Acta Derm Venereol 2003; 83: 206–209
`
`CLINICAL REPORT
`
`The Prevalence of Onychomycosis in Patients with Psoriasis and
`other Skin Diseases
`
`GITTE KIELLBERG LARSEN, MERETE HAEDERSDAL and ELSE L. SVEJGAARD
`
`Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
`
`Onychomycosis among psoriasis patients is reported with
`varying prevalence. This prospective, controlled study
`investigates the occurrence of onychomycosis among
`inpatients with psoriasis versus inpatients with other skin
`diseases. The inclusion period was 15 months. Scrapings
`from clinically abnormal nails (both fingernails and
`toenails) were examined using microscopy and culture.
`The prevalence of onychomycosis in patients with psoriasis
`was 17/79~21.5% compared to 18/142~12.7% for
`(p~0.13).
`patients with other
`skin diseases
`In 17
`mycologically positive psoriasis patients, dermatophytes,
`yeasts and moulds were isolated in 8, 10 and 4 cases,
`respectively, and in 18 mycologically positive patients
`with other skin diseases in 12, 7 and 5, respectively.
`Onychomycosis occurred more frequently in men than
`in women (psoriasis patients (p~0.02), patients with
`other skin diseases (p~0.03)). Psoriasis patients had a
`higher frequency of abnormal nails (82.3%) compared
`to patients with other skin diseases (37.3%) (pv0.01)
`and more severe affection of their toenails than patients
`with other skin diseases (pv0.01). It is concluded that
`the frequency of onychomycosis among inpatients with
`psoriasis compared to inpatients with other skin diseases
`is not significantly different. Key words: dermatophytes;
`fungal infection; dermatology.
`
`(Accepted January 16, 2003.)
`
`Patients with psoriasis often have nail abnormalities.
`These are due to psoriasis itself, but may also occur in
`combination with onychomycosis (4, 5). Nail abnormal-
`ities in psoriasis may present as pitting, oil spots,
`subungual hyperkeratosis as well as thickening and
`change in colour of the nail. Excepting the first two
`abnormalities mentioned,
`the clinical manifestations
`may be confused with onychomycosis, and it is there-
`fore clinically difficult to distinguish between psoriasis
`and onychomycosis. Psoriasis of the nail may cause a
`higher susceptibility for infection with dermatophytes.
`In contrast, an infection with dermatophytes theore-
`tically might induce a local Ko¨ bner reaction. It is
`therefore important to clarify how frequent onycho-
`mycosis occurs in psoriasis patients. In the literature
`there are reports of variable frequencies of onycho-
`mycosis in psoriatics. The prevalence has been estimated
`(i) to be higher than among comparable healthy con-
`trols (4), (ii) to occur with almost the same frequency
`(5, 6), and (iii)
`to occur with a lower frequency
`compared to healthy controls (7).
`The aim of this study was to examine the prevalence
`of onychomycosis among inpatients with moderate to
`severe psoriasis and also among inpatients with other
`skin diseases.
`
`Acta Derm Venereol 2003; 83: 206–209.
`
`MATERIALS AND METHODS
`
`Gitte Kiellberg Larsen, Department of Dermatology
`and Venereology, University of Copenhagen, Bispebjerg
`Hospital, Bispebjerg Bakke 23, DK-2400 Copenhagen
`NV, Denmark. E-mail: gittekiellberg@dadlnet.dk
`
`Onychomycosis in toenails is the most common nail
`disorder with a prevalence of 4.1% in patients from
`Danish general practices (pers. comm., Svejgaard).
`Prevalences of 2.7% and 8.4% have been observed in
`England and Finland, respectively (1, 2). The frequency
`increases with age, and onychomycosis occurs more
`often in men than in women and more often in toenails
`than in fingernails. Onychomycosis is mainly caused
`by dermatophytes, of which Tricophyton (T.) rubrum
`plays the main role, while yeasts are responsible for
`about 5% and non-dermatophyte moulds for 1 – 3% (3).
