WHITE PAPER
Synchro REPLA:Y
Laser Treatment of Onychomycosis:
Our Experience with Long-Pulse Nd:YAG
SYNCHRO REPLA:Y
DEKA White Paper
November 2016
Laser Treatment of Onychomycosis:
Our Experience with Long-Pulse Nd:YAG
Andrea Bassi1, M.D. – Elisa Margherita Difonzo2, M.D. - Paolo Bonan1, M.D.
1
2
: Donatello Laser-Dermosurgery Unit, Villa Donatello, Florence, Italy
: Department of Translational Medicine and Surgery (Dermatological Unit), University of Florence, Florence, Italy
Introduction
Material and Methods
ungal nail infections are chronic diseases that lead
to progressive destruction of the nail plate. Once
regarded as a problem of little clinical significance, they
currently constitute a major medical problem, both
epidemiologically and therapeutically[1-3]. Most cases
of onychomycosis are caused by the dermatophytes
Trichophyton rubrum and, to a lesser extent,
Trichophyton interdigitale. In about 15% of cases, the
causative agent is a mould, more common in hot and
humid climates. Finally, the very rare onychomycoses
caused by Candida generally affect the fingernails, often
associated with infection of the periungual tissues[4-7].
e used the Synchro REPLA:Y system Nd:YAG
1064 nm laser (DEKA - Florence, Italy). From the nail
infection outpatient facility, patients over the age
of 18 were selected, according to the exclusion and
inclusion criteria shown in Tables 1 and 2.
F
The main problem with onychomycosis remains its
treatment. To date, in fact, despite the availability of
topical (predominantly amorolfine and ciclopiroxolamine)
and systemic (mainly terbinafine) medications which
are effective against other anatomo-clinical forms of
mycosis, the percentage of failures and recurrences
still remains high, even after prolonged therapy lasting
several months[8-10]. Since the nail plate is a hard,
compact structure, and not very permeable, it is difficult
to obtain a uniform distribution of both topical and
systemic medications and an effective concentration
thereof throughout the thickness of the nail plate[11-12].
Systemic treatment is often contraindicated in the
elderly and/or in patients with multimorbidity due to
the risk of drug interference and organ damage[13].
W
Diagnosis confirmed by direct mycological examination and
culture with isolation of Trichophyton rubrum or Trichophyton
interdigitale.
Signature of consenting party (informed consent) age 18 and
over.
Distal-lateral subungual onychomycosis.
Presence of negative prognostic factors (subungual
hyperkeratosis > 2 mm, involvement of the lunula, spikes,
dermatophytoma, etc.).
Failure to respond to topical and systemic antifungal medication
properly administered for at least 4 months.
Contraindication to systemic antifungal treatment (presence of
liver disease, etc., possible pharmacological interferences).
Table 1: Inclusion criteria.
Onychomycosis with isolation of non-dermatophytic
filamentous fungi.
For these reasons, in recent years, both relatively older
and newer physical treatments have been introduced
and tested, such as light therapy, photodynamic
therapy, CO2 laser therapy, laser diode, and lately the
Nd:YAG laser.
White superficial onychomycosis, initial and limited forms of the
distal-lateral subungual variety.
Below we present our experience of treating
consenting patients selected from our case studies
with the Nd:YAG laser. We selected patients who had
already received medical treatment without benefit
and/or patients with some of the negative prognostic
indicators.
Presence of other nail and/or foot diseases (psoriasis, bacterial
infections, etc.).
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Presence of tinea pedis or another anatomical/clinical form of
dermatophytosis.
Discontinuation of systemic antifungal treatment in the
previous 3 months or of topical treatment in the previous
month.
Table 2: Exclusion criteria.
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SYNCHRO REPLA:Y
DEKA White Paper
ID
November 2016
Age
Gender
Clinical Diagnosis
Etiological Agent
Previous Treatments
1
36
F
DSO (*) with hyperkeratosis
> 2mm; left hallux
T.rubrum
Itraconazole for 6 months
2
62
M
Halluxes SOP (**)
T.interdig
Ciclopirox lacquer for 7 months
3
41
M
DSO with hyperkeratosis > 2mm; 1st, 2nd
and 3rd left foot toes
T.rubrum
Terbinafine for 4 months
4
42
M
DSO with spike; left hallux
T.rubrum
Amorofine lacquer for 6 months
5
66
M
DSO right hallux
T.rubrum
Itraconazole for 5 months
6
53
M
Total dystrophic onychomycosis
of left hallux
T.rubrum
Itraconazole for 4 months and
Terbinafine for 3 months
7
43
M
Total dystrophic onychomycosis
of left hallux
T.rubrum
Fluconazole for 8 months
8
62
F
Halluxes SOP
T.interdig
Ciclopirox lacquer for 6 months
9
70
F
DSO right hallux
T.rubrum
Itraconazole for 5 months
10
43
M
Halluxes SOP
T.rubrum
Ciclopirox lacquer for 8 months
11
35
M
DSO right hallux with spike
T.rubrum
Fluconazole for 6 months
12
70
F
DSO with hyperkeratosis > 2mm;
left hallux
T.rubrum
None
(*) Distal Subungual Onychomycosis; (**) Subungual Onychomycosis Proximal
Table 3: General characteristics of the study.
