A Rare Presentation of Progressive Disseminated Histoplasmosis in an Immunocompetent Patient from a Non-Endemic Region
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Medical Mycology Case Reports 2 (2013) 103–107 Contents lists available at ScienceDirect Medical Mycology Case Reports journal homepage: www.elsevier.com/locate/mmcr A rare presentation of progressive disseminated histoplasmosis in an immunocompetent patient from a non-endemic region M.V.S. Subbalaxmi a,n, P. Umabala b, Roshni Paul c, Naval Chandra a, Y.S. Raju a, Shivaprakash M. Rudramurthy d a Department of General Medicine, Nizam's Institute of Medical Sciences, Hyderabad 500082, Andhra Pradesh, India b Department of Microbiology, Nizam's Institute of Medical Sciences, Hyderabad 500082, Andhra Pradesh, India c Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad 500082, Andhra Pradesh, India d Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India article info abstract Article history: Histoplasmosis is an important systemic fungal infection in endemic areas. In India, the disease has been Received 2 January 2013 reported from several parts of the country, most cases being from eastern India considered to be endemic Received in revised form for the disease. There have been very few cases reported from the state of Andhra Pradesh, in the 12 April 2013 southern part of India. We report a case of progressive disseminated histoplasmosis presenting with Accepted 15 April 2013 bleeding manifestations in an immune competent patient from the state of Andhra Pradesh. & 2013 International Society for Human and Animal Mycology. Published by Elsevier B.V All rights Keywords: reserved. Histoplasmosis PDH Immunocompetent host Thrombocytopenia India 1. Introduction in a patient with no underlying risk factor for progressive dissemi- nated histoplasmosis. Histoplasmosis caused by the dimorphic fungus Histoplasma capsulatum presents most commonly as pulmonary and progressive disseminated (PDH) forms [1].Approximately10%ofindividuals 2. Case infected with histoplasmosis may develop progressive disseminated histoplasmosis which usually presents with fever, malaise, hepa- A male farmer aged 56 years from Adilabad district, in Andhra tosplenomegaly and lymphadenopathy. Other manifestations of Pradesh, was admitted on day 0 to a tertiary care hospital in PDH include pancytopenia, renal failure, disseminated intra vascular Andhra Pradesh, south India with complaints of hematuria and coagulation (DIC), skin lesions, gastrointestinal manifestations like epigastric pain for last 15 days. Epigastric pain was more after diarrhea, vomiting, neurologic manifestations like encephalopathy, taking food but there was no history of radiation. He complained focal parenchymal lesions and sometimes adrenal insufficiency [1]. of nausea though there was no history of vomiting and fever. Progressive disseminated histoplasmosis is usually seen in immu- Patient was admitted to another hospital 5 days prior to the nocompromised patients such as persons with HIV infection [1].In present admission for evaluation of his epigastric pain. Upper India histoplasmosis has been reported from different pockets in gastrointestinal endoscopy was done there, which revealed gas- the eastern, north eastern, northern, western and southern parts of tritis. In view of very low platelet counts he was referred to our the country [2–10].We report a case of progressive disseminated hospital. There was no history of smoking or substance abuse or histoplasmosis in an immunocompetent patient, presenting with travel outside the state of Andhra Pradesh to any regions known to bleeding manifestations from the state of Andhra Pradesh in the be endemic for histoplasmosis. southern part of India. This case merits discussion due to the rarity At admission on day 0, general physical examination revealed of the presentation mimicking immune thrombocytopenic purpura, petechiae on his right shoulder and tenderness in the epigastric area. Rest of the general examination and systemic examination were normal. Laboratory work up done on day +1 revealed hemoglobin n fl Corresponding author. Tel.: +91 409490457909. 12.1 g/dl; mean corpuscular volume 86 ; total leukocyte count E-mail address: [email protected] (M.V.S. Subbalaxmi). 