Contact Sensitivity in Patients with Leg Ulcerations: a North American Study

STUDY Contact Sensitivity in Patients With Leg Ulcerations A North American Study

Liliana Saap, MD; Simone Fahim, MD; Emily Arsenault, MD; Melanie Pratt, MD; Tad Pierscianowski, MD; Vincent Falanga, MD; Anita Pedvis-Leftick, MD

Objectives: (1) To determine the prevalence of aller- had no positive patch test result. The most common al- gen sensitivity in patients with past or present leg ulcers lergens were Myroxylon pereirae (balsam of Peru) (30% in 2 North American study centers vs European study [16/54]), bacitracin (24% [13/54]), fragrance mix (20% findings and the North American Contact Dermatitis [11/54]), wood tar mix (20% [11/54]), propylene glycol Group (NACDG) database and (2) to delineate a stan- (14% [7/52]), neomycin sulfate (13% [7/54]), benzal- dard battery of allergens for patch testing in North Ameri- konium chloride (13% [7/54]), carba mix (11% [6/54]), can patients that is representative of the newer dress- nickel sulfate (11% [6/54]), and control gel hydrocol- ings and wound care products. loid (11% [6/54]).

Design: Fifty-four patients, with or without dermatitis, Conclusions: Comparable to European study findings, were prospectively entered in the study. The patients were there is a high incidence of positive patch test results in patch tested to the NACDG standard series and a com- patients with past or present leg ulcerations. The inci- prehensive supplemental series of 52 allergens. dences of the most common allergens in our patient population were higher than those seen in the NACDG, ex- Setting: Wound healing clinics at Boston University Roger cept for nickel. Using a modified leg ulcer series along Williams Medical Center and University of Ottawa. with the standard NACDG series is important in evalu- ating patients with leg ulcers. Results: Sixty-three percent (n=34) of patients had 1 or multiple positive patch test results, and 37% (n=20) Arch Dermatol. 2004;140:1241-1246

URING THE PAST 2 DE- It is suspected that the high inci- cades, European studies dence of sensitization in the leg ulcer pa- have investigated con- tient population is due to (1) the intrin- tact sensitivity in pa- sic allergenic properties of different tients with chronic leg ul- ointments and wound products used to cerations.D The frequency of positive patch heal the ulcer, (2) the excessive duration test results found in this patient popula- of use of these products, and (3) the dis- tion has ranged from 40% to 82.5%, and rupted skin barrier (increased permeabil- sensitivities have involved 1 or multiple ity and inflammation) to which these prod- allergens.1-10 One study4 found a direct re- ucts are applied.11 These conditions can lationship between the duration of leg ul- From the Department of Dermatology and Skin Surgery, cers and the number of multiple positive CME course available at Boston University Roger allergen sensitivities. These authors’ find- www.archdermatol.com Williams Medical Center, ings suggest that an ulcer of long dura- Providence, RI (Drs Saap, tion has greater opportunity for contact lead to contact dermatitis of the leg, ulti- Arsenault, Falanga, and with different allergens and leads to in- mately impairing healing and prolonging Pedvis-Leftick); Department of creased sensitivity to these allergens. morbidity associated with leg ulcer- Dermatology, University of Patients with leg ulcers frequently be- ations. Recurrence of leg ulcers may be due Ottawa, Ottawa, Ontario come sensitized to topical allergens. Ex- to persistent or recurrent dermatitis. (Drs Fahim, Pratt, and amples of these allergens include neomy- Although several groups have stud- Pierscianowski); and cin sulfate, lanolin alcohols, Myroxylon ied contact sensitization in leg ulcer pa- Departments of Dermatology and Biochemistry, Boston pereirae (balsam of Peru), Amerchol L101, tients in Europe, the incidence of sensiti- University, Boston, Mass colophony, fragrance mix, propylene gly- zation has not been studied in North (Dr Falanga). The authors have col, paraben mix, budesonide, tixocortol- America, to our knowledge. In addition, no relevant financial interest in 21-pivalate, thiuram mix, and nickel sul- many new wound care products have not this article. fate, among others.1-10 been recently tested for contact sensitiza-

