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Year : 2017  |  Volume : 7  |  Issue : 1  |  Page : 56-58  

Visceral leishmaniasis-associated hemophagocytosis: A tale of two unexpected diagnoses from a nonendemic region


1 Department of Pathology, Dr. RPGMC, Kangra, Himachal Pradesh, India
2 Department of Medicine, Dr.RPGMC, Kangra, Himachal Pradesh, India

Date of Acceptance30-Sep-2016
Date of Web Publication16-Mar-2017

Correspondence Address:
Rashmi Kaul Raina
C-15, Type-V Quarters, Dr. RPGMC Campus, Tanda, Kangra - 176 001, Himachal Pradesh
India
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DOI: 10.4103/2229-5070.202288

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   Abstract 

A case of visceral leishmaniasis (VL)-associated hemophagocytic lymphohistiocytosis (HLH) in an immunocompetent native from a nonendemic area was reported. The patient belonged to Ravi river valley area (altitude 996 meters above the mean sea level) of Chamba, Himachal Pradesh, India. VL and HLH were not a differential diagnosis. Identification of the Leishman-Donovan bodies and hemophagocytosis in bone marrow aspirate and biopsy provided the diagnosis. The patient recovered to the treatment with amphotericin B.

Keywords: Hemophagocytic syndrome, kala-azar, macrophage activation syndrome


How to cite this article:
Raina RK, Raina S, Sharma M. Visceral leishmaniasis-associated hemophagocytosis: A tale of two unexpected diagnoses from a nonendemic region. Trop Parasitol 2017;7:56-8

How to cite this URL:
Raina RK, Raina S, Sharma M. Visceral leishmaniasis-associated hemophagocytosis: A tale of two unexpected diagnoses from a nonendemic region. Trop Parasitol [serial online] 2017 [cited 2017 Mar 29];7:56-8. Available from: http://www.tropicalparasitology.org/text.asp?2017/7/1/56/202288


   Introduction Top


Visceral leishmaniasis (VL) is a disease of low altitude. Leishmaniasis is considered to be almost absent in highlands as higher altitudes negatively affect the distribution of vector.[1] However, from the endemic eastern states of India, mainly Bihar, West Bengal, Jharkhand, and East Uttar Pradesh, the epidemiological shifts are taking place, and new foci have been reported from natives of nonendemic areas such as sub-Himalayan region of Uttarakhand and Himachal Pradesh.[2],[3],[4] Even with classical presentation, the first diagnosis is always other than kala-azar in patients of nonendemic area. With a low index of suspicion, atypical presentation of VL is a diagnostic dilemma in these places. Hemophagocytic lymphohistiocytosis (HLH)-associated VL is a rare and difficult to diagnose clinicopathological condition as features of both overlap and leading to delayed treatment.[5] This is a presentation of an unusual case of VL in a native of nonendemic region of India. The patient presented with atypical clinical features and was unexpectedly diagnosed through the identification of the Leishman-Donovan bodies and hemophagocytosis in bone marrow aspirate. The patient had never visited VL-endemic region in his life. The patient recovered to treatment with amphotericin B.


   Case Report Top


A 40-year-old male, agriculturist, smoker, nonalcoholic, native of Ravi river valley area (altitude 996 meters above the mean sea level) in Chamba district of Himachal Pradesh, India was admitted in September 2014 with history of fever for 1 month. Fever was high grade recorded up to 105°F and associated with chills without rigors. The patient had history of malaise and easy fatigability for last 3 weeks. Review of other systems was normal. He had no significant past history. Treatment records revealed that he received a course of antibiotic from his primary care physicians without any relief. He denied ever visiting any endemic area of VL. On examination, pallor was present and he was febrile. No icterus and lymphadenopathy were present. His body mass index was 21. Per abdomen examination revealed massive splenomegaly (palpable 8 cm below the left costal margin) and hepatomegaly (liver span 16 cm). Rest of the examination was normal. On hematological investigations, pancytopenia was observed. Hemoglobin was 6.7 g%, leukocyte count was 600 mm 3 (neutrophils-41%, lymphocytes-42%, and monocytes-14%), platelet count was 36,000 mm 3, and corrected reticulocyte count was 1.2%. Erythrocyte sedimentation rate was 102 mm/h. Peripheral smear showed macrocytic normochromic picture and was negative for malaria parasite. The results of serial hemogram and biochemistry are shown in [Table 1]. A prothrombin time of 16 s was recorded (international normalized ratio 1.34), with a normal activated partial thromboplastin time. Blood glucose and renal function were normal. Hepatitis B surface antigen, anti-hepatitis C virus, and human immunodeficiency virus serology were negative. Chest X-ray was normal. Ultrasound of the abdomen showed hepatosplenomegaly and dilated portal vein (15.3 mm). Upper gastrointestinal endoscopy was normal. Empiric treatment for neutropenic fever was prescribed. Blood and urine culture were sterile. Bone marrow aspiration and biopsy were performed. Bone marrow morphology was normocellular with normoblastic erythropoiesis. M:E ratio was 1.5:1. Myeloid and megakaryocytic series were normal in maturation and morphology. There was a marked increase in histiocytes with a prominent hemophagocytosis. Amastigote forms of Leishmania donovani were seen both intracellularly and extracellularly [Figure 1]. Serum ferritin was significantly raised (18,500 ng/ml) and triglycerides were 274 mg/dl. The diagnosis of HLH was established as 6 out of 8 diagnostic criteria (5 out of 8 are required) were fulfilled; fever, splenomegaly, cytopenias, hyperferritinemia, hypertriglyceridemia, and hemophagocytosis in the bone marrow.[6] The final diagnosis of VL with secondary hemophagocytic syndrome was made. The patient was started with amphotericin B 1 mg/kg on alternate days and given 15 infusions. The patient became afebrile after the first dose of amphotericin B. At discharge, spleen tip was just palpable and liver span was normal. Hematological and biochemical parameters at discharge are shown in [Table 1]. The patient remained asymptomatic at the end of 3 months and 6 months during follow-up.
Table 1: Serial hemogram and biochemistry before and after treatment

