ARTICLE
Auteur(s) : Alexandro Bonifaz, Pamela
Cruz-Aguilar, Rosa María Ponce
Dermatology Service and Mycology Department. Hospital General de
México OD. Sánchez-Azcona 317-202. Col del Valle, CP, 03020 México
D. F.
accepté le 5 Septembre 2006
Onychomycosis is a mycosis that occurs throughout the world and is
caused by dermatophytes, yeasts and molds. Dermatophytes are the
major causative agents and produce up to 90% of the toenail
infections [1-3]. Molds are saprophyte fungi living in the soil and
some are phytopathogens. Traditionally they have been considered as
contaminating fungi or secondary pathogens [3, 4] of the skin and
nails; however, some of them may behave as primary pathogens, e.g.,
Scopulariopsis brevicaulis and Scytalidium dimidiatum [3, 5].
Prevalence of mold onychomycosis ranges from 1.45 to 22% according
to the geographical area and the diagnostic criteria used [5-10].
The major mold fungi that cause onychomycosis are: Scopulariopsis
brevicaulis, Fusarium sp, Aspergillus sp., Scytalidium hyalinum
and, recently, Onychocola canadensis [12-14]. This is a
retrospective study reporting a series of cases of mold
onychomycosis and their clinical and mycological features.
Material and methods
This is a retrospective study of 78 proven cases of mold
onychomycosis, of a total of 5,221 cases of onychomycoses seen at
the Mycology Department, Dermatology Service, General Hospital of
Mexico, during a 14-year period (January 1992-December 2005). The
mycological diagnosis consisted of a direct examination with 20%
potassium hydroxide of the nail scrapings; the first observation
under the microscope occurred at 10 to 20 minutes, and the second
one at one hour. The specimens obtained for culture were grown in 2
tubes with Sabouraud dextrose agar and 2 tubes with Sabouraud
dextrose agar plus antibiotics (Mycosel); they were incubated at
28 °C for 4 weeks, and cultures were checked every week.
The diagnosis of onychomycosis by molds was made considering the
following criteria: the clinical presentation of onychomycosis; a
positive direct examination, with mycologic structures in the nail
specimen; substantial growth of the fungus in three consecutive
cultures; no concomitant isolation of dermatophytes and/or
yeasts.
Results
This retrospective study was conducted in a 14-year period during
which a total of 5,221 patients with proven onychomycoses (clinical
and mycological examination) were assessed; 78 cases (1.49%) were
caused by molds. Table 1( Table 1 )
summarizes the demographics of the patients with mold
onychomycosis. The youngest patient was 9 years old and the oldest
83, with a mean age of 44.1 years. The associated factors included,
among others, peripheral vascular disease in 12/78 cases, contact
with dirt in 10/78 cases, trauma in 7/78 cases and diabetes
mellitus in 5/78 cases (4 patients with type-2 and one patient with
type-1 diabetes). Other associated factors were psoriasis, and
swimming. It is worthwhile mentioning two patients who each had a
lymphoma and acquired immunodeficiency syndrome. In 39/78 (50.0%)
cases no associated factors were observed.
The clinical presentation and the aetiologic agents are
summarized in table 2( Table 2 ). Main
location was the toenails in 75/78 cases; fingernails in 2/78
cases, and both locations in 2/78 cases. The clinical manifestation
of onychomycosis was as follows: 54/78 cases (69%) occurred with
distal and lateral subungual onychomycosis (DLSO), 4/78 cases (5%)
with superficial white onychomycosis (WSO), two cases (2%) with
proximal subungual onychomycosis (PSO), 11/78 cases (14%) with DLSO
and melanonychia, one of them together with paronychia, 3/78 cases
(4%) with DLSO and onycholysis, and 5/78 cases (5%) with total
dystrophic onychomycosis (TDO).
