Treatment of Onychomycosis – a Clinical Study

ORIGINAL PAPER doi: 10.5455/medarh.2015.69.173-176

© 2015 Laura Pajaziti, Ermira Vasili Med Arh. 2015 Jun; 69(3): 173-176
This is an Open Access article distributed under the terms of the Received: March 12th 2015 | Accepted: May 24th 2015
Creative Commons Attribution Non-Commercial License (http://
creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted
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provided the original work is properly cited.

Treatment of Onychomycosis – a Clinical

Study
Laura Pajaziti1, Ermira Vasili2
1
Clinic of Dermatology, UHCC Prishtina, Kosovo
2
Clinic of Dermatology, UHC “Mother Teresa”, Tirana, Albania

Corresponding author: Laura Pajaziti, MD. Clinic of Dermatology. UHCC, Prishtina, Prishtina, Kosovo.

ABSTRACT
Introduction: Onychomycosis is a fungal infection of the nail unit. Anatomical and physiological characteristics of the nail apparatus im-
pose the need for long-term treatment to achieve complete cure. Goal: The main goal of this project is to study the effectiveness of several
treatment protocols for onychomycosis based on Scoring Clinical Index for Onychomycosis (SCIO). Material and methods: The study
included 133 patients with onychomycosis, diagnosed by KOH microscopy and culture. Based on disease severity, patients were grouped
into groups with SCIO values: 6-9, and 12-16. These groups were randomly subdivided to 5 subgroups according to the given treatment
protocols: fluconazole 150 mg 1x weekly, itraconazole continual therapy, itraconazole pulse therapy, terbinafine 250 mg/d, and terbinafine
+ ciclopirox 8% lacquer, respectively. The cure rate was evaluated at the end of 48 week. Results: The obtained cure rates according to the
above mentioned protocols were: 92.30%, 81.81%, 83.33%, 90.90%, and 100%, respectively for groups of patients with SCIO values 6 – 9.
Within patients with SCIO values 12-16, were achieved cure rates as follows: 78.57%, 78.57%, 75%, 80%, and 86.66%. Conclusions: There
was no statistically significant difference in cure rate between five treatment protocols applied in this study. In patients with high SCIO
values is expected a decrease in cure rate.
Key words: onychomycosis, SCIO, treatment protocols.

1. INTRODUCTION are the mainstay therapy for onychomycosis (1). In use

Onychomycosis is a chronic fungal infection of the nail are terbinafine, itraconazole and fluconazole. Extensive
unit, which gradually destroys the nail plate (1). At the research on the use of these drugs show low level risk for
beginning, fungal nail infections are asymptomatic, and the appearance of side effects. Fluconazole has not been
the only complaints of the affected persons are cosmetic. approved by the FDA, however is used in other countries
Later, with the disease progression, the nail plates become for onychomycosis treatment (4). The aim of this study is
deformed, which may be followed by difficulties during to evaluate the effectiveness of several treatment proto-
prolonged standing and walk (if the disease is localized cols for onychomycosis based on SCIO.
on toenails), obstacles during writing and typing (when
fingernails are affected), pain, paresthesia, discomfort and 2. MATERIAL AND METHODS
loss of dexterity (2). Treatment of onychomycosis is main- The study included 133 patients with OM. They were
ly based on systemic therapy, excluding superficial form of subject of clinical nail examination and sampled for di-
onychomycosis, or the mildest cases when only the distal rect microscopy and culture. The sample collection was
margin of the nail plate is affected. Therefore, treatment taken separately from each nail, provided that the patient
modality can be determined according to clinical form of didn’t receive systemic antifungal therapy or applied top-
onychomycosis, or SCIO values. SCIO is a mathematical ical antifungals for at least 2 weeks. The material was col-
tool that enables evaluation of the disease severity (3). It is lected from the most proximal part of the affected nail.
based on key factors which affect development of onycho- Direct microscopy was repeated in cases with negative or
mycosis and treatment success. Antimycotics used earlier suspicious results. For fungal culture was used Sabourod
(griseofulvine and ketoconazole) had their limitations be- peptone-glucose agar. The evaluation of the disease sever-
cause of side effects such as nausea, headache, skin rash, ity was based on SCIO onycho-index and calculated by
hypersensitivity, fotosensitivity, drug interaction, hepato- electronic calculator in the link: http://www.onychoin-
toxicity, the need for long use and frequent relapse after dex.com. The disease severity was the main criterion ac-
the cessation therapy. Nowadays, allylamines and azoles cording to which the sample stratification was done, and

