- Email: [email protected]
Regional variation in prevalence and etiology of allergic contact dermatitis
STUDY
Regional Variation in Prevalence and Etiology of Allergic Contact Dermatitis Trevor R. Thompson and Donald V. Belsito Background: The 1994-1996 North American Contact Dermatitis Group (NACDG) patch test results were the first, since the inception of the NACDG in 1970, to include results from a medium-sized metropolitan city in the Midwest. Objective: The aim of this study was to determine whether the causative allergens of allergic contact dermatitis (ACD) in the Midwest differ from those in other regions of the United States and, if so, whether occupational or other factors account for the observed differences. Methods: Retrospective analyses of patch test data collected at the University of Kansas Medical Center (Kansas City, KS) were compared with the data collected by the other NACDG centers. Results: Patients in Kansas City were statistically more likely to react to potassium dichromate, formaldehyde and its releasers, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and glutaraldehyde. Occupational exposures to chromium and formaldehyde were increased significantly among patients from Kansas City, although the percentages of the local population engaged in these occupations did not differ from those in other NACDG cities. Equal percentages of workers in Kansas City and nationally had occupationally related allergy to glutaraldehyde, although the overall rate of glutaraldehyde was higher among patients from Kansas City. Most cases of relevant allergy to MCI/MI were cosmetically induced both in Kansas City and nationally. Conclusions: The current findings show significant regional differences in causal allergens. The increased percentages of patients seen with ACD to formaldehyde, formaldehyde-releasing agents, and potassium dichromate in Kansas City were likely caused by the referral of greater numbers of work-related cases. However, occupationally acquired ACD to MCI/MI and glutaraldehyde were not more frequent in Kansas City than nationally, suggesting that other factors might be operative. Although awareness of national trends is important, dermatologists must be cognizant of regional variations in allergen sources within their communities and referral networks. Copyright 2002, Elsevier Science (USA). All rights reserved.
P
ATCH TESTING PROVIDES a basis for determining the cause of allergic contact dermatitis (ACD) and enables investigators to monitor trends in the rate of reactivity to allergens in their communities. The North American Contact Dermatitis Group (NACDG) gathers patch test results from participating centers around the United States and Canada. NACDG test centers conduct patch testing using a standardized technique and a standard tray of allergens, which includes newly marketed chemicals to search for the introduction of new allergens into the environment. The 1994-1996 NACDG study1 included patch test results from the University of Kansas Medical Center in Kansas City, KS. The results provided from this central Midwestern site to the NACDG for its biennial analysis were the first from this region since the inception of the NACDG in 1970.1-5 Because of variances in patch test results related to climactic, environmental, social, occupational, and cultural factors, as well as local prescribing From the Division of Dermatology, University of Kansas Medical Center, Kansas City, KS. Address reprint requests to Donald V. Belsito, MD, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160. Funding was provided by the Division of Dermatology, University of Kansas Medical Center, Kansas City, KS Copyright 2002, Elsevier Science (USA). All rights reserved. 1046-199X/02/1304-0005$35.00/0 doi:10.1053/ajcd.2002.36643
habits, this study was designed to assess for differences in the causative allergens of ACD in the central United States compared with other regions in the United States.
Materials and Methods Between July 1, 1994 and June 30, 1996, 3,120 patients suspected of having allergic contact dermatitis were evaluated by the 12 dermatologists of the NACDG. In addition to the Kansas City location, the other NACDG sites were located in Hershey, PA; New York, NY; Louisville, KY; Ft Myers, FL; San Francisco, CA; Cincinnati, OH; Baltimore, MD; New Orleans, LA; Winston-Salem, NC; Portland, OR; and Cleveland, OH. All patients were patch tested to a standard tray of 49 allergens. In July 1995 budesonide was added to the standard tray and tested on 1,678 patients nationally. During this same time period, 141 patients were patch tested at the University of Kansas Medical Center for inclusion in the NACDG study. Ninety-one of these 141 patients were tested to budesonide. All patients were patch tested using Finn Chambers (Epitest Ltd Oy, Tuusula, Finland) on Scanpor tape (Norgesplaster Aksjeselskap, Vennesia, Norway), which were applied on the back as previously described.3 In Kansas City, the patches were removed after 48 hours and the test sites evaluated at that time and again 96 hours after initial placement. Patients were not tested if they had (1) applied topical corticosteroids to patch test sites within the prior week; (2) taken immunosuppressive drugs, in-
American Journal of Contact Dermatitis, Vol 13, No 4 (December), 2002: pp 177-182
177
Thompson and Belsito
178
Table 1. Demographic Data for Patients Evaluated in Kansas City, KS (1994 through 1996)
Avg age (yrs) Max age (yrs) Min age (yrs) Standard deviation White Black Hispanic Asian Other
Men (n ⫽ 68)
Women (n ⫽ 73)
Total (n ⫽ 141)
50.4 84.0 10.6 18.0 63 4 1 0 0
53.5 94.0 21.8 17.6 62 8 1 2 0
52.0 94.0 10.7 17.8 125 12 2 2 0
Table 2. Distribution of Dermatitis in Kansas City, KS Versus Other NACDG Centers Dermatitis Site
KUMC (%)
NACDG (%)
Hand Face Foot Scattered/generalized Arm Trunk Leg Neck Eyelids
45 22 17 13 11 9 8 8 6
37 21 8 9 16 11 11 8 7
Results cluding oral corticosteroids, within the prior 2 weeks; or (3) had medical conditions that could compromise the evaluation of skin sensitization. For this report, patch test reactions were interpreted as follows: negative reaction (0), macular erythema (?), erythema, infiltration, possibly papules (1⫹), erythematous papules and/or vesicles (2⫹), spreading blisters and/or crust with ulceration (3⫹), or irritant reaction (IR).3 A positive patch test result was defined as a 1⫹, 2⫹, or 3⫹ reaction. Relevance of the patch test reactions was determined historically by verifying that the putative allergen was either a known skin contactant (probable), had a high likelihood of contact with the patient’s skin (possible), or by patch testing with the actual material or product containing the allergen (definite). Patient demographics and patch test results were tabulated on forms standardized among the 12 centers.4 The history, skin examination, and patch test results were used to determine the diagnostic groups as previously described3: allergic contact dermatitis, irritant contact dermatitis, atopic dermatitis, psoriasis, stasis dermatitis, nummular dermatitis, photodermatitis, other dermatitis, other dermatoses, seborrheic dermatitis, or pompholyx. The source of the exposure was defined as occupational, medical, cosmetic, or other. For comparison of the Kansas City data to that from the other testing centers, the results from Kansas City were compared with the national totals minus the Kansas City data using the 2 test with Yates’ correction. A 2-tailed probability of less than 5% was taken as indication of a statistically significant difference. For those allergens that were found to have an increased rate of reactivity in Kansas City, a linkage to occupational exposure was sought. If such linkage was found, then a comparison of employment patterns between the Kansas City metropolitan area and the 11 other NACDG centers (averaged data from the Bureau of Labor Statistics, May 1995 and the US Census 1990)6 for those industries was undertaken using the KolmogorovSmirnoff test.