`
`Patients
`
`Patients with psoriasis and patients with other skin diseases
`were included from the in-patient clinic, at the Department
`of Dermatology, Bispebjerg University Hospital, Copenha-
`gen, during October 1999 – January 2001. The study was
`approved by the Regional Scientific-Ethical Committee and
`informed consent was obtained from all participants. The
`ages of the included patients were §18 years and ƒ70 years.
`Patients were excluded if systemic or topical antimycotic
`drugs were given within the last four months or within the
`last month, respectively. For each patient age, sex, and type
`of skin disease was registered, and for patients with psoriasis
`also the duration of disease.
`
`Clinical examination
`
`The following parameters were clinically scored: Area of
`abnormal nails: 0~no change, 1~0 – 30%, 2~30 – 60%,
`3~w60% change of the nail area. Hyperkeratosis, onycho-
`lysis, paronychial inflammation, colour change of the nail,
`
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`Onychomycosis in patients with psoriasis
`
`207
`
`pitting and oil spots were graded separately on a 4-point
`scale: 0~no changes, 1~mild, 2~moderate and 3~severe
`changes of each of the evaluated parameters. A total score
`was summarized for the parameters, except for pitting and
`oil spots, which are not specific features in onychomycosis.
`Three investigators took part in the clinical examinations.
`Each patient was examined by one doctor.
`
`Statistical methods
`
`Non-parametric statistics was used for data presentation and
`comparisons between groups. Consequently, medians with 25th
`and 75th percentiles were used for descriptive statistics and
`the Mann-Whitney test for 2-group unpaired comparisons.
`Fisher’s exact test was used for frequency analysis. Pƒ0.05
`was regarded as statistically significant.
`
`Mycological examination
`
`Only clinically abnormal nails were examined for onychomy-
`cosis. Nail scrapings were obtained from a maximum of four
`fingernails and/or four toenails from each individual. The
`material was examined with direct microscopy using Calco-
`fluor white (8) and a fluorescence microscope. Cultures were
`performed on Sabouraud-glucose-agarzchloramphenicol¡
`cycloheximid.
`Dermatophytes were identified according to their macro-
`and microscopic morphology. Dermatophytes identified only
`by microscopy were also considered significant for derm-
`atophyte infection (4). Yeasts were further identified using
`CHROM-agar Candida (9). Moulds were not further iden-
`tified, and only those with positive microscopy¡positive
`culture were registered as moulds.
`
`RESULTS
`
`Seventy-nine patients with psoriasis and 142 with other
`skin diseases were included in the study. Patients with
`psoriasis had a higher frequency of abnormal finger-
`nails and toenails (82.3%) as compared to other derm-
`(pv0.01)
`atological patients (37.3%)
`(Table I). The
`overall median duration of psoriasis was 22 (10 – 31)
`years. For psoriasis patients with onychomycosis the
`disease duration was 25 (14 – 30) years and for those
`without onychomycosis it was 20 (8 – 30) years (p~
`0.30).
`Table II illustrates the frequencies of onychomycosis
`
`Table I. Demographic data of patients with psoriasis and other skin diseases
`
`Psoriasis patients
`
`Patients with other skin diseasesa
`
`Overall
`
`Women
`
`Men
`
`Overall
`
`Women
`
`Men
`
`Age, median (25th – 75th percentiles)
`Number (n, (%))
`Patients with:
`Abnormal nails (n, (%))
`Abnormal toenails only (n, (%))
`Abnormal finger-nails only (n, (%))
`
`49 (43 – 60)
`79 (100)
`
`54 (44 – 63)
`34 (43.0)
`
`47 (40 – 57)
`45 (57.0)
`
`51 (33 – 58)
`142 (100)
`
`50 (28 – 57)
`65 (45.8)
`
`51 (38 – 60)
`77 (54.2)
`
`65* (82.3)
`62* (78.5)
`35* (44.3)
`
`26* (32.9)
`25* (31.6)
`11** (13.9)
`
`39* (49.4)
`37* (46.8)
`24* (30.4)
`
`53 (37.3)
`49 (34.5)
`11 (7.7)
`
`20 (14.1)
`17 (12.0)
`6 (4.2)
`
`33 (23.2)
`32 (22.5)
`5 (3.5)
`
`aMainly erysipelas, atopic dermatitis, eczema, sclerodermia and bullous skin diseases. Data are compared for subgroups of patients with psoriasis
`and other skin diseases. *pv0.01, **pv0.02.
