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Dermatologic Therapy, Vol. 21, 2008, S35–S38 Printed in the United States · All rights reserved

© 2008 Wiley Periodicals, Inc.

DERMATOLOGIC THERAPY

ISSN 1396-0296

Blackwell Publishing Inc

Sensitizing potential of triclosan and triclosan-based skin care products in patients

with chronic eczema

D

ONATELLA

S

CHENA

, A

NASTASIA

P

APAGRIGORAKI

& G

IAMPIERO

G

IROLOMONI

Section of Dermatology and Venereology, Department of Biomedical and Surgical Sciences, University of Verona, Verona, Italy

ABSTRACT:

Triclosan is a lypophilic chlorophenol biocide with broad-spectrum antibacterial andantifungal activity. Triclosan-based topical products have been shown to be tolerated and beneficialin atopic dermatitis. The aim of this study was to evaluate the sensitizing potential of triclosan andtriclosan-based creams in patients affected by eczematous dermatitis. Two hundred and seventy-fivepatients affected by chronic eczema (allergic contact dermatitis, irritant contact dermatitis, atopiceczema, nummular eczema, stasis dermatitis) were patch tested with standard patch test series aswell as triclosan and triclosan-based products. Standard patch test series resulted positive in 164patients (61%), with nickel sulfate, house dust mites, fragrance mix, propolis, thimerosal, myroxylonpereira, potassium dichromate, wool alcohols, and p-phenylenediamine the most common sensitizinghaptens. Only two patients developed positive reactions to triclosan (0.7%) and four (1.4%) totriclosan-based products. The present study’s results confirm that triclosan is well tolerated and has avery low sensitizing potential even in high-risk patients affected by eczema.

KEYWORDS:

allergic contact dermatitis, chronic eczema, sensitization, triclosan

Introduction

Triclosan (2,4,4

′

-trichloro-2-hydroxydiphenyl ether)is a stable, lypophilic chlorophenol biocide withbroad-spectrum antibacterial and antifungalactivity. It is generally more effective againstgram-positive than in gram-negative bacteria ormoulds. Triclosan functions through multiplemechanisms of action, but as a biocide it actsprincipally by disruption of cell membranes. Atbacteriostatic and sub-bacteriostatic concentrationsit affects enoyl reductase-mediated fatty acid syn-

thesis (1,2). Some microorganisms such as

Myco-bacterium tuberculosis

,

Pseudomonas aeruginosa

,and

Malassezia

species are intrinsically extremelyresistant (3,4). Triclosan has been safely used formany years across a broad range of dental,medical, cosmetic (emollient, soaps, deodorants,toothpastes, mouthwash), and household products.More recently, it has been increasingly used inthe management of atopic dermatitis and contactdermatitis, as well as in the prevention of infectionsin intensive care units (4–6). Indeed, triclosan hasa low toxicity and its use is associated with a verylow incidence of contact sensitization and irrita-tion even when applied on damaged skin (6). Theaim of this study was to evaluate the sensitizingpotential of triclosan and triclosan-based topicalagents in high-risk populations such as patientsaffected by chronic eczema and sensitized to dif-ferent haptens.

Address correspondence and reprint requests to: Donatella Schena MD, Clinica Dermatologica, Ospedale Civile Maggiore, Piazzale A. Stefani 1, 37126 Verona, Italy, or email: donatella.schena@azosp.vr.it.

Schena et al.

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Materials and methods

Two hundred and seventy-five patients wereenrolled. They were 169 women and 106 men,with an age range of 1–85 years, and a mean andmedian age of 42.2 and 42 years, respectively.Fifty-five patients were affected by atopic dermatitis,122 by allergic contact dermatitis, 62 by irritantcontact dermatitis, 20 by stasis dermatitis, and 16patients by nummular eczema. All patients weresubmitted to patch testing with the standardseries (Firma, Florence, Italy) elaborated by theItalian Society of Allergological, Occupational,and Environmental Dermatology (SIDAPA series,www.sidapa.com), and were also patch testedwith triclosan 2% in petrolatum, and triclosan-containing creams (product 1 ENVINCER3 magraand product 2 ENVINPLUS magra, Envicon, Verona,Italy). Product 1 is an O/W cream containing otherthan triclosan 0.3%, piroctone olamine 0.1%,tocopheryl acetate, phospholipids, glycyrrhetinicacid, ceramide 3, and cholesterol; product 2 is anO/W cream containing other than triclosan 0.3%,piroctone olamine 0.1%, glycyrrhetinic acid, bis-abolol, tocopheryl acetate, and phospholipids.Patch tests were carried out with Haye’s testchambers applied onto the back and left in placefor 2 days. Readings were performed after 48 and96 hours, and scored according to the recommen-dation of the International Contact DermatitisResearch Group (7). Subjects sensitized to triclosan,product 1, and product 2 also underwent repeatedopen application test (ROAT).