In the mycologic tests of the cases, which included direct KOH
examination, septate filaments and a few thin filaments were
observed in 43 cases. The causative agents isolated in the culture
were: Scopulariopsis brevicaulis in 34/78 cases; Aspergillus niger
in 13/78 cases; Aspergillus terreus in 8/78; Aspergillus fumigatus
in 5/78 cases; Fusarium oxysporum in 7/78 cases; Fusarium solani in
3/78 cases, Cladosporium sp in 3/78 cases, and one single case of
Aspergillus flavus, Curvularia lunata, Cephalosporium sp and one
unclassified dematiaceous fungus, respectively.
Table 1 Demographics
|
Total number of cases
|
78
|
|
Youngest
|
9 years
|
|
Oldest
|
83 years
|
|
Mean age
|
44.1 years
|
|
Female
|
49/78 (63%)
|
|
Male
|
29/78 (37%)
|
|
Predisposing factors
|
|
- Peripheral vascular disease
|
12/78 (15%)
|
|
- Contact with soil
|
10/78 (13%)
|
|
- Trauma
|
7/78 (9%)
|
|
- Diabetes mellitus
|
5/78 (6%)
|
|
- Lymphoma
|
1/78 (1.2%)
|
|
- HIV-AIDS
|
1/78 (1.2%)
|
|
- Others
|
2/78 (2.4%)
|
|
- None
|
40/78 (51.2%)
|
Table 2 Clinical and etiologic data
|
Location
|
Data (%)
|
|
Fingernails
|
2/78 (2.0%)
|
|
Toenails
|
75/78 (96%)
|
|
Finger & toenails
|
2/78 (2.0%)
|
|
Type of onychomycosis
|
|
|
Distal and lateral subungual (DLSO)
|
54 cases (69%)
|
|
Proximal subungual (PSO)
|
2 cases (2%)
|
|
Superficial white (SWO)
|
4 cases (5%)
|
|
DLSO/melanonychia*
|
11 cases (14%)
|
|
DLSO/onycholysis
|
3 cases (4%)
|
|
Total dystrophic (TDO)
|
4 cases (5%)
|
|
*1 case with paronychia
|
|
|
Etiology
|
|
|
Scopulariopsis brevicaulis
|
34 cases (43.5%)
|
|
Aspergillus niger
|
13 cases (16.6%)
|
|
Aspergillus terreus
|
8 cases (10.2%)
|
|
Aspergillus fumigatus
|
5 cases (6.5%)
|
|
Aspergillus flavus
|
1 case (1.2)
|
|
Fusarium oxysporum
|
7 cases (9%)
|
|
Fusarium solani
|
3 cases (4%)
|
|
Cladosporium sp
|
3 cases (4%)
|
|
Alternaria alternata
|
1 case (1.2%)
|
|
Curvularia lunata
|
1 case (1.2%)
|
|
Cephalosporium sp (Acremonium sp)
|
1 case (1.2%)
|
|
Dematiaceous (not classified)
|
1 case (1.2%)
|
Discussion
Onychomycosis by molds is infrequent and the global prevalence
varies depending on the geographical region studied and the
diagnostic criteria used [12-14]. Particularly in Mexico, Arenas
[15] reported a 4% prevalence in a shorter period (1994-1996). Our
study reports a prevalence of 1.49% in a 14-year period, as opposed
to the 22% prevalence reported in India by Ramani et al. [11],
probably due to the predominantly tropical and humid climate.
As regards age, the world literature states that the number of
cases under 50 years of age is infrequent [16] and it increases
among elderly patients (> 60 years) [8, 17]. In our study the
highest incidence occurred in the 30-40 year age group (mean age
44.1 years), which accounted for 54% of cases. The male-to-female
ratio was 1: 1.6, probably because females see the doctor more
often or for cosmetic reasons.
It is very important to analyze the associated predisposing
factors, since traditionally molds were considered exclusively as
contaminating fungi or secondary pathogens that affected only the
nails that had a history of trauma or disease [3, 9, 16]. 50.0% of
the patients had one associated factor, with major ones being
peripheral vascular disease, contact with dirt, and history of
trauma and diabetes mellitus. In 10/12 patients with peripheral
vascular disease Scopulariopsis brevicaulis was isolated. This is
an interesting finding according to the report by Kacalak-Rzepka et
al. [18], which states that peripheral circulation disorders of the
lower limbs are a predisposing factor for infection by this mold.
