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Exposures and Outcomes of Children With Urticaria Seen in a Pediatric Practice-Based Research Network
A Case-Control Study
Jennifer Plumb, MD, MPH;
Chuck Norlin, MD;
Paul C. Young, MD;
for the Utah Pediatric Practice Based Research Network
Arch Pediatr Adolesc Med. 2001;155:1017-1021.
ABSTRACT
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Objectives (1) To determine the duration, outcome, and associated findings of urticaria
in children seen by general pediatricians; (2) to compare the exposure to
foods, medications, insect stings or bites, and the presence of other symptoms
in children with urticaria with controls; (3) to determine general pediatricians'
management of urticaria.
Design Case-control.
Participants Children with urticaria seen by Utah Pediatric Practice Based Research
Network members between August 1, 1999, and August 31, 2000. Control patients
were matched for age and sex.
Main Outcome Measures Duration of urticaria; associated symptoms; personal and family history
of atopy; medications; ingestion of peanuts, nuts, shellfish, tomatoes, strawberries,
or eggs; being stung by an insect; suspected cause, diagnostic studies; treatment.
Results Fifty-two cases and 47 controls were enrolled. The mean duration of
urticaria was 8.9 days (range, 1-50 days). Seventeen patients (33%) and 1
control patient were taking antibiotics (odds ratio [OR], 22.3; 95% confidence
interval [CI], 2.8-176;  2, P<.001).
Fourteen patients and 5 controls had gastrointestinal symptoms (OR, 3.1; 95%
CI, 1.02-9.4; 2, P = .04). There
were no differences between cases and controls for other symptoms, personal
or family history of atopy, ingestion of the foods listed, insect sting, or
other medications. A cause was suspected in 28 patients (54%): a "viral illness"
(19%), antibiotics (15%), or a combination (35%).
Conclusions Patients were more likely than controls to be taking an antibiotic and
were more likely to have a personal or family history of atopy or to report
ingesting foods commonly associated with urticaria. A viral illness was the
most common cause suspected by pediatricians.
INTRODUCTION
URTICARIA or hives is a common skin condition in children that, because
of its dramatic appearance and occasional association with life-threatening
anaphylactic reactions, frequently results in a visit to a physician. Although
most children with urticaria are probably seen by primary care physicians,
the literature regarding diagnosis and treatment is primarily based on studies
of adults seen by dermatologists,1, 2
children seen in dermatology clinics,3 hospitalized
children,4, 5 or studies carried
out in emergency departments.6 Of these studies,
all but one, which reported on the use of prednisone in adult patients, were
conducted outside of North America. The findings in these studies may not
be generalizable to pediatric patients with urticaria in the United States.
Margolis and Nisi7 described urticaria in an
Ohio family practice. Their retrospective medical record review series from
a primary care setting of 72 patients included 16 who were younger than 17
years.
Most studies attempt to ascribe etiologies to urticaria based on histories
of atopy or of reported exposures to foods, medicines, infections, or other
agents. However, no study has compared the frequencies of such exposures with
those of similar children who did not have urticaria. Opinions expressed in
review articles by specialists in pediatric dermatology8, 9
or pediatric allergy10, 11 seem
to be based on the authors' experiences supplemented by their reviews of the
limited primary literature. Thus, these too may offer advice regarding management
that may not be applicable to the typical patient seen in a pediatric practice.
To overcome the limitations of previous studies and to provide data
that might better assist in decision making by primary care physicians, we
designed a study of children with urticaria who were being seen in primary
care pediatric offices. The study had 3 principal objectives: (1) to determine
the duration, outcome, and associated findings of children with urticaria
seen in pediatric practice; (2) to compare children with urticaria with controls
matched for age and sex with respect to ingestion of foods commonly believed
to be associated with urticaria, medication exposure, presence of symptoms
of other illnesses, and being stung or bitten by an insect; and (3) to determine
the management of children with urticaria by primary care physicians.
METHODS
The study was conducted from August 1, 1999, to August 31, 2000, in
the offices of pediatricians and physician assistants who are members of the
Utah Pediatric Practice Based Research Network (UPPBRN). Participating members
of the UPPBRN were asked to enroll every child with urticaria whom they saw.
