PEDIATRICS Vol. 105 No. 1
January 2000,
p. e3
ELECTRONIC ARTICLE:
Does Sensitization to Contact Allergens Begin in Infancy?
Anna L. Bruckner, MD*,
William L. Weston, MD*, and
Joseph G. Morelli, MD*
From the Departments of * Pediatrics and Dermatology, University
of Colorado Health Sciences Center, Denver, Colorado.
 |
ABSTRACT |
Objective. Because previous studies have
found allergic contact sensitization common in children by 5 years of
age, our aim was to determine the prevalence of positive epicutaneous
test results in children <5 years of age and to determine whether
sensitization to contact allergens was as common in infancy.
Methods. We recruited 95 asymptomatic children 6 months to
5 years of age from well-child visits at Denver area pediatric
practices for epicutaneous patch testing using the T.R.U.E. Test
system. Allergens were placed on the skin for 48 hours, and at a later follow-up visit, positive reactions were evaluated.
Results. A total of 85 patients completed the study. Of
these, 20 (24.5%) had 1 or more positive reactions to the tested
allergens. Positive reactors ranged from 6 to 65.5 months of age, with
an average of 30.4 months of age. Of the children, 16 reacted to 1 allergen, and 4 reacted to 2. Eleven positive reactions were observed
to nickel, followed by 8 to thimerosal. Other positive reactions were
to neomycin, cobalt, and kathon CG.
Conclusions. Children as young as 6 months of age may be
sensitized to contact allergens. Within this pediatric population, the
prevalence of sensitization is 24.5%. Sensitization to contact
allergens may occur in infants.
Key words:
allergic contact
dermatitis,
allergic contact sensitization,
epicutaneous testing,
infants,
young children.
Allergic contact dermatitis (ACD) is an inflammatory
reaction of the skin that follows percutaneous absorption of antigen from the skin surface and recruitment of previously sensitized, antigen-specific T lymphocytes into the skin. Contact allergens are
usually low molecular weight substances that are able to penetrate the
stratum corneum of the skin. These antigens are processed by epidermal,
Langerhans' cells that migrate to regional lymph nodes. In the lymph
node, the antigen is presented to T lymphocytes that undergo
proliferation and clonal expansion. These T cells then enter the
vasculature and circulate throughout the body. With subsequent exposure
to the antigen, sensitized T lymphocytes release inflammatory
mediators, producing a localized dermatitis that may last 3 to 4 weeks
if untreated. Depending on the strength of the allergen, 1 or many
exposures are needed for this process to occur. Sensitization is
long-lived, believed to be 30 years to a lifetime.1-4
Although sensitivity to contact allergens occurs in ~10% of the
adult population,5 the exact incidence and prevalence of
sensitization in children is not known.6 Historically, it
was believed that ACD was rare in children, owing to a presumed paucity
of exposure to contact allergens and to a less susceptible immune
system.7 There have been recent series, however, demonstrating a higher level of ACD in children than previously expected. Epicutaneous patch testing in symptomatic children with dermatitis has revealed positive reactions in 15% to 52% of
subjects.8-19 Additionally, 2 previous studies have
examined contact sensitization in asymptomatic, healthy children:
Weston et al20 found a sensitization rate of 20% and
Barros et al21 found a rate of 13%.
All these studies have included a wide range of children, up to 18 years of age, with none exclusively addressing infants or young
children. Aside from a few case reports describing ACD in children as
young as 1 week of age,22,23 there is little in the
literature regarding contact sensitization in the youngest children.
Because the study of Weston and colleagues20 demonstrated
that contact sensitization occurs by the age of 5, our goal was to
determine the prevalence of positive epicutaneous test results in
children <5 years of age and to determine whether sensitization to
contact allergens was as common at a very young age.
| |
METHODS |
Children between the ages of 6 months and 5 years who presented
for routine well-child care at Denver area pediatric practices were
recruited to participate in the study. Parents were given information
about the study, and informed consent was obtained. General information
regarding the age, sex, past medical history, and parental concerns
about the child's skin also was obtained. Patients were not enrolled
if they had an active dermatitis on their back, or if they had an
infectious disease with fever, because the development of an exanthem
could interfere with the interpretation of results.