Two patients with immunosuppression (HIV-AIDS and lymphoma, with
isolates of F. solani and F. oxysporum, respectively) deserve a
special mention. The latter association is relevant since some
authors have suggested that untreated onychomycosis due to Fusarium
in immunocompromised patients may constitute a route of entry for
disseminated hyalohyphomycoses [19, 20].
The most frequent clinical presentation was distal and lateral
subungual onychomycosis (DLSO), which accounted for 69% and is
indistinguishable from the disease caused by dermatophytes. Authors
like Romano et al. [21] and Ramani et al. [11] also reported DLSO
as the predominant clinical form. In contrast with this, some
authors [10, 22-25] mention that periungual inflammation is very
suggestive of mold infection; however, in our study only one case
was detected. It is necessary to emphasize in this fact, since most
of our cases were practically similar to infections due to
dermatophytes. In 95% of cases the toenails were affected and this
is so frequent as most of the molds live in dirt [17]. This may
also be attributed to the local environmental conditions,
peripheral vascular disease, slow nail growth, and the fact that
toenails are more vulnerable to repeated trauma [11, 17].
Despite the long list of isolated molds, only a few species are
regularly identified as causes of onychomycosis. They include
Scopulariopsis brevicaulis, Fusarium sp, Acremonium sp, Aspergillus
sp, Scytalidium sp, and Onychocola canadensis [12-14, 26]. The
following molds were isolated in a descending order: Scopulariopsis
brevicaulis, Aspergillus sp and Fusarium sp, which accounted for
43.5%, 34.5% and 13.0%, respectively, similar to what Romano et al.
[21] reported. The frequency of the aetiological agents isolated
varies by geographical area.
Concerning the mycological study, in the direct examination,
filaments could be observed in 55% of cases. Filaments are similar
to the structures observed in dermatophytic infections. In the rest
of the samples, structures suggestive of infection caused by molds
were observed. In the case of Scopulariopsis brevicaulis, filaments
and the characteristic conidia (lemon-shaped) were seen, which was
suggestive of the causative agent. In the cases caused by
Aspergillus sp “aspergillar heads” suggestive of infection by this
mold were present in only two specimens and both cases were
Aspergillus niger. All of the ungual specimens of Fusarium
infection had thin filaments, virtually indistinguishable from
dermatophytes. It is therefore important to grow cultures in media
with and without cycloheximide to prove the etiological agent and
indicate the best treatment for each case.
This is an extensive study of cases of mold onychomycosis, an
entity to be taken into account because its clinical
characteristics are very similar to diseases caused by
dermatophytes. This is extremely important for proper treatment
selection, since not all antifungals have a spectrum that covers
this type of fungi [10, 23].
Acknowledgements
Financial support: None. Conflict of interest: None.
References
1 Pereiro M, Toribio J. Epidemiology of onychomycosis.
State of art. J Mycol Med 2002; 12: 175-82.
2 Hay RJ, Baran R, Haneke E. Fungal
(Onychomycosis) and other infections involving the nail apparatus.
In: Baran R, Dawber RPR, de Berker DAR,
Haneke E, Tosti A, eds. Baran & Dawber’s. Diseases of
the nails and their management. 3nd edition. Oxford: Blackwell
Science, 2001: 129-59; (Chap 4).
3 Ellis DH, Marley JE, Watson AB,
Williams TG. Significance of non-dermatophyte molds and yeasts
in onychomycosis. Dermatology 1997; 194(Suppl 1): 40-2.
4 Gupta AK, Ryder JE, Baran R,
Summerbell RC. Non-dermatophyte onychomycosis. Dermatol Clin
2003; 21: 257-68.
5 Greer DL. Evolving role of nondermatophytes in
onychomycosis. Int J Dermatol 1995; 34: 521-2.
6 Williams HC. The epidemiology of onychomycosis in
Britain. Br J Dermatol 1993; 129: 101-9.
7 Midgley G, Moore MK, Cook JC, Phan QG.
Mycology of nail disorders. J Am Acad Dermatol 1994; 31:
S68-S74.
