Journal of Dermatological Treatment

ISSN: 0954-6634 (Print) 1471-1753 (Online) Journal homepage: http://www.tandfonline.com/loi/ijdt20

Do Sunscreen Prevent Recurrent Herpes Labialis in

Summer?

Vittorio Mazzarello, Marco Ferrari, Gabriella Piu, Valeria Pomponi & Giuliana
Solinas

To cite this article: Vittorio Mazzarello, Marco Ferrari, Gabriella Piu, Valeria Pomponi & Giuliana
Solinas (2018): Do Sunscreen Prevent Recurrent Herpes Labialis in Summer?, Journal of
Dermatological Treatment, DOI: 10.1080/09546634.2018.1481921

To link to this article: https://doi.org/10.1080/09546634.2018.1481921

Accepted author version posted online: 28

May 2018.

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DO SUNSCREEN PREVENT RECURRENT HERPES LABIALIS IN SUMMER?

Sunscreen preventing Herpes labialis

Manuscript word: 2568 Tables: 2

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Vittorio Mazzarello1, Marco Ferrari1, Gabriella Piu1, Valeria Pomponi1, Giuliana Solinas2

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Skinlab, Department of Biomedical Sciences, University of Sassari, Italy
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Laboratory of Biostatistics, Department of Biomedical Sciences, University of Sassari, Italy
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Corresponding author: Vittorio Mazzarello MD, Skinlab, Department of Biomedical Sciences, University of Sassari,

Viale San Pietro 43, 07100 Sassari, Italy. Tel: +39079228536 Fax: +39079228520 E-mail: vmazza@uniss.it
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Funding sources: This article has no funding source.

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Conflict of interest: The authors have no conflict of interest to declare.

Abstract

Background: Research results on the efficacy of sunblock sticks in avoiding or reducing herpes

labialis (HL) recurrences are contradictory and has shown mixed results, with some protection

reported under experimental conditions that could not be replicated under natural conditions.

Objective: The purpose of the present work was to carry out an in vivo test on the effectiveness of a

protective lip product in preventing recurrent HL in natural conditions during summer.

Methods: An exploratory randomized crossover study was performed on 20 adult volunteers who

served as their own controls during the analysis. The study was conducted between May and July

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2017 around the summer solstice. During the 2- month period, volunteers had to perform normal

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daily activities and go to the beach in Sardinia; thirty subjects applying SPF 30 protection and thirty

without protection.

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Results: In individuals with stick protection, the number of HL attacks was significantly reduced.
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Based on association between different parameters, which emerged from the medical history and

the post-test questionnaire, it was found that male individuals over 44 years of age and with
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Fitzpatrick skin type 2 were the most exposed to recurrence.

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Conclusion: HL recurrence rate can be reduced by using sunblock stick in summer.

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Keywords: Herpes labialis; YV exposure; sunblock.

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Introduction

Herpes labialis (HL) is an infection of the mouth area that affects the area between the vermilion

border and the skin. The HL is caused by herpes simplex virus type 1 (HSV-1). The latter is a DNA

virus, with a diameter of 150-200 nm, which is transmitted by direct inter-human contact of herpetic

lesions or through healthy carriers saliva. Almost 100% of the adult population hosts the herpes

simplex virus (HSV) at the latent state and are therefore potentially exposed to HL, but only 20%,

due to a decline in cellular immunity, present with a form of recurrent herpes labialis (RHL) that

may occur with variable frequency. Several factors triggering HRL have been described: physical

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stress (general infections, menstrual cycle) and mental stress, drugs and sun exposure. Under the

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influence of these causes the viral reactivation occurs: the viral genome passes from cell to cell up

to the labial region where the virus replication will occur leading to the appearance of typical

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erythematous vesicular lesions. Several studies have shown a correlation between UV exposure and
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the onset of RHL.1-2-3 A systematic epidemiological review carried out in 2008 identified 9 diseases

that show sufficient evidence of a causal relationship with UV exposure: among these the HL
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reactivation is indicated.4 The 25%-50% of RHL occurrences are believed to be attributed to UV

