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Research JAMA Dermatology | Original Investigation Pediatric Contact Dermatitis Registry Data on Contact Allergy in

Research

JAMA Dermatology | Original Investigation

Pediatric Contact Dermatitis Registry Data on Contact Allergy in Children With Atopic Dermatitis

Sharon E. Jacob, MD; Maria McGowan, MD; Nanette B. Silverberg, MD; Janice L. Pelletier, MD; Luz Fonacier, MD; Nico Mousdicas, MD; Doug Powell, MD; Andrew Scheman, MD; Alina Goldenberg, MD, MAS

IMPORTANCE Atopic dermatitis (AD) and allergic contact dermatitis (ACD) have a dynamic relationship not yet fully understood. Investigation has been limited thus far by a paucity of data on the overlap of these disorders in pediatric patients.

OBJECTIVE To use data from the Pediatric Contact Dermatitis Registry to elucidate the associations and sensitizations among patients with concomitant AD and ACD.

DESIGN, SETTING, AND PARTICIPANTS This retrospective case review examined 1142 patch test cases of children younger than 18 years, who were registered between January 1, 2015, and December 31, 2015, by 84 health care providers (physicians, nurse practitioners, physician assistants) from across the United States. Data were gathered electronically from multidisciplinary providers within outpatient clinics throughout the United States on pediatric patients (ages 0-18 years).

EXPOSURES All participants were patch-tested to assess sensitizations to various allergens; history of AD was noted by the patch-testing providers.

MAIN OUTCOMES AND MEASURES Primary outcomes were sensitization rates to various patch-tested allergens.

RESULTS A total of 1142 patients were evaluated: 189 boys (34.2%) and 363 girls (65.8%) in the AD group and 198 boys (36.1%) and 350 girls (63.9%) in the non-AD group (data on gender identification were missing for 17 patients). Compared with those without AD, patch-tested patients with AD were 1.3 years younger (10.5 vs 11.8 years; P < .001) and had longer history of dermatitis (3.5 vs 1.8 years; P < .001). Patch-tested patients designated as Asian or African American were more likely to have concurrent AD (odds ratio [OR], 1.92; 95% CI, 1.20-3.10; P = .008; and OR, 4.09; 95% CI, 2.70-6.20; P <.001, respectively). Patients with AD with generalized distribution were the most likely to be patch tested (OR, 4.68; 95% CI, 3.50-6.30; P < .001). Patients with AD had different reaction profiles than those without AD, with increased frequency of reactions to cocamidopropyl betaine, wool alcohol, lanolin, tixocortol pivalate, and parthenolide. Patients with AD were also noted to have lower frequency of reaction to methylisothiazolinone, cobalt, and potassium dichromate.

CONCLUSIONS AND RELEVANCE Children with AD showed significant reaction patterns to allergens notable for their use in skin care preparations. This study adds to the current understanding of AD in ACD, and the continued need to investigate the interplay between these disease processes to optimize care for pediatric patients with these conditions.

JAMA Dermatol. doi:10.1001/jamadermatol.2016.6136 Published online February 22, 2017.

Author Affiliations: Author affiliations are listed at the end of this article.

Corresponding Author: Alina Goldenberg, MD, MAS, Resident, Department of Dermatology, University of California–San Diego, 8899 University Center Lane, Ste 350, Loma Linda, CA 92122

(Reprinted) E1

Copyright 2017 American Medical Association. All rights reserved.

Copyright 2017 American Medical Association. All rights reserved.

