JSTR MEETING NOTES
Japanese Society of Thoracic Radiology
Disseminated Pulmonary Penicilliosis in a
Rheumatoid Arthritis Patient
Kentarou Akata, MD,* Kazuhiro Yatera, MD,* Takatoshi Aoki, MD, PhD,w Masami Fujii, MD,w
Shunsuke Kinoshita, MD,w Toshinori Kawanami, MD,* Hiroshi Ishimoto, MD,*
Masanori Hisaoka, MD, PhD,z Yukunori Korogi, MD, PhD,w and Hiroshi Mukae, MD*
Key Words: Penicillium marneei, disseminated penicilliosis,
computed tomography, antitumor necrosis factor-a inhibitor,
rheumatoid arthritis
(J Thorac Imaging 2014;29:W14W16)
P enicilliosis is an infectious disease caused by Penicillium
marneei and is commonly seen in patients with
acquired immunodeciency syndrome in southern and
southeastern Asian countries.1 Although infection by P.
marneei is increasing with an increase in the number of
individuals being infected with human immunodeciency
virus (HIV), indicating a direct association between the 2,
non-HIV cases have also been reported.2 Because the
radiologic ndings of penicilliosis mimic tuberculosis, it
may be dicult to make a prompt and accurate diagnosis,
especially in non-HIV patients. We describe a case of dis-
seminated penicilliosis presenting as pulmonary miliary
nodules on computed tomography (CT), which occurred in
a non-HIV patient with rheumatoid arthritis (RA) treated
with combined biological response modier drugs (bio-
logics) and methotrexate (MTX).
CASE REPORT
A 56-year-old Japanese man with RA had been treated with
MTX and iniximab (IFX) for 2 years. He had been travelling to
Thailand on business for 10 to 20 days a month for 5 months. While
in Thailand, he experienced general fatigue, fever, loss of appetite,
and sweating, and his symptoms worsened despite receiving intra-
venous clindamycin, ceftriaxone, and prednisolone (20 mg/d) at a
local hospital. Thirteen days after presenting to the hospital in
Thailand, he returned to Japan and was admitted to our hospital.
Upon admission, he was alert and demonstrated a high-grade
fever (39.21C) and severe hypoxemia with hypocapnia (PaO2/
From the Departments of *Respiratory Medicine; wRadiology; and
zPathology and Oncology, University of Occupational and Envi-
ronmental Health, Fukuoka, Japan.
The authors declare no conicts of interest.
Reprints: Takatoshi Aoki, MD, PhD, Department of Radiology,
University of Occupational and Environmental Health, 1-1
Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka 807-8555, Japan
(e-mail: a-taka@med.uoeh-u.ac.jp).
Copyright r 2013 by Lippincott Williams & Wilkins
W14 | www.thoracicimaging.com
PaCO2 84/28.3 Torr under 10 L/min mask oxygen support). Lymph
nodes were not palpable. Chest auscultation, abdominal, neuro-
logical, and dermal ndings, and extremities were normal. Labo-
ratory ndings on admission demonstrated an elevated serum
C-reactive protein without leukocytosis. Serum b-D-glucan was
negative on admission but increased to 42.4 pg/mL on the third day
of hospitalization. Chest CT demonstrated diuse miliary nodules
with a random distribution (Figs. 1A, B), ground-glass opacities,
bilateral pleural eusions, and diuse mediastinal lymphadeno-
pathy. Hepatosplenomegaly was shown on abdominal CT.
Although his sputum and gastric uid were negative for acid-
fast bacilli, he was initially treated with antituberculous agents
(isoniazid, rifampicin, and ethanbutol) with concomitant
discontinuation of MTX and IFX. However, his respiratory failure
and chest radiologic ndings worsened. Ventilator support was
started on the third day of hospitalization. Cytologic specimens in
the bronchoalveolar lavage uid demonstrated yeast-like fungi with
septal formation in the fungal bodies that were characteristic for
Penicillium species (Fig. 2). Pathologic ndings of the biopsy
specimens obtained from bone marrow, liver, and transbronchial
lung biopsy also showed the same fungi as those in the bron-
choalveolar lavage uid. Disseminated penicilliosis was suspected,
and intravenous administration of liposomal amphotericin B with
hydrocortisone (300 mg/d) was eective. Ventilatory support was
subsequently discontinued on the eighth day of hospitalization.
Despite this clinical improvement, a follow-up chest CT showed
that the diuse miliary nodules had worsened, and the galaxy
sign had appeared (Figs. 1C, D). Amphotericin B followed by
micafungin and subsequent administration of voriconazole with
hydrocortisone were administered, and his symptoms ameliorated.
He was discharged on the 48th day of his admission.
DISCUSSION
P. marneei is a temperature-dependent dimorphic fun-
gus that is exceptionally virulent compared with other Pen-
icillium species. Infection by P. marneei is an opportunistic
disease, and most of the reported cases have been associated
with acquired immunodeciency syndrome. It is now the third
most opportunistic infectious disease (after cryptococcosis and
miliary tuberculosis) in HIV-infected patients in Thailand.3
The natural host of P. marneei is the bamboo rat, and
the infectious route into humans is inhalation of con-
idiospores, which causes pulmonary infection. This is fol-
lowed by hematological systemic dissemination, especially
to the liver, spleen, and lymph nodes.1 Non-HIV cases of
penicilliosis have been described in patients with systemic
lupus erythematosus,2 but, to our knowledge, there have
been no previously reported case of penicilliosis in patients
with RA. The patient described in this report had an
immunodeciency related to RA and was also treated with
IFX and MTX for 2 years. We hypothesize that immune
J Thorac Imaging  Volume 29, Number 2, March 2014
J Thorac Imaging  Volume 29, Number 2, March 2014 Disseminated Pulmonary Penicilliosis in RA Patient