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exposure as a consequence of local immunosuppression. The UV dose capable of triggering the

recurrence of the virus is equal to 4 MED.3 The recurrence time of RHL after exposure may be
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immediate (within 48 hours) or delayed (after 2-7 days);2 this is the time required for virus
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reactivation at the latency site, transport of the virus up to the skin surface (it is estimated that the

speed, demonstrated in vitro, is 3-5mm/hour) and virus replication in the epithelium with
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production of typical lesions (> 24 hours).5-6-7 Due to these reasons numerous sunblock sticks can

be found on the market, formulated to protect the vermilion and the surrounding skin from the

harmful effects of sun's rays, which are recommended as short-term preventive therapies. However,

research results on efficacy of these sticks in avoiding or reducing RHL recurrences are

contradictory and have shown mixed results, with some protection effect reported under

experimental conditions that could not be replicated under natural conditions. In fact, there are two
small randomized controlled trials with crossover design that have shown a reduction in relapses

after exposure to artificial ultraviolet with sun protection of the lips.3-8 In another study conducted

on 51 patients, which was performed under natural conditions, the use of a high protective factor

sunscreen lotion did not result in a lower incidence of HL.9 Because of these contradictions, the

purpose of our work was to test in vivo in natural conditions during the summer period the

effectiveness of a protective lip product in preventing RHL relapse.

Materials and Methods

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Product

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This lipstick with a Sun Protection Factor (SPF) 30 is produced by Kelemata srl (Torino, Italy),

having the following INCI composition: Aloe barbadensis leaf extract, Aroma, Beta-sitosterol, Bis-

diglyceryl polyacyladipate-2, Butyl

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methoxydibenzoylmethane, Butyloctyl salicylate,
an
Butyrospermum parkii butter, Caprylic/capric triglyceride, Cera alba, Dimethyl capramide,

Ethylhexyl methoxycinnamate, Glyceryl behenate, Glyceryl laurate, Helianthus annuus seed oil,
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Octocrylene, Olus oil, Parfum, Propolis cera, Retinyl palmitate, Ricinus communis seed oil,
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Squalene, Tocopherol.
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Participants
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Twenty healthy adults aged 18-55 with a history of RHL in summer (at least 1 attack) were

recruited at the Skinlab of the Department of Biomedical Sciences of the Sassari University Medical
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School (Sardinia, Italy) according to the principles of the current version of the Declaration of

Helsinki. Subjects with Fitzpatrick skin type 1 or 4, pregnant or lactating women, and those with a

history of contact hypersensitivity to cosmetic products or oral antiviral agents within 30 days

before enrolment were excluded. After meeting inclusion and exclusion criteria, informed consent

was obtained from each participant by the research coordinator.

Study design

An exploratory randomized crossover study was performed on 20 adult volunteers who served as

their own controls in the analysis. The sample size was estimated for crossover sample mean with

80% power, a value of delta=0.2 and significance level of α=0.05.10 The study was conducted

between May and July 2017 around the summer solstice; for each volunteer the study period lasted

sixty days: thirty with protection and thirty without protection. The month with or without product

application was randomly assigned to each patient so as 10 subjects started the trial without

protection and 10 with protection and the opposite during the following month. During the 2

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months, the volunteers had to perform normal daily activities and go to the beach in northern

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Sardinia (the same areas as in the previous years) during sunny days without clouds, at least once a

week staying at the beach at least for 3 hours around noon. The beach had to be at the latitude

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between the villages of Bosa and La Maddalena (between 40°.17 N and 41°.12 N). During the
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month when volunteers had to use a protection, they were requested to apply the sunblock stick

before going out or going to the sea on the vermilion and lip skin, 2 times consecutively creating a
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double protective layer. The protection was repeated every 2 hours, after eating or drinking,
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smoking and after a swim in the sea. At the end of each month, a questionnaire for statistical

elaboration of results was filled in at the Skinlab. The questionnaire contained questions about the
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number of days and hours spent on the beach, the beach location and how the stick had been used.
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In the case of HL, a clinical diagnosis with a Tzancke smear was performed and in doubtful cases a

viral test pad was used.

