Case Report

Disseminated histoplasmosis with conjunctival

involvement in an immunocompromised patient
Arun Shirali, Jyoti Kini1, Anjith Vupputuri, Maria Kuruvila2, M. Venkatraya Prabhu
Departments of Medicine, 1Pathology and 2Dermatology and Venereology, Kasturba Medical College, Mangalore,
Karnataka, India

Address for correspondence:

Dr. Anjith Vupputuri, Department of Medicine, Kasturba Medical College, Light House Hill Road, Mangalore, Karnataka - 575 001, India.
E-mail: anjithv@yahoo.com

Abstract
We report a case of disseminated histoplasmosis in a 37-year-old male acquired immunodeficiency syndrome
patient from south India. The patient presented with high-grade fever, cough, conjunctival nodule and
papulonodular hyperpigmented skin lesions. Histology of skin lesions and conjunctival nodule showed
numerous intracellular Periodic Acid Schiff-positive rounded yeast cells within macrophages. Bone marrow
aspirate confirmed disseminated histoplasmosis. The patient showed dramatic response after starting
treatment with Amphotercin B.

Key words: Acquired immunodeficiency syndrome, conjunctival histoplasmosis, disseminated histoplasmosis, India

INTRODUCTION treatment, presented with high-grade fever, cough

with expectoration of 6 weeks duration and
Histoplasmosis refers to a granulomatous
multiple papulonodular lesions on the face, neck
infection caused by Histoplasma capsulatum, a
and chest of 2 weeks duration. The lesions were
dimorphic fungus. The fungus has two variants.
sudden in onset and were gradually progressive.
H. capsulatum var. capsulatum, which is more
ubiquitous, generally causes a subclinical
On examination, he had multiple, discrete,
infection. Symptomatic disease presents as
mildly tender, hyperpigmented, papulonodular
a spectrum ranging from chronic progressive
lesions, distributed over the face [Figure 1],
pulmonary infection to acute fulminant, or
neck, chest, back and oral cavity. Some of them
chronic, disseminated histoplasmosis. Infections
showed ulcerations and crusting. A bright red,
due to H. capsulatum var. duboisii are restricted
elevated, non-mobile, bulbar conjunctival nodule
to West Africa. The pulmonary and disseminated
with congestion was present in the right eye
forms of histoplasmosis are very common in
[Figure 2]. He had generalized lymphadenopathy
acquired immunodeficiency syndrome (AIDS)
and non-tender hepatomegaly. Examination of
patients. H. capsulatum infection is uncommon in
the respiratory system revealed bilateral coarse
India, with only occasional case reports published
in the literature. We report one such rare case of crackles. Other systemic examination and fundus
disseminated histoplasmosis. examination were unremarkable.

On investigation, his hemoglobin was 6.5 gm/

CASE REPORT dL, total count was 2220/mm 3, differential count
A 37-year-old male farmer, hailing from Puttur, was neutrophils 81, lymphocytes 15, monocytes 2
Karnataka, a known case of AIDS on antiretroviral and eosinophils 2 and his platelet count was

How to cite this article:

Shirali A, Kini J, Vupputuri A, Kuruvila M, Prabhu MV. Disseminated histoplasmosis with conjunctival involvement in an immunocompro-
mised patient. Indian J Sex Transm Dis 2010;31:35-8.
DOI: 10.4103/0253-7184.68999

