Occupational airbornecontact allergy tocyanamide and dibenzylphosphite

Caterina Foti1, Domenico Bonamonte1,Mauro Carino2, Valentina Mastrandrea1 andGianni Angelini1

1Department of Internal Medicine,Immunology and Infectious Diseases – Unitof Dermatology, University of Bari, and2Salvatore Maugeri Foundation, Care andResearch Institute, Division of OccupationalMedicine, Cassano Murge, Bari, Italy

Key words: airborne contact allergy;chemical workers; cyanamide; dibenzylphosphite; occupational; phosphorylcreatine.

Case Report

A 45-year-old man had been employedas a chemical worker since 1996 inan industry producing pro-drugs. InMay 2001, the factory began toproduce phosphorylcreatine, with ahalf-enclosed working cycle, and ourpatient was deputed to supervise itssynthesis. After 20 days, he developedsevere eczematous dermatitis withdiffuse, symmetrical involvement ofthe face, including the eyelids, theregion under the chin and the retroauri-cular folds. The symptoms disappearedwhen away from the workplace, withthe aid of topical corticosteroidtreatment and systemic antihistamines.On return to work on the same job, thepatient developed a new dermatitisepisode. He was then relocated to adifferent area of the plant and thedermatitis did not recur.

The patient was patch tested withthe Italian Society of Allergological,Occupational and EnvironmentalDermatology (SIDAPA) standardseries with negative results. Furtherpatch testing was performed withthe substances used in the synthesisof phosphorylcreatine (Table 1).Readings were made on D2 and D4.

The patient showed positive reactionsto dibenzyl phosphite, cyanamideand phosphorylcreatine. Photopatchtests with the above substances werenegative. 5 healthy volunteers werenegative to cyanamide 1% pet. anddibenzyl phosphite 0�1% pet.

Discussion

Phosphorylcreatine synthesis includesthe use of sarcosine methyl esterhydrochloride, dibenzyl phosphiteand cyanamide as reagents. Mostlikely, sensitization to phosphoryl-creatine was due to the presence ofdibenzyl phosphite and cyanamideresidues, because patch tests withphosphorylcreatine pure grade 5%and phosphorylcreatine pure grade1% gave a weak positive and a nega-tive reaction, respectively. Cyanamideis an organic amide used in differentsettings, such as in chemistry, inantirust solutions, or in drugs fortreating alcoholism. There have beensporadic reports of contact dermatitisfrom cyanamide, especially in health-care workers preparing and adminis-

tering drugs to treat alcoholism (1, 2).Calnan reported a case of a positivepatch test to cyanamide in a chemistwho had handled the substance (3).

To our knowledge, this is the1st report of allergic contact derma-titis from dibenzyl phosphite [phos-phonic acid bis(phenyl-methyl)ester:(HO)P(OCH2C6H5)2] (Fig. 1), a sub-stance used in the pharmaceuticalindustry as a phosphorylating agentfor converting pro-drugs.

The eczematous dermatitis weobserved affected a chemical workerdelegated to quality control proce-dures in the industrial synthesis ofphosphorylcreatine. Chemical work-ers not directly involved in industrialproduction processing, but assignedto supervising or coordinating plantprocedures, are usually considered atlow risk of occupational dermatitis(4). For this reason, they may becomeinclined to disregard the use of pro-tective measures because they are notdirectly exposed to chemical prod-ucts. In our case, the failure toobserve protective measures and thepresence of phosphorylcreatine and

Table 1. Patch test results

D2 D4

SIDAPA standard series – –Benzyl alcohol 1% pet. – –Cyanamide 1%, 0�1% and 0�01% pet. þþ þþPhosphorylcreatine raw 5% and 1% pet. þþ þþPhosphorylcreatine ‘pure grade’ 5% pet. þ þPhosphorylcreatine ‘pure grade’ 1% pet. – –Pyridine 1% pet. – –Dibenzyl phosphite 1%, 0�1%, 0�01% and 0�001% pet. þþ þþSarcosine methyl ester hydrochloride 5% pet. – –

SIDAPA¼ Italian Society of Allergological, Occupational and Environmental Dermatology.

O

OO

H

P

Fig. 1. Chemical structure of dibenzyl phosphite.

CONTACT POINTSCONTACT DERMATITIS: 2003 48: 272–290 * ISSN 0105-1873 * COPYRIGHT # BLACKWELL MUNKSGAARD 2003 * ALL RIGHTS RESERVED

* CONTRIBUTIONS TO THIS SECTION WILL NOT UNDERGO PEER REVIEW, BUT WILL BE REVIEWED BY THE EDITOR *

its reagents in the environmentfavoured the onset of airborne aller-gic contact dermatitis.

References

1. Goday Bujan J J, Yanguas Bayona I,Soloeta Arechavala R. Allergic con-tact dermatitis from cyanamide: reportof 3 cases. Contact Dermatitis 1994:31: 331–332.

2. Conde-Salazar L, Guimaraens D,Romero L, Harto A. Allergic contactdermatitis to cyanamide (carbodiimide).Contact Dermatitis 1981: 7: 329–330.

3. Calnan C D. Cyanamide. ContactDermatitis Newsletter 1970: 7: 150.

4. Jolanki R & Kanerva L. Chemists. In:Handbook of Occupational Dermatology,Kanerva L, Elsner P, Wahlberg J E,Maibach H I (eds): Berlin, Heidelberg,New York, Springer-Verlag, 2000:882–885.

Address:Prof Caterina FotiClinica DermatologicaPoliclinicoPiazza Giulio Cesare, 1170124 BariItalyTel: þ390 80 5478919Fax: þ390 80 5478954e-mail: c.foti@dermatologia.uniba.it

Allergic contactdermatitis due toperupok wood

Shin Tanaka, Yoshinari Matsumoto andYasuhiko Tamada

Department of Dermatology, Aichi MedicalUniversity, Aichi, Japan

Key words: allergic contact dermatitis;occupational; patch test; perupok; woods.

Case Report

A 56-year-old botanist visited ourhospital because he had come intocontact with perupok, and 1 monthafter this, a rash spread all over hisbody. The result of skin biopsy sug-gested allergic contact dermatitis. Apatch test with perupok sawdust(50% pet.) resulted in a ?þ reactionat D2, þ at D3 and D7. This same

patch test preparation was negativein 10 normal control patients. Theeruption disappeared after 2 weeksof treatment with oral prednisoloneand topical corticosteroid.

Discussion

Perupok (Lophopetalum dubium,Lophopetalum floribundum) is ashrub mainly found in SoutheastAsia. Although not as useful a woodas many others, it has recently beenused more because of a serious short-age of wood throughout the world.There have been no cases of contactdermatitis from perupok until now.

Most cases of contact dermatitisfrom wood are occupational inforestry (1–3). The possibility of con-tact dermatitis from treatment ofwood also has to be considered(4, 5). Our test wood did not have anysuch additives. We, therefore, diag-nosed allergic contact dermatitisfrom perupok itself. Vigilance willcontinue to be required, if newlyused woods are to be detected ascauses of contact dermatitis (5, 6).

References

1. Mitchell J, Rook A. BotanicalDermatology. Vancouver: Greengrass,1979.

2. Estlander T, Jolanki R, Kanerva L.Occupational allergic contact derma-titis eczema caused by obeche andteak dusts. Contact Dermatitis 1999:41: 164.

3. Kumar A, Freeman S. Leukodermafollowing occupational allergic con-tact dermatitis. Contact Dermatitis1999: 41: 94–98.

4. Goransson K. Contact urticaria andrhinoconjunctivitis from tropicalwood (Lauan, Philippine Red Maho-gany). Contact Dermatitis 1980: 6:223–224.

5. Holst R, Kirby J, Magnusson B.Sensitization to tropical woods givingerythema multiforme-like eruptions.Contact Dermatitis 1976: 2: 295–296.

6. Wood B, Calnan C D. Toxic woods.Br J Dermatol 1976: 94 (Suppl. 13):1–97.

Address:Shin TanakaAichi Medical University NagakuteAichi-gunAichi 480-1195, JapanTel: þ81 561 6399914Fax: þ81 561 6399914e-mail: shin-t@aichi-med-u.ac.jp

Labial edema dueto an acrylicdental prosthesis

D. P. Ruiz-Genao, M. J. Moreno de Vega,J. Sanchez Perez and A. Garcıa-Dıez

Department of Dermatology, HospitalUniversitario de la Princesa, C/Diego de Leon62, 28006 Madrid, Spain

Key words: (meth)acrylates; allergic contactcheilitis; cross-sensitivity; dental prostheses;labial edema.

Occupational allergic contact dermati-tis caused by (meth)acrylates isrelatively common in dental personnel(1), whereas denture material-inducedreactions to acrylates in dental patientsare less common (2–7). Stomatitis(2–4), burning mouth syndrome (5)and cheilitis (6) are adverse oralmucousmembrane reactions fromacrylic dentalprostheses in dental patients.

Case Report

A 72-year-old woman had had hermetallic dental prosthesis changed toa metallic and acrylic one 3 years ago.Approximately a week after thechange, she reported edema and aburning sensation of both lips thatdisappeared after the removal of theprosthesis and reappeared hours afterits replacement. From that timeonwards, because of these symptoms,she had used 3 different dental pros-theses, made exclusively of acrylates,continuing to have flare-ups of edemaof both lips that were progressivelymore intense and clearly related totheir use. No erythema, ulceration orcheilitis were present. No wheals orother cutaneous lesions were observed.

Patch tests with the Spanish stand-ard series, a dental screening series(Chemotechnique Diagnostics AB,Malmo, Sweden) and a (meth)acry-lates series (Chemotechnique Diag-nostics AB) were positive to methylmethacrylate 2% pet. (MMA),2-hydroxyethyl methacrylate 2%pet. (2-HEMA), 2-hydroxypropylmethacrylate 2% pet. (2-HPMA),ethyleneglycol dimethacrylate 2%pet. (EGDMA), gold sodium thiosul-fate and para-phenylenediamine(Table 1). Reading of patch testswith the (meth)acrylate series wasnegative after 30min.

CONTACT POINT 273

According to the manufacturer,the components of the powder andliquid of the last acrylic denturebase material used by the patientwere: (1) powder containing poly-methyl methacrylate, benzoyl perox-ide and cadmium and ferric saltsand (2) liquid containing MMA,EGDMA and hydroquinone. Thepatient started to use a dental pros-thesis made of nickel and chrome,and the edema of the lips resolved.

Discussion

In contrast to the usual clinical pre-sentation of allergic reactions toacrylics (4–6), our patient did nothave typical oral symptoms. Instead,she developed recurrent episodes ofedema of the lips as an expression ofa delayed hypersensitivity reactionclearly related to the use of differentacrylic prostheses. These ceased assoon as the exposure to the allergenstopped. Patch tests showed negativeresults after 30min. Positive patchtests read at D2 and D4 to (meth)acrylates allowed the diagnosis.

Atypical clinical forms of allergicreactions to acrylic dental prostheseshave been previously reported (3, 7):chronic urticaria without mucosal orperioral lesions (7) and stomatitis andedema of the tongue, lips, eyelids andhands (3). In our case, patchtesting with monomeric acrylic resinsand repeated exposure to the pros-thesis provided confirmation of con-tact allergy. Patch testing showed apositive reaction not only to MMAbut also to 2-HEMA, 2-HPMA andEGDMA, some of which may beexplained by cross-reactivity (8).

References

1. Kanerva L, Elsner P, Wahlberg J E.Handbook of Occupational Dermatol-ogy. Heidelberg, Berlin: Springer-Verlag, 2000.

2. Kanerva L, Alanko K, Estlander T.Allergic contact gingivostomatitisfrom temporary crown made of

methacrylates and epoxy diacrylates.Allergy 1999: 54: 1316–1321.

