Key Points
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There are many different causes of rhinitis in children and 50% of all cases of rhinitis are caused by allergy.
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On the basis of timing and duration of allergen exposure, allergic rhinitis is classified as seasonal, perennial or mixed (perennial with seasonal exacerbation).
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A careful history and physical examination are the most effective diagnostic tools for the identification of allergic rhinitis in children.
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Diagnostic tests for allergic rhinitis include in vivo skin testing and in vitro serum IgE antibody immunoassay.
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Specific treatment options for allergic rhinitis include environmental control for allergen avoidance, pharmacotherapy and immunotherapy.
Rhinitis is defined as inflammation of the membranes lining the nose and is characterized by one or more of the following nasal symptoms: sneezing, itching, rhinorrhea and nasal congestion. Rhinitis is frequently accompanied by symptoms that involve the eyes, ears and throat. Approximately 50% of all cases of rhinitis are caused by allergy. In allergic rhinitis, symptoms arise as a result of inflammation induced by an immunoglobulin E (IgE)-mediated immune response to specific allergens that involves the release of inflammatory mediators and the activation and recruitment of cells to the nasal mucosa. A careful history and physical examination are the most effective tools for diagnosing allergic rhinitis, and specific diagnostic testing should be pursued when indicated. Management options for allergic rhinitis include treatment with pharmacologic agents and preventative measures such as environmental controls and immunotherapy.
Epidemiology
There are several limitations regarding epidemiologic studies of allergic rhinitis. First, most data regarding the true prevalence of allergic rhinitis are difficult to interpret because the majority of studies use either a physician diagnosis of disease or results from patient-administered surveys and/or phone interviews. Results of both types of studies are likely to under-report the actual prevalence of allergic rhinitis. Additionally, most epidemiologic studies focus on seasonal allergic rhinitis because of the easy identification of symptoms association with pollen exposure. Perennial allergic rhinitis is more difficult to identify because its symptom complex often overlaps with chronic sinusitis, recurrent upper respiratory tract infections and vasomotor rhinitis.
The current prevalence of allergic rhinitis in the USA is reported to be approximately 30% for adults and 42% for children. In 2013, allergic rhinitis was reported to affect about 60 million people in the USA, with about 40% of those affected being children. The Allergies, Immunotherapy, and RhinoconjunctivitiS (AIRS) surveys reported seasonal symptoms in 78% of subjects with the most common triggers being pollen (53%), dust (26%) and grass (26%), and nasal congestion being the most bothersome symptom. The frequency of allergic rhinitis in the general population has risen in parallel with that of all IgE-mediated diseases during the past decade. The International Study of Asthma and Allergies in Childhood (ISAAC) showed that the prevalence of allergic rhinitis in US children rose from 13.4% in 1994 to 19.1% in 2003.
Sex
At ages 6 to 7, boys with allergic rhinitis outnumber girls; however, at ages 13 to 14, girls outnumber boys. In general, equal numbers are affected during adulthood.
Age
Symptoms of allergic rhinitis develop before the age of 20 years in approximately 80% of cases. Children in families with a bilateral family history of allergy generally have symptoms before puberty; those with a unilateral family history tend to have symptoms later in life or not at all.
Risk Factors
The frequency of allergic rhinitis increases with age and positive allergy skin tests have been identified as a significant risk factor for disease development. Disease prevalence is higher in more affluent socioeconomic classes, minorities, areas with heavy outdoor air pollution, individuals with a family history of allergy, firstborn children and individuals born during pollen season. Childhood studies have confirmed that disease risk is increased in those with early introduction of food or formula, maternal tobacco smoking, indoor allergen exposure, elevated serum IgE levels, positive allergy skin tests and parental allergic disorders. Recent studies demonstrated associations between obesity, nutrition, vitamin D deficiency, stress/anxiety, poor housing and allergic predisposition. Maternal diets high in antioxidants and omega-3 fatty acids, and pediatric diets high in antioxidants and food diversity are associated with decreased risks of atopy. Additionally, probiotics have been found to be effective in treating pediatric atopy.
