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DOI: 10.4103/2224-3151.115828
Atypical presentation of visceral
leishmaniasis (kala-azar)
from non-endemic area
Quick Response Code:
Yatendra Singh, Paramjeet Singh, Subhash Chandra Joshi, Mohammad Khalil
Department of Medicine,
Government Medical
College, Haldwani, India
Abstract
Leishmaniasis is a major public health problem in various part of world; it has also
emerged in new geographic areas and host populations. Visceral infection can
remain subclinical or become symptomatic, with an acute, subacute or chronic
course. Kala-azar, or visceral leishmaniasis (VL), presents as fever, pancytopenia
and hypergammaglobulinaemia. The presence of splenomegaly is characteristic
of VL. It may be absent in immunocompromised patients, who may present
atypically. Absence of splenomegaly is rare in immunocompetent patients, though
it may occur in the early stages. Atypical presentations can be challenging to the
clinician. This paper presents an atypical presentation of kala-azar, with multiorgan failure in the absence of splenomegaly or fever.
Address for correspondence:
Dr Yatendra Singh, Room no. 32
Sr Hostel Government Medical
College, Haldwani 263139, India
Email: [email protected]
Key words: kala-azar without splenomegaly, multi-organ failure, pancytopenia,
visceral leishmaniasis
Introduction
Leishmaniasis is a vector-borne zoonosis with variable clinical
presentations, in the form of visceral, cutaneous (of localized
or diffuse types) and mucocutaneous types, depending upon
the Leishmania species and immune responses of the hosts.
Visceral leishmaniasis (VL) is endemic in various parts of India,
mainly Bihar, West Bengal and Orissa, as well as neighbouring
countries such as Nepal and Bangladesh. Recent increases
in the number of cases have been reported from nonendemic
areas of India.1 Atypical presentation of VL in an nonendemic
area can lead to a diagnostic dilemma. This paper reports VL
in a patient from a nonendemic region of India, who presented
with pancytopenia and multi-organ failure in the absence of
splenomegaly or fever.
Case History
The patient gave written informed consent for publication.
The patient was a 32-year-old woman, who did not smoke or
consume alcohol and who worked as a labourer in her native
region, Uttarakhand, India. She was admitted to hospital with
a 4-week history of weakness, vomiting, abdominal pain,
progressive dyspnoea, loss of appetite and weight loss. She was
severely anaemic and two units of packed red blood cells had
been transfused prior to admission. Intravenous ceftriaxone
at 1 g twice a day had been administered by her general
practitioner for the past 5 days, but brought no symptomatic
relief. No significant past history was present. She had never
visited any area endemic for VL.
On physical examination, the patient was tachypnoeic and
tachycardic, with mild jaundice and severe pallor. Abdominal
examination revealed mild hepatomegaly, with tenderness in
the right hypochondrium. The remaining systemic examination
was normal. A chest radiograph was normal. Ultrasonography
of the abdomen revealed early medical renal disease and mild
hepatomegaly.
Laboratory investigations revealed that haemoglobin
was 38 g/L and normocytic normochromic anaemia with
pancytopenia was observed on peripheral smear examination;
total serum bilirubin was 54.72 µmol/L and serum creatinine
was 291.7 µmol/L. The transaminases were raised (serum
glutamic oxaloacetic transaminase [SGOT] – 766 IU, serum
glutamic pyruvic transaminase [SGPT] – 555 IU). Total
serum proteins were 65 g/L and albumin was 15 g/L. Others
tests, including arterial blood gas analysis, were in the normal
range. Tests for enteric fever, dengue, malaria, HIV and viral
hepatitis (A, B, C and E) were negative. The thyroid profile,
WHO South-East Asia Journal of Public Health | January-March 2014 | 3 (1)
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Singh et al.: Atypical presentation of visceral leishmaniasis
iron profile and vitamin B12 values were normal. Antinuclear
antibodies (ANA), cytoplasmic and perinuclear antineutrophil
cytoplasmic antibodies (c-ANCA and p-ANCA) and direct
Coombs’ tests were negative.
The patient had a working diagnosis of pyrexia with
pancytopenia, so Napier’s aldehyde test was done and found
to be positive. To confirm the diagnosis of VL, a rK39
strip test and bone marrow examination were carried out.