The demographic data for patients seen in Kansas City is given in Table 1. The average age for the 141 patients tested in Kansas City was 52 years (range, 10 to 94 years), compared with 47 years (range, 4 to 96) nationally (excluding Kansas City). The patient population from Kansas City included a greater percentage of men (48%) than the national study (38%).1 In Kansas City, the average age for the men was 50.4 ⫾ 18.1 years and for the women 53.5 ⫾ 17.6 years. The racial breakdown of our patients was similar to that in our metropolitan area: 89% white, 9% African-American, 1% Hispanic, and 1% Asian. As shown in Table 2, the five most common dermatitic sites in Kansas City were hands (45%), face (22%), feet (17%), scattered generalized (13%), and arm (11%), whereas the most common sites nationally were hands (37%), face (21%), arms (16%), legs (11%), and trunk (11%).1 The most frequent diagnoses were similar nationally and in Kansas City: allergic contact dermatitis accounted for over 50% of the diagnoses, followed by irritant contact dermatitis and other dermatitis (Table 3). The 10 most commonly encountered allergens in Kansas City were the same as those found nationally (Table 4). However, in Kansas City, reactions to formaldehyde were seen more frequently than reactions to nickel. Occupational exposures were associated with 13% of all positive reactions in the Kansas City population. Cosmetic exposures were noted in nearly 40% of all positive reactions. Similar data from the NACDG during that time period were not available. Overall, patients from Kansas City were found to have higher rates of allergic reactions to 26 of the 50 allergens tested compared with patients studied nationally (Table 4). Allergens with significantly (P ⬍ .05) higher positive Table 3. Final Diagnosis of Patients Undergoing Patch Testing: Kansas City Versus Other NACDG Centers
Allergic Dermatitis Irritant Dermatitis Other Dermatitis
KUMC (%)
NACDG (%)
63 18 19
59 24 17
Regional Variations in Prevalence and Etiology of ACD
179
Table 4. Patch Test Results to the 1994-1996 NACDG Standard Tray: Kansas City, KS Versus Other NACDG Centers
Allergen Benzocaine Mercaptobenzothiazole Colophony P-phenylenediamine Imidazolidinyl urea Cinnamic aldehyde Lanolin alcohol Carba mix Neomycin sulfate Thiuram mix Formaldehyde Ethylenediamine dihydrochloride Epoxy resin Quaternium-15 P-tert-butylphenol formaldehyde resin Mercapto mix N-isopropyl-n-phenylenediamine Potassium dichromate Balsam of Peru Nickel sulfate Diazolidinyl urea DMDM hydantoin Imidazolidinyl urea Bacitracin Mixed dialkyl thioureas MCI/MI Paraben mix Methyldibromoglutaronitrile/phenoxyethanol Fragrance mix 2-bromo-2-nitropropane-1,3-diol Sesquiterpene lactone mix Thimerosal Chloroxylenol (PCMX) DMDM hydantoin Diazolidinyl urea Ethyleneurea melamine formaldehyde BHA Glutaraldehyde Ethyl acrylate Glyceryl thioglycolate Toluene sulphonamide formaldehyde resin Methyl methacrylate Cobalt chloride Tixocortol-21-pivalate Budesonide MCI/MI Propylene glycol Glutaraldehyde BHT Phenoxyethanol
Concentration and Vehicle
KUMC, No.
KUMC, Pos %
NACDGKUMC, No.
NACDGKUMC, Pos %
Yates 2
P Value
5% pet 1% pet 20% pet 1% pet 2% aq 1% pet 30% pet 3% pet 20% pet 1% pet 1% aq 1% pet 1% pet 2% pet 1% pet 1% pet 0.1% pet 0.25% pet 25% pet 2.5% pet 1% pet 1% pet 2% pet 20% pet 1% pet 100ppm aq 12% pet 1% pet 8% pet 0.5% pet 0.2% pet 0.1% pet 1% pet 1% aq 1% aq 5% pet 2% pet 1% pet 0.1% pet 1% pet 10% pet 2% pet 1% pet 1% pet 0.1% pet 100 ppm pet 10% aq 2% pet 2% pet 1% pet
141 141 141 141 141 141 141 141 140 141 138 141 141 140 141 141 141 135 141 139 141 141 141 141 141 141 141 141 141 141 141 141 141 141 141 141 141 140 141 141 141 141 141 141 91 141 141 141 141 141
3.5 2.1 4.3 7.8 3.5 1.4 0.7 2.8 9.3 7.1 14.5 2.1 2.8 12.1 2.8 0.7 1.4 5.9 9.9 12.9 7.1 3.5 6.4 9.9 0.0 6.4 2.1 2.8 12.8 5.0 0.0 7.8 0.7 5.0 6.4 7.8 0.0 5.0 0.0 3.5 0.7 0.7 8.5 2.1 1.1 5.7 2.1 1.4 0.0 0.0
2,971 2,974 2,972 2,970 2,960 2,971 2,973 2,974 2,964 2,974 2,973 2,972 2,973 2,970 2,973 2,974 2,972 2,971 2,971 2,969 2,944 2,941 2,939 2,938 2,934 2,934 2,945 2,933 2,941 2,933 2,932 2,934 2,933 2,923 2,919 2,930 2,935 2,935 2,933 2,934 2,936 2,939 2,946 2,950 1,587 2,937 2,936 2,935 2,935 2,943
2.6 2.1 2.5 6.8 2.6 2.4 3.4 5.8 11.2 6.8 9.0 2.9 2.2 9.1 2.7 2.3 2.3 1.8 10.4 14.4 3.5 2.2 2.9 9.1 0.7 2.8 1.8 2.0 14.1 2.2 0.9 10.5 1.2 2.0 3.6 4.9 0.5 2.1 1.9 5.1 1.6 1.2 8.0 2.3 1.1 2.9 1.1 0.7 0.2 0.0
0.20 0.08 0.99 0.10 0.20 0.25 2.31 1.73 0.32 0.00 4.20 0.09 0.05 1.17 0.03 0.89 0.18 9.10 0.00 0.12 3.83 0.52 4.22 0.04 0.25 4.66 0.00 0.18 0.09 3.51 0.49 0.80 0.02 4.53 2.25 1.86 0.06 4.07 1.75 0.38 0.27 0.02 0.00 0.02 0.27 2.73 0.62 0.28 0.18 *
NS NS NS NS NS NS NS NS NS NS ⬍.05 NS NS NS NS NS NS ⬍.01 NS NS ⬍.05 NS ⬍.05 NS NS ⬍.05 NS NS NS ⫽.06 NS NS NS ⬍.05 NS NS NS ⬍.05 NS NS NS NS NS NS NS NS NS NS NS NS
*Division by zero error.