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 METHODS Table 1. Leg Ulcer Series Developed at Our Study Centers* We prospectively recruited 54 patients (19 men and 35 wom- 10% Pet abietic acid 20% Pet gentamicin sulfate en; mean±SD age, 65.24±13.96 years) with past or present leg Alginate dressings Hydrocolloids ulcerations, regardless of etiology or presence or absence of der- Calcium alginate dressing Control gel hydrocolloid matitis. Twenty-two patients were recruited at the Advanced 2% Pet aluminum chloride Thin polyurethane Wound Healing Center of Boston University Roger Williams hexahydrate Medical Center, and 32 patients were recruited at the Wound 50% Pet amerchol L101 Hydrogels 0.25% Aqs ammonium Hydroactive gel Care Center of Ottawa Civic Hospital, Ottawa. Patients were tetrachloroplatinate excluded from participation in the study if they were receiv- (platinum) ing an oral prednisone dosage of 20 mg/d or higher, or if they Hydrogel with propylene glycol were receiving any oral immunosuppressive therapy (ie, cy- Antimicrobial barrier–silver Collagen hydrogel closporine, azathioprine, methotrexate, mycophenolate mofetil, release dressing or cyclophosphamide). Informed consent was obtained from 5% Pet butylated Hydrofibers all patients in accord with each study center’s human research hydroxyanisole (BHA) committee, and the study protocols conformed to the ethical 20%* Pet cetyl stearyl alcohol Hyaluronic acid ester guidelines of the 1975 Declaration of Helsinki. 0.2% Pet chloroacetamide Sodium carboxymethyl cellulose A comprehensive questionnaire was filled out by all the 0.5% Aqs chlorhexidine 1.5% Hydrogen peroxide cream patients and included a detailed history of ulcer duration, heal- digluconate ing times, frequencies of ulcer recurrence, past and present ul- 1% Pet 4-chloro-3-cresol 3% Aqs hydrogen peroxide cer treatment, any associated dermatitis, and allergic reac- (PCMC) 1% Aqs clotrimazole 0.1% Pet iodopropynyl tions. A physical examination was performed at the initial butylcarbamate evaluation and consisted of the following: general appearance, 5% Pet clioquinol evaluation of skin disease and presence and severity of any der- Composite Mupirocin cream matitis, description of lower extremity ulcerations, and evalu- Nonadherent perforated Mupirocin ointment ation of the vascular state, including dorsalis pedis pulses, ankle- absorbent dressing brachial index by Doppler testing (if the patient did not have Compression bandages Specialty absorptives diabetes mellitus), and results of Doppler testing of the arter- Paste bandage Cadexomer iodine gel ies and veins, if previously performed. Layer 1 (soft cotton 2% Pet sorbic acid Patch tests consisting of 110 allergens affixed to 8-mm- padding) diameter Finn Chambers were applied and taped in a standard- Layer 2 (orthopedic wool) 5% Pet sulfanilamide ized order to hairless skin on the backs of the patients. The patch Layer 3 (light elastic Topical steroids pet test allergens consisted of the 2001 standard series from the compression) NACDG (Dr Pratt, written communication, July 10, 2001) and Layer 4 (self-adherent 0.5% Amcinonide† a leg ulcer series designed at our study centers consisting of 52 compression bandage) Table 1 0.25% Pet dodecyl gallate 1% Betamethasone-17-valerate allergens ( ). The leg ulcer series included a battery of Debriding agents 1% Clobetasol-17-propionate cosmetic allergens, topical medicaments, and wound care prod- Papain-urea ointment 1% Dexamethesone-21- ucts typically used in patients with leg ulcers at our 2 study cen- phosphate ters and other North American wound healing centers. This leg Collagenase ointment 1% Triamcinolone acetonide ulcer series incorporated representative samples of the major types Foams Transparent film dressing of dressings and products used in wound healing, such as trans- Polyurethane foam 2% Pet triclosan parent films, foams, hydrogels, hydrocolloids, alginates, hydro- Silicone foam 2% Pet triethanolamine fibers, and composite dressings, as well as topical antibiotics, an- 1% Framycetin sulfate 12% Pet wood tar mix (pine, birch, tiseptics, debriding agents, and topical corticosteroids. juniper, beech) Patch test results were read 48 hours and 96 or 120 hours 2% Pet fuscidic acid 20% Pet zinc oxide after application and were interpreted following the NACDG pro- tocol.12 Reactions that were evaluated as 1+ to 3+ (1+, weak posi- Abbreviations: Aqs, aqueous; PCMC, p-chloro-m-cresol; Pet, petrolatum. tive; 2+, strong positive; and 3+, extremely strong positive) were *Tested by Ottawa group separately as cetyl alcohol and stearyl alcohol. included in the results, while equivocal reactions were ex- †Tested by Ottawa group only. cluded. Clinical relevance was determined for each positive result based on previously published criteria.12 Spearman rank correlation coefficient was used to determine any association between ulcer duration and number of positive allergen sensitivities. tion. This is particularly important considering that wound care clinics in North America may have different sensitization patterns compared with those in Europe because RESULTS of differences in the wound care products used. The goals of this study were the following: (1) to determine the incidence of allergen sensitivity in pa- The results of our study showed that 63% (n=34) of the tients with past or present leg ulcers in 2 North Ameri- patients had 1 or more allergen sensitizations. Fifty-two per- can study centers, (2) to compare the incidence and fre- cent (n=28) of the patients had more than 1 allergen sen- quency of these sensitivities with those in patients studied sitization, and 11% (n=6) had only 1 positive allergen sen- in Europe, (3) to compare the frequencies of the com- sitization. Thirty-seven percent (n=20) of the patients had mon allergens in the study with those in the North Ameri- no positive allergen sensitization. The following data fur- can Contact Dermatitis Group (NACDG) database, and ther subdivide the 34 patients who had positive allergen test (4) to establish a standard battery of allergens for patch results: 1 positive allergen test result, 11% (n=6); 2 posi- testing in North American patients. tive results, 4% (n=2); 3 positive results, 17% (n=9); 4 posi-

