North American Contact Dermatitis Group Research Articles

Cross-Reactions between Xanthates and Rubber Additives

We previously described allergic contact dermatitis from xanthates used in the recovery of metals from mining ores. We observed cross-reactions with carbamates, believed to be due to the common "dithio" nucleus shared by both groups. The present study was undertaken to establish the rate of cross-reactions between xanthates and rubber additives. Between November 2002 and December 2005, 1,220 consecutive patients were patch-tested with sodium isopropyl xanthate 10% in petrolatum (pet) and with potassium amyl xanthate 10% pet and later 5% pet, in addition to the North American Contact Dermatitis Group standard series and other series as required by their conditions. Fifty-one patients reacted to xanthates, carbamates, or thiurams; 26 reacted to xanthates only, and these reactions were felt to be irritant. Twenty-five patients reacted to xanthates and/or to one or more of the rubber additives, 12 had positive reactions to xanthates and to either carba mix or thiuram mix, 10 reacted to xanthates and carba mix, 9 reacted to xanthates and thiuram mix, and 8 showed positive reactions to xanthates and both mixes. However, 13 patients had positive reactions to carba mix and thiuram mix but did not react to xanthates. Six patients reacted to other rubber additives such as mercaptobenzothiazole, black rubber mix, and mixed dialkyl thioureas. Five of these patients also reacted to xanthates, 4 reacted to xanthates and carba mix, and 3 reacted to xanthates, carba mix, and thiuram mix. Of patients sensitized to carbamates, thiurams, or mercaptobenzothiazole, 50% exhibit cross-reactions with xanthates. Xanthates are irritants, and their patch-test concentrations should be lowered to 5% or less.

Contact dermatitis of the hands: Cross-sectional analyses of North American Contact Dermatitis Group Data, 1994-2004

Hand dermatitis, including irritant and allergic contact dermatitis (ACD), is common. To evaluate allergens, relevant irritants, sources and occupations associated with hand contact dermatitis using North American Contact Dermatitis Group (NACDG) data. A cross-sectional analysis of 22,025 patients patch tested between 1994 and 2004. Hand involvement was found in 6953 patients; 959 had ACD as the only diagnosis. In these 959 patients, the 12 most frequent relevant allergens were quaternium-15 (16.5%), formaldehyde (13.0%), nickel sulfate (12.2%), fragrance mix (11.3%), thiuram mix (10.2%), balsam of Peru (9.6%), carba mix (7.8%), neomycin sulfate (7.7%), bacitracin (7.4%), methyldibromoglutaronitrile/phenoxyethanol 2.0% (7.4%), cobalt chloride (6.5%), and methyldibromoglutaronitrile/phenoxyethanol 2.5% (6.3%). Rubber allergens were most commonly associated with occupation. One third of patients with hand ACD had identifiable relevant irritants. Cross-sectional analyses prevent evaluation of causal associations. In NACDG patients with hand ACD, the most common allergens included preservatives, metals, fragrances, topical antibiotics, and rubber additives.

Common Contact Allergens Associated with Eyelid Dermatitis: Data from the North American Contact Dermatitis Group 2003-2004 Study Period

Allergic contact dermatitis can be manifest as an eruption confined to the eyelids. In regard to this specific presentation, only limited information on which to base the selection of patch tests for proper evaluation is available. To identify the contact allergens most frequently found to be both patch test positive and relevant when only the eyelids are involved. Data collected from 2003 to 2004 by the North American Contact Dermatitis Group (NACDG) were analyzed for relevant allergens in the setting of dermatitis on the eyelids only. Data on eyelid dermatitis patients whose relevant allergens were not among the 65 allergens used for screening during this study period were also tabulated. Data showed that 268 patients had only eyelid dermatitis and a final diagnosis of allergic contact dermatitis. In 193 (72%) of these, reactions were of current relevance and were identified from a screening series of 65 allergens. The top 26 allergens identified 65% of cases (175 cases). Gold was the most frequently encountered allergen (22 of 175 cases [12.5%]). Of the 268 cases, 33 showed relevant reactions to an allergen that was not among the 65 NACDG standard screening allergens. No specific allergen was identified in the remaining 42 cases. The top 26 allergens identified in this study represent a potential eyelid dermatitis screening series.

