ARTICLE
Tinea pedis and onychomycosis are usually caused by anthropophilic dermatophytes,
such as Trichophyton rubrum or Trichophyton mentagrophytes variety
interdigitale, with a low frequency of infection due to non-dermatophytic
moulds [1]. Scopulariopsis brevicaulis, Aspergillus sp., Fusarium sp.
and Scytalidium dimidiatum are the most frequent species.
Onychocola canadensis is a keratinophilic mould described in
1990 as the cause of onychomycosis [2]. First isolated in Canada [2],
it was found in New Zealand [3] and then in France [4], near Strasbourg.
Recently, five clinical cases of onychomycosis of the toenails due to
Onychocola canadensis were observed in Lorraine, in elderly patients
[5, 6]. In all cases, O. canadensis was repeatedly isolated in
pure culture (in one case associated with Candida ciferrii). For
these five strains, a study of sensitivity to antifungal products in
vitro was performed.
Patients and methods
Case 1
Mr Georges G., 81-year-old, retired farmer, who had never travelled
outside of France, was hospitalized in November, 1994, in the Dermatological
Service for drug eruption. He also had onychomycosis on both big toenails
and whitish-yellow spots were observed. Toenails were moderately thickened
and were friable with subungual debris. There was a mild intertrigo between
the toes. Onychocola canadensis was found associated with the intertrigo
and in both big toenails. The toenails were treated locally with econazole
powder and 250 mg of terbinafine were taken daily.
Case 2
Mrs Adele C. an 78-year-old woman, was obese and had diabetes mellitus
and arteritis. In December 1994, she had eschars on the heels and ulcers
on both legs. There were also lesions of the toenails. The affected toenails
(Fig. 1) were thickened
and were friable and light yellow. Onychocola canadensis was isolated
in pure culture. A second examination one month later showed Onychocola
canadensis associated with Candida albicans. The patient was
treated with amorolfine nail lacquer. She lives in a small village not
far from Nancy (eastern France) where she owns and works in a small grocery
store.
Case 3
Mrs Madeleine H. an 84-year-old woman was hospitalized in January 1995,
in the Dermatological Service. She had ulcers on both legs as a result
of arteritis. There was also an onychomycosis of the big toenail on the
right foot which was hyperkeratotic and yellow in color. The big toenail
of the left foot had been removed surgically because of a painful, infected
lesion. Some of the other nails were also yellow and friable. Onychocola
canadensis associated with Candida ciferrii was isolated and
amorolfine nail lacquer was prescribed as treatment. The patient had worked
as a barmaid until December 1994.
Case 4
Mrs Marie-Thérèse J. 54-year-old woman was hospitalized
in May, 1995 for a drug eruption. In addition to obesity, she had arterial
hypertension with kidney deficiency and a cardiomyopathy and diabetes
mellitus not requiring insulin. There was also eczema on her feet and
her toenails were friable and yellowish. A mycological sampling under
direct examination showed small spores and Onychocola canadensis
was isolated in pure culture. The patient had never been out of France.
A treatment by cyclopirox nail lacquer was applied.
Case 5
Mrs Jeannine B. 70-year-old woman, was hospitalized in July, 1995 for
erysipelas of the leg resulting from ulcers in that area. Her previous
medical history included arterial hypertension, cardiac arrhythmia as
a result of auricular fibrillation, and a previous erysipelas which had
occurred 19 years earlier. In addition, she presented an intertrigo of
the feet and changes to all the toenails. They were slightly hyperkeratotic,
very friable and yellowish. The patient had never left France and lived
in the country. She had worked in a small cafe combined with a grocery
store. Some mycological samplings were taken from her feet to find the
origin of the erysipelas. Several colonies of Candida albicans
were isolated from the intertrigo (the direct examination was negative)
and Onychocola canadensis was isolated in pure culture from the
toenails. A nail biopsy showed fungal elements. A treatment of amorolfine
nail lacquer was applied.
Mycological diagnosis
Under direct examination of the subungual keratin, spores which were
round to barrel-shaped (2-3 µm in diameter) were found in all of
the patients. They were associated with filaments, which were thin in
diameter, irregular in caliber (2-5 µm) and tortuous (Fig.
2).
For the culture, we used the conventional media, Sabouraud Dextrose
Chloramphenicol Agar and Sabouraud Dextrose Chloramphenicol Cycloheximide
Agar.