reactions in Kansas City by the 2 test with Yates’ correction were formaldehyde, DMDM hydantoin, imidazolidinyl urea, diazolidinyl urea, glutaraldehyde, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and potassium dichromate. Differences in the incidence of reac-
tivity to potassium dichromate were the most statistically significant (P ⬍ .01). Occupational exposure related to potassium dichromate accounted for 50.0% (4 of 8 patients) of the positive reactions detected in Kansas City; nationally, 23.5% of
180
Thompson and Belsito
positive reactions to chromate were deemed occupational. In Kansas City, hand/arm dermatitis was the presenting symptom in all of these occupational cases. Occupational ACD was seen in a construction laborer, a driver of cement trucks, a weigher/measurer, and a dental hygienist. A comparison of employment by general industry between the Kansas City metropolitan area and the 11 other NACDG centers (averaged data from the Bureau of Labor Statistics, May 1995 on the US Census, 1990)6 displayed no statistical differences in the percentage of the populations employed in these industries (Kolmogorov-Smirnoff test). The Kansas City data also showed significantly (P ⬍ .05) increased positive reactions to formaldehyde and formaldehyde-releasing agents (DMDM hydantoin, imidazolidinyl urea, and diazolidinyl urea). One other formaldehyde-releasing agent tested, 2-bromo-2-nitropropane-1, 3-diol (Bronopol), also was noted to be more common in Kansas City, although the statistical association was weaker (P ⫽ .06). Quaternium-15 was the only formaldehyde releaser to which the incidence of reactivity in Kansas City was not statistically different from the national results (P ⫽ .28). Occupational exposure related to formaldehyde and formaldehyde-releasing agents was noted in 2-bromo-2nitropropane-1,3-diol (43% of cases), formaldehyde (25%), quaternium-15 (24%), and diazolidinyl urea (10%); nationally, these percentages were 0%, 19.7%, 8.1% and 3.2%, respectively. A further review of the work-related exposures in Kansas City showed that no occupation was represented more than once among the 8 individuals with occupational ACD to formaldehyde or formaldehyde-releasing allergens. The exposed workers included a janitor, a photoengraver, a materials handler/stocker, a machinist, a hairdresser, a dental technician, a truck driver, and a cashier. Again, a comparison of employment in these industries between the Kansas City metropolitan area and the 11 other NACDG centers (averaged data from the Bureau of Labor Statistics, May 1995 and the US Census 19906) displayed no statistical differences in the percentage of the populations employed in these industries (Kolmogorov-Smirnoff test). The increased MCI/MI reactivity in Kansas City was statistically significant (P ⬍ .05) for the 100 ppm aq. formulation and less significant (P ⬍ .10) for the 100 ppm pet. formulation. In Kansas City, occupational exposure accounted for 11% of the allergic reactions seen. This latter number does not differ from that seen nationally (12%). Allergic reactions to glutaraldehyde (1% pet.) also were statistically more frequent in Kansas City (P ⬍ .05). Five of the 7 individuals (71.4%) sensitized to glutaraldehyde in the Kansas City population had occupationally acquired disease, an incidence rate that does not statistically differ from that found nationally (68.8%). Three of these 5 patients were dental hygienists/assistants. The other 2 were a machinist and a supervisor of production operations.
Discussion The inclusion of data from Kansas City in the 1994-1996 results expands the scope of the NACDG patch test studies to the midwestern United States. The initial analysis of patch test results from Kansas City compared with patch test results at the 11 other NACDG test centers shows statistically significant differences for 7 (14%) of the allergens tested: formaldehyde, DMDM hydantoin, imidazolidinyl urea, diazolidinyl urea, glutaraldehyde, MCI/MI, and potassium dichromate. Potassium dichromate displayed the most significant difference from the 11 other centers (P ⬍ .01). The overall incidence of allergic reactions to potassium dichromate in Kansas City was 5.9% compared with 1.8% for the other 11 centers. Potassium dichromate sensitivity steadily decreased nationally from 1972 (7.6%) to 1996 (2.0%).1-5 However, recently, there has been resurgence in the frequency of positive reactions to chromium in the NACDG’s patient population: 2.8% in the 1996 to 1998 period7 and 5.8% in 1998 to 2000 (preliminary data, personal communication, NACDG). International patch test studies in a general population have found higher incidences of potassium dichromate sensitivity ranging up to 11.0%.8-15 Hexavalent chromium allergy is the most common cause of occupational allergic contact dermatitis, especially in men.15 Chromium sensitization can occur from a wide array of sources, most commonly from tanned leather or cement. Standard Portland cement consists of clinker (95%) and gypsum (5%). Although ferrous sulfate additives or dilution of clinker in cement with slag from iron blast furnace processing may decrease the hexavalent chromium present in cement,15-17 the cement available in Kansas City, as with most United States cities, is not so treated. Blended cement substitutes slag, fly ash, or calcine clay for a portion of the clinker in cement because of the cost and availability of clinker. Although blended cement use has increased, blended cement accounts for only a small proportion (⬍.2%) of total cement use in Kansas and Missouri compared with standard Portland cement: (United States Geological Survey in January 1998).18 Because Kansas City does not differ from the other NACDG centers in the proportion of workers involved in construction, the higher percentage of occupationally related cases to chromate in Kansas City suggests a referral bias for this center. Unfortunately, because the NACDG did not begin Standard Industrial Coding for occupations until July 1, 1996, this hypothesis could not be verified. The data from Kansas City shows an increased rate of positive reactions to formaldehyde and most of the formaldehyde-releasing agents (DMDM hydantoin, imidazolidinyl urea and diazolidinyl urea and 2-bromo-2-nitropropane-1, 3-diol [Bronopol]). Among the formaldehyde releasers, quaternium-15 was the only one to which the incidence of reactivity in Kansas City was not different
Regional Variations in Prevalence and Etiology of ACD
from the national results. As was seen for chromate, occupational exposure to formaldehyde and formaldehyde-releasing agents was more commonly seen in Kansas City, suggesting a referral bias for this center. Among those individuals in Kansas City with occupationally related disease to formaldehyde and its releasers, the janitor,19 photoengraver,20 machinist,21 hairdresser,22 and dental technician23 worked in industries in which higher rates of formaldehyde allergy had been described previously. Nonetheless, in addition to their occupational uses, formaldehyde-releasing preservatives are common in cosmetics, where they are incorporated for their broad-spectrum antimicrobial activity. Formaldehyde production from formaldehyde-releasing agents is facilitated on the skin because of its pH and temperature.24 Allergic reactions may occur to the formaldehyde-releasing preservative, formaldehyde, or both. The increased MCI/MI reactivity in Kansas City was statistically significant (P ⬍ .05) for the 100 ppm aqueous formulation and less significant (P ⬍ .10) for the 100 ppm petrolatum formulation. Nationally, the rate of positive patch test reactions to MCI/MI (100 ppm aq.) increased between 1994 and 1996, when compared with prior studies in 1988 and 1989 and 1991 and 1992 (1.9% and 1.8%, respectively)25. The frequency of MCI/MI reactions in Kansas City and nationally may reflect an increased use of MCI/MI as a biocide in cosmetics, toiletries, and industrial products.26 Over 90% (10 of 11) of MCI/MI reactions (aq. and pet. combined) were related to cosmetic exposure, with one case of exposure from both cosmetics and the workplace and another case with exposure from cosmetics and topical medication. With the recent increases in ACD to MCI/MI, continued monitoring of MCI/MI sensitivity will be important in the future. Glutaraldehyde (1% pet.) also showed a statistically significant difference (P ⬍ .05), yet glutaraldehyde (.2% pet.) displayed no statistically significant difference. Falsenegative reactions with the weaker concentration or falsepositive reactions at the higher concentration may explain the differing results with the concentrations studied. Because of concerns with false-negatives, the NACDG replaced glutaraldehyde (.2% pet.) with glutaraldehyde (.5% pet.) for study in its subsequent standard tray. Glutaraldehyde is utilized as a cold sterilizer in the health care industry because of its antimicrobial, antiviral, and fungicidal activity in an alkaline solution. Occupational exposure accounted for more than 70% (5 of 7 patients) of sensitizations with dental hygienists accounting for 60% (3 of 5) of the occupational cases. Hand dermatitis occurred in 80% (4 of 5) patients with occupational ACD to glutaraldehyde. This finding further highlights the association between ACD owing to glutaraldehyde and the sterilization of dental equipment.27,28 The current findings show significant regional differences in patch test results. Whereas an awareness of national patch test trends is important, dermatologists
181
should be cognizant of regional variations in allergen sources within their community and referral network. Although it could not be verified, the increased percentage of patients seen with ACD to formaldehyde, formaldehydereleasing agents, and potassium dichromate in Kansas City were likely caused by the referral of greater numbers of work-related cases to this center. The findings that a greater percentage of men and a greater number of cases of hand dermatitis were seen in Kansas City are consistent with this hypothesis. However, occupationally acquired ACD to MCI/MI and glutaraldehyde were not more frequent in Kansas City than nationally, suggesting that other factors, such as climactic, environmental, social, and cultural, as well as local prescribing habits, might be operative in Kansas City.
