Download Risk factors associated with onychomycosis

JEADV (2004) 18, 48–51
OR IG INAL AR T ICLE
Risk factors associated with onychomycosis
Blackwell Publishing Ltd.
B Sigurgeirsson,†* Ó Steingrímsson‡
Departments of †Dermatology and ‡Microbiology, University of Iceland and Landspitali, University Hospital, Reykjavik, Iceland. *Corresponding author,
Hú,læknastö,in, Smáratorg 1, 200 Kópavogur, Iceland, E-mail: [email protected]
ABSTRAC T
Objective To examine possible risk factors related to onychomycosis.
Background Onychomycosis is a common disease with multifactorial aetiology, but little is known about
the risk factors for this disease.
Patients and methods Questions related to signs, symptoms and possible risk factors associated with
onychomycosis were sent to 3992 persons aged 16 years and older selected randomly from the Icelandic
National Registry. Patients with suspected onychomycosis, based on photographs, were offered mycological
examination. Data from the questionnaire and the results of mycological examination were used to calculate
the odds ratio (OR) for several factors that might be associated with onychomycosis.
Results Two thousand four hundred and eighty-six subjects responded to the questionnaire. Prevalence for
mycologically determined onychomycosis was 11.1% in the Icelandic population. A history of the following
factors more than doubled the risk of onychomycosis: cancer (OR 3.44; 95% CI 1.15–10.35), psoriasis (OR
2.44; 95% CI 1.61–3.72), tinea pedis interdigitalis (OR 3.93; 95% CI 3.11–4.95), the moccasin form of tinea
pedis (OR 4.26; 94% CI 3.34–5.45), parents with onychomycosis (OR 2.59; 95% CI 1.89–3.53), children
with onychomycosis (OR 3.48; 95% CI 2.05–5.88), spouse with onychomycosis (OR 2.53; 95% CI 1.72–
3.72), regular swimming activity (OR 2.57; 95% CI 2.00–3.30) and age 50 years or older (OR 2.74; 95% CI
2.19–3.42).
Conclusions Several risk factors are associated with onychomycosis. Knowledge of these risk factors is
important when treating and educating patients with onychomycosis.
Key words: onychomycosis, risk factors, prevalence
Received: 19 July 2002, accepted 13 February 2003
Introduction
Onychomycosis is a common disease of the nail. The prevalence in population-based studies ranges from 2 to 11%.1–3
For many years griseofulvin was the only available oral
therapy. The newer azoles and allylamines have dramatically
improved cure rates.4 Recent studies have demonstrated
that recurrence, either by reinfection or relapse of previous
infection, is seen in up to 50% of cases.5 It has also been
demonstrated that patients who fail standard therapy
regimens can in many cases be successfully treated with
an individualized treatment regimen.5 It is known that
onychomycosis is associated with several risk factors such as old
age,6 psoriasis,7 diabetes8 and individuals involved with
sport activities.9 It would be of great value in the prevention
48
and treatment of onychomycosis if further risk factors for this
disease could be identified. The objectives of this study were to
examine the risk factors, known and unknown, for onychomycosis in a large population-based sample of individuals.
Patients and methods
Questions related to signs and symptoms of onychomycosis,
detailed in a questionnaire, were sent to 3992 persons aged
16 years and older, selected randomly from the Icelandic
National Registry. The Registry includes information about
all living Icelanders. The questionnaire included photographs
of nails infected with dermatophytes, normal nails and also
other nail diseases. The respondents were asked to compare
these with their own nails. To ensure the reliability of this
© 2004 European Academy of Dermatology and Venereology
Risk factors for onychomycosis 49
method, a preliminary quality control study was carried out
on patients with onychomycosis. Out of 55 patients seen for
onychomycosis at our clinic, 50 (91%) identified themselves
with photographs of nails with confirmed onychomycosis
rather than other nail disorders or normal nails. Included in
the questionnaire were questions about nail status, duration
of disease and localization of nail disease, and several questions
on possible risk factors for onychomycosis. The part of the
study that relates to the prevalence of onychomycosis in
Iceland has already been published.1
At the time of the study there were 229 263 persons aged
16 years or older in the National Registry, so 1.74% of the
Icelandic population aged 16 years and older were included
in the study.