The rK39 immunochromatographic strip was positive for
anti-K39 antibody. Intracellular and extracellular amastigotes
(Leishman–Donovan bodies) were visualized directly in
Giemsa-stained bone-marrow aspirate.
The patient was started on amphotericin B, at a dose of 0.5 mg/
kg/day after 1 week and this was continued for 3 weeks. By the
seventh day of treatment, she had improved symptomatically
as well as biochemically. Three units of whole blood were also
transfused to maintain her haemoglobin levels. At discharge,
the spleen tip was just palpable and the liver was not palpable.
The patient is under regular follow-up and is asymptomatic.
Discussion
VL ranges over the intertropical zones of America and
Africa, and extends into temperate regions of South America,
Southern Europe and Asia. There are an estimated 12 million
cases worldwide, with one and a half to two million cases
occurring each year.2 Ninety per cent of the VL cases in the
world are in Bangladesh, India, Nepal, Sudan and Brazil. VL
is a chronic infectious disease caused by Leishmania donovani
and characterized by irregular fever, hepatosplenomegaly,
weight loss, pancytopenia and hypergammaglobulinaemia.
There is infiltration of the reticuloendothelial system with
amastigotes, which gives rise to the clinical and biochemical
features. Splenomegaly is an important feature of the clinical
presentation, owing to the hyperplasia of the reticuloendothelial
cells that are filled with parasites. In one series, splenomegaly
was reported to be present in 100% of patients,3 but it may
be absent in immunocompromised patients, such as those
who are HIV positive, renal transplant recipients, those with
haematological malignancies and those on long-term steroids.
Rarely, it may be absent in acute cases, or in the early stages
of the disease.4,5
Milder forms of liver involvement occur in 17% of individuals
with VL,6 and are structurally and functionally reversible
after treatment. Pathophysiologically, liver involvement in
VL is typically self-limiting and involves a mononuclear celldominated granulomatous inflammation mediated by cytokines,
chemokines and reactive oxygen and nitrogen species.7 Several
authors have described renal pathological changes in VL.8,9
The main pathophysiological mechanism responsible for
renal impairment in VL probably includes the deposition of
immune complexes. The most frequent pathologies found are
proliferative glomerulonephritis and interstitial nephritis. The
development of acute kidney injury is an important clinical
complication in individuals with VL, which appears to increase
the mortality rate in this group of patients.10 The patient in this
study had both hepatic and renal involvement.
70
VL misdiagnosed as connective tissue disorders is well
reported in the literature . Haematological abormalities found
in systemic lupus erythematosus, namely anaemia, leukopenia
or lymphocytopenia and thrombocytopenia due to the presence
of auto-antibodies, can also be found in kala-azar. Leishmania
donovani infection induces nonspecific and specific antibody
production, much of which is probably due to parasite-released
substances, which act as B-cell mitogens. As a consequence of
B-cell hyperactivity, Leishmania donovani infection may cause
hypergammaglobulinaemia and production of auto-antibodies
such as ANA.11–13 This may cause confusion in diagnosis. For
this reason, a careful clinical approach is required to reach a
definitive conclusion. For similar reasons, the patient in this
study was also investigated for these biochemical markers and
antibodies.
Conclusion
The case is presented to highlight the atypical presentation of
VL in a nonendemic region where the index of suspicion is
low. The patient presented with pancytopenia and multi-organ
failure, in the absence of splenomegaly and fever, which is an
unusual presentation of kala-azar.
Delayed diagnosis due to atypical manifestations can lead to
fatal outcomes for patients. Instead of relying solely on the
classical clinical features of VL, simple laboratory findings
like pancytopenia, altered albumin/globulin ratio and positive
aldehyde and rK39 strip tests can help make an early diagnosis,
even in atypical cases, thereby reducing the mortality of VL.
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How to cite this article: Singh Y, Singh P, Joshi SC, Khalil M.
Atypical presentation of visceral leishmaniasis (kala-azar) from
non-endemic area. WHO South-East Asia J Public Health 2014;
3(1): 69–71.
Source of Support: Nil. Conflict of Interest: Nil.Contributorship: YS –
introduction and discussion; PS – introduction and discussion; SCJ – case
history; MK – data collection.
WHO South-East Asia Journal of Public Health | January-March 2014 | 3 (1)
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