References 1. Marks JG, Belsito DV, DeLeo VA, et al: North American Contact Dermatitis Group patch test results for the detection of delayed-type hypersensitivity to topical allergens. J Am Acad Dermatol 38:911-918, 1998 2. Rudner EJ, Clendenning WE, Epstein E, et al: Epidemiology of contact dermatitis in North America. 1972. Arch Dermatol 108:537-540, 1979 3. Storrs FJ, Rosenthal LE, Adams RM, et al: Prevalence and relevance of allergic reactions in patients patch tested in North America—1984 to 1985. J Am Acad Dermatol 20:1038-1045, 1989 4. Nethercott JR, Holness DL, Adams RM, et al: Patch testing with a routine screening tray in North America, 1985 through 1989: I. frequency of response. Am J Contact Dermatitis 2:122-129, 1991 5. Marks JG, Belsito DV, DeLeo VA, et al: North American Contact Dermatitis group standard tray patch test results (1992 to 1994). Am J Contact Dermatitis 6:160-165, 1995 6. Carpenter A, Provorse C: Facts about the Cities (ed 2). New York, NY, Wilson Co, 1996 7. Marks JG Jr, Belsito DV, De Leo VA, et al: North American Contact Dermatitis Group patch-test results, 1996-1998. Arch Dermatol 136:272273, 2000 8. Hogan DJ, Hill M, Lane PR: Results of routine patch testing of 542 patients in Saskatoon, Canada. Contact Dermatitis 19:120-124, 1988 9. Massone L, Anonide A, Borghi S, et al: Positive patch test reactions to nickel, cobalt, and potassium dichromate in a series of 576 patients. Cutis 47:119-122, 1991 10. Lim JTE, Goh CL, Ng SK, et al: Changing trends in the epidemiology of contact dermatitis in Singapore. Contact Dermatitis 26:321-326, 1992 11. Castiglioni G, Carosso A, Manzoni S, et al: Results of routine patch testing of 834 patients in Turin. Contact Dermatitis 27:182-185, 1992 12. Bruckner-Tuderman L, Konig A, Schnyder UW: Patch test results of the dermatology clinic Zurich in 1989: Personal computer-aided statistical evaluation. Dermatology 184:29-33, 1992 13. Wang XM, Lin YF, Cheng XF, et al: Patch testing with the European standard series in Shanghai. Contact Dermatitis 30:173, 1994 14. Bangha E, Elsner P: Sensitizations to allergens of the European standard series at the Department of Dermatology in Zurich 1990-1994. Dermatology 193:17-21, 1996 15. Zachariae COC, Agner T, Menne T: Chromium allergy in consecutive patients in a country where ferrous sulfate has been added to cement since 1981. Contact Dermatitis 35:83-85, 1996 16. Roto P, Sainio H, Reunala T: Addition of ferrous sulfate to cement and risk of chromium dermatitis among construction workers. Contact Dermatitis 35:83-85, 1996 17. Goh CL, Gan SL: Change in cement manufacturing process, a cause for decline in chromate allergy? Contact Dermatitis 34:51-54, 1996
182
Thompson and Belsito
18. Van Oss H, Dunkelberger E: USGS Mineral Industry Surveys: Cement in March 1998. Reston, VA: U.S. Dept. of Interior, U.S. Geological Survey. Online. Available: http://minerals.er.usgs.gov/minerals/pubs/commodity/ cement/17000398.pdf. 24 June 1998 19. Hansen KS: Occupational dermatoses in hospital cleaning women. Contact Dermatitis 9:343-51, 1983 20. Flyvholm MA, Menne T: Allergic contact dermatitis from formaldehyde. A case study focussing on sources of formaldehyde exposure. Contact Dermatitis 27:27-36, 1992 21. Grattan CE, English JS, Foulds IS, et al: Cutting fluid dermatitis. Contact Dermatitis 20:372-376, 1989 22. Holness DL, Nethercott JR: Dermatitis in hairdressers. Dermatol Clin 8:119-126, 1990 23. Kiec-Swierczynska M, Krecisz B, Krysiak B, et al: Occupational allergy to
24. 25.
26. 27.