Indian J Sex Transm Dis & AIDS 2010; Vol. 31, No. 1 35
 Shirali, et al.: Disseminated histoplasmosis
1.69 lakhs. Peripheral smear showed microcytic
hypochromic red blood cells, anisopoikilocytosis,
polychromasia and reduced leucocyte count and
toxic granules with no evidence of hemolysis.
The erythrocyte sedimentation rate was 140
mm/h. The CD4 count was 150/µL. Serum lactate
dehydrogenase (LDH) was 842 IU/L. The Venereal
Disease Research Laboratory (VDRL) test was
non-reactive. Urine and stool examinations were
within normal limits. Liver and renal function
tests were normal. Blood culture was negative.
Chest roentgenogram showed reticulonodular
pattern with hilar lymphadenopathy. Sputum
examination for Mycobacterium tuberculosis was
negative.
Leishman-stained bone marrow aspirate smears
showed a reactive marrow with few extracellular
and intracellular H. capsulatum within
macrophages [Figure 3].
Figure 1: Papulonodular lesions over the face with crusting
Figure 3: Bone marrow aspirate smears showing a reactive marrow
with few extracellular and intracellular histoplasma within macrophages
(Leishman stain, x100)
36
Skin biopsy specimen showed dermis with
aggregates of numerous macrophages containing
rounded to oval organisms surrounded by a
clear space within the cytoplasm. The organisms
were positive for Periodic Acid Schiff (PAS)
stain, confirming H. capsulatum infection. There
was minimal inflammatory response around the
macrophages.
Histopathological examination of the conjunctival
specimen showed numerous macrophage aggregates
with 2–4 µm PAS-positive yeast-like forms of H.
capsulatum [Figure 4].
The patient was started on IV Amphotericin B
at a dose of 1 mg/kg/day. Antiretroviral therapy
with zidovudine, lamivudine and efavirenz was
continued. He became afebrile within 48 h after
starting treatment. The skin lesions and the
conjunctival lesion healed within 10 days. He
was then switched over to oral itraconazole 200
mg twice daily and discharged with an advice to
continue the drug for his lifetime.
Figure 2: Conjunctival nodule with congestion in the right eye
Figure 4: Histopathological section of the conjunctival specimen
showing numerous macrophage aggregates with Period Acid Schiff
(PAS)-positive histoplasma (PAS stain, x100)
Indian J Sex Transm Dis & AIDS 2010; Vol. 31, No. 1
 Shirali, et al.: Disseminated histoplasmosis
DISCUSSION
Histoplasmosis, acquired by inhalation of
mycelial fragments and microconidia, is most
often self-limiting but can nonetheless cause
potentially lethal infection in patients with
pre-existing conditions. It remains a frequent
cause of opportunistic infection among
patients whose immune system is impaired
either by pharmaceutical agents or by human
immunodeficiency virus (HIV) in endemic
areas. Histoplasmosis can present as pulmonary
histoplasmosis or progressive disseminated
histoplasmosis (PDH). H. capsulatum var. duboisii
presents a natural cutaneous infection, whereas
cutaneous dissemination is rare in H. capsulatum
var. capsulatum infection and is mostly associated
with AIDS. There are few cases of eye involvement
in histoplasmosis reported in the past but isolated
conjunctival involvement is very rare and thus far,
to the best of our knowledge, there is only one
case reported in the literature.[1]
In HIV-infected individuals, the risk factors
for the development of histoplasmosis are CD4
count of <200 cells/µL, history of exposure to
chicken coops and a known positive serology
for complement fixing antibodies prior to
illness. [2] Fever and weight loss are found in
90% of the patients with AIDS and PDH. The
most common physical findings include rales,
hepatosplenomegaly and lymphadenopathy.
Mucosal ulcers are not common in the acute form
but are common in the subacute and chronic
forms. Skin lesions are highly variable, ranging
from plaques, papules and nodules with or
without crusting. This variability is found to have
a significant association with the immune status
of the patient (as measured by CD4+ cell count).
[3,4]
In the absence of history of local trauma,
conjunctival involvement is due to hematogenous
seeding similar to mucocutaneous loci of infection.
Chest X-ray typically demonstrates widely scattered
nodular opacities or a diffuse reticular pattern. [5]
Serum LDH is elevated in most of the cases and
serum LDH >600 IU/L can be used as a diagnostic
clue for disseminated histoplasmosis.[6,7]
Histoplasmosis is sporadically reported from India
and is considered to be endemic in certain areas
of East India,[8] but recent case reports from south
India and a retrospective study by Subramanian et
al. indicate that histoplasmosis has no particular
predilection to East India.[9,10] Our patient had the
risk factors of exposure to soil and AIDS with CD4
count of 150 cells/µL. He also had clinical features
Indian J Sex Transm Dis & AIDS 2010; Vol. 31, No. 1
and investigations consistent with histoplasmosis
as described in the literature, but our case is
unique from the remainder of the reported cases
as it has extensive involvement of skin, bone
marrow and conjunctiva, confirmed on microscopic
examination. The conjunctival lesion was similar
to the mucocutaneous lesions seen in patients
with systemic histoplasmosis. A further culture
or immunofluorescence could not be performed
for definitive identification and subtyping due
to financial constraints. However, the dramatic
response to Amphotercin B, characterized by
improvement of skin lesions and the patient
becoming afebrile, cannot be overemphasized.
Thus, in the current scenario of AIDS pandemic,
a high index of suspicion has to be maintained
in diagnosing rare opportunistic infections like
histoplasmosis even in non-endemic parts of the
world. Serum LDH can be used as a diagnostic
clue. A timely diagnosis and appropriate medical
intervention results in a good prognosis.
ACKNOWLEDGMENT
We thank Dr. K. N. Chowta, Dr. Bipin K. Patel, Dr. Abul
Fazil (Department of Medicine), Dr. Urmila K., Dr. Radha
Pai, Dr. Chaya Prasad (Department of Pathology) and
Dr. Anupama Karanth (Department of Ophthalmology),
Kasturba Medical College, Mangalore, for their valuable
support.
REFERENCES
1. Knox DL, O’Brien TP, Green WR. Histoplasma granuloma of the
conjunctiva. Ophthalmology 2003;110:2051-3.
2. McKinsey DS, Spiegel RA, Hutwagner L, Stanford J, Driks MR,
Brewer J, et al. Prospective study of histoplasmosis in patients
infected with human immunodeficiency virus: Incidence, risk
factors and pathophysiology. Clin Infect Dis 1997;24:1195-203.
3. Bonifaz A, Chang P, Moreno K, Fernández-Fernández V, Montes
de Oca G, Araiza J, et al. Disseminated cutaneous histoplasmosis
in acquired immunodeficiency syndrome: Report of 23 cases. Clin
Exp Dermatol 2009;34:481-6.
4. Cunha VS, Zampese MS, Aquino VR, Cestari TF, Goldani LZ.
Mucocutaneous manifestations of disseminated histoplasmosis in
patients with acquired immunodeficiency syndrome: Particular
aspects in a Latin-American population. Clin Exp Dermatol
2007;32:250-5.
5. Conces DJ Jr, Stockberger SM, Tarver RD, Wheat LJ.
Disseminated histoplasmosis in AIDS: Findings in chest
radiographs. Am J Roentgenol 1993;160:15-9.
6. Corcoran GR, Al-Abdely H, Flanders CD, Geimer J, Patterson
TF. Markedly elevated serum lactate dehydrogenase levels are a
clue to the diagnosis of disseminated histoplasmosis in patients
with AIDS. Clin Infect Dis 1997;24:942-4.
7. Butt AA, Michaels S, Greer D, Clark R, Kissinger P, Martin DH.
Serum LDH level as a clue to the diagnosis of histoplasmosis.
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PK. Histoplasmosis in eastern India: The tip of the iceberg. Trans
R Soc Trop Med Hyg 1999;93:540-2.
9. Bhagwat PV, Hanumanthayya K, Tophakhane RS, Rathod RM.
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MS, Mathai D. Disseminated histoplasmosis. J Assoc Physicians
India 2005;53:185-9.
Source of Support: Nil. Conflict of Interest: None declared.

