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Case Report

Pratap Singh1, Sanjay

Progressive Disseminated Histoplasmosis
Kumar2, Pramila in an Immunocompetent Host with
Dharmshaktu3, Dinesh
Meher4, Vijay Kumar5 Reversible CD4 Lymphocytopenia
Associate Professor,
Resident, Department of
Medicine, Associate
Professor, Department of We report an 18-year-old male patient presented to us with complaints of fever and
Pathology, Dr Ram Manohar progressive weight loss for past 4 months. On examination, he also had multiple
Lohia Hospital & PGIMER, umbilicated papular to nodular lesions over his chin and forehead region. Blood
New Delhi. count revealed anemia with leukopenia. An excisional biopsy of the skin lesion was
Associate Professor, suggestive of cutaneous histoplasmosis. On further investigations for anemia and
Department of Medicine, leukopenia, he was found to have bone marrow histoplasmosis on trephine biopsy.
Lady Hardinge Medical Patient’s serology for HIV I and II was negative but his CD4 counts were low. Patient
College, Dr Ram Manohar received amphotericin B and itraconazole. He showed remarkable improvement in
Lohia Hospital & PGIMER,
New Delhi.
his general condition and blood counts. A repeat CD4 count done at 4 months of
treatment was also normal. Progressive disseminated histoplasmosis (PDH)
Correspondence to: presenting as cutaneous lesions in an immunocompetent host is very rare and has
Dr Sanjay Kumar, been reported in a few cases only.
Department of Medicine,
Lady Hardinge Medical Keywords: Progressive disseminated histoplasmosis, reversible CD4 depletion.
College, Dr Ram Manohar
Lohia Hospital & PGIMER,
New Delhi.

E-mail Id: drpratapsingh@ Histoplasmosis is a fungal infection and prevalent worldwide, in which Ohio and Mississippi river valleys of North America have the highest prevalence. There are a
few case reports of this fungal infection from non-endemic regions too.1-3 In India,
histoplasmosis has been reported in large numbers from eastern states like West
Bengal,4,5 and a few cases from southern states as well.6,7 Other regions of the
country rarely see any cases of histoplasmosis. Histoplasmosis is most commonly
seen in immunosuppressed patients8 but there are a few case reports in
immunocompetent hosts as well.9,10

Case Presentation
An 18-year-old, unmarried male patient, resident of Delhi (central India), presented
to our hospital with complaints of low-grade prolonged fever, loss of appetite and
weight loss of 10 kg in last 4 months. No history of high-risk behavior, promiscuous
sexual activities or blood transfusion in the past. He was a non-smoker and non-
alcoholic. There was also no history of exposure to bird’s dropping or recent travel to
How to cite this article:
endemic parts of the country. There was no past history of tuberculosis, diabetes
Singh P, Kumar S, mellitus or any other chronic systemic illness.
Dharmshaktu P et al.
Progressive Disseminated On examination, the patient was of thin-built male with stable vitals. There were
Histoplasmosis in an multiple umbilicated papular to nodular lesions over forehead and chin, without any
Immunocompetent Host erythema or tenderness (Fig. 1).
with Reversible CD4
Lymphocytopenia. J Adv Res He had pallor, but no icterus, clubbing, cyanosis, or peripheral lymphadenopathy.
Med 2016; 3(2&3): 14-17. The abdominal examination revealed mild, non-tender hepatosplenomegaly, but no
ISSN: 2349-7181
free fluid. The chest and cardiovascular examination did not reveal any abnormality.

© ADR Journals 2016. All Rights Reserved.