We used the T.R.U.E. Test system for epicutaneous testing in this
study. T.R.U.E. Test (Glaxo Wellcome, Research Triangle Park, NC) is a
prepackaged, commercially available kit, containing 24 allergens (see
Table 1 for allergens tested). Each antigen is impregnated in a .81 cm2 polyester
patch affixed to surgical tape. There are 2 rows of 6 equally spaced
patches per strip of tape. These patches were placed on the child's
upper back, outlined with ink to enable the reader to determine the
location of the patches, and then reinforced with another layer of
paper tape. Parents were given instructions to leave the patches in
place for 48 hours and not to bathe the back during that time. The
patches were removed at 48 hours by the parent at home, and the child
returned to clinic 4 or 5 days (96 to 120 hours) after initial
application of the patches to read the reactions. Reactions were scored
according to the North American Contact Dermatitis Group scale: 0 = no skin change, 1+ = macular nonconfluent erythema or rim pattern, 2+ = confluent redness, and 3+ = redness plus blistering, each within the
.81 cm2 area. Reactions of 2+ and 3+ were
considered significant, whereas 1+ reactions were likely irritant
reactions and were not included in the final analysis of results.
| |
RESULTS |
A total of 95 subjects ranging from 6 to 67.5 months in age were
enrolled in the study. The average age was 31.4 months. There were 54 males (57%) and 41 females (43%). Of the patients, 13 (14%) reported
a history of eczema or atopic dermatitis, and 5 (5%) reported a family
history of ACD. A single patient had a history of rash over the
earlobes that occurred after wearing costume jewelry a few years before
and had not since recurred.
Of the subjects. 85 successfully completed the study. The remaining 10 were either lost to follow-up or failed to keep the patches on for 48 hours. At least 1 positive reaction was observed in 20 subjects
(24.5%). These children ranged from 6 to 67 months of age, with a mean
of 30.4 months of age. Of the children, 9 (45%) were <18 months of
age, and 11 (55%) were older, 10 (50%) were male, and 10 (50%) were
female. Table 2 demonstrates the age,
sex, and allergens causing positive reactions in these subjects. Of
note, the 1 patient with a history of earlobe dermatitis was sensitized
to nickel (patient 19) but had discontinued earring use.
Of the subjects, 16 had 1 positive reaction, and 4 had 2 positive
reactions. No subjects had 3 or more positive reactions. There were 11 reactions to nickel and 8 reactions to thimerosal, making these
substances our most prevalent allergens. Positive reactions also were
observed to kathon CG, neomycin, cobalt and p-tert butylphenol
formaldehyde resin (PTBFR). All allergens causing positive reactions
and the prevalence of those reactions are shown in Table
3.
Irritant reactions to tape were observed in 7 children (7.4%). There
were also 5 children who removed their patches within 24 hours of
placement because of discomfort. The remainder of the subjects reported
no problems and seemed to tolerate the patch testing well.
| |
DISCUSSION |
A review of the English literature reveals only 2 studies about
allergic contact sensitization in asymptomatic children. Barros et
al21 studied 562 school children from 5 to 14 years of age
and found that 13.3% were sensitized to 1 or more contact allergens.
Weston et al20 studied 314 children from 6 months to 18 years of age and found a 20.3% prevalence of at least 1 positive
reaction. Within that group, 129 children were 
5 years of age, and 26 (20%) had positive skin test results. Our study examined 85 children
from 6 to 67.5 months of age and found a prevalence of 24.5%
sensitization.
By targeting patients who presented for well-child care, we were able
to obtain a patient population that is likely to reflect that of the
Denver area. The low percentage of patients with skin problems in our
sample group suggests that our results are not skewed. We were able to
limit the number of falsepositive reactions in our study in 2 ways. We counted only 2+ or 3+ reactions as significant, limiting the
number of irritant reactions that might be considered relevant.
Irritant reactions tend to fade quickly, and all our patients followed
up at least 48 hours after removal of their patches. By waiting for
irritant reactions to clear, and by only including the strongest
reactions as positive, we feel that our positive reactions are a more
accurate reflection of true sensitization. Our prevalence of 24.5%
sensitization is consistent with that previously found by Barros et
al21 and Weston and colleagues20 and is a
general reflection of sensitization in children 5 years of age.
Our most prevalent allergen was nickel with 12.9% of the population
sensitized. Nickel is a strong sensitizer, and it is not surprising
that we found this many positive reactions. Although nickel is known to
produce irritant reactions in children, we performed late readings when
irritant reactions should subside and true allergic reactions persist,
and therefore, we believe our nickel reactions represent allergy. Metal
components such as snaps and buckles are common parts of infants' and
children's clothing. Additionally, youngsters are frequently touched
by caretakers wearing jewelry or may even wear jewelry themselves.
Numerous studies of children with dermatitis have indicted nickel as a common allergen, often as the most prevalent allergen as
well.8-19 In the previous study by Weston et
al,20 nickel was the second most prevalent allergen with
7.6% sensitized, whereas Barros et al21 demonstrated only
5.7% of his population sensitized (7th most prevalent allergen).
Although direct comparisons of these numbers would not be valid owing
to differences in sample ages and size, it is interesting that our
prevalence is greater and that a number of our youngest patients were
sensitized to nickel.