There were no exclusion criteria. Children who were seen more than once for
the same episode of urticaria were enrolled only once. Parents of children
with urticaria were invited by the physician to participate. The purpose and
procedures of the study were explained and informed consent to permit telephone
follow-up by the investigators was obtained. Using a checklist (Figure 1), physicians recorded the date of onset, presence or absence
of other symptoms, personal and family history of atopy, medications taken
in the past 14 days, ingestion of peanuts, nuts, shellfish, tomatoes, strawberries,
or eggs in the 48 hours prior to onset, and whether the child had been stung
or bitten by an insect during the same interval. The arbitrary times chosen
to assess exposures to foods, insects, and medicines, and for the presence
of other symptoms were developed by consensus of the members of the research
network as representing their usual practice. Physicians were asked to identify
as a control the next child whom they saw of the same sex and age. For children
younger than 5 years the age of the control was to be within 6 months of the
age of the index patient and, for index patients older than 5 years, the age
of the control was to be within 1 year of the index patient. Parents of this
child completed a checklist that contained the same items indicated above.
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Sample physician checklist.
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On a checklist for each patient, physicians indicated the suspected
cause, their degree of certainty about the cause, the diagnostic study results
obtained, and the treatment recommended. Parents were contacted by telephone
by one of the investigators (J.P.) at 2 to 3, 14, and 30 days after their
visit to determine the duration of the urticaria, whether additional symptoms
had developed, whether medications were used, and whether they caused any
adverse effects. The study was approved by the institutional review boards
of both the University of Utah Health Science Center and Primary Children's
Medical Center (Salt Lake City). Odds ratios (ORs) with 95% confidence intervals
(CIs) were calculated to compare patients with controls with respect to exposures
to possible etiologic agents. Odds ratios whose 95% CIs did not include 1.0
were judged to be significant. Descriptive statistics were used to characterize
various aspects of the patients and 2 or t tests were used to test for differences between patients and controls.
An  of .05 was considered to be significant. Analyses were performed
using StatView (Abacus Concepts, Berkeley, Calif).
RESULTS
During the study period, 52 patients with urticaria were enrolled by
14 pediatricians and 1 physician's assistant, with 1 to 10 patients per physician.
None of the parents who were asked to participate refused. For 5 of the patients
no control was identified. Patients ranged in age from 6 months to 18 years
(mean age, 69 months) and 29 (56%) were female. Successful telephone contacts
were made with 46 of the parents.
The 46 parents who were successfully contacted reported a mean duration
of 8.9 days (range, 1-50 days). The median duration was 5 days and 33 (72%)
reported that the urticaria had cleared within 10 days of onset.
Table 1 shows the ORs with
95% CIs for exposures to potential etiologic agents or the presence of other
symptoms reported by parents of patients and controls. Significant differences
were found in reported antibiotic use and the presence of gastrointestinal
symptoms. Parents of 17 patients (33%) reported antibiotic use in the previous
2 weeks compared with parents of one of the controls (OR, 22.3; 95% CI, 2.8-176)
(2, P<.001). Fourteen patients
(27%) were noted to have gastrointestinal symptoms compared with 5 controls
(11%) (OR, 3.1; 95% CI, 1.02-9.4; 2, P
= .04). Confidence intervals of the ORs included 1.0 for all other factors
studied. This suggests that there were no significant differences between
patients and controls with respect to the presence of fever, sore throat,
upper respiratory tract symptoms, a personal or family history of atopy, ingestion
of the 6 foods, medications other than antibiotics, or of being stung or bitten
by an insect.
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Odds Ratios of Exposures: Cases and Controls*
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Physicians reported performing laboratory tests on 7 of the 52 patients:
4 were tested for group A streptococcal pharyngitis (all negative), 2 had
complete blood cell counts performed, and 1 had a urinalysis. A cause was
suspected by physicians in 28 of the patients (54%): "viral illness" (19%),
antibiotics (15%), or a combination (35%). Physicians reported that they were
"less than 50% certain" of the cause for 60% of the patients. No physician
reported "100% certainty" for any of the patients, but in 15 (30%) certainty
was reported as being between 75% and 90%. Antihistamines were recommended
for 41 (79%) of the patients and prednisone for 3. Of the children for whom
medications were recommended or prescribed, all but 3 reportedly took them
as directed. Drowsiness or irritability believed to be secondary to the medications
was reported by 30% of the parents and 2 discontinued the medications because
of these adverse effects.
