Treatment of Recalcitrant Viral Warts with Photodynamic Therapy with Mal and Red Light

doi:10.4236/jcdsa.2013.31017

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Journal of Cosmetics, Dermatological Sciences and Applications, 2013, 3, 117-120

http://dx.doi.org/10.4236/jcdsa.2013.31017 Published Online March 2013 (http://www.scirp.org/journal/jcdsa)

117

Treatment of Recalcitrant Viral Warts with Photodynamic

Therapy with Mal and Red Light

Montserrat Fernández Guarino*, Antonio Harto, Pedro Jaén

Dermatology Departament, Hospital Universitario Ramón y Cajal, Madrid, Spain.

Email: *[email protected]

Received January 21st, 2013; revised February 23rd, 2013; accepted March 4th, 2013

ABSTRACT

Background: Photodynamic therapy (PDT) is a treatment for non-melanoma skin cancer. In recent years, its use has

expanded to new indications. Viral warts (VW) are some of the most promising. Methods: A retrospective, descriptive,

observational study was carried out. Patients who did not respond to cryotherapy were selected and were occluded with

methyl aminolevulinate (MAL) for three hours and they were illuminated with red light. Tolerance to treatment was

evaluated using a visual analog scale for pain (from 0 to 10). Results: A total of 15 patients with 134 VW were treated.

A complete response was obtained in 13 of 15 patients (87%) and in 127 of 134 lesions (95%). The mean number of

sessions was 3.1 (range 1 to 6) and the average pain score was 3.1 (range 0 to 8). Conclusions: PDT is a treatment that

offers good results in the treatment of VW that are resistant to routine treatment. The treatment was well tolerated in our

patient group.

Keywords: Photodynamic Therapy; Viral Warts; Red Light

1. Background

Photodynamic therapy (PDT) is a technique that is

increasingly being used for off-label indications. Viral

warts (VW) are one of the most promising indications.

Previous studies indicate clearances of between 42% -

92% of lesions with aminolevulinic acid (ALA) and

different incoherent light sources [1,2]. The primary li-

mitation of this treatment is pain.

2. Objective

The purpose of our study was to evaluate the results of

PDT in the treatment of VW with methyl aminole-vu-

linate (MAL) and red light and to evaluate treatment

tolerance.

3. Material and Methods

A retrospective, descriptive, observational study was

carried out. Patients who did not respond to at least one

correctly-applied routine treatment, always including

cryotherapy, were selected. After curettage of the lesions,

MAL was occluded for 3 hours and illuminated with red

light (Aktilite®, 630 nm, 37 J/cm2, 8 minutes). Three

sessions were applied, once per week for three weeks.

The patient rested for three-week and another three-week

cycle was applied (once per week) until a response was

obtained. Afterwards, patients were subjected to quar-

terly follow-up for one year without treatment. Pain was

measured after each session using a visual analog scale

of 0 to 10.

4. Results

A total of 15 patients with 134 VW were treated (Table 1)

A complete response was obtained in 13 of 15 patients

(87%) and in 127 of 134 lesions (95%), see Figures 1

and 2. The mean number of sessions was 3.1 (range 1 to

6) and the average pain score was 3.1 (range 0 to 8).

5. Discussion

VW is a common pathology that is treated with kera-

tolytics, cryotherapy, electrocoagulation and antimitotic

agents (podophyllin, bleomycin, retinoids). More re-

cently, new therapeutic approximations have been used

with immunomodulators such as imiquimod cream, laser

or PDT. Cryotherapy continues to be the most widely

used treatment due to its simplicity, safety, speed, effi-

cacy and low cost. However, it is not uncommon to en-

counter persistent VWs despite multiple cryotherapy ses-

sions.

There are several mechanisms of action that explain

the antiviral properties of PDe HPV-infected T. First, th

*Corresponding author.

Treatment of Recalcitrant Viral Warts with Photodynamic Therapy with Mal and Red Light

118

Table 1. Results of the treatment.

NUMBER OF

PATIENTS

NUMBER OF

LESIONS

COMPLETE

RESPONSE/PATIENT

COMPLETE

RESPONSE/LESION

NUMBER OF

SESIONS (RANGE)

PAIN

(RANGE)

134

-3 sole

-7 periungual

-123 hands

13/15

87%

127/134

95%

46/15

3.1

(1 - 6)

39/15

2.6

(0 - 8)

Table 2. Published studies on PDT for verruca vulgaris.

AUTHOR/

YEAR

NO.

