An Update on Pediatric Allergic Contact Dermatitis Patch Testing for Common Allergens
ABSTRACT: Allergic contact dermatitis (ACD) in children is a significant problem in the United States and worldwide that should be a diagnostic consideration in pediatric patients with chronic dermatitis, regardless of an atopic designation. Among the top allergens associated with ACD in U.S. children are nickel, medications, paraphenylenediamine, and numerous chemicals and other substances used as food additives. Evaluation includes a thorough history, analysis of the clinical distribution of the dermatitis, and, when indicated, patch testing. National policies, directives, and regulations are vital to decreasing sensitization rates to many allergens implicated in ACD in children.
Pediatric allergic contact dermatitis (ACD) has become an increasingly recognized condition in the last decade, with recent U.S. prevalence estimates ranging from 41% to 77% based on confirmed positive patch-test reactions in children.1
Reports of cases of ACD in children that were not necessarily confirmed with patch testing also have increased. For example, car seat dermatitis, the clinical distribution of which corresponds to areas of contact with an infant-toddler seat, has attracted recent attention. While an allergen has not yet been confirmed as the culprit, car seat dermatitis is suspected to be related to the “shiny type of material” found in the seat pad.2 The reaction might be either an irritant contact dermatitis or an ACD caused by a number of plausible materials ranging from adhesives and resins to chemicals and biocides such as dimethyl fumarate (DMF), which is applied to shipped goods to prevent mold growth. In March 2009, the European Union banned the importation of goods containing DMF.3 That said, the American Contact Dermatitis Society (ACDS) designated DMF as the Allergen of the Year in 2011 to bring awareness to the fact that it still was being used in overseas manufacturing and shipping worldwide.4
REACTIONS TO MEDICATIONS
The astute parent or clinician sometimes can make a temporal association in lieu of definitive patch testing results. For example, Mussani and colleagues5 reported the case of a 3-year-old girl who received a diagnosis of systemic contact dermatitis (SCD) to clioquinol-hydrocortisone topical cream, which manifested clinically as baboon syndrome (which originally referred to symmetrical erythema of the gluteal area; involvement of flexural and/or intertriginous folds now also is recognized as a form of SCD6). The girl’s parents declined confirmatory patch testing, which also has been our clinical experience at times in suspected pediatric cases of contact dermatitis. The authors made the diagnosis based on the clinical examination and exposure history, along with a trial of avoidance of clioquinol-hydrocortisone cream. The parents also declined a provocative use test, which also reflects our experience.
It is more difficult to perform confirmatory provocation tests in pediatric patients than in adults, since many parents outright do not want their children to be subjected again to a potential flare-up of dermatitis after symptoms of the initial reaction have resolved. Mussani and colleagues’ case also points out the very realistic difficulty of patch testing, where certain allergens, such as medications, are not readily available for patch testing.
Reactions to Nickel
Nickel (the ACDS 2008 Allergen of the Year7) is another common allergen that often is the culprit in cases of ACD that are diagnosed without confirmatory patch tests. Nickel has been the most prevalent allergen in patients of all ages for the last 3 decades at patch testing centers worldwide.3
Many patients can associate dermatitis of the earlobes with costume jewelry or infraumbilical dermatitis with belt buckles or snaps on pants; in these cases, the history reveals the diagnosis. For example, Kaye and colleagues8 described a case of nickel SCD in 2012, in which a 10-year-old boy had swallowed a Canadian quarter (which before 2001 were made almost entirely of nickel) and then developed erythroderma and fever. The coin had become lodged in the child’s stomach lining, and after endoscopic removal, the patient recovered completely. Confirmatory patch testing was deemed not medically necessary.
Coins are one of many common items that contain this ubiquitous sensitizer. In fact, the European Union in July 2001 issued a directive to regulate consumer nickel exposure, specifying that items intended to be in direct and prolonged contact with the skin could not release nickel at more than 0.5 µg/cm2/week.9 While this measure did positively change the epidemiology of nickel allergy in Europe, further interventions still are called for. As Thyssen and colleagues9 put it, “Regulation is a toothless tiger if compliance is not appropriately checked and enforced.” Regulation of consumer nickel exposure has yet to be established in the United States.