COMMENT
Our study is the first that we are aware of to describe children with
urticaria who were seen in primary care pediatric offices in the United States
and to use a case-control design to compare them with similar children without
urticaria. While the mean duration of urticaria was about 9 days, it had resolved
within 5 days in half of the children in our study. We found that a specific
cause was not identified in most of the patients and that when pediatricians
did suspect a particular cause, their confidence that there was a true cause
and effect relationship was relatively low. Laboratory tests were done infrequently,
and most children were treated with antihistamines, which were well tolerated.
Although viral or group A streptococcal infections, the ingestion of
certain foods, or being stung by an insect have been suggested in the literature
to be causally associated with urticaria,7, 8, 9, 10, 11
we found that a positive history was no more likely to be reported in children
with urticaria than in matched children who were being seen in the office
on the same day for some other reason. Similarly, children with hives were
no more likely to be atopic or to have first-degree relatives with asthma,
hay fever, or atopic dermatitis compared with control children. However, children
with hives were significantly more likely to be taking or to have recently
taken antibiotics. We suspect that the barely significant difference between
patients and controls with respect to the presence of gastrointestinal symptoms
is probably a chance finding given the many variables (14) and the fact that
the lower limit of the 95% CI was 1.02. In contrast, the difference in use
of antibiotics seems statistically robust and is likely to be clinically valid.
This study has several important limitations. First, it is likely that
some children with urticaria who were seen by Utah PPBRN physicians were not
enrolled in the study because of time pressures or other reasons. Thus, some
selection biases, possibly toward including children with more severe manifestations,
could have been present. Additionally, children with hives who were not brought
to the pediatrician were not included in the study. Second, we were unable
to estimate the prevalence of urticaria because we were unable to accurately
determine how many patients were seen by reporting physicians during the study
period. Third, the physicians are all from Utah and their patients, mostly
white and middle class, may not be representative of children seen by pediatricians
in the general population of the United States. The pediatrician's diagnostic
and management choices may also not be representative of pediatricians in
general. The wide CIs for some of the items being compared between the patients
and controls reflects the infrequent occurrence of some of the exposures.
For example, only 1 child with urticaria reported ingestion of shellfish in
the previous 48 hours compared with no children from the control group.
Even though we found an association between antibiotic use and hives,
a case-control study cannot prove causality. One should not conclude that
the items with no association could not be causal; it is also possible that
the items with no association could be causal. However, one should be very
cautious in attributing a cause and effect relationship if the conclusion
is based only on a history of exposure since we found that a history of exposure
was just as likely to be obtained from parents of children who did not have
urticaria as it was from parents of children who did.
Our study calls into question many of the associations reported in previous
reports and repeated in review articles. For example, Legrain et al3 reported that based on "a careful history and physical
examination . . . drug intake and infection accounted for 37.5% of all cases
of urticaria," in their series of 40 infants hospitalized for urticaria at
a children's hospital in Bordeaux, France. Similarly, physicians in our study
suspected this combination in 44% of their patients but when we compared children
with and without urticaria we found that the 2 groups were equally likely
to report a history of such exposures. The role of foods as a cause for urticaria
remains uncertain. Legrain et al3 reported
that 25% of their cases were caused by foods while Mortureux et al4 and associates indicated that 11% of their cases were
food related. Kauppinen et al5 from Finland
found a similar number in children (13%) but a greater number in adults (25%),
and other figures as high as 62% have been quoted.9
We found no differences in histories of recent ingestion of 6 foods reportedly
associated with urticaria8, 9 between
patients and controls. Other foods sometimes associated with allergic reactions
such as chocolate, cows' milk, or soy were not included in our history checklist.
Without further evaluation, such as skin testing or blinded challenge, attributing
a child's hives to ingestion of a particular food should be a tentative conclusion.