Med Arh. 2015 Jun; 69(3): 173-176 173

Treatment of Onychomycosis – a Clinical Study

FLU ITRc ITRp TB TB+CPX

Mean value 8.39 7.86 8.36 8.52 8.51
SCIO 1
St. Dev. 0.82 1.08 0.94 0.71 0.86
Mean value 4.73 4.01 3.79 4.27 2.08
SCIO 12
St. Dev. 1.54 (SCIO 48),
1.83 no significant difference
1.22 resulted (F=0.602,
1.68 p=0.663) at the significance level p > 0.5
1.76
th
Mean value 0.42 The obtained
0.61 results at the 48
0.56 week, which represent
0.32 mycological cure, are expressed in
0.00
percentage values. Z Test Calculator for 2 population proportions is used to compare the results
SCIO 48 St. Dev. 1.07 1.35 1.30 1.07 0.00
of the each protocol with each one. It was concluded no significant difference in the treatment
Mycological evaluation 92.30% (12/13)efficiency
81.81%
between these 5 treatment protocols at the significance level100%
(9/11) 83.33% (10/12) 90.90% (10/11) 0.05.(12/12)
Table 1. Performance of treatment with different protocols within the group of patients with initial SCIO values 6–9

FLU Table
ITRc1 Performance of treatment with different
ITRp TB protocols withinTB+CPX
the group of patients with
Mean value 13.64 13.33 13.83 initial SCIO values 6 - 9
13.33 13.86
SCIO 1
St. Dev. 0.81 0.00 1.08 FLU 0.00
ITRc ITRp 1.11 TB TB+CPX
Mean value 7.28 SCIO Mean value7.68 8.39
8.21 1 7.86
6.18 8.36 6.38 8.52 8.51
SCIO 12 St. Dev. 0.82 1.08 0.94 0.71 0.86
St. Dev. 2.15 1.90 2.30 1.75 2.64
SCIO 12
no significant Mean value
difference between4.73 4.01
those groups1.00 3.79
at the significance level 0.05, given that F2.08
4.27 = 1.593
Mean value 1.82 1.55 St. Dev. 1.81 1.54 1.83 1.22 1.13 1.68 1.76
and p = 0.186, and consequently the groups were comparable.
SCIO 48 St. Dev. 2.55 SCIO
2.5748 Mean value
2.86 0.42 0.61
2.07 0.56 2.36 0.32 0.00
St. Dev. guideline,
1.07 1.35 1.30 with1.07 0.00
Mycological evaluation 78.57% (11/14) Based on SCIO
78.57% treatment
(11/14) 75% (12/16) for patients
80%with onychomycosis
(12/15) 86.66% SCIO values 12
(13/15) – 16,
Mycological 92.30% 81.81% 83.33% 90.90% 100%
was used the scheme of extended duration: itraconazole 200mg per day for 16 weeks continually;
Table 2. Performance of treatment with different protocols among the evaluation
patients with(12/13) (9/11) 12–16(10/12)
initial SCIO values (10/11) (12/12)
itraconazole pulse therapy – 4 pulses and terbinafine 16 weeks continually.

groups with SCIO values: 6–9, and 12-16 were formed. Table 2 Performance of treatment with different protocols among the patients with initial SCIO
These groups were randomly subdivided to 5 subgroups values 12 to
Clinical cure trend according - 16
treatment protocols
during one year
according to the given treatment protocols: fluconazole FLU ITRc ITRp TB TB+CPX
9
(FLU) 150 mg 1x weekly, itraconazole continual therapy,SCIO 1 Mean value 13.64 13.33 13.83 13.33 13.86
8 Dev.
St. 0.81 0.00 1.08 0.00 1.11
200mg/d (ITRc), itraconazole pulse therapy, 1 week per
SCIO 12 7 value
Mean 7.28 8.21 7.68 6.18 6.38
Disease severity-SCIO