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No. of Relevance, % Patients Total Allergen* Sensitized Patients, No. % Sensitized Definite Probable Possible Past Unknown 25% Balsam of Peru 16 54 30 6 82 6 6 2% Bacitracin 13 54 24 31 38 31 8% Fragrance mix 11 54 20 18 64 9 12% Wood tar mix 11 54 20 9 18 45 18 9 30% Propylene glycol 7 52 14 14 14 71 20% Neomycin sulfate 7 54 13 14 29 57 0.1% Benzalkonium chloride 7 54 13 57 14 14 3% Carba mix 6 54 11 50 33 17 Control gel hydrocolloid 65411671717 2.5% Nickel sulfate 6 54 11 17 17 67 1% Aqs formaldehyde 5 54 9 100 2% Quaternium-15 5 54 9 100 0.5% Bronopol 5 54 9 80 20 Lanolin (wool alcohol 30%) 5 54 9 40 60 2.5% Euxyl K 400 5 54 9 100 Hydrogel with propylene glycol 5 54 9 80 20 5% Ethylene urea melamine 4 54 7 75 25 formaldehyde Cadexomer iodine gel 4 54 7 75 25 1% Framycetin sulfate 4 54 7 25 25 50 2% Imidazolidinyl urea 3 46 7 100 0.5% Sodium gold thiosulfate 3 54 6 33 33 33 Thin polyurethane hydrocolloid 3 54 6 67 33 0.25% Potassium dichromate 3 54 6 67 33 50% Amerchol L101 2 54 4 100 2% Fuscidic acid 2 54 4 50 50 Hydroactive gel 2 54 4 100 5% Benzocaine 2 54 4 50 50 1% Glyceryl monothioglycolate 2 54 4 50 50 0.1% Thimerosal 2 54 4 100 1% Diazilodinyl urea 2 54 4 100 1% Cobalt 2 54 4 50 50

Abbreviation: Aqs, aqueous. *Allergens in bold are part of the leg ulcer series.