Patients with suspected nail changes based on photographs were offered a clinical examination with mycological
sampling. Direct examination of specimens was performed
after nail scrapings had been immersed in 5% KOH solution
containing dimethyl sulfoxide. Specimens were inoculated
on Sabouraud’s glucose agar containing chloramphenicol
0.05 g/L and on mycobiotic agar. Plates were incubated at
30°C for 3 weeks and examined at weekly intervals. Risk
calculations were based on the individual’s response after
studying the accompanying photographs. Information regarding
concomitant disorders was derived from the questionnaire,
but no attempt was made to further verify this information.
We calculated the odds ratio (OR) for each risk factor with
a 95% confidence interval (CI).10 Results with the lower CI
> 1 were considered significant.
Results
Of the 3992 subjects, 2486 responded (62.3%): this included
1117/1964 (56.9%) males and 1369/2028 (67.5%) females.
The estimated prevalence based on positive mycology was
11.1% in the Icelandic population. When only patients with
a positive growth of a dermatophyte were considered the
prevalence was 8.4%.1
The questionnaire included questions related to other skin
disorders, signs and symptoms suggestive of fungal infections
of the skin, genetic factors, lifestyle, chronic disorders and
atopic diseases (Table 1).
Onychomycosis was more common in males than females,
with an OR of 1.28 (95% CI 1.03 –1.59).
Of the atopic disorders the risk of onychomycosis was
slightly increased in patients with a history of angioedema
(OR 1.65; 95% CI 1.12–2.42), urticaria (OR 1.36; 95% CI
1.06 –1.73) and asthma (OR 1.52; 95% CI 1.07–2.17).
When chronic disorders were examined, patients with a
history of cancer had a high risk of developing onychomycosis
(OR 3.44; 95% CI 1.15 –10.35). In patients with gastrointestinal
(OR 1.86; 95% CI 1.03 –3.36) and rheumatological disorders (OR
1.88; 95% CI 1.25 –2.83) the associated risk was low.
Table 1 Possible risk factors associated with onychomycosis based on a
questionnaire
Odds ratio
95% Confidence interval
Atopic eczema
Angioedema
Urticaria
Asthma
0.69
1.65
1.36
1.52
0.44–1.10
1.12–2.42*
1.06–1.73*
1.07–2.17*
Chronic disorders
Cancer
Heart
Lung
Gastrointestinal
Endocrinological
Rheumatological
Neurological
3.44
1.63
1.34
1.86
1.48
1.88
0.62
1.15–10.35*
0.91–2.92
0.69–2.59
1.03–3.36*
0.73–2.97
1.25–2.83*
0.08–4.86
Skin disorders
Psoriasis
Eczema
Other
2.44
0.91
1.28
1.61–3.72*
0.58–1.44
0.88–1.87
Fungal infections of the skin
Tinea pedis (interdigitalis)
Tinea pedis (moccasin type)
Dry palms
3.93
4.26
1.60
3.11–4.95*
3.34–5.45*
1.11–2.32*
2.59
3.48
2.53
0.98
1.89–3.53*
2.05–5.88*
1.72–3.72*
0.51–1.87
2.57
0.99
1.62
2.74
1.13
2.00–3.30*
0.73–1.34
0.73–3.60
2.19–3.42*
0.90–1.42
Atopic disorders
Genetic factors
Parents with onychomycosis
Children with onychomycosis
Spouse with onychomycosis
Others living in same household
with onychomycosis
Lifestyle
Regular swimmer
University education
Nursing home
Aged 50 or older
Smoking
*A significant association with onychomycosis.
Fungal infections were strongly associated with onychomycosis. High risk was found in patients with the interdigital
(OR 3.93; 95% CI 3.11–4.95) and the moccasin form (OR
4.26; 95% CI 3.34 –5.45) of tinea pedis. Slightly elevated risk
was even associated with a history of dry palms (OR 1.60;
95% CI 1.11–2.32), which might be suggestive of an id reaction in some of these patients.