Pioneers of Venereology
Noguchi Hideyo (1876-1928)
Japanese pathologist. He identified Treponemes in brain of patients with general paresis and tabes dorsalis.
He used tissue impregnated with silver nitrate to visualize spirochaetes.

Neisser Albert (1855-1916)

German dermatologist. He did pioneering work in the diagnosis and treatment of venereal diseases in
the late 19th and early 20th century. He discovered gonococcus, the bacterium that causes gonorrhea in
1879. His discovery was largely due to the new development in the field of bacteriology such as Nobel
Laureate Robert Kochs smear test, the staining techniques and the new Zeiss microscope. He also research
on lupus, and with August Paul von Wassermann, on syphilis and contributed to the formulation of the
chemotherapeutic agent Salvarsan in 1910 along with his old school mate Paul Ehrlich. Neisser completed
his medical studies from Breslau in 1877 and turned to Dermatology purely by chance by becoming an
assistant physician to Oskar Simon in the dermatology clinic where he worked for years and identified
the gonococcus. He became a lecturer in dermatology in Leipzig in 1880 and 2 years later, at the age
of 27, became professor of Skin Venereal Diseases at Breslau. In 1907 Neisser became the first clinical
dermatologist to be named full time professor of dermatology at Breslau.

Ricord Philippe (1800-1889)

America-born French physician. He conducted series of experiments in which he inoculated pus from
urethral discharge, genital ulcer or draining bubo into patient’s own thigh. Performed more than 2500
inoculation and published results of his experiments in his TRAITE PRATIQUE MALADIES VENERIENNES.
He concluded that an ulcerated chancre when re-inoculated will always reproduce a chancre while re-
inoculation of pus from gonorrhea and material from secondary syphilis will not produce chancre. He
understood that both syphilis and gonorrhea are different diseases.

He proposed a simple scheme of classifying syphilis which was as follows.

a) A primary lesion, a chancre, the first manifestation of an infection.
b) Secondary lesions, resulting from that infection
c) Tertiary lesions (gummas) which rarely appear before the end of six month but whose development could
be delayed by many years.

Rhazes (860-932)
Persian physician. He gave full account of urethral discharge and its treatment by irrigation. He emphasized
on importance of catheterization in case of urinary retention and urethral stricture.

Schaudinn Fritz (1871-1906)

German zoologist. He examined a fresh preparation which Hoffmann had prepared from an eroded vulval
papule in a woman with secondary syphilis. Several pale spiral organisms were seen which rotated about
their long axis and move backwards and forward undergoing movements of flexion or angulation. They
called the organism Spirochaeta pallida and subsequently found it in both fresh and giemsa stained
preparations from 11 patients with early syphilis. They were able to differentiate the pale finely coiled
Spirochaeta pallidum and dark, thicker Spirochaeta refringens which were often present in many non
syphilitic specimens. He co-discovered, with Erich Hoffmann in 1905, the causative agent of syphilis,
Spirochaeta pallida (also known as Treponema pallidum). Work was carried out at the Berlin Charité Clinic.

38 Indian J Sex Transm Dis & AIDS 2010; Vol. 31, No. 1