DERMATOLOGICA SINICA 34 (2016) 118e119
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CORRESPONDENCE
Asymptomatic meningeal and pulmonary cryptococcosis during the
course of low-dose prednisolone therapy for bullous pemphigoid
Dear Editor,
We report herein an elderly Japanese patient who developed
meningeal and pulmonary cryptococcosis asymptomatically during
the course of prednisolone therapy for bullous pemphigoid (BP)
with a maintenance dosage of 4 mg/d.
A 90-year-old Japanese woman presented with a 1-month history of itchy erythema. On physical examination, multiple edematous erythema and erythematous papules were seen on her
breasts, abdomen, lower back, and right upper arm. There was a
firm blister, 20 mm in size, on her lower abdomen. Her past medical
history was significant for hypertension and chronic renal failure. A
BP180NC16A enzyme-linked immunosorbent assay test was positive, with a value of 44 U/mL (cutoff 9 U/mL). A whole-body
computed tomography (CT) scan ruled out paraneoplastic pemphigoid. We diagnosed her with BP and prednisolone monotherapy,
administered at an initial dosage of 15 mg/d with a gradual
tapering, led to complete disappearance of eruptions.
Seven months after the administration of prednisolone, she was
admitted to our hospital with high fever caused by emphysematous
cystitis. At the time, she had been treated for BP with oral prednisolone at 4 mg/d for 2 months. Her laboratory values showed the
following: elevated white blood cell count of 9200/mm3 (range:
4000e8000/mm3), mild anemia [hemoglobin was 11.0 g/dL (range:
12.0e15.0 g/dL), hematocrit 31.4 % (range: 37.0e45.0 %)], normal
platelets 33 104/mm3 (range: 16e36 104/mm3 ), C-reactive
protein < 0.1
mg/dL
(range:
<0.299
mg/dL),
beta-Dglucan < 6.0 pg/mL (range: < 6.0 pg/mL), blood urea nitrogen
21 mg/dL (range: 7e30 mg/dL), and an elevated creatinine level
of 1.61 mg/dL (range: 0.4e0.8 mg/dL). The urine Gram stain visualized gram-negative bacteria and Escherichia coli was detected using
urine culture. A chest x-ray on admission revealed a faint nodule in
the right lung field (Figure 1). Intravenous ceftriaxone was initiated,
and her fever resolved, however, the nodule seen in the chest x-ray
did not regress. CT revealed a round and cavitary nodule, 1 cm in
diameter, in the right lung field (Figure 2). Etiologically, pulmonary
cavitary disease in immunocompromised patients is associated
with fungal infections such as Aspergillus, Coccidioides, and Cryptococcus.1 Therefore, the lung nodule, which had not been detected in
the CT at the initiation of prednisolone therapy, led us to search for
Conflicts of interest: The authors declare that they have no financial or nonfinancial conflicts of interest related to the subject matter or materials discussed
in this article.
fungal infections. Sputum smear and culture were negative, but
positive serum cryptococcal antigen was identified. A lumbar puncture showed a cryptococcal antigen with a titer of 1:64 in the cerebrospinal fluid, and Cryptococcus neoformans was confirmed with
culture of the fluid using the BD Phoenix system (Becton, Dickinson
Diagnostics, Sparks, MD, USA). The patient did not develop headache, personality changes, or symptoms suspicious of central nervous system involvement. Given her age and impaired renal
function, oral fluconazole was administered. Oral steroid was maintained and BP did not flare up during hospitalization. C. neoformans
was negative in the cerebrospinal fluid culture 3 months after
discharge and the lung nodule decreased in size as shown in the CT.
Cryptococcosis is an invasive fungal infection causing substantial morbidity and mortality among immunocompromised patients,
including individuals positive for human immunodeficiency virus
and those receiving chronic glucocorticoid treatment.2 It is common for dermatologists to use low-dose corticosteroids for BP therapy; however, there has been only one report of cryptococcosis
Figure 1 A chest x-ray on admission showed a faint nodule in the right lung field
(black arrow).
http://dx.doi.org/10.1016/j.dsi.2015.11.004
1027-8117/Copyright © 2016, Taiwanese Dermatological Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).
Correspondence / Dermatologica Sinica 34 (2016) 118e119
119
been low and she had never complained of any respiratory symptoms. A chest x-ray might have led to early detection of her fungal
infection. Our case demonstrated that even low-dose systemic
prednisolone can cause asymptomatic cryptococcosis. In addition,
a chest x-ray and serum cryptococcal antigen testing4 might be useful as a screening tool for cryptococcosis, especially in asymptomatic cases like ours.
Hanako Koguchi-Yoshioka*, Noriko Hashimoto-Azuma
Department of Dermatology, Minoh City Hospital, Osaka, Japan
Miwa Takamure, Fumihisa Soga
Department of Neurology, Minoh City Hospital, Osaka, Japan
Eriko Hideshima, Ryutaro Komuro
Department of Diabetes and Endocrinology, Minoh City Hospital, Osaka, Japan
Chiho Matsumoto
Department of Dermatology, Minoh City Hospital, Osaka, Japan
*
Figure 2 Computed tomography of the lung revealed a round and cavitary nodule,
1 cm in diameter, in the right field (black arrow).
developing during steroid therapy for BP.3 The patient had been
treated with oral prednisolone at 17.5 mg/d for 1 year when she
was diagnosed with cutaneous and pulmonary cryptococcosis.
Our patient had been treated with prednisolone for 7 months at a
lower dosage (15 mg/d), with a gradual tapering to 4 mg/d; however, she asymptomatically developed cryptococcal meningitis, which
the previous patient did not, and her clinical course would be critical if we had missed the meningitis. How could we have found her
asymptomatic cryptococcal infection? A chest x-ray on admission
for cystitis showed a faint nodule in the right lung field. We had
not performed chest x-rays because the corticosteroid dose had
Corresponding author. Department of Dermatology, Minoh City Hospital, Osaka,
5-7-1 Kayano, Minoh, Osaka 562-0014, Japan.
E-mail address: [email protected] (H. Koguchi-Yoshioka).
References
1. Gadkowski LB, Stout JE. Cavitary pulmonary disease. Clin Microbiol Rev 2008;21:
305e33.
2. Brizendine KD, Baddley JW, Pappas PG. Predictors of mortality and differences in
clinical features among patients with Cryptococcosis according to immune status. PloS One 2013;8:e60431.
3. Sugiura K, Sugiura N, Yagi T, et al. Cryptococcal cellulitis in a patient with bullous
pemphigoid. Acta Derm Venereol 2013;93:187e8.
4. Kaplan JE, Vallabhaneni S, Smith RM, Chideya-Chihota S, Chehab J, Park B. Cryptococcal antigen screening and early antifungal treatment to prevent cryptococcal meningitis: a review of the literature. J Acquir Immune Defic Syndr
2015;68:S331e9.
Received: Aug 24, 2015
Revised: Oct 23, 2015
Accepted: Nov 16, 2015