Patch Test Reactions to Topical Anesthetics: Retrospective Analysis of Cross-Sectional Data from the North American Contact Dermatitis Group 2001-2004

Patch Test Reactions to Topical Anesthetics: Retrospective Analysis of Cross-Sectional Data from the North American Contact Dermatitis Group 2001-2004

Shoe Allergens: Review of the Literature and Retrospective Analysis of Cross-Sectional Data from the North American Contact Dermatitis Group 2001-2004

Warshaw, Erin M.; Schram, Sarah E.; Belsito, Donald V.; DeLeo, Vincent A.; Fowler, Joseph F. Jr.; Maibach, Howard I.; Marks, James G. Jr.; Mathias, Toby C.G.; Pratt, Melanie D.; Rietschel, Robert L.; Sasseville, Denis; Storrs, Frances J.; Taylor, James S.; Zug, Kathryn A. Author Information

Relationship of patch test positivity in a general versus an eczema population

Using previously generated data from multicenter studies European Environmental and Contact Dermatitis Research Group (EECDRG) and North American Contact Dermatitis Group (NACDG), we compare patch test positivity of random sample and eczema populations, attempting to ascertain how one might extrapolate frequency from an eczema group to a general population. We included population-based mathematical estimates for patch test reaction in the general population using the Multinational MONItoring of trends and determinants in Cardiovascular disease MONICA and Clinical Epidemiology and Drug-Utilization Research (CE-DUR) systems. Data analysis provides a ratio of eczema population:random sample population for each allergen and an overall ratio of all allergens 5:1 for actual data and 6:1 for population-based estimates (according to the MONICA and CE-DUR systems). If the positivity rate were the same in each population, the ratio would approximate 1. The individual allergen ratios ranged from formaldehyde at 11.6 to parabens at 1.0, with respect to the NACDG. Some differences may be explained by exposure (neomycin) being greater in patients than in random population. Materials of ubiquitous exposure - i.e. fragrance mix and nickel - had ratios closer to 1. Taken together, data obtained in eczema patients may be viewed as part of a complex biology and may eventually be of use in aiding validation of predictive dermatotoxilogic assays and in public health assessments.

Should Macular Erythema Reactions Be Counted as Positive Allergic Patch-Test Reactions?

Positive allergic patch-test results are generally described as erythematous papules, vesicles, or a spreading reaction with crust and ulceration. This description excludes milder reactions, including macular erythema. Our aim was to investigate the prevalence and relevance of reactions graded as macular erythema at Mayo Clinic. Between January 2001 and June 2004, patients suspected of having allergic contact dermatitis were patch-tested with our institution's standard patch test, a screening series of 68 to 72 allergens. In total, 2,823 patients were patch-tested with 193,530 allergen applications. Reactions were interpreted with the North American Contact Dermatitis Group scale, including and excluding reactions graded as macular erythema. Irritant reactions were excluded from calculations. For this study, scores for current, questionable, and past relevance were combined. On day 5, with the exclusion of reactions graded as irritant, 7,274 allergen applications were associated with reactions, including 3,082 (42.4%) that were graded as macular erythema. Of the macular erythema reactions, 2,430 (78.8%) were graded as relevant. The rate of reaction in our patients was 2.2% if macular erythema was excluded, 3.8% if all macular erythema reactions were included, and 3.4% if only those macular reactions deemed relevant were included. Patch-test reactions rated as macular erythema are common and may be of clinical relevance. For the purposes of patient education, they should not be disregarded. Consideration should be given to including these reactions when reporting patchtest results.