At the end of a growth period of 4 weeks, small, round, fluffy colonies
appeared. We observed colors ranging from light grey to yellowish grey
and, on the underside, a brown pigment which diffused into the agar. All
the strains were resistant to cycloheximide and were urease positive.
The colonies were a bright rose colour, on a culture of tetrazolium salts.
Hyalin filaments, regular in diameter, appeared with rare arthrospores
on Sabouraud Chloramphenicol Dextrose Agar. When we reseeded Onychocola
canadensis in a weak solution (water 2% Agar) arthrospores formed
more quickly and identification was easy. The arthrospores were cylindrical,
unicellular or sometimes bicellular (2.5-4.3 µm width) and formed
chains perpendicular to the filaments which bore them (Fig.
3).
The hair perforation test in vitro was performed: none of the
five strains were able to break down the keratin of hair.
The histology of the nail was performed in four cases (nos
1, 2, 3, 5), filaments and small fungal elements were observed. They were
associated with perforating organs in two cases (Fig.
4). Fungal elements were located in the ventral layer.
The study of sensitivity to antifungals was performed.
For this study, the MIC technique was applied using a technique already
described [1].
The dilutions ranged from 0.005 to 50 µg/ml. All the strains were
sensitive to amorolfine and terbinafine and resistant to griseofulvin
and cyclopiroxolamine. Onychocola canadensis was moderately sensitive
to ketoconazole (Table I).
Discussion
Our patients were predominantly elderly women (average age 73 years)
who had marked arterio-venous problems and leg ulcers (4 out of 5 cases).
In other cases already described [3, 4], patients were also more frequently
female (8 out of 13), the youngest was 46 years old, the oldest was 90
years old. In the cases described by Sigler et al. [3], scaling
lesions were found on both palms in a 51-year-old female. The other patients
had toenail infections.
Onyxis provoked by O. canadensis is rarely accompanied by intertrigo
(unlike in that due to dermatophytes), but when present, intertrigo is
dry, non-inflammatory and without cracking in the interdigital region.
A nail, when infected by O. canadensis, is globally attacked,
and can include all of the nails. The infection originates on the distal
part of the nail and is able to spread to the matrix. The nail then becames
yellow-white, very fragile and scaled. The bed of the nail turns into
a white powder. The colour change is discrete with no increase in separation
between the healthy and the unhealthy nail area, as in dermatophyte infections.
Throughout, no perionyxis is observable.
According to our in vitro studies, terbinafine and amorolfine
were efficacious. In another study, Onychocola canadensis was found
to be sensitive in vivo to griseofulvin (six months after treatment
there was an improvement, but therapy was discontinued after 6 months
because of gastrointestinal distress) [3]. We did not observe this sensitivity
to griseofulvin in vitro (Table
I). Treatment of this onychomycosis occurring in elderly patients,
often excessively medicated, should be applied locally.
Nail varnish containing an antifungal agent (cyclopirox, amorolfine)
could be administered, but the patient would probably need the assistance
of someone in order to properly apply the treatment. In cases of onychomycosis,
long term and widespread terbinafine treatment which, in vitro,
has good antifungal action on O. canadensis, could be prescribed
in a sequential manner. Itraconazole could also be prescribed because
of its excellent penetrating qualities in nail keratin. Nevertheless itraconazole,
has not yet been authorized in France for treatment of this condition.
CONCLUSION
The onychomycosis due to Onychocola canadensis can be suspected
in elderly patients with arteriovenous problems, associated with leg ulcers.
Toenails are yellowish, friable, thickened, with subungual powder. The
mycological diagnosis is based on the presence of small spores found by
direct examination associated with fine filaments. Isolating Onychocola
canadensis in culture is possible if it is kept in tubes for 4 weeks
and reseeded later in a weak culture medium.
Three strains were deposited in the Institut Pasteur Microfungus collection
service. Patient G.G., IP 2305-95; patient A.C., IP 2307-95 ; patient
M.H., IP 2306-95.
Acknowledgements
We would like to thank Dr. A.J. Woodgyer (New Zealand) who gave us one
of his strains and Dr. H. Koenig who identified the first strain. We gratefully
acknowledge the Laboratories P. Fabre, Sanofi Winthrop, Sandoz and Roche
which gave us the antifungal products. Thanks are also due to Annette
Tary for the expert secretarial assistance and Emily Porter for the translation.
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