`
`Table II. Mycological results from patients with psoriasis and other skin diseases
`
`Psoriasis
`
`Non- psoriasis
`
`Total no. of
`patients n~79
`
`Patients with
`abn. fn n~35
`
`Patients with
`abn. tn n~62
`
`Total no. of
`patients n~142
`
`Patients with
`abn. fn n~11
`
`Patients with
`abn. tn n~49
`
`Dermatophytes total
`Trichphyton rubrum
`Trichophyton mentagrophytes
`Epidermophyton floccosum
`Positive microscopy
`Yeasts total
`Candida albicans
`Candida krusei
`Trichosporon beigelii
`Moulds, non-dermatophytes total
`TOTAL number of patients
`
`8 (10.1%)
`6
`1
`0
`1
`10 (12.7%)
`2
`7
`1
`4 (5.1%)
`17 (21.5%)
`
`1 (1.3%)
`0
`0
`0
`1
`5 (6.3%)
`0
`5
`0
`0 (0%)
`6 (7.6%)
`
`8 (10.1%)
`6
`1
`0
`1
`7 (8.9%)
`2
`4
`1
`4 (5.1%)
`19 (24.1%)
`
`12 (8.5%)
`3
`5
`1
`3
`7 (4.9%)
`2
`5
`0
`5 (3.5%)
`18 (12.7%)
`
`0 (0%)
`0
`0
`0
`0
`2 (1.4%)
`1
`1
`0
`1 (0.7%)
`3 (2.1%)
`
`12 (8.5%)
`3
`5
`1
`3
`5 (3.5%)
`1
`4
`0
`4 (2.8%)
`21 (14.8%)
`
`Onychomycosis occurred in 17 patients with psoriasis and in 18 non-psoriatics. The occurrence of mixed infections makes the number of positive
`organisms exceed the number of patients. Furthermore, some patients had onychomycosis in both their fingernails and toenails. Abn.
`fn~abnormal fingernails. Abn. tn~abnormal toenails.
`Data are compared for subgroups of patients with psoriasis and other skin diseases (non-psoriasis).
`No significant differences were found.
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`208
`
`G. Kiellberg Larsen et al.
`
`in patients with psoriasis (17/79~21.5%) and in patients
`with other skin diseases (18/142~12.7%) (p~0.13).
`
`Dermatophytes
`Dermatophytes were demonstrated in 8 of 79 psoriasis
`patients (10.1%), (mainly T. rubrum), compared to 12 of
`142 (8.5%) non-psoriatics (mainly T. mentagrophytes)
`(p~0.85). Dermatophytes were found more frequently
`in men than in women in both psoriasis and non-
`psoriasis patients, i.e. 8 versus 0 (p~0.02) and 11 versus
`1 (p~0.03), respectively. Dermatophytes in fingernails
`were found in one person only (Table II).
`The median age of psoriasis patients with derm-
`atophytosis (51.5, 40.5 – 64 years) was similar to the
`median age of psoriasis patients without dermatophy-
`tosis (49, 42.5 – 59 years) (p~0.75). For non-psoriatics
`with dermatophytosis the median age (57.5, 52 – 65
`years) was significantly higher than for those without
`dermatophytosis (50, 30.5 – 57 years) (p~0.01).
`
`Yeast
`Yeasts were demonstrated in 10 of 79 psoriasis patients
`(12.7%), (mainly Candida (C.) krusei), and in 7 of 142
`non-psoriatics (4.9%),
`(p~0.08).
`(mainly C. krusei)
`Furthermore, there was no significant difference between
`women and men having yeast in their nails, neither
`(p~0.74), nor among the
`among the psoriatics
`non-psoriatics (p~0.47).
`
`Moulds, non-dermatophytes
`Moulds were demonstrated from only a few patients;
`4 psoriasis patients and 5 patients with other skin
`diseases.