Contact Urticaria from Carboxymethylcellulose in White Chalk

Carboxymethylcellulose (CMC) is widely used in consumer goods, foods, and medicaments as a binder, emulsifier, and viscosity enhancer. Cases of immediate and delayed allergic reactions to this anionic cellulose polymer have been reported. To report a case of contact urticaria from CMC in chalk, with possible cross-reaction to methyl hydroxyethylcellulose (MHEC). Patch tests with readings at 48 and 96 hours were performed with the North American Contact Dermatitis Group standard series and benzisothiazolinone. Open and prick tests with readings after 30 minutes were performed with two brands of chalk as well as with various petrolatum and aqueous dilutions of CMC, MHEC, oleic acid, and calcium carbonate. The patient developed strong urticarial reactions during open tests with both powdered chalks and had milder reactions to the open test with CMC 10% aqueous (aq) and to prick testing with CMC 0.1% aq. No reaction to MHEC or any of the other ingredients of the chalks was observed. No relevant delayed reaction was noted. CMC can cause contact urticaria. It remains unclear why our patient reacted more strongly to the chalk than to CMC itself. We speculate that the abrasive nature of the chalk enhances the cutaneous penetration of CMC or that calcium carbonate, the main ingredient of the chalk, acts as an adjuvant. It is also possible that CMC and MHEC cross-react and that our negative results with MHEC may be due to improper testing technique or concentrations.

Delayed-Type Hypersensitivity to Fragrance Materials in a Select North American Population

In published reports from Europe, 3- and 4-(4-hydroxy-4-methylpentyl)cyclohexene-1-carboxaldehyde (HMPCC) (Lyral) has been described as a common cause of allergic contact dermatitis (ACD). In Europe, the rates of reaction to HMPCC among patients undergoing patch testing for suspected ACD have varied from 1.2 to 17.0%, depending on the country. Data on the incidence of sensitivity to HMPCC among North Americans with suspected ACD have not been reported. The goals of this study were (1) to assess the incidence of delayed-type hypersensitivity reactions to HMPCC among patients undergoing patch testing for evaluation of eczematous dermatitis at six centers throughout North America; (2) to determine the most appropriate concentration of HMPCC to use in performing patch tests; and (3) to compare and contrast the incidence rates for HMPCC hypersensitivity to those for other fragrance materials screened with the North American Contact Dermatitis Group (NACDG) screening tray, which includes fragrance mix, Myroxilon pereirae (balsam of Peru), cinnamic aldehyde, ylang ylang oil, jasmine absolute, and tea tree oil. This report represents the prospective multicenter data on patients tested with the fragrance-related allergens on the NACDG standard screening tray and with HMPCC at 5%, 1.5%, and 0.5% concentrations in petrolatum. Statistical analyses were performed with Student's t-test (two tailed) and the chi-square test. Data from 1,603 patients evaluated at five US sites and one Canadian site were analyzed. Most patients (87.8%) were Caucasian. The majority (67%) were women, and 26.2% had a history consistent with atopic dermatitis. The patients ranged in age from 1 to 88 years, and the mean +/- standard deviation was 46.3 +/- 16.5 years. Myroxilon pereirae (balsam of Peru) and fragrance mix were the most frequent patch-test-positive fragrance allergens (6.6% and 5.9%, respectively). Cinnamic aldehyde (1.7%), ylang ylang oil (0.6%), jasmine absolute (0.4%), HMPCC (0.4% for 5% HMPCC, 0.3% for 1.5% HMPCC, and 0.2% for 0.5% HMPCC), and tea tree oil (0.3%) less frequently yielded positive reactions. Men were more likely than women to be allergic to cinnamic aldehyde. Women were more likely than men to be allergic to jasmine absolute. Atopic patients were no more likely to react to fragrance materials than were nonatopic patients. Patients who reacted to jasmine absolute tended to be older than the general population whereas those who reacted to tea tree oil tended to be younger than the general population. There were no other demographic differences between patients who reacted to a given fragrance material and the entire population studied. Testing with fragrance mix and balsam of Peru failed to identify the majority of patients in this study who were found to be sensitized to jasmine absolute, HMPCC, or tea tree oil. HMPCC is an uncommon allergen in the North American population. We recommend testing with 5% HMPCC in petrolatum for those patients suspected of having a fragrance allergy.

