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Case Reports

Indian Pediatrics 2004;41:605-607 

Hemophagocytic Syndrome Associated with Visceral Leishmaniasis


Nurten Koçak
Makbule Eren
Aysel Yüce
Fatma Gümrük*

From the Hacettepe University, Faculty of Medicine, Department of Pediatrics, Sections of Gastroenterology and *Hematology, Ankara-Turkey.

Correspondence to: Dr. Aysel Yuce, Hacettepe University, Faculty of Medicine, Department of Pediatrics, Section of Gastroenterology, 06100 Ankara-Turkey.
E-mail: [email protected]

Manuscript received: August 8, 2003; Initial review completed: September 24, 2003;
Revision accepted: October 29, 2003.

Abstract:

Hemophagocytosis, either primary (familial) or secondary (reactive), is a life threatening condition in childhood. Etiology should be vigorously searched to avoid a diagnosis of primary hemophagocytosis and treatment with cytotoxic drugs. A child with visceral leishmaniasis causing hemophagocytosis is presented.

Keywords: Hemophygocytosis, Leishmaniasis.

Visceral leishmaniasis (kalaazar) is a sys-temic disease caused by the dissemination of the intracellular parasite of genus leishmania, through the reticuloendothelial system. The infection is endemic in most Mediaterranean countries, southern Europe, Middle East, East Africa, China, India and Turkey(1,2). It may mimic or lead to several types of hemato-logical disorders including pancytopenia and hemolysis. Recently, hemophagocytic syndrome has been reported(3-9).

Differentiation between primary and secondary hemophagocytic syndrome is extremely important. Hemophagocytosis associated with such infectious illnesses resolves with treatment of the underlying infections, while cytotoxic drugs are used for the treatment of primary cases. We report a child with visceral leishmaniasis as a rare cause of the hemophagocytic syndrome.

Case Report

A previously healthy 18 month-old-girl presented with fluctuating fever (39-40ºC) for one month. Physical examination revealed pallor and distended abdomen with hepato-megaly and splenomegaly (6 cm and 4 cm below the costal margins respectively). Neither lymphadenopathy nor any bleeding signs were observed. Serological markers for Epstein-Barr virus, cytomegalovirus, toxoplasmosis, hepatitis A and B viruses were negative; salmonella and brucella agglutinins were negative and blood cultures could not demonstrate any infectious agent.

Blood counts showed pancytopenia with hemolglobin concentration of 7.1 g/dL, white blood cell count 2400/mm3 and platelet 33000/mm3; red cell morphology was normal. Serum levels of aspartate aminotransferase (AST) 492 IU/L, alanine aminotransferase (ALT) 315 IU/L, gamma-glutamyltransferase (GGT) 303 IU/L, triglycerides 297 mg/dL, erythrocyte sedimentation rate 68 mm/hour, C-reactive protein 12.2 mg/dL and ferritin 15000 ng/mL, were all elevated. Fibrinogen level (214 mg/dL) was normal. On bone marrow aspiration marked erythrocyte and lymphocyte phagocyted histiocytes and leishmania amastigotes were observed. Liposomal amphotericin B (AmBisome®) was administered immediately (starting with 0.5 mg/kg/day and gradually increased to 2 mg/kg/day was given on the first 3 days. Treatment was continued with 2 mg/kg/day on the following 2 days and an additional 2 mg/kg/day on day 15). Treatment was well tolerated. Symptoms and clinical findings improved gradually. Fever was controlled and hepatosplenomegaly regressed. One month after the end of therapy, physical examination revealed further regression of hepato-splenomegaly (3 cm below costal margins). Marked improvement of hemoglobin (10.7 g/dL), white blood count (9800/mm3) and platelet count (358000/mm3) were observed.

Discussion

Hemophagocytic syndrome is a disorder characterized by nonmalignant infiltration of vital organs by activated lymphocytes and macrophages. Engulfment of any hemato-logical cell type in bone marrow and reticuloendothelial system by these activated cells, called hemophagocytosis is the hall mark of the disease(3). This may result in pancytopenia, fever, organ enlargement, neurological dysfunction and disseminated intravascular coagulation(3). Hemophago-cytic syndrome may be classified as primary, which may be further, subclassified as sporadic and familial and secondary that is reactive to an underlying medical illness(3). Identification of an etiological cause may not be easy and moreover the clinical course of the triggering infection and hemophago-cytosis may coincide and lead to delay in diagnosis.