We were unable to find reports of the etiology of hives being verified by
an experimental technique such as blinded food challenge. Of course, immediate
reactions of an anaphylactic nature following ingestion of a food should be
carefully evaluated and treated with great caution. Because of different definitions
of atopy, it is not surprising that its potential association with urticaria
varies, with studies reporting 20%,3 26%,1 29%,7 and 50% rates
of occurrence.4 Our findings showed that 33%
of the children with hives were atopic, which was defined as having a history
of asthma, seasonal rhinitis, or atopic dermatitis. This percentage is in
line with these studies but it should be considered in light of the fact that
43% of controls also had a history of atopy. As expected, we found greater
percentages when a first-degree relative of patients (58%) and controls (66%)
had one of the atopic conditions. This was not significantly different.
Similar to many conditions seen in primary care practice, uncertainty
regarding the etiology of urticaria is common. In a family practice setting,
no cause was identified for 54% of the patients.7
The pediatricians in our study suspected a cause in 52% of the patients but
they generally expressed low degrees of certainty about the particular cause.
All but one of our patients had acute urticaria, the exception being
a child whose urticaria finally resolved on day 50, about 1 week longer than
the arbitrary separation between acute and chronic (6 weeks' duration). Chronic
urticaria seems to be much less common even in specialty clinics1, 2, 3, 4
so it is not surprising that it is rare in primary care settings. A carefully
performed case-control study of children with chronic urticaria might produce
different results from ours.
Studies of diseases and conditions conducted in practice-based research
networks may provide different results from those conducted in specialty clinics
or academic centers. Using a case-control design in pediatric practice-based
research networks, we found that recent antibiotic use was significantly more
common in children with urticaria but that other agents, such as foods, insect
bites and stings, or symptoms suggesting infection, were no more common in
children with urticaria than in age- and sex-matched children who were being
seen in a primary care pediatrician's office for reasons other than urticaria.
Physicians seeing children in settings similar to ours should inquire about
antibiotic use as well as the other factors but should be cautious in attributing
a cause and effect relationship based only on a history of exposure.
AUTHOR INFORMATION
The Utah Pediatric Practice Based Research
Network
Salt Lake City: Carrie Byington, MD, The South
Main Clinic; Mark Briesacher, MD, The Bryner Clinic; Karla Feindt, MD, University
Hospital Pediatric Clinic; Christian Herrera, MD, The Greenwood Center, UUHN;
Louis Melini, PA, Steve Lynch, MD, Willow Creek Pediatrics; Kathleen McElligott,
MD, Chuck Norlin, MD, Charles Ralston, MD, University Hospital Pediatric Clinic; American Fork: Gordon Glade, MD, Utah Valley Pediatrics; Sandy: Jeff Schmidt, MD, Mark Valentine, MD, IHC Health
Center Sandy; West Jordan: Robert Terashima, MD; Park City: Leslie Webster, MD, Summit Pediatrics.
What This Study Adds
Descriptions of urticaria in children and recommendations for management
are based primarily on reports and reviews of hospitalized children or those
seen by dermatologists. Understanding the condition as it is commonly seen
in general pediatric practice may provide information that is more helpful
to primary care practitioners. A case-control design allows comparison of
children with and without urticaria with respect to associated exposures or
other possible causal factors.
Exposures to foods often cited as potential causes of urticaria, symptoms
of other illnesses, and insect stings or bites are as common in controls as
in children with urticaria. Children with hives are more likely to be taking
antibiotics than are controls. Children with hives who are seen by general
pediatricians differ little from matched controls. Thus, attributing a relationship
between exposure to a particular substance or an associated illness based
only on a history of exposure may be unwarranted.
Accepted for publication April 12, 2001.
This study was supported by a grant from the Primary Children's Medical
Center Foundation, Salt Lake City.
Presented in part as a poster at the Pediatric Academic Societies Meeting,
Boston, Mass, May 12-16, 2000.
From the Departments of Pediatrics, University of Indiana School of
Medicine, Indianapolis (Dr Plumb); and the University of Utah School of Medicine,
Salt Lake City (Drs Norlin and Young).
Corresponding author: Paul C. Young, MD, Department of Pediatrics,
University of Utah School of Medicine, 50 N Medical Dr, Salt Lake City, UT
84132 (e-mail: paul.young{at}hsc.utah.edu).
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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
Prior Antibiotic Use Common in Children Who Develop Urticaria
Krowchuk
AAP Grand Rounds 2001;6:63-64.
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