Socioeconomic Impact
Because of the high prevalence of allergic rhinitis, impaired quality of life, costs of treatment and the presence of co-morbidities such as asthma, sinusitis and otitis media, it has a tremendous impact on society. The severity of allergic rhinitis ranges from mild to seriously debilitating. The cost of treating allergic rhinitis and indirect costs related to loss of workplace productivity resulting from the disease are significant and substantial. Allergic rhinitis was noted as the illness that caused the greatest loss of productivity in the workplace. The estimated cost of allergic rhinitis, based on direct and indirect costs, was approximately $11 billion for 2005, exclusive of costs for associated medical problems such as sinusitis and asthma. In children with allergic rhinitis, the quality of life of both the parents and the child, including the ability to learn, may be affected.
Pathophysiology
Under normal conditions, the nasal mucosa quite efficiently humidifies and cleans inspired air. This is the result of orchestrated interactions of local and humoral mediators of defense. In allergic rhinitis, these mechanisms do not function appropriately and contribute to signs and symptoms of the disorder.
Components of the Allergic Response
The tendency to develop IgE, mast cell and T helper cell type 2 (Th2) lymphocyte immune responses is inherited by atopic individuals. Exposure to threshold concentrations of allergens for prolonged periods of time leads to the presentation of the allergen by antigen-presenting cells to CD4 + T lymphocytes, which then release interleukin (IL)-3, -4 and -5 and other Th2 cytokines. These cytokines drive proinflammatory processes, such as IgE production, against these allergens through the mucosal infiltration and actions of plasma cells, mast cells and eosinophils. Once an individual becomes sensitized, subsequent exposures trigger a cascade of events that result in the symptoms of allergic rhinitis. The response in allergic rhinitis can be divided into two phases: the early-phase response and the late-phase response.
Early Phase
During periods of continuous allergen exposure, increasing numbers of IgE-coated mast cells traverse the epithelium, recognize the mucosally deposited allergen, and degranulate. Products of this degranulation include preformed mediators such as histamine, tryptase (mast cell-specific marker), chymase (connective tissue mast cells only), kininogenase (generates bradykinin), heparin and other enzymes. In addition, mast cells secrete several inflammatory mediators de novo, including prostaglandin D 2 and sulfidopeptidyl leukotrienes C 4 , D 4 and E 4 . These mediators cause blood vessels to leak and produce the mucosal edema and watery rhinorrhea that are characteristic of allergic rhinitis. Glands secrete mucoglycoconjugates and antimicrobial compounds and dilate blood vessels to cause sinusoidal filling and thus occlusion and congestion of nasal air passages. These mediators also stimulate sensory nerves, which convey the sensation of nasal itch and congestion, and recruit systemic reflexes such as sneezing. These responses develop within minutes of allergen exposure and thus constitute the early-phase allergic response. Sneezing, itching and copious, clear rhinorrhea are characteristic symptoms during early-phase allergic responses, although some degree of nasal congestion can also occur.
Late Phase
The mast cell-derived mediators released during early-phase responses are hypothesized to act on postcapillary endothelial cells to promote the expression of vascular adhesion molecule and E-selectin, which facilitate the adhesion of circulating leukocytes to the endothelial cells. Chemoattractant cytokines such as IL-5 promote the infiltration of the mucosa with eosinophils, neutrophils and basophils, T lymphocytes and macrophages. During the 4- to 8-hour period after allergen exposure, these cells become activated and release inflammatory mediators, which in turn reactivate many of the proinflammatory reactions of the immediate response. This cellular-driven, late inflammatory reaction is termed the late-phase response . This reaction may be clinically indistinguishable from the early phase, but congestion tends to predominate. Eosinophil-derived mediators such as major basic protein, eosinophil cationic protein and leukotrienes have been shown to damage the epithelium, leading ultimately to the clinical and histologic pictures of chronic allergic disease.
