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Pediatr Drugs 2004; 6 (4): 233-250

THERAPY IN PRACTICE 1174-5878/04/0004-0233/$31.00/0

© 2004 Adis Data Information BV. All rights reserved.

Allergic Rhinitis in Children


Diagnosis and Management Strategies

William E. Berger
Department of Pediatrics, Division of Allergy and Immunology, University of California, Irvine, California, USA

Contents
Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
1. The Impact of Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
1.1 Worldwide Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
1.2 Consequences of Untreated Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
1.3 Economic Burden of Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
2. Pathophysiology of Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
3. Recognizing and Diagnosing Pediatric Allergic Rhinitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238
4. Management of Allergic Rhinitis in Children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
4.1 Environmental Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
4.2 Immunotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
4.3 Pharmacologic Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
4.3.1 Antihistamines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
4.3.2 Cromoglycates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
4.3.3 Corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
4.3.4 Decongestants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
4.3.5 Anticholinergics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
4.3.6 Leukotriene Antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245

Abstract The incidence of allergic rhinitis has been increasing for the last few decades, in keeping with the rising
incidence of atopy worldwide. Allergic rhinitis has a prevalence of up to 40% in children, although it frequently
goes unrecognized and untreated. This can have enormous negative consequences, particularly in children, since
it is associated with numerous complications and comorbidities that have a significant health impact on quality
of life. In fact, allergic rhinitis is considered to be a risk factor for asthma.
There are numerous signs of allergic rhinitis, particularly in children, that can alert an observant clinician to
its presence. Children with severe allergic rhinitis often have facial manifestations of itching and obstructed
breathing, including a gaping mouth, chapped lips, evidence of sleep deprivation, a long face, dental malloclu-
sions, and the allergic shiner, allergic salute, or allergic crease. The medical history is extremely important as it
can reveal information regarding a family history of atopy and the progression of atopy in the child. It is also
important to identify the specific triggers of allergic rhinitis, because one of the keys to successful management
is the avoidance of triggers.
A tripartite treatment strategy that embraces environmental control, immunotherapy, and pharmacologic
treatment is the most comprehensive approach. Immunotherapy has come to be viewed as potentially prophylac-
tic, capable of altering the course of allergic rhinitis. The most recent guidelines for the management of allergic
rhinitis issued by the WHO recommend a tiered approach that integrates diagnosis and treatment, in which
234 Berger

allergic rhinitis is subclassified both by frequency, as either intermittent or persistent, and by severity, as either
mild or moderate to severe. Oral or topical antihistamines and intranasal corticosteroids are the mainstay of
pharmacologic therapy for allergic rhinitis, depending upon its severity, and several agents have been approved
for use in children aged 5 years old and younger.

Allergic rhinitis has a looming presence in the pediatric popula- changes, and increased atmospheric or indoor pollution – the
tion. Considered the most common chronic condition of child- purported suggestions remain speculative, at best.[11,16,17,19,20]
hood, with a prevalence of up to 40% in children, allergic rhinitis Evidence of the increasing prevalence of childhood allergic
is also one of the most under recognized and untreated disor- rhinitis spans several countries and age groups. However, caution
ders.[1-3] It is defined as an inflammation of the nasal mucous must be exercised when interpreting the data, in light of the
membranes, the clinical expression of which includes symptoms tremendous variability in the prevalence rates reported in different
of nasal congestion, rhinorrhea, sneezing, itching of the nose or studies. Some of this variability can be attributed to the lack of
throat, and conjunctivitis.[4] The quintessential IgE-mediated reac- uniform criteria for determining atopy and rhinitis, and to restric-
tion, allergic rhinitis can be triggered by a sensitivity to seasonal or tions that limit the study cohorts to discrete subpopulations of
perennial aeroallergens. patients with allergic rhinitis. Consequently, studies that utilize
Relegated to the status of a petty annoyance by many clinicians self-reported questionnaires that preclude physician diagnosis of
because allergic rhinitis is not life threatening, its deleterious rhinitis or confirmation of atopy by skin tests lead to higher
effects on patients’ quality of life are often minimized, rendering prevalence rates.[21] Conversely, studies that focus exclusively on
them all the more insidious. Yet, despite its trivialization, the hay fever and neglect to include patients triggered by other season-
impact of pediatric allergic rhinitis should not be underestimated. al or perennial allergens lead to lower prevalence rates.[21]
Untreated allergic rhinitis can lead to complications and comorbi- Two trends have emerged from the data, both of which are
dities that result in disfigurement and death.[4] It also imposes a relevant to the clinical diagnosis of allergic rhinitis. The first
staggering economic burden, due to the sheer magnitude of the reflects the natural history of the expression of atopy during
affected population, the chronicity of the condition, and the treat- development, whereby the incidence of allergic rhinitis increases
ment costs of disease sequelae. These, combined with the degree with progressing age throughout childhood, reaching peak preva-
to which allergic rhinitis diminishes quality of life, are a testament lence levels during adolescence.[16] Superimposed on this is the
to the enormity of its impact.[5-9] increasing prevalence of atopy across time, as evidenced by the
higher prevalence rates for each age group during the latter part of
1. The Impact of Allergic Rhinitis the twentieth century, compared with earlier decades, a trend that
is particularly apparent in longitudinal studies.
In the US, one of the first epidemiologic studies of allergic
1.1 Worldwide Prevalence rhinitis in childhood was conducted by Freeman and Johnson in
1964, who administered a self-reported questionnaire to Denver
In parallel with the increasing incidence of atopy worldwide, schoolchildren.[22] The prevalence of seasonal allergic rhinitis,
the prevalence of allergic rhinitis has risen steadily over the last 50 restricted to hay fever, was 16% in eighth graders (13-year-olds)
years.[10-13] Since this is too short a period for genetic changes to and 22% in twelfth graders (17-year-olds), reflecting the rise in
have evolved in such a pandemic fashion, many have attributed the atopy throughout childhood with peak frequencies occurring
increased prevalence to extrinsic environmental changes caused during adolescence. An additional 7.3% of eighth graders and
by pervasive industrialization.[3,8-11,14-17] However, this notion has 5.6% of twelfth graders had perennial allergic rhinitis, yielding
been refuted by evidence of an inverse association between air overall prevalence rates for allergic rhinitis of 23.3% at age 13
pollution and allergic rhinitis symptoms, particularly among chil- years and 27.6% at age 17 years. Similar frequencies were report-
dren in Leipzig and Munich following German reunifica- ed in a 1969 study by Hagy and Settipane of 690 college freshmen,
tion.[12,18,19] While considerable efforts have been made to identify 162 (23.5%) of whom had allergic rhinitis, as determined by
the causative changes – improved hygiene, fewer childhood infec- physical examination.[23,24] By their senior year, an additional
tions due to the advent of antibiotics and vaccinations, dietary 3.1% (26.6% in total) had allergic rhinitis. Long-term follow-up of