Patch test results from the Mayo Clinic Contact Dermatitis Group, 1998-2000

Patch testing is a diagnostic tool for the evaluation of patients with suspected allergic contact dermatitis. A standard series of allergens similar to that used by the North American Contact Dermatitis Group (NACDG) is used at Mayo Clinic. Our aim was to report the results of patch testing with a standard series at Mayo Clinic from July 1, 1998, to Dec 31, 2000 and to compare our findings with those of the NACDG during the same period. The results of patch testing with the standard series at Mayo Clinic were examined. Positive reaction rates were compared between Mayo Clinic and the NACDG. During the 30-month period, 1324 Mayo Clinic patients were patch tested with a standard series of allergens (mean, 60 allergens), whereas the NACDG standard series during this period included 50 allergens. Overall, 917 patients (69.3%) had at least one positive reaction and 606 patients (45.8%) had two or more positive reactions. The 10 allergens used both by Mayo Clinic and by the NACDG that most frequently caused positive reactions were nickel sulfate hexahydrate, balsam of Peru (Myroxylon pereirae), neomycin sulfate, cobalt chloride, fragrance mix, potassium dichromate (0.25%), thimerosal, bacitracin, formaldehyde, and glutaraldehyde. Statistically significant differences in positive reaction rates (P < .05) were observed for 12 of the 43 allergens common to both Mayo Clinic and the NACDG. With large standard patch test series, one can identify commonly encountered and potentially relevant contact allergens.

A baseline quality-of-life assessment using Skindex-16+5 in patients referred for patch testing to a north american contact dermatitis group (NACDG) test center

A baseline quality-of-life assessment using Skindex-16+5 in patients referred for patch testing to a north american contact dermatitis group (NACDG) test center

Neoprene

Neoprene is a synthetic rubber with many common uses, including use in shoe insoles and adhesives, orthopedic braces, and gloves. Many cases of type IV hypersensitivity from neoprene contact have been reported. Thioureas, the most commonly used vulcanization accelerators in the manufacture of neoprene, are responsible for the majority of these cases. However, thioureas are not included in the TRUE Test whereas the North American Contact Dermatitis Group standard tray contains only mixed dialkyl thioureas. Since most data indicate that many cases will be missed when only mixed dialkyl thioureas are used for screening, a more complete thiourea panel should be used when neoprene hypersensitivity is suspected.

Contact Sensitivity in Patients With Leg Ulcerations

(1) To determine the prevalence of allergen sensitivity in patients with past or present leg ulcers in 2 North American study centers vs European study findings and the North American Contact Dermatitis Group (NACDG) database and (2) to delineate a standard battery of allergens for patch testing in North American patients that is representative of the newer dressings and wound care products. Fifty-four patients, with or without dermatitis, were prospectively entered in the study. The patients were patch tested to the NACDG standard series and a comprehensive supplemental series of 52 allergens. Wound healing clinics at Boston University Roger Williams Medical Center and University of Ottawa. Sixty-three percent (n = 34) of patients had 1 or multiple positive patch test results, and 37% (n = 20) had no positive patch test result. The most common allergens were Myroxylon pereirae (balsam of Peru) (30% [16/54]), bacitracin (24% [13/54]), fragrance mix (20% [11/54]), wood tar mix (20% [11/54]), propylene glycol (14% [7/52]), neomycin sulfate (13% [7/54]), benzalkonium chloride (13% [7/54]), carba mix (11% [6/54]), nickel sulfate (11% [6/54]), and control gel hydrocolloid (11% [6/54]). Comparable to European study findings, there is a high incidence of positive patch test results in patients with past or present leg ulcerations. The incidences of the most common allergens in our patient population were higher than those seen in the NACDG, except for nickel. Using a modified leg ulcer series along with the standard NACDG series is important in evaluating patients with leg ulcers.