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Statistical Analysis

Results were tabulated using Microsoft Excel 2016 and analyzed using descriptive statistics. The

two-proportions z-test is used to compare two observed proportions of HL lesions. Further,

statistical evaluation of data was performed using non-parametric Wilcoxon signed-rank test. The
association between observed variables was evaluated with Spearman correlation. Statistical

package, Stata SE 15.0 was used for analysis with P < 0.05 considered as statistically significant.

Results

Demographic characteristics of the participants are shown in Table 1. All volunteers had at least one

RHL event on the same period during the previous year and six of them had more than one. During

the time period under the study with sunscreen, sixteen volunteers used the solar stick every day

and four subjects only at the seaside. During the test one subject (5%) out of twenty treated with

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sunblock stick developed HL. Instead ten subjects (50%) out of twenty non- treated with sunblock

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stick developed HL; one of the untreated subjects had two events of RHL. This difference was

statistically significant (z test=3.19, p-value=0.0014). Descriptive statistics, mean (SD) and p-value,

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between all observed variables are displayed in Table 2. Only the mean number of HL attacks
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between subjects with and without sun protection were statistically significant. The number of HL

attacks was analyzed by gender, age, number of sunny hours, Fitzpatrick skin type as exposure
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variables on number of HL events. Considering the distribution of age of sample, the 50th
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percentile (44 years) was chosen to divide the sample into two groups: group A with age <44 years

and group B with age ≥44 years. Only in female patients, the use of sunblock stick reduces
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significatively the number of events (z=-2.646, p=0.008). Likewise, in group A the number of
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events was significantly reduced (z= -2.828, p=0.0047). In individuals with stick protection and

Fitzpatrick skin type 3, the number of HL attacks was significantly reduced (z=-2.449, p=0.0143).
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The association between total sunny hours and number of events without protection of stick is not

significant (rho Spearman=0.21, P=0.38).

Limitations

This study was conducted on a small number of subjects to evaluate possible multivariable

associations between different parameters. However, a larger study is needed to confirm results.

Our study provides evidence for effect sizes that are needed for future sample size calculations.

Discussion

Ultraviolet light is a potent stimulus for the reactivation of HL: in a previous study lesions

developed in nearly three-quarters of patients in the placebo group when exposed to 4 MED of

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artificial UV light.3 In order to prevent or reduce the risks of reactivation, sunblock sticks are

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available on the market to be applied on lips during periods or conditions of increased sun exposure.

Two randomized controlled trials with a crossover design demonstrated, using a solar simulator, the

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effectiveness of lip sunscreens in reducing RHL after UV exposure. The first study was conducted
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on thirty-eight patients: it showed that after exposure to artificial ultraviolet, equal to 4 MED, HL

was developed in twenty-seven patients (71%) treated with placebo. In contrast, when SPF 15
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sunscreen was applied during UV exposure, no lesion developed on thirty-five patients.3 The
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second work carried out on nineteen individuals, exposed to four MED for ten minutes of ultraviolet

light under artificial conditions, found that sunscreen significantly reduces relapses compared to
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placebo: one on nineteen (5%) with sun protection against eleven on nineteen out of 19 (58%) with
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placebo.8 Despite these results, the protective efficacy of sunblocks against recurrence is still

contradictory because only one work has been carried out in natural conditions on fifty-one
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volunteer skiers showing that a SPF 15 sun screen compared to placebo was not effective to prevent

reactivation of the virus.9 Our exploratory study aimed to evaluate, under natural conditions, if a

solar SPF 30 stick was effective to reduce RHL in volunteers who suffer from this disease mainly

during summer. The environment chosen for the present study was a full sun exposure on the beach.

