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Uncommon cause of hepatosplenomegaly in an immunocompetent patient

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Q1: What does the bone marrow show?

The bone marrow was cellular with myeloid preponderance and a few atypical cells. Amastigotes of Leishmania donovani (LD bodies) were present with an average parasite density of 1–10 parasites per 10 oil immersion fields or 3+ (see fig 1, p 478; LD bodies are arrowed).1

Q2: What is the diagnosis and what further corroborative tests may be done?

The diagnosis is visceral leishmaniasis. Further tests include the aldehyde test and ELISA to document the presence of IgG antibodies against leishmania antigen in blood. Both these tests were positive in this patient. Other serological methods such as the indirect fluorescent antibody test and the direct agglutination test may also be used for the diagnosis.

Q3: What is atypical in this patients’ presentation?

The classical presentation of visceral leishmaniasis in immunocompetent individuals is that of high grade fever with hepatosplenomegaly in the setting of a visit to or residence in an endemic area. There were the two atypical features in this patient. Firstly, he lived in a non-endemic zone and had no history of travel to any known endemic area in the country. Secondly, the absence of fever, which is usually the presenting symptom, was striking, especially with no evidence of immunodeficiency detectable.

Q4: How is this condition treated?

Sodium stibogluconate is the traditional drug of choice, given parenterally in doses of 20 mg/kg body weight for four weeks. However, with increasing resistance to this compound, especially in the endemic areas, it is gradually being replaced by amphotericin B which is infused intravenously in doses of 0.5–1 mg/kg daily up to a total of 20 mg/kg. Amphotericin is a toxic drug and may produce acute febrile reactions, myalgia, and vomiting after each infusion. Dose related nephotoxicity is the major long term concern and may manifest as azotaemia, acidosis, and hypokalaemia.

Discussion

Visceral leishmaniasis, or kala-azar as it is popularly called, is a chronic infectious disease caused by parasites of the L donovani complex and characterised by irregular fever, splenomegaly, hepatomegaly, weight loss, pancytopenia, and hypergammaglobulinaemia. The overall prevalence of leishmaniasis is 12 million cases worldwide spread over 82 countries mainly in Asia, Africa, and the Americas, with an annual incidence of 500 000 new cases.2 Ninety percent of these cases occur in endemic or hyperendemic areas, and are particularly concentrated in India, Nepal, Bangladesh, Kenya, Ethiopia, Sudan, and parts of South America,3 though sporadic cases have been described from all over the world. In India, it is a serious problem in the states of Bihar, Bengal, Assam, Sikkim, Eastern Uttar Pradesh, and Tamil Nadu. Cases have also been reported from Gujarat, Jammu and Kashmir, Himachal Pradesh, and Maharashtra.4 In recent years, HIV-leishmania coinfection has been steadily rising particularly in the Mediterranean basin (Spain, Italy) and France.5 Here, we report an interesting patient with florid visceral leishmaniasis and heavy parasitaemia (>100 LD bodies/100 oil fields) but without any fever or history of visit to an endemic area.

The spectrum of clinical disease of kala-azar ranges from asymptomatic infection (which may flare up due to malnutrition or immunosuppression) to full blown visceral involvement.6 Fever is the commonest symptom followed by abdominal discomfort, anorexia, wasting, and cough. Epistaxis occurs in 44%–55% of patients. Most of the subclinical cases occur in the endemic areas, and are much more common in children and young adults. Diagnosis is made by demonstration of the parasite in stained smears or cultures of the aspirate from the bone marrow or spleen, although serological tests such as the indirect fluorescent antibody test, direct agglutination test, and ELISA are gaining popularity. Single peripheral blood smear examinations give a yield of only up to 46% in daytime samples and up to 66% in night samples, hence are not considered to be a reliable diagnostic modality. Splenic aspiration gives a higher yield (up to 98% compared with 80%–85% for bone marrow aspirate) but may cause haemorrhage.

Apart from other known causes of massive splenomegaly such as chronic myeloid leukaemia and myelofibrosis, the possibility of hyperactive malarial splenomegaly, formerly called tropical splenomegaly syndrome, should also be kept in mind. Hyperactive malarial splenomegaly is an immunological disorder related to chronic exposure to malaria. It is primarily a diagnosis of exclusion and is characterised by massive splenomegaly, absence of malaria parasite in the peripheral blood smear, high titres of antimalaria antibodies, hyperglobulinaemia, pancytopenia, and lymphocytic infiltration of hepatic sinusoids.7 Since visceral leishmaniasis and hyperactive malarial splenomegaly have many clinical and laboratory features in common, these two conditions should be differentiated, as was conclusively done in this patient by the demonstration of LD bodies in the bone marrow aspirate.

There were two unusual features in this patient. Firstly, he lived in a non-endemic zone and even on repeated questioning, denied any history of travel to any known endemic area in the country. Though there have been reports of asymptomatic individuals with amastigote forms in the bone marrow and peripheral smear,8 they were residents of known endemic areas and had significantly lower parasitic load (<10/1000 oil fields).

Secondly, the patient was always afebrile. He also had no evidence of immunodeficiency. However, he may have been specifically immunosuppressed due to a high antigenic load to leishmania parasite leading to lack of an inflammatory response resulting in absence of fever. Such observations have been reported previously in leishmaniasis,9 lepromatous leprosy, and tuberculosis. Due to these atypical features, kala-azar was not considered as a likely possibility until the bone marrow aspirate revealed the diagnosis, after which the aldehyde test and ELISA testing to detect antileishmania antibodies were done. In the absence of fever and significant travel history, other known modes of transmission of this disease should be considered, such as congenital transmission, via blood transfusion or due to a novel autochthonous focus.10 Since our patient had never received a blood transfusion and at this age congenital transmission is rather unlikely, the possibility of an autochthonous focus should also be considered. Consequently, in a tropical country like India, where kala-azar causes hundreds of deaths annually, such atypical presentations should be borne in mind to make a rapid diagnosis of this potentially fatal, but fully treatable disease.

Final diagnosis

Visceral leishmaniasis.

References

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