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doI 10.11603/IJMMR.2413-6077.2020.1.10978

DISSEMINATED HISTOPLASMOSIS LEADING TO HAEMOPHAGOCYTIC 
LYMPHOHISTIOCYTOSIS IN AN IMMUNOCOMPETENT PATIENT  
(case report)

*I.D. Khan1, M. Brijwal2, I. Joshi3, B. Singh1, B. Poonia1, G. Gonimadatala1,  
S. Mangalesh1, A. Yadav1, H. Rajput1, N. Bhuttay1

1 – ARMY COLLEGE OF MEDICAL SCIENCES AND BASE HOSPITAL, NEW DELHI, INDIA
2 – ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA

3 – VELLORE INSTITUTE OF TECHNOLOGY, VELLORE, INDIA

Background: Emerging fungal infections can pose a serious threat in contemporary healthcare due to host 
variations, clinical presentation and emerging resistance. Histoplasma capsulatum is a thermally dimorphic 
fungus, which acts as a Trojan horse by residing inside macrophages. Histoplasmosis is an emerging infection 
and its association with hemophagocytic lymphohistiocytosis (HLH) in immunocompetent patients has been 
scantily reported in the literature.

Objective. The aim of the study was to explore disseminated histoplasmosis with the help of case report.
Methods: A case report of histoid leprosy is presented.
Results: A male patient of 47 yearsof age, under treatment for chronic obstructive pulmonary disease for 

five years and diabetes mellitus Type-II for two years, presented with fever of unknown origin (FUO) with evidence 
of HLH in the bone marrow. Core biopsy of the liver and spleen showed a dense tissue infiltrate with vacuolated 
histiocytes containing Histoplasma capsulatum, eosinophils, some lymphocytes and plasma cells.

Conclusion: Histoid leprosy is a discrete infrequent form of multibacillary leprosy with distinctive clinical, 
bacteriological and histomorphological features. Histopathologic examination with modified fite stain remains 
the mainstay of diagnosis.

KEY WORDS: histoplasmosis; hemophagocytic lymphohistiocytosis.

*Corresponding author: Dr. Inam Danish Khan, Associate 
Professor, Department of Clinical Microbiology and Infectious 
Diseases, Army College of Medical Sciences and Base Hospital, 
New Delhi 110010, India. E-mail: titan_afmc@yahoo.com 

I.d. Khan et al.

Introduction
Histoplasma capsulatum is a thermally 

dimorphic fungus, which acts as a Trojan Horse 
by residing inside macrophages [1]. Most 
individuals with intact cellular immunity are 
asymptomatic. A patient presented with fever 
of unknown origin (FUO) with evidence of 
hemophagocytic lymphohistiocytosis (HLH) in 
the bone marrow. Emerging fungal infections 
can pose a serious threat in contemporary 
health care due to host variations, clinical 
presentation and emerging resistance [2-8]. 
There are diagnostic stringencies in resource 
limited facilities [9, 10]. Histoplasmosis is an 
emerging infection and its association with HLH 
in immunocompetent patients has been scan-
tily reported in the literature [11-16].

Case Report
A male patient of 47 years old, under treat-

ment for chronic obstructive pulmonary disease 
for five years and diabetes mellitus Type-II for 
two years, presented with rashes around knee 

for 6 months, fever for 2 weeks and black stools 
for 3 days. Pallor, pedal edema, hepatomegaly 
7 cm below right subcostal margin and sple-
nomegaly 9 cm below left subcostal margin 
were evidenced. Investigated for FUO, hemo-
globin was 5.5-8.3 gm/dl, total leucocytes 3600-
4200/cumm with normal differential, serum 
ferritin was 306 ng/dl, while other tests were 
non-contributory towards diagnosis. CT thorax 
and abdomen revealed hepatosplenomegaly, 
retroperitoneal lymphadenopathy with mild 
ascites and solitary lesion in spleen. Colonoscopy 
was non-contributory. Bone marrow aspirate 
and biopsy showed evidence of HLH (Fig. 1).  

While on treatment, the patient succumbed 
to his illness. Consented post-mortem needle 
biopsy from liver, spleen, lungs and kidneys was 
done. Core biopsy of the liver and spleen 
showed a dense tissue infiltrate with vacuolated 
histiocytes containing histoplasma capsulatum, 
eosinophils, some lymphocytes and plasma 
cells.