Subsets of the T helper lymphocytes are the likely orchestrators of the chronic inflammatory response to allergens. Th2 lymphocytes promote the allergic response by releasing IL-3, IL-4, IL-5 and other cytokines that promote IgE production, eosinophil chemoattraction and survival in tissues and mast cell recruitment. Cytokines released from Th2 lymphocytes and other cells may circulate to the hypothalamus and result in fatigue, malaise, irritability and neurocognitive deficits that are commonly noted in patients with allergic rhinitis. Cytokines produced during late-phase allergic responses can be reduced by glucocorticoids.
Role of Th17 Cells
Recently, Th17 cells have been identified as an important regulator of immune responses in allergic rhinitis. These cells produce IL-17A which increases the production of proinflammatory cytokines. After an allergic subject is challenged intranasally with a relevant allergen repeatedly, the amount of allergen required to produce an immediate response decreases. This effect is termed priming and is hypothesized to be a result of the influx of inflammatory cells that occurs during late-phase allergic responses, with IL-17A having a role in priming toward the development of immune responses against new allergens. This response is clinically significant because exposure to one relevant allergen may promote an exaggerated response to other allergens in a susceptible individual. The priming phenomenon highlights the need to fully identify the spectrum of allergens to which an individual patient reacts. Additionally, it emphasizes the need to intervene in the allergic cascade at an early time point via the prompt initiation of preseasonal, prophylactic, antiinflammatory therapy.
Classification
Allergic rhinitis is classified as seasonal or perennial based on the timing and duration of allergen exposure. Overall, approximately 20% of all cases are strictly seasonal, 40% are perennial, and 40% are mixed (perennial with seasonal exacerbation).
Seasonal Allergic Rhinitis
Tree, grass and weed pollens and outdoor mold spores are common seasonal allergens. The symptoms typically appear during a defined season in which aeroallergens are abundant. The length of seasonal exposure to these allergens is dependent on geographic location. Therefore, familiarity with the pollinating season of the major trees, grasses and weeds of the locale makes the syndrome easier to diagnose. Certain outdoor mold spores also display seasonal variation with the highest levels in the summer and fall months.
Typical symptoms during pollen exposure include the explosive onset of profuse, watery rhinorrhea; nasal congestion and itching; and sneezing; along with frequent allergic symptoms of the eye. The onset and offset of symptoms usually track the seasonal pollen counts. However, hyperresponsiveness to irritant triggers, which develops from the inflammatory reaction of the late phase and priming responses, often persists after cessation of the pollen season. Such triggers include tobacco smoke, noxious odors, changes in temperature, and exercise.
Perennial Allergic Rhinitis
Year-round exposure to dust mites, cockroaches, indoor molds and cat, dog and other danders leads to persistent tissue edema and infiltration with eosinophils, mast cells, Th2 lymphocytes and macrophages. Perennial allergic rhinitis can also be caused by pollen in areas where pollen is prevalent perennially.
A universally accepted definition of perennial rhinitis does not exist. Most often, it is defined as persisting for longer than 9 months each year and producing two or more of the following symptoms: serous or seromucus hypersecretion, nasal blockage caused by a swollen nasal mucosa, and sneezing paroxysms. Nasal congestion and mucus production (postnasal drip) symptoms predominate in most patients, and sneezing, itching and watery rhinorrhea may be minimal. Because late-phase reactivity is commonly ongoing, it becomes difficult to distinguish early- from late-phase reactions, therefore the history of trigger factor exposure is often difficult to decipher.
Perennial Allergic Rhinitis with Seasonal Exacerbation
Symptoms of allergic rhinitis may also be perennial with seasonal exacerbation, depending on the spectrum of allergen sensitivities.
Differential Diagnosis
The causes of rhinitis are summarized in Box 24-1 . The most common form of nonallergic rhinitis in children is infectious rhinitis. The symptoms of allergic rhinitis are frequently confused with those of infectious rhinitis when patients complain of a constant cold. Symptoms persisting longer than 2 weeks should prompt a search for a cause other than acute viral infection. If tests for atopy are negative, foreign body rhinitis should be considered in the differential diagnosis. In such cases, symptoms may be acute or chronic and unilateral or bilateral, and the nasal discharge may be bloodstained or foul smelling. Exacerbation of rhinitis symptoms with predominant, clear rhinorrhea in patients with a known history of allergic rhinitis may be difficult to diagnose. The difference between active infection and allergy should be noted. When the history or physical examination is not diagnostic, a nasal smear may be obtained to aid in differentiation. The presence of more than 5% eosinophils suggests allergic disease, whereas a predominance of neutrophils suggests infection.