To avoid the influence of latitude on intensity of solar radiation we have imposed the frequency of

beaches within 40-41°. In fact, they showed a slight latitude gradient of RHL and all the forms of
HL appear to be more severe in warm climates, than in northern latitudes. 11-12-13 Rooney criticized

Mills's work by stating that the UV dose received by volunteer skiers received during the trial, the,

was 1-3 MED per day, which is lower than the 4 MED needed to trigger recurrence.3 Four MED is

a dose of UV light equivalent to 80 minutes of exposure under midday, mid-summer sun for fair

skinned, untanned individuals, at sea level.14 In the present study these values were reached and

exceeded by our volunteers several times during the 2 months of study. In fact, each volunteer

remained at the beach at around 12 am with an average of 4.5 ± 0.95 hours in the period with stick

and 4.3 ± 0.94 hours in the period without stick exceeding the aforementioned dose. Moreover, to

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make the total amount of solar irradiance equal in the two sequential study periods, the days at the

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time of the summer solstice (June 21) were selected, when the sun reaches its highest point in the

sky and chosen to use the stick randomly so that in the end ten patients used the sunblock lipstick

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and ten did not use anything neither in the per-solstice period (May-June) or the post-solstice period
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(June-July). Among other criticisms on Mills's work, it can be added that the amount of sunscreen

applied by skiers on the lips is not reported, unlike the two tests with artificial light where it is
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indicated that the sticks have been applied on lips with sufficient dose to respect the SPF value.
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Today it is recommended to spread the sunscreen on the skin in two layers in such a way that its

thickness is as close as possible to 2mg/cm2, which is what enables to achieve the expected SPF.15
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In our study, all volunteers were asked to apply the sunblock several times on the double-layer lips.
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Results demonstrated that sunscreen is effective in protecting the upper lip from reactivating the

HL. Actually, only one volunteer out of twenty had a RHL during the period of sunscreen use
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versus ten out of twenty without sunscreen during the studied period. One volunteer from the latter

had two sequential RHLs. These results are similar to those reported by Duteil in 1998. 8 The single

event during the period with labial photoprotection was unleashed in the last week, the eleven

events of the period without photoprotection appeared from the second week of exposure. All

lesions were clinically diagnosed with the help of Tzank's cytodiagnostic examination. From the

association between the different parameters, which emerged with the medical history and the post-
test questionnaire, it was found that male individuals with age above 44 years, and with Fitzpatrick

skin type 2 are the most exposed to recurrence. With age, the production of melanin is reduced and

is reduced in subjects with phototype 2 resulting in lower protection from UV rays. Males are more

at risk because perhaps they have a reduced compliance to drugs compared to female as shown in

several works.16 These individuals with RHL should protect vermilion and lips from UVs more than

others.

Conclusion

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In summary, our results indicate that the recurrence rate of HL can be reduced by using a sunblock

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stick with a SPF 30. In fact 50% of the 20 volunteers in this study developed HL during direct

summer sun exposition while only 5% among volunteers who applied a sunscreen.

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References
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1. Perna JJ el al. Reactivation of latent herpes simplex virus infection by ultraviolet light: a

human model. J Am Acad Dermatol. 1987; 17:473-8.

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2. Spruance SL et al. The natural history of ultraviolet radiation-induced herpes simplex

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labialis and response to therapy with peroral and topical formulations of acyclovir. J Infect

Dis. 1991; 163:728-34.

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3. Rooney JF et al. Prevention of ultravioletlight-induced herpes labialis by sunscreen. Lancet

1991; 338:1419–21.

4. Lucas RM et al. Estimating the global disease burden due to ultraviolet radiation exposure.

Int J Epidemiol. 2008; 3:654-67.

5. Openshaw Het al. Herpes simplex virus infection in sensory ganglia: immune control,

latency, and reactivation. Fed Proc. 1979; 38:2660-4.