month (ITRp), terbinafine (TB) 250 mg/d and, TB + ci- Flu

St.
6 Dev. 2.15 1.90 2.30 1.75 2.64
clopirox (CPX) 8% lacquer, topicaly 1/d, respectively. The48 Mean
SCIO 5 value 1.82 1.55 1.81 ITRc
1.00 1.13
patients underwent regular controls by a dermatologist St.
4 Dev. 2.55 2.57 2.86 2.07
ITRp 2.36
every month. At each control was measured the length Mycological
3 78.57% 78.57% 75% 80%TB 86.66%
evaluation (11/14) (11/14) (12/16) (12/15) (13/15)
of the new proximal portion of the nail plate. Measure- 2 TB+CPX
1
ments of liver enzymes levels were performed in regular
0
basis, too. SCIO values were calculated at the 12th and 48ththe follow up of the
During clinical cure, it was evident a slightly greater improvement in
SCIO I SCIO 12 SCIO 48
patients
week. In order to assess eradication of the fungal infec- treated with terbinafine (Figure 2). However, by comparing SCIO values obtained at the
tion, KOH microscopy was performed at the end end of of the 48Figure
the
th
week,1.resulted
Clinicalnocure trenddifference
significant accordingbetween
to different treatment
the groups (F=0.348, p=0.845) at
Figureprotocols
1 Clinical in
cure trend according
patients with SCIOto different
6–9. treatment protocols in patients with
the significance level p > 0.05.
48 week. The cure rate was evaluated at the end of the
th
SCIO 6 - 9.
48th week. Statistical processing of obtained data is done
Trend of clinical improvement with different protocols
by ANOVA and Z–electronic calculator. along 1 year
There were 74 patients with initial SCIO values 12 – 16 divided randomly into 5 subgroups
16,00
3. RESULTS according to the treatment protocols (Table 2). By ANOVA testing is confirmed that there was
14,00
Table 1 shows patients with initial SCIO values 6–9
Disease severity SCIO

12,00
grouped according to the treatment protocols. ANOVA Flu
10,00
confirmed that there was no significant difference be- ITRp
8,00
tween the groups at the significance level p>0.05 (F = 1.036 6,00
ITRc

and p=0.397), consequently the groups were comparable. 4,00

TB

At the week 12, in patients treated with combined ther- 2,00

TB+CPX

apy (TB+CPX) was achieved a significant improvement 0,00

compared to other groups treated with monotherapy SCIO I SIO 12 SCIO 48
(Figure 1). However, by comparing the results of clinical
Figure 2. Trend of clinical improvement under different proto-
evaluation between the groups, at the end of the 48th weekFigure 2 Trend of clinical improvement under different protocols in patients with
cols in patients with SCIO 12-16.
(SCIO 48), no significant difference resulted (F=0.602, SCIO 12-16.
p=0.663) at the significance level p>0.5 The obtained re- ment protocols (Table 2). By ANOVA testing is confirmed
sults at the 48th week, which represent mycological cure, that there was no significant difference between those
are expressed in percentage values. Z Test Calculator for groups at the significance level 0.05, given that F = 1.593
2 population proportions is used to compare the results and p=0.186, and consequently the groups were compa-
of the each protocol with each one. It was concluded no rable.
significant difference in the treatment efficiency between Based on SCIO treatment guideline, for patients with
these 5 treatment protocols at the significance level 0.05. onychomycosis with SCIO values 12-16, was used the
There were 74 patients with initial SCIO values 12-16 scheme of extended duration: itraconazole 200mg per
divided randomly into 5 subgroups according to the treat- day for 16 weeks continually; itraconazole pulse therapy