Allergic Rhinitis
Seasonal
Perennial
Perennial with seasonal exacerbation
Nonallergic Rhinitis
Structural/mechanical factors
Deviated septum/septal wall anomalies
Hypertrophic turbinates
Adenoidal hypertrophy
Foreign bodies
Nasal tumors
Benign
Malignant
Choanal atresia
Infectious
Acute
Chronic
Inflammatory/immunologic
Wegener granulomatosis
Sarcoidosis
Midline granuloma
Systemic lupus erythematosus
Sjögren’s syndrome
Nasal polyposis
Physiologic
Ciliary dyskinesia syndrome
Atrophic rhinitis
Hormonally induced
Hypothyroidism
Pregnancy
Oral contraceptives
Menstrual cycle
Exercise
Atrophic
Drug induced
Rhinitis medicamentosa
Oral contraceptives
Antihypertensive therapy
Aspirin
Nonsteroidal antiinflammatory drugs
Reflex induced
Gustatory rhinitis
Chemical or irritant induced
Posture reflexes
Nasal cycle
Environmental factors
Odors
Temperature
Weather/barometric pressure
Occupational
Nonallergic Rhinitis with Eosinophilia Syndrome
Perennial Nonallergic Rhinitis (Vasomotor Rhinitis)
Emotional Factors
Allergy, mucociliary disturbance and immune deficiency may predispose certain individuals to the development of chronic infection. Mucociliary abnormalities may be congenital, as in primary ciliary dyskinesia, Young syndrome or cystic fibrosis, or they may be secondary to infection. Similarly, immune deficiency may be congenital or acquired.
Tumors or nasal polyps ( Figure 24-1 ) as well as other conditions (e.g. nasal septal deviation, adenoidal or nasal turbinate hypertrophy) can produce nasal airway obstruction. Nasal polyps are common in children with cystic fibrosis but not in children with allergic rhinitis. Nasal septal deviation and nasal turbinate or adenoidal hypertrophy may block the flow of nasal secretions, leading to rhinorrhea or postnasal drip as well as causing nasal blockage. Reduced airflow through the nasal passages in infants may be caused by congenital choanal atresia. Refractory, clear rhinorrhea may be caused by cerebrospinal fluid leak, even in the absence of trauma or recent surgery.
Evaluation and Management
History and Physical Examination
A careful history and physical examination are the most effective diagnostic tools for the identification of allergic rhinitis. The key to accurate and timely diagnosis is a heightened awareness of the condition and its potential co-morbidities. Allergic rhinitis in children is often undiagnosed or misdiagnosed as other disorders such as recurrent colds. To make an accurate and efficient diagnosis, the clinician must be knowledgeable about and attentive to the symptoms and signs of rhinitis, ask specific questions directed at the presence and cause of rhinitis symptoms at each well-child visit, and understand the differential diagnosis of allergic rhinitis in children (see Box 24-1 ). The clinician must be aware of the co-morbidities of allergic rhinitis (asthma, sinusitis, otitis media), pursue specific diagnostic tests when indicated, and often administer therapeutic trials of antiinflammatory medications.
The signs and symptoms of allergic rhinitis are summarized in Box 24-2 . Typical symptoms of allergic rhinitis include sneezing, itching, clear rhinorrhea and congestion. Congestion may be bilateral or unilateral and may alternate from side to side. It is generally more pronounced at night. With nasal obstruction, the patient is likely to be a mouth breather, and snoring can be a nocturnal symptom. As such, sleep disturbances and daytime tiredness or concentration problems may indicate the presence of an allergic disorder. With chronic disease, abnormalities of facial development, dental malocclusion and the allergic facies may ensue, with an open mouth and gaping habitus.