`
`Severity of nail affection (total score)
`The total scores of clinical toenail affection did not
`differ from those of clinical fingernail affection within
`psoriasis patients (p~0.54) and within patients with
`other skin diseases (p~0.11) (Fig. 1). However, the
`psoriasis patients had a significantly higher total score
`for their toenails (19.0, 9.0 – 38.0) compared to the
`non-psoriatics (7.0, 4.0 – 16.0) (pv0.01) (Fig. 1). No
`differences were seen between the two groups concern-
`ing fingernails (p~0.83).
`In both patient groups, the severity of nail affection
`in patients with onychomycosis did not differ from that
`in patients without onychomycosis (Fig. 2).
`
`Fig. 1. The total scores of clinically abnormal fingernails (FN) and
`toenails (TN) are illustrated for patients with psoriasis (PS) and
`patients with other skin diseases (NonPS). The box extends from
`the 25th percentile to the 75th percentile with a horizontal line at
`the median value (50th percentile); whiskers extend from the mini-
`mum value to the maximum value.
`
`psoriatics included might have found a significantly
`higher frequency of yeasts in this patient group.
`Several clinical, controlled studies have been pub-
`lished (Table III). As in our study, Staberg et al. (5)
`and Sta¨nder et al. (6) did not find significant differences
`between the prevalences of dermatophytes in psoriasis
`patients compared to non-psoriasis patients (12.3%
`and 9.8%, respectively). Gupta et al. found a higher
`prevalence (8.0%) in the psoriasis group (4). However,
`as can be seen from Table III this prevalence did not
`differ from Sta¨nder et al. (6). Go¨ tz et al. (7) found a
`lower prevalence in the psoriasis group (14%) compared
`to the non-psoriasis group (32.7%), but a higher
`prevalence compared to the psoriasis groups in the
`studies mentioned above. The very high amount of
`dermatophytes in the nails of the control group is
`probably due to a high occurrence of fungal infections
`in the Ruhr district where the controls came from (7).
`
`DISCUSSION
`
`The present study is a prospective, controlled study,
`in which the prevalences of dermatophytes and yeasts
`were not significantly higher in psoriasis patients than
`in patients with other skin diseases (p~0.85 and p~
`0.08, respectively) (Table II). A higher number of the
`
`Fig. 2. The total scores of abnormal toenails are illustrated for
`patients with psoriasis (PS) and for patients with other skin diseases
`(NonPS)
`for both positive (Pos. myc.) and negative (Neg. myc.)
`mycological examinations. The box extends from the 25th percentile
`to the 75th percentile with a horizontal line at the median value
`(50th percentile); whiskers extend from the minimum value to the
`maximum value. Onychomycosis in fingernails was seen in only a
`few patients and, therefore, is not illustrated.
`
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`Onychomycosis in patients with psoriasis
`
`209
`
`Table III. Review of studies on onychomycosis in psoriasis patients
`
`Author, year
`
`Psoriasis patients
`
`Non-psoriasis
`
`Zaias (11) 1969
`Go¨ tz (7) 1974
`Feuerman (10) 1976
`Staberg (5) 1983
`Gupta (4) 1997
`Sta¨ nder (6) 2001
`Present study 2002
`
`n
`
`15
`100
`120
`78
`561
`250
`79
`
`Dermatophytes (%)
`
`Yeast (%)
`
`n
`
`Dermatophytes (%)
`
`Yeast (%)
`
`0
`14.0
`24.2
`12.3
`8.0
`9.8
`10.1
`
`Some*
`16.0
`15.0
`15.4
`0.5
`23.9
`12.7
`
`n.d.
`1000
`n.d.
`41
`922
`102
`142
`
`n.d.
`32.7
`n.d.
`9.8
`4.4
`10.8
`8.5
`
`n.d.
`n.d.
`n.d.
`9.8
`0.3
`6.9
`4.9
`
`Some of the studies included both fingernails and toenails (5, 6, 10, present study), while others only included toenails (4, 7). n.d.~ not done.
`*From subungual debris in 40 psoriatic nails of 15 patients, 22 yeasts were isolated.
`
`Staberg et al. found a tendency towards a higher
`prevalence of yeasts in the psoriasis group, but it was
`not significantly different from that of the non-psoriasis
`patients (5). Sta¨ nder et al. found a significantly higher
`prevalence of yeasts in the psoriasis group with nail
`changes (23.9%)
`(6). Gupta et al.
