Volume 15 Number 10
October 2009
DOJ
Contents
Cutaneous pseudallescheria boydii infection in a renal
transplant patient: A case report
José Carlos Cardoso, David Serra, Raquel Cardoso, José Pedro
Reis, Óscar Tellechea, Américo Figueiredo
Dermatology Online Journal 15 (10): 8
Serviço de Dermatologia, Hospitais da Universidade de Coimbra, Coimbra,
Portugal. ze_carlos_cardoso@yahoo.com.br
Abstract
We describe the case of a 59-year-old male renal transplant
recipient who presented with a 1 month history of nodular,
erythematous, and crusted lesions on the anterior surface of the left
leg. There was no history of trauma. The patient had no systemic
signs or symptoms. A skin biopsy revealed evidence of a deep
fungal infection, with septate and branching hyphae amongst the
dermal inflammatory infiltrate, but the culture was negative. Initial
treatment with itraconazole proved ineffective and new lesions
appeared. New tissue samples were obtained for culture, allowing
the isolation of Pseudallescheria boydii. The patient underwent
surgical excision of the lesions combined with voriconazole 400
mg/day for 2 months. After this period no new lesions appeared
and the patient has remained without recurrence after 2 years of
follow-up. Pseudallescheria boydii is an opportunistic fungus that
can cause systemic infection mainly in immunocompromised
patients that manifests as pulmonary, osteoarticular, ocular,
vascular, cutaneous or central nervous system disease. Resistance
to therapy can occur with infection progression and high mortality.
Treatment with the combination of an antifungal agent, mainly
voriconazole, and surgery, when feasible, probably provide the best
results in cutaneous infections.
Introduction
In the last few decades infections caused by opportunistic
agents, particularly certain species of fungi, have gained
importance because of the increasing number of
immunocompromised patients, namely transplant recipients [1].
Pseudallescheria boydii (the teleomorphic form of
Scedosporium apiospermum) is a ubiquitous fungus known to be
an agent of mycetoma in immunocompetent individuals. The
incidence of this infection has become elevated in parallel with the
increased numbers of immunocompromised patients, particularly
solid organ transplant recipients [2, 3, 4, 5]. Along with the
potential seriousness of the disease caused by this agent, with
potential disseminated disease and fatal outcome, its importance
relates also to the facts that it morphologically resembles other
fungi (Aspergillus sp.), and it shows resistance to multiple
antifungal agents, including amphotericin B [2, 3, 5, 6].
We report the case of a renal transplant recipient with
cutaneous infection caused by Pseudallescheria boydii.
Case report
A 59-year-old male patient, renal transplant recipient for
about 4 years, presented with a 1-month history of three lesions on
the anterior aspect of his left leg. The lesions were asymptomatic
and the patient had no systemic signs or symptoms. There was no
history of previous trauma. His past medical history was
remarkable for hypertension, ischemic heart disease and chronic
renal failure. Beginning in 2001 he required dialysis and underwent
renal transplantation in 2004. His usual medication included
tacrolimus, mycophenolate mofetil, prednisolone, valsartan,
furosemide, and omeprazole. By the time of our first observation
he had already been treated with oral cefaclor and topical fusidic
acid, with no response. Examination disclosed four erythematous,
violaceous exudative nodules on the anterior aspect of the left leg,
in a roughly linear, sporotrichoid-like, distribution (Fig. 1).
Figure 1
Figure 2
Figure 1. Three plaques with crusted surface and a nodular lesion on the
left leg, in a sporotrichoid pattern of distribution
Figure 2. Granulomatous infiltrate in the dermis, composed of histiocytes,
lymphocytes, multinucleated giant cells and numerous neutrophils with
associated nuclear dust (H&E, x400).
Histological examination of one lesion revealed a
granulomatous dermal infiltrate composed of lymphomononucleate
and polymorphonuclear cells (Fig. 2). PAS staining disclosed a
small number of septate and branching hyphae in the deep dermis
(Fig. 3). Fite-Faraco staining was negative. Mycological and
mycobacterial cultures were negative. Empiric treatment with
itraconazole was started at 100 mg twice a day.
Figure 3
Figure 4
Figure 3. Septate and branching hyphae among the dermal infiltrate
(Left, H&E; Right, PAS stain; x400)
Figure 4. Final outcome after surgical excision and 2 months of therapy
with voriconazole
After 2 months of treatment, there was no improvement and
new lesions had appeared on the same leg. New tissue samples for
exhaustive microbiological studies were collected and allowed the
isolation of Pseudallescheria boydii (confirmed in 2 samples). The
patient underwent surgical excision of the lesions combined with
voriconazole 400 mg/day for two months, with a good response
(Fig. 4). The only side effect was a transient decrease in renal
function associated with increased tacrolimus levels, due to
interaction with voriconazole, which completely reversed after
dose adjustments.
No recurrence was seen after 2.5 years of follow-up.
Discussion
The variety of agents and possible manifestations of infections
in immunocompromised patients requires an tissue biopsies for
histopathology and culture. The present case is a good example that
highlights some important issues.
First, the clinical picture of P. boydii infection is quite
variable and can include a sporothricoid-like distribution of lesions.
This has been reported in the literature, but is more commonly
associated with other agents (namely sporotrichosis and some
atypical mycobacterial infections) [3, 7].
Second, the morphological characteristics of P. boydii in
tissue biopsies include the formation of septate hyphae branching
at 45º angles, morphologically similar to Aspergillus [2, 3, 5, 8]
and, to a lesser extent, Fusarium [8, 9]; this can be a pitfall in the
diagnosis. We highlight here the importance of the use of repeated
cultures (or other techniques, when available), especially in cases
of therapeutic failure, as in our patient.
Finally, P. boydii is frequently resistant to multiple antifungal
agents, including those usually used in the treatment of systemic
mycoses in immunocompromised hosts, most notably amphotericin
B [2, 3, 5, 6]. In vitro susceptibility studies have found
voriconazole to be the most effective drug, followed by
posaconazole [10, 11]. Accumulated clinical experience seems to
support voriconazole efficacy, with several reports of good
response to this drug. However, to our knowledge, controlled
studies are lacking [9,12, 13, 14]. Surgical treatment, whenever
possible, seems to be of value: there are several reports of
successful treatment combining antifungal and surgery, for
cutaneous but also extracutaneous disease [14, 15, 16].
In conclusion, the accurate diagnosis and early treatment are
extremely important in the management of fungal infections in
immunocompromised patients, in order to avoid dissemination of
the disease and a consequent unfavorable prognosis.
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