E2 Research Original Investigation Contact Allergy in Children With Atopic Dermatitis A topic dermatitis (AD)

E2

Research Original Investigation

Contact Allergy in Children With Atopic Dermatitis

A topic dermatitis (AD) and allergic contact dermatitis (ACD) are 2 of the most commonly recognized pediat- ric inflammatory skin disorders, but they have a dy-

namic relationship that isnot fullyunderstood. For patientswith AD, concomitant undiagnosed ACD may result in treatment- resistant disease 1 leading to increased patient morbidity, eco- nomic burden, and lost work and/or school days. 2 Diagnosis of ACD in patients with AD is associated with improvements in cutaneous symptoms as patients become able to avoid de- tected allergens that could potentially aggravate their under- lying AD. 1 Because AD is most commonly a disease of child- hood, and trends show that the incidence of AD and atopy are increasing, 3 understanding the interplay between AD and ACD is especially important in the pediatric population. A limited number of studies have investigated the over- lap of AD and ACD in children. Multiple studies found in- creased sensitization rates to various allergens among chil- dren with AD, including potassium dichromate, Compositae mix, disperse blue, balsam of Peru, fragrance mix, and lanolin. 1,4,5 However, these study were limited by small sample size, narrow age range, and restricted geographical distribu- tion of test patients. One of the largest evaluations of chil- dren with ACD was done by Zug et al 6 from the North Ameri- can Contact Dermatitis Group (NACDG), which evaluated 7 years of patch-test results from children 0 to 18 years of age, with a total of 883 children within the sample. Zug et al 6 reported that children had increased prevalence of atopic dis- orders compared with adults. However, AD was not a pri- mary focus of this study, and no demographic analysis was per- formed for patients with concomitant AD and ACD. 6 The Pediatric Contact Dermatitis Registry (PCDR) was de- veloped to gather data on pediatric ACD, its associated demo- graphics, and related conditions. Established in 2014, the PCDR is a collaborative,multidisciplinary, nationwide registry of 1142 patch-tested childrenwith data provided by 252 health care pro- viders (physicians, nurse practitioners, physician assistants) from all 50 states. 7 Herein, using data from the PCDR, we fo- cus specifically on the interplay between AD and ACD, with the goal of elucidating the sensitizations among patients with AD.

of elucidating the sensitizations among patients with AD. Methods This retrospective case reviewwas approved by the
of elucidating the sensitizations among patients with AD. Methods This retrospective case reviewwas approved by the

Methods

This retrospective case reviewwas approved by the Loma Linda University internal review board. In 2015, data for this study were gathered from the PCDR, a multidisciplinary, electronic data registry of patch-test results from children 0 to 18 years of age in the United States. Methodology for the PCDR devel- opment and a full description of providers contributing to the registry may be found elsewhere. 7 The data collected for each case included a deidentified database collecting demographic information (age, sex, race); medical history, including diagnosis of AD; clinical informa- tion on active dermatitis (anatomic location and duration); and logistical information regarding the patch-testing technique (type of patch test used, date of patch test, time intervals for patch-test evaluation, and allergen results). Allergen results were reported as either positive, relevant positive, or irritant;

Key Points

Question Does having atopic dermatitis (AD) influence sensitization patterns and allergic contact dermatitis development among children?

Findings In this retrospective case review, which included 1142 children younger than 18 years, those with AD had statistically significant increased frequency of reactions to cocamidopropyl betaine, wool alcohol, lanolin, tixocortol pivalate, and parthenolide, and lower frequency of reaction to methylisothiazolinone, cobalt, and potassium dichromate.

Meaning Children with AD showed significant reaction patterns to allergens found in their skin care preparations