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
Allergic Rhinitis in Children 235

this population revealed that at 40 years of age, the prevalence of 31.7%.[31] In 3631 university students in Thailand the prevalence
allergic rhinitis had increased to 31%, which represented a cumu- of allergic rhinitis was 26.3%, while a prevalence of 41.5% was
lative prevalence of 42%.[25] found in 4102 12 to 15-year-olds in Singapore.[32,33] Among
Other US studies also have indicated that the prevalence of schoolchildren in the UK, three different ISAAC studies demon-
allergic rhinitis increases throughout childhood and peaks during strated prevalence rates for allergic rhinitis of 23.1% in 6 to
adolescence. These studies include two population-based studies 7-year-olds, 19.4% in 12 to 14-year-olds, and 28.9% in 13 to
of physician-diagnosed allergic rhinitis, an early one by Broder et 14-year-olds.[34-36]
al.[26] reported in 1974, and the second National Health and Nutri-
tion Examination Survey (NHANES II) reported by Gergen and 1.2 Consequences of Untreated Allergic Rhinitis
Turkeltaub in 1992.[27] In the Broder et al. study of seasonal and
perennial allergic rhinitis in a rural Michigan community during Allergic rhinitis is characterized by a constellation of nasal,
the mid-1960s, peak prevalence rates of 15.4% occurred in 16 to eye, ear, throat, and palate symptoms. Prominent among them are
24-year-olds.[26] Similarly, in the NHANES II study, which was itching, sneezing, congestion, rhinorrhea, cough, and postnasal
conducted on a nationwide population of 17 100 children during drip. In addition to the spectrum of localized symptoms, many
1976–80 and utilized confirmatory skin prick tests (SPTs), hay patients with rhinitis also experience more global effects including
fever was found to be the most common chronic illness of child- headache, fatigue, sleep disturbances, loss of olfaction (anosmia),
hood, with a prevalence of 6% in 6 to 11-year-olds that increased and cognitive impairment, some of which are related to the con-
to a prevalence of 9% in 18 to 24-year-olds.[27] gestion.[4] While fatigue can be partially attributed to disrupted
A much higher prevalence of allergic rhinitis was reported in sleep, cognitive impairment and fatigue also are associated with
1994 by Wright et al.[1] in a longitudinal survey of 747 children the effects of proinflammatory mediators on the hypothalamus.[4]
living in Tucson, Arizona who had been followed from birth. By Chronic nasal obstruction can cause pronounced sleep distur-
6 years of age, 42% of the children had physician-diagnosed bances, such as sleep apnea and disordered sleep, which together
allergic rhinitis. Although the high prevalence of allergic rhinitis with fatigue, may induce systemic effects including irritability,
in this population in part reflects the increasing incidence of atopic weakness, malaise, decreased appetite, and poor growth, seriously
disease during the 1990s, it was also suggested to be due, in part, diminishing quality of life.[4,37,38] Thus, in addition to the more
to the disproportionately large number of atopic individuals with than 2 million absentee school days attributed to allergic rhinitis
respiratory disorders who move to Tucson to benefit from the each year in the US, school performance can be further impaired
climate. Owing to the fact that atopy is known to be an inherited by cognitive dysfunction related to the disease itself, and the
trait, it is not surprising that the frequency of allergic rhinitis is sedative effects of first-generation antihistamines. Perhaps the
high among children of these individuals. most unfortunate consequences of untreated childhood allergic
These trends are even more apparent in international preva- rhinitis are its psychologic ramifications. Children with allergic
lence studies of allergic rhinitis. For example, in the 10-year rhinitis are more likely to exhibit low self-esteem, shyness, depres-
interval between 1971 and 1981, the prevalence of physician- sion, anxiety, and fearfulness.[38]
diagnosed seasonal allergic rhinitis increased from 4.4% to 8.4% Children are especially susceptible to the complications of
in 55 000 18-year-old recruits to the Swedish army.[28] Similarly, untreated allergic rhinitis, due to the plasticity of their growing
between 1977 and 1991, the prevalence of physician-diagnosed bodies. Permanent disfigurement, particularly in the face and head
allergic rhinitis tripled from 5.0% to 14.9% in 7394 Finnish can occur from chronic gaping of the mouth in an effort to
adolescents aged between 12 and 18 years.[29] overcome obstructed breathing. Excessive mouth breathing can
To facilitate standardized comparisons among studies in differ- result in increased facial length, a high arched palate, class II
ent countries, a questionnaire was developed by the International dental malloclusions, and retrognathic maxilla and mandible.[4,39]
Study of Asthma and Allergies in Childhood (ISAAC) steering As an organ-specific manifestation of atopy, allergic rhinitis
committee.[3,30] A few representative studies conducted during the rarely occurs in isolation. Rather, it often coexists with other
last few years using the ISAAC questionnaire confirm the high comorbid conditions that have a common allergic etiology, includ-
prevalence rates of allergic rhinitis around the globe. In Brazil, the ing otitis media, conjunctivitis, nasal polyposis, pharyngitis, sinu-
prevalence of allergic rhinitis in a cohort of 3005 6 to 7-year-olds sitis, atopic dermatitis, and asthma.[4,37,38] Increasingly, atopy is
was 28.8%, and in 3008 13 to 14-year-olds the prevalence was thought to play a prominent role in otitis media due to obstruction

