Allergic Rhinitis and Associated Disorders

F. Estelle

R. Simons

Allergic rhinitis, or inflammation of the nasal mucosa, is the most common chronic disease of the respiratory tract and the most common of all allergic diseases, with physician-diagnosed allergic rhinitis occurring in up to 42% of 6-year-olds in the United States. It may be associated with allergic conjunctivitis, and also may be associated with chronic sinusitis or otitis media with effusion; moreover, 40% of young individuals with allergic rhinitis have concomitant asthma.

EPIDEMIOLOGY

Risk factors for allergic rhinitis include genetic susceptibility, early sensitization to allergens (total serum immunoglobulin E [IgE] of greater than 100 IU/mL before age 6 years), atopic dermatitis, high socioeconomic status, heavy exposure to indoor allergens, maternal tobacco smoking, and/or early introduction to cow’s milk formula or solid foods in infancy.

Allergic rhinitis is often underdiagnosed, undertreated, and trivialized because it is not life-threatening; however, it may affect appearance and behavior, and may impair cognitive and psychomotor performance. It is a major cause of school absenteeism and diminished quality-of-life in the pediatric population.

Seasonal (intermittent) allergic rhinitis is commonly caused by nonflowering, wind-carried plant pollens. In temperate climates, symptoms are caused by tree pollens during the early spring, grass pollens during the late spring and early summer, ragweed and other weed pollens during the late summer and autumn, and outdoor molds during both the spring and the autumn. Due to a priming effect on the nasal mucosa during continued daily allergen exposure, less allergen is required to trigger severe nasal symptoms late in the pollen season than is required early in the season. Perennial (persistent) allergic rhinitis is triggered by indoor allergens such as animal danders, house dust mites, and indoor molds. In subtropical and tropical climates, pollens and outdoor molds cause perennial, rather than seasonal, rhinitis. Food allergens do not trigger allergic rhinitis as such, although they may trigger nasal symptoms during full-blown anaphylaxis, a severe acute allergic reaction involving many body systems.

PATHOPHYSIOLOGY

Allergic rhinitis involves the overexpression of IgE and the interaction of specific IgE with airborne allergens. Mucosal inflammation is characterized by an epithelial accumulation of eosinophils, mast cells, and basophils, along with endothelial and epithelial cell activation, up-regulation of dendritic (antigen-presenting cells) and, in persistent disease, CD4⁺ T lymphocyte accumulation and activation. The release of chemical mediators of inflammation, including histamine and leukotrienes, from activated effector cells (primarily mast cells and basophils); the synthesis and release of T helper (Th2) cytokines (interleukin [IL]-4, IL-5, IL-9, and IL-13); and the coordinate expression of chemokine and cell adhesion molecules characterize the immediate and late allergic response.

DIAGNOSIS

The cardinal symptoms of allergic rhinitis are paroxysmal sneezing, itching (sometimes manifest as grimacing or “picking” the nose), watery, profuse rhinorrhea (nasal discharge), and nasal congestion/stuffiness. The diagnosis is based on characteristic symptoms and signs in the absence of upper respiratory tract infections, and the exclusion of other, less common disorders in the differential diagnosis (Box 424.1). Allergic rhinitis symptoms may occur not only on exposure to airborne allergens, but also on exposure to irritants such as tobacco smoke, strong odors (paint fumes, perfumes), car exhaust fumes, and other pollutants, and may be triggered by physical factors such as cold air exposure or the ingestion of hot or spicy liquids
and foods. Associated symptoms include noisy or hypernasal breathing, oronasal breathing, snoring, loss of olfaction or taste, halitosis, itching of the palate or pharynx, and repeated throat clearing or cough secondary to postnasal drip or drainage of nasal secretions into the pharynx. Ocular symptoms such as redness, itching, or tearing also may be present (see the section, Allergic Conjunctivitis). Systemic symptoms include malaise and disturbed nocturnal sleep with or without sleep apnea, and subsequent daytime fatigue.

BOX 424.1 Differential Diagnosis of Rhinitis

Allergic: seasonal (intermittent) or perennial (persistent)

Infectious: usually viral (if bacterial, consider the possibility of immune deficiency disease)

Eosinophilic nonallergic rhinitis

Vasomotor rhinitis

Sinusitis (acute, subacute, recurrent, or chronic)

Adenoid hypertrophy

Foreign body

Anatomic variations: nasal septum deviation, unilateral choanal atresia

Trauma: septal hematoma, fracture of nasal bones, synechiae

Benign tumors: nasal polyps, dermoid cysts, meningomyelocele

Malignant tumors: nasal glioma

Granulomatous disease: Wegener’s granulomatosis, sarcoid

Rhinitis medicamentosa: topical decongestants

Medications: nonsteroidal antiinflammatory agents, cocaine, some antihypertensives, beta-adrenergic blockers, oral contraceptives

Hormonal changes: hypothyroidism, pregnancy

Cerebrospinal fluid rhinorrhea

Ciliary dyskinesia

In children with allergic rhinitis, an examination of the nose sometimes reveals a transverse external wrinkle, secondary to rubbing and dorsal manipulation, also known as the “allergic salute.” Inspection through an otoscope or a flexible fiberoptic rhinoscope usually reveals edema of the nasal mucosa, which may be pale, violaceous, or red in color. Watery, opaque, or mucoid secretions may be noted in the nasal cavity or on the posterior pharyngeal wall, and there may be evidence of recent epistaxis. Nasal polyps are uncommon in children; if they are observed, the diagnosis of cystic fibrosis must be considered.