grading of results was not included in the survey. Positive patch-test (PPT) reactions included any reaction from macu- lar erythema to a 3+ reaction as defined by the International Contact Dermatitis Research Group. Relevance of a PPT was interpreted and defined by the diagnosing providers and sub- mitted within the survey, not verified by the primary investi- gative team. The medical history and diagnostic findings were not verified by independent review because medical records were not accessible to the primary investigative team. Spe- cifically, the diagnosis of AD was made by the case-entering provider on a case-by-case basis. Within this analysis, the percentage of PPT (PPT%) was de- fined for each allergen as the sum of patients who had a posi- tive reaction divided by the total number of patients patch- tested for that specific allergen. The percentage of clinically relevant positive patch tests (RPPT%) for each allergen was cal- culated using the same approach. The percentage of having at least 1 positive or relevant reaction was calculated by divid- ing the sum of patients with at least 1 positive or relevant re- action, respectively, by the total patients within the study. Caseswere arranged into 2 statistically independent groups (patientswith AD and thosewith non-ADmedical history) based on case-entering provider’s documentation. Data were ana- lyzed with the independent t test for continuous variables, the χ 2 test for binary variables; odds ratios (ORs) and 95% CIs and P values were confirmed through univariate logistic regres- sion using SPSS statistical software (version 22.0; SPSS Inc).

using SPSS statistical software (version 22.0; SPSS Inc). Results Overall, of 1142 pediatric patch test cases
using SPSS statistical software (version 22.0; SPSS Inc). Results Overall, of 1142 pediatric patch test cases

Results

Overall, of 1142 pediatric patch test cases registered between January 1 and December 31, 2015, by 84 unique providers, 552 patients (49%) had a history of AD (data on concurrent AD were available for 98% of the entries). 7 In 338 patients (30%), AD and ACD were concurrent diagnoses reported by the data-entering provider. The mean age of patients with AD was significantly younger than the rest of the study populous—10.5 vs 11.8 years old (P < .001). Almost two-thirds of both AD and non-AD groups were female; sex was not significantly different between pa- tients with AD and the rest of the study population. (Gender identification was missing for 17 patients.) Most patients were

JAMA Dermatology Published online February 22, 2017 (Reprinted)

Copyright 2017 American Medical Association. All rights reserved.

Copyright 2017 American Medical Association. All rights reserved.

Contact Allergy in Children With Atopic Dermatitis Original Investigation Research Table 1. Demographics of 1142

Contact Allergy in Children With Atopic Dermatitis

Original Investigation Research

Table 1. Demographics of 1142 Children Referred for Patch Testing

Variable

 

AD Group (n = 552) a

Non-AD Group (n = 565)

OR (95% CI)

P Value

Age, mean (SD), range, y

10.5 (4.7)

11.8 (4.6)

(0.91-0.96)

<.001

Sex b

 
   

Male

189 (34.2)

198 (36.1)

.50

 

Female

363 (65.8)

350 (63.9)

0.90 (0.70-1.20)

Race/ethnicity

 
 

White, non-Hispanic

274 (49.6)

377 (66.7)

0.49 (0.38-0.63)

<.001

 

Hispanic/Latino

98 (17.8)

81 (14.3)

1.29 (0.94-1.80)

.12

   

Asian

52 (9.4)

29 (5.1)

1.92 (1.20-3.10)

.008

 

African American

106 (19.2)

31 (5.5)

4.09 (2.70-6.20)

<.001

Location of dermatitis

 
 

Generalized

220 (39.9)

70 (12.4)

4.68 (3.50-6.30)

<.001

   

Head

 

All

191 (34.6)

236 (41.8)

0.74 (0.58-0.94)

.01

 

Face

70 (12.7)

88 (15.6)

0.79 (0.56-1.10)

.17

 

Ears

14 (2.5)

25 (4.4)

0.56 (0.29-1.10)

.10

 

Eyes

20 (3.6)

20 (3.5)

0.94 (0.54-1.90)

>.99

 

Oral

8 (1.4)

38 (6.7)

0.20 (0.94-0.44)

<.001

   

Neck

75 (13.6)

52 (9.2)

1.50 (1.10-2.30)

.02

   

Torso

122 (22.1)

107 (18.9)

1.20 (0.91-1.60)

.20

 

UEs

198 (35.9)

167 (29.6)

1.30 (1.00-1.70)

.03

 

LEs

148 (26.8)

125 (22.1)

1.30 (0.90-1.70)

.07

   

Groin

14 (2.5)