6. Lycke E et al. Uptake and transport of herpes simplex virus in neurites of rat dorsal root

ganglia cells in culture. J Gen Virol. 1984 ;65:55-64.

7. Blank H et al. Experimental human reinfection with herpes simplex virus. J Invest Dermatol.

1973; 61:223-5.

8. Duteil L et al. Assessment of the effect of a sunblock stick in the prevention of solar-

simulating ultraviolet light-induced herpes labialis. J Dermatol Treat. 1998; 9: 11–4.

9. Mills J et al. Recurrent herpes labialis in skiers. Clinical observations and effect of

sunscreen. Am J Sports Med. 1987; 15:76–78.

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10. Chow S.C., Shao J. & Wang H. Sample Size Calculations in Clinical Research. Chapman

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and Hall/ CRC Press, New York, USA; 2003.

11. Young TB et al. Cross-sectional study of recurrent herpes labialis. Prevalence and risk

factors, Am J Epidemiol. 1988; 127:612-25.

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12. Axell T et al. Occurrence of recurrent herpes labialis in an adult Swedish population. Acta

Odontol Scand. 1990; 48:119-23.

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13. Reichart PA. Oral mucosal lesions in a representative cross-sectional study of aging
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Germans, Community Dent Oral Epidemiol. 2000, 28:390-98.

14. Pathak MA, Fitzpatrick TB, Greitor F, Kraus EW. Preventive treatment of sunburn,
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dermatoheliosis, and skin cancer with sun protective agents. Dermatology in general
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medicine. 3rd ed. New York:, McGraw Hill; 1987:1507-22.

15. Teramura T et al. Relationship between sun-protection factor and application thickness in
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high-performance sunscreen: double application of sunscreen is recommended. Clin Exp

Dermatol. 2012; 37:904-8.

16. Kyngas H, Lahdenpera T. Compliance of patients with hypertension and associated factors.

J Ad Nurs. 1999; 29:832–9.

Demographics of subjects

Characteristic Frequency

n 20
drop-out 0
Male 8
Female 12
White 20
Black 0

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Asian 0
Fitzpatrick skin type 2 10

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Fitzpatrick skin type 3 10

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Age (range) 30 - 54
Age (mean and SD) 43.5 (6.51)
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Number HLR june 2016 17
Mean and SD 0,85 (0,68)
Number HLR july 2016 16
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Mean and SD 0,8 (0,76)

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Table 1 - Demographics of the volunteers enrolled in this study.

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 total sunny
Experimental periods beach days hours/day at sea RHL attacks
hours
Pre-solstice - 10 volunteers with
7,9 (4,24) 4,35 (0,95) 35,5 (22,7) 0,3 (0,47)
sunscreen and 10 without
Post-solstice - 10 volunteers with
9,9 (6,57) 4,45 (0,94) 43,25 (29,3) 0,3 (0,57)
sunscreen and 10 without
p-value 0,369 0,687 0,439 0,807
Pre and Post-solstice - 20 volunteers
8,45 (4,66) 4,5 (0,96) 38,7 (24,6) 0,05 (0,22)
with sunscreen

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Pre and Post-solstice - 20 volunteers
9,35 (6,49) 4,3 (0,92) 40,05 (28,4) 0,55 (0,60)
without sunscreen

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p-value 0,902 0,421 0,956 0,0016

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Table 2 - Descriptive statistics, mean (SD) and p-value, between all observed variables.
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Table Legend
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Table 1 - Demographics of the volunteers enrolled in this study.

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Table 2 - Descriptive statistics, mean (SD) and p-value, between all observed variables. Pre-

solstice period corrisponding to end of May to June, before the summer solstice. Post-solstice
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period: end of June to July. Due to randomization of these periods we had 10 subjects with
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sunscreen and 10 without sunscreen alternating. During the two periods no differences in solar

exposure are reported: only the mean number of HL attacks between subjects with and without

protection resulted statistically significant.