3. Bauer A, Wollina U. Denture-inducedlocal and systemic reactions to acrylate.Allergy 1998: 53: 722–723.

4. VilaplanaJ,RomagueraC,CornellanaF.Contact dermatitis and adverse oralmucous membrane reactions relatedto the use of dental prostheses. ContactDermatitis 1994: 30: 80–84.

5. Agner T, Menne T. Sensitization toacrylates in a dental patient. ContactDermatitis 1994: 30: 249–250.

6. Kobayashi T, Sakuraoka K,Hasegawa Y, Konohana A, KuriharaS. Contact dermatitis to an acrylicdental prosthesis. Contact Dermatitis1996: 35: 370–371.

7. Lunder T, Rogi-ButinaM. Chronic urti-caria from an acrylic dental prosthesis.Contact Dermatitis 2000: 43: 232–233.

8. Kanerva L, Jolanki R, Estlander T. 10years of patch testing with the (meth)acrylate series. Contact Dermatitis1997: 37: 255–258.

Address:Dr Ruiz-GenaoDepartment of DermatologyHospital Universitario de la PrincesaC/Diego de Leon 6228006 Madrid, Spain

Irritant paronychia withonychodystrophycaused bycyanoacrylate nail glue

Caterina Foti1, Nicoletta Cassano2, AnnaConserva1 and Gino A. Vena1

1Department of Internal Medicine,Immunology and Infectious Diseases, Unit ofDermatology, University of Bari, 70124 Bari,and 2Istituto Dermopatico dell’Immacolata,IDI, I.R.C.C.S., 00167 Rome, Italy

Key words: artificial nails; cosmetics;cyanoacrylate; irritant contact dermatitis;nail glue.

Case Report

A 37-year-old woman presented witha 1-month history of paronychia,onycholysis and onychodystrophy ofall the fingernails. She had used pre-formed acrylic nails for 3 consecutivemonths, applying frequently (once ortwice a week) a nail glue (Fing’rs1

nail glue, Zurich, Switzerland) tokeep the artificial nails adherent tothe nail plates. The packaging of theglue declared the presence of cyano-acrylate, without specifying whichone, and lacked a full list of ingredi-ents. After the sudden onset of paro-nychia, she decided to remove theplastic nails and saw dystrophicchanges of fingernails.

The patient was patch tested withthe Italian standard series (meth)-acrylates series (Chemotechnique,Malmø, Sweden), her own nail glue10% pet. and the glue as is directlyapplied on the skin. Patch testing waspositive (þþ) at D2 and D4 only tonickel sulfate. Discontinuation of theuse of artificial nails resulted in rapidhealing of the paronychia and grad-ual improvement in the onychody-strophy, with residual onychorrhexisafter 6 months.

Discussion

Cyanoacrylate glues are used asadhesives for preformed acrylicnails. Contact allergy to cyanoacry-lates is considered to be unlikely, asthey bind strongly with keratin andrapidly polymerize on the skin.Nevertheless, allergic contact derma-titis from cyanoacrylates, especiallyethyl cyanoacrylate, contained innail glues has been reported (1–3).Ena et al. (4) also described a case ofacute leukonychia, developing afteraccidental penetration of a cyano-acrylate glue onto the nail plate.

The toxic effects, related to long-term application of cyanoacrylateglues on nail plates and folds, areunknown; the frequency of onycho-dystrophies caused by these gluesmay be underestimated, consideringthat the use of preformed artificialnails occurs on already dystrophicnails in many cases.

References

1. Fitzgerald D A, Bhaggoe R, English JS C. Contact sensitivity to cyanoacry-late nail-adhesive with dermatitis atremote sites. Contact Dermatitis1995: 32: 175–176.

Table 1. Positive patch test results

D2 D4

p-Phenylenediamine 1% pet. þþ þþGold sodium thiosulfate 2% pet. þ þþMethyl methacrylate 2% pet. þþ þþ2-hydroxyethyl methacrylate 2% pet. þ þþ2-hydroxypropyl methacrylate 2% pet. þ þþEthyleneglycol dimethacrylate 2% pet. þ þþ

274 CONTACT POINT

2. Guin J D, Baas K, Nelson-AdesokanP. Contact sensitization to cyano-acrylate adhesive as a cause of severeonychodystrophy. Int J Dermatol1998: 37: 31–36.

3. Kanerva L, Estlander T. Allergiconycholysis and paronychia causedby cyanoacrylate nail glue, but notby photobonded methacrylate nails.Eur J Dermatol 2000: 10: 223–225.

4. Ena P, Mazzarello V, Fenu G,Rubino C. Leukonychia from 2-ethyl-cyanoacrylate glue. Contact Dermatitis2000: 42: 105–106.

Address:Prof. Caterina Foti, MDUnit of DermatologyM.I.D.I.M. DepartmentUniversity of BariPoliclinico – Piazza Giulio Cesare, 1170124 Bari, ItalyTel: þ39 080 5478996Fax: þ39 080 5478920e-mail: c.foti@dermatologia.uniba.it

Contact urticaria fromdill

J. Monteseirın, J. L. Perez-Formoso,M. Hernandez, M. C. Sanchez-Hernandez,M. J. Camacho, I. Bonilla, A. Chaparro andJ. Conde

Departamento de Medicina, ServicioRegional de Inmunologıa y Alergia, HospitalUniversitario Virgen Macarena, Facultad deMedicina, Universidad de Sevilla, Spain

Key words: allergy; contact urticaria; dill;IgE; plants.

Foods and spices of the parsleyfamily (Umbelliferae, formerly Apia-ceae) include anise, caraway, corian-der, cumin, celery, lovage, fennel,parsley, carrot and dill. Some ofthese have been associated withvarious allergic reactions includingcontact dermatitis, anaphylaxis,gastroenteritis and asthma (1–4). Wereport a patient with contact urti-caria who handled several differentplants.

A 32-year-old housewife with apersonal history of atopy was inves-tigated in our department. Shereported that during the previous 1year, she had developed symptoms

when handling dill plants. There wasa history of rhinitis and asthma.

Serum total immunoglobulinE (IgE) was 325 kUL�1 (HYCORBiomedical Inc.-IZASA, Barcelona,Spain). Specific IgE to dill (andother allergens) was detected withenzyme-linked immunosorbent assay(ELISA), which was performedwith the commercial kit (HYCOR)using activated paper disc as solidphase.

The allergenic extract wasspecially prepared at 5% w/v in phos-phate-buffered saline (PBS) (0�15M),pH7�2, using the following proced-ure: 5 g of dill in 100ml of PBS;extraction overnight at room tem-perature with stirring; centrifugationat 25 000� g for 15min; supernatantprefiltered and dialysed against PBScontaining thimerosal in a tube withcut-off of 3500Da at 4 ˚C for 24 h;filtration with Millipore filters of0.8 mm. The same procedure was fol-lowed to obtain the extracts fromanise, caraway, coriander, cumin,celery, lovage, fennel, parsley andcarrot.

The solid phase was prepared fromthe extracts.

We detected specific IgE to dill(IgE ELISA Score (IES): 5�6), anise(IES: 2�5), cumin (IES: 3) and carrot(IES: 4). We did not detect specificIgE to the other members of the pars-ley family. Prick tests were positive todill (þþþþ), anise (þþ), cumin(þþþ) and carrot (þþþ) and nega-tive to the other extracts. All theseextracts were negative in 6 non-atopic and in 6 atopic control sub-jects. The patient had positive pricktest (Bial-Arıstegui, Bilbao, Spain)and specific IgE (HYCOR) to grassand Olea europaea pollen extracts.Both skin tests and ELISA to salmonwere negative.

Patch tests with extracts of dill andother members of the parsley familyextracts were applied for D2, andreadings made at D2, D3 and D7.All these extracts were negative inthe patient and in 6 non-atopic and6 atopic control subjects.

The various members of the pars-ley family have antigens that areeither in common or cross-react(4, 5). The patient reported heredemonstrated positive tests to othermembers of the Umbelliferae in add-ition to dill.

To our knowledge, this is the 1stcase report of allergic contact

urticaria caused by dill. The patientno longer had symptoms after avoid-ing further contact with dill.

References

1. Bock S A. Anaphylaxis to coriander: asleuthing story. J Allergy Clin Immunol1993: 91: 1232–1233.

2. Boxer M, Roberts M, Grammer L.Cumin anaphylaxis: a case report.J Allergy Clin Immunol 1997: 99:722–723.

3. Helbling A, Lopez M, Schwartz H J,Lehrer S B. Reactivity of carrot-specific IgE antibodies with celery,apiaceous spices, and birch pollen.Ann Allergy 1993: 70: 4995–4999.

4. Freeman G L. Allergy to fresh dill.Allergy 1999: 54: 531–532.

5. Jensen-Jarolin E, Leitner A,Hirschwehr R et al. Characterizationof allergens in Apiaceae spices: anise,fennel, coriander and cumin. Clin ExpAllergy 1997: 27: 1299–1306.

Address:Dr J. MonteseirınAsuncion 2741011 SevillaSpainFax: þ34 954907041e-mail: fmonteseirinm@meditex.es

Occupational allergiccontact dermatitis frompolyurethane/methacrylates inwindscreen repairchemical

Christophe-J. Le Coz

Cabinet de Dermatologie, 19, rue del’Observatoire, F-67000 Strasbourg, France

Key words: fingertips; hand dermatitis;occupational; semiopen test; UV-curableresins; (meth)acrylic resins; windscreen.

Case Report

A 24-year-old man was referred withrecurrent occupational dermatitis.Lesions had started on his fingertips3 weeks before his seeking medicaladvice. They had then spread topalmar aspect, perionychium anddorsum of his fingers. The patienthad been employed for 6 months in

CONTACT POINT 275

a small company and his jobconsisted in replacing windscreensand repairing small defects. For thislast task, he mostly worked with aglass cleaner, a wiper and a primerand a chemical system to repairwindscreen defects. This system wasused either to repair big defects witha pressure system injecting resin, oremployed as such to repair smalldefects, the resin being applieddirectly to the defect. The patientdid not use the pressure system, butapplied the liquid resin directlywithout protective gloves. Thismono-component resin Glass Medic1

repair system (AGSI, Kempston, UK)available in a small bottle, was appliedto small defects, covered with a trans-parent plastic film and then rapidlycured under ultraviolet (UV) light(around 5min). The safety data sheetindicated that the chemical wascomposed of polyurethane/methacrylicresin at >50% concentration, acrylicacid and maleic acid. Patch tests wereperformed, using the Finn Chambertechnique (Epitest, Tuusula, Finland),with the revised ICDRG standardseries (1), additional allergens, methylacrylate, ethyl acrylate, butyl acrylateand 2-hydroxyethyl acrylate, each0�1% pet. and methyl methacrylate2% pet. The patient’s own materialswere tested in semiopen tests, on5� 5 cm2 areas: the windscreen cleanerand the diluents as is, and the wind-shield repair polyurethane/methacrylate-based resin 1 p. 1000 (v/v) in acetone.A positive (þ) reaction was observedafter 3 days to the resin only, whichpersisted for more than 2 weeks. Afterseveral severe relapses of his dermatitisdue to further minimal contact withcontaminated gloves, the patient almostcompletely avoided contact with thisproduct and the lesions progressivelycleared. In this small company, thewind-shield repair chemical system was thenmade available only in encapsulatedform.