25 (4.4)

0.56 (0.30-1.10)

.10

 

Buttocks

18 (3.3)

28 (5)

0.65 (0.40-1.20)

.17

Duration of dermatitis, mean (SD), y

3.5 (4)

1.8 (2.6)

(1.10-1.20)

<.001

 

≥1 RPPT

233 (42.2)

308 (54.5)

0.61 (0.48-0.77)

<.001

 

≥1 PPT

337 (61.1)

499 (88)

0.64 (0.49-0.82)

<.001

Abbreviations: AD, atopic dermatitis; LE, lower extremity; PPT, positive patch test result; RPPT, relevant positive patch test result; UE, upper extremity.

a Data were missing for 25 cases regarding medical history of AD.

b Data on gender identification were missing for 17 patients.

listed as white non-Hispanic, and this category was signifi- cantly more likely to be within the non-AD study population (P < .001). However, those patch-tested patients designated as Asian (OR, 1.92; 95% CI, 1.2-3.1; P = .008) or African American (OR, 4.09; 95% CI, 2.7-6.2; P < .001) were significantly more likely to have AD (Table 1). Location of dermatitis prompting patch testing was sig- nificantly differed among patients with AD compared with

thosewithout. Patientswith AD had 4.68 times the odds of hav- ing a generalized dermatitis (OR, 4.68; 95% CI, 3.5-6.3; P < .001) and 1.3 times the odds of having dermatitis on the upper ex- tremities (OR, 1.3; 95% CI, 1.0-1.7; P = .03) compared with pa- tients without AD. Patients with AD had significantly longer history of dermatitis than those without AD: 3.5 years vs 1.8 years ( P < .001). Overall, 42.2% of patch-tested children with AD had at least 1 RPPT, and 61.1% had at least 1 PPT (Table 1). Furthermore, the top 21 prevalent allergens with PPT were assessed among patients with AD, in comparison with the rest of the study sample (Table 2). Specifically, in comparison with the patients without AD, those with AD had 7.4 times the odds of having an RPPT to cocamidopropyl betaine (CAPB)

( P = .008), 4.2 times the odds of having an RPPT to wool al-

cohol ( P = .047), 4 times the odds of having an RPPT to lano- lin (P = .053), 5.3 times the odds of having an RPPT to tixocor- tol pivalate (P = .02), and 7.6 times the odds of having an RPPT to parthenolide ( P = .006). For MI, cobalt, and potassium dichromate, patients with AD had statistically significantly lower odds of having an RPPT comparedwith the non-AD study

population. No statistically significant difference was seen in RPPT rates to nickel among patients with AD compared with the rest of the study sample (OR, 2.39; P = .13) (Table 2).

rest of the study sample (OR, 2.39; P = .13) (Table 2). Discussion Demographics Patients with
rest of the study sample (OR, 2.39; P = .13) (Table 2). Discussion Demographics Patients with

Discussion

Demographics

Patients with AD who were referred for patch testing were, on average,more than 1 year younger than their counterpartswith- out AD and had lived with some form of dermatitis for more than twice as long (3.5 years vs 1.6 years, respectively). Al- though sex was not significantly different between AD and non-AD groups, girls were patch-tested more often than boys at a 2:1 ratio, consistent with referral patterns noted in prior studies. 6,8,9 It remains to be determined as to why girls are re- ferredmore frequently for patch testing; however, thismay in- dicate that female children have a higher incidence of con- tact allergy. If so, increased topical product exposure may be a relevant sensitization route in girls. White children who underwent patch testing were found to be the least likely to have concomitant AD, whereas patch- tested Asians and African Americans had significantly higher odds of having AD. The predilection for those with various an- cestries and ethnic backgrounds who are referred for patch test- ing to have a greater likelihood to have ACD and concomitant AD has not been fully elucidated in the literature, and, to our knowledge, we are the first to report such an association. Prior

(Reprinted) JAMA Dermatology Published online February 22, 2017

E3

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Research Original Investigation Contact Allergy in Children With Atopic Dermatitis E4 Table 2. Top Allergens

Research Original Investigation

Contact Allergy in Children With Atopic Dermatitis

E4

Table 2. Top Allergens Among 1142 Children With AD Referred for Patch Testing

 

No. (%) a

Patient No.