Our next most prevalent allergen was thimerosal, a preservative found
in vaccines and topical medications such as eye drops. There has been
much controversy in the adult literature about the relevance of
thimerosal sensitization, but vaccines seem to play a large role in
sensitization in children.25,26 Osawa et al27
demonstrated that diphtheria-tetanus-pertussis vaccination
produces sensitivity to thimerosal in a guinea pig model. The American
Academy of Pediatrics recommends that children begin routine
vaccinations at 2 months of age, a process that continues until they
are ready for school entry.28 In light of the number of
vaccinations that children receive these days, it is not surprising
that thimerosal is frequently reactive in skin testing. We found that
9.4% of our subjects were sensitized to thimerosal. In contrast,
Weston et al20 previously found only 3.5%, and Barros et
al21 found 14.9%, differences likely attributable to
varying exposures and test methods. The majority of our thimerosal
reactions occurred in children >18 months of age, possibly suggesting
that thimerosal is a weak allergen and that multiple exposures are
needed to produce sensitization.
Sensitivity to preservatives other than thimerosal was less common.
Only 2.4% of our patients reacted to kathon CG and 1.2% to PTBFR.
Because of our small sample size, it is not surprising that there were
no reactions to other preservatives. Preservatives are unfortunately a
ubiquitous component of topical preparations and can cause significant
problems of contact allergy, even in children. Conti et
al29 studied sensitization to preservatives in 811 Italian
children with atopic dermatitis or other eczema and found 4.9% reacted
to kathon CG, whereas ~1% reacted to other preservatives such as
formaldehyde and imidazole urea. Similar to our study, a previous study
by Weston et al20 also demonstrated a lower prevalence of
sensitivity to preservatives such as formaldehyde (1.5%), Quaternium
15 (1.5%), and PTBFR (.9%). Conversely, Barros et al21
found a high amount of sensitization to PTBFR with 13.8% of his
subjects reacting.
Metals other than nickel did not play a large role in sensitization.
Only 1 patient (1.2%) was sensitized to cobalt, and no positive
reactions to potassium dichromate were noted. Sensitivity to all 3 metals can be seen together, but we did not observe this phenomenon.
Weston et al20 observed that 7.6% of his population were
sensitized to potassium dichromate, which he attributed to exposure to
shoe leather. Barros et al21 found only 1.1% positive to
potassium dichromate but did find 3.4% of subjects reacting to cobalt.
A surprising finding of our study was that only 1 patient (1.2%)
reacted to neomycin, a common allergen in the past. Both Weston et
al21 and Barros et al20 found neomycin to be
the most prevalent allergen in their studies: Barros and colleagues
found 18.4% positive and Weston and co-workers found 8.1% positive.
Neomycin is a topical antibiotic, often used as a first-aid medication
for minor cuts and scrapes. It is also a known allergen that has been
removed from several popular children's skin preparations, and this
fact could account for the decrease in its rate of sensitization.
As previously mentioned, there have been case reports of ACD in
infants, but no formal studies addressing infants and ACD as a group.
Seidenari et al23 described 3 cases of ACD in children <1
year of age: 6- and 12-month-old infants allergic to nickel and a
12-month-old child allergic to para-phenylenediamine. Fisher22 described a 7-month-old infant who developed nickel dermatitis to the snaps in his sleepwear and a 1-week-old infant
with ACD to the epoxy resin in his vinyl identification band. In a
clinical update, Fisher30 also summarized the past work of
Strauss, who demonstrated that infants can be sensitized to poison ivy
extract, and the work of Uhr, who showed that premature infants also
can be sensitized to allergens. These cases illustrate that the immune
system of an infant is capable of producing the responses necessary to
evoke ACD. From our results, we offer that sensitization within the
general pediatric population frequently occurs at a young age. Of our
patients with positive reactions, 45% were <18 months of age. Given
the variety of clothing, topical medications, and skin care products
available today, the skin of infants and young children is exposed to a
wide range of allergens, and this level of sensitization is not
surprising.
The T.R.U.E. Test system has not been previously used in children <5
years of age. In older children, the sensitivity and specificity of
this testing system are not different from other contact allergy
testing systems.
| |
CONCLUSION |
In summary, we found that 24.5% of asymptomatic children from 6 months to 5 years of age were sensitized to 1 or more contact allergens. Nickel and thimerosal were the most prevalent allergens. We
also found that children as young as 6 months of age can be sensitized
to allergens, and that approximately one half of our sensitized
children were <18 months of age. Sensitization to contact allergens
begins in infancy and continues to be common in older infants and young
children.
| |
FOOTNOTES |
Received for publication Apr 26, 1999; accepted Jul 7, 1999.
Reprint requests to (W.L.W.) Department of Dermatology, Box
B-153, University of Colorado Health Sciences Center, 4200 E Ninth Ave,
Denver, CO 80262. E-mail: william.weston{at}exchange.uchsc.edu
| |
ABBREVIATIONS |
ACD, allergic contact dermatitis;
PTBFR, p-tert
butylphenol formaldehyde resin.
| |
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Abstract
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