021 Contact Sensitivity in Patients with Leg Ulcerations: A North American Study

Background: Over the last two decades, there have been a number of studies in Europe on contact sensitivity in patients with chronic leg ulcerations with a frequency of positive patch test results ranging from 40 to 82.5%. The prevalence of sensitization has not been studied in North America. Furthermore, many of the newer dressings and wound care products in the market have not been studied for contact sensitivity in patients with chronic wounds. Objectives: 1) To determine the prevalence of allergen sensitivity in patients with history of leg ulcers in two North American study centers, 2) to compare our results to the European studies and to the North American Contact Dermatitis Group (NACDG) database and 3) to help delineate a standard battery of allergens for patch testing in North American leg ulcer patients Methods: 54 patients with an active or past leg ulcer were prospectively entered in the study. The patients were patch tested to both the NACDG Standard series, as well as, a comprehensive supplemental series of 48 allergens including wound care medicaments and dressings. Results: 63% of patients were sensitized to at last one allergen. The most common allergens were Balsam of Peru (29.6%), bacitracin (24.1%), fragrance mix (20.4%), wood tar mix (20.4%), propylene glycol (13.5%), neomycin sulfate (13%), benzalkonium chloride (13%), carba mix (11.1%), nickel sulfate (11.1%) and Duoderm CGF (11.1%). Duoderm CGF was the most allergenic dressing in our study group. Conclusion: There is a high incidence of positive patch tests in patients with past or current leg ulcerations. Using a modified leg ulcer series along with the standard NACDG series is very important in evaluating patients with leg ulcers.

From road rash to top allergen in a flash: bacitracin.

Bacitracin is an antibiotic that is produced by Bacillus subtilis, which is used in several types of consumer products, including cosmetics and ophthalmic and cutaneous ointments. To call attention to the rising allergic contact dermatitis associated with bacitracin. Mass usage has resulted in an increasing number of clinically relevant allergic contact dermatitis reactions and near fatal anaphylaxis. The North American Contact Dermatitis Group has recorded its emergence as a leading allergen and continues to monitor the ever-growing allergic reaction rates. The clinical impact, scientific evidence, and need for medical cost containment all advocate the discontinuation of routine usage of bacitracin in clean surgical wounds.

Allergy to Cocamidopropyl Betaine and Amidoamine in North America

The prevalence of allergy to cocamidopropyl betaine (CAPB) in North America has not been previously reported. The aim of this study was to report on the most recent data on allergy to CAPB and a related allergen, amidoamine (AA). Data was collected by the North American Contact Dermatitis Group from consecutive patients presenting for patch testing for diagnosis of presumed allergic contact dermatitis (ACD) from January 1, 2001, through December 31, 2001. Of 975 patients tested, 15 were patch-test positive to CAPB, 25 had positive reactions to AA, and 18 had positive reactions to both CAPB and AA. The most frequent site of dermatitis from CAPB was the head and neck region. In North America, both CAPB and AA are useful allergens for detecting ACD.

North American Contact Dermatitis Group Patch-Test Results, 2001-2002 Study Period

Allergic contact dermatitis is a significant cause of cutaneous disease affecting many individuals in the home and at the workplace. Patch testing is the most worthwhile diagnostic tool for the evaluation of patients with suspected allergic contact dermatitis. This study reports the results of patch testing from January 1, 2001, to December 31, 2002, by the North American Contact Dermatitis Group (NACDG). Patients were tested with an extended screening series of 65 allergens. A standardized patch-testing technique was used. Data from these patients were recorded on a standardized computer entry form and analyzed. Sixty-five allergens were tested on 4,913 patients. The top 10 allergens remain the same in this study period as in the 1999-2000 study period: nickel sulfate (16.7%), neomycin (11.6%), Myroxilon pereirae (balsam of Peru) (11.6%), fragrance mix (10.4%), thimerosal (10.2%), sodium gold thiosulfate (10.2%), quaternium-15 (9.3%), formaldehyde (8.4%), bacitracin (7.9%), and cobalt chloride (7.4%). Of the 4,913 patients tested, 69% had at least one positive allergic patch-test reaction. Of all patients, 15.8% had occupation-related dermatitis; 15.4% were determined to have irritant contact dermatitis, and 11.1% of the 15.4% had a relevant reaction to an occupational irritant. Of all patients tested, 16.7% had a relevant reaction to an allergen not in the NACDG standard series, and 5.5% had a relevant reaction to an occupational allergen not in the standard series. Our findings once again reinforce the need for a more comprehensive group of diagnostic allergens than those found in the standard screening kits. The usefulness of patch testing is enhanced when a greater number of allergens are tested, especially nonstandard allergens occupationally encountered.