VW PS

OCCLUSI

(hours)

LIGHT

SOURCE

LIGHT

DOSAGE

(J/cm2)

NO. OF

SESSIONS

RESPONSE

(%) COMMENTS

Stender

1999 250 ALA 5 White, blue or

red 40 3 73-42-28% -White light is more effective

Stender

2000 232 ALA 4 Waldman

590 - 700 nm 70 2 - 5 56% -Statistically significant compared to placebo

Fabbrocini

2001 64 ALA 5 Tunsten

400 - 700 nm 50 Maximum of 975% -Curettage and keratolytics

Schroeter

2005 48 ALA 4-8 Versalight

400 -720 nm 100 1 - 7

(mean 2.3) 88%

Ziolkowski

2006 18 ALA 4 Waldman

400 - 700 nm 70 1 - 6 67% -Previous treatment with 3% azone

-Group without azone had a 37% response

Schroeter

2007 40 ALA 5 Versalight

400 - 720 nm 100 1 - 13

(mean 4.5) 90% -No recurrences at 6 months

Wang 2007 12 ALA 4 Waldman

400 - 700 nm 50 2 - 4

(mean 3.6) 42% -4/12 severe pain persisted for 24 hours

Yoo 2009 40 MAL 3 Aktilite 630 nm 50 1 - 3

(mean 2.2) 90% -Uses first CO2 laser

Lu 2010 18* ALA 4 635 nm laser 120 Maximum 394% -Flat warts

Fernandez-

Guarino

2010

235 MAL 3 PDL 395 nm 7mm

9 J/cm2

Maximum of 6

(mean 5.25)53% -No incomplete responses obtained

-Response per patient: 26%

NO.: number; VW: Viral wart; PAC: patients; PS: photosensitizer; PDL: Pulsed dye laser; *: Number of patients with flat warts.

Figure 1. Image of a plantar wart previous to treatment

with photodynamic therapy.

cells proliferate more rapidly than normal circulating

cells. This leads to selective accumulation of the pho-

tosensitizer [3]. On the other hand, PDT has been shown

to destroy infected keratinocytes and inactivate viral

Figure 2. Image of the same plantar wart after five sessions

of treatment with photodynamic therapy (MAL, red light,

630 nm, 37 J/cm2, 8 minutes).

Replication [4]. Giomi, in an interesting recently publi-

shed study, studied the immunological response of PDT

on genital warts [5]. He found a progressive increase in

Treatment of Recalcitrant Viral Warts with Photodynamic Therapy with Mal and Red Light 119

perilesional CD4 T-lymphocytes during the first month.

These findings appear to suggest that there is an ability

of PDT to induce a specific immune response.

There are several published studies on the use of PDT

in VW (see Table 2) [2,6-14]. These studies found an

efficacy of 42% - 90%. The first studies were by Stender

[6,7] ALA and found that white light is more effective

than red or blue. The majority of studies use ALA as the

photosensitizer and long wave light sources and red

surroundings in order to achieve greater penetration. One

of the studies uses a diode laser with a very good res-

ponse in flat warts (94%) [13] and another uses a pulsed

dye laser in verruca vulgaris with a more moderate res-

ponse [14]. All used repeated sessions in order to achieve

a response in the lesions and all noted that the use of

ablative methods prior to PDT (keratolytics, azone, CO2

laser) increases the response to treatment by favoring

penetration of the photosensitizer and the light source.

[10,11,14] Few studies had a long patient follow-up.

Only one evaluated the response at 6 months [2]. Our

results are good if we compare them to the published

literature, though our study included a small patient series.

Without a doubt, the most limiting factor for treating

VWs with PDT is the pain, which occurs in all treatment

modalities, and leads to discontinuing the session in up to

20% of patients. [15] The pain is characteristically in-

tense and persists for up to 24 hours after treatment. It is

very notable that patients tolerated the pain well in [16]

our study (mean pain of 3.1) versus previous publications.

When we begin to apply PDT in the treatment of VW,

we select laser as the light source in order to try and

improve tolerance to treatment [14]. However, we have

achieved better tolerance with red light.

PDT with MAL and red light is a promising treatment

that is well tolerated in the management of VWs that are

resistant to standard treatments. Nevertheless, there are

few studies of adequate sample size and design that sup-

port its scientific evidence, so new studies on this subject

are needed.

REFERENCES

[1] I. M. Stender, J. Lock-Anderson and H. C. Wulf, “Recal-

citrant Hand and Foot Warts Successfully Treated with

Photodynamic Therapy with Topical Aminolaevulinic

Acid: A Pilot Study,” Journal of Clinical & Experimental

Dermatology, Vol. 24, No. 3, 1999, pp. 154-159.

doi:10.1046/j.1365-2230.1999.00441.x

[2] C. A. Schroeter, L. Kaas, J. J. Waterval, P. M. Bos and H.

A. Neumann, “Successful Treatment of Periungual Warts

Using Photodynamic Therapy: A Pilot Study,” Journal of

the European Academy of Dermatology and Venereology,

Vol. 21, No. 9, 2007, pp. 1170-1174.

[3] E. V. Ross, R. Romero, N. Kollias, C. Crum and R. R.