The 19 nails were affected by onychomycosis confirmed
by clinical and mycological examination.
Specifically, subjects were chosen who presented
with distal or lateral subungual onychomycosis with
hyperkeratosis over 2 mm thick or other adverse
prognostic factors, subjects previously treated without
clinical or mycological cure. The general characteristics
of the 12 patients who completed the study and
about whom we have written are shown in Table 3.
As can be seen, no less than 11 of the 12 patients had
already been unsuccessfully treated with topical and/
or systemic antifungal treatment for several months.
In order to validate the parameters for the experiment,
some fragments of infected nail plate, inoculated on a
medium made up of Sabouraud agar with antibiotics
plus actidione, were irradiated at different pulse
durations and fluences. At 24 hours after inoculation,
one of the two inocula from each plate was irradiated,
measuring growth after 15 days, the time it takes
for colonies of dermatophytes to be conventionally
considered negative (Figure 1).
The parameters able to completely inhibit fungal growth
were as follows: spots of 5 mm, fluence of 35 J/cm2
with a single pulse of 5 ms and frequency of 1.5 Hz.
2
A further test was carried out on a fingernail fragment
infected by Trichophyton rubrum in order to measure
how much laser energy was absorbed. Using the
parameters described above, we therefore irradiated
a screen containing a central hole with an infected nail
fragment and an energy meter on the other side of the
hole (Figure 2). After successive irradiations with single
pulses, the percentage of energy absorbed by the nail
was calculated to be 37.5%, very encouraging data
when we consider, for example, the low percentage
of systemic drug that the nail would be able to absorb
The interval between one laser session and the next
was 15 days, during which time surviving fungal
elements are able to reactivate their metabolism, thus
returning to a vital state. The maximum number of
treatment sessions was 7. After that time, any patients
whose clinical condition had remained stationary
or worsened had to discontinue laser treatment, in
favour of medical treatment associated with chemical
avulsion with urea on the infected nail plate.
The follow-up visit was performed 2 months after the
end of treatment with a physical examination and
mycological investigations. The infected area was
treated using a standard method: three concentric
movements from the middle outwards and three in
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SYNCHRO REPLA:Y
A
November 2016
B
Figure 1. Cultures on a Sabouraud medium of nail plate fragments infected by T.rubrum. After 15 days: (A) no growth in the inoculum on
the right irradiated 24 hours after inoculation; growth of T. rubrum on the non-irradiated left inoculum. (B) colony reverse confirming the
lack of growth and highlighting the red colour, typical of this dermatophyte in the non-irradiated inoculum.
the opposite direction from the periphery towards the
middle, for a total of 6 passes. As far as possible, we
tried to avoid irradiating the same area more than once
on each pass, so as to make the treatment uniform.
During treatment the nail plate surrounding the
infected area and the periungual folds were protected
with a bandage.
Considering that Nd:YAG laser light is absorbed to
a greater extent by water, before each session the
nail plate needed to be hydrated, so the patient was
recommended to apply an occlusive dressing, in order
to seal in a topical medication containing urea at 30%
for 3 days.
Results
A
up visit. At the same point, mycological healing was
confirmed for all 10 patients (Figures 3-6).
With regard to the side effects, all we can report is
a burning sensation localized around the treatment
area, reported by almost all patients about halfway
through each session, which disappeared quickly
using an external cooling system. We observed no
long-term side effects: specifically, no alterations in
shape, surface, colour and nail plate growth occurred.
In conclusion, it can be said that the treatment was
well-tolerated, with no significant side effects.
Finally, we wish to point out the excellent compliance
on the part of those patients who adhered completely
to the treatment, also given that they had already
been unsuccessfully treated for several months with
medical treatment and/or a systemic regimen.
s can be seen from Table 4, the results of the
treatment are the following: 10 of the 12 patients
showed a positive response after a number of sessions
that varied from 3 to 7 (mean 5.3). In the remaining
2 patients, even though the maximum number of 7
scheduled sessions had been reached, no clinical
improvement had been obtained while the mycological
investigations remained positive. We therefore decided
to switch over to a medical treatment with terbinafine,
associated with chemical avulsion with urea at 40% of
the infected part of the nail plate.
Going into more detail, in 8 of the 10 patients who
responded to treatment healing was both clinical and
mycological; only 2 patients showed a slight nail plate
dystrophy that was no longer evident at the follow-
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Figure 2. Practical model consisting of a screen with a central
hole where the nail fragment is placed, with a power meter on the
other side to measure the energy which passes through without
being absorbed by the nail fragment.