tive results, 9% (n=5); 5 positive results, 2% (n=1); and ing dermatitis on the affected leg, and 22 (56%) of these pa- more than 5 positive results, 20% (n=11). tients had positive contact sensitivity to at least 1 allergen. The most common allergens found in our patients A prior study4 showed that longer ulcer duration is from the NACDG standard series and the rates of sensi- associated with a higher number of allergen contact sen- tization to these allergens were balsam of Peru (30% sitivities. However, in our study we did not find an as- [16/54]), bacitracin (24% [13/54]), fragrance mix (20% sociation between ulcer duration and number of posi- [11/54]), propylene glycol (14% [7/52]), neomycin tive allergen sensitivities (Spearman rank correlation (13% [7/54]), benzalkonium chloride (13% [7/54]), coefficient, −0.013; P=.93). carba mix (11% [6/54]), nickel (11% [6/54]), lanolin Therewere189positiveallergensamongthe54patients. (9% [5/54]), formaldehyde (9% [5/54]), 2-bromo-2- Twenty (11%) of these had a definite relevance, 19 (10%) nitropropane-1,3-diol (bronopol) (9% [5/54]), methyl- hadaprobablerelevance,106(56%)hadapossiblerelevance, dibromo glutaronitrile phenoxyethanol (Euxyl K400) 22(12%)hadapastrelevance,and21(11%)hadanunknown (9% [5/54]), and quaternium-15 (9% [5/54]) relevance. Relevance for allergens is given in Table 2. (Table 2). The most common allergens found from the A high cross-reactivity was found between positive leg ulcer series were wood tar mix (20% [11/54]), con- allergic reactions to balsam of Peru and wood tar mix. trol gel hydrocolloid (11% [6/54]), hydrogel with pro- In 55% (6/11) of patients allergic to wood tar mix, al- pylene glycol (9% [5/54]), cadexomer iodine gel (7% lergy was also present to balsam of Peru, and 38% (6/ [4/54]), framycetin sulfate (7% [4/54]), and thin poly- 16) of patients allergic to balsam of Peru were also aller- urethane hydrocolloid (6% [3/54]). Table 3 lists the gic to wood tar mix. In addition, and not surprisingly, rare positive allergens found in our patient population. 60% (3/5) of patients allergic to hydrogel with propyl- Of the 54 patients, 15 denied having dermatitis on the ene glycol were also allergic to propylene glycol, while lower extremity with present or past ulceration. However, 43% (3/7) of patients allergic to propylene glycol were 11 (73%) of these patients had positive contact sensitivity also allergic to hydrogel with propylene glycol. Another to at least 1 allergen. Of the 54 patients, 39 admitted to hav- interesting finding was that 75% of patients allergic to