Anderson, “Selectivity of Protoporphyrin IX Fluorescence

for Condylomata after Topical Application of 5-Aminol-

aevulinic Acid: Implications for Photodynamic Treat-

ment,” British Journal of Dermatology, Vol. 137, No. 5,

1997, pp. 736-742.

doi:10.1111/j.1365-2133.1997.tb01110.x

[4] J. North, H. Neyndorff, D. King and J. G. Levy, “Viral

Inactivation in Blood and Red Cell Concentrations with

Benzoporphyrin Derivative,” Blood Cells, Vol. 18, No. 1,

1992, pp. 129-139.

doi:10.1111/j.1365-2133.2010.10089.x

[5] B. Giomi, F. Pagnini, A. Cappuccini, B. Bianchi, L. Ti-

radritti and G. Zuccati, “Immunological Activity of Photo-

dynamic Therapy of Genital Warts,” British Journal of

Dermatology, Vol. 164, No. 2, 2011, pp. 448-451.

[6] I. M. Stender, J. Lock-Anderson and H. C. Wulf, “Recal-

citrant Hand and Foot Warts Successfully Treated with

Photodynamic Therapy with 5-Aminolaevulinic Acid. A

Pilot Study,” Journal of Clinical & Experimental Der-

matology Research, Vol. 24, No. 3, 1999, pp. 154-159.

doi:10.1046/j.1365-2230.1999.00441.x

[7] I. M. Stender, R. Na, H. Fogh, C. Gluud and H. C. Wulf,

“Photodynamic Therapy with 5 Aminolaevulinic Acid

Placebo for Recalcitrant Foot and Hand Warts: Random-

ized Double Blind Trial,” Lancet, Vol. 355, No. 9208,

2000, pp. 963-966.| doi:10.1016/S0140-6736(00)90013-8

[8] G. Fabbrocini, M. P. Constanzo, A. M. Riccardo, M.

Quarto, A. Colasanti, G. Roberti, et al., “Photodynamic

Therapy with Topical 5-Aminolaevulinic Acid for the

Treatment of Plantar Warts,” Journal of Photochemistry

and Photobiology B, Vol. 61, No. 1, 2001, pp. 30-34.

doi:10.1016/S1011-1344(01)00141-5

[9] C. A. Schroeter, J. Pleunis, V. N. Tot Pannerden, T. Re-

inneke and H. A. Neumann, “Photodynamic Therapy:

New Treatment for Therapy Resistant Plantar Warts,” Der-

matologic Surgery, Vol. 31, No. 1, 2005, pp. 71-75.

doi:10.1111/j.1524-4725.2005.31011

[10] P. Ziolkowski, B. J. Osiecka, M. Siewinski, A. Brono-

wicz, J. Ziolkowska and H. Gerber-Leszczyszyn, “Pre-

treatment of Plantar Warts with Azone Enhaces the Ef-

fects of 5-Aminolaevulinic Acid Photodynamic Therapy,”

Journal of Environmental Pathology Toxicology and On-

cology, Vol. 25, No. 1-2, 2006, pp. 403-409.

doi:10.1615/JEnvironPatholToxicolOncol.v25.i1-2.250

[11] C. A. Schroeter, L. Kaas, J. J. Waterval, P. M. Bos and H.

A. Neumann, “Successful Treatment of Periungual Warts

Using Photodynamic Therapy: A Pilot Study,” Journal of

the European Academy of Dermatology and Venereology,

Vol. 21, No. 9, 2007, pp. 1170-1174.

[12] Y. S. Wang, Y. K. Tay, C. Kwok and E. Tan, “Photody-

namic Therapy with 20% Aminolevulinic Acid for the

Treatment of Recalcitrant Viral Warts in an Asian Popu-

lation,” International Journal of Dermatology, Vol. 46,

No. 11, 2007, pp. 1180-1184.

doi:10.1111/j.1365-4632.2007.03210.x

[13] K. H. Yoo, B. J. Kim and M. N. Kim, “Enhanced Effi-

cacy of Photodynamic Therapy with Methyl-5-Aminol-

aevulinic Acid in Recalcitrant Periungual Warts after Ab-

lative Carbon Dioxide Fractional Laser: A Pilot Study,”

Dermatologic Surgery, Vol. 35, No. 12, 2009, pp. 1927-

Treatment of Recalcitrant Viral Warts with Photodynamic Therapy with Mal and Red Light

120

1932. doi:10.1111/j.1524-4725.2009.01307.x

[14] Y. G. Lu, J. J. Wi, Y. He, H. Z. Yang and Y. D. Yang,

“Efficacy of Topical Aminolevulinic Acid Photodynamic

Therapy for the Treatment of Verruca Planae,” Photo-

medicine and Laser Surgery, Vol. 28, No. 4, 2010, pp.

561-563. doi:10.1089/pho.2009.2566

[15] M. Fernández-Guarino, A. Harto and P. Jaen, “Treatment

of Recalcitrant Viral Warts with Pulsed Dye Laser MAL-

PDT,” Journal of Dermatological Treatment, Vol. 22, No.

4, 2011, pp. 226-228.

[16] I. M. Stender, F. M. Borgbjerg, J. Villumsen, J. Lock-

Andersen and H. C. Wulf, “Pain Induced by Photody-

namic Therapy of Warts,” Photodermatology, Photoim-

munology & Photomedicine, Vol. 22, No. 6, 2006, pp. 304-

309. doi:10.1111/j.1600-0781.2006.00259.x