28.
aldehydes in health care workers. Clinical observations. Experiments. Int J Occup Med Environ Health 11:349-358, 1998 Fowler JF, Skinner S: Contact dermatitis due to cosmetic preservatives. Am J Contact Dermatitis 2:143-144, 1991 Marks JG, Moss JN, Parno JR, et al: Methylchloroisothiazolinone/methylisothiazolinone (Kathon CG) biocide: Second United States multicenter study on human skin sensitization. Am J Contact Dermatitis 4:87-89, 1993 Cronin E, Hannuksela M, Lachapelle JM: Frequency of sensitization to the preservative Kathon CG. Contact Dermatitis 18:274-279, 1988 Nethercott JR, Holness DL, Page E: Occupational contact dermatitis due to glutaraldehyde in health care workers. Contact Dermatitis 18:193-196, 1988 Shaffer MP, Belsito DV: Allergic contact dermatitis to glutaraldehyde in health-care workers. Contact Dermatitis 43:150-156, 2000
Regional Variation in Prevalence and Etiology of Allergic Contact Dermatitis Trevor R. Thompson and Donald V. Belsito Background: The 1994-1996 North American Contact Dermatitis Group (NACDG) patch test results were the first, since the inception of the NACDG in 1970, to include results from a medium-sized metropolitan city in the Midwest. Objective: The aim of this study was to determine whether the causative allergens of allergic contact dermatitis (ACD) in the Midwest differ from those in other regions of the United States and, if so, whether occupational or other factors account for the observed differences. Methods: Retrospective analyses of patch test data collected at the University of Kansas Medical Center (Kansas City, KS) were compared with the data collected by the other NACDG centers. Results: Patients in Kansas City were statistically more likely to react to potassium dichromate, formaldehyde and its releasers, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and glutaraldehyde. Occupational exposures to chromium and formaldehyde were increased significantly among patients from Kansas City, although the percentages of the local population engaged in these occupations did not differ from those in other NACDG cities. Equal percentages of workers in Kansas City and nationally had occupationally related allergy to glutaraldehyde, although the overall rate of glutaraldehyde was higher among patients from Kansas City. Most cases of relevant allergy to MCI/MI were cosmetically induced both in Kansas City and nationally. Conclusions: The current findings show significant regional differences in causal allergens. The increased percentages of patients seen with ACD to formaldehyde, formaldehyde-releasing agents, and potassium dichromate in Kansas City were likely caused by the referral of greater numbers of work-related cases. However, occupationally acquired ACD to MCI/MI and glutaraldehyde were not more frequent in Kansas City than nationally, suggesting that other factors might be operative. Although awareness of national trends is important, dermatologists must be cognizant of regional variations in allergen sources within their communities and referral networks. Copyright 2002, Elsevier Science (USA). All rights reserved.
P
ATCH TESTING PROVIDES a basis for determining the cause of allergic contact dermatitis (ACD) and enables investigators to monitor trends in the rate of reactivity to allergens in their communities. The North American Contact Dermatitis Group (NACDG) gathers patch test results from participating centers around the United States and Canada. NACDG test centers conduct patch testing using a standardized technique and a standard tray of allergens, which includes newly marketed chemicals to search for the introduction of new allergens into the environment. The 1994-1996 NACDG study1 included patch test results from the University of Kansas Medical Center in Kansas City, KS. The results provided from this central Midwestern site to the NACDG for its biennial analysis were the first from this region since the inception of the NACDG in 1970.1-5 Because of variances in patch test results related to climactic, environmental, social, occupational, and cultural factors, as well as local prescribing From the Division of Dermatology, University of Kansas Medical Center, Kansas City, KS. Address reprint requests to Donald V. Belsito, MD, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160. Funding was provided by the Division of Dermatology, University of Kansas Medical Center, Kansas City, KS Copyright 2002, Elsevier Science (USA). All rights reserved. 1046-199X/02/1304-0005$35.00/0 doi:10.1053/ajcd.2002.36643
habits, this study was designed to assess for differences in the causative allergens of ACD in the central United States compared with other regions in the United States.
Materials and Methods Between July 1, 1994 and June 30, 1996, 3,120 patients suspected of having allergic contact dermatitis were evaluated by the 12 dermatologists of the NACDG. In addition to the Kansas City location, the other NACDG sites were located in Hershey, PA; New York, NY; Louisville, KY; Ft Myers, FL; San Francisco, CA; Cincinnati, OH; Baltimore, MD; New Orleans, LA; Winston-Salem, NC; Portland, OR; and Cleveland, OH. All patients were patch tested to a standard tray of 49 allergens. In July 1995 budesonide was added to the standard tray and tested on 1,678 patients nationally. During this same time period, 141 patients were patch tested at the University of Kansas Medical Center for inclusion in the NACDG study. Ninety-one of these 141 patients were tested to budesonide. All patients were patch tested using Finn Chambers (Epitest Ltd Oy, Tuusula, Finland) on Scanpor tape (Norgesplaster Aksjeselskap, Vennesia, Norway), which were applied on the back as previously described.3 In Kansas City, the patches were removed after 48 hours and the test sites evaluated at that time and again 96 hours after initial placement. Patients were not tested if they had (1) applied topical corticosteroids to patch test sites within the prior week; (2) taken immunosuppressive drugs, in-
American Journal of Contact Dermatitis, Vol 13, No 4 (December), 2002: pp 177-182
177
Thompson and Belsito
178
Table 1. Demographic Data for Patients Evaluated in Kansas City, KS (1994 through 1996)
Avg age (yrs) Max age (yrs) Min age (yrs) Standard deviation White Black Hispanic Asian Other
Men (n ⫽ 68)
Women (n ⫽ 73)
Total (n ⫽ 141)
50.4 84.0 10.6 18.0 63 4 1 0 0
53.5 94.0 21.8 17.6 62 8 1 2 0
52.0 94.0 10.7 17.8 125 12 2 2 0
Table 2. Distribution of Dermatitis in Kansas City, KS Versus Other NACDG Centers Dermatitis Site
KUMC (%)
NACDG (%)
Hand Face Foot Scattered/generalized Arm Trunk Leg Neck Eyelids
45 22 17 13 11 9 8 8 6
37 21 8 9 16 11 11 8 7
Results cluding oral corticosteroids, within the prior 2 weeks; or (3) had medical conditions that could compromise the evaluation of skin sensitization. For this report, patch test reactions were interpreted as follows: negative reaction (0), macular erythema (?), erythema, infiltration, possibly papules (1⫹), erythematous papules and/or vesicles (2⫹), spreading blisters and/or crust with ulceration (3⫹), or irritant reaction (IR).3 A positive patch test result was defined as a 1⫹, 2⫹, or 3⫹ reaction. Relevance of the patch test reactions was determined historically by verifying that the putative allergen was either a known skin contactant (probable), had a high likelihood of contact with the patient’s skin (possible), or by patch testing with the actual material or product containing the allergen (definite). Patient demographics and patch test results were tabulated on forms standardized among the 12 centers.4 The history, skin examination, and patch test results were used to determine the diagnostic groups as previously described3: allergic contact dermatitis, irritant contact dermatitis, atopic dermatitis, psoriasis, stasis dermatitis, nummular dermatitis, photodermatitis, other dermatitis, other dermatoses, seborrheic dermatitis, or pompholyx. The source of the exposure was defined as occupational, medical, cosmetic, or other. For comparison of the Kansas City data to that from the other testing centers, the results from Kansas City were compared with the national totals minus the Kansas City data using the 2 test with Yates’ correction. A 2-tailed probability of less than 5% was taken as indication of a statistically significant difference. For those allergens that were found to have an increased rate of reactivity in Kansas City, a linkage to occupational exposure was sought. If such linkage was found, then a comparison of employment patterns between the Kansas City metropolitan area and the 11 other NACDG centers (averaged data from the Bureau of Labor Statistics, May 1995 and the US Census 1990)6 for those industries was undertaken using the KolmogorovSmirnoff test.