Genetic factors seem to play a role, as elevated risk was
found in patients who had children (OR 3.48; 95% CI 2.05–
5.88) or parents (OR 2.59; 95% CI 1.89 –3.53) with onychomycosis. Direct transmission to members of the same
household cannot be excluded as slightly elevated risk was
found in patients whose spouse (OR 2.53; 95% CI 1.72–3.72)
had onychomycosis.
The risk in regular swimmers was increased (OR 2.57;
95% CI 2.00–3.30) and age obviously played a role, with
© 2004 European Academy of Dermatology and Venereology JEADV (2004) 18, 48 – 5 1
50 Sigurgeirsson and Steingrímsson
increased risk in those 50 years or older (OR 2.74; 95% CI
2.19 –3.42).
Discussion
Knowledge about risk factors for onychomycosis is
important. It is known that patients with psoriasis,7 diabetes8
and immunosupression11 are more prone to onychomycosis.
Onychomycosis also increases with age6 and most studies
have showed higher prevalence among males. It is also known
that sport activity increases the risk of onychomycosis;9
for instance, a high prevalence has been demonstrated in
swimmers.12
In the present study we examined several risk factors. We
found it interesting to examine the atopic disorders, as there
have been several reports of patients with atopic disorders
and onychomycosis. In some of these cases it has been
reported that with treatment of onychomycosis the signs and
symptoms of the atopic disorders have disappeared. This
suggests that in selected cases, patients can have reactive disorders as a result of a fungal infection.13–16 In the present
study we were not able to determine the nature of the association between these disorders and onychomycosis, but
patients with asthma, urticaria and angioedema were more
likely to have onychomycosis. This could be explained by an
allergic reaction to the fungus that causes the atopic disease
or by the fact that patients with these disorders are more
prone to onychomycosis.
Immunosuppressive states such as human immunodeficiency virus (HIV) infection are known to be associated with
onychomycosis.17 To our knowledge the association of cancer and onychomycosis has not been demonstrated before. It
is possible that immunosuppression, which often follows
advanced malignant disease, increases the risk of onychomycosis. The treatment of the cancer can also play a role in
making the patient more susceptible to a fungal infection. The
same arguments apply for rheumatological disorders, which
also seem to be associated with increased risk of onychomycosis. We have no ready explanation for the increased risk
associated with gastrointestinal disorders. No risk was seen
with endocrinological disorders, although the association with
diabetes has been clearly demonstrated in the literature.8
The association between onychomycosis and psoriasis
has been reported before7 and is probably more frequent
than previously thought.18 We were not able to demonstrate
an association of eczema or other skin disorders with
onychomycosis.
It is not surprising that patients with a history of other
fungal infections of the feet have a higher risk of onychomycosis. The highest risk was associated with the moccasin
form of tinea pedis. Even patients who described dry fissuring palms had a higher risk of onychomycosis. We believe
that in this case the dry palms can be a sign of an id reaction.19
Genetic factors are thought to play a role in the susceptibility of onychomycosis.20 In this study we found increased
risk in patients whose parents or children had onychomycosis, but elevated risk was not found when other members of
the same household had onychomycosis. The risk was also
increased when the spouse had onychomycosis, which points
to transmission to the subject from the spouse.
We found increased risk in swimmers. This has been demonstrated before12 and also in relation to other sports.9 We
also found that the risk of onychomycosis was higher in
those aged 50 years or older. This has been reported previously in several studies.6,21 We did not find an association
with smoking. A recent study has shown an increased risk of
onychomycosis in heavy smokers.22 Our study, however,
included too few heavy smokers to make that kind of analysis
possible.
We have demonstrated several important risk factors that
are associated with onychomycosis. Increased risk was
found in patients with a history of atopic disorders, chronic diseases, psoriasis, other fungal infections of the skin, sport and
increased age. A possible genetic link was also demonstrated.
Knowledge about risk factors is important for those who
treat patients with onychomycosis. Many of the risk factors
we have shown to be associated with onychomycosis have
not been reported before. A questionnaire study is in essence
a crude tool and the results must therefore be interpreted
with caution until they have been further investigated in
other studies.
References
1 Sigurgeirsson B, Steingrimsson O, Sveinsdottir S. Prevalence of
onychomycosis in Iceland: a population-based study. Acta Derm
Venereol 2002; 82: 467–469.