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
236 Berger

of the eustachian tube. Several intranasal challenge studies have nature of the airways, and has led some clinicians to regard the two
demonstrated the relationship between eustachian tube obstruction disorders as clinical manifestations of a disease continuum within
and provocation with either histamine or aeroallergens, which can a common airway.[49] Although the reason that rhinitis is more
lead to middle ear effusion and hearing deficit, and ultimately common in individuals with asthma than the reciprocal is unclear,
cause speech impairment.[37,38,40-43] the association is thought to reflect inflammation throughout the
By far the most serious comorbidity of allergic rhinitis is airway that manifests in gradations, initially appearing as nasal
asthma, due to its associated mortality. Dysfunction of the upper symptoms and progressing to asthma.[55,56] However, this hypo-
and lower airways frequently occurs in tandem, as demonstrated thesis is difficult to distinguish from that of rhinitis as a causative
by numerous epidemiologic studies. The prevalence of asthma in agent in asthma.[44] Nevertheless, the relationship between the two
patients with allergic rhinitis approaches 38%, considerably higher diseases is further strengthened by several shared traits including
than the 5–10% prevalence of asthma in the general popula- their common genetic predisposition, the contiguity of their affect-
tion.[16,44-47] It is not uncommon for patients with rhinitis to have ed respiratory mucosae, their provocation by identical aeroal-
bronchial hyperresponsiveness, regardless of an asthma diagnosis, lergens, and the inflammatory nature of both conditions, which is
and its presence, particularly during rhinitis exacerbations, is often mediated by identical cellular and molecular constituents.[38,46]
a harbinger of asthma.[44,46,48-56] Their pathophysiologic link is also supported by compelling evi-
dence that successful pharmacologic treatment of allergic rhinitis
Conversely, allergic rhinitis has been shown to be nearly ubiq-
can improve concomitant asthma and that immunotherapy for
uitous in patients with asthma, including children.[36,44,49-51,57,58] In
allergic rhinitis can prevent the allergic march to asth-
a French population-based study with 9720 participants, allergic
ma.[1,44-55,64-74] Physicians are encouraged to check for the presence
rhinitis was 6- to 8-fold more common in participants with asthma
of rhinitis in all children who are symptomatic for asthma.[75] A
than in participants who did not have asthma.[58] Among 13 to
recent population-based study of 1245 people by Yawn et al.[75]
14-year-old British schoolchildren, 53% of boys and 61% of girls
demonstrated that 52% of individuals with asthma had allergic
with asthma also had rhinitis.[36] A US study of 100 atopic adoles-
rhinitis, and of these, rhinitis was initially diagnosed in two thirds
cents with asthma conducted by Kapsali et al.,[57] which confirmed
atopy using SPTs, found a 96.0% prevalence of rhinitis. There also of asthmatic patients before the age of 10 years.
appears to be a temporal relationship in the onset of asthma and Sinusitis caused by obstruction of the sinus ostia is a common
rhinitis, whereby the rhinitis frequently precedes or is coincident problem in the pediatric population which often coexists with
with the asthma.[48-51,53-56,59-61] In the Kapsali et al. study,[57] this allergic rhinitis and with asthma.[37,38] Studies have determined
type of temporal relationship was reported by 72% of study that up to 70% of children with allergic rhinitis have abnormal
participants. Another study of 13 to 17-year-olds with both rhinitis sinus radiographs.[76,77] For sinusitis to be considered chronic in
and asthma revealed that 59% either had rhinitis first or initially the pediatric population, symptoms must persist for at least 12
had symptoms of both diseases occurring within the same year.[59] weeks, or six episodes of acute sinusitis must occur within a
Since the timing in the aforementioned studies is based on patient year.[78] The association between sinusitis and asthma was first
recall, the results of a prospective, longitudinal study reported in noted by Galen nearly 2000 years ago, and symptomatic sinusitis
1994 by Settipane et al.[62] are considered more conclusive. In the has been reported to coexist in up to 72% of patients with asthma.
follow-up of a study reported earlier, in which there was no Sinusitis has been increasingly overlooked in young children, or
evidence of asthma in the 690 college freshmen who participated mistakenly diagnosed as upper respiratory infection, due to the
in 1961, participants with rhinitis were three times more likely to misconception that because children’s sinuses are not yet fully
develop asthma than those without rhinitis (prevalence rates of developed the sinuses are absent.[37,79-84] This is unfortunate be-
10.5% vs 3.6%) during the ensuing 23 years.[23,62] Among the cause pediatric sinusitis can have an enormous impact on quality
participants with coexisting asthma and seasonal allergic rhinitis, of life, despite the fact that children rarely manifest acute signs of
rhinitis preceded the development of asthma in 44.8%, and both sinusitis, such as fever, headache, or purulent discharge.[37,85]
diseases developed simultaneously in 34.5%.[62] Instead, persistent cough, halitosis, sore throat, earache, malaise,
It is not surprising, then, that allergic rhinitis is considered a and irritability are frequently indicative of childhood sinusitis and
risk factor for the development of asthma.[1,3,44-52,54,56,63] The fre- successful medical or surgical treatment of the sinusitis can dra-
quent coexistence of asthma and rhinitis also highlights the unified matically improve concomitant asthma.[86-96]

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
Allergic Rhinitis in Children 237

1.3 Economic Burden of Allergic Rhinitis 12 years of age accounted for approximately 38% of these costs, or
$US2.3 billion, even though costs related to school absences were
The economic impact of allergic rhinitis is staggering. Most excluded. As seen in table I, the cost of allergic rhinitis exceeded
estimates have been tabulated for the general population, although that of sinusitis, otitis media, and asthma.
a few studies have focused exclusively on children. Based on These relative costs are also evident in independent studies
extrapolation of a 1987 National Medical Expenditure Survey of conducted in children, although in most of these studies asthma
the overall US population, the direct costs of allergic rhinitis,
was the primary diagnosis and allergic rhinitis was the comorbid
alone, in 1994 were $US1.15 billion.[97] An additional $US86
condition. For example, according to information gathered by the
million in indirect costs was due to 811 000 missed days of work,
National Health Interview Survey in the US, among the 2.7 million
4 230 000 days of reduced productivity, and 824 000 absentee
children (<18 years old) who had asthma in 1988, there were 10.1
days from school.[97] On a typical day, 10 000 children are absent
million asthma-related absentee days from school, 7.3 million
from school because of allergic rhinitis.[98] In another report,
days of bed restriction, 200 000 hospitalizations, and 12.9 million
conservative estimates for the direct and indirect costs of hay fever
contacts with physicians.[102] The cost of asthma increases by
in the overall US population in 1990 were $US1.8 billion, and
approximately 50% when rhinitis is present.[3,75,103] In a 1992 US
these increased to $US2.7 billion by 1995.[4,99] Considering that
expenditures for pharmacotherapy, the cornerstone of modern study by Grupp-Phelan et al.[103] in the state of Washington,
treatment, constitute only approximately 7–25% of total costs, the children with allergic rhinitis who made multiple medical visits
economic burden of allergic rhinitis to society and patients and were 12 times more likely to be diagnosed with asthma during that
their families is steep.[100] year than children without rhinitis. The high healthcare utilization
A more thorough analysis of the direct costs of allergic rhino- rates of these children were attributed specifically to allergic
conjunctivitis in the general US population in 1996, which includ- rhinitis, the cost of which (mean medical expenditure of
ed the direct treatment costs of comorbid conditions, was reported $US902.48 per year for rhinitis or sinusitis) was comparable to the
by Ray et al.[101] As shown in table I, while direct medical cost of asthma alone ($US890.52 per year). However, the mean
expenditures, by definition, excluded costs due to lost work pro- medical cost for asthma with comorbid allergic rhinitis was con-
ductivity, inclusion of expenditures for comorbid conditions in- siderably higher ($US1538 per year). Given that successful treat-
creased the total medical costs to $US5.9 billion. Children under ment of rhinitis or sinusitis can markedly improve asthma as well,

