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Onychomycosis Caused by Nigrospora sphaerica in an Immunocompetent Man

Article  in  Archives of dermatology · June 2009

DOI: 10.1001/archdermatol.2009.80 · Source: PubMed

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Yi-Ming Fan Wen li

Guangdong Medical University, Zhanjiang, China Northeastern University (Shenyang, China)
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A
B
Figure 1. Generalized granuloma annulare on the abdomen before (A) and
after (B) treatment with adalimumab, 40 mg/wk for 12 weeks.
Figure 2. Lymphocytic perivascular infiltrate and an interstitial infiltrate
composed of epithelioid macrophages surrounding foci of necrobiotic
collagen in a palisaded arrangement consistent with granuloma annulare
(hematoxylin-eosin, original magnification ⫻100).
HLA-DR regions. Results showed that the subjects
were monozygous twins with the HLA-A01, HLA-B08,
and HLA-DR3(17) antigens of AH8.1.
Comment. The present case illustrates a rapid
response of disseminated GA to adalimumab in identi-
cal twins with AH8.1. Although TNF-␣ inhibitors have
been shown to help ameliorate some forms of DGA,3,4
it is not yet clear if patients with TNF polymorphisms
are more likely to respond to TNF-␣ blocking agents.
Clinicians should carefully consider the potential
risks of adalimumab therapy in any off-label use of
this medication. Determining the HLA type of adali-
mumab responders could help identify any further
correlation between adalimumab efficacy in DGA and
AH8.1.
Keith Allen Knoell, MD
(REPRINTED) ARCH DERMATOL/ VOL 145 (NO. 5), MAY 2009
611
Downloaded from www.archdermatol.com at Guangdong Medical College, on May 18, 2009
©2009 American Medical Association. All rights reserved.
Correspondence: Dr Knoell, Department of Dermatol-
ogy, University of Virginia, Charlottesville, VA 22908
(kk3p@virginia.edu).
Financial Disclosure: None reported.
Funding/Support: A portion of the adalimumab used in
this case was donated by Abbott Laboratories.
Role of the Sponsor: Abbott Laboratories had no role in
the design and conduct of this study; in the collection,
analysis, and interpretation of data; in the preparation
of the manuscript; or in the review or approval of the
manuscript.
1. Fayyazi A, Schweyer S, Eichmeyer B, et al. Expression of IFNgamma, coex-
pression of TNFalpha and matrix metalloproteinases and apoptosis of T lym-
phocytes and macrophages in granuloma annulare. Arch Dermatol Res. 2000;
292(8):384-390.
2. Hertl MS, Haendle I, Schuler G, Hertl M. Rapid improvement of recalcitrant
disseminated granuloma annulare upon treatment with the tumor necrosis
factor-alpha inhibitor, infliximab. Br J Dermatol. 2005;152(3):552-555.
3. Shupack J, Siu K. Resolving granuloma annulare with etanercept. Arch Dermatol.
2006;142(3):394-395.
4. Kreuter A, Altmeyer P, Gambichler T. Failure of etanercept therapy in dis-
seminated granuloma annulare. Arch Dermatol. 2006;142(9):1236-1237.
5. Candore G, Lio D, Colonna Romano G, Caruso C. Pathogenesis of autoim-
mune diseases associated with 8.1 ancestral haplotype: effect of multiple gene
interactions. Autoimmun Rev. 2002;1(1-2):29-35.
6. Heffernan MP, Smith DI. Adalimumab for treatment of cutaneous sarcoidosis.
Arch Dermatol. 2006;142(1):17-19.
Onychomycosis Caused by Nigrospora
sphaerica in an Immunocompetent Man
Nigrospora is rarely an opportunistic pathogen in hu-
mans. To our knowledge, there have been 4 reports on
Nigrospora-induced human eye and skin infections in the
literature.1-3 However, none of these cases included defi-
nite clinicopathologic evidence or species identifica-
tion. Herein, we report the first case to our knowledge
of Nigrospora sphaerica–induced onychomycosis in
humans.
Report of a Case. A 21-year-old man presented with an
increasing discoloration of the right first toenail in Sep-
tember 2006. On examination, the whole dorsal surface
of the nail plate of the right first toenail was found to be
eroded in a powdery, turbid, white patch, and the lateral
nail plates showed a brownish discoloration, without sub-
ungual hyperkeratosis and onycholysis (Figure 1A). The
nail plates of the right second and third toenails were also
studded with a few well-circumscribed white patches, but
other toenails and toe webs were normal.
Potassium hydroxide preparation from nail scrap-
ings showed numerous ovoid chlamydospores, lobi-