Allergen

RPPT

PPT

OR

P Value b

1

Nickel sulfate

63 (12.0)

121 (22.0)

2.38

.13

2

Fragrance mix 1

52 (9.6.0)

63 (12.0)

0.05

.84

3

Balsam of Peru (Myroxylon pereirae )

38 (7.0)

45 (8.3)

0.35

.63

4

Bacitracin

29 (5.4)

41 (7.6)

0.9

.40

5

Formaldehyde

28 (5.2)

34 (6.3)

1.2

.31

6

Cocamidopropyl betaine c

27 (6.3)

36 (8.4)

7.4

.008

7

Propylene glycol c

25 (5.8)

33 (7.8)

2.8

.11

8

Wool alcohol

25 (4.6)

29 (5.4)

4.2

.047

9

Lanolin c

26 (6.0)

30 (7.0)

4.0

.053

10

Bronopol

19 (3.5)

23 (4.3)

0.005

>.99

11

Neomycin sulfate

18 (3.3)

33 (6.1)

3.77

.06

12

Quaternium 15

18 (3.3)

27 (5.0)

1.91

.19

13

Colophony

17 (3.1)

17 (3.1)

3.53

.07

14

Tixocortol-21-pivalate

15 (2.8)

17 (3.1)

5.33

.02

15

MCI/MI

13 (2.4)

18 (3.3)

2.17

.17

16

Cobalt d

13 (2.4)

47 (8.7)

0.16

.02

17

Fragrance mix 2 c

13 (3.0)

19 (4.4)

3.64

.07

18

MI c,d

12 (2.8)

14 (3.2)

0.16

.01

19

Potassium dichromate d

11 (2.0)

15 (2.8)

0.19

.03

20

Compositae mix c

10 (2.3)

13 (3.0)

1.81

.20

21

Parthenolide

10 (1.8)

11 (2.0)

7.65

.006

Abbreviations: AD, atopic dermatitis; MCI/MI, methylchloroisothiazolinone/ methylisothiazolinone; OR, odds ratio; PPT, positive patch test result; RPPT, relevant positive patch test result.

a Percentages reflect the proportion of PPT out of the total number of children with AD known to be patch-tested with that allergen. The denominator varied for each allergen—representing the total number of children with AD known to be patch-tested with that specific allergen. Unless otherwise marked, the denominator was 540 for allergens; and for the allergens not on the TRUE test (SmartPractice) the denominator was 429.

b P value compares RPPT with each allergen among patients with AD, compared with everyone else.

c Represents allergen not on the TRUE test.

d For MI, cobalt, and potassium dichromate, the ORs and P values represent negative association.

large-scale assessments of patch-tested patients by the NACDG may have had a type II error in assessing the component of race in the association of AD and ACD because itwasnoted that blacks were underrepresented in NACDG studies. 10,11 Possible theo- ries for our findings among African American and Asian pa- tients with AD include a possibility that they are more likely to be referred for patch testing because of increased rates of treatment-resistant AD as associatedwith filaggrinmutations, 12 underlying genetic predilection for AD, 12 reduced minority ac- cess to epicutaneous allergy testing, or more frequent misdi- agnosis of AD in these racial groups. Conversely, Asian and Afri- can American patients without ADmay have been less likely to be referred for patch testing for various reasons and, thus, were not captured by our data registry. Future larger studies are nec- essary to further elucidate the aforementioned associations be- tween AD and ACD across diverse populations.