The demographic data for patients seen in Kansas City is given in Table 1. The average age for the 141 patients tested in Kansas City was 52 years (range, 10 to 94 years), compared with 47 years (range, 4 to 96) nationally (excluding Kansas City). The patient population from Kansas City included a greater percentage of men (48%) than the national study (38%).1 In Kansas City, the average age for the men was 50.4 ⫾ 18.1 years and for the women 53.5 ⫾ 17.6 years. The racial breakdown of our patients was similar to that in our metropolitan area: 89% white, 9% African-American, 1% Hispanic, and 1% Asian. As shown in Table 2, the five most common dermatitic sites in Kansas City were hands (45%), face (22%), feet (17%), scattered generalized (13%), and arm (11%), whereas the most common sites nationally were hands (37%), face (21%), arms (16%), legs (11%), and trunk (11%).1 The most frequent diagnoses were similar nationally and in Kansas City: allergic contact dermatitis accounted for over 50% of the diagnoses, followed by irritant contact dermatitis and other dermatitis (Table 3). The 10 most commonly encountered allergens in Kansas City were the same as those found nationally (Table 4). However, in Kansas City, reactions to formaldehyde were seen more frequently than reactions to nickel. Occupational exposures were associated with 13% of all positive reactions in the Kansas City population. Cosmetic exposures were noted in nearly 40% of all positive reactions. Similar data from the NACDG during that time period were not available. Overall, patients from Kansas City were found to have higher rates of allergic reactions to 26 of the 50 allergens tested compared with patients studied nationally (Table 4). Allergens with significantly (P ⬍ .05) higher positive Table 3. Final Diagnosis of Patients Undergoing Patch Testing: Kansas City Versus Other NACDG Centers
Allergic Dermatitis Irritant Dermatitis Other Dermatitis
KUMC (%)
NACDG (%)
63 18 19
59 24 17
Regional Variations in Prevalence and Etiology of ACD
179
Table 4. Patch Test Results to the 1994-1996 NACDG Standard Tray: Kansas City, KS Versus Other NACDG Centers
Allergen Benzocaine Mercaptobenzothiazole Colophony P-phenylenediamine Imidazolidinyl urea Cinnamic aldehyde Lanolin alcohol Carba mix Neomycin sulfate Thiuram mix Formaldehyde Ethylenediamine dihydrochloride Epoxy resin Quaternium-15 P-tert-butylphenol formaldehyde resin Mercapto mix N-isopropyl-n-phenylenediamine Potassium dichromate Balsam of Peru Nickel sulfate Diazolidinyl urea DMDM hydantoin Imidazolidinyl urea Bacitracin Mixed dialkyl thioureas MCI/MI Paraben mix Methyldibromoglutaronitrile/phenoxyethanol Fragrance mix 2-bromo-2-nitropropane-1,3-diol Sesquiterpene lactone mix Thimerosal Chloroxylenol (PCMX) DMDM hydantoin Diazolidinyl urea Ethyleneurea melamine formaldehyde BHA Glutaraldehyde Ethyl acrylate Glyceryl thioglycolate Toluene sulphonamide formaldehyde resin Methyl methacrylate Cobalt chloride Tixocortol-21-pivalate Budesonide MCI/MI Propylene glycol Glutaraldehyde BHT Phenoxyethanol
Concentration and Vehicle
KUMC, No.
KUMC, Pos %
NACDGKUMC, No.
NACDGKUMC, Pos %
Yates 2
P Value
5% pet 1% pet 20% pet 1% pet 2% aq 1% pet 30% pet 3% pet 20% pet 1% pet 1% aq 1% pet 1% pet 2% pet 1% pet 1% pet 0.1% pet 0.25% pet 25% pet 2.5% pet 1% pet 1% pet 2% pet 20% pet 1% pet 100ppm aq 12% pet 1% pet 8% pet 0.5% pet 0.2% pet 0.1% pet 1% pet 1% aq 1% aq 5% pet 2% pet 1% pet 0.1% pet 1% pet 10% pet 2% pet 1% pet 1% pet 0.1% pet 100 ppm pet 10% aq 2% pet 2% pet 1% pet
141 141 141 141 141 141 141 141 140 141 138 141 141 140 141 141 141 135 141 139 141 141 141 141 141 141 141 141 141 141 141 141 141 141 141 141 141 140 141 141 141 141 141 141 91 141 141 141 141 141
3.5 2.1 4.3 7.8 3.5 1.4 0.7 2.8 9.3 7.1 14.5 2.1 2.8 12.1 2.8 0.7 1.4 5.9 9.9 12.9 7.1 3.5 6.4 9.9 0.0 6.4 2.1 2.8 12.8 5.0 0.0 7.8 0.7 5.0 6.4 7.8 0.0 5.0 0.0 3.5 0.7 0.7 8.5 2.1 1.1 5.7 2.1 1.4 0.0 0.0
2,971 2,974 2,972 2,970 2,960 2,971 2,973 2,974 2,964 2,974 2,973 2,972 2,973 2,970 2,973 2,974 2,972 2,971 2,971 2,969 2,944 2,941 2,939 2,938 2,934 2,934 2,945 2,933 2,941 2,933 2,932 2,934 2,933 2,923 2,919 2,930 2,935 2,935 2,933 2,934 2,936 2,939 2,946 2,950 1,587 2,937 2,936 2,935 2,935 2,943
2.6 2.1 2.5 6.8 2.6 2.4 3.4 5.8 11.2 6.8 9.0 2.9 2.2 9.1 2.7 2.3 2.3 1.8 10.4 14.4 3.5 2.2 2.9 9.1 0.7 2.8 1.8 2.0 14.1 2.2 0.9 10.5 1.2 2.0 3.6 4.9 0.5 2.1 1.9 5.1 1.6 1.2 8.0 2.3 1.1 2.9 1.1 0.7 0.2 0.0
0.20 0.08 0.99 0.10 0.20 0.25 2.31 1.73 0.32 0.00 4.20 0.09 0.05 1.17 0.03 0.89 0.18 9.10 0.00 0.12 3.83 0.52 4.22 0.04 0.25 4.66 0.00 0.18 0.09 3.51 0.49 0.80 0.02 4.53 2.25 1.86 0.06 4.07 1.75 0.38 0.27 0.02 0.00 0.02 0.27 2.73 0.62 0.28 0.18 *
NS NS NS NS NS NS NS NS NS NS ⬍.05 NS NS NS NS NS NS ⬍.01 NS NS ⬍.05 NS ⬍.05 NS NS ⬍.05 NS NS NS ⫽.06 NS NS NS ⬍.05 NS NS NS ⬍.05 NS NS NS NS NS NS NS NS NS NS NS NS
*Division by zero error.