Table I. Medical expenditures attributable to allergic rhinitis/conjunctivitis and related airway disorders ($US million dollars; 1996 values) [reproduced from
Ray et al.,[101] with permission from Elsevier]
Airway disorder Inpatient hospital Outpatient physician Hospital Ambulatory Department Prescription Totala
discharges office visits outpatient visits emergency costs
surgery
Allergic rhinitis/ conjunctivitis b 937.1 260.5 b 72.6 593.2 1863.4
Chronic OM and eustachian tube 49.6 540.1 232.8 14.7 326.4 320 1483.5
disorder
Sinusitis 88.2 436 117.1 3 78.3 294.6 1017.3
Asthma 523.4 156.3 84.4 b 86 156.5 1006.7
Acute upper respiratory infection 12.8 82.3 30.7 b 36.4 49.1 211.8
Pharyngitis and tonsillitis 7.8 63.7 21.4 0.1 36.8 35.9 165.7
Other conjunctivitis b 33.2 16 0.3 20.3 18.2 88
Chronic rhinitis b 30.1 8.9 b 3.7 19.6 62.3
Rhinorrhea b 19.7 b 1 11.4 32
Total 681.8 2299 771.8 19.1 660.5 1498.5 5930.7
a Prescriptions included prescribed and over-the-counter medications ordered during visits to the physician office, hospital outpatient department, or
emergency department. They did not include costs for refills.
b Nonsignificant expenditures according to the criteria of the National Center for Health Statistics.
OM = otitis media.

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
238 Berger

it is prudent to be alert to the signs of rhinitis and sinusitis in all • Rhinorrhea, pruritus, and sneezing as a result of disturbances in
children diagnosed with asthma. the autonomic nervous control of nasal function that lead to
cholinergic predominance.[3,4,104-106,109,112,116-119]
The majority of these initial symptoms are mediated by the
2. Pathophysiology of Allergic Rhinitis
binding of released histamine to H1 receptors located on sensory
nerves, secretory cells in the mucous glands, and capacitance
Allergic rhinitis is a prototype of IgE-mediated disease, mani-
vessels in the nose, although leukotrienes, which are approximate-
festing as a biphasic response that can be provoked by seasonal
ly 5000 times more potent than histamine, also cause congestion
allergens, such as pollens found in the outdoor environment or
and rhinorrhea.[104,113,115,119-127] While a variety of mediators (e.g.
perennial allergens such as dust mites and animal dander, that exist
tryptase, leukotrienes, kinins, and prostaglandins) have been de-
throughout the year and are usually found indoors.[3,4,39,104,105] The
tected in the nasal secretions of patients with allergic rhinitis,
acute symptoms of the immediate or early phase reaction occur
histamine is clearly the most prominent mediator by virtue of its
within minutes of exposure to an aeroallergen, beginning with ability to reproduce the clinical features of acute allergic rhinitis
sneezing followed by an increase in nasal secretions.[39,104,105] when introduced in nasal challenge studies; histamine is released
After 5 minutes, reduced airflow develops as a result of mucosal from mast cells during the early phase reaction, and from baso-
swelling. Acute symptoms of the early phase usually abate within phils during the late phase reaction.[3,4,104-106,114,118,124]
1 hour. Approximately half of patients with rhinitis also experi- Mast cells also release other substances that regulate the in-
ence a late phase reaction in the ensuing 4–8 hours, when the flammatory response. For example, they are known to elaborate
influx of inflammatory cells to the nasal mucosa causes a recur- specific cytokines, including tumor necrosis factor-α, interleukin
rence of symptoms, particularly congestion.[104-106] Continued ex- (IL)-4, IL-5, and IL-6, and IL-13, which further modulate the
posure to allergens leads to chronic inflammatory changes within immune response by attracting eosinophils and T-helper (Th)-2
the nasal mucosa, the consequences of which are hyperirritability lymphocytes, and increasing the density of intercellular adhesion
of the turbinates, characterized by enhanced sensitivity to all molecules (ICAM).[108,116,128,129] ICAM-1 and vascular cell adhe-
exacerbants of rhinitis (aeroallergens and irritants), and priming sion molecule-1, among others, serve as binding anchors that
whereby the dose of allergen required to produce symptoms is direct immune cells to the site of inflammation, such that by
greatly diminished.[39,104] 3 hours after allergen challenge, there is a rich infiltration of
The clinical changes in the early and late phase reactions are eosinophils, neutrophils, basophils, Langerhans’ cells, and Th
orchestrated by the release of numerous mediators from an ac- cells, which elicit the late phase reaction.[3,4,39,104,115,118,130-132]
cumulating variety of inflammatory cells. Upon re-exposure of an These cells, in turn, release an even broader spectrum of cytokines
atopic individual to an inhaled allergen, the crosslinking of specif- and mediators, the clinical consequences of which are increased
ic surface IgE molecules by a bound allergen induces resident mast edema, nasal irritability, and proliferation of cells lining
the epithelium, which typifies chronic nasal inflamma-
cells in the nasal mucosa to degranulate and release both
tion.[104,106-108,118,124,130-133]
preformed mediators such as histamine, tryptase, kinins, and en-
zymes with N-a-tosyl L-arginine methyl ester (TAME)-esterase
activity, and newly synthesized mediators such as prostaglandin 3. Recognizing and Diagnosing Pediatric
D2 and sulfidopeptide leukotrienes (LTC4, LTD4, and Allergic Rhinitis
LTE4).[3,4,104-115] In turn, the cascade of mediators induces a com-
plex series of localized reactions characteristic of inflammation. By far the most important diagnostic tool for allergic rhinitis is
the patient history. Diagnosing the condition is facilitated by
Release of mast cell mediators, and to a lesser extent, mediators
collecting details regarding the natural history of allergy during
from eosinophils and neutrophils, leads to the clinical expression
the patient’s development and the presence of atopy in family
of the following acute symptoms that typify the early phase
members. Since genetic determinants of atopy dictate that a pre-
reaction.
disposition to allergic rhinitis is familial, and the incidence of
• Congestion caused by mucosal permeability, vasodilation, and allergic rhinitis increases with an increasing number of atopic
edema. relatives, it is important to ascertain the presence of all atopic
• Increased mucous secretion. conditions in both the patient and the immediate family. Thus,

