DEFINITION

Rhinitis is characterized by sneezing; rhinorrhea; obstruction of the nasal passages; conjunctival, nasal, and pharyngeal itching; and lacrimation. It can be classified as allergic or nonallergic based on the presence or absence of IgE specific for relevant antigens. A clinical history of rhinitis symptoms occurring in a temporal relationship to allergen exposure and documentation of sensitization to an environmental allergen are required for diagnosis. Although commonly seasonal due to elicitation by airborne pollens, it can be perennial in an environment of chronic exposure to house dust mites, animal danders, or insect (cockroach) products. The overall prevalence in North America has increased in the past 20 years and is 10–30%, with the peak prevalence (>30%) occurring in the fifth decade.

PREDISPOSING FACTORS AND ETIOLOGY

Allergic rhinitis generally occurs in atopic individuals, often in association with atopic dermatitis, food allergy, urticaria, and/or asthma. Up to 50% of patients with allergic rhinitis manifest asthma, whereas 70–80% of individuals with asthma and 80% of individuals with chronic bilateral sinusitis experience allergic rhinitis. Female sex, particulate air pollution exposure, and maternal tobacco smoking increase the risk of developing allergic rhinitis.

Wind-pollinated trees, grasses, and weeds produce sufficient quantities of pollen suitable for wide distribution by air currents to elicit seasonal allergic rhinitis. The dates of pollination of these species historically varied little from year to year in a particular locale but may differ in another climate. In the temperate areas of North America, trees typically pollinate from March through May, grasses in June and early July, and weeds from mid-August to early October. Molds, which are widespread in nature because they occur in soil or decaying organic matter, propagate spores in a pattern that depends on climatic conditions. Climate change is impacting these patterns with early tree pollination and prolonged ragweed season with the delay of the first frost. In laboratory studies, exposure to high car bon dioxide concentrations increases pollen production in ragweed and timothy grass. Perennial allergic rhinitis occurs in response to allergens that are present throughout the year, including animal dander, cockroach-derived proteins, mold spores, or dust mites such as Dermatophagoides farinae and Dermatophagoides pteronyssinus. Dust mites are scavengers of human skin and excrete cysteine pro tease allergens in their feces. Similarly, cockroach allergens are fecal cysteine proteases.

PATHOPHYSIOLOGY AND MANIFESTATIONS

 Episodic rhinorrhea, sneezing, obstruction of the nasal passages with lacrimation, and pruritus of the conjunctiva, nasal mucosa, and oropharynx are the hallmarks of allergic rhinitis. The nasal mucosa is pale and boggy, the conjunctiva congested and edematous, and the pharynx generally unremarkable. Swelling of the turbinates and mucous membranes with obstruction of the sinus ostia and eustachian tubes precipitates secondary infections of the sinuses and middle ear, respectively. A growing number of patients with seasonal allergic rhinitis demonstrate pollen-associated food allergen syndrome characterized by oropharyngeal pruritus and/or mild swelling following the ingestion of plant-based foods in the same plant family as a tree, grass, or weed, which contain cross-reacting allergens.

The nose presents a large mucosal surface area through the folds of the turbinates and serves to adjust the temperature and moisture content of inhaled air and to filter out particulate materials >10 μm in size by impingement in a mucous blanket; ciliary action moves the entrapped particles toward the pharynx. Entrapment of pollen and digestion of the outer coat by mucosal enzymes such as lysozymes release protein allergens. The initial interaction occurs between the allergen and intraepithelial mast cells and then proceeds to involve deeper perivenular mast cells, both of which are sensitized with specific IgE. During the symptomatic season when the mucosae are already swollen and hyperemic, there is enhanced adverse reactivity to the seasonal pollen as well as irritants such as tobacco smoke and fragrances. Biopsy specimens of nasal mucosa during seasonal rhinitis show submucosal edema with infiltration by eosinophils, along with some basophils and neutrophils, and intraepithelial mast cells.

