Amaro, C

Cravo, M

Fernandes, C

Gonçalo, Margarida

Santos, R

Cristina Amaro

Mariana Cravo

Cândida Fernandes

Raquel Santos

Margarida Gonçalo

Crossref

Contact Dermatitis

Undisclosed methyldibromo glutaronitrile causing allergic contact dermatitis in a NSAID cream

CHUC Institutional Repository

Name not available

Repositório Institucional dos Hospitais da Universidade de Coimbra

Contact Dermatitis • Contact PointsCONTACT ALLERGY TO A PRESERVATIVE IN A TOPICAL DRUG • AMARO ET AL.Undisclosed methyldibromo glutaronitrile causing allergic contactdermatitis in a NSAID creamCristina Amaro1, Mariana Cravo2, Caˆndida Fernandes1, Raquel Santos1 and Margarida Gonc¸alo21Department of Dermatology, Hospital de Curry Cabral, 1069-166 Lisbon, Portugal and 2Department of Dermatology, Hospitais da Universidade de Coimbra,Coimbra, Portugaldoi:10.1111/j.1600-0536.2012.02091.xKey words: allergic contact dermatitis; Euxyl K 400; methyldibromo glutaronitrile; preservative; topical drug.The allergenicity of methyldibromo glutaronitrile (MDBGN) (1,2-dibromo-2,4-dicyanobutane) is well recog-nized, both in occupational and in non-occupational set-tings (1). Used as a preservative, alone or in combinationwith phenoxyethanol (Euxyl K 400), in metalworkingfluids, cosmetics, adhesives, andmoist toilet tissues, itwasidentified as an increasingly important allergen soon afterits launch in the 1980s (2, 3). The increasing rates ofsensitization to this preservative prompted the EuropeanCommission to restrict its use, first in leave-on (4), andlater also in rinse-off cosmetics (5). Despite these recom-mendations, which have shown to be successful in reduc-ing the prevalence of contact allergy to this molecule (3),someimportantconsumerproducts, suchas topicaldrugs,are still not subject to regulatory intervention.We report two cases of allergic contact dermatitiscaused by MDBGN in a topical non-steroidal anti-inflammatory cream.PatientsCase Report 1In April 2006, a 53-year-old male electrician presentedwithanextensive bullous eczema, initially localized tooneleg, knee, and arm, followed by a widespread eczematousreaction. On the days before, the patient reported havingappliedReumoxican cream(MedinfarLaboratories,Por-tugal), a topical non-steroidal anti-inflammatory creamcontaining piroxicam. He also had used, for longer peri-ods, Reumon gel (Bial Laboratories, Portugal), a non-steroidal anti-inflammatory gel containing etofenamate.Systemic steroids were needed to control the reaction.Correspondence: Cristina Amaro, Department of Dermatology, Hospital deCurry Cabral, Rua da Beneficeˆncia, no. 8, 1069-166 Lisbon, Portugal. E-mail:cristinacamaro@sapo.ptConflicts of interest: The authors have declared no conflicts.Case Report 2In November 2008, a 77-year-old female presentedwith a 2-week history of eczematous bullous lesionsaffecting both hands and the lower back, after havingappliedReumoxican cream(Medinfar Laboratories) anda topical antihistamine cream containing promethazine(Fenergan; Vito´ria Laboratories, Amadora, Portugal).The patient was treated with topical corticosteroids, withcomplete remission of the dermatitis in a few days.Patch TestsPatch testing was performed using Finn Chambersand according to the International Contact DermatitisResearch Group criteria, with the Portuguese baselineseries. Photopatch tests were performed in duplicatewith a non-steroidal anti-inflammatory drug (NSAID)series or a more extended photopatch test series andpatients’ own products, with irradiation of one set atD2 with 5 J/cm2 ultraviolet A (UVA). Both patientsreacted to MDBGN 0.3% pet. (Trolab) [+++, patient 1(Fig. 1a), and++, patient 2] and to Reumoxican cream(Fig. 1b), inbothnon-irradiatedand irradiatedareas,withidentical intensity. Piroxicam10% pet. (ChemotechniqueDiagnostics) patch and photopatch testing gavenegative results. Patient 2 reacted also to the irradiatedFenergan cream containing promethazine (++). Thispatientwas further patch-testedwith all of the ingredientsof Reumoxican cream, andhad a positive reaction (++)to Euxyl K 400 1% pet. (Medinfar Laboratories).MDBGN and phenoxyethanol were identified in theReumoxican labelled ingredients (0.4% Euxyl K 400,and therefore 0.08%MDBGN).DiscussionTopical NSAIDs are widely prescribed by family physi-cians, and are used as over-the-counter drugs for their© 2012 John Wiley & Sons A/SContact Dermatitis, 67, 171–177 173Contact Dermatitis • Contact PointsDRAWING HELPED THE PHYSICIAN TOMAKE THE CORRECT DIAGNOSIS • FRIIS ET AL.(a) (b)Fig. 1. (a) Positive patch test reaction tomethyldibromo glutaronitrile 0.3% pet. and(b) Reumoxican cream (case 1).analgesic/anti-inflammatory effects in cream or gelformulations. They have been reported to cause aller-gic or photoallergic contact dermatitis, particularly fromthe active ingredients.We report two cases of allergic con-tact dermatitis resulting from the use of Reumoxicancream, with negative reactions to the active ingredientpiroxicam. Both patients reacted to MDBGN, which wasidentified as an ingredient of this topical drug.This broad-spectrum biocide is, indeed, considered tohave caused an epidemic of contact allergy in Europe,and was therefore banned from cosmetics and toiletries,owing to high sensitization rates (3, 6).TheotherwisesuccessfulEUlegislationdoesnot includetopical drugs, which still occasionally contain this preser-vative. Moreover, unlike the situation with cosmetics,full labelling of ingredients is not compulsory for topicaldrugs and medical devices in some European countries.We stress the urgent need to extend regulatory interven-tions to topically applied medications, so that they can bemore safely used.References1 Zachariae C, Johansen J D, Rastogi S C,Menne´ T. Allergic contact dermatitis frommethyldibromo glutaronitrile – clinicalcases from 2003. Contact Dermatitis 2005:52: 6–8.2 Heratizadeh A, Killig C, WormM et al.Quantitative repeated open applicationtesting with a rinse-off product inmethyldibromo glutaronitrile-sensitivepatients: results of the IVDK. ContactDermatitis 2010: 62: 330–337.3 Johansen J D, Veien N, Laurberg G et al.Decreasing trends in methyldibromoglutaronitrile contact allergy – followingregulatory intervention. Contact Dermatitis2008: 59: 48–51.4 Commission of the European Communities.Commission directive 2003/83/EC of 24September 2003. Off J Eur Union 2003:L238: 23–27.5 Commission of the European Communities.Commission directive 2007/17/EC of 22March 2007. Off J Eur Union 2007: L82:27–30.6 Johansen J D, Veien N K, Laurberg G,Kaaber K, Thormann J, Lauritzen M,Avnstorp C. Contact allergy tomethyldibromo glutaronitrile – data from a‘front line’ network. Contact Dermatitis2005: 52: 138–141.© 2012 John Wiley & Sons A/S174 Contact Dermatitis, 67, 171–177

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Undisclosed methyldibromo glutaronitrile causing allergic contact dermatitis in a NSAID cream

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