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SYNCHRO REPLA:Y
DEKA White Paper
November 2016
ID
Clinical Diagnosis
No. of Sessions
Outcome
1
DSO (*) with hyperkeratosis > 2mm;
left hallux
6
Mycological cure; clinical persistence of
slight dystrophy of the nail plate (Fig.3)
2
Halluxes SOP (**)
4
Clinical and
mycological cure
3
DSO with hyperkeratosis > 2mm;
1st, 2nd and 3rd left foot toes
7
Clinical and mycological cure
4
DSO with spike; left hallux
3
Clinical and mycological cure (Fig.4)
5
DSO right hallux
4
Clinical and mycological cure (Fig.5)
6
Total dystrophic onychomycosis of left hallux
6
Mycological cure; clinical persistence of
slight dystrophy of the nail plate (Fig.6)
7
Total dystrophic onychomycosis of left hallux
7
Clinical and mycological cure
8
Halluxes SOP
4
Clinical and mycological cure
9
DSO right hallux
5
Clinical and mycological cure
10
Halluxes SOP
4
Clinical and mycological cure
11
DSO right hallux with spike
7
Conditions stationary
12
DSO with hyperkeratosis > 2mm; left hallux
7
Conditions stationary
(*) Distal Subungual Onychomycosis; (**) Subungual Onychomycosis Proximal
Table 4: Results.
Discussion and Conclusions
O
ur study confirmed the in-vitro antifungal effect
of long-pulse Nd:YAG laser at 1064 nm both against
Trichophyton rubrum and Trichophyton interdigitale
(species isolated from almost all patients with
dermatophytic onychomycosis), identifying the most
appropriate parameters to use.
The 1064 nm wave performs an extremely selective
photothermolysis[14]: indeed, as it is poorly absorbed
A
by keratin (less than 30%), it is able to penetrate much
of the nail plate and thus to exert its fungicidal action
on the fungal cells in the deeper layers and in the nail
bed, leaving the surrounding tissue intact. This ability
to achieve deep penetration makes it possible to treat
forms of onychomycosis with significant subungual
hyperkeratosis, even without having to precede
the treatment with chemical avulsion. The 1064 nm
wavelength generates temperatures above 60°C with
uniform heat distribution, which plays a fungicidal
role both by denaturing the membrane proteins, and
B
Figure 3. Distal subungual onychomycosis of the left hallux with hypercheratosis > 2mm. (A) Clinical picture prior to treatment; (B) clinical
picture after 6 sessions. A slight dystrophy of the nail plate persists; mycological investigations repeated at 2 months resulted negative.
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DEKA White Paper
A
SYNCHRO REPLA:Y
November 2016
B
Figure 4. Distal subungual onychomycosis of the left hallux with spike. (A) Clinical picture prior to treatment. (B) Clinical and mycological
cure after 3 sessions.
A
B
Figure 5. Distal subungual onychomycosis of the right hallux. (A) Clinical picture prior to treatment. (B) Clinical and mycological cure after 4
sessions.
A
B
Figure 6. Total dystrophic onychomycosis of the left hallux. (A) Clinical picture prior to treatment. (B) Mycological cure after 6 sessions
with minimal dystrophic outcomes of the nail plate.
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SYNCHRO REPLA:Y
by producing oxygen-free radicals[15-17]. The selective
photothermolysis on Trichophyton rubrum is particularly
significant. As is known, this dermatophyte produces
two pigments: the first, xanthomegnin, is responsible
for its characteristic red colony reverse; the second,
melanoid, is expressed in one particular variety of
Trichophyton rubrum, namely melanoides. In-vitro
studies document that xanthomegnin absorbs the 532
nm wavelength, while the melanoid pigment absorbs
the 1064 nm one[18-22].
In our study, we found healing in 10 of the 12 patients,
that manifested after just 3-4 sessions, performed 15
days apart, making a total of 45-60 days. These results
are all the more significant considering that we chose
onychomycosis with adverse prognostic factors (size,
presence of subungual hyperkeratosis, spikes) and
which had not responded to medical treatment for up
to as long as eight months. These are clearly the most
difficult cases to treat, so the Nd:YAG laser should be
considered a valid therapeutic option, especially in
cases of subungual distal onychomycosis with little or
no subungual hyperkeratosis.
We also wish to highlight the absence of significant
side effects, apart from the mild burning sensation
during each session, which on no occasion, however,
led to withdrawal treatment. As mentioned above,
patients were compliant with the treatment, despite
their reluctance caused by the ineffectiveness of
previous therapy, and at each laser session they saw
improvements in their symptoms until they had fully
recovered.
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SYNCHRO REPLA:Y
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