Discussion

This report illustrates a recentlydescribed mode of sensitization to(meth)acrylic compounds, which canoccur in people working in the car orcar-glass repair industry. The firstcase of dermatitis from a glass repairchemical based on (meth)acrylicUV-curable resins was reported byPedersen (2) in a workman repairingminor damage in car windscreens.The patient had positive reactions

to 2-hydroxyethyl methacrylate(2-HEMA) and methyl methacrylate,but his own material, namely TEAMGLAS, prep 20, was not tested. Arecent report describes a patientwith right thumb pulp and indexfinger dermatitis probably due tooccupational contact with acrylic-based windscreen glass repair resin.He secondarily developed an allergiccontact dermatitis due to an electro-surgical earthing plate coated withacrylic adhesive (3). Patch testingwas positive to the patient’s ownresin 2% pet., and several (meth)acrylates. In the present report, thesensitizer was probably the poly-urethane/methacrylate, a UV-curablepolymer without CAS number. Poly-urethane/methacrylate is preparedfrom (1) polyurethane components,namely a diisocyanate (toluene,hexamethylene or isophorone diiso-cyanate) and a polyol (polyethyleneglycol PEG 200, PEG 400 or PEG1000), (2) the UV-curable resin2-HEMA and (3) other additivesand catalysts (4). Its chemical for-mula is illustrated in Fig. 1. Thispolymer is used as an anaerobicsealant or threadlocker ingredient,for use on threaded fasteners andflange sealing applications. It can beuse in 2-component glues used tobond metals and ferrites.

Clinical data are similar in patientswith delayed hypersensitivity to(meth)acrylic resins: an acquiredpruritic fingertip dermatitis thatprogressively spreads over the fingersand hands, with occupational features.When safety data sheets are lacking,patch testing can be performed withthe patient’s own material diluted inacetone in a semiopen test. In ourcase, a 1 p. 1000 concentration wasable to elicit a positive reaction,probably without risk of active sensi-tization to any acrylic resins present.According to its preparationmodalitiesand to its chemical formula, sensitivityto polyurethane/methacrylate could bedetected by a positive reaction to

2-HEMA, this hapten either acting asthe offending agent present as animpurity in the chemical or, morelikely, being the epitope and markerof delayed sensitivity.

Like Pedersen (2), this reportemphasizes a situation frequentlyobserved in small companies.Workersoften handle chemicals without gloves,these often being used only after theonset of dermatitis. As information onsafety data sheets and packages israrely read, caution should be rein-forced for occupational allergens, withthe labelling Xr43 clearly indicated onmaterials.

References

1. Lachapelle J M, Ale S I, Freeman Set al. Proposal for a revised interna-tional standard series of patch tests.Contact Dermatitis 1997: 36: 121–123.

2. PedersenNB.Allergic contact dermatitisfrom acrylic resin repair of windscreens.Contact Dermatitis 1997: 39: 99.

3. Banerjee P,White I R. Allergic contactdermatitis at the application site of anelectrosurgical earthing plate occur-ring in a windscreen repairer. ContactDermatitis 2001: 44: 97.

4. Ghosh S, Krishnamurti N. Prepara-tion and properties of UV-curablepolyurethane methacrylate cationo-mers and their use as adhesives.Polym-Plast Technol Eng J, 2001: 40:539–559.

5. Lepoittevin J P, Le Coz C. Dictionaryof occupational allergens: chemicalstructures, sources and references. In:Handbook of Occupational DermatologyKanerva L, Elsner P, Wahlberg J E,Maibach H I (eds): Berlin/Heidelberg,Springer-Verlag, 2000: 1125–1191.

Address:Christophe-J. Le CozCabinet de Dermatologie19, rue de l’ObservatoireF-67000 StrasbourgFranceTel: þ33 0 3 88 60 13 12Fax: þ33 0 3 88 60 82 99e-mail: christophe.lecoz@wanadoo.fr

O

O

O NR

N OO

O

H H

O

O

O

O

OH

R= or

Fig. 1. Chemical formulae of polyurethane/dimethacrylate and 2-HEMA (5).

276 CONTACT POINT

Corticosteroid contactallergy from a nasalspray in a child

Ana Paula Cunha1, Alberto V. Mota1,M. Antonia Barros1, A. Bonito-Victor2 andCarlos Resende1

1Dermatovenereology Department, and2Pediatrics Department, S. Joao Hospital andFaculty of Medicine, Porto, Portugal

Key words: allergic contact dermatitis;budesonide; child; medicaments; nasalspray; peri-nasal; topical corticosteroids.

Case Report

A 9-year-old boy presented witherythema, oedema and scalingaround the nose and complaints ofsevere pruritus. The lesions persistedfor 2 years and had started 3 weeksafter beginning treatment with bude-sonide nasal spray (Pulmicort1

Nasal Aqua: AstraZeneca, Barcar-ena, Portugal) for allergic rhinitis.

There was a history of previoususe of other topical corticoster-oids, as both creams and nasalsprays. Patch tests showed positivereactions to Pulmicort1 nasal spray(as is), corticosteroid mix, tixocortolpivalate and budesonide, othercorticosteroids tested all beingnegative (Table 1). The patient wasinstructed to stop the use of nasalsprays, and progressive improvementof the skin lesions was observedthereafter.

Comments

Budesonide is a synthetic, non-halogenated, moderately potent top-ical corticosteroid, with a 16a-, 17a-butylidene dioxy portion used in thetreatment of inflammatory dermatosesand also widely in nasal sprays to treatrhinitis and bronchial asthma (1). Itseems to be a more important sensi-tizer when used as a nasal spray (2).

Several cases of allergic contactdermatitis from this drug, in bothointments and nasal sprays, havebeen reported in adults, but antigen-determinant structure and cross-reactivity between this agent and theother corticosteroids remain unclear (3).

Considering the widespread use ofbudesonide nasal sprays, sensitivity tothem is considered uncommon (4). Inchildren, this must be even rarer; therebeing only 1 description of 2 cases ofperi-oral allergic contact dermatitisfrom inhaled budesonide (5).

Cross-reaction studies are essentialto recommending safe substitutes tothe allergic patient (6). Cross-reactionevaluation is also important to definethe best markers of corticosteroidhypersensitivity (7). Concerning bude-sonide cross-reactions, it is knownthat patients with allergic contactdermatitis from this drug do notcross-react to amcinonide, as alsodid occur in our case, while patientswith contact allergic contact derma-titis from amcinonide generally docross-react to budesonide (8).

In our case, it is likely that corti-costeroid nasal sprays sensitized thepatient to both budesonide and tixo-cortol pivalate. This report illustratesa very unusual allergic contact derma-titis from inhaled corticosteroids in achild.

References

1. Gamboa PM, Jauregui I, Antepara I.Contact dermatitis from budesonidein a nasal spray without cross-reactivityto amcinonide. Contact Dermatitis1991: 24: 227–228.

2. Jorro G, Rochina A, Morales C,Burches E, Pelaez A. Contact allergyto topical budesonide in a nasalspray. Contact Dermatitis 1993: 28:254.

3. Noda H, Matsunaga K, Noda T et al.Contact sensitivity and cross-reactivityof budesonide. Contact Dermatitis1993: 28: 212–215.

4. Veraldi S, Fallahdar D, Riboldi A.Allergic contact dermatitis frombudesonide. Contact Dermatitis1993: 28: 116.

5. Held E, Ottevanger V, Petersen V S,Weismann K. Peri-oral dermatitis inchildren receiving budesonide inhal-ation therapy. Eur J Pediatr Dermatol1995: 5: 141–144.

6. Dooms-Goossens A, Andersen K E,Brandao F M et al. Corticosteroidcontact allergy: an EECDRG multi-centre study. Contact Dermatitis1996: 35: 40–44.

7. Lepoittevin J A, Drieghe J, Dooms-Goossens A. Studies in patients withcorticosteroid contact allergy. ArchDermatol 1995: 131: 31–37.

8. Meding B, Dahlberg E. Contactallergy from budesonide in a nasalspray. Contact Dermatitis 1986: 14:253–254.

Address:Dr Ana. Paula CunhaServico de Dermatologia e VenereologiaAlameda Prof Hernani Monteiro4202-51 PortoPortugalTel: 00351 933200408Fax: 00351 225096320

Table 1. Patch test results

Substance Concentration (%) Vehicle D2 D4 D7

Pulmicort1 nasal spray As is pet. _ þ þþTixocortol pivalate (1) pet.

Corticosteroid mix Budesonide (0�1) – þ þþHydrocortisone-17-butyrate (1)

Tixocortol pivalate 1 pet. _ þ þþBudesonide 0�1 pet. _ þ þþþAmcinonide 0�1 pet. _ _ _Betamethasone-17-valerate 1 pet. _ _ _Triamcinolone acetonide 1 pet. _ _ _Clobetasol-17-propionate 1 pet. _ _ _Hydrocortisone-17-butyrate 0�1 pet. _ _ _Alclomethasone dipropionate 1 pet. _ _ _Dexamethasone phosphate 1 pet. _ _ _

CONTACT POINT 277

Patch testing withthin-layer chromatograms

M. Bruze, M. Frick and L. Persson

Department of Occupational andEnvironmental Dermatology, MalmoUniversity Hospital, S-205 02 Malmo,Sweden

Key words: clinical relevance; contactallergy; exposure; identification ofsensitizers; isolation; paper chromatography;thin-layer chromatography; TLC; TLC-patchtest.

When thinking of an inexpensiveshortcut for the isolation andidentification of a sensitizer, aDutch investigation from the 1960scame to mind. In that study, paperchromatograms were patch testedin the process of identifying thesensitizer in tulips (1). In this paper,we report on an updated versionof this methodology, thin-layerchromatography patch test/testing,and briefly on our own experiencewith it during the past 3 years.

Materials and Methods

Thin-layer chromatography (TLC)plastic roll 500� 200 cm (silica gel60F254) (VWR International, Stock-holm, Sweden) is cut into 18� 18 cmstrips. Samples to be tested aredeposited on one spot each from a10mL capillary pipette, along astraight line with at least 2 cmbetween each spot. These samplesare prepared in the same way, includ-ing diluent and concentrate, as whennormally patch tested upon the back.30mL of each sample is then appliedon the TLC plastic roller patch. Thisis double the volume used in the regu-lar patch test procedure with filterpaper in the small Finn Chamber(Epitest Ltd Oy, Tuusula, Finland).Double spots are applied for eachsample that is to be investigated,one to be used as a patch test andthe other to be used as a comparisonand reference when reading the patchtest. When the product tested is sus-pected to contain a specific allergen,this allergen is naturally also appliedon the TLC plastic roll as a referencesubstance.

The 18� 18 TLC plastic roll chro-matogram is developed in a tanklined with solvent-saturated filterpaper. It is attached in the tank, sothat the chromatogram is straight, byclips on a welded stainless steel con-struction (Fig. 1). When the chroma-togram is developed, the plate isinvestigated in UV light to detectspots that are not coloured. Thespots are then marked on the chro-matogram. In some cases, such aswith diglycidylether of bisphenol A,the chromatograms are sprayed withreagents turning the non-visible spotsviolet (2).

If the separation is successful, eachspot gives rise to a band of welldefined and separated spots. Thesebands are cut out from the chroma-togram in pieces of about 2�5� 18 cmand are then applied on the upperarm using Scanpor (NorgesplasterA/S, Vennesla, Norway) tape. Theposition of the TLC-patch test(TLC-PT) is carefully marked. TheTLC-PT is removed after 2 days andread after 1 additional day (D) andpreferably also on D7 according toInternational Contact DermatitisResearch Group (ICDRG) criteria.When reading the patch tests, the 2ndchromatogram, deriving from thedouble sample, is used as a referenceto determine to which spot/spots thepositive reaction(s) correspond(s) to.

Results

We have used TLC-PT for productssuch as textiles, plastics, food, plants,

perfumes, drugs and grease, particu-larly in the following 3 situations.

(1) When a patient patch tests posi-tively both to a separate sensitizersuch as a textile dye and to acoloured textile garment, TLC-PT can demonstrate that thepatient tests positively both to thereference substance (textile dye)applied separately on the TLCplate and to the reference sen-sitizer (textile dye) in the textile.

(2) When a patient patch tests posi-tively to a compound product, itis valuable to test the ingredientsto specify the allergy. When theingredients cannot be obtainedfrom the manufacturers, thedermatologist may test with theingredients identified and alreadyavailable. If the patient tests posit-ively to one of these, TLC-PT canbe used to show that the reactivityis directed towards only 1 sub-stance, i.e. the reference sensitizer.