174 Med Arh. 2015 Jun; 69(3): 173-176

 Treatment of Onychomycosis – a Clinical Study

– 4 pulses and terbinafine 16 weeks continually. During spectively. According to Roberts and his collaborators (1),
the follow up of the clinical cure, it was evident a slightly terbinafine is superior in comparison with itraconazole in
greater improvement in patients treated with terbinafine vitro as well as in vivo against dermatophyte caused on-
(Figure 2). However, by comparing SCIO values obtained ychomycosis, and should be considered as first line med-
at the end of the 48th week, resulted no significant differ- ication, while itraconazole should be considered as the
ence between the groups (F=0.348, p=0.845) at the signif- best alternative of terbinafine. Cohen (13), reports that
icance level p > 0.05. clinical experiments have documented the superiority of
By comparing the results of mycological cure obtained terbinafine over other antifungal agents for onychomyco-
with different treatment protocols, expressed in percent- sis treatment.
age values, no significant difference among the groups of Studies on the efficacy of fluconazole in treating ony-
patients with initial SCIO value 12-16 was achieved at the chomycosis, revealed high cure rates, but also the neces-
significance level 0.05. sity for long term treatment. According to Welch and his
collaborators (14), investigations have resulted with cure
4. DISCUSSION rate in the range 80-90% after administration of 150 mg
Treatment of onychomycosis is still challenging. In or- fluconazole once-weekly for an average of 6-9 months. In
der to evaluate the superiority of one antifungal agent a study (15) with 362 patients with toenail onychomyco-
over the other, a lot of comparative studies have been sis, 3 treatment protocols with fluconazole once weekly
done. Fluconasole wasn’t included in these studies. were administered in doses: 150mg, 300 mg, and 450mg.
In a study (5) with 53 patients with toenail onychomy- At the sixth month, achieved mycological cure rates were:
cosis caused by dermatophytes, 27 patients were treated 53%, 59%, and 61%, respectively. In another study, 349
with itraconazole 200 mg/daily, while other 26 of them patients with thumbnail onychomycosis, treated with flu-
were treated with terbinafine 250 mg/daily for 3 months. conazole 150mg 1 x per week, achieved clinical cure rate
The achieved clinical and mycologic cure rate for group 76% after six months (16).
treated with itraconazole was 60.9% and 64.7% for terbin- For itraconazole is characteristic that its concentra-
afine group, while remained other patients had improve- tion in nail unit remains high even after the cessation
ment. In another study (6), 60 patients divided into 3 of therapy (17). Therefore, itraconazole may be admin-
groups, were treated with 250mg/d terbinafine, 500 mg/d istered in pulse therapy regimens (intermittent dosing),
terbinafine for a week per month, and 400mg/d itracon- every 4 week. Several studies have documented efficacy
azole for a week per month, respectively. In the all 3 groups of itraconazole administered as continuous therapy 200
the response to the treatment was similar, about 80% cure mg per day, or twice daily for 1 week per month (2 or 3
rate, and without significant difference. Honeyman et al. pulses) (18, 19, 20).
(7) have treated 85 patients with itraconazole 200mg/d, Combination of topical therapy with the newer oral
and other 82 patients with terbinafine 250mg/d for 4 antifungal agents may increase the efficacy in onychomy-
months. At the end of the month 12, clinical cure rate for cosis treatment (21) and shorten the duration of therapy.
terbinafine group was 57.8%, and 62.6% for itraconazole Therefore, the objective of several studies was the investi-
group. The mycologic cure rate for terbinafine was 95.3% gation of efficacy of combined therapy in onychomycosis
and 84.3% for itraconazole. treatment. Avner et al. (22) in 2005 compared treatment
By analyzing the results of these studies concluded that efficacy of terbinafine 250mg/d for 16 weeks as monother-
largely doesn’t exist significant difference in treatment apy with the combination therapy: terbinafine 250mg/d
efficacy between itraconazole and terbinafine. Howev- for 16 weeks + ciclopirox olamine 8% lacquer solution for
er, in researches with larger number of patients, terbin- 9 months. Mycological cure rate was 64.7% for monother-
afine treatment efficacy resulted to be greater than that apy and 88.2% for the combination therapy. Other authors
of itraconazole, and this difference was significant (8, 9). (23, 24) in their publications have reported the superiority
In a study with 151 patients with dermatophyte caused of combination therapy over monotherapy based on the
toenail onychomycosis, was compared treatment effica- lower treatment cost as well, also.
cy between terbinafine 250mg/d and intermittent ther- In our study, different protocols were applied for on-
apy with itraconazole (10). The continuous therapy with ychomycosis treatment: fluconazole 150mg weekly,
terbinafine showed superiority and the relapse rate was itraconazole 200mg/daily, itraconazole 400mg/daily, ev-
very low in comparison with intermittent therapy (10). ery 4 week of the month, terbinafine 250mg/daily, and ter-
Brautigam et al. (11), included 86 patients in the study, binafine 250mg/daily in combination with 8% ciclopirox
divided into 2 groups. To the first group was administered lacquer 1/daily. Patients were categorized into two groups
250 mg/d terbinafine, and to the second one, 200 mg/d based on the disease severity which was assessed by SCIO.
itraconazole. The achieved mycologic cure rates were 81% Differences in the treatment outcomes proved to be not
for terbinafine group, and 63% for itraconazole group. In statistically significant as in studies with a small number
a study by De Backer et al. (12), 186 patients with toe- of patients of the other authors.
nail onychomycosis were treated with 250 mg/d terbina-
fine, and other 186 patients with itraconazole 200 mg /d 5. CONCLUSION
during 12 weeks. The difference in the treatment efficacy Despite the fact that the combination therapy achieved
resulted significant, given that the clinical and mycologi- better results compared to monotherapy, there was no
cal cure rates for terbinafine were 73% and 76%, while the significant difference in cure rate between five treatment
obtained cure rates for itraconazole were 48% and 50% re- protocols applied in this study. In patients with high SCIO

Med Arh. 2015 Jun; 69(3): 173-176 175

Treatment of Onychomycosis – a Clinical Study

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CONFLICTS OF INTEREST: NONE DECLARED. 13. Cohen AD, Medvesovsky E, Shalev R, et al. An independent
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