High Ultraviolet A Protection Affords Greater Immune Protection Confirming that Ultraviolet A Contributes to Photoimmunosuppression in Humans

Solar radiation causes immunosuppression that contributes to skin cancer growth. Photoprotective strategies initially focused on the more erythemogenic ultraviolet B. More recently, the relationship of ultraviolet A and skin cancer has received increased attention. We hypothesized that if ultraviolet A contributes significantly to human ultraviolet-induced immune suppression, then increased ultraviolet A filtration by a sunscreen would better protect the immune system during ultraviolet exposure. Two hundred and eleven volunteers were randomized into study groups and received solar-simulated radiation, ranging from 0 to 2 minimum erythema dose, on gluteal skin, with or without sunscreen, 48 h prior to sensitization with dinitrochlorobenzene. Contact hypersensitivity response was evaluated by measuring the increase in skin fold thickness of five graded dinitrochlorobenzene challenge sites on the arm, 2 wk after sensitization. Clinical scoring using the North American Contact Dermatitis Group method was also performed. Solar-simulated radiation dose-response curves were generated and immune protection factor was calculated using a nonlinear regression model. Significance of immune protection between study groups was determined with the Mann-Whitney-Wilcoxon exact test. The sunscreen with high ultraviolet A absorption (ultraviolet A protection factor of 10, based on the in vivo persistent pigment darkening method) and a labeled sun protection factor of 15 demonstrated better immune protection than the product that had a low ultraviolet A absorption (ultraviolet A protection factor of 2) and a labeled sun protection factor of 15. Nonlinear regression analysis based on skin fold thickness increase revealed that the high ultraviolet A protection factor sunscreen had an immune protection factor of 50, more than three times its sun protection factor, whereas the low ultraviolet A protection factor sunscreen had an immune protection factor of 15, which was equal to its labeled sun protection factor. This study demonstrates that ultraviolet A contributes greatly to human immune suppression and that a broad-spectrum sunscreen with high ultraviolet A filtering capacity results in immune protection that exceeds erythema protection. These results show that high ultraviolet A protection is required to protect against ultraviolet-induced damage to cutaneous immunity.

North American Contact Dermatitis Group Patch-Test Results, 1998 to 2000

Patch testing is the most worthwhile diagnostic tool for the evaluation of patients with suspected allergic contact dermatitis.This study reports patch-testing results from July 1, 1998, to December 31, 2000, by the North American Contact Dermatitis Group.Patients were tested with the same screening series of allergens, using a standardized patch-testing technique. The data from these patients were recorded on a standard computer entry form and analyzed.Fifty allergens were tested on over 5,800 patients. Amidoamine, benzophenone-3, and iodopropynyl butylcarbamate were the new allergens. The top 10 allergens in frequency of positive reactions were identical to those of our 1996-to 1998-study period. The incidence of allergic nickel reactions continues to go up, leading all the test substances by 16.2%.Our findings reinforce the need for a more comprehensive group of diagnostic allergens than is found in the T.R.U.E. TEST, which is sold in the United States.

North American Contact Dermatitis Group Patch-Test Results, 1998 to 2000

Patch testing is the most worthwhile diagnostic tool for the evaluation of patients with suspected allergic contact dermatitis. This study reports patch-testing results from July 1, 1998, to December 31, 2000, by the North American Contact Dermatitis Group. Patients were tested with the same screening series of allergens, using a standardized patch-testing technique. The data from these patients were recorded on a standard computer entry form and analyzed. Fifty allergens were tested on over 5,800 patients. Amidoamine, benzophenone-3, and iodopropynyl butylcarbamate were the new allergens. The top 10 allergens in frequency of positive reactions were identical to those of our 1996-to 1998-study period. The incidence of allergic nickel reactions continues to go up, leading all the test substances by 16.2%. Our findings reinforce the need for a more comprehensive group of diagnostic allergens than is found in the T.R.U.E. TEST, which is sold in the United States.