Results

In this study the present authors wanted to evalu-ate the sensitizing potential of triclosan in high-risk patients affected by chronic eczema andsensitized to different haptens. One hundred andsixty-four patients (61%), 120 women and 44 men,showed reactive to at least one hapten of the stan-dard patch test series (FIG. 1). Patients affected byallergic contact dermatitis (122 of 275; 44.36%)were always positive to one or more haptens, withthe following top five most frequent haptens:nickel sulfate (38 patients; 31.1%), dermato-phagoides (34 patients; 27.9%), fragrance mix (16patients; 13.1%), propolis (11 patients; 9%), andKathon CG (6 patients; 4.9%). Patients with irritantcontact dermatitis (62 of 275; 23.6%) showedpositive to standard patch test series in 39 cases(63%), although in none of the patients was thisreactivity judged relevant to the eczema. Patients

with atopic dermatitis (55 of 275; 20%) demon-strated positive patch test reaction in 39 cases(71%), with the following top five most repre-sented haptens: nickel sulfate (15 patients; 27.3%),dermatophagoides (7 patients; 12.7%), propolis(7 patients; 12.7%), fragrance mix (6 patients;10.9%), and thimerosal (6 patients; 10.9%). Patientsaffected by stasis dermatitis (20/275; 7.27%) andnummular eczema (16/275; 5.81%) resulted posi-tive in 11 (45%) and 5 cases (31.3%), respectively.The haptens inducing positive patch test reac-tions are listed in Table 1. Seventy-seven patients(28%) showed reactivity to multiple haptens, with34 (12.3%) and 33 (12%) patients reactive to atleast two or three different haptens, respectively.

Table 2 reports the results and the clinicaldetails of patients showing sensitization to triclosanor triclosan-based products. Only 6 of 275 patients(2.1%), 3 women and 3 men, showed hyper-reactivity to at least one of the three additionalsubstances (triclosan, product 1 and product 2).Two of 275 patients (0.7%) showed positive patchtest reaction to triclosan alone. They were affectedby perioral irritant contact eczema in one caseand allergic contact eczema to thimerosal of theeyelids in the other. Four patients resultednegative to triclosan alone, but showed a strongor severe patch test reaction to product 1 and/orproduct 2. These patients had allergic contactdermatitis either localized to arms and legs ordiffuse, and resulted sensitized also to haptens ofthe standard series. ROAT showed positive reac-tions in five of the six patients: four of them sensi-tized to product 1 and/or product 2 (compoundallergy) and only one of them to triclosan. The fourpatients sensitized to product 1 and/or 2 under-went further patch test with all the ingredients ofthe creams, and demonstrated sensitization to

FIG. 1. Results of patch testing. ACD, allergic contactdermatitis; ICD, irritated contact dermatitis.

The sensitizing potential of triclosan

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piroctone olamina in only one case; the otherthree patients were negative and interpreted likecompound allergy. None of the 88 atopic patients,55 of them affected by atopic dermatitis, resultedsensitized to one or more of additional substances(triclosan, product 1, and product 2). Finally, onlythree patients showed irritant reaction to patchtest with triclosan.

Discussion

The results of the present authors’ study demon-strate a very low prevalence of sensitization totriclosan (2 of 275 patients; 0.7%) and to twoleave-on products containing triclosan (4 of 275patients; 1.4%) in a population of patients at highrisk of sensitization. Indeed, the present authorstested patients affected by different type ofeczema, including patients with atopic dermatitisand stasis dermatitis. The previously mentioned

results are in accordance with published datareporting infrequent contact sensitization totriclosan (8,9). The Swiss Contact DermatitisResearch Group reported a prevalence of sensit-ization to triclosan of 0.8% in a large studyinvolving 2,295 patients (10). Other studies haveconfirmed a low incidence of sensitization totriclosan mainly induced by the use of triclosan-containing deodorants (11).