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
Allergic Rhinitis in Children 239

while the likelihood of developing atopic disease is only 13% • The ‘allergic salute’, the upward rubbing of the nose with the
when neither parent is atopic, 29% of patients with one atopic palm of the hand in an attempt to reduce persistent itching and
parent develop allergies (these tend to arise later in life), and 47% open the nasal passages.[4,38,138,142]
of patients with two atopic parents develop allergies (these arise Other signs visible on the face are a chronic gaping of the
during childhood); the risk of atopy increases to 72% when both mouth or constant mouth breathing, increased facial length, red-
parents have the same allergic manifestation.[16,38,134,135] Epidemi- ness and itchiness of the eyes, excoriation above the upper lip,
ologic factors regarding allergic rhinitis can provide additional chapped lips, and signs of fatigue.[4,39,117]
clues to its existence. Risk factors for allergic rhinitis include a Beyond that, diagnosing allergic rhinitis in the pediatric popu-
high socioeconomic status and few siblings, as well as exposure to lation often presents unique challenges because children lack the
tobacco smoke, and an elevated IgE level in cord blood or in the ability to verbalize their symptoms, some of which may have been
serum prior to 6 years of age.[1,3,4,20,136,137] present for so long that they are accepted as normal. Therefore, an
Besides a family history of allergy, the other important risk awareness of the cardinal signs of allergic rhinitis and alertness to
factor for developing allergic rhinitis is early exposure to perennial their presence is of prime importance. Less localized clues that aid
allergens.[19] Mounting evidence indicates that the conditions in the recognition of allergic rhinitis are a nasal voice, halitosis,
under which an allergen is encountered in infancy may have frequent sore throats, a cough, weakness, malaise, irritability, and
lifelong effects on the development of atopy. There seems to be a a general sense of not looking or feeling well.[142] Probing ques-
critical period during early infancy when an individual who is tions may uncover additional clues such as snoring, poor appetite,
genetically predisposed to atopy is at greatest risk of sensitization learning and attention problems, and sleep disturbances. As men-
upon exposure to food or aeroallergens.[4,19] Early signs of atopy tioned, allergic rhinitis commonly coexists with other comorbidi-
that may herald allergic rhinitis include food allergies during ties and atopic conditions, the presence of which adds to the
infancy and early childhood, which begin with atopic dermatitis likelihood of a diagnosis of allergic rhinitis. A diagnosis of allergic
and may be accompanied by nasal or gastrointestinal symp- rhinitis is often overlooked because its presentation can be con-
toms.[4,138-140] Upon repeated exposure to aeroallergens, which fused with that of recurrent upper respiratory tract infections.
may be constantly present in the home or recur annually with the Features indicative of infectious rhinitis are the presence of sore
seasons, the clinical expression of atopy may progress to allergic throat accompanied by fever, purulent secretions after the third
rhinitis and/or asthma later in childhood. Reactions to seasonal day, and the absence of associated atopic symptoms or conditions.
allergens usually do not appear until after the child is 2–3 years old The primary purpose of a physical examination is to eliminate
because at least two seasons of exposure are required to elicit anatomic abnormalities as the cause of rhinitis. Mechanical ob-
sensitization.[38,139] However, by 4 years of age, approximately struction can be distinguished from allergic rhinitis by the absence
28% of children are atopic, and sensitization to inhaled allergens of sneezing, rhinorrhea, and itching.[33] In allergic rhinitis, nasal
(19.2%) are considerably more common than to foods discharge is usually thin and clear, unless there is comorbid
(3.5%).[139,140] The incidence of rhinitis increases throughout sinusitis, in which case there may be postnasal drip and cough. The
childhood, peaking at 12–15 years of age.[139,141] Symptoms usu- turbinates appear pale, boggy, and cyanotic.[117,135] Patients may
ally worsen for the first two or three seasons and then stabilize, complain of fullness and ‘popping’ of the ears; itchiness of the
although they may entirely disappear in approximately 20% of eyes, ears, throat, or palate; and loss of the sense of smell and taste.
children. While sinusitis in older children usually manifests as pressure over
the cheeks and around the eyes, young children do not usually
A great deal can be learned about the possible presence of
have headaches or facial pain or pressure, instead, persistent
allergic rhinitis from the patient’s physical appearance at the initial
cough, nasal congestion, halitosis, and irritability are indicative of
visit. This is particularly true of children with severe rhinitis, in
sinusitis.[21,37,85,86]
whom casual observation of the following three facial hallmarks
While ancillary tests are de rigeur for allergists, they are seldom
of allergic rhinitis can provide the first hints.
used in the primary care setting. However, certain tests may be
• The ‘allergic shiner’, a darkening of the lower eyelid due to helpful in confirming suspected allergic rhinitis, particularly cyto-
suborbital edema. logic tests of nasal secretions to detect the presence of eosinophils
• The ‘allergic crease’, a transverse skin line above the tip and or neutrophils, which are commonplace in allergic rhinitis and
below the bridge of the nose caused by constant rubbing. sinusitis, respectively.[3,4,143] In patients between 4 months and 7