(3) For certain products, TLC-PTmay be a shortcut for the identi-fication of a new or initiallyunknown sensitizer in a com-pound product. We have success-fully used it for identification ofthe sensitizer in grease and arecurrently using it for the identifi-cation of sensitizers in food,plants and drugs.

To exemplify the methodology,the epoxy resin widely used in stand-ard patch test series can be used asan example. Diglycidylether ofbisphenol A, the monomer with amolecular weight of 340, is con-sidered to be the major sensitizer

Fig. 1. Development of thin-layer chromatogram plastic roller that is straightenedout and fixed to the tank in an upright position by attachment to metal clips.

278 CONTACT POINT

and patch testing with a TLC-PT ofthis resin confirms this (Fig. 2).

The TLC-PT also has its limita-tions. All substances are not amen-able to TLC, because they cannot bevisualized on a chromatogram. How-ever, even if a positive reaction isnoted to a ‘non-detectable’ spot on aTLC-PT, the silica can then bescraped off and extracted and usedfor further investigations. The pro-blem with the ‘undetectable’ sensiti-zer is that of developing a mobilephase to enable separation. Anotherlimitation of TLC-PT is its detectionlimits. If the patch test reaction to thecompound product is weak, the con-centration of the sensitizer in theTLC chromatogram is likely to bebelow the individual elicitation leveland thus result in a false negativereaction, unless this is not compen-sated for by applying a larger volumeon the TLC plate.

In conclusion, TLC-PT is or can bea valuable tool for most dermatolo-gists with an interest incontact derma-titis and its chemistry and who havesome access to laboratory facilities.

References

1. Verspyck Mijnssen G A W. Pathogen-esis and causative agent of ‘tulip fin-ger’. Br J Dermatol 1969: 81: 737–745.

2. Fregert S, Trulsson L. Simple methodsfor demonstration of epoxy resins ofbisphenol A type. Contact Dermatitis1978: 4: 69–72.

Address:Magnus BruzeDepartment of Occupational andEnvironmental DermatologyMalmo University HospitalS-205 02 MalmoSwedenTel: þ46 40 33 1760Fax: þ46 40 33 6213e-mail: magnus.bruze@skane.se

Contact allergy to decylglucoside in antisepticafter body piercing

Christophe-J. Le Coz1 and Marie-ThereseMeyer2

1Cabinets de Dermatologie, 19, rue del’Observatoire, and 2Cabinets deDermatologie, 4, rue Charles de Foucault,F-67000 Strasbourg, France

Key words: alkyl glucosides; allergic contactdermatitis; antiseptics; CAS nos. 58846-77-8,68515-73-1, 141464-42-8, 28211-18-9; cocoglucoside; patch testing.

Case Report

A 29-year-old woman with no historyof allergy had an umbilical piercingin August 2002. For wound care,she used �2 daily a chlorhexidinedigluconate-based antiseptic gel. After2 weeks, she developed acute eczemaon the treated area that spreads overthe whole abdomen and cleared afterthe withdrawal of the gel and topicalcorticosteroids. Patch testing wasperformed with the revised ICDRGseries (1), additional allergens, thepatient’s own antiseptic gel, a similarantiseptic solution containing thesame ingredients at the same percent-ages but without decyl glucoside orhydroxyethylcellulose and chlorhexi-dine digluconate 0�5% aq. Readingsat D2/D3 showed a þþ/þþþ reac-tion to the gel only.

Breakdown of gel was performedinto 4 ingredients provided by thefirm, diluted in water at concen-trations identical to that in the pro-duct, namely hydroxyethylcellulose,glycerin, chlorhexidine digluconateand decyl glucoside. A þþþreaction to decyl glucoside 0�55%aq. (commercial product used 1% inthe gel formula is a 55% decyl gluco-side aqueous solution) confirmeddelayed hypersensitivity to this com-ponent only.

Discussion

Decyl glucoside or decyl D-glucoside,also named decyl-beta-D-glucopyra-noside, belongs to the alkyl gluco-sides family and is obtained by thecondensation of the fatty alcoholdecyl alcohol and a D-glucose poly-mer (Fig. 1). Industrially, the glucose

Fig. 2. Positive thin-layer chromatograph-patch test reaction to a spotcorresponding to the monomer (MW¼ 340) on the chromatogram shown in thefigure in a patient positive to epoxy resin in the standard series.

CONTACT POINT 279

is obtained from maize or wheatand the fatty alcohol from coconutoil. Decyl glucoside is marketedunder several names including AG-10LK, Atlas G-73500, Oramix NS10 and Plantaren 2000.

This non-ionic surfactant andcleansing agent has been widely usedfor several years, due to its foamingpower and good tolerance in rinse-offproducts like shampoos, hair dyesand colours, and soaps. Decyl gluco-side is also employed in leave-on pro-ducts such as no-rinsing cleansingmilks, lotions and several sunscreenagents and is contained as a stabiliz-ing surfactant of organic microparti-cles in sunscreen agent Tinosorb1 M.Totally biodegradable, decyl gluco-side is found in several ‘gentle’ and‘natural’ cleansers. Although classi-fied among irritants, a 55% aqueoussolution of decyl glucoside tested at10% dilution in 100 volunteers wasneither irritant nor sensitizing. How-ever, despite its chemical structureand reactivity, decyl glucoside couldbe a sensitizer. Other glucosides areused for similar properties (2), likecoco glucoside and lauryl (dodecyl)glucoside in cosmetics, and cetearylglucoside as a surfactant and emulsi-fying agent because of its higher vis-cosity. In practice, and probably dueto their manufacturing processes, suchalkyl glucosides are blends of severalcopolymers based on several fattyalcohols and a glucoside polymer.For example, coco glucoside, pro-vided by Cognis in Plantacare1 818UP, contains C6 (max 0�5%),C8 (24–30%), C10 (15–22%), C12

(37–42%), C14 (12–18%) and C16

(max 4%) fatty alcohols, while decylglucoside in Plantacare1 2000 UPcontains C6 (max 1%), C8 (33–40%),C10 (21–28%), C12 (27–32%), C14

(9–12%) and C16 (max 1%) alcohols(3).

Such variations may explain someuncertainty when searching for theprecise CAS no. of decyl glucoside.3 CAS nos. are found in the Inter-national Cosmetic Ingredient Dic-tionary and Handbook (2), 58846-77-8, 68515-73-1 and 141464-42-8.On the INCI website, however, theCAS no. for decyl glucoside is only54549-25-6 (4) and concerns a C8�10

alkyl polyglucoside, i.e. a glucosidepolymer condensed with octanoland/or decanol. CAS no. 58846-77-8designates n-decyl-a-D-glucopyrano-side or n-decyl-b-D-glucopyranoside.CAS no. 68515-73-1 refers to C8�10

glucoside based on octyl- and decylglucoside too but is not mentioned onthe INCI website (3). CAS no.141464-42-8 is sometimes attachedto C6�16 alkyl polyglycoside cocoglucoside too (3), also containingdecyl glucoside.

Although unlikely to be rare, con-tact allergies to topical antisepticsused after body piercing are seldomreported. This case seems to be thefirst of delayed-type hypersensitivityto decyl glucoside, largely employedas a safe cosmetic ingredient. Its usein a leave-on product probablyencouraged the induction of contactallergy. Because alkyl glucosides arecomparable mixtures, it is likely thatpatients sensitive to decyl glucoside

may also react to other alkyl gluco-sides and vice versa.

References

1. Lachapelle J M, Ale S I, Freeman Set al. Proposal for a revised inter-national standard series of patchtests. Contact Dermatitis 1997: 36:121–123.

2. Wenninger J A, Canterbery R C,McEwen G N Jr (eds). In: Interna-tional Cosmetic Ingredient Dictionaryand Handbook, 8th edition. Washing-ton DC, The Cosmetic, Toiletry, andFragrance Association, 2000.

3. http://www.cognis.com4. http://dg3.eudra.org/F3/home.html

Address:Christophe-J. Le CozCabinets de Dermatologie19, rue de l’ObservatoireF-67000 StrasbourgFranceTel: þ33 0 3 88 60 13 12Fax: þ33 0 3 88 60 82 99e-mail: christophe.lecoz@wanadoo.fr

The positivity ratio –another parameter toassess the diagnosticquality of a patch testpreparation

Johannes Geier1, Wolfgang Uter2, HolgerLessmann1 and Axel Schnuch1

1Information Network of Departments ofDermatology (IVDK), Georg AugustUniversity, Department of Dermatology,Gottingen, Germany, 2Department of MedicalInformatics, Biometry and Epidemiology,University of Erlangen-Nurnberg, Erlangen,Germany

Key words: false-positive reactions; patchtesting; positivity ratio; quality control;reaction index.

The proportion of doubtful or irritantpatch test reactions, in relation to aller-gic positive reactions, varies betweenallergens. The reaction index (RI) (1) isdefined, where the number of allergicreactions is a, of doubtful reactions q,and of irritant reactions i, as (a� q� i)/(aþqþ i), thus ranging from� 1,whenall observed test reactions are doubtful

OO

OH

HO OO

co

OO

O

OH

O

co: 1 to 3

CAS: 68515-73-1

CAS: 54549-25-6

HO HO

HO

HOHO

OH OH

OH

OH

OHOH

Fig. 1. Molecular structures found for decyl glucoside.

280 CONTACT POINT

or irritant, to þ 1, when only allergicpositive test reactions occur. An IVDKanalysis showed that 13 standard seriesallergens hadapositiveRI at day 3 (D3)(2).

To some allergens, e.g. AmercholL-101 (50% petrolatum), benzalko-nium chloride (0�1% pet.), benzoylperoxide (1% pet.), cocamidopropylbetaine (1% aqueous), 1,3-diphenyl-guanidine (1% pet.), octyl gallate(0�3% pet.), phenyl mercuric acetate(0�05% pet.), or propylene glycol(20% aq.), the majority of positivereactions are no stronger than þaccording to international guidelines(3) and national criteria of the DKG(4). In most cases with a þ reaction tosuch allergens, no clinical relevancecan be found (5–9). Thus, these reac-tions probably have to be regarded asfalse-positive, irritant reactions.Whereas, if morphology alone wasconsidered, these reactions wouldcommonly be regarded as allergic.Similarly, contact allergy to one of itscomponents can be detected in only39% of patients with a þ reaction tofragrance mix (8% pet.), but in 69% ofthose with aþþ and in 93% of thosewith aþþþ, reaction (10). Patientswith an irritant reaction to sodiumlauryl sulfate (SLS) 0�5% aq. hadsignificantly more weak positivereactions to several allergens of thestandard series and a vehicle andpreservative series (11), lending stillfurther support to the concept, wellknown among experienced patchtesters (12, 13), that þ reactions arenot always allergic.

Against this background, we pro-pose the positivity ratio (PR) as anadditional measure of the diagnosticquality of a patch test preparation.The PR is the percentage of þ reac-tions among the total of positivereactions (i.e.þ, þþ, or þþþ)observed, and can be defined as:

(n(þ) � 100)=n(þ þþ þþþ)

Asymptotic or exact confidence lim-its can additionally be computed forthis binomial proportion to quantifyprecision.

Based on patch test data of theIVDK for the years 1999–2001(n¼ 28,138 patients), we analysedthe PR and RI of 7 selected allergensfrom the standard series, as well as ofthe above-mentioned problematicallergens. Patch testing was per-formed according to the guidelinesof the DKG (4). Allergens werepurchased from Hermal, Reinbek,Germany. Test reactions at D3 wereincluded in this data analysis.

The results are shown in Table 1.With the exception of formaldehyde,the PR of the 7 standard allergensranged from 48% to 72%. In con-trast, with the exception of AmercholL-101, the PR of the problematicallergens ranged from 82% to 94%.It therefore appears that a PR ofaround 80% might be regarded asthe borderline between good andnot so good test preparations in thisanalysis.