`found that
`the
`occurrence of yeasts in the psoriasis group was almost
`the same as in the non-psoriasis group (4).
`The investigations of Feuerman et al. (10) and Zaias
`(11) represent uncontrolled studies with very divergent
`results, i.e. dermatophytes present in 24.2% of abnor-
`mal nails versus 0 (Table III).
`Nail involvement in psoriasis is common, with reported
`incidences varying from 10% to 50% (11). In this study,
`82.3% had nail abnormalities (Table I). The patients
`in our study were recruited from the inpatient clinic,
`and could be assumed to be more severely affected than
`patients from the outpatient clinic, and this might
`explain the high occurrence of nail abnormalities. We
`found that the severity of nail affection could not be
`used as a marker of onychomycosis (Fig. 2).
`In the present study, only clinically abnormal nails
`were examined for onychomycosis, because onycho-
`mycosis
`is uncommon in normal appearing nails
`according to Gupta et al., i.e. 0.7% (4).
`As in other studies (5 – 7), the occurrence of yeast
`was relatively high. The presence of C. krusei in most
`of the cases is noteworthy. Actually, the number of
`psoriasis patients with yeast infection was higher than
`for those infected with dermatophytes. This finding
`differs from the distribution of pathogens in onycho-
`mycosis in the general population of otherwise healthy
`individuals,
`in which dermatophytes are the domi-
`nating cause of infection in more than 90%. Probably,
`the altered subungual
`tissue and onycholysis may
`facilitate the invasion of yeasts. Furthermore, the fast
`
`turnover of the nails in psoriasis patients theoretically
`may constitute an effective defence against dermato-
`phytes. We considered moulds as secondary invaders,
`as repeated cultures were not within the scope of this
`investigation.
`
`REFERENCES
`
`1. Roberts DT. Prevalence of dermatophyte onychomycosis
`in the United Kingdom: results of an omnibus survey.
`Br J Dermatol 1992; 126 Suppl. 39: 23 – 27.
`2. Heikkila¨ H, Stubb S. The prevalence of onychomycosis
`in Finland. Br J Dermatol 1995; 133: 699 – 703.
`3. Summerbell RC, Kane J, Krajden S. Onychomycosis,
`tinea pedis and tinea manuum caused by non-dermato-
`phytic filamentous fungi. Mycoses 1989; 32: 609 – 619.
`4. Gupta AK, Lynde CW, Jain HC, Sibbald RG, Elewski
`BE, Daniel CR, et al. A higher prevalence of onycho-
`mycosis in psoriatics compared with non-psoriatics: a
`multicenter study. Br J Dermatol 1997; 136: 786 – 789.
`5. Staberg B, Gammeltoft M, Onsberg P. Onychomycosis
`in patients with psoriasis. Acta Derm Venereol 1983; 63:
`436 – 438.
`6. Sta¨ nder H, Sta¨ nder M, Nolting S. Frequency of fungal
`involvement in nail psoriasis. Hautarz 2001; 52: 418 – 422.
`7. Go¨ tz H, Patiri C, Hantschke D. Das Wachstum von Derm-
`atophyten auf normalem und psoriatischem Nagelkeratin.
`Mykosen 1974; 17: 373 – 377.
`8. Haldane DJM, Robart E. A comparison of calcofluor
`white, potassium hydroxide, and culture for the labora-
`tory diagnosis of superficial
`fungal
`infection. Diagn
`Microbiol Infect Dis 1990; 13: 337 – 339.
`9. Odds FC, Bernaerts R. CHROMagar Candida, a new
`differential
`isolation medium for presumptive identifi-
`cation of clinically important Candida species. J Clin
`Microbiol 1994; 32: 1923 – 1929.
`10. Feuerman E, Alteras I, Aryelly J. The incidence of
`pathogenic fungi
`in psoriatic nails. Castellania 1976;
`4: 195 – 196.
`11. Zaias N. Psoriasis of the nail: a clinical-pathologic study.
`Arch Dermatol 1969; 99: 567 – 579.
`
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