Visceral leishmaniasis has been rarely defined as an etiological cause of hemo-phagocytic syndrome. Pancytopenia, hemo-lysis, megaloblastic findings, fibrinolysis, cold agglutinin syndrome and hemophago-cytic syndrome are some of the hemato-logical abnormalities observed in visceral leish-maniasis(3-9). Diagnostic delay might cause severe complications and death occurs in 90% patients without specific antileishmanial treatment(8). Definitive diagnosis of visceral leishmaniasis is established by isolating the organisim from spleen, bone marrow and liver. Amastigotes and hemophagocytic cells were seen on bone marrow smears of our patient. Particularly in young children visceral leishmaniasis presenting with hemophago-cytic syndrome may cause considerable diagnostic difficulty since its clinical signs coincides with hemophagocytic syndrome and results in over treatment with cytotoxic drugs(9). Clinical signs and laboratory abnormalities of our case were compatible with the proposed diagnostic criterion for hemophagocytic syndrome(3).

Treatment of reactive hemophagocytic syndrome depends on the treatment of underlying cause. Liposomal amphotericin B provides sufficient drug levels in tissue and persistent detectable levels are observed 14 days after treatment(10). Our patient also improved under liposomal amphotericin B treatment. The drug was well tolerated with no side effects.

In conclusion the early diagnosis and appropriate treatment of visceral leishmaniasis is important. Although the prominent bone marrow hemophagocytosis, high fever and pancytopenia may lead to diagnostic confusion, patients with hemo-phagocytic syndrome should be vigorously screened for visceral leishmaniasis, before accepting the case as primary hemophago-cytosis and starting cytotoxic therapy.

Contributors: NK, ME and AY did the clinical work up. FG did hematological work up. AY reviewed the final draft and will be the guarantor.

Funding: None.

Competing interests: None stated.

 

 References

 

1. Melby PC. Leishmania. In: Behrman RE, Kliegman RM, Jenson HB eds. Nelson Textbook of Pediatrics, 16th edn. Philadelphia, WB Saunders, 2000; pp 1041-1045.

2. Hicsonmez G, Ozsoylu S. kala-azar in childhood: a survey of clinical and laboratory findings and prognosis in 44 childhood cases. Clin Pediatr (Phila) 1972; 11: 465-467.

3. Fisman DN. Hemophagocytic syndromes and infection. Emerg Infectious Diseases 2000; 6: 601-608.

4. Hemophagocytic lymphohistiocytosis asso-ciated with visceral leishmaniasis. Pediatr Hematol Oncol 2001; 18: 65-70.

5. Granert C, Elinder G, Ost A, Henter JI. Kala-azar in a one-year-old Swedish child. Diag-nostic difficulties because of active hemo-phagocytosis. Acta Pediatr 1993; 82: 794-796.

6. Russo R, Nigro LC, Minniti S, Montineri A, Gradoni L, Caldeira L. Visceral leishmaniasis in HIV infected patients: treatment with high dose liposomal amphotericin B (AmBisome). J Infect 1996; 32: 133-137.

7. Kokkini G, Vrionis G, Liosis G, Papaefstathiou J. Cold agglutinin syndrome and hemo-phagocytosis in systemic leishmaniasis. Scand J Hematol 1984; 32: 441-445.

8. Tunc B, Ayata A. Hemophagocytic syndrome: a rare life-threatening complication of visceral leishmaniasis in a young boy. Pediatr Hematol Oncol 2001; 18: 531-536.

9. Gegnaire MH, Galambrun C, Stephan JL. hemophagocytic syndrome: A misleading complication of visceral leishmaniasis in children - A series of twelve cases. Pediatrics 2000; 106: e58.

10. US Food and Drug Administration approval of AmBisome (liposomal amphotericin B) for treatment of visceral leishmaniasis. Clin Infect Dis 1999; 28: 42-48.

 

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