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
240 Berger

years of age, the levels of nasal eosinophils and basophils correlate


highly with one another, and high levels of both are indicative of
aeroallergen sensitization.[4] Nasal allergen challenge tests in chil-
dren are reserved for research purposes.[144] Standard radiographs
and CT scans may be useful in patients with chronic sinusitis, and
CT scans can also help visualize septal deviation.
One of the most important aspects of the physical examination
is the identification of allergic triggers that provoke symptoms.
For the most part, triggers of seasonal allergic rhinitis are pollens,
and the onset of symptoms coincides with pollen production. In
temperate climates, tree pollens are produced in early Spring and
elicit the fewest reactions (9%); grass pollens appear in late Spring
and early Summer and elicit an intermediate frequency of reac-
tions (40%); and ragweed pollens, which cause hay fever, appear
in late summer and early fall and elicit the most prevalent reactions
(75%).[16] Perennial allergens found year-round in the indoor
environments include dust mites, molds, cockroach parts, products
that contain feathers, and animal saliva and dander. SPTs are the
gold standard for identifying specific allergens, with the caveat
that a positive result in children <2 years old produces a smaller
wheal-and-flare than in older children due to lower levels of
specific IgE.[4,38,117,142,144,145] In vitro tests are an expensive alterna-
tive that should be limited to patients who cannot tolerate skin Fig. 1. Patient rhinitis screen.
testing.[144] In the absence of definitive SPTs, which are used
infrequently in the primary care setting, the recently developed severe, patients must exhibit either disrupted sleep, daily function-
Patient Rhinitis Screen can aid in identifying an allergic etiology al impairment, abnormal school performance, or troublesome
and specific triggers (see figure 1).[146] Created by allergists specif- symptoms. The severity of the responses along with the spectrum
ically for use by primary care practitioners, the Patient Rhinitis of response directs the selection of the optimal management pro-
Screen is a patient questionnaire that separates triggers into aller- gram for the individual patient with rhinitis.
gens and nonimmunogenic irritants, and records the temporal
Most patients with allergic rhinitis initially present to the pri-
pattern of symptom exacerbation.
mary care setting, either with complaints suggesting allergic rhini-
To replace older guidance, which is organ specific and fails to tis, or with unrecognized allergic rhinitis. In either event, the Joint
account for the range of comorbidities of rhinitis, the WHO has Task Force on Practice Parameters in Allergy, Asthma, and Immu-
recently proposed the Allergic Rhinitis and its Impact on Asthma nology suggests in its 1998 guidelines that the initial evaluation of
(ARIA) guidelines.[3,147] These guidelines, intended for non- a patient with rhinitis symptoms be performed by a primary care
specialists as well as specialists in allergy/immunology, otorhino- physician.[4] Based on findings at the initial evaluation, the patient
laryngology, and pneumonology, are evidence based, address co- should either be treated empirically in the primary care setting or
morbidities of rhinitis and pediatric issues, and link management referred to an allergist-immunologist for consultation. Indications
strategies to the diagnosis.[3,147] In addition, the ARIA guidelines for referral include:
reclassify allergic rhinitis in a manner similar to the three-tiered
approach used to classify asthma and propose changes in terminol- • a prolonged history of rhinitis;

ogy used to describe rhinitis. Under these guidelines, rhinitis is • the presence of complications (e.g. otitis media, sinusitis) or
described as intermittent or persistent, with gradations from mild comorbid allergic or respiratory conditions (e.g. asthma);
to moderate to severe in each of these two categories (see figure 2). • prior corticosteroid use or prolonged treatment with multiple
Persistent rhinitis is defined as being present for more than 4 days/ medications;
week, at least 4 weeks annually. To be considered moderate to • treatment that is either ineffective or produces adverse events;

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
Allergic Rhinitis in Children 241

• symptoms that significantly interfere with the patient’s func- D. farinae, those subsequently exposed to the lowest levels (<2
tional ability (e.g. sleep disturbances, impaired work perform- μg/g) of allergen showed the greatest conversion to negative SPTs
ance) or reduce quality of life; after 2.4 years.[149]
• the need to further define allergic/environmental triggers of
Depending upon the allergen, avoidance may entail several
rhinitis.
steps (see table II). For perennial allergens, increasing ventilation
4. Management of Allergic Rhinitis in Children and purifying indoor air can help minimize exposure, but the most
effective approach is removal of the allergen.[3,4,142] Washing of
In recent years, preventive strategies have gained prominence
pets, especially cats, is significantly less effective than washing
in the management of allergic rhinitis. Two preventive measures
contaminated items and/or removing the animal from the home,
used in treating allergic rhinitis are avoidance of identified triggers
although this can be emotionally difficult.[144,148] A good compro-
by environmental control and the use of immunotherapy.[3,4] To-
gether with pharmacotherapy, they constitute a tripartite approach mise is having the pet live outdoors. Avoidance of dust mites
to the management of allergic rhinitis. requires a concerted effort to both control the reservoirs that serve
as breeding grounds and reduce humidity to below 50%, partic-
4.1 Environmental Control ularly in the patient’s bedroom.[3,142,144,148] Since dust mites thrive
on exfoliated human skin, frequent washing of bedding with
Logic dictates that eliminating the presence of an offending
allergen can prevent symptom exacerbation; however, this ap- special cleansers and encasing mattresses and pillows with imper-
proach requires identification of the offending allergen, and its meable allergen-proof coverings is required.[3,4,141,144] When of-
success varies with the allergen. In atopic families, parents should fending pollens are in season, it is important to keep windows and
be instructed about the importance of allergen avoidance during
Table II. Allergen avoidance measures
early infancy and childhood when sensitization first occurs.[4,148]
Alternatively, secondary prevention, when avoidance is initiated House dust mites

sufficiently early following sensitization, may reduce IgE produc- Enclose mattress, box spring, and pillows in allergen-proof casings

tion and abolish sensitization.[144,148] For example, in children with Wash bed linen weekly in hot water (130°F)

positive SPTs to Dermatophagoides pteronyssinus and/or Reduce indoor humidity to <50%


Vigorously clean inside the house, including closets and furniture

Allergic rhinitis Use benzyl benzoate or tannic acid cleanser


Remove curtains from bedroom windows or wash frequently
Remove carpeting from floors
Replace feather duvets and pillows with synthetic products
Intermittent Persistent Remove stuffed animals from bed, or wash them weekly
• ≤4 days per week or • >4 days per week and Use a HEPA filter
• ≤4 weeks per year • >4 weeks per year
Pollens and outdoor molds
Avoid fresh-cut grass, do not mow lawn
Use air conditioning on an indoor cycle and an air purifier
Mild Moderate-severe Reduce outdoor exposure during periods of high pollen counts and stay
One or more items: inside with windows and doors closed
• Normal sleep
• No impairment of daily Shower after outdoor activities to remove pollen and avoid contaminating
activities, sport, leisure • Abnormal sleep
• Impairment of daily bedding
• Normal work and school
functioning and activities, sport, leisure Pets
• No troublesome symptoms • Abnormal work and school
functioning Remove pet from the home whenever possible
• Troublesome symptoms
Consider making the pet an outdoor animal
Fig. 2. Proposed classification of rhinitis by the WHO. Revised classifica- Cat allergen can be reduced by frequent (every 2 weeks) bathing of the
tion of allergic rhinitis based on recommendations presented in the WHO cat
guidelines. Rhinitis is classified as either intermittent or persistent, each
Thoroughly wash cat-contaminated items
category being further subdivided by symptom severity into either mild or
moderate to severe.[3] HEPA = high efficiency particulate air.