Dermatitis Type

Patientswithgeneralizeddermatitisweresignificantlymore likely to be patch-tested than thosewith other distributions. This find- ing is consistentwith those of other studies, such as the study by Isaksson et al, 1 which found that scattered generalized dermati- tis was themost common distribution in patch-tested children. Patch-tested patients with AD were less likely to have a PPT and RPPT than those in the non-AD group. According to one pathophysiologic theory, this finding may be due to an under- lyingmisbalanced T H 1/T H 2 ratio in severe atopy. 13-16 It has been noted that patients with severe AD have a conspicuously lower rate of ACD compared with the general population, and com- pared with those with mild to moderate AD. 17-19 T H 1 response is limited in severe atopy, with an underlying increase in T H 2; however, T H 1 is critical in development of ACD; thus, these patients with severe AD are in a sense protected from highly

sensitizing agents. 16,19 With our current data set, it is not pos- sible to separate severe AD from mild to moderate AD; there- fore, further research is necessary to elucidate this point.

Allergens

Certain trends insensitizationhavebeennoted inourstudy.Many of themost common allergens, such as fragrancemix, balsam of Peru, bacitracin, formaldehyde, or propylene glycol,were found in similar ratios across both groups (patients with AD and non- AD). Nickel, for example, is themost common positive allergen, but there was no significant difference in rates of PPT from pa- tientswith AD comparedwith thosewithout AD, consistentwith results of previous studies. 4 Specifically, sensitization to 5 aller- gens was notedmore frequently in patients with AD than those without AD to a statistically significant degree: CAPB, wool alcohol, lanolin, tixocortol pivalate, and parthenolide (a compo- nent of Compositae). These sensitizers are frequently associated with topical medicaments and skin care products. Patients with AD face inherent amplified risk of sensitiza- tion because they are primarily treated with topical regimens leading to increased exposure to product-based chemicals, they pathophysiologically have an impaired epidermal barrier, and these chemicals have been reported to have potentially en- hancing absorption through the skin. 15,20-23 Cocamidopropyl betaine is a surfactant composed of a co- conut oil derivative combined with dimethylaminopropyl- amine and monochloroacetic acid. It is frequently found in shampoos, cleansers, contact lens solutions, and antiseptics. 24 In 2004, it was named “Allergen of the Year” by the American Contact Dermatitis Society (ACDS) and has been noted as an emerging allergen in pediatrics, especially in younger age groups. 4,25 Our findings correlated with those of other studies, such as Shaughnessy et al, 20 whonoted that atopic patientswere

JAMA Dermatology Published online February 22, 2017 (Reprinted)

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Copyright 2017 American Medical Association. All rights reserved.

Contact Allergy in Children With Atopic Dermatitis more likely to be allergic to CAPB, and

Contact Allergy in Children With Atopic Dermatitis

more likely to be allergic to CAPB, and Zug et al, 6 who found that therewas an increased prevalence of PPT to amidoamine, a pre- cursor to CAPB. The frequency of sensitization in patients with mild to moderate AD may be related to increased absorption, due to both the penetratingnature ofCAPB and the inherent sus- ceptibility for absorption in AD skin. 20-22 Parthenolide is a sesquiterpene lactone found in Compositae plants, such as ragweed, feverfew, dandelions, sunflowers, and daisies. 24 Exposure to parthenolidemay occur in nature, and is associated with summer-exacerbated dermatitis and airborne- patterndermatitis,or as acomponentof topicalpreparationssuch asmoisturizers and cleansers. 24,26 While our study showed that patients with AD had significantly higher rates of allergy to par- thenolide, the samewas not true for Compositae, suggesting that other elements of Compositae may more frequently be respon- sible for sensitization in patients without AD. Lanolin is a compound of esters, polyesters, alcohols, and acids extracted from natural wool by using solvents or detergents. 4,27 It is a popular component ofmany skin prepara- tions, especially commonly used products in AD, because of its properties as an emollient,moisturizer, emulsifier, adhesive, and plasticizer. 24 Because lanolin is a natural compound, it varies in composition based on its source and processing methods, ex- plaining why some patientsmay tolerate certain lanolin prepa- rations butnot others. 6,24,28 Wool alcoholsmay be removed from