The mucosal surface fluid contains IgA and IgE, which apparently arrives by diffusion from plasma cells in proximity to mucosal surfaces. IgE fixes to mucosal and submucosal mast cells, and the intensity of the clinical response to inhaled allergens is quantitatively related to the naturally occurring pollen dose. In sensitive individuals, the introduction of allergen into the nose is associated with sneezing, nasal obstruction, and discharge, and the fluid contains histamine, PGD2 , and leukotrienes. Thus, the mast cells of the nasal mucosa and submucosa generate and release mediators through IgE dependent reactions that are capable of producing tissue edema and eosinophilic infiltration.

DIAGNOSIS

The diagnosis of seasonal allergic rhinitis depends largely on an accurate history of symptoms lasting >4 weeks coincident with the pollination of the offending allergen. The continuous character of perennial allergic rhinitis due to allergens found in the home or place of work makes historic analysis difficult, but there may be variability in symptoms that can be related to exposure to animal dander, dust mite and/or cockroach allergens, fungal spores, or work-related allergens such as latex. Patients with perennial rhinitis commonly develop the problem in adult life and manifest nasal congestion and a postnasal discharge, often associated with thickening of the sinus membranes demonstrated by radiography. Perennial nonallergic rhinitis with eosinophilia syndrome (NARES) occurs in the middle decades of life and is characterized by nasal obstruction, anosmia, chronic sinusitis, and prominent eosinophilic nasal discharge in the absence of allergen sensitization. The term vasomotor rhinitis or perennial nonallergic rhinitis designates a condition of enhanced reactivity of the nasopharynx in which a symptom complex resembling perennial allergic rhinitis occurs with nonspecific stimuli, including chemical odors, temperature and humidity variations, and position changes but occurs without tissue eosinophilia or an allergic etiology. Other entities to be excluded are structural abnormalities of the nasopharynx, including nasal foreign bodies in children, symptoms due to exposure to irritants, gustatory rhinitis associated with cholinergic activation that occurs while eating or ingesting alcohol, hypothyroid ism, upper respiratory tract infection, hormonal rhinitis, including pregnancy, atrophic rhinitis in populations outside the United States and Europe, prolonged topical use of α-adrenergic agents in the form of nasal sprays (rhinitis medicamentosa), and the use of certain systemic agents such as β-adrenergic antagonists, ACE inhibitors, direct vasodilators (hydralazine), α1-adrenergic receptor antagonists, estro gens, progesterone, nonsteroidal anti-inflammatory drugs, gabapentin, phosphodiesterase-5 inhibitors, and psychotropics (risperidone, chlorpromazine, amitriptyline).

The nasal secretions of allergic patients can be rich in eosinophils, and a modest peripheral eosinophilia can be observed. Local neutrophilia implies infection. Total serum IgE may be moderately elevated, but the demonstration of immunologic specificity for IgE is critical to an etiologic diagnosis. A skin test by the intracutaneous route (puncture or prick) with the allergens of interest provides a rapid and reliable approach to identifying allergen-specific IgE that has sensitized cutaneous mast cells. A positive intracutaneous skin test with 1:10–1:20 weight/volume of extract has a high predictive value for the presence of allergy. An intradermal test with a 1:500–1:1000 dilution of 0.05 mL may follow if indicated by history when the intracutaneous test is negative, but while more sensitive, it is less dependable due to the reactivity of some asymptomatic individuals at the test dose.

Enzyme-linked immunosorbent assays (ELISAs) employing anti IgE bound to either a solid-phase or a liquid-phase particle provide rapid and cost-effective determinations of IgE. Measurements of specific anti-IgE in serum are obtained by its binding to an allergen and quantitation by subsequent uptake of labeled anti-IgE. As compared to the skin test, the assay of specific IgE in serum is less sensitive but has high specificity.

TREATMENT

Although allergen avoidance is the most cost-effective means of managing allergic rhinitis, only in the case of animal dander and possibly dust mites is it feasible. Treatment with pharmacologic agents represents the standard initial approach to seasonal or perennial allergic rhinitis. Oral long-acting H1 antihistamines, such as fexofenadine, loratadine, desloratadine, cetirizine, and levocetirizine, are effective for nasopharyngeal itching, sneezing, and watery rhinorrhea and for such ocular manifestations as itching, tearing, and erythema, but they are less efficacious for the nasal congestion. They reduce nasal and ocular symptoms by about one-third. These antihistamines are less lipophilic and more H1 selective, thus minimizing their ability to cross the blood-brain barrier and therefore diminishing their sedating and anticholinergic effect; they do not differ appreciably in efficacy for relief of rhinitis and/or sneezing.