2 Heikkila H, Stubb S. The prevalence of onychomycosis in Finland.
Br J Dermatol 1995; 133: 699 –703.
3 Roberts DT. Prevalence of dermatophyte onychomycosis in the
United Kingdom: results of an omnibus survey. Br J Dermatol 1992;
126 (Suppl. 39): 23 –27.
4 Evans EG, Sigurgeirsson B. Double blind, randomised study of
continuous terbinafine compared with intermittent itraconazole
in treatment of toenail onychomycosis. Br Med J 1999; 318:
1031–1035.
5 Sigurgeirsson B, Olafsson JH, Steinsson JB et al. Long-term
effectiveness of treatment with terbinafine vs itraconazole in
onychomycosis: a 5-year blinded prospective follow-up study. Arch
Dermatol 2002; 138: 353 –357.
6 Pierard G. Onychomycosis and other superficial fungal infections of
the foot in the elderly: a pan-European survey. Dermatology 2001;
202: 220 –224.
7 Gupta AK, Lynde CW, Jain HC et al. A higher prevalence of
onychomycosis in psoriatics compared with non-psoriatics: a
multicentre study. Br J Dermatol 1997; 136: 786 –789.
© 2004 European Academy of Dermatology and Venereology JEADV (2004) 18, 48–51
Risk factors for onychomycosis 51
8 Gupta AK, Konnikov N, MacDonald P et al. Prevalence and
epidemiology of toenail onychomycosis in diabetic subjects: a
multicentre survey. Br J Dermatol 1998; 139: 665 – 671.
9 Caputo R, De Boulle K, Del Rosso J et al. Prevalence of superficial
fungal infections among sports-active individuals: results from the
Achilles survey, a review of the literature. J Eur Acad Dermatol
Venereol 2001; 15: 312 –316.
10 Vitenbroek DG. Simple interactive statistical analysis, SISA 1997.
http://home.clara.net/sisa/ (1 January 2002).
11 Gregory N. Special patient populations: onychomycosis in the
HIV-positive patient. J Am Acad Dermatol 1996; 35: S13 –S16.
12 Gudnadottir G, Hilmarsdottir I, Sigurgeirsson B. Onychomycosis in
Icelandic swimmers. Acta Derm Venereol 1999; 79: 376 –377.
13 Schwartz HJ, Ward GW. Onychomycosis, Trichophyton allergy and
asthma – a causal relationship? Ann Allergy Asthma Immunol 1995;
74: 523–524.
14 Elewski BE, Schwartz HJ. Asthma induced by allergy to Trichophyton
rubrum. J Eur Acad Dermatol Venereol 1999; 12: 250 –253.
15 Wilson BB, Deuell B, Mills TA. Atopic dermatitis associated with
dermatophyte infection and Trichophyton hypersensitivity. Cutis
1993; 51: 191–192.
16 Klein PA, Clark RA, Nicol NH. Acute infection with Trichophyton
rubrum associated with flares of atopic dermatitis. Cutis 1999; 63:
171–172.
17 Gupta AK, Taborda P, Taborda V et al. Epidemiology and
prevalence of onychomycosis in HIV-positive individuals. Int J
Dermatol 2000; 39: 746 –753.
18 Staberg B, Gammeltoft M, Onsberg P. Onychomycosis in patients
with psoriasis. Acta Derm Venereol 1983; 63: 436 –438.
19 Veien NK, Hattel T, Laurberg G. Plantar Trichophyton rubrum
infections may cause dermatophytids on the hands. Acta Derm
Venereol 1994; 74: 403 –404.
20 Zaias N, Tosti A, Rebell G et al. Autosomal dominant pattern of
distal subungual onychomycosis caused by Trichophyton rubrum.
J Am Acad Dermatol 1996; 34: 302–304.
21 Gupta AK, Jain HC, Lynde CW et al. 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 –248.
22 Gupta AK, Gupta MA, Summerbell RC et al. The epidemiology of
onychomycosis: possible role of smoking and peripheral arterial
disease. J Eur Acad Dermatol Venereol 2000; 14: 466 –469.
© 2004 European Academy of Dermatology and Venereology JEADV (2004) 18, 48 – 5 1