4000/cmm with normal differential count; platelet count 10,000/cmm. 2211-7539/$ - see front matter & 2013 International Society for Human and Animal Mycology. Published by Elsevier B.V All rights reserved. http://dx.doi.org/10.1016/j.mmcr.2013.04.003 104 M.V.S. Subbalaxmi et al. / Medical Mycology Case Reports 2 (2013) 103–107 ESR was within normal limits. Peripheral blood smear showed (Fig. 2A). Large number of histiocytes, some foamy, filled with tiny thrombocytopenia (Fig. 1A) with giant platelets (Fig. 1B). Complete intracytoplasmic yeasts were seen. There were a few yeasts lying urine examination showed plenty of red blood cells. Random extracellularly. These were oval, 2–3 m in size with a slightly blood sugar, glycosylated hemoglobin, coagulation profile, liver eccentric nucleus and a clear zone around the nucleus (Fig. 2B). and renal function tests serum lipase were all within normal As these organisms had to be differentiated from others with limits; serum amylase was 150 U/ml and LDH 2260 U/L. ELISAs for similar morphology, trephine sections were subjected to special anti-nuclear antibodies, HIV antibody and HIV antigen were all staining with periodic acid schiff (PAS) (Fig. 3A) and silver negative. methanamine (SM) (Fig. 3B),which showed yeast cells morpholo- In view of the age and persisting thrombocytopenia, a bone gically suggestive of H. capsulatum. marrow aspiration and biopsy were done on day +3 to rule out As the bone marrow aspirate was not sent for culture at the lymphoma. Bone marrow aspirate was particulate with normal first instance, repeated bone marrow aspiration was done on day cellularity, M:E ratio was 2:1, with normal erythropoeisis and +7 for confirmation of histoplasmosis. The aspirate was inoculated myelopoeisis. Megakaryocytes were slightly increased in number on to brain heart infusion agar, Sabouraud's dextrose agar with Fig. 1. Leishman stain: peripheral blood smear showing (A) thrombocytopenia (  400) with (B) giant platelets (  1000). Fig. 2. (A) Giemsa  400: BMA particulate with normal cellularity, M:E ratio 2:1, normal erythropoiesis, myelopoiesis, megakarycytes slightly increased in number with normal morphology. (B) Giemsa  400 (inset Giemsa  1000): histiocytes showing intracytoplasmic yeasts. M.V.S. Subbalaxmi et al. / Medical Mycology Case Reports 2 (2013) 103–107 105 Fig. 3. Trephine section showing yeast cells stained with PAS (A) and SM (B) (  400). 2.1. Imaging Chest radiograph and ultrasound scanning of abdomen which were done on day +3 of hospital stay were normal. 2.2. Treatment The patient’s platelet counts at admission were 10,000/cmm and were continuing to fall further for which he received platelet transfusions on alternate days. On day +8, patient was started on treatment with injection amphotericin B deoxycholate at a daily dose of 1 mg/kg b wt. Pain abdomen gradually subsided and the patient’s appetite improved. Platelet count increased to 30,000/ cmm on day +13 i.e. after 5 days of starting of amphotericin. Patient was given amphotericin B deoxycholate for 14 days Fig. 4. Lactophenol cotton blue mount (  400): large, rounded, single-celled, tuberculate macroconidia and small, pyriform shaped microconidia of Histoplasma followed by itraconazole 200 mg twice a day with a plan to capsulatum. (For interpretation of the references to color in this figure caption, the continue for 1 year. Platelet count was 50,000/cmm at discharge reader is referred to the web version of this article.) on day +22. ' chloramphenicol, and Sabouraud s dextrose agar with cyclohex- 2.3. Follow up and outcome imide and chloramphenicol. As H. capsulatum is a CDC/NIH risk group 3 agent, handling of clinical material and isolates were done Patient reported to the general medicine outpatient depart- in the Class II Bio Safety Cabinet with BSL2 practices, containment ment for follow up on day +52. Patient showed marked clinical ' 1 equipment and facilities. On Sabouraud s dextrose agar at 25 C, improvement and platelet counts on that day were 150,000/cmm. + colonies appeared after 1 week of incubation i.e. on day 14. The Platelet count was 160,000/cmm at the next folloup on day+112. colonies were highly folded, adherent, initially white, turning buff- The patient's renal function and liver function were monitored brown. Microscopic morphology showed the presence of charac- throughout the course of treatment with antifungals till his last teristic large, rounded, single-celled, tuberculate macroconidia and visit (day 112) to the outpatient department for follow up and small, pyriform shaped microconidia (Fig. 4), based on which the were found to be within normal limits. fungus provisionally was identified as H. capsulatum. The isolate was sent to the National Culture Collection of Pathogenic Fungi (NCCPF), Postgraduate Institute of Medical Education and 3. Discussion Research, Chandigarh, for confirmation. At NCCPF, the identity of the isolate was confirmed by morphology, conversion to yeast H. capsulatum causing histoplasmosis is presently classified into phase and sequencing of rDNA. For extraction of DNA, the isolate six distinct clades based on combined data analysis of partial was inoculated in Sabouraud dextrose broth and incubated in a sequences of four protein encoding genes of 46H. capsulatum shaker incubator (130 rpm) at 35 1C for 5 days. The cells were