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 Table 3. Rare Positive Allergens in Patients With Leg Ulcers 30 NACDG Database Leg Ulcer Patients No. of 25 Patients Total No. of Allergens* Sensitized Patients % Sensitized 20 100% Di alpha 1 53† 2 tocopherol 1% Mercapto mix 1 54 2 15 1% Aqs cocamidopropyl 1542 betaine 0.01% Aqs 1542 10 methylchloroisothiazo- linone (Kathon CG) Frequency of Allergen Sensitivity, % Frequency of Allergen Sensitivity, 5 20% Colophony 1 54 2 0.1% Aqs amidoamine 1 54 2 10% Tosylamide 1542 0 Balsam Bacitracin Fragrance Propylene Carba Nickel formaldehyde resin of Peru Mix Glycol Mix Sulfate 4.5% Aqs dimethylol 1542 dihydroxyethylene urea Frequency of allergen sensitivity in patients with leg ulcers in the present 1% 1542 study compared with the 1998 to 2000 North American Contact Dermatitis Tixocortol-21-pivalate Group (NACDG) database. 0.1% Budesonide 1 54 2 1% Hydrocortisone-17 1542 butyrate 5% Lidocaine 1 54 2 1% P-phenylenediamine 1 54 2 vs 9%), fragrance mix (20% vs 11%), propylene glycol 33% Benzophenone 1 54 2 (14% vs 4%), and carba mix (11% vs 5%). The fre- 1% Mixed dialkyl 1542 quency of contact sensitization to nickel was higher in thiourea the NACDG database (16% vs 11%) (Table 2 and Figure). 2.5% Tetracaine 1 54 2 We also compared the most frequent allergens in our 1% DMDM hydantoin 1 54 2 study group with those in several European studies 1% Ethylenediamine 1542 dihydrochloride (Table 4). We found the following differences in aller- 5% Compositae mix 1 54 2 gen sensitization: balsam of Peru (30% vs 3.4%-40%), baci- 0.5% Glutaraldehyde 1 54 2 tracin (24% vs 13.1%), fragrance mix (20% vs 7.4%- 12% Paraben mix 1 54 2 28%), wood tar mix (20% vs 1.8%-15.0%), propylene 1% Disperse blue 106 1 54 2 glycol (14% vs 0%-8.3%), neomycin (13% vs 2%- Collagen hydrogel 1542 34.0%), benzalkonium chloride (13% vs 2.8%-15.32%), 20% Cetyl alcohol 1542 20% Gentamicin sulfate 1542 carba mix (11% vs 1.7%-8.6%), nickel (11% vs 0%- Papain-urea debriding 1542 16.7%), formaldehyde (9% vs 0.67%-8.0%), Quater- enzyme nium-15 (9% vs 0%-4.9%), lanolin (9% vs 8.5%- Calcium alginate 1542 33.3%), Euxyl K400 (9% vs 0%), and hydrogel with dressing propylene glycol (9% vs 8.3%)2-11 (Tables 2 and 4). Mupirocin cream 1542 Collagenase 1542 COMMENT Abbreviations: Aqs, aqueous; DMDM, dimethylol dimethyl hydantoin. *Allergens in bold are part of the leg ulcer series. The frequency of contact allergen sensitivity has been shown to be high in the leg ulcer population in multiple studies performed in Europe. Studies1-11 showed that the framycetin sulfate dressing were also allergic to neomy- frequency of positive patch test results ranges from 40% cin (3 of 4 patients) and bacitracin (3 of 4 patients). to 82.5%. However, many of these studies are older, and Control gel hydrocolloid and thin polyurethane hy- until the present study, the frequency of allergen sensi- drocolloid are known to contain pentaerythritol tetrani- tivity had not been studied in the North American leg trate ester of hydrogenated rosin. This is a tackifying agent ulcer population, to our knowledge. In addition, the stud- that commonly cross-reacts with colophony.13 However, ies performed in Europe did not necessarily incorporate only 17% (1/6) of patients with a positive patch test re- many of the allergens, wound dressings, medicaments, sult to control gel hydrocolloid and 25% (1/4) of patients and ointments that are being used in the management with a positive patch test result to thin polyurethane hy- of leg ulcers in North America. drocolloid were also allergic to colophony. The sole pa- In this investigation, we determined the frequency tient allergic to colophony was allergic to control gel hy- of allergen sensitivity in leg ulcer patients at 2 North drocolloid and thin polyurethane hydrocolloid. American wound healing centers. In agreement with the We compared the allergens with the highest fre- prior European studies, our results showed a high frequencies in our study population with the 1998 to 2000 quency of allergen sensitivity in our population of leg NACDG data14 and found that patients with leg ulcer- ulcer patients. Sixty-three percent (n=34) of all pa- ations had higher frequencies of positive contact sensi- tients were sensitized to 1 or more allergens, and 37% tization to balsam of Peru (30% vs 12%), bacitracin (24% (n=20) of patients were not sensitized to any allergen.

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 Table 4. Frequency of Most Common Allergens Found in North American Patients With Leg Ulcerations Compared With Similar European Studies*