lanolin, and this refined lanolin has been noted to elicit fewer re- sponses than lanolin with retained wool alcohol. 24 Tixocortol is a class A corticosteroid found in nasal sprays, inhalers, topical hemorrhoid preparations, and buccal and throat medications. Its use in nasal sprays is noteworthy be- cause many patients with AD may also be using these to treat another significant atopic syndrome, allergic rhinitis. Al- though tixocortol is not typically an ingredient in topical medicaments, 24 other class A corticosteroids, including hy- drocortisone, are frequently available over the counter. Sensitization to 3 specific allergens was found to be sta- tistically more common in patients without AD. These were methylisothiazolinone (MI), cobalt, and potassium dichro- mate. MI is a preservative that is commonly used as a cos- metic preservative for its activity against bacteria and fungi.

MI has been well established as a potent allergen, similar to

poison ivy. Following with the theory of T H 1/T H 2 imbalance, 3 patients with AD would be less likely to be sensitized to strong sensitizers than their counterparts without AD, 29 which is con- sistent with our findings on MI. Cobalt is a metal that is commonly combined with other metals, such as nickel. 24 These cobalt alloys are then used in commonplace items (eg, jewelry, dental and orthopedic im- plants, and belt buckles). 24 Cobalt may also be used as pig- ment for porcelain and glass, watercolor paints, crayons, tat- toos, and hair dye. Historically, cobalt allergy was seen to be

inexorably linked to concomitant exposure to nickel. How- ever, it is increasingly recognized as an independent sensitizer. 30 Two studies 31,32 from the 1980s and 1990s noted cobalt PPT in- dependent of nickel PPT at rates ranging from 21% to 32%, and themost recent NACDG data showed 40% of patients with PPT

to cobalt did not have PPT to nickel. 30 Cobalt was named

“Allergen of the Year” in 2016 by the ACDS. 30

Original Investigation Research

Potassium dichromate, an inorganic salt, used inmanufac- turing andconstruction.Historically, those at risk forACD tochro- mium were textile workers, leather tanners, smelters, and con- struction workers who work with cement. 24 Similar to cobalt, it is used as a pigment in yellow and green tattoo inks, green felt fabric, cosmetics, radiator coolants, and dental and orthopedic implants. 24 Presumably, in children, sensitization to potassium dichromate is more likely due to pigments rather than occupa- tionalmetal work. Our findings that potassium dichromate was skewed toward patientswithout AD are not fully in concordance with other studies.For example,Belloni-Fortina et al 4 found that Italian children with AD had greater prevalence in PPT to potas- sium dichromate. Future larger studies are necessary to further elucidate the relationship of potassium dichromate sensitivity in patients with AD with specific focus on relevant sources of exposure in children worldwide. Overall, our study provides vital information on the relation- ship between AD and ACD in pediatric patch-tested patients in the United States. This data set demonstrated that of children evaluated with patch testing, those who had an underlying his- tory of AD tended to be significantly younger, a higher percent- age were of Asian or African American descent, and they were more likely tohave a generalized-distribution and/or forearmdis- ease and prolonged duration dermatitis compared with those withoutAD.The allergens found tohavesignificantlyhigher rates of PPT and RPPT in patientswith AD comparedwith thosewith- out ADwere onescommonly found in over-the-counter skincare products associated with either treatment of AD or gentle skin care, including CAPB, wool alcohol, lanolin, tixocortol pivalate, andparthenolide.PatientswithADhadnotably lower ratesofPPT or RPPT to MI.