Discussion
Histoplasmosis is an endemic infection in 

most of the USA, Asia and Africa caused by 

International Journal of Medicine and Medical Research 
2020, Volume 6, Issue 1, p. 14-18
copyright © 2019, TNMU, All Rights Reserved



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ISSN 2413-6077. IJmmR 2020 Vol. 6 Issue 1 I.d. Khan et al.

infectious bat and birdexcretions. Disseminated 
histoplasmosis, classically described in the 
immunocompromised, can occur in immuno-
competent patients. Clinical presentations vary 
depending on the size of the inoculum, host’s 
immune status and presence of underlying lung 
disease. Overt symptoms occur in 5% healthy 
individuals after low-level exposure; however 
75% may get affected with heavy exposure. 
Mostly asymptomatic, mild flu-like illness, fever, 
chills, sweating, cough, chest and joint pain may 
occur. Acute histoplasmosis may last 1-5 days 
whereas chronic histoplasmosis, mostly asso-
ciated with lung infections, can last 10-21 days 
and is associated with weight loss, persistent 
fatigue and night sweats. Associated acute or 
subacute pulmonary disease, progressive dis-
seminated disease, pericarditis, arthritis, me-
diastinitis, hepatomegaly, splenomegaly and 
bone marrow suppression may occur [17-19]. 
The patient presented with fever, fatigue, 
polyarthralgia, skin rashes and black stools with 
underlying chronic obstructive pulmonary 
disease. Along with anemia and hepato spleno-
megaly, the clinical picture fits histoplasmosis 
[11-16].

HLH is an overwhelming inflammatory 
response, resulting in cytokine storm and 
activation of monocyte-macrophage system 
resulting in multiorgan dysfunction. It is a 
secondary phenomenon to infections, malig-
nancies, autoimmune disorders and drug 
reaction. HLH is associated with high mortality 
although successful treatment has been re-
gistered [11,14,15].

Diagnosis of histoplasmosis involves stai-
ning, isolation, serology and antigen detection. 
Bone marrow gives the highest diagnostic yield. 
Antigen detection in urine and serum by radio-
immunoassay is useful in an immunocom-
promised patient when antibody production 
may be impaired. Other laboratory abnormalities 
include anemia, leukopenia, pancytopenia, 
elevated liver enzymes, increased ferritin and 
lactate dehydrogenase. Our diagnosis was 
based on clinical presentation and histo-
pathology of liver and spleen [6], when culture 
was negative.

A high index of suspicion is required as 
100% mortality seen in untreated histoplasmosis, 
can fall to 70% when adequately treated with 
Amphotericin-B [4, 20-25]. 

Risk factors for acquiring acute or chronic 
histoplasmosis in immunocompetent patients 
are for farmers and travelers having prolonged 
contact with rural or endemic environment, 
speleologists/spelunkers coming in contact 
with bat guano, and farmers coming in contact 
with soil enriched with bird guano. Heavy 
infective inoculum leads to acute presentation 
whereas low inoculum may lead to asymptomatic 
or chronic infection. Prolonged exposure to 
endemic area in Brazil led to histoplasmosis in 
43.9-82.9% of immunocompetent patients [26-
29].

Conclusion
Disseminated histoplasmosis needs to be 

differentiated from common diseases like 
tuberculosis, lymphoma or metastatic mali-
gnancy. Emerging opportunistic resistant 
infections warrant a high degree of clinical 
intuition and mental mobility for optimal 
management.

Funding
This research received no external funding.
Conflict of Interests
The authors declare no conflict of interest.
Author’s Contributions
I.D. Khan – study concept/design, conduct 

of study, drafting and manuscript revision, final 
approval of manuscript; M. Brijwal – study 
concept/design, final approval of manuscript; 
I. Joshi – study concept/design, final approval 
of manuscript; B. Singh – conduct of study; 
B. Poonia, G. Gonimadatala, S. Mangalesh, 
A. Yadav – statistical analysis, drafting and 
manuscript revision; H. Rajput – drafting and 
manuscript revision, N. Bhuttay – drafting and 
manuscript revision.

Fig. 1. Photomicrograph: HPE 400X; Bone marrow 
aspirate with Histoplasma, increased histiocytes and 
evidence of hemophagocytosis.