FIGURE 1. Initial chest CT images obtained on admission show disseminated small nodules with a random distribution and ground-
glass opacity in both lungs (A and B). Eight days after the initial CT, these lesions have progressed (C and D), and the galaxy sign is
observed in the right upper lobe (C, arrow).

suppression from these medications may be the cause of
disseminated penicilliosis in this patient.
Symptoms of disseminated penicilliosis include fever,
anemia, body weight loss, skin eruption, lymphadenopathy,
and cough.3 The diagnosis of penicilliosis is usually based
on the detection of P. marneei from aected lesions. Skin
and blood are reported to be appropriate sites, and bone
marrow, lymph nodes, and lungs are also detectable sites.
Pathologic ndings of this disease show a growth of yeast-
like fungi with septal formation in the fungal bodies, and
pus formation, necrosis, and granuloma tissues are seen in
its more progressed state. P. marneei is susceptible to
amphotericin B, itraconazole, ketoconazole, and vor-
iconazole, but it is resistant to uconazole.
Chest radiograph ndings of penicilliosis are variable
and include consolidations, nodules, diuse alveolar opac-
ities, mediastinal lymphadenopathy, and pleural eusion.
To our knowledge, there is only 1 previously published case
report that documents the chest CT ndings of penicilliosis.
Santiso et al4 reported that in the case studied by them
bilateral diuse nodular opacities and ground-glass attenu-
ation were demonstrated. In the patient described in this
report, diuse miliary nodules with a random distribution
were observed on chest CT. Considering the distribution of
miliary nodules and the clinical context of this case, gran-
uloma-forming infection, such as miliary tuberculosis and
fungal infection, was suspected. The galaxy sign, which is
described as an irregularly marginated pulmonary nodule
formed by a conuence of multiple smaller nodules,5 was
also seen in this case. This sign represents small granulomas
that have coalesced and become inseparable, simulating the
appearance of a larger nodule. Although this sign was rst
described in sarcoidosis, cases of tuberculosis and pneu-
moconiosis have subsequently been reported in association
with this nding.5 Epidemiological and clinical data are
helpful for narrowing the dierential diagnosis in cases of
the galaxy sign. Although the mechanism by which this sign
formed after this patient started appropriate therapy is
unknown, immune reactions such as immune recovery
syndrome due to cessation of biologics and MTX may have
potentially contributed to this phenomenon.
In conclusion, disseminated penicilliosis is rare, espe-
cially in non-HIV patients. However, physicians should
consider this infection in patients who present with imaging
ndings of diuse military lung nodules with a history of
travel to an endemic area of penicilliosis.

FIGURE 2. Photomicrographs of the lung biopsy specimen (Grocott staining) showing sterigmata of P. marneffei (A, arrows) and the
characteristic transverse septum (B, arrow) in the conidium. Each bar represents 20 mm.

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Akata et al
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