Katsarou-Katsari Reichert- Perrenaud et al,10 1998 Pénétrat and LeCoz Wilson Kulozik Fräki Angelini Our et al,9 Ramelet11 Gallenkemper et al,7 1973- 1994- et al,6 Paramsothy et al,5 et al,3 et al,2 Allergens Study 1999 1999 et al,8 1998 1998 1974 1995 1991 et al,4 1988 1988 1979 1975 Balsam of Peru 30 39.27 25 22.2 40 17.5 8.0 9.9 11.0 3.4 21.4 4.8 Bacitracin 24 13.1 Fragrance mix 20 25.06 31 8.3 28 12.0 7.4 16.0 11.9 Wood tar mix 20 2.8 15.0 11.0 3.4 4.5 1.8 Propylene glycol 14 2.5 8.3 8 0 0 0 Neomycin 13 14.48 18 16.7 2 15.0 8.0 19.8 14.0 16.9 34.0 16.3 Benzalkonium 13 15.32 11 2.8 chloride Carba mix 11 8.6 4.0 1.7 Control gel 11 hydrocolloid Nickel sulfate 11 5.29 16.7 4 0 0 14.8 10 2.3 Free formaldehyde 9 0.83 5.6 4 8.0 2.5 1 4.2 0.67 Quartenarium-15 9 0 0 4.9 2 0 Bronopol 9 Lanolin 9 19.49 30 33.3 14 15.0 12.0 23.4 26 18.6 22.9 8.5 Euxyl K400 9 0 Hydrogel- 9 8.3 propylene glycol

*Allergens in bold are part of the leg ulcer series while the other allergens are part of the Standard NACDG [North American Contact Dermatitis Group] Series.

Of the 16 most common allergens, 13 were from the that there may be other allergens in control gel hydro- standard NACDG series, while 3 were from the leg ulcer colloid that we have not yet identified. The essential point series developed at our study centers (Table 2). In addi- is that hydrocolloids, although important in wound care, tion, cadexomer iodine gel, framycetin sulfate, thin poly- can cause contact dermatitis. This should not necessar- urethane hydrocolloid, Amerchol L101, fuscidic acid, and ily restrict use of these dressings but should make us aware hydroactive gel are allergens from the leg ulcer series that that, in a wound that is not healing, a contact dermatitis showed allergen sensitivity and should be considered in to the dressing may be an exacerbating factor. leg ulcer patients who have contact dermatitis and a his- Another wound care product found to cause a high tory of exposure to these products. frequency of contact sensitivity was hydrogel with pro- In designing this investigation, we tried to be rep- pylene glycol. We believe that the most likely allergen resentative of the main categories of wound dressings and in this product is propylene glycol, as 60% (3/5) of pa- wound care products. We included alginate and com- tients allergic to this hydrogel were also allergic to pro- posite dressings, compression bandages, debriding agents, pylene glycol. This emphasizes the importance of know- foams, topical antibiotics, hydrocolloids, hydrogels, hy- ing all the ingredients in a wound care product before drofibers, topical antiseptics, and topical corticoste- using it. roids, among others. Our goal was not to single out a par- The frequency of allergen sensitivity was high in pa- ticular product but to see what categories tend to produce tients with no history of leg dermatitis (73% [11/15]), sug- a higher frequency of contact sensitivity. In this en- gesting that these patients are at higher risk of developing deavor, products commonly used for fragrance were the contact sensitivity. We also found a high cross-reactivity most allergenic (ie, balsam of Peru, fragrance mix), fol- between patients sensitized to balsam of Peru and wood lowed by nonprescription topical antibiotics and prod- tar mix, which has been shown in prior investigations.19 ucts found in commonly used cosmetic and personal care In our study population, we were not able to find a products (ie, wood tar, propylene glycol, benzalkonium correlation between ulcer duration and number of aller- chloride, lanolin, Amerchol L101, and formaldehyde- gen sensitivities, as had been shown in a prior study.4 releasing agents).15 Of the wound dressings, control gel However, ulcer duration was determined through a pa- hydrocolloid had the highest frequency of sensitization. tient questionnaire, which may have introduced recall This is thought to be due to pentaerythritol ester of hy- bias. Recall bias may also be an important factor in de- drogenated rosin, a tackifying agent that commonly cross- termining relevance to the allergens tested, as many pa- reacts with colophony.13 In addition, there have been case tients had difficulty remembering products used on their reports of other hydrocolloids causing contact dermati- legs. In addition, many patients with past contact der- tis thought to be due to this component.16-18 However, matitis may have been inappropriately diagnosed as hav- only 1 of 6 patients allergic to control gel hydrocolloid ing stasis dermatitis or cellulitis, making relevance more in our study was also allergic to colophony, indicating difficult to interpret in this setting.

