is produced in excess in falciparum malaria, also induce phagocytosis8. It is important to note that the benign haemophagocy­tosis can be differentiated from the malignant histiocytosis by the greater involvement of the bone marrow than other reticulo-endothelial tissue, the mature appearance of the proliferating phagocytic cells and by the improvement in the clinical condition after successful therapy4. However, even benign haemophagocytosis may prove fatal, because of the resulting pancytopenia. It can easily be reverted by treating the underlying cause and supporting the patient during pancy­topemc phase.

References

1. Cattani, J., Davidson, D. and Engers, H. Malaria. 11th Programme report, 1993. Geneva, Tropical Disease Research, 1993, PP. 15-25.
2. Warrell, D.A., Molyneux, M.E. and Beales, P.F. Severe and complicated malaria (2nd ed). Trans. R. Soc. Trop. Med. Hyg., 1990;84(Suppl 2): 1-10.
3. Scott, RB. and Robb-Smith A.H.T Histolytic medullary reticulosis. Lancet, 1939;2:194-195.
4. Risdall, R.J., McKenna, R.W., Nesbit, ME. et at. Virus- Associated haemo­ phagocytic syndrome: A benign histiocytic proliferation distinct from malignant histiocytosis. Cancer, 1979;44:993- 1002.
5. Suster, S., Hilscnbeck, S. and Rywlin, AM. Reactive histiocytic hyperplasia with haemophagocytosis in haematopoictic organs: A re-evaluation of the benign haemophagocytic proliferation. Hum. Pathol., 1988: 19:705-712.
6. Groopman, J.E. and Golde, D.W. The histocyte disorders: A pathophysiologic analysis. Ann. Intern, Med., 1981,94:95-107.
7. Simrell, CR., Margolick, J.B., Crabtree, OR. et at. Lymphokine- induced phagocytosis in angiocentric immunoproliferative lesions (AlL) and malignant lymphoma arising in AlL. Blood, 1985;65:1469- 1476.
8. Clark, I.A. and Chaudhry, G. Tumour necrosis factor may contribute to the anaemia of malaria by causing dyserythropoiesis and erythrophagocytosis. Br. J.Haematol., 1988;70:99-103.

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