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
242 Berger

doors closed, with air conditioning and air purifiers circulating primarily in patients with asthma, its benefits far outweigh the
indoor air.[4,142,148] potential risks; patients should be observed for 20–30 minutes
following therapy for signs of anaphylaxis.[3,4,71,141,173-176]
4.2 Immunotherapy Recent efforts have focused on determining the efficacy and
safety of alternatives to the standard subcutaneous delivery route
Traditionally, immunotherapy has been reserved for patients for immunotherapy, some of which may be more convenient for
with severe symptoms of rhinitis, asthma, or Hymenoptera ana- children, and on combining standard immunotherapy with mono-
phylaxis, who cannot avoid allergen exposure, as described in the clonal anti-IgE antibody treatment. Some studies, but not all, have
1998 WHO position paper on immunotherapy.[4,141,150] However, shown intranasal or oral immunotherapy to be effective in adults,
increasing evidence indicates that rather than merely being a but more studies have demonstrated efficacy and safety of sublin-
treatment, immunotherapy may actually provide prophylaxis capa- gual immunotherapy (SLIT) in adults and children.[177-191] SLIT
ble of altering the clinical course of allergic rhinitis by preventing has been evaluated for the treatment of allergies to house dust
the development of multiple sensitizations and asth- mites, ragweed pollen, and grass pollen in children with asthma
ma.[3,71,73,151-157] In fact, a recent retrospective review of 1000 and/or allergic rhinitis and the efficacy of SLIT appears to be long
patients with allergic rhinitis treated with immunotherapy revealed lasting (>4–5 years). Adverse effects are manageable and are
a complete response in 860 patients (symptoms improved to the primarily oral itching/burning and gastrointestinal symptoms. The
extent that the need for further pharmacologic treatment was WHO considers SLIT to be an acceptable therapy for respiratory
eliminated) and a partial response in the remaining 140 patients allergies in children.[188]
(improvement enabled the use of pharmacotherapy only to control
breakthrough symptoms).[158] 4.3 Pharmacologic Treatment
These notions on the prophylactic role of immunotherapy were
recently endorsed by the American College of Allergy, Asthma, In most patients with allergic rhinitis, avoidance and supportive
and Immunology and have prompted the WHO to define allergen measures do not provide adequate control of symptoms, necessi-
immunotherapy as ‘therapeutic vaccination’.[150,159] The effective- tating treatment with pharmacologic therapy. A progressive man-
ness of immunotherapy has been demonstrated by its ability to agement strategy, the ARIA guidelines (see also section 3), has
prevent new sensitizations in adults and children with asthma who been proposed by the WHO that integrates diagnosis and treatment
were monosensitized to house dust mites, and to induce prolonged by focusing on symptomatology and effect on quality of life.[3,192]
(up to 6 years) remissions in adults and children with seasonal The paradigm for this stepwise approach is to provide evidence-
allergic rhinitis undergoing grass pollen immunotherapy.[72,160-163] based treatment that addresses symptoms and then to evaluate
Additionally, the preventive allergy treatment studies conducted treatment response. Accordingly, in addition to avoidance mea-
by Moller et al. have shown that grass pollen immunotherapy can sures that remain the cornerstone of management, the guidelines
prevent the development of asthma in children with allergic rhini- recommend oral or intranasal antihistamines as first-line treatment
tis.[73,152,153] Pathophysiologic evidence indicates that immuno- for mild intermittent allergic rhinitis, and supplementation with
therapy accomplishes this by inhibiting allergen-induced increases brief courses (<10 days) of intranasal decongestants (see figure 3).
in nasal basophils and eosinophils, reducing the levels of early- For moderate-to-severe intermittent rhinitis, the guidelines recom-
and late-phase response mediators (e.g. histamine, kinins, TAME- mend oral or intranasal antihistamines, intranasal corticosteroids,
esterase), and triggering a switch from Th2 to Th1 cytokine pro- and cromolyn sodium (sodium cromoglicate). Persistent allergic
duction.[3,71,157,164-172] rhinitis requires maintenance therapy that should be re-assessed
Guidelines for the administration of immunotherapy have been 2–4 weeks after initiation of treatment. First-line therapy for mild
published by numerous international organizations.[3] Most recom- persistent allergic rhinitis is antihistamines (oral or intranasal) or
mend that immunotherapy only be initiated in children when high- cromolyn sodium, which should be ‘upgraded’ to intranasal corti-
quality allergen extracts are available, the efficacy and safety of costeroids if improvement is inadequate. Patients with moderate-
which have been documented in clinical studies.[4] For maximal to-severe persistent disease who do not respond to intranasal
effectiveness, immunotherapy should be initiated early in the corticosteroids should be further evaluated to determine the cause
course of allergic rhinitis.[71,150,157] Although immunotherapy does of treatment failure. Symptom-specific treatments can be com-
carry a low (one fatality per 2 million doses) risk of fatality, bined with intranasal corticosteroids to alleviate persistent symp-

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
Allergic Rhinitis in Children 243

Allergic rhinitis

Mild intermittent Moderate-severe intermittent Mild persistent Moderate-severe persistent

Oral or intranasal Oral or intranasal Oral or intranasal Intranasal corticosteroids


antihistamine antihistamine antihistamine If no response
Or Or Or evaluate reason for
cromoglycate sodium cromolyn cromoglycate treatment failure
± and add
Or If no improvement use
intranasal decongestant antihistamine for
intranasal corticosteroids intranasal corticosteroids
(<10 days) sneezing, itching or
± rhinorrhea
intranasal decongestant
Ipratropium bromide for
(<10 days)
rhinorrhea
After 3 months
step down to mild persistent
therapy

Fig. 3. Algorithm for step approach to treatment.[3,192]