The data also show that the PRand the RI are inversely related.This correlation is statistically signif-icant (p< 0�0001); the Spearman cor-relation coefficient was � 0�920.Except for formaldehyde, all stan-dard allergens in this analysis have alow PR (< 75%) and a high RI(� 0�5), while, with the exception ofAmerchol L-101, all problematicallergens have a high PR (> 80%)and a low RI (� 0). Reactions to for-maldehyde and Amerchol L-101 donot quite fit into this pattern, butcan be regarded as borderline cases.These test preparations are known tobe moderately irritant, and in thecase of formaldehyde, poor reprodu-cibility of patch tests is well known(14).

The combination of a low RI witha high PR, such as we found withthe problematic allergens, indicates

many doubtful or irritant reactionsand a high proportion of þ reactions.2 interpretations are possible. If theallergen is moderately irritant withonly weak sensitizing potential, andone to which few patients areexposed, it is probably being testedat too high a concentration. In thiscase, not only the doubtful reactions,but also some of the þ reactions arepresumably irritant, rather than aller-gic. If, conversely, the allergen is amoderately strong sensitizer, towhich many patients are exposed, itis possibly being tested at too low aconcentration, and not only the þreactions, but also a high proportionof the doubtful reactions are possiblyweak allergic reactions (15). How-ever, it is difficult to distinguishbetween such irritant reactions andgenuine, albeit weak, allergic reac-tions without resorting to therepeated open application test(ROAT) or provocative use test(PUT). These, together with serialdilution testing, are probably thebest approach to resolve uncertaintyabout allergens with such a reactionprofile of RI and PR.

In the final analysis, the assess-ment of a weak positive reaction asallergic or irritant in each individualcase has to be made according to thepatient’s history and exposure andaccording to the clinical pattern ofthe dermatitis. In this respect, noschematic rules can be deduced fromRI and PR, though these parametersmay help to optimize patch test pre-parations, and may be an aid in inter-preting such reactions.

References

1. Brasch J, Henseler T. The reactionindex – a parameter to assess the qual-ity of patch test preparations. ContactDermatitis 1992: 27: 203–204.

2. Brasch J, Geier J, Henseler T. Evalua-tion of patch test results by use of thereaction index. An analysis of data

Centres of the IVDK contributing to this study (in alphabetical order): Aachen (H.Dickel, S. Erdmann), Augsburg (A. Ludwig),Berlin BenjaminFranklin (B. Tebbe,R. Treudler), Berlin BWK(A.Kohler), BerlinCharite (T. Zuberbier), Bochum (Ch. Szliska,M. Straube,M.Freitag),Dortmund (P.J. Frosch,C. Pirker,R.Herbst),Duisburg (J. Schaller),Dresden (G.Richter,R.Aschoff),Erlangen (M. Fartasch, M. Hertl, V. Mahler), Essen (U. Hillen), Gera (J. Meyer), Gottingen (Th. Fuchs, J. Geier), Graz (W.Aberer, B. Kranke), Halle (G. Gaber, D. Lubbe), Heidelberg University of.-Hautklinik (A. Schulze-Dirks, M. Hartmann, U.Jappe),HeidelbergAbt.Klinische Sozialmedizin (H.Dickel, T.L.Diepgen),Homburg/Saar (P.Koch), Jena (A.Bauer,M.Kaatz,W.Wigger-Alberti, S. Schliemann-Willers), Kiel (J. Brasch), Krefeld (M. Lilie, A.Wallerand, S.Wassilew), Lubeck (J. Grabbe),Mainz (D.Becker),Mannheim (Ch. Bayerl),Marburg (I. Effendy,H. Loffler),Munchen Schwabing (M.Agathos),MunchenTU(J. Rakoski), Nurnberg (I.Muller), Osnabruck (W.Uter, S.M. John, H.J. Schwanitz, N. Schurer), Rostock (H.Heise), Tubingen(G. Lischka),Ulm (H.Gall†, P.Gottlober,G. Staib),Wurzburg (J. Arnold,A. Trautmann),Wuppertal (O.Mainusch, J.Raguz).

CONTACT POINT 281

recorded by the Information Networkof Departments of Dermatology(IVDK). Contact Dermatitis 1995: 33:375–380.

3. Wahlberg J E. Patch testing. In:Rycroft R J G, Menne T, Frosch P J,Lepoittevin J-P, eds. Textbook of Con-tact Dermatitis, 3rd edn. Berlin:Springer, 2001: 435–468.

4. Schnuch A, Aberer W, Agathos Met al. fur die Deutsche Kontaktaller-gie-Gruppe: Leitlinien der DeutschenDermatologischenGesellschaft (DDG)zur Durchfuhrung des Epikutantestsmit Kontaktallergenen. Hautarzt2001: 52: 864–866.

5. Fuchs T, Meinert A, Aberer W,Bahmer F A et al. Benzalkonium-chlorid – relevantesKontaktallergen oderIrritans? Hautarzt 1993: 44: 699–702.

6. Aberer W, Fuchs T, Peters K-P,Frosch P J. Propylenglykol: KutaneNebenwirkungen und Testmethodik.Literaturubersicht und Ergebnisseeiner Multicenterstudie derDeutschen Kontaktallergiegruppe(DKG). Dermatosen Beruf Umwelt1993: 41: 25–27.

7. MoraMorillas I, Aguilar Martinez A,Sanchez Lozano J L. Garcia Perez A.Is benzoyl peroxide an irritant orsensitizer? Contact Dermatitis 1987:16: 232–233.

8. Uter W. Lack of patch test reactivityto 3-dimethylaminopropylamine inGerman hairdressers. Contact Der-matitis 1999: 41: 231.

9. Geier J, Schnuch A. Kontaktallergiedurch Pravention. Dermatol BerufUmwelt 2000: 48: 139–140.

10. Schnuch A, Geier J, Uter W, FroschPJ. Another look on allergies to fra-grances: frequencies of sensitisationto the fragrance mix and its constitu-ents. Results from the IVDK. ExogenDermatol, in press.

11. Geier J, Uter W, Pirker C, Frosch PJ.Patch testing with the irritant sodiumlauryl sulfate (SLS) is useful in inter-preting weak reactions to contactallergens as allergic or irritant.Contact Dermatitis, 2003: 48: 99–107.

12. Shuster S. Patch-test sensitivity andreproducibility in individuals andpopulations. Am J Contact Dermati-tis 1992: 3: 74–78.

13. De Groot A C, Frosch P J. Adversereactionstofragrances.Aclinical review.Contact Dermatitis 1997: 36: 57–86.

14. Brasch J, Henseler T, Aberer W,Bauerle G et al. Reproducibility ofpatch tests. A multicenter study ofsynchronous left- versus right-sidedpatch tests by the German ContactDermatitis Research Group. J AmAcad Dermatol 1994: 31: 584–591.

15. Schnuch A, Geier J, Brasch J, UterW. The preservative iodopropynylbutylcarbamate. frequency of allergicreactions and diagnostic considera-tions. Results from the IVDK. Con-tact Dermatitis 2002: 46: 153–156.

Address:Johannes Geier, MDIVDK an der Universitats-Hautklinikvon-Siebold-Str. 337075 GottingenGermanyTel:þ 49 551 39 89 84Fax:þ 49 551 39 60 95e-mail: jgeier@med.uni-goettingen.de

Table 1. Reaction index (RI) and positivity ratio (PR) of 7 standard allergens and 8 problematic allergens. Data of the IVDK,1999–2001

Allergen preparation

Number ofpatientstested

Number ofpatients withpositivereaction

Number of patientswith doubtful orirritant reaction

PR(exact 95%-confidenceinterval) RI

Allergens of the standard seriesNickel sullfate 5% pet. 25,369 3,563 507 48%

(47–50%)0�8

4-Phenylenediamine base 1% pet. 25,451 1,095 334 57%(53–59%)

0�5

Thiuram mix 1% pet. 25,446 682 176 57%(53–61%)

0�6

Fragrance mix 8% pet. 25,403 3,021 945 67%(65–69%)

0�5

Potassium dichromate 0�5% pet. 25,572 1,054 387 68%(65–71%)

0�5

Balsam of Peru 25% pet.(Myroxylon Pereirae)

25,442 2,725 1019 72%(71–74%)

0�5

Formaldehyde 1% aq. 25,503 438 254 81%(77–84%)

0�3

Problematic allergensAmerchol L-101 50% pet. 17,763 1,056 456 77%

(74–80%)0�4

Benzoyl peroxide 1% pet. 4,796 485 494 82%(78–85%)

0�0

Phenylmercuric acetate 0�05% pet. 16,746 1268 2301 85%(83–87%)

� 0�3

Propylene glycol 20% aq. 16,832 388 373 86%(82–89%)

0�0

Benzalkonium chloride 0�1% pet. 17,862 109 118 91%(84–96%)

0�0

Octyl gallate 0�3% pet. 16,935 598 1461 92%(89–94%)

� 0�4

Cocamidopropyl betaine 1% aq. 17,324 397 611 94%(92–96%)

� 0�2

1,3-Diphenylguanidine 1% pet. 6,364 162 180 94%(89–97%)

� 0�1

282 CONTACT POINT

Photocontact dermatitisdue to dexketoprofen

E. Cuerda Galindo, J. J. Goday Bujan, J. delPozo Losada, J. Garcıa Silva, C. PenaPenabad and E. Fonseca

Department of Dermatology, Hospital JuanCanalejo, Xubias de Arriba 84, 15006A Coruna, Spain

Key words: arylpropionic acid; cross-sensitivity; dexketoprofen; non-steroidalanti-inflammatory drugs; photocontactdermatitis.

Case Report

A 27-year-old woman presented withan itchy lesion on her right handafter applying Enangel1 (dexketo-profen trometamol 1�25%, LaboratoryMenarini, Barcelona, Spain) for joinpain and after 2 days of sun exposure.Patch test results with the Spanishstandard series were negative. Patchtesting without UVA irradiation withnon-steroidal anti-inflammatory drugs(NSAIDs) and dexketoprofen wasnegative. Photopatch testing (followingirradiation with UVA 7�5 J/cm2) waspositive for ketoprofen 1% pet. anddexketoprofen 1% pet. at 1 and 3 days(Table 1).

Patch and photopatch tests weredone with the components of Enan-gel1 (dexketoprofen, trometamol,lavender essence HBE-8028, ethylalcohol 96% and carbomer; kindlyprovided by Laboratory Menarini),and only dexketoprofen was positiveon photopatch testing. Controls in 6healthy controls (patch and photo-patch test to dexketoprofen) wereperformed with negative results.

Discussion

Photocontact dermatitis due totopical dexketoprofen has onlyrecently been described (1). It is wellknown that topical use of NSAIDsfrequently induces photosensitivityreactions (2, 3).

Dexketoprofen is an NSAID ofthe arylpropionic acid group, theirchemical structures sharing commonelements such as the benzoyl radicaland the thiophene ring (4). Cross-reactions have been reported betweenketoprofen and other arylpropionicderivatives such ibuproxam (5),tiaprofenic acid (6), suprofen (7),piketoprofen (8) and flurbiprofen(9). But, cross-reactivity has notbeen demonstrated in other cases ofcontact dermatitis due to piketoprofen(10) or ketoprofen (11).

The photoallergic reaction toketoprofen appears to be related tothe benzophenone structure, thusexplaining the cross-reaction betweenthe arylpropionic derivatives, fenofi-brate and oxybenzone (5).

In the case of contact photoallergyfrom dexketoprofen, fenofibrate andtopicals containing benzophenonesor ketoprofen are contraindicated(12). In the study performed withour NSAIDs series (Table 1), somearyl propionic derivatives did notshow cross-reactivity with dexketo-profen (naproxen and ibuprofen).Other arylpropionic derivatives thatdo not contain the benzophenonemoiety in their structure (such asnaproxen) may thus still be used.