J. Adv. Res. Med. 2016; 3(2&3) Singh P et al.

Figure 1.Multiple Papular to Nodular Skin Lesions over Chin Region

Investigations necrosis. Ultrasound abdomen revealed

hepatosplenomegaly. CECT abdomen ruled out
The blood count revealed bicytopenia (hemoglobin 7.2 involvement of adrenal glands. Serum protein
gm/dL, total leucocyte count 3200/mm3 with polymorph electrophoresis revealed hypergammaglobulinemia.
75%, lymphocyte 20%, eosinophil 3% and monocyte 2%. Skin biopsy showed ill-defined non-caseating
Platelet count was 2.5 lac/mm3 and erythrocyte granulomas with macrophages showing yeast forms of
sedimentation rate (ESR) was 38 mm in first hour. The histoplasma capsulatum (Fig. 2). Fungal stain was also
anemia was normocytic normochromic on peripheral positive. Bone marrow aspiration and biopsy showed
smear examination. The biochemical tests revealed a normal hematopoiesis with presence of yeast forms of
total protein of 7.5 gm/dL, albumin 2.5 gm/dL, globulin histoplasma capsulatum (Figs. 3, 4).
5.0 gm/dL with reversal of albumin-globulin ratio. The
serum LDH level was 308 IU/L. Other routine The patient was thus diagnosed as a case of progressive
biochemical tests, like bilirubin, transaminases, alkaline disseminated histoplasmosis (PDH). He underwent
phosphatase, urea, and creatinine were normal. The further investigations to look for any underlying
blood culture and urine culture were sterile after 48 immune dysfunction. Serology for HIV I and II was
hours of incubation. Sputum examination did not reveal negative on two occasions while the CD4 count was low
any organism by Gram’s or acid-fast staining. Chest X- at 161/µL (normal 500-1200 cells/mm3). The bone
ray was normal; however, the contrast enhanced CT marrow aspirate cultures were also positive for
chest revealed left hilar and pre-tracheal histoplasma capsulatum at 1 month.
lymphadenopathy with foci of calcification but no

Figure 2.Multiple Ill-Defined Non-caseating Granulomas Present with Yeast Forms of Histoplasma Capsulatum
(Arrow) in the Skin Biopsy

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Singh P et al. J. Adv. Res. Med. 2016; 3(2&3)

Figure 3.Normal Hematopoiesis and Macrophages with Yeast Form of Histoplasma

Capsulatum in Bone Marrow Aspiration

Figure 4.Yeast Forms within Macrophages on Silver Methanamine and PAS Stain on Bone Marrow Biopsy (Arrow)

Differential Diagnosis he was discharged on oral Itraconazole. He visited again

3 weeks later with fading skin lesions and was on
Patient presenting with longstanding fever, loss of regular follow up. At fourth month, the CD4 count was
appetite, significant weight loss, bicytopenia and also repeated to exclude the possibility of idiopathic
hepatosplenomegaly in India, the first provisional CD4 cell lymphocytopenia which was normal at 584
diagnosis that was considered was disseminated cells/mm3. An extensive workup for primary
tuberculosis. Other differential would include visceral immunodeficiency states could not be done due to the
leishmaniasis, lymphoma, leukemia, and HIV-AIDS. Once non-availability of the same at our hospital and also
we got a report of skin and bone marrow biopsy little because the patient belongs to a poor social strata and
was of doubt that we were dealing with progressive could not afford expensive tests.
disseminated histoplasmosis. The HIV report came out
to be negative, but the CD4 count was low. Due to lack Outcome and Follow-Up
of sufficient funds, we could not investigate further to
rule out primary immunodeficiency. The patient responded very well to the treatment and,
till today, has not shown any new or recurrent infection
Treatment on follow up.

Patient was started on intravenous amphotericin B at a Discussion

dose of 0.5 mg/kg/day with gradual escalation to 1
mg/kg/day for 4 weeks and then oral itraconazole at a Histoplasmosis is a fungal infection caused by
dose of 200 mg daily which was continued for 6 months. histoplasma capsulatum var capsulatum and
There was marked improvement of his symptoms and histoplasma capsulatum varduboisii. Our patient

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J. Adv. Res. Med. 2016; 3(2&3) Singh P et al.

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Date of Acceptance: 27th Sep. 2016

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