toms; antihistamines can be administered for sneezing, itching, or on congestion or postnasal drainage (table III).[4,111,114,124,193-198]
rhinorrhea, or ipratropium bromide for rhinorrhea alone. As symp- The second-generation antihistamines have enhanced specificity
toms improve (e.g. after 3 months of therapy during the pollen and do not cross the blood-brain barrier, resulting in less sedation
season), treatment should be reduced in a stepwise fashion. than the first-generation antihistamines.[193-197] Four second-gener-
As a consequence of its exclusive focus on allergic rhinitis, this ation oral antihistamines have been approved for use in children in
type of treatment algorithm represents an improvement over that the US: cetirizine, fexofenadine, and loratadine and its major
of the 1998 guidelines issued by the Joint Task Force on Practice metabolite desloratadine. Desloratadine, thus far only approved
Parameters in Asthma, Allergy, and Immunology (see also section for children >12 years of age, has been shown to be more potent
3) which also emphasises the importance of obtaining a differ- than loratadine in preclinical studies and has some effect on nasal
ential diagnosis of rhinitis.[4] Treatment recommendations of the congestion as evaluated as part of the total symptom com-
International Consensus Report on the Diagnosis and Management plex.[199,200] Most of these antihistamines also possess anti-inflam-
of Rhinitis are similar to the ARIA guidelines, except that they do matory activities such as inhibiting the synthesis and release of
not delineate a stepwise approach.[141] They recommend use of mediators, impeding the influx of inflammatory cells, including T
either oral nonsedating antihistamines, topical antihistamines, or lymphocytes, and reducing the expression of adhesion mole-
topical cromolyn sodium for mild occasional symptoms of allergic
cules.[194-196,198,201-211] The absence of sedative effects is critical for
rhinoconjunctivis; oral nonsedating antihistamines or intranasal
children, since rhinitis itself can impair cognition. As demonstra-
corticosteroids plus topical cromolyn sodium for moderate allergic
ted in a study comparing diphenhydramine, a first-generation
rhinoconjunctivitis with prominent eye symptoms; and combina-
antihistamine, with loratadine and placebo in children with aller-
tion therapy with an intranasal corticosteroid and either a topical
gic rhinitis, and in a group of age-matched nonatopic control
antihistamine or topical cromolyn sodium for moderate rhinocon-
individuals, cognition in all the atopic children was considerably
junctivitis with prominent nasal symptoms.
poorer than in their nonatopic peers.[212] While these effects were
4.3.1 Antihistamines
not reversed by loratadine, they were exacerbated by diphenhydra-
Antihistamines, which act as reversible competitive antagonists mine.
of histamine at the H1 receptor, have a rapid onset of action and Topical antihistamines are potentially useful alternatives in
effectively reduce symptoms of rhinorrhea, pruritus, and sneezing, children. The topical antihistamines, represented by azelastine
as well as conjunctivitis, although most have little objective effect and, in some countries outside the US, levocabastine, possess anti-

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
244 Berger

Table III. Effectiveness of pharmacologic therapy for allergic rhinitis


Pharmacologic agent Early Late Inflammation Congestion Rhinorrhea Sneezing Nasal Ocular
phase phase pruritus symptoms
Cromoglycates + + ± ± ± ± ± ±
Anticholinergics – – – – + – – –
Decongestants – – – + – – – –
Topical corticosteroids ± + + + + + ? ±
First-generation oral + – ? – + + + +
antihistamines
Second-generation oral + ? ? ± + + + +
antihistamines
Topical antihistamines + + ? + + + + +
+ indicates prominent effect; ± indicates moderate effect; – indicates little effect; ? indicates unknown.

inflammatory activities. Azelastine was recently approved for use and mometasone, which was recently approved for use in children
in children over 5 years of age with allergic rhinitis. It has been 3 years of age and over.[142,244]
shown to relieve sneezing, postnasal drip, rhinorrhea, cough, Although the adverse effect profiles of the intranasal cortico-
conjunctival symptoms, and itching of the nose, eyes, ears, throat, steroids are markedly improved over those of oral corticosteroids,
and palate in 93% of patients between 6 and 11 years of age.[213,214]
caution is still required. Local adverse effects can include nasal
The clinical efficacy of azelastine undoubtedly reflects its spec-
irritation and low frequencies of ocular effects, bloody nasal
trum of anti-inflammatory properties: reducing the synthesis of
discharge, and septal perforation.[4,244-246] Patients should be con-
Th2 cytokines, interfering with tyrosine phosphorylation, decreas-
tinually monitored for the presence of mucosal erosions, the
ing the expression of several oncogenes, and diminishing expres-
predecessor to septal perforation, and instructed to direct the spray
sion of the transcriptional activator nuclear factor-κβ, which regu-
lates gene expression.[213-224] away from the septum.[4] The potential growth-suppressive effects
of intranasal corticosteroids in children have also raised concern
4.3.2 Cromoglycates and have prompted these agents to be class labeled by the US
Mast cell stabilizers, such as intranasal cromolyn sodium, FDA.[4] One study of beclomethasone showed growth suppression
which are available without prescription in the US, prevent the of 1cm in children treated for 1 year, and another implicated
degranulation and release of mediators from mast cells.[4,142,225] budesonide.[247,248] However, these effects were shown to be mini-
They are considered the safest allergic rhinitis treatments avail- mal with fluticasone in the short term and, over 1 year, for
able, ideal for the pediatric population, and are effective for mometasone.[249,250] Long-term studies of intranasal, or even in-
pruritus, sneezing, and rhinorrhea (table III). However, for maxi- haled, corticosteroids have shown virtually no effect on final adult
mal effectiveness they must be administered prophylactically prior height.[251-254] Thus, concerns about growth suppression are not
to allergen exposure, and must be administered every 4 hours, reflective of the results of the newer, long-term studies and there-
which may interfere with adherence. fore should not be a reason to eliminate these effective agents from
the treatment armamentarium for allergic rhinitis.[254]
4.3.3 Corticosteroids
Corticosteroids, the most potent drugs available for treating
4.3.4 Decongestants
seasonal and perennial allergic rhinitis (table III), act at the cellular
and molecular levels to prevent the synthesis and release of Intranasal decongestants are α-adrenergic agonists that cause
cytokines; inhibit the IgE-mediated release of basophil- and mast local vasoconstriction and thereby reduce congestion (table
cell-derived mediators; and reduce the recruitment and circulatory III).[4,142,245] While long-acting topical decongestants such as oxy-
levels of proinflammatory cells.[226-243] Six topical intranasal corti- metazoline are more convenient, they should not be used for more
costeroids have been approved for use in the US for children than 5–7 days (rebound congestion can develop).[4,38] Because of
6 years of age and older with allergic rhinitis: beclometasone, their cardiovascular adverse effects, oral decongestants are not
budesonide, flunisolide, fluticasone propionate, triamcinolone, recommended for children.[3]

© 2004 Adis Data Information BV. All rights reserved. Pediatr Drugs 2004; 6 (4)
Allergic Rhinitis in Children 245

4.3.5 Anticholinergics Acknowledgments


Topical anticholinergics reduce secretions induced by parasym-
pathetic stimulation, and may have a slight effect on congestion. Preparation of this review was supported by an unrestricted educational
Ipratropium bromide is effective in reducing both the severity and grant from MedPointe Inc. Dr Berger serves in a consulting capacity for
multiple pharmaceutical companies including MedPointe Inc.
duration of rhinorrhea in children and adults.[4] It is particularly
beneficial in perennial allergic rhinitis, and its combined use with
beclomethasone was found to be superior to either agent alone for References
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Leukotriene antagonists, which include montelukast and zafir- 3. Bousquet J, the Allergic Rhinitis and its Impact on Asthma (ARIA) Workshop
Group. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol 2001
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management of allergic rhinitis with proven clinical benefit in 4. Dykewicz M, Fineman S. Diagnosis and management of rhinitis: complete guide-
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