References

1. Valenzuela N, Puig L, Barnadas M A,Alomar A. Photocontact derma-titis due to dexketoprofen. ContactDermatitis 2002: 47: 237.

2. BagheriH,LhiamberV,MontastrucJL,Chouni-Lahanne N. Photosensitivity

to ketoprofen: mechanisms and phar-macoepidemiological data. Drug Saf2000: 22: 339–349.

3. Ophoswongse S, Maibach H. Topicalnonsteroidal antiinflammatory drugs:allergic and photoallergic contactdermatitis and phototoxicity. ContactDermatitis 1993: 29: 57–64.

4. Sugiura M, Hayakawa R, Xie Z,Sigiura K, Hiramoto K, Shamoto M.Experimental study on phototoxicityand the photosensitization potentialof ketoprofen, suprofen, tiaprofenicacid and benzophenone and thephotocross-reactivity in guinea pigs.Photodermatol Photoimmunol Photo-med 2002: 18: 82.

5. Cusano F, Capozzi M. Photocontactdermatitis from ketoprofen withcross-reactivity to ibuproxam. Con-tact Dermatitis 1992: 27: 50–51.

6. Le Coz C J, Botthaender A, ScrivenerJ N et al. Photocontact dermatitisfrom ketoprofen and tiaprofenicacid: cross-reactivity study in 12consecutive patients. Contact Derma-titis 1998: 38: 245–252.

7. Kurumayi Y, Oshiro Y, Miyamoto C,Keong Ch, Kotoh T, Nishioko K.Allergic photocontact dermatitis dueto suprofen. Photopatch testing andcross-reaction study. Contact Der-matitis 1991: 25: 218–223.

8. Garcıa Bara M T, Matheu V, Perez A,Dıaz M P, Martınez M J,Zapatero L. Contact photoderma-titis due to ketoprofen and piketopro-fen. Alergol Immunol Clin 1999: 14:148–150.

9. Kawada A, Haragana Y, Maeda A,Yudate T, Tezuka T. Contactdermatitis due to flurbiprofen.Contact Dermatitis 2000: 42: 167–168.

10. Goday J J, Oleaga J M, Gonzalez M,Del Pozo J, Fonseca E. Photoallergicdermatitis from piketorpofen. ContactDermatitis 2000: 43: 315.

11. Miralles J C, Negro J M, Sanchez-Gascon F, Garcıa M. Ketoprofencontact dermatitis with good piketo-profen tolerance. Alergol ImmunolClin 2001: 16: 105–108.

12. Durieu C, Marguery MC, Gionardo-Labadie F, Journe F, Loche F,

Table 1. Results of patch test

Patch test Photopatch test

Allergen % Vehicle D2 D4 D1 D3

Standard series — — — —NSAIDs seriesKetoprofen 1% pet. — — þþ þþRest of NSAIDs — — — —

Constituents of Enengel1Dexketoprofen 1% pet. — — þþ þþ

5% pet. — — þþ þþOther constituents — — — —

NSAIDs¼ non-steroidal anti-inflammatory drugs.

CONTACT POINT 283

Bazex J. Allergies de contact photo-aggravees et photoallergies de contactau ketoprofene: 19 cas. Ann DermatolVenereol 2001: 128: 1020–1024.

Address:Esther Cuerda GalindoDepartment of DermatologyCHU Juan CanalejoXubias de Arriba 8415006 A Coruna, Spaine-mail: ecuerda@mundo-r.com

Contact urticaria due toketoprofen

T. Suzuki, A. Kawada, Y. Hashimoto,R. Isogai, Y. Aragane and T. Tezuka

Department of Dermatology, Kinki UniversitySchool of Medicine, Ohno-Higashi 377-2,Osaka-Sayama City, Osaka 589-8511, Japan

Key words: contact urticaria; cross-sensitivity; diclofenac; ketoprofen;loxoprofen; medicaments; non-steroidalanti-inflammatory drugs.

Case Report

A 24-year-old woman was seen inJanuary 2003 to investigate thecause of contact urticaria, whichhad been diagnosed in 2000. Wealand flare with itching had developedover the shoulder 1 h after shehad applied a poultice (Mohrus1,Hisamitsu Pharmaceut. Co. Ltd,Osaka, Japan) containing 0.3% keto-profen for muscle pain, followingwhich skin lesions had spread to thewhole body, with oropharyngealswelling.

Patch tests were performed on theback with ketoprofen 1%, 5% and10% pet., a constituent of the base,benzophenone-3 10% pet. and 2other non-steroidal anti-inflammatorydrugs (NSAIDs), loxoprofen sodium20% and 10% pet. and diclofenacsodium 10% pet. At 1 h afterapplication, urticarial responsesappeared at the sites of ketoprofen1%, 5% and 10% pet., loxoprofensodium 20% and 10% pet. anddiclofenac sodium 10% pet. thatfaded by 4h. These substancesshowed no reactions in 5 normalcontrol subjects.

Discussion

The common causes of contact urti-caria are foodstuffs, topical medica-tions, metals and various chemicals(1). In medicaments, some antibiotics,e.g. bacitracin, cephalosporins, chlor-amphenicol, gentamicin, neomycin,penicillin, rifamycin and streptomycin,tend to induce contact urticaria (1),whereas NSAIDs are very rare sensi-tizers. Ketoprofen frequently causescontact and photocontact dermatitisand photosensitivity (2, 3). Urticarialdrug eruptions from ketoprofen (4),loxoprofen sodium (5) or diclofenacsodium (6) are rarely seen, andno cases of contact urticaria fromthese drugs are reported in theliterature.

This case showed positive skintests to ketoprofen, loxoprofensodium and diclofenac sodium,which have 2-phenyl acetate in com-mon between their structures (Fig. 1),suggesting cross-sensitivity betweenthem.

References

1. Rietschel R L, Fowler J F Jr. Con-tact urticaria. In: Fisher’s ContactDermatitis, Rietschel R L, Fowler, J FJr, (eds), 5th edition. Philadelphia:Lippincott Williams & Wilkins, 2001:581–604.

2. Litt J Z, Ketoprofen. In: DrugEruption Reference Manual 2000,Litt J Z (ed.). New York: The Parthe-non Publishing Group, 2000:310–311.

3. Kawada A, Aragane Y, Asai M,Tezuka T. Simultaneous photocon-tact sensitivity to ketoprofen andoxybenzone. Contact Dermatitis2001: 44: 370.

4. Frith P, Dolovich J, Hargreave F E.Life-threatening asthma, urticaria,and angiooedema after ketoprofen.Lancet 1978: 2: 847–848.

5. Kimura M, Kawada A, Hiruma M,Ishibashi A. A case of urticarialdrug eruption from loxoprofensodium. Clin Exp Dermatol 1997: 22:303–304.

6. Gala G, Blanco R, Quirce S, Perez-Camo I, Alvarez-Fernandez J A,Diez-Gomez M L. Diclofenac-

O

O

CH3

CH3

CHCO2H Ketoprofen

CH2 CHCO2Na.2H2O

ClCl

NH

CH2COONa

Loxoprofen sodium

Diclofenac sodium

Fig. 1. Chemical structures of ketoprofen, loxoprofen sodium and diclofenacsodium.

284 CONTACT POINT

induced urticaria with aspirin toler-ance. Allergy 1998: 53: 623–624.

Address:Akira Kawada, MD, PhDDepartment of DermatologyKinki University School of MedicineOhno-Higashi 377-2Osaka-Sayama CityOsaka 589-8511JapanTel: þ81 72 366 0221Fax: þ81 72 368 2120e-mail: kawada@med.kindai.ac.jp

Contact dermatitis dueto eugenol used to treatoral lichen planus

Yasuyuki Fujita, Tadamichi Shimizu, WataruNishie and Hiroshi Shimizu

Department of Dermatology, HokkaidoUniversity Graduate School of Medicine,N15W7 Kita-ku, Sapporo, 060-8638, Japan

Key words: allergic contact dermatitis;dentistry; eugenol; medicaments; non-specific oral ulceration; oral lichen planus.

Case Report

A 66-year-old man, with a history ofhepatitis C viral infection and dentaltreatment (for more than 10 years),presented with painful erosions onthe lips and buccal mucosa, whichhe had been experiencing for 8years. In a dental clinic nearby, hehad been prescribed topical and oralcorticosteroid for this as oral lichenplanus. In spite of these treatments,the erosions had gradually becomeexacerbated over the last 2 years andformed non-specific ulceration.A biopsy taken from the upper lipshowed a loss of mucous epitheliumand haemorrhage. Saw-toothedacanthosis, liquefaction and band-like lymphocytic infiltration of thesuperficial dermis were also noted atthe wound periphery. Histologicalfindings and the clinical history cor-responded with oral lichen planus,but the formation of non-specificulceration suggested some additionaldisease such as contact dermatitis. Hehad been prescribed an ointmentfor the past 2 years, containinghaemodialysate from calf’s blood

(Solcoseryl1), lidocaine hydrochloride(Xylocaine1) and eugenol for thepurposes of ulcer treatment andlocal anaesthesia. We stopped theointment, and the ulcer and painmarkedly improved with 2 weeks oftreatment with mometasone furoate(Fulmeta1) ointment. He was patchtested with a series of metals and anas-is test of the ointments that he hadused. He showed a positive reaction(þ) only to the ointment and eugenol(2% and 0�2% pet.) at D3.

Comment

Eugenol is yellowish oil, which isextracted from cloves and cinnamonleaves (1). Its main property is anaes-thetic, and it is much used in dentis-try in the form of zinc oxide-eugenol(ZOE) cement. It is well documentedthat eugenol has the potential tocause contact dermatitis, especiallyamongst dental workers (2, 3).In addition, a case of oral contactdermatitis has also been reporteddue to mouthwash containing eugenol(4). Eugenol is also widely used as acomponent of perfumes and essentialoils. 27% of domestic and occupa-tional products with aroma availablein Europe contain eugenol (5). About2�5% of patients suspected of perfumeallergy have a positive reaction toeugenol on patch testing (6).

Sometimes contact sensitivity onthe lips causes a lichenoid reaction,which can be diagnosed as lichenplanus (7). In our case, re-biopsyafter epithelialization showed thecharacteristic pathological findingsof lichen planus. Together, based onthese findings, we confirmed thediagnosis of oral lichen planus,which was mixed with and exacer-bated by contact dermatitis.

While eugenol is usually used asZOE, some dentists apply it for itsanaesthetic effect for certain oral dis-orders such as lichen planus. Derma-tologists should be aware thateugenol, widely used in dentistry,may cause oral contact dermatitis.

References

1. Hendee W R. Evaluation of thehealth hazard of clove cigarettes.JAMA 1988: 260: 3641–3644.

2. Kanerva L, Estlander T, Jolanki R.Dental nurse’s occupational allergiccontact dermatitis from eugenol usedas a restorative dental material with

polymethylmethacrylate. ContactDermatitis 1998: 38: 139–140.

3. Rudzki E, Rebandel P, Grzywa Z.Patch tests with occupational contac-tants in nurses, doctors and dentists.Contact Dermatitis 1989: 20: 247–250.

4. Vilaplana J, Grimalt F, Romaguera C,Conellana F. Contact dermatitis fromeugenol in mouthwash. ContactDermatitis 1991: 24: 223–224.

5. Rastogi S C, Heydorn S, Johansen JD,Basketter D A. Fragrance chemicalsin domestic and occupational pro-ducts. Contact Dermatitis 2001: 45:221–225.

6. Wohrl S, Hemmer W, Focke M,Gotz M, Jarisch R. The significanceof fragrance mix, balsam of Peru,colophony and propolis as screeningtools in the detection of fragranceallergy. Br J Dermatol 2001: 145:268–273.

7. Yiannias J A, Azhary R A, Hand J H,Pakzad S Y, Rogers R S III. Relevantcontact sensitivities in patients with thediagnosis of oral lichen planus. J AmAcad Dermatol 2000: 42: 177–182.