reactions in Kansas City by the 2 test with Yates’ correction were formaldehyde, DMDM hydantoin, imidazolidinyl urea, diazolidinyl urea, glutaraldehyde, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), and potassium dichromate. Differences in the incidence of reac-
tivity to potassium dichromate were the most statistically significant (P ⬍ .01). Occupational exposure related to potassium dichromate accounted for 50.0% (4 of 8 patients) of the positive reactions detected in Kansas City; nationally, 23.5% of
180
Thompson and Belsito
positive reactions to chromate were deemed occupational. In Kansas City, hand/arm dermatitis was the presenting symptom in all of these occupational cases. Occupational ACD was seen in a construction laborer, a driver of cement trucks, a weigher/measurer, and a dental hygienist. A comparison of employment by general industry between the Kansas City metropolitan area and the 11 other NACDG centers (averaged data from the Bureau of Labor Statistics, May 1995 on the US Census, 1990)6 displayed no statistical differences in the percentage of the populations employed in these industries (Kolmogorov-Smirnoff test). The Kansas City data also showed significantly (P ⬍ .05) increased positive reactions to formaldehyde and formaldehyde-releasing agents (DMDM hydantoin, imidazolidinyl urea, and diazolidinyl urea). One other formaldehyde-releasing agent tested, 2-bromo-2-nitropropane-1, 3-diol (Bronopol), also was noted to be more common in Kansas City, although the statistical association was weaker (P ⫽ .06). Quaternium-15 was the only formaldehyde releaser to which the incidence of reactivity in Kansas City was not statistically different from the national results (P ⫽ .28). Occupational exposure related to formaldehyde and formaldehyde-releasing agents was noted in 2-bromo-2nitropropane-1,3-diol (43% of cases), formaldehyde (25%), quaternium-15 (24%), and diazolidinyl urea (10%); nationally, these percentages were 0%, 19.7%, 8.1% and 3.2%, respectively. A further review of the work-related exposures in Kansas City showed that no occupation was represented more than once among the 8 individuals with occupational ACD to formaldehyde or formaldehyde-releasing allergens. The exposed workers included a janitor, a photoengraver, a materials handler/stocker, a machinist, a hairdresser, a dental technician, a truck driver, and a cashier. Again, a comparison of employment in these industries between the Kansas City metropolitan area and the 11 other NACDG centers (averaged data from the Bureau of Labor Statistics, May 1995 and the US Census 19906) displayed no statistical differences in the percentage of the populations employed in these industries (Kolmogorov-Smirnoff test). The increased MCI/MI reactivity in Kansas City was statistically significant (P ⬍ .05) for the 100 ppm aq. formulation and less significant (P ⬍ .10) for the 100 ppm pet. formulation. In Kansas City, occupational exposure accounted for 11% of the allergic reactions seen. This latter number does not differ from that seen nationally (12%). Allergic reactions to glutaraldehyde (1% pet.) also were statistically more frequent in Kansas City (P ⬍ .05). Five of the 7 individuals (71.4%) sensitized to glutaraldehyde in the Kansas City population had occupationally acquired disease, an incidence rate that does not statistically differ from that found nationally (68.8%). Three of these 5 patients were dental hygienists/assistants. The other 2 were a machinist and a supervisor of production operations.
Discussion The inclusion of data from Kansas City in the 1994-1996 results expands the scope of the NACDG patch test studies to the midwestern United States. The initial analysis of patch test results from Kansas City compared with patch test results at the 11 other NACDG test centers shows statistically significant differences for 7 (14%) of the allergens tested: formaldehyde, DMDM hydantoin, imidazolidinyl urea, diazolidinyl urea, glutaraldehyde, MCI/MI, and potassium dichromate. Potassium dichromate displayed the most significant difference from the 11 other centers (P ⬍ .01). The overall incidence of allergic reactions to potassium dichromate in Kansas City was 5.9% compared with 1.8% for the other 11 centers. Potassium dichromate sensitivity steadily decreased nationally from 1972 (7.6%) to 1996 (2.0%).1-5 However, recently, there has been resurgence in the frequency of positive reactions to chromium in the NACDG’s patient population: 2.8% in the 1996 to 1998 period7 and 5.8% in 1998 to 2000 (preliminary data, personal communication, NACDG). International patch test studies in a general population have found higher incidences of potassium dichromate sensitivity ranging up to 11.0%.8-15 Hexavalent chromium allergy is the most common cause of occupational allergic contact dermatitis, especially in men.15 Chromium sensitization can occur from a wide array of sources, most commonly from tanned leather or cement. Standard Portland cement consists of clinker (95%) and gypsum (5%). Although ferrous sulfate additives or dilution of clinker in cement with slag from iron blast furnace processing may decrease the hexavalent chromium present in cement,15-17 the cement available in Kansas City, as with most United States cities, is not so treated. Blended cement substitutes slag, fly ash, or calcine clay for a portion of the clinker in cement because of the cost and availability of clinker. Although blended cement use has increased, blended cement accounts for only a small proportion (⬍.2%) of total cement use in Kansas and Missouri compared with standard Portland cement: (United States Geological Survey in January 1998).18 Because Kansas City does not differ from the other NACDG centers in the proportion of workers involved in construction, the higher percentage of occupationally related cases to chromate in Kansas City suggests a referral bias for this center. Unfortunately, because the NACDG did not begin Standard Industrial Coding for occupations until July 1, 1996, this hypothesis could not be verified. The data from Kansas City shows an increased rate of positive reactions to formaldehyde and most of the formaldehyde-releasing agents (DMDM hydantoin, imidazolidinyl urea and diazolidinyl urea and 2-bromo-2-nitropropane-1, 3-diol [Bronopol]). Among the formaldehyde releasers, quaternium-15 was the only one to which the incidence of reactivity in Kansas City was not different
Regional Variations in Prevalence and Etiology of ACD
from the national results. As was seen for chromate, occupational exposure to formaldehyde and formaldehyde-releasing agents was more commonly seen in Kansas City, suggesting a referral bias for this center. Among those individuals in Kansas City with occupationally related disease to formaldehyde and its releasers, the janitor,19 photoengraver,20 machinist,21 hairdresser,22 and dental technician23 worked in industries in which higher rates of formaldehyde allergy had been described previously. Nonetheless, in addition to their occupational uses, formaldehyde-releasing preservatives are common in cosmetics, where they are incorporated for their broad-spectrum antimicrobial activity. Formaldehyde production from formaldehyde-releasing agents is facilitated on the skin because of its pH and temperature.24 Allergic reactions may occur to the formaldehyde-releasing preservative, formaldehyde, or both. The increased MCI/MI reactivity in Kansas City was statistically significant (P ⬍ .05) for the 100 ppm aqueous formulation and less significant (P ⬍ .10) for the 100 ppm petrolatum formulation. Nationally, the rate of positive patch test reactions to MCI/MI (100 ppm aq.) increased between 1994 and 1996, when compared with prior studies in 1988 and 1989 and 1991 and 1992 (1.9% and 1.8%, respectively)25. The frequency of MCI/MI reactions in Kansas City and nationally may reflect an increased use of MCI/MI as a biocide in cosmetics, toiletries, and industrial products.26 Over 90% (10 of 11) of MCI/MI reactions (aq. and pet. combined) were related to cosmetic exposure, with one case of exposure from both cosmetics and the workplace and another case with exposure from cosmetics and topical medication. With the recent increases in ACD to MCI/MI, continued monitoring of MCI/MI sensitivity will be important in the future. Glutaraldehyde (1% pet.) also showed a statistically significant difference (P ⬍ .05), yet glutaraldehyde (.2% pet.) displayed no statistically significant difference. Falsenegative reactions with the weaker concentration or falsepositive reactions at the higher concentration may explain the differing results with the concentrations studied. Because of concerns with false-negatives, the NACDG replaced glutaraldehyde (.2% pet.) with glutaraldehyde (.5% pet.) for study in its subsequent standard tray. Glutaraldehyde is utilized as a cold sterilizer in the health care industry because of its antimicrobial, antiviral, and fungicidal activity in an alkaline solution. Occupational exposure accounted for more than 70% (5 of 7 patients) of sensitizations with dental hygienists accounting for 60% (3 of 5) of the occupational cases. Hand dermatitis occurred in 80% (4 of 5) patients with occupational ACD to glutaraldehyde. This finding further highlights the association between ACD owing to glutaraldehyde and the sterilization of dental equipment.27,28 The current findings show significant regional differences in patch test results. Whereas an awareness of national patch test trends is important, dermatologists
181
should be cognizant of regional variations in allergen sources within their community and referral network. Although it could not be verified, the increased percentage of patients seen with ACD to formaldehyde, formaldehydereleasing agents, and potassium dichromate in Kansas City were likely caused by the referral of greater numbers of work-related cases to this center. The findings that a greater percentage of men and a greater number of cases of hand dermatitis were seen in Kansas City are consistent with this hypothesis. However, occupationally acquired ACD to MCI/MI and glutaraldehyde were not more frequent in Kansas City than nationally, suggesting that other factors, such as climactic, environmental, social, and cultural, as well as local prescribing habits, might be operative in Kansas City.