Limitations

Our study had several limitations. Our resultsmay have been af- fected bymisclassification bias because our data were gathered from a variety of providers,which could lead to possible variabil- ity in classifying patients as having AD, a relevant positive re- sponse, or a particular distribution of dermatitis. The variability in protocol and antigen panels from patch tests performed by the enrolled providers heightens this potential bias. In addition, be- cause the rates of positive and relevant positive results depend on the relative frequency of allergens tested, the overall results may have been affected by differences in the types of patch tests usedby individualproviders,possibly leading tocertain allergens beingoverrepresentedorunderrepresented.Because theprimary study investigatorsdidnothave access topatientmedical records, no confirmation of AD status or any additional medical history wasavailableasaquality-controlmeasure.Finally,our resultsmay alsobeprivy toselectionbias for theproviderswho registered into the study, those who entered cases into the registry, and ulti- mately, the patients evaluated by these providers—because they may not be representative of the general population.

they may not be representative of the general population. Conclusions Future largerstudies arenecessary to further
they may not be representative of the general population. Conclusions Future largerstudies arenecessary to further

Conclusions

Future largerstudies arenecessary to further elucidate the results presented in this discussion.To date, the PCDR continues to pro- vide the largest comprehensive collection of US-only pediatric

(Reprinted) JAMA Dermatology Published online February 22, 2017

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Copyright 2017 American Medical Association. All rights reserved.

Research Original Investigation patch-test cases fromwhich ongoing research findings and ques- tionsmaycontinue

Research Original Investigation

patch-test cases fromwhich ongoing research findings and ques- tionsmaycontinue tostem.Continuedcollaborationbetweenpa- tients, health care providers,manufacturers, and policymakers

Contact Allergy in Children With Atopic Dermatitis

is needed to shed light on the global and local epidemic of ACD, and toprevent futuremorbidity fromcommercial allergens toour children.

E6

ARTICLE INFORMATION

Accepted for Publication: December 22, 2016.

Published Online: February 22, 2017.

Author Affiliations: Department of Dermatology, Loma Linda University, Loma Linda, California (Jacob); Department of Internal Medicine, Loma Linda University, Loma Linda, California (McGowan); Departments of Dermatology and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, New York (Silverberg); Department of Pediatric Dermatology, Eastern Maine Medical Center, Bangor (Pelletier); University of Vermont School of Medicine, Burlington (Pelletier); Department of Allery Immunology, State University of New York at Stony Brook, Stony Brook, New York (Fonacier); Department of Allery Immunology, Winthrop University Hospital, Mineola (Fonacier); Department of Dermatology, Indiana University Health, Indianapolis (Mousdicas); Department of Dermatology, University of Utah, Salt Lake City (Powell); Clinical Dermatology, Northwestern University, Chicago, Illinois (Scheman); Department of Dermatology, University of California–San Diego, San Diego (Goldenberg).

Author Contributions: Drs Jacob and Goldenberg, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Jacob, Goldenberg. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Jacob, McGowan, Scheman, Goldenberg. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Jacob, McGowan, Goldenberg. Obtained funding: Jacob, Goldenberg. Administrative, technical, or material support:

Jacob, Silverberg, Fonacier, Goldenberg. Supervision: Jacob.

Conflict of Interest Disclosures: Dr Jacob received an American Contact Dermatitis Society Mid-Career Development award to support an education endeavor in information technology acquisition in association with this project. She was the coordinating principal investigator for the PREA-1 and PREA-2 Trials. No other disclosures are reported.

Funding/Support: This study was supported in part by Society for Pediatric Dermatology pilot project grant.

Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Susan Nedorost, MD, Director, Graduate Medical Education, UH Cleveland Medical Center, and Professor, Dermatology, CWRU School of Medicine, for insightful review and mentorship. She was not compensated for her assistance.

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JAMA Dermatology Published online February 22, 2017 (Reprinted)

Copyright 2017 American Medical Association. All rights reserved.

Copyright 2017 American Medical Association. All rights reserved.