Address:Dr Tadamichi ShimizuDepartment of DermatologyHokkaido University Graduate Schoolof MedicineN15W7 Kita-kuSapporo 060-8638, JapanTel: þ81 11 716 1161x5962Fax: þ81 11 706 7820e-mail: michiki@med.hokudai.ac.jp

Allergic contactdermatitis from1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy) ethyl]-1H-imidazole in awater-basedmetalworking fluid

Willem P. Piebenga and Henk B. van derWalle

Centrum voor Huid en Arbeid, Arnhem (Gld),The Netherlands

Water-based metalworking fluids(MWF) frequently cause irritantcontact dermatitis (1, 2), and someof their constituents, especiallybiocides, may induce allergic contactdermatitis (3).

Key words: allergic contact dermatitis;fungicide; imazalil; water-basedmetalworking fluid.

CONTACT POINT 285

Case Report

A 53-year-old metalworker with nohistory of skin disorders developedeczema on his hands. In the earlyphase of the eczema, there wasalmost complete recovery after 2–3days off work, but restarting his jobresulted in recurrence after 4–5 days.Over the years, despite topical cortico-steroids and emollients, his eczemaworsened. For complete recovery, aperiod of 3–4 weeks off work becamenecessary. When he visited our cen-tre, there was no recovery anymoredespite 1 year off work. Furtherquestioning revealed that a fewyears before there had been a changein the brand of metalworking fluid(MWF). Examination showed achronic severe dermatitis of bothhands and wrists. Patch tests wereperformed with the European stand-ard series, cosmetic and metalworkingseries, together with 2 preparationsof his own MWF. We could notobtain any information from themanufacturer of his MWF and itscomponents. There were positivereactions to colophonium, abieticacid and his MWF (Table 1). Later,we were able to obtain the coopera-tion of the manufacturer of theMWF in providing information. Abiocide, 4,4-methylenebismorpholineand a fungicide, 1-[2-(2,4-dichloro-phenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (Fungamet, Janssen Phar-maceutica, Beerse, Belgium], wereused. Neither ingredient had been

tested previously. Further patch tests(Table 2) were performed and gave apositive reaction to Fungamet; controltesting in 4 persons being negative.

Discussion

As far as we know, 1-[2-(2,4-dichloro-phenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole (CAS no. 73790-28-0) hasnever before been reported as apotential allergen in MWF (2–4).The trademark name is Fungametor Imazalil, which is a solutionof 70% 1-[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole in30% monoethylene glycol. For veter-inary or agriculture purposes, this isbetter known as enilconazole andused for dermatophytic infections ofhorses, cows and dogs as well as inthe control of plant-pathogenicfungi (6). There is 1 previous reportof contact sensitivity to enilconazole(5, 6).

References

1. Huhner A, Fartasch M, Hornstein OP, Diepgen T L. The irritant effect ofdifferent metalworking fluids. Con-tact Dermatitis 1994: 31: 220–225.

2. Kanerva L, Elsner P, Wahlberg J E,Maibach H I (eds). Handbook ofOccupational Dermatology. Berlin:Springer, 2000.

3. Rietschel R L, Fowler Jr, Joseph F.Fisher’s Contact Dermatitis, 5thedition. Philadelphia: LippincottWilliams & Wilkins, 2001.

4. De Boer E M. Occupational Dermati-tis by Metalworking Fluid. Thesis.Amsterdam: Vrije Universiteit, 1989.

5. Dooms-Goossens A, Matura M,Drieghe J, Degreef H. Contact allergyto imidazoles used as antimycoticagents. Contact Dermatitis 1995: 33:73–77.

6. Van Hecke E, De Vos L. Contactsensitivity to enilconazole. ContactDermatitis 1983: 9: 144.

Address:Willem P. PiebengaCentrum voor Huid en ArbeidWagnerlaan 556815 AD ArnhemThe NetherlandsTel: þ26 378 7815Fax: þ26 378 7812e-mail: info@huidenarbeid.nl

Contact allergy toDisperse Blue 106/124mix in consecutiveGerman, Austrian andSwiss patients

Wolfgang Uter1*, Johannes Geier2* andBjorn M. Hausen3*1Department of Medical Informatics,Biometry and Epidemiology, University ofErlangen-Nurnberg, Erlangen, 2InformationNetwork of Departments of Dermatology(IVDK), Georg August University,Department of Dermatology, Gottingen, and3Dermatology Centre, Buxtehude, Germany

Key words: clinical epidemiology, contactallergy; Disperse Blue 106/124; textile dyedermatitis.

Recently, we reported an increasingfrequency of contact allergy toDisperse Blue (DB) 106/124 in select-ively tested patients in Germany andAustria (1). Since May 2001, a mix ofDB 106 and 124 (1% pet., Hermal/Trolab, Reinbek, FRG) was patchtested in consecutive patients in thecentres of the German ContactDermatitis Group (DKG) and theInformation Network of Depart-ments of Dermatology (IVDK)(http://www.ivdk.org) listed in thefootnote. The mix was added to thestandard series in a so-called ‘moni-tor series’. Results obtained up to theend of July 2002 are presented.

Table 1. Initial positive patch test results

Test substance D2 D4

Colophonium (20% pet.) þþ þþþAbietic Acid (10% pet.) þþþ þþþOwn MWF concentrate (10% MEK) þ þþOwn MWF as used (undiluted) þþ þþ

MWF¼metalworking fluid.

Table 2. Further positive patch test results in patient and controls

Test substance Subject D2 D4

Fungamet (1% eth.) Patient ?þ þControl 1 – –Control 2 – –Control 3 – –Control 4 – –

4,4-methylenebismorpholine (0�3% aq.) Patient – –Control 1 – –Control 2 – –Control 3 – –Control 4 – –

286 CONTACT POINT

3041 patients were patch testedwith DB 106/124 mix in 13 centres.Overall, 40 patients reacted posi-tively, the grading of reactions beingsimilar to that in the previous study(1). The national and regional vari-ation differed remarkably: in 3 centres,less than 0�5% positives; in 2, noreactions at all; and in the remaining8 centres, at least 1% positives, withBasel ranking top (6�2%, P< 0�05 forBasel versus the remaining centres).Concomitant reactivity to p-phenyl-enediamine (PPD) hardly exceededchance (Cohen’s k¼ 0�051, 95%CI¼ 0�00–0�11), with marked asym-metry (i.e. many more positive reac-tions to PPD among the discordantpairs, P< 0�0001, exact McNemar’stest) very similar to the previousanalysis.

Logistic regression analysis ofimportant patient characteristics(MOAHLFA index (2)) as potentialrisk factors for positive reactivity toDB 106/124 showed significantlyincreased risk in females and patientsaged 40 or older (P< 0�05), althoughthe power of the study was limited byits small size (Table 1). Model fit, asassessed with theHosmer& Lemeshowtest, was excellent (P¼ 0�903).

In conclusion, contact allergy to DB106and124 appears frequent enough inconsecutive patients to warrant furtherinvestigation. In some countries, highproportions of sensitized patients havebeen reported (3, 4), in linewith ourownobservations from Basel, Switzerland.However, the degree of exposure islargely unknown; possibly, importedclothing poses a particular risk (5).Taken together, these facts sufficientlysupport the current inclusion of the DBmix as a valuable screening agent (6) inthe European standard series.

References

1. Uter W, Geier J, Lessmann H,Hausen B M. Contact allergy toDisperse Blue 106 and Disperse Blue124 in German and Austrianpatients, 1995 to 1999. ContactDermatitis 2001: 44: 173–177.

2. Schnuch A, Geier J, Uter W, et al.National rates and regional differ-ences in sensitization to allergensof the standard series. Populationadjusted frequencies of sensitization(PAFS) in 40,000 patients from amulticenter study (IVDK). ContactDermatitis 1997: 37: 200–209.

3. Menezes Brandao F, Altermatt C,PecegueiroM, Bordalo O, Foussereau J.Contact dermatitis to Disperse

Blue 106. Contact Dermatitis 1985: 13:80–84.

4. Seidenari S, Giusti F, Massone F,Mantovani L. Sensitization to dis-perse dyes in a patch test populationover a five-year period. Am J ContactDermat 2002: 13: 101–107.

5. Platzek T, Wannack T, Stahlmann R,Riecke K, Lang C, Hocker H.Textilfarbstoffe – Regulation undexperimentelle Studien. Bundesge-sundheitsbl Gesundheitsforsch Gesund-heitsschutz 2001: 44: 695–704.

6. Pratt M, Taraska V. Disperse Bluedyes 106 and 124 are common causesof textile dermatitis and should serveas screening allergens for this condi-tion. Am J Contact Dermat 2000: 11:30–41.

Address:Wolfgang UterDepartment of Medical InformaticsBiometry and EpidemiologyUniversity of Erlangen-NurnbergErlangen, Germanye-mail: wolfgang.uter@rzmail.uni_erlangen.de

Nickel-induced angularcheilitis due toorthodontic braces

P. D. Yesudian1 and A. Memon2

1Department of Dermatology, RoyalLiverpool University Hospital, Liverpool, and2Department of Dermatology, DistrictGeneral Hospital, Ormskirk, UK

Key words: angular cheilitis; nickel;orthodontic brace.

Case Report

A 12-year-old boy presented with a10-month history of persistent sore-ness and splitting in the angles of themouth. He denied lip licking or use ofany cosmetic preparations on his faceor lips and had not changed his tooth-paste recently. The only relevant pastmedical history was the insertion ofmetallic orthodontic braces, 2 monthsprior to the onset of the rash. Therewasno personal or family history of atopy.On examination, an angular cheilitiswas evident, with some fissuringassociatedwith it. There was no eczema

*For the IVDK and The Germa Contact Dermatitis Research Group. Centres ofthe IVDK contributing to this analysis (in alphabetical order): Basel (A. Bircher),Dresden (R. Aschoff), Gottingen (Th. Fuchs), Graz (W. Aberer, B. Kranke), Halle/Saale (G. Gaber, D. Lubbe), Homburg/Saar (P. Koch), Jena (A. Bauer, M. Kaatz,S. Schliemann-Willers), Krefeld (M. Lilie, A. Wallerand, S. Wassilew), Lubeck(J. Grabbe), Marburg (I. Effendy, H. Loffler), Munchen Schwabing (M. Agathos),Ulm (P. Gottlober, G. Staib, H. Pillekamp, R. Hinrichs) and Wurzburg (J. Arnold,A. Trautmann).

Table 1. Comparative demographic characteristics of patients reacting positivelyto Disperse Blue (DB) 106/124 mix (1% pet.), May 2001 to July 2002, supplementedwith results of a logistic regression analysis, outcome ‘DB positive’ versus ‘DB negative’

Total tested(n¼ 3041)

Positive(n¼ 40) OR (95% CI)

Male M 35�0 20�0 0�45* (0�19–0�95)Occupationaldermatitis

O 12�2 7�5 0�80 (0�18–2�60)

Atopic dermatitis A 17�6 17�5 1�23 (0�48–2�75)Hand dermatitis† H 22�9 17�5 0�44 (0�10–3�08)Leg dermatitis† L 10�6 10�0 0�35 (0�07–2�55)Face dermatitis† F 14�6 12�5 0�35 (0�07–2�52)Age 40þ A 64�2 82�5 2�69* (1 21–6�82)

*Significant (P< 0�05).†Additional sites contained in model to allow for full coding: arm, feet, head(excluding face) or neck, trunk with axillae, anogenital (as reference), ‘other’ andmissing site – none of these sites being a significant explanatory factor.

CONTACT POINT 287

around the mouth and no evidence ofgingivostomatitis or erosions of theoral mucosa. Bacterial andmycologicalswabs from the angles of the mouthwere negative. The condition had failedto respond to a variety of emollients,topical corticosteroids and antifungalsprescribed by the general practitioner(GP). A clinical diagnosis of nickel-induced angular cheilitis due toorthodontic braces was made.