8 Gupta AK, Jain HC, Lynde CW, MacDonald P,
Cooper EA, Summerbell RC. Prevalence and epidemiology of
onychomycosis in patients visiting physicians offices: A
multicenter Canadian survey of 15,000 patients. J Am Acad Dermatol
2000; 43: 244-8.
9 Gianni C, Cerri A, Crosti C. Non-dermatophytic
onychomycosis. An underestimated entity? A study of 51 cases.
Mycoses 2000; 43: 29-33.
10 Tosti A, Piraccini BM, Lorenzi S.
Onychomycosis caused by nondermatophytic molds: Clinical features
and response to treatment of 59 cases. J Am Acad Dermatol 2000; 42:
217-24.
11 Ramani R, Srinivas CR, Ramani A, Girija Ratna
Kumari T. Shivananda PG. Molds in onychomycosis. Int J
Dermatol 1993; 32: 877-8.
12 Denning DW, Evans EGV, Kibbler CC,
Richardson MD, Roberts MM, Rogers TR, et al.
Fungal nail diseases: a guide to good practice (report or a working
group of the British society for medical mycology). BMJ 1995; 311:
1277-81.
13 Gupta AK, Horgan-Bell CB, Summerbell RC.
Onychomycosis associated with Onychocola canadensis: Ten case
reports and review of the literature. J Am Acad Dermatol 1998; 39:
410-7.
14 Gupta AK, Cooper EA, MacDonald P,
Summerbell RC. Utility of inoculum counting (Walshe and
English Criteria) in clinical diagnosis of onychomycosis caused by
nondermatophyte filamentous fungi. J Clin Microbiol 2001; 39(6):
2115-21.
15 Arenas R, Ocejo D. Onicomicosis: frecuencia actual
en un departamento de dermatología de la Ciudad de México.
Dermatología Rev Mex 1997; 41: 171-5.
16 Walshe MM, English MP. Fungi in nails. Br J
Dermatol 1966; 78: 198-207.
17 André J, Achten G. Onychomycosis. Int J Dermatol
1987; 26: 481-90.
18 Kacalak-Rzepka A, Maleszka R, Turek-Urasinska K, Kempinska A,
Ratajczak-Stefanska V, Rozewicka M. Investigations concerning
agents influencing the clinical course of onychomycosis caused by
mould fungus Scopulariopsis brevicaulis. 10th Congress of the
European Confederation of Medical Mycology. Mikol Lek 2004; 11
(Suppl 1): 30-1.
19 Girmenia C, Arcese W, Micozzi A,
Martino P, Bianco P, Morace G. Onychomycosis as a
possible origin of disseminated Fusarium solani infection in a
patient with severe aplastic anemia. Clin Infect Dis 1992; 14:
1167.
20 Veglia KS, Marks VJ. Fusarium as pathogen: a case
report of Fusarium sepsis and review of the literature. J Am Acad
Dermatol 1987; 16: 260-3.
21 Romano C, Gianni C, Difonzo EM. Retrospective
study of onychomycosis in Italy: 1985-2000. Mycoses 2005; 48:
42-4.
22 Baran R, Tosti A, Piraccini BM. Uncommon
clinical patterns of Fusarium nail infection: report of three
cases. Br J Dermatol 1997; 136: 424-7.
23 Tosti A, Piraccini BM, Stinchi C,
Lorenzi S. Onychomycosis due to Scopulariopsis brevicaulis:
clinical features and response to systemic antifungals. Br J
Dermatol 1996; 135: 799-802.
24 Tosti A, Piraccini BM. Proximal subungual
onychomycosis due to Aspergillus niger: report of two cases. Br J
Dermatol 1998; 139: 156-7.
25 Hay RJ, Moore MK. Clinical features of superficial
fungal infections by Hendersonula toruloidea and Scytalidium
hyalinum. Br J Dermatol 1984; 110: 677-83.
26 Mugge C, Haustein UF, Nenoff P. Causative
agents of onychomycosis: a retrospective study. J Dtsch Dermatol
Ges 2006; 4: 218-28.
|
Printable version
Version PDF