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Figure 1: Bone marrow aspiration smear shows: (a) Macrophages with engulfed erythroid cells and lymphocytes (hemophagocytosis). (b) Megakaryocyte with engulfed Leishman-Donovan bodies (Giemsa, ×1000)

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   Discussion Top


Even with classical presentation, the clinical possibility of VL in the differential diagnosis is very low in patients from nonendemic region. The diagnosis is difficult and further delayed in the presence of atypical and rare manifestations. Although clinical spectrum of VL from nonendemic region is generally similar to that of the patients from endemic region of India but certain uncommon manifestations such as leishmanial lymphadenopathy has been reported by us in our previous study from nonendemic region.[2] Case reports of HLH secondary to VL have been documented in literature rarely. They generally refer to pediatric patients and are from VL-endemic regions.[5],[7],[8],[9] In bone marrow cytology, mild to moderate hemophagocytosis was observed in 70% of cases of VL from subhilly nonendemic region of India.[10] However, these patients were not evaluated for the secondary HLH. The diagnosis of HLH-associated VL can be quite challenging even in endemic areas because presentation of both the conditions is similar and the clinicopathological features observed overlap.[5],[7] HLH is classified into primary or genetic HLH and secondary or reactive HLH. Secondary HLH has been shown to be associated with a myriad of malignant disorders, autoimmune diseases, and infections such as viral, bacterial, fungal, and parasitic infections including VL. Either type is caused by uncontrolled activation of T-helper lymphocytes and histiocytes/macrophages with uncontrolled hemophagocytosis and overproduction of inflammatory cytokines leading to fever, hepatosplenomegaly, cytopenias, liver dysfunction, hyperferritinemia, and hypertriglyceridemia.[6] Infection-associated HLH resolves with treatment of the underlying infection, whereas in the primary form, cytotoxic drugs are the mainstay of therapy.[8] Our patient presented to us with fever, hepatosplenomegaly, and pancytopenia. Bone marrow aspiration and biopsy revealed marked increase in histiocytes with a prominent hemophagocytosis. Amastigote forms of L. donovani were seen both intracellularly and extracellularly. Clinical presentation, hematology investigations, and findings on bone marrow morphology led to the suspicion of secondary HLH. Hyperferritinemia, hypertriglyceridemia, and liver dysfunction, further fulfilled the diagnostic criteria for this syndrome.[6] The patient was successfully treated with amphotericin B. HLH should be included in the differential diagnosis of patients who present with persistent high fever, hepatosplenomegaly, and pancytopenia. Even in nonendemic area, clinicians and pathologists should keep in mind VL as the inciting etiology of secondary HLH.

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Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Bhunia GS, Kesari S, Jeyaram A, Kumar V, Das P. Influence of topography on the endemicity of kala-azar: A study based on remote sensing and geographical information system. Geospat Health 2010;4:155-65.  Back to cited text no. 1
    
2.
Raina S, Mahesh DM, Kaul R, Satindera KS, Gupta D, Sharma A, et al. A new focus of visceral leishmaniasis in the Himalayas, India. J Vector Borne Dis 2009;46:303-6.  Back to cited text no. 2
    
3.
Verma SK, Ahmed S, Shirazi N, Kusum A, Kaushik RM, Barthwal SP. Sodium stibogluconate-sensitive visceral leishmaniasis in the non-endemic hilly region of Uttarakhand, India. Trans R Soc Trop Med Hyg 2007;101:730-2.  Back to cited text no. 3
    
4.
Singh S, Biswas A, Wig N, Aggarwal P, Sood R, Wali JP. A new focus of visceral leishmaniasis in Sub-Himalayan (Kumaon) region of northern India. J Commun Dis 1999;31:73-7.  Back to cited text no. 4
    
5.
Ucar S, Zorlu P, Yarali NE, Tanir G. Hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis: A case report. Arch Dis Child 2014;99:A303.  Back to cited text no. 5
    
6.
Henter JI, Horne A, Aricó M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007;48:124-31.  Back to cited text no. 6
    
7.
Cançado GG, Freitas GG, Faria FH, de Macedo AV, Nobre V. Hemophagocytic lymphohistiocytosis associated with visceral leishmaniasis in late adulthood. Am J Trop Med Hyg 2013;88:575-7.  Back to cited text no. 7
    
8.
Mokhtari M, Kumar PV. Visceral leishmaniasis-associated hemophagocytosis: A single center experience. Arch Iran Med 2013;16:471-3.  Back to cited text no. 8
    
9.
Bode SF, Bogdan C, Beutel K, Behnisch W, Greiner J, Henning S, et al. Hemophagocytic lymphohistiocytosis in imported pediatric visceral leishmaniasis in a nonendemic area. J Pediatr 2014;165:147-153.e1.  Back to cited text no. 9
    
10.
Chandra H, Chandra S, Kaushik RM. Visceral leishmaniasis with associated common, uncommon, and atypical morphological features on bone marrow aspirate cytology in nonendemic region. J Trop Med 2013;2013:861032.  Back to cited text no. 10
    


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