ARTICLE IN PRESS

Respiratory Medicine (2007) 101, 863–864

CASE REPORT

Transformation of pulmonary histoplasmosis to

sarcoidosis: A case report
Jonathan H. Wynbrandt, Elliot D. Crouser

Division of Pulmonary, Critical Care, and Sleep Medicine, Ohio State University Medical Center, 1654 Upham Drive,
202 Means Hall, Columbus, OH 43210, USA

Received 9 August 2006; accepted 14 August 2006

KEYWORDS Summary
Sarcoidosis; Histoplasmosis, a dimorphic fungus, and sarcoidosis, a disease of unknown etiology, share
Histoplasmosis; many clinical features, including typical manifestations of granulomatous inflammation
Transformation; involving the lungs and mediastinal lymphatics in association with constitutional
Granulomatous; symptoms. As such, they are often difficult to distinguish based upon clinical presentation.
Genetics Recent studies suggest that sarcoidosis may be triggered by infectious agents. Here we
present a case of documented pulmonary histoplasmosis that evolved into sarcoidosis. This
case supports the notion that infections promote sarcoidosis in predisposed hosts.
& 2006 Elsevier Ltd. All rights reserved.

Introduction documented pulmonary infection with histoplasmosis who

First described in 1877 by Dr. Jonathan Hutchinson,
sarcoidosis, a non-caseating granulomatous disease affect-
ing multiple organs, remains a mystery in its etiology and
pathogenesis. It is commonly believed that sarcoidosis arises
when a genetically susceptible host is exposed to various
environmental triggers.1 Histoplasma capsulatum, the
pathogen responsible for pulmonary histoplasmosis, is a
common cause of self-limited granulomatous inflammation
in the lungs of residents of the Ohio and Mississippi Valleys,
and is difficult to distinguish from sarcoidosis in the clinical
setting.2 Here we describe a case of an individual with a
Corresponding author. Tel.: +1 614 293 4919.
E-mail address: wynbrandtl@aol.com (J.H. Wynbrandt).
subsequently developed pulmonary sarcoidosis.
Case report
A 55-year-old previously healthy white male presented with
several weeks of progressive shortness of breath, night
sweats, weight loss and dry non-productive cough. His
symptoms developed soon after the belfry of the church, of
which he was the pastor, underwent a cleaning to remove
copious amounts of bat guano. He and his secretary both
developed pulmonary and constitutional symptoms, and
were eventually referred to a local pulmonologist when
their symptoms failed to improve with oral antibiotics. The
Pastor’s evaluation included a chest X-ray, which demon-
strated patchy right middle and lower lobe infiltrates, and

0954-6111/$ - see front matter & 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.rmed.2006.08.011
 ARTICLE IN PRESS
864
an elevated urine histoplamosis antigen. The patient was
treated with itraconazole for 12 weeks with initial improve-
ment in some of his symptoms, particularly the constitu-
tional symptoms. However, the dyspnea and cough
continued to progress despite antifungal therapy. He was
then referred to a tertiary hospital for further evaluation. A
CT scan of the chest showed prominent bilateral interstitial
infiltrates with evidence of fibrosis at the lung bases, and
pulmonary function tests demonstrated mild restrictive
physiology. He was subsequently referred for an open lung
biopsy, which demonstrated prominent granulomatous
pneumonitis with moderate intra-alveolar septal fibrosis.
Special stains and cultures for fungus and acid-fast bacilli
were negative. He was treated with oral corticosteroids with
good results, including subjective improvement of his
pulmonary symptoms and objective improvements in his
pulmonary function parameters over the next 6 months. Of
note, his secretary recovered from her case of pulmonary
histoplasmosis uneventfully.
Discussion
It is often difficult to distinguish sarcoidosis from pulmonary
infections (mycobacterial, fungal) based solely on clinical
presentation. Here we describe a case in which pulmonary
histoplasmosis evolved into a chronic non-infectious pul-
monary disease, which pathologically conformed to the
diagnosis of sarcoidosis. It is unlikely that the onset of
sarcoidosis preceded pulmonary histoplasmosis, because the
patient had no symptoms even during jogging, prior to the
cleaning of the belfry of his church. Although we can find no
precedent for a case of documented pulmonary histoplas-
mosis transforming into sarcoidosis, there are plenty of
cases wherein the diagnosis of sarcoidosis preceded the
onset of histoplasmosis,3 suggesting that the original
diagnosis of sarcoidosis was erroneous or that sarcoidosis
or associated treatment predisposes to fungal infection. In
this case, it would appear that uncontrolled pulmonary
granulomatous inflammation (sarcoidosis) evolved after the
resolution of pulmonary histoplasmosis and, as such, may
represent a persistent inflammatory response to fungal
antigens.
The putative relationship between environmental expo-
sures and sarcoidosis was recently explored in A Case-
J.H. Wynbrandt, E.D. Crouser
Control Etiologic Study of Sarcoidosis (ACCESS), which
showed positive correlations between certain environmental
and occupational exposures and sarcoidosis.1 High risk
exposures included agricultural employment and work
environments associated with exposures to mold and
mildew.4 Other investigations suggest that exposure to
certain infections, including mycobacteria, viruses, and
propionobacteria, predispose to sarcoidosis.5 However,
efforts to identify specific infectious agents have not
consistently demonstrated an association with sarcoidosis.
Moreover, a recent study revealed a strong association
between a mutation of a gene located on chromosome six
(butyrophilin-like 2), which is believed to regulate T-cell
activity, and sarcoidosis in Germans,6 and similar mutations
appear to contribute to disease in North Americans.7 The
current case, and other reports demonstrating retained
byproducts of infectious agents in the tissues of patients
with sarcoidosis,8 supports the likelihood that sarcoidosis is
a disease in which environmental factors, including infec-
tious agents, together with a genetic predisposition of the
host, combine to influence disease phenotype.
References
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