Reactions to PPD
Paraphenylenediamine (PPD), an antioxidant used in hair dye, in 2006 was named the ACDS Allergen of the Year.10 Exposure rates to PPD, also known as black henna, are on the rise, notably in association with its use in temporary tattooing in combination with natural plant-derived henna.11 These tattoos often are applied at local fairs, amusements parks, and boardwalks and aboard cruise ships.11 PPD is added to henna to increase the intensity and longevity of the tattoo, as well as to expedite drying, but the chemical has the potential to cause significant and lifelong sensitization.11 Moreover, children as young as 30 months have been reported to have received temporary tattoos, provoking significant reactions.11 Of note, PPD is one of only 5 chemicals named as ‘‘strong sensitizers” by the U.S. Consumer Product Safety Commission.12,13
The American Academy of Dermatology issued a position statement in 2008 endorsing a ban on the practice of applying PPD-adulterated henna tattoos.14 Since then, New Jersey, Oklahoma, and Florida have introduced legislation regarding black henna tattoos.11 In 2013, the U.S. Food and Drug Administration (FDA) issued a consumer warning about the health risks of black henna.15 Note that because black henna is not sold commercially in the United States, the FDA requirement for labeling of ingredients does not apply.12,15
Canada’s Food and Drugs Act prevents the sale of black henna temporary tattoos, and Europe and New Zealand both have issued directives warning about the potential sensitization risks and/or have made recommendations about PPD concentration.11,16
Patch Testing in Children
The clinical condition of ACD might be overlooked when the exposure source is not as obvious as earlobe dermatitis or a black henna tattoo. This is can be especially true in patients with chronic contact dermatitis, in very young patients, and when exposure is a contributing factor in atopic dermatitis.17,18 In these cases, patch testing might be the only way to determine the role of contact allergy.19 A significant number of these children have been patch tested at many international centers, with positive patch test (PPT) reactions noted to a variety of chemicals and substances in a variety of categories, including nickel, cosmetics, fragrances, and preservatives.17,20,21
The first reported patch test studies confirming that ACD was equally prevalent in U.S. children as it was in adults were in 2008.1,22 Patch testing was also confirmed to be safe and efficacious in children with ACD.1,22 In their study, the North American Contact Dermatitis Group (NACDG) found no significant difference in the frequency of at least one relevant PPT when comparing children (aged 0-18 years) and adults.22
Most children reported to have undergone patch testing have done so at tertiary care centers after having been referred by a dermatologist or allergist; therefore, the rates of PPT reactions have been significantly higher (41% to 83%) than in unselected asymptomatic patients from the general population (13.5% to 24.5%).23 Moreover, owing to the distribution of patients in referral populations at United States-based referral centers, a significant number of tested patients have been white and Hispanic rather than Asian and African American, and thus the results may not be representative of the prevalence of ACD in the general population.23
Allergic Contact Dermatitis From Black Hair Dye: Case 1
A 16-year-old Somali girl presented with a 30-day history of bilateral arm swelling and painful vesicular eruptions. Five days before presentation, she had used henna and black hair dye to tattoo her skin. She had used henna since childhood for decorative
purposes. However, outlining an intricate design with hair dye was new for her.
The girl was hospitalized for severe allergic contact dermatitis and treated with systemic corticosteroids, diphenhydramine, and daily dry dressing changes. Ibuprofen also was given to help relieve discomfort.
The patient remained afebrile and was discharged on hospital day 2 with close follow-up and daily dressing changes. She was advised to avoid contact with all hair-dye products.
Case and photo courtesy of Jennifer A. Jewell, MD, and Lorraine L. McElwain, MD
Pediatric Patch Testing Methodology
Patch testing is considered the gold standard for the diagnosis of ACD in children and adults, although the commercially available patch test device does not carry an FDA indication for children. Nonetheless, a recent study evaluating the efficacy and safety of panels 1.1, 2.1, and 3.1 of the Thin-layer Rapid Use Epicutaneous (TRUE) Test, from SmartPractice Denmark, in children and adolescents aged 6 to 18 years concluded that the device is efficacious and safe in the pediatric population.24
In Europe and the United States, a significant number of referral centers that test children base their allergen selection on an individual patient’s history and clinical distribution of dermatitis, eliminating the placement of irrelevant patches. Such individualized, comprehensive patch testing can prove cumbersome and often is not readily accessible, which leads to lower detection rates.1
The techniques for pediatric patch testing have been reviewed in detail.25-29 For instance, in 2007, the German Contact Dermatitis Research Group29 published recommendations for patch testing in children, emphasizing the importance of allergen removal after 24 hours so as not to induce irritant reactions. The group did state, however, that the same allergen test concentrations used in adults should be used in children, supporting the conclusions of previous studies. Moreover, an allergen read also was encouraged at 48 hours, along with an additional delayed reading after 72 hours, as in adult populations.