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©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 number of allergens to test in patients with leg ulcers, Table 5. Minimum Recommended Patch Tests based on our results. If the patient has been exposed to for Patients With Leg Ulcerations allergens or wound care products not included in this leg ulcer series or the standard NACDG series, these al- 25% Balsam of Peru 3% Carba mix lergens can be easily added. 2% Bacitracin 30% Lanolin 8% Fragrance mix Formaldehyde-releasing agents 12% Wood tar mix Hydrocolloids Accepted for publication April 30, 2004. 30% Propylene glycol Hydrogels 20% Neomycin sulfate Cadexomer iodine gel This study was supported by grants AR42936, AR46557, Framycetin sulfate Other products used by patient and DK067836 from the National Institutes of Health, Bethesda, 0.1% Benzalkonium chloride Products considered for future Md (Dr Falanga). Drs Fahim, Saap, and Arsenault received use by the patient the 2002 Alexander A. Fisher Resident Gold Award from the American Contact Dermatitis Society, Chicago, Ill. Data from this study were presented at the American Compared with the NACDG database, patients with Contact Dermatitis Society 14th Annual Meeting; March 20, leg ulcers had a higher frequency of contact sensitization 2003; San Francisco, Calif; Residents and Fellows Sympo- to balsam of Peru, bacitracin, fragrance mix, propylene gly- sium at the 62nd Annual Meeting of the American Academy col, and carba mix. This higher frequency of allergen sen- of Dermatology; February 8, 2004; Washington, DC; 65th sitization makes sense because many wound care regi- Meeting of the Society for Investigative Dermatology; April mens incorporate products with all of these allergens. 28, 2004; Providence, RI; and the 15th Annual Meeting of the Furthermore, the disturbed skin barrier in patients with Wound Healing Society; May 24, 2004; Atlanta, Ga. leg ulcers is thought to be a major mechanism for in- Correspondence: Anita Pedvis-Leftick, MD, Depart- creased allergen sensitivity in this patient population. ment of Dermatology and Skin Surgery, Boston University The European contact allergen studies of patients Roger Williams Medical Center, 50 Maude St, Providence, with leg ulcers showed variability in results of the aller- RI 02908 ([email protected]). gens tested. Some of the European studies showed similar high frequencies of sensitization to the following allergens compared with our study: balsam of Peru,3,7-9,11 REFERENCES fragrance mix,4,7,9,11 benzalkonium chloride,9,11 nickel,4,6,8 and hydrogel with propylene glycol.8 Allergen sensitivi- 1. Truchetet F. Batterie allergologique des ulce`res de jambe. Ann Dermatol Vene- 2-6,8-11 3-11 reol. 1999;126:364-368. ties to neomycin and lanolin were higher in the 2. Angelini G, Rantuccio F, Meneghini CL. Contact dermatitis in patients with leg European studies. However, sensitivities to the follow- ulcers. Contact Dermatitis. 1975;1:81-87. 3. Fra¨ki JE, Peltomen L, Hopsu-Havu VK. Allergy to various components of topical prepa- ing allergens were lower in the European studies com- rations in stasis dermatitis and leg ulcers. Contact Dermatitis. 1979;5:97-100. 3 2-5,8,10 pared with our study: bacitracin, wood tar mix, pro- 4. Paramsothy Y, Collins M, Smith AG. Contact dermatitis in patients with leg ul- pylene glycol,3,5,7-10 carba mix,4-6 formaldehyde,2-4,6-10 cers. Contact Dermatitis. 1988;18:30-36. 4-6,9,10 8 5. Kulozik M, Powell SM, Cherry G, Ryan TJ. Contact sensitivity in community- quaternium-15, Euxyl K400. Control gel hydro- based leg ulcer patients. Clin Exp Dermatol. 