Triclosan is increasingly used in preventinginfections in intensive care units as differentstudies have documented the elimination ofmethicillin-resistant

Staphylococcus aureus

formby using hand detergents based on triclosan (12–14). Moreover, controlled studies have shown theefficacy of triclosan in the treatment of moderateto severe atopic dermatitis and contact dermatitis(12,15,16), with reduced skin colonization bydifferent bacteria and

Candida

spp., and also withsubstantial improvement of pruritus and skinsigns (15,16). Besides, it has been demonstrated

Table 1. Haptens that induced a positive patch test reaction

Hapten Positive patients Hapten Positive patients

Nickel sulfate 50 (18.2%) Carba mix 6 (2.2%)Dermatophagoides 47 (17.1%) Cobalt chloride 6 (2.2%)Fragrance mix 21 (7.6%) Thiuram mix 6 (2.2%)Propolis 18 (6.5%) Colophony 5 (1.8%)Thimerosal 16 (5.8%) Goldsodiumthiosulfate 5 (1.8%)Myroxylon pereirae 14 (5.1%) Neomycin sulfate 5 (1.8%)Potassium dichromate 13 (4.7%) 4-tert-Butylformaldehyde resin 4 (1.4%)Kathon 9 (3.2%) Formaldehyde 4 (1.4%)Wool alcohols 9 (3.2%) Ethylenediamine dihydrochloride 3 (1.1%)p-Phenylenediamine (PPD) 7 (2.5%) Phenol formaldehyde resin 2 (0.7%)

Table 2. Patch tests, ROAT results, and clinical details of patients with sensitized and/or irritated reactionat triclosan and triclosan based skin products

Sex Age Diagnosis Location

Path test 1

ROAT

Patch test 2

SIDAPA series Triclosan Product 1 Product 2Ingredients

of the creams

F 65 ICD Perioral – – – + + – – – – – – – – – – – –M 27 ACD Eyelids Thimerosal + + + + – – – – – – + + – – –F 77 ACD Generalized Kathon + + PPD + + + – – – + + – – – + + – – –F 42 ACD Elbows, legs Nickel sulphate + + – – – + + + + + + Piroctone

olamine + +M 67 ACD Back Potassium

Dichromate + + Carba mix + +

– – – – – + + + + + + – – –

M 22 ACD Arms, legs Potassium Dichromate + +

– – – + + + + + + – – –

F, female; M, male; S, Skin; R, respiratory; ICD, irritant contact dermatitis; ACD, allergic contact dermatitis; – – – , negative; +, weak reaction; + +, strong reaction; + + +, extreme reaction.

Schena et al.

S38

that triclosan can decrease the wheal induced byintradermal injection of histamine. Triclosan,being a lipophilic phenol, penetrates the skin andstabilizes the lipid membranes, which is a majoraspect of phenol’s biological activity. Lipid-solublephenols interact with and inactivate the prostag-landins or other lipid inflammatory mediatorsdirectly, or may affect their synthesis by interactionwith precursors. This property partly explainstriclosan’s antiinflammatory effect (17). Anotherstudy has shown that triclosan can decrease theeffect of topical application of nickel in sensitizedpatients and reduce the effects of topical applica-tion of sodium lauryl sulfate by inhibiting thecyclooxygenase and lipooxygenase pathways ofarachidonic acid and prostaglandin E

2

production(18). The development of resistance to triclosanand its transferability have been demonstrated bysome authors who do not agree with the extensiveuse of this biocide that potentially may result inthe selection of resistant organism. Indeed, thereis some evidence that exposure to triclosan inclinical use results in the emergence of

Escherichiacoli

and

Salmonella enterica

strains that areresistant to triclosan, but these microorganismsare not relevant to the skin environment (4). More-over, change in triclosan susceptibility did notaffect susceptibility toward chemically unrelatedantimicrobials.

In conclusion, triclosan, product 1, and product2 are well tolerated and are rarely sensitizingin patients affected by chronic eczema. Noneof the patients affected by atopic dermatitisshowed sensitized to triclosan or triclosan-basedproducts, and therefore these products can besuitable for pathogen reduction and improvementof this disease.

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