Current consensus is that patch testing can be performed in children older than 12 years in the same manner as in adults.30-34 On the other hand, in children younger than 6 years of age, patch testing usually is reserved for cases with the highest index of suspicion. Notably, patients even less than 1 year old have been patch tested and found to have clinically relevant allergens.1 Many such children have been tested with the individually directed comprehensive technique, so as to minimize unnecessary exposure and to adjust for the limited surface area available for patch placement.23 Furthermore, while many studies have shown an increasing prevalence of ACD through adolescence,35-38 three European studies published between 1998 and 2005 show peak sensitization occurring in patients aged 3 years and younger.28,39,40 In a more recent Italian study, 200 of 321 children aged 3 to 36 months were found to have at least one PPT reaction.41
Another challenge to testing young children is their level of activity during patch test placement and while the patches is in place. Therefore, special attention to properly securing the patches is necessary.42 Tools such as games and videos used to distract children during patch application have been found to be helpful.43
Clinical Relevance
While proper patch testing protocols and allergen selection can be vital to the proper diagnosis of ACD, interpretation and the assignment of relevance to PPT results also are critical, because there may be only partial concordance between a PPT reaction and ACD.23
A PPT reaction, also known as contact allergy, indicates that an individual is sensitized to a given allergen. It is important to note that a PPT reaction may or may not indicate the cause of the patient’s dermatitis. As in adults, relevance is assigned by analyzing the PPT result against the child’s history, allergen exposures, and sites of dermatitis. This requires knowledge of where the tested substances are found in the patient’s environment. A PPT reaction may account for all, part, or none of the patient’s active dermatitis. Many pediatric patch testing studies have yielded impressive results regarding relevance, with one study showing an 83% prevalence rate of PPT reactions in patients aged 1 to 18, and 77% clinical relevance.1
ACD and Culprit Allergens
In another study performed between 2004 and 2006, University of Miami investigators found that 95.6% of 69 patients aged 10 months to 16 years had at least one PPT reaction.44 Of note, 76.7% of the patients with PPT reactions had test results with definite or probable clinical relevance. Moreover, many of the children with PPT reactions also carried a diagnosis of atopic dermatitis; however, this was not found to be statistically significant, given the referral bias.
The University of Miami authors also compared the top 10 culprit allergens identified at their institution with those identified by investigators at the Mayo Clinic in Rochester, Minnesota (1998-2000, adult data45; 2000-2006, pediatric data46), by the NACDG (2001-2004, adult and pediatric data),22,47 and by investigators at the Ottawa Hospital (1996-2006, pediatric data).20 Nickel was found to be the top allergen across all of these studies, with its clinical relevance as high as 26%.22 Other top allergens found across nearly all groups included Myroxylon pereirae (balsam of Peru, a flavoring added to foods such as ketchup48), cobalt chloride, neomycin sulfate, fragrance mix, gold sodium thiosulfate, thimerosal, and formaldehyde. The accompanying Table lists a number of allergens that are frequently associated with ACD in children worldwide.23
Furthermore, Jacob and colleagues recently reviewed all the North American–based studies and case reports and suggested a basic pediatric patch test series based on the most prevalent allergens with the highest clinical relevance.49
Allergic Contact Dermatitis From Black Hair Dye: Case 2
The children in these photographs—a brother and sister—had received black henna tattoos. The tattoo sites became pruritic 2 days after application in both siblings. Eleven days later, the color had faded, but an exact outline of the original tattoos remained. The lesions were papular, eczematous, erythematous, and extremely pruritic (A and B).
The children were treated with topical corticosteroids and oral antihistamines. The rash persisted in both children 22 days after the tattoos had been applied. At day 30, the lesions still were evident in the form of a hypopigmented macula that marked the outline of the original art (C and D). It is possible that these hypopigmented lesions will become permanent marks.
Case and photos courtesy of Angel Cadiz, MD
Elise M. Herro, MD, is a dermatology resident at the University of Texas Health Science Center, San Antonio. She discloses no relevant financial relationships.
Sharon E. Jacob, MD, is a pediatric contact dermatitis specialist and an associate clinical professor in the division of dermatology at the University of California, San Diego, and Rady Children’s Hospital–San Diego, and an associate professor of dermatology at Loma Linda University School of Medicine in Loma Linda, California. She discloses that she is an investigator for the safety and efficacy trial of the SmartPractice Thin-layer Rapid Use Epicutaneous (TRUE) Test in children and adolescents.
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45. Wetter DA, Davis MDP, Yiannias JA, et al. Patch test results from the Mayo Clinic Contact Dermatitis Group, 1998-2000. J Am Acad Dermatol. 2005;53(3):416-421.
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