Itching of the nose, ears, palate or throat
Sneezing episodes
Thin, clear rhinorrhea
Nasal congestion
Sinus headache
Eustachian tube dysfunction
Mouth breathing or snoring
Chronic postnasal drip
Chronic, nonproductive cough
Frequent throat clearing
Sleep disturbance
Daytime fatigue
Older children blow their noses frequently, whereas younger children do not. Instead, they sniff, snort and repetitively clear their throats. Their voices may be abnormally hyponasal. Nasal pruritus may stimulate grimacing and twitching and picking of the nose. The latter may result in epistaxis. Children often have the allergic salute, an upward rubbing of the nose with the palm of the hand. This often produces an allergic nasal crease, which is an accentuated, horizontal skin fold over the lower third of the nose. Children with allergic rhinitis may also have recurrent sinusitis or otitis media, eczema or asthma. Patients may also complain of red, itchy eyes, along with itchy throat and ears. They may also lose their senses of smell and taste. Increased symptoms are frequently noted with increased exposure to the responsible allergen.
With development of the allergic reaction, clear nasal secretions will be evident and the nasal mucous membranes will become edematous without much erythema. The mucosa appears boggy and blue-gray. With continued exposure to the allergen, the turbinates will appear swollen and can obstruct the nasal airway. Conjunctival edema, itching, tearing and hyperemia are frequent findings in patients with associated allergic conjunctivitis. Allergic rhinitis patients, particularly children with significant nasal obstruction and venous congestion, may also demonstrate edema and darkening of the tissues beneath the eyes. These ‘shiners’ are not pathognomonic for allergic rhinitis; they can also be seen in patients with chronic rhinitis and/or sinusitis.
In severe cases, especially during the peak pollen season, mucous membranes of the eyes, Eustachian tube, middle ear and paranasal sinuses may be involved. This produces conjunctival irritation (itchy, watery eyes), redness and tearing, ear fullness and popping, itchy throat and pressure over the cheeks and forehead. Malaise, weakness and fatigue may also be present. The coincidence of other allergic syndromes, such as atopic eczema or asthma, and a positive family history of atopy point toward an allergic pathology. Approximately 20% of cases are accompanied by symptoms of asthma.
Diagnostic Tests
Laboratory confirmation of the presence of IgE antibodies to specific allergens such as dust mites, pollens and animal dander is helpful in establishing a specific allergic diagnosis, especially if the history of specific allergen exposure is not clear cut. Although skin testing can be performed on any child of any age, children younger than 1 year may not display a positive reaction. Often the child with seasonal respiratory allergy will not have a positive test until after two seasons of exposure. Clinicians should be selective in the use of allergens for skin testing and should use only common allergens of potential clinical importance. The most useful allergens for testing in the child with perennial inhalant allergy are dust mite, animal dander and fungi. Allergens important in the diagnosis of seasonal allergic rhinitis are weed, grass and tree pollen. Because there is a significant geographic specificity with regard to pollens, the importance of these seasonal allergens varies not only by season of the year but also by geographic distribution. Therefore allergens used for skin testing must be individualized and should be selected on the basis of prevalence in the patient’s geographic area, as well as home and school environments.
There are two methods for specific IgE antibody testing: in vivo skin testing and in vitro serum testing. Each has advantages and disadvantages ( Table 24-1 ). At the present time, properly performed skin tests are the best available method for detecting the presence of allergen-specific IgE. The skin prick, which is also called the puncture or epicutaneous skin test , is the preferred method of IgE antibody testing. In vitro tests are acceptable substitutes for skin tests in the following circumstances: (1) the patient has abnormal skin conditions such as dermatographism or extensive dermatitis; (2) the patient cannot or did not discontinue antihistamines or other interfering medications; (3) the patient is very allergic by history and anaphylaxis is a possible risk; and (4) the patient is noncompliant for skin testing. To avoid false-negative tests, most antihistamine medications should be withheld for 72 hours because antihistamines suppress the skin results.
