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.