form conidiophores, pear-shaped conidia, and a few hya-
line septate hyphae. Periodic acid–Schiff–stained sections
found numerous purple spores with a few fungal fila-
ments among onychocytes in the body of the nail
(Figure 2). Fungal culture revealed that the same colo-
nies were grown at 27°C in Sabouraud dextrose agar me-
dium without antibiotics after 1 week.
Microscopically, gray, branched, and septate aerial hy-
phae differentiated into the conidiophores. The conidi-
ogenous cells on the conidiophores were lateral or ter-
minal, inflated, hyaline, and ampulliform in shape, with
a single conidium at their attenuated apexes. The ma-
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 A B
Figure 1. Patient’s toe before and after treatment. A, White discoloration on
the whole dorsal surface of the nail plate of the right first toenail. B, After
treatment, clinical cure of nail plate.
Figure 2. Histomycologic image of nail clippings showing purple spores and
hyphae (periodic acid–Schiff stain, original magnification ⫻1000).
ture conidia were spherical or oblate, usually single celled
(occasionally polycelled), black, and smooth walled
(Figure 3). The isolate was identified as N sphaerica based
on the morphologic features and DNA sequence analysis.
Results of nail plate infection testing and gelatin liq-
uefaction tests were positive. An in vitro antifungal sus-
ceptibility test found that the strain was very sensitive
to itraconazole, clotrimazole, amphotericin B, and ny-
statin and resistant to fluconazole, ketoconazole, econa-
zole, and flucytosine.
The patient was treated with a 5-month course of oral
itraconazole pulse therapy at a dose of 400 mg once daily
for 1 week per month. Mycologic and clinical cures were
obtained after 3 and 10 months, respectively (Figure 1B),
and no recurrence was recorded.
Comment. The diagnosis of nondermatophytic onycho-
mycosis requires repeated isolation of the suspected agents
on 2 or more separate occasions in the absence of der-
matophyte growth.4 Histomycologic analysis of nail clip-
pings can distinguish the invading fungi from coloniz-
(REPRINTED) ARCH DERMATOL/ VOL 145 (NO. 5), MAY 2009
612
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©2009 American Medical Association. All rights reserved.
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Figure 3. Microculture on Sabouraud dextrose agar at 27°C after 1 week
showing spherical or oblate black and single-celled conidia developing from
conidiogenous cells (original magnification ⫻400).
ing or contaminating agents.5 In the present study, nail
specimens were collected and analyzed on 2 different oc-
casions before treatment to exclude the possibility of false-
positive results. Repeated isolation of N sphaerica from
the patient’s nail scrapings and clippings, positive re-
sults of histomycologic analysis, and good effect of an-
tifungal treatment are strong evidence for its etiologic role.
The molecular typing of the isolate provided a defini-
tive identification of N sphaerica, though the DNA se-
quence information for the genus Nigrospora is incom-
plete in GenBank. Our patient had a rapid response to
oral itraconazole pulse therapy, indicating that itracona-
zole is effective in the treatment of onychomycosis caused
by N sphaerica.
Yi-Ming Fan, MD
Wen-Ming Huang
Wen Li
Guo-Xue Zhang, MM
Correspondence: Dr Fan, Department of Dermatology,
Affiliated Hospital of Guangdong Medical College, Zhan-
jiang, Guangdong 524001, China (ymfan1963@163
.com).
Financial Disclosure: None reported.
Additional Contributions: Feng-Yan Bai, MD, pro-
vided fungal identification and helped with the manu-
script.
1. Muralidhar S, Sulthana M. Nigrospora causing corneal ulcer—a case report.
Indian J Pathol Microbiol. 1997;40(4):549-551.
2. Talwar P, Sehgal SC. Mycotic infections of the eye in Chandigarh and neigh-
bouring areas. Indian J Med Res. 1978;67:929-933.
3. Pritchard RC, Muir DB. Black fungi: a survey of dematiaceous hyphomycetes
from clinical specimens identified over a five-year period in a reference
laboratory. Pathology. 1987;19(3):281-284.
4. Gupta AK, Ryder JE, Baran R, Summerbell RC. Non-dermatophyte onychomycosis.
Dermatol Clin. 2003;21(2):257-268.
5. Piérard GE, Quatresooz P, Arrese JE. Spotlight on nail histomycology. Der-
matol Clin. 2006;24(3):371-374.
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