References 1. Marks JG, Belsito DV, DeLeo VA, et al: North American Contact Dermatitis Group patch test results for the detection of delayed-type hypersensitivity to topical allergens. J Am Acad Dermatol 38:911-918, 1998 2. Rudner EJ, Clendenning WE, Epstein E, et al: Epidemiology of contact dermatitis in North America. 1972. Arch Dermatol 108:537-540, 1979 3. Storrs FJ, Rosenthal LE, Adams RM, et al: Prevalence and relevance of allergic reactions in patients patch tested in North America—1984 to 1985. J Am Acad Dermatol 20:1038-1045, 1989 4. Nethercott JR, Holness DL, Adams RM, et al: Patch testing with a routine screening tray in North America, 1985 through 1989: I. frequency of response. Am J Contact Dermatitis 2:122-129, 1991 5. Marks JG, Belsito DV, DeLeo VA, et al: North American Contact Dermatitis group standard tray patch test results (1992 to 1994). Am J Contact Dermatitis 6:160-165, 1995 6. Carpenter A, Provorse C: Facts about the Cities (ed 2). New York, NY, Wilson Co, 1996 7. Marks JG Jr, Belsito DV, De Leo VA, et al: North American Contact Dermatitis Group patch-test results, 1996-1998. Arch Dermatol 136:272273, 2000 8. Hogan DJ, Hill M, Lane PR: Results of routine patch testing of 542 patients in Saskatoon, Canada. Contact Dermatitis 19:120-124, 1988 9. Massone L, Anonide A, Borghi S, et al: Positive patch test reactions to nickel, cobalt, and potassium dichromate in a series of 576 patients. Cutis 47:119-122, 1991 10. Lim JTE, Goh CL, Ng SK, et al: Changing trends in the epidemiology of contact dermatitis in Singapore. Contact Dermatitis 26:321-326, 1992 11. Castiglioni G, Carosso A, Manzoni S, et al: Results of routine patch testing of 834 patients in Turin. Contact Dermatitis 27:182-185, 1992 12. Bruckner-Tuderman L, Konig A, Schnyder UW: Patch test results of the dermatology clinic Zurich in 1989: Personal computer-aided statistical evaluation. Dermatology 184:29-33, 1992 13. Wang XM, Lin YF, Cheng XF, et al: Patch testing with the European standard series in Shanghai. Contact Dermatitis 30:173, 1994 14. Bangha E, Elsner P: Sensitizations to allergens of the European standard series at the Department of Dermatology in Zurich 1990-1994. Dermatology 193:17-21, 1996 15. Zachariae COC, Agner T, Menne T: Chromium allergy in consecutive patients in a country where ferrous sulfate has been added to cement since 1981. Contact Dermatitis 35:83-85, 1996 16. Roto P, Sainio H, Reunala T: Addition of ferrous sulfate to cement and risk of chromium dermatitis among construction workers. Contact Dermatitis 35:83-85, 1996 17. Goh CL, Gan SL: Change in cement manufacturing process, a cause for decline in chromate allergy? Contact Dermatitis 34:51-54, 1996
182
Thompson and Belsito
18. Van Oss H, Dunkelberger E: USGS Mineral Industry Surveys: Cement in March 1998. Reston, VA: U.S. Dept. of Interior, U.S. Geological Survey. Online. Available: http://minerals.er.usgs.gov/minerals/pubs/commodity/ cement/17000398.pdf. 24 June 1998 19. Hansen KS: Occupational dermatoses in hospital cleaning women. Contact Dermatitis 9:343-51, 1983 20. Flyvholm MA, Menne T: Allergic contact dermatitis from formaldehyde. A case study focussing on sources of formaldehyde exposure. Contact Dermatitis 27:27-36, 1992 21. Grattan CE, English JS, Foulds IS, et al: Cutting fluid dermatitis. Contact Dermatitis 20:372-376, 1989 22. Holness DL, Nethercott JR: Dermatitis in hairdressers. Dermatol Clin 8:119-126, 1990 23. Kiec-Swierczynska M, Krecisz B, Krysiak B, et al: Occupational allergy to
24. 25.
26. 27.
28.
aldehydes in health care workers. Clinical observations. Experiments. Int J Occup Med Environ Health 11:349-358, 1998 Fowler JF, Skinner S: Contact dermatitis due to cosmetic preservatives. Am J Contact Dermatitis 2:143-144, 1991 Marks JG, Moss JN, Parno JR, et al: Methylchloroisothiazolinone/methylisothiazolinone (Kathon CG) biocide: Second United States multicenter study on human skin sensitization. Am J Contact Dermatitis 4:87-89, 1993 Cronin E, Hannuksela M, Lachapelle JM: Frequency of sensitization to the preservative Kathon CG. Contact Dermatitis 18:274-279, 1988 Nethercott JR, Holness DL, Page E: Occupational contact dermatitis due to glutaraldehyde in health care workers. Contact Dermatitis 18:193-196, 1988 Shaffer MP, Belsito DV: Allergic contact dermatitis to glutaraldehyde in health-care workers. Contact Dermatitis 43:150-156, 2000