Children with allergic rhinitis may have “allergic shiners,” a term used to describe the dark discoloration of the infraorbital regions secondary to obstruction of venous drainage. If they are chronic oronasal breathers, they may have hypertrophied gingival mucosa, a gaping expression, a long, retrognathic facies with a high, narrow palate, and orthodontic anomalies such as posterior dental crossbite. Lymphoid tissue associated with the upper airways, including adenoids and tonsils, may be hypertrophied, and anterior cervical lymph nodes may be enlarged. If adenoid hypertrophy is severe, alveolar hypoventilation, hypoxemia, hypercarbia, hypoxic pulmonary vasoconstriction, and cor pulmonale may be present.

Diagnostic Tests

The diagnosis of allergic rhinitis is based on clinical history and physical examination, and it can be confirmed by the identification of eosinophils as the predominant cells in nasal secretions. Supportive evidence is provided by positive epicutaneous (prick) tests to airborne allergens such as tree, grass, and weed pollens; molds; house dust mites; and cat, dog, and other animal danders, performed along with histamine (positive) and diluent (negative) control tests. If severe atopic dermatitis precludes skin testing, or if withdrawal of an H₁-antihistamine for the requisite 7 days before skin testing is not feasible, allergen-specific IgE can be measured in serum using radioallergosorbent tests or enzyme-linked allergosorbent tests. Positive skin tests to allergen(s) and/or elevated allergen-specific IgE alone cannot be used to “diagnose” allergic rhinitis, because sensitization to allergens may occur in the absence of symptoms. Other tests, which are not necessary for the clinical diagnosis, but are useful in research, include the measurement of peak inspiratory flow, and intranasal allergen challenge under controlled conditions in the laboratory, followed by quantitation of mediators such as histamine and leukotrienes in nasal secretions and of immunochemically identified inflammatory cells in the nasal mucosa.

THERAPY

Treatment involves both pharmacologic and nonpharmacologic approaches (Table 424.1). Allergic rhinitis itself never
causes mortality, and it is therefore essential that the medications used to treat this disease are safe for long-term use in children; specifically, that they do not adversely affect linear growth, cognitive or psychomotor development, behavior, or sleep. Pharmacologic management must be individualized: requirements range from an antihistamine as-needed in a child with mild seasonal allergic rhinitis, to an intranasal glucocorticoid used daily in a child with severe perennial rhinitis and supplemented with additional medications from other classes when symptoms exacerbate. Polypharmacy should be avoided. This may be difficult to accomplish in children who express many different allergic phenotypes concurrently; for example, a child with allergic rhinitis, allergic conjunctivitis, asthma, and atopic dermatitis.

TABLE 424.1. MANAGEMENT OF ALLERGIC RHINITIS

Medication Class	Examples	Route of Administration	Symptoms Relieved	Safety
Corticosteroids	Fluticasone propionate, mometasone furoate	Intranasal	Congestion, itching, rhinorrhea, sneezing	Generally safe for long-term use
H₁-antihistamines*	Cetirizine, fexofenadine, loratadine	Oral	Itching, rhinorrhea, sneezing, and congestion	Second-generation drugs are nonsedating and safe for long-term use
H₁-antihistamines	Azelastine, ketotifen	Intranasal	Itching, rhinorrhea, sneezing, and congestion	Safe for short-term use
Leukotriene modifiers	Montelukast	Oral	Congestion, itching, rhinorrhea, sneezing	Safe for long-term use
Decongestants* (alpha-adrenergic agonists)	Pseudoephedrine	Oral	Congestion	Safe for short-term use
Decongestants* (alpha-adrenergic agonists)	Oxymetazoline, xylometazoline	Intranasal	Congestion	Use for 5 days maximum
Antiallergics*	Cromolyn sodium, lodoxamide tromethamine, nedocromil sodium, pemirolast	Intranasal	Modest efficacy in prevention of symptoms	Safe for long-term use
Anticholinergics	Ipratropium bromide	Intranasal	Rhinorrhea	Safe for short-term use
One or more medications in this class is available over-the-counter in the United States. Nonpharmacologic Interventions: Child and family education with regard to triggers for symptoms, recurrent or persistent inflammatory nature of allergic rhinitis; concomitant disorders; treatment options. Avoidance of airborne allergens and irritants such as cigarette smoke: easier said than done and easier done than maintained. Allergen-specific immunotherapy: selected children with moderate-severe disease. The efficacy and safety of complementary and alternative treatments, which are widely used for children with allergic rhinitis and associated disorders, remains to be determined. See Physicians’ Desk Reference* or other current resource for information about doses and formulations, and the youngest age for which a drug has received U.S. Food and Drug Administration (FDA) approval for use.