1988;13:82-84. colloid and 2-bromo-2-nitropropane-1,3-diol (bro- 6. Wilson CL, Cameron J, Powell SM, Cherry G, Ryan TJ. High incidence of contact nopol) were not tested in any of the European studies. dermatitis in leg-ulcer patients. Clin Exp Dermatol. 1991;16:250-253. 3 7. LeCoz CJ, Scrivener Y, Santinelli F, Heid E. Sensibilisation de contact au cours Bacitracin was tested in a European study and showed des ulce`res de jambe. Ann Dermatol Venereol. 1998;125:694-699. a frequency of 13.1% vs 24% in our study (25/192 vs 13/ 8. Gallenkemper G, Rabe E, Bauer R. Contact sensitization in chronic venous in- 3 sufficiency: modern wound dressings. Contact Dermatitis. 1998;38:274-278. 54) (Tables 2 and 4). This increase of contact allergen 9. Reichert-Pe´ne´trat S, Barbaud A, Weber M, Schmutz JL. Leg ulcers: allergologic sensitivity to bacitracin may be secondary to increased studies of 359 cases [in French]. Ann Dermatol Venereol. 1999;126:131-135. use of this allergen during the past 10 years, as has been 10. Katsarou-Katsari A, Armenaka M, Kastenis K, et al. Contact allergens in patients 20,21 with leg ulcers. J Eur Acad Dermatol Venereol. 1998;11:9-12. speculated in other recent studies. 11. Perrenaud D, Ramelet AA. Chronic leg ulcers and eczema. Curr Probl Dermatol. In conclusion, we showed that allergen sensitivity is 1999;27:165-169. high in the North American leg ulcer population. The fre- 12. Marks JG Jr, Belsito DV, DeLeo VA, et al; North American Contact Dermatitis Group. Patch test results for the detection of delayed-type hypersensitivity to topi- quency of positive allergen sensitivity is increased com- cal allergens. J Am Acad Dermatol. 1998;38:911-918. pared with the NACDG database and has some marked dif- 13. Sasseville D, Tennstedt D, Lachapelle JM. Allergic contact dermatitis from hydrocolloid dressings. Am J Contact Dermatitis. 1997;8:236-238. ferences to previous studies done in Europe. In a patient 14. Marks JG Jr, Belsito DV, DeLeo VA, et al. North American Contact Dermatitis Group whose leg ulcer is not healing, it is important to consider patch-test results, 1998 to 2000. Am J Contact Dermatitis. 2003;14:59-62. that a contact allergy might be impeding healing. This is 15. Marks JG Jr, Elsner P, DeLeo VA. Contact & Occupational Dermatitis. 3rd ed. St Louis, Mo: Mosby–Year Book Inc; 2002. particularly important because it can sometimes be diffi- 16. Grange-Prunier A, Couillet D, Grange F, Guillaume JC. Allergic contact dermati- cult to differentiate infection from contact dermatitis in pa- tis to the Comfeel hydrocolloid dressing. Ann Dermatol Venereol. 2002;129(pt tients with chronic ulcers. Based on our results, it may also 1):725-727. 17. Downs AM, Sharp LA, Sansom JE. Pentaerythritol-esterified gum rosin as a sen- be important to avoid products with fragrances, formalde- sitizer in Granuflex hydrocolloid dressing. Contact Dermatitis. 1999;41:162-163. hyde-releasing preservatives, propylene glycol, and non- 18. Mallon E, Powell SM. Allergic contact dermatitis from Granuflex hydrocolloid dressing. Contact Dermatitis. 1994;30:110-111. prescription topical antibiotics in this patient population. 19. Roesyanto ID, van den Akker TW, van Joost TW. Wood tars allergy, cross- Patch testing patients with leg ulcers to the stan- sensitization and coal tar. Contact Dermatitis. 1990;22:95-98. dard NACDG series and the leg ulcer series is a useful 20. Smack DP, Harrington AC, Dunn C, et al. Infection and allergy incidence in am- bulatory surgery patients using white petrolatum vs bacitracin ointment: a ran- adjunct to standard wound care, as it can aid in tailor- domized controlled trial. JAMA. 1996;276:972-977. ing treatment to each patient. Table 5 lists a minimum 21. Zaki I, Shall L, Dalsiel KL. Bacitracin. Contact Dermatitis. 1994;31:92-94.

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