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Information about authors 
Dr Inam Danish Khan – Associate Professor, Clinical Microbiology and Infectious Diseases, Army 

College of Medical Sciences and Base Hospital, New Delhi 110010, India.
ORCID https://orcid.org/0000-0002-9824-8711, e-mail: titan_afmc@yahoo.com 
Dr Megha Brijwa  – Associate Professor, Clinical Microbiology and Infectious Diseases, All India Institute 

of Medical Sciences, New Delhi 110029, India 
ORCID https://orcid.org/0000-0003-4907-7036, e-mail: megha.brijwal@yahoo.com 
Ishitta Joshi – Research Scholar, Vellore Institute of Technology, Vellore, India 
ORCID https://orcid.org/0000-0003-2298-201X, e-mail: ishittajshi@yahoo.co.in
Bhagwat Singh – MBBS student, Army College of Medical Sciences, New Delhi 110010, India. 
ORCID https://orcid.org/0000-0002-0337-6754, e-mail: bhagwatsinghacms@gmail.com 
Bindu Poonia – MBBS student, Army College of Medical Sciences, New Delhi 110010, India. 
ORCID https://orcid.org/0000-0003-2916-3797, e-mail: bindupooniaacms@gmail.com
Geethanjali Gonimadatala – MBBS student, Army College of Medical Sciences, New Delhi 110010, 

India. 
ORCID https://orcid.org/0000-0002-9372-4002, e-mail: geethugacms78@gmail.com 
Mangalesh Sridhar – MBBS student, Army College of Medical Sciences, New Delhi 110010, India. 
ORCID https://orcid.org/0000-0002-2645-39949824-8711, e-mail: mangaleshsacms@gmail.com 
Akanksha Yadav – MBBS student, Army College of Medical Sciences, New Delhi 110010, India. 
ORCID https://orcid.org/0000-0003-2087-8366, e-mail: akiacms@gmail.com 
Himanshu Rajput – MBBS student, Army College of Medical Sciences, New Delhi 110010, India. 
ORCID https://orcid.org/0000-0003-1240-8444, e-mail: himanshurajput@gmail.com 
Nehal Bhuttay – MBBS student, Army College of Medical Sciences, New Delhi 110010, India. 
ORCID https://orcid.org/0000-0002-1207-2648, e-mail: nehalbhuttay56acms@gmail.com 

ДИСЕМІНОВАНИЙ ГІСТОПЛАЗМОЗ ЯК ЕТІОЛОГІЧНИЙ ЧИННИК  
ГЕМОФАГОЦИТАРНОГО ЛІМФОГІСТІОЦИТОЗУ У ІМУНОКОМПЕТЕНТНОГО 
ПАЦІЄНТА (клінічний випадок) 

*I.D. Khan1, M. Brijwal2, I. Joshi3, B. Singh1, B. Poonia1, G. Gonimadatala1,  
 S. Mangalesh1, A. Yadav1, H. Rajput 1, N. Bhuttay1

1 – ARMY COLLEGE OF MEDICAL SCIENCES AND BASE HOSPITAL, NEW DELHI, INDIA
2 – ALL INDIA INSTITUTE OF MEDICAL SCIENCES, NEW DELHI, INDIA

3 – VELLORE INSTITUTE OF TECHNOLOGY, VELLORE, INDIA

Вступ. Зростання кількості та частоти грибкових інфекцій може становити серйозну загрозу 
сучасній системі охорони здоров’я через варіативність клінічного перебігу, симптомів та ознак 
захворювання, резистентність до лікування. Histoplasma capsulatum – це диморфний гриб, який 
поводиться як «троянський кінь» проникаючи всередину макрофагів. Гістоплазмоз – захворювання, що 
останнім часом все частіше діагностується, однак про його взаємозв’язок з гемофагоцитарним 
лімфогістіоцитозом у імунокомпетентних осіб надзвичайно мало інформації. 

Мета роботи на прикладі клінічного випадку дослідити перебіг дисемінованого гістоплазмозу.  
Методи. Описано клінічний випадок гістоїдної лепри у пацієнта.  
Результати. Чоловік, 47 років, котрий останніх п’ять років лікувався від ХОЗЛ та цукрового діабету 

другого типу, звернувся до лікаря зі скаргами на лихоманку невідомого генезу. Було діагностовано 
гемофагоцитарний лімфогістіоцитоз кісткового мозку. На препаратах печінки та селезінки посмертної 
біопсії органів знайдено щільний тканинний інфільтрат  з вакуолізованими гістіоцитами, які містили 
Histoplasma capsulatum, еозинофіли, невелику кількість лімфоцитів та плазмоцитів.

Висновки. Гістоїдна лепра – рідкісна форма мультибацилярної лепри з характерними клінічними, 
бактеріологічними та гістомофологічними ознаками. Проведення гістологічного дослідження дозволяє 
діагностувати захворювання.  

КЛЮЧОВІ СЛОВА: гістоплазмоз; гемофагоцитарний лімфогістіоцитоз.

I.d. Khan et al.



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accepted 02 June 2020.

This is open access article distributed under the Creative Com-
mons Attribution License, which permits unrestricted use, 
distribution, and reproduction in any medium, provided the  
original work is properly cited.

I.d. Khan et al.