ARTICLE
Auteur(s) : Takeshi
Uenotsuchi, Yoichi Moroi, Kazunori Urabe, Shuji Fukagawa, Gaku
Tsuji, Tetsuo Matsuda, Masutaka Furue
Department of Dermatology, Graduate School of Medical Sciences,
Kyushu University, Fukuoka, 812-8582, Japan
accepté le 14 Octobre 2004
Chronic granulomatous disease (CGD) is a rare inherited disorder of
phagocytic cells [1]. The pattern of inheritance is either X-linked
or autosomal recessive [1, 2]. CGD is due to a phagocytic defect in
NADPH-mediated oxidation that leads to susceptibility of the host
to many catalase-positive bacteria (Staphylococcus aureus,
Escherichia coli, Klebsiella, Enterobacteria, Serrattia,
Salmonella, and Pseudomonas) and fungi (Asperigillus and Candida)
[1]. The symptomatology usually emerges during the first two years
of life [2]. The major clinical manifestations are pyoderma,
pneumonia, gastro-intestinal involvement, lymphadenitis, liver
abscess, and osteomyelitis [2]. Fungal infections are a major cause
of morbidity and mortality in CGD patients. Aspergillus accounts
for 20% of all infections in CGD patients, and it is associated
with a 50% mortality rate [3]. Due to
sulfamethoxazole-trimethoprim, interferon (IFN)-γ and antifungal
drugs, the prognosis for patients appears to be improving
[4].Alternaria species are ubiquitous fungal saprophytes that have
a worldwide distribution [5, 6]. Although recognized as a plant
pathogen, this species of fungus, Alternaria, is an uncommon cause
of disease in a man [6]. Most Alternaria infections in humans are
cutaneous, occurring most often in patients with immunologic
impairment and far less often in healthy individuals [6-9].
Alternaria is often a contaminant, when isolated, rather than a
true pathogen [6]. To diagnose someone with alternariosis, the
fungal elements should be apparent within the tissue and subsequent
cultures, and correct identification is desirable [7].Herein, we
report a case of dermal alternariosis in a 69-year-old man with
X-linked CGD. To our knowledge, this is the first presentation of a
case with isolated cutaneous involvement due to Alternaria
alternata associated with CGD.
Case report
A 69-year-old man was referred to our outpatient department with a
one-month history of an erythematous lesion of his right hand,
which had been treated as a superficial fungal infection with
topical application of bifonazole that failed to respond ( (figure 1) ). He
suffered from X-linked CGD and had a history of frequent bacterial
infection. He had been treated with interferon (IFN)-γ. Laboratory
studies disclosed the following values: WBC count, 4,160
cells/mm3 (46.4% polymorphonuclear cells, 45.7%
lymphocytes, 2.6% eosinophils, 4.8% monocytes, and 0.5% basophilic
cells); and CRP, 0.17 mg/dl. A biopsy of the lesion showed
pseudoepitheliomatous hyperplasia and dermal infiltration of
chronic inflammatory cells ( (figure 2) ). Although
fungal elements could not be detected with periodic acid-Schiff
(PAS) staining and the initial cultures from biopsy specimen were
negative for fungi, bacteria and mycobacteria, we clinically
diagnosed the lesion as a fungal and bacterial infection and
initiated treatment with oral itraconazole, 100 mg daily and oral
minocyclin, 100 mg daily. Instead of improving, the lesion spread,
became indurated and was covered with scales. Repeated microscopic
examinations and cultures of superficial scrapings were negative.
Five months after the first biopsy, a skin biopsy was performed
again ( (figure
3) ). The histopathologic findings were quite similar to
those of the first biopsy. The specimen showed
pseudoepitheliomatous hyperplasia and dermal infiltration of mixed
inflammatory cells. Grocott-Gomori methenamine-silver staining and
PAS staining revealed the presence of septate hyphae ( (figure 4) ). Cultures of
the biopsy specimen and superficial scrapings for fungi were made
on potato dextrose agar. After 5 days of incubation at room
temperature, there were gray-white colonies with a dark-brown
underside. The same colonies were obtained from a biopsy specimen
and superficial skin scrapings. Microscopic examination revealed
that the fungus had erect, brown, multicellular conidiophores,
producing unbranched conidial chains, with a cylindrical beak and
muriform septation. From the macroscopic appearance of colonies and
morphological features of the conidia, the fungus was identified as
Alternaria alternata ( (figure 5) )[10].
Fluconazole 200 mg daily was effective; after 24 weeks, the
lesion disappeared with slight pigmentation. Four more weeks of
treatment were added after clinical resolution.
Discussion
Cutaneous alternariosis has been classified into two types: an
epidermal type and a dermal type [5, 7, 11]. In the epidermal type,
the organism appears in the epidermis, never invades the dermis,
and hyphae are the predominant elements; the dermal type, however,
shows hyphae and yeast-like cells invading the dermal layer. Almost
all reports of cutaneous alternariosis are dermal type [7].
In addition to morphological identification, nowadays the rapid
and reliable identification of Alternaria alternata is available by
combination of the internal transcribed spacer (ITS) region and
polymerase chain reaction (PCR) of the trihydroxynaphthalene
reductase gene, Brm2, with specific primers for Alternaria
alternata [12].
Lyke et al. reviewed 89 cases of cutaneous alternariosis [13].
Most cases (73 cases) occurred in patients with immunodeficiency
and/or significant underlying disease such as kidney or liver
transplant recipients, those receiving chemotherapy for lymphoma,
myeloproliferative syndrome, cancer, and nephritic syndrome.
Furthermore, 52 of the 89 cases developed in the setting of
systemic steroid administration. Nine additional cases were
associated with endogenous hypercorticism (i.e., Cushing’s disease
or syndrome). There were few reports with congenital
immunodeficiency.
Because cutaneous alternariosis cases are relatively infrequent
and multicenter case-controlled studies are often not feasible,
there is no consensus treatment for cutaneous Alternaria infections
[8, 14]. For the treatment of cutaneous alternariosis, several
therapies have been proposed. These include: (i) surgical removal
of the lesion, when possible; (ii) cessation or reduction of the
corticosteroids or immunosuppressive therapy; and (iii) antifungal
therapy with intralesional injections of miconazole/amphotericin B,
and griseofulvin, as well as systemic administration of miconazole,
amphotericin B, itraconazole, ketoconazole, fluconazole,
flucytosine, and terbinafine [9, 15]. Review of the literature
concerning cutaneous alternariosis suggests that itraconazole is
the preferred drug of choice. However, some cases reported that
itraconazole was not sufficiently effective, and the selection of
drugs still seems to be an area of debate. Relapse occurs
frequently, even after prolonged treatment for many months, and
long-term follow-up and extending treatment for at least 1 month
after clinical resolution is advised [5, 16].
The treatment with oral itraconozole, 100 mg daily, was not
effective in the present case. Looking back, it seemed that the
dose of itraconazole was low. With a higher dose, the lesion might
have been cured. Because of the increasing number of
immunocompromised hosts, we will encounter more cases of cutaneous
alternariosis in the future.
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