He was patch tested with theEuropean standard series and histoothpaste. There was a strongpositive reaction to nickel sulfateon day 2 (D2) þþ and D4 þþþ.No reactions were seen with theremaining patch tests. This confirmedour clinical suspicion of nickel-inducedangular cheilitis due to orthodonticbraces. Removal of the braces resultedin complete remission of the angularcheilitis. Follow-up over a period of18 months has shown no recurrenceof the condition.

Discussion

Angular cheilitis is an eczematous erup-tion of the skin and contiguous labialmucous membrane at the angle of themouth. A variety of aetiological factorshave been described, including candi-dosis, bacterial infections, mechanicalirritation, nutritional deficiencies andconditions associated with hypersali-vation, which causes maceration andinflammation. Atopic and seborrhoeiceczema can also be associated with thiscondition (1). Our patient had none ofthese other aetiological factors, andswabs ruled out the possibility of aninfective cause.

A variety of metals are used inorthodontic braces and wires. Stainlesssteel is the most frequently used alloyand consists of chromium, nickel,molybdenum, iron, carbon, silicon andmanganese (2). Even though nickel andothermetals used in dentistry have beenknown to cause oral lichenoid reactions(3), nickel sensitivity is more commonlyassociated with a generalized skineruption includingurticaria andeczema(4). Contact cheilitis and stomatitishave been reported from nickel (5, 6).However, the occurrence of angularcheilitis following contact sensitivity tonickel in braces has not been reported.Nickel is released from such metallicdevices by contact between saliva (5)and orthodontic braces. Subsequent

stagnation of saliva in the angles of themouth, a factor more likely in patientswearing braces, makes this a probablesite of sensitization, resulting in angularcheilitis. We suggest patch testing inpatients wearing braces presentingwith angular cheilitis. Removal of thebraces or substitution of nickel withvitallium can be suggested in thosefound to be allergic to the metal.

References

1. ChampionRH,Burton J L, BurnsDA,Breathnach S M (eds). Textbook ofDermatology, 6th edition: Oxford,Blackwell Science, 1998.

2. Grimalt F, Romaguera C. Acutenickel dermatitis from a metalimplant. Contact Dermatitis 1980: 6:441.

3. Hay I C, Ormerod A D. Severe oraland facial reaction to 6 metals inrestorative dentistry. Contact Derma-titis 1998: 38: 216.

4. Jones T K, Hansen C A, Singer M T,Kessler H P. Dental implications ofnickel hypersensitivity. J ProsthetDent 1986: 56: 507–509.

5. Thomas P, Rueff F, Przybella B.Cheilitis due to nickel contact allergyin a trumpet player. Contact Derma-titis 2000: 42: 351–352.

6. van Loon L A J, van Elsas P W, vanJoost T H, Davidson C L. Contactstomatitis and dermatitis to nickeland palladium. Contact Dermatitis1984: 11: 294–297.

Address:P. D. Yesudian10 C LinkRoyal Liverpool University HospitalLiverpool L7 8XP, UKTel: þ44 151 706 200Fax: þ44 151 706 597e-mail: pdyesudian@hotmail.com

Allergic contactreactions to dental gold

Helene Meyer Tvinnereim1, Birgitte FosLundekvam1, Tore Morken2, Morten E.Berge3 and Lars Bjorkman1

1Dental Biomaterials Adverse Reaction Unit,2Department of Dermatology, and3Department of Odontology, University ofBergen, Arstadveien 17, N-5009 Bergen,Norway

Key words: allergic contact; dental patients;dermatitis; gold alloys; lichenoid eruptions.

Case Report

A 62-year-old, non-smoking, full-time housewife, with no family orpersonal history of atopy, presentedwith a lichenoid intra-oral reaction toan 11-unit fixed gold-acrylic restor-ation inserted 7 years earlier, in 1993.Within a short time after insertion,she developed angular cheilitis andcomplained of temporomandibularjoint pain, oral muscular pain, oraldryness and perioral dermatitis. In1994, this progressed to eyelid derma-titis. Patch testing with the Europeanstandard series was negative. Thepatient’s discomfort continued, andin 1997 the symptoms resembledthose of temporomandibular disorders(TMDs). The patient had whitelesions bilaterally on the buccalmucosa. A biopsy confirmed lichenplanus.

In 1998, patch testing with adental screening series (Chemotech-nique Diagnostics, Tygelsjo, Sweden)showed positive reactions to goldsodium thiosulfate 2% (pet.) (þþ)and potassium dicyanoaurate 0�1%aq. (þþ) at day 3. However, thepatient had, at that time, no signs ofcontact stomatitis, and the clinicalrelevance of the positive tests wasquestioned. She had no reactions toher gold ring.

In February 2000, the patientshowed lichenoid reactions bilat-erally on the buccal mucosa (Fig. 1).She complained of a burning sensa-tion, metallic taste and dryness in theoral cavity and throat. As a tentativetreatment, the fixed gold/acrylicpartial denture was removed, aswere also 3 single gold crowns. Theywere replaced with fixed restorationsin titanium/ceramic. Intra-radiculargold posts were not removed becauseof the risk of complications (e.g. rootfracture). After removal of the goldrestorations, the lichenoid reactionhealed within the next few weeks.The oral dryness was reduced, andthe patient had no complaints oforal discomfort (Fig. 2).

Discussion

During recent years, there has beenincreasing interest in allergic reactions

288 CONTACT POINT

to gold compounds (1–3). An over-representation of gold allergies hasbeen found among patients withdental restorations containing gold(4, 5). However, in many cases, theclinical relevance of a positive patchtest has been uncertain. Thus, it hasbeen suggested that gold sodiumthiosulfate should not be included inthe standard series but applied only

when allergic contact dermatitis fromgold is suspected or for research pur-poses (6). Ahlgren et al. (7) found astatistically significant positive corre-lation between the amount of dentalgold restorations and contact allergyto gold.

In the present case, the patient wasexposed to a relatively large numberof tooth surfaces restored with gold.

The patient’s recovery is an indica-tion of gold allergy as the cause ofher discomfort and of the lichenoidcontact reaction of the oral mucosa.The patient acquired the diagnosis ofTMD, even though she had normalocclusion. It could be hypothesizedthat the oral pain and discomfortwas in part related to the gold allergy.However, as insertion of fixedrestorations is an extensive mode oftreatment, removal of gold restora-tions is recommended only whenobjective signs or clinically relevantcontact allergy (i.e. local reactionsor dermatitis) are present.

References

1. Bjorkner B, Bruze M, Moller H. Highfrequency of contact allergy to goldsodium thiosulfate. An indication ofgold allergy? Contact Dermatitis1994: 30: 144–151.

2. Silva R, Pereira F, Bordalo O, et al.Contact allergy to gold sodium thio-sulfate. A comparative study. ContactDermatitis 1997: 37: 78–81.

3. Ahnlide I, Bjorkner B, Bruze M,Moller H. Exposure to metallic goldin patients with contact allergy togold sodium thiosulfate. Contact Der-matitis 2000: 43: 344–350.

4. Bruze M, Edman B, Bjorkner B,Moller H. Clinical relevance ofcontact allergy to gold sodiumthiosulfate. J Am Acad Dermatol1994: 31: 579–583.

5. Vamnes J S, Morken T, Helland S,Gjerdet N R. Dental gold alloys andcontact hypersensitivity. ContactDermatitis 2000: 42: 128–133.

6. Bruze M, Andersen K E. Gold – acontroversial sensitizer. EuropeanEnvironmental and Contact Derma-titis Research Group. Contact Der-matitis 1999: 40: 295–299.

7. Ahlgren C, Ahnlide I, Bjorkner B,et al. Contact allergy to gold is corre-lated to dental gold. Acta DermVenereol 2002: 82: 41–44.

Address:Helene Meyer TvinnereimDental Biomaterials Adverse ReactionUnitUniversity of Bergen/UNIFOBN-5009 BergenNorwaye-mail: helene.tvinnereim@odont.uib.no

Fig. 1. Reactions to gold restorations on the buccal mucosa.

Fig. 2. Buccal mucosa 8 months after removal of gold restorations.

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Allergic contactdermatitis due topropylene glycol andparabens in anultrasonic gel

Patricia Eguino, Ana Sanchez, Nerea Agesta,Olatz Lasa, Juan Antonio Raton, and JoseLuis Dıaz-Perez

Department of Dermatology, CrucesHospital, 48903 Barakaldo, Bizkaia, Spain

Key words: allergic contact dermatitis;parabens; preservatives; propylene glycol;ultrasonic gel.

Case Report

A 62-year-old man developed derma-titis 24 h after an ultrasonic gel hadbeen applied on his right leg. He hada previous history of circulatoryproblems and stasis dermatitis onboth legs. Also, he had had occa-sional intolerance to some facialcosmetics. The ultrasound gel usedwas Aquasonic 100 transmission gel(Parker Laboratory Inc., NJ, USA).The eruption subsided in 4 days withtopical corticosteroids.

Patch testing with our standardseries (GEIDC) and the ultrasonic gelwas positive to fragrance mix,Myroxy-lon Pereirae resin, paraben mix andthe gel. We asked the manufacturer forthe components of the gel, and they sent

us the different ingredients blinded tous, in the same concentrations as in thegel, listed as humectant and preserva-tives M and P. Patch tests wereperformed with these and were positiveto all 3 atD4. 14 controlswere negative.The manufacturer informed us thatthese components were propyleneglycol, methyl paraben and propylpar-aben, though they refused to give ustheir exact concentrations. Later, itwas confirmed that, in the case of theparabens, both were presented at bac-teriostatic concentrations (<3%).Further patch tests with propyleneglycol at several known concentrationswere declined by the patient.

Discussion

Allergic contact dermatitis fromultrasonic gels is rare, consideringtheir daily use all over the world.Most of the previously reportedcases of allergic contact dermatitiswere due to propylene glycol (1–4)and Euxyl K-400 (5–7). Positivepatch tests with the other preserva-tives (methyl and propylparabens)have not been previously describedin association with allergic contactdermatitis from ultrasonic gels,though imidazolidinyl urea (8) hasbeen so reported.

References

1. Funk J O, Maibach H I. Propyleneglycol dermatitis: reevaluation of anold problem. Contact Dermatitis 1994:31: 236–241.

2. Catanzaro J M, Smith J G. Propyleneglycol dermatitis. J Am Acad Dermatol1991: 24: 90–95.

3. Aberer W, Fuchs Th, Peters K P,Frosch P J. Propylenglykol: KutaneNebernwirkungen und Testmethodik.Literaturubersicht und Ergebnisseeiner Multicenterstudie der DeutschenKontaktallergiegruppe (DKG). DermBeruf Umwelt 1993: 41: 25–27.

4. UterW,SchwanitzHJ.Contact derma-titis from propylene glycol in ECGelectrode gel. Contact Dermatitis1996: 34: 230–231.

5. Gebhart M, Stuhlert A, Knopf B.Allergic contact dermatitis due toEuxyl K-400 in an ultrasonic gel.Contact Dermatitis 1993: 29: 272.

6. Leitner B, Hemmer W, Focke M.Kontaktdermatitis auf Ultraschall-ghel. Dematosen 1999: 47: 164–165.

7. Erdmann S B, Sachs B, Merk H F.Allergic contact dermatitis due tomethyl dibromoglutaronitrile inEuxyl K-400 in an ultrasonic gel.Contact Dermatitis 2001: 44: 39–40.

8. Ando M, Ansotegui I J, Munoz D,Fernandez de Corres L. Allergiccontact dermatitis from imidazolidi-nyl urea in an ultrasonic gel. ContactDermatitis 2000: 42: 109–110.

Address:Patricia EguinoDepartment of DermatologyCruces Hospital48903 BarakaldoBizkaia, Spain

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