Intranasal high-potency glucocorticoids are the most effective drugs available for the relief of persistent rhinitis, seasonal or perennial, and are effective in relieving nasal congestion as well as ocular symptoms. They provide efficacy with substantially reduced side effects as compared with this same class of agent administered orally. Their most frequent side effect is local irritation, with fungal overgrowth being a rare occurrence. The currently available intra nasal glucocorticoids are equally effective for nasal symptom relief, including nasal congestion, achieving up to 70% overall symptom relief with some variation in the onset of benefit. The nasal antihistamines azelastine and olopatadine as a first-line option may benefit individuals with nonallergic rhinitis and intermittent or mild allergic rhinitis, as well as have additive benefit to intranasal steroids in persistent allergic rhinitis, but they have an adverse effect of dysgeusia in some patients. Alternative nasal decongestants for significant mucosal edema or unresponsive nasal congestion include α-adrenergic agents such as phenylephrine or oxymetazoline; however, the duration of their efficacy is limited because of rebound rhinitis (i.e., 7- to 14-day use can lead to rhinitis medicamentosa) and such systemic responses as hypertension. Oral α-adrenergic agonist decongestants containing pseudoephedrine can improve management of nasal congestion, generally in combination with an antihistamine. These pseudoephedrine combination products can cause insomnia and are precluded from use in a variety of patient populations, such as those with narrow-angle glaucoma, urinary retention, uncontrolled hypertension, cerebrovascular dis ease, marked coronary artery disease, or a first-trimester pregnancy. The CysLT1 antagonist montelukast is approved for treatment of both seasonal and perennial rhinitis. However, it is less effective than H1 antihistamines and nasal glucocorticoids, and reports of neuropsychiatric events have led to increased U.S. Food and Drug Administration precautions. Cromolyn sodium nasal spray inhibits mast cell degranulation and can be used prophylactically on a continuous basis during allergen season or as needed before a known exposure. Topical ipratropium is an anticholinergic agent effective in reducing rhinorrhea, including that of patients with perennial nonallergic symptoms. For concomitant allergic conjunctivitis, topical treatment with cromolyn sodium is effective in treating mild allergic symptoms, and topical antihistamines such as olopatadine, azelastine, ketotifen, or epinastine administered to the eye provide rapid relief of itching and redness and are more effective than oral antihistamines.

Immunotherapy

Immunotherapy consists of repeated exposure to the allergen(s) considered to be specifically responsible for the symptom complex. Two forms of immunotherapy, subcutaneous (SCIT) and sublingual (SLIT), are currently available. Randomized, controlled studies of ragweed, grass, dust mite, and cat dander allergens administered via SCIT for treatment of allergic rhinitis have demonstrated significant improved symptom control over medications alone with the advantage of providing a durable benefit, as well as a reduction in asthma symptoms, medication use, and bronchial hyperreactivity in allergic asthma. Clinical practice guidelines recommend a duration of SCIT of 3–5 years, with discontinuation being based on minimal symptoms over two consecutive seasons of exposure to the allergen. Clinical benefit appears related to the administration of a high dose of relevant allergen, gradually uptitrating concentration and advancing from weekly to monthly intervals. SCIT injections occur in a licensed treatment site; 2–3% of SCIT patients experience a systemic reaction, including anaphylaxis, over a 12-month period. The majority of these reactions occur soon after injection, and thus, patients should remain at the treatment site for at least 30 min after allergen administration. Local reactions with erythema and induration are not uncommon and may persist for 1–3 days. SLIT is prepared as a tablet to be dissolved under the tongue at home after the first dose. The efficacy of SLIT is comparable to SCIT but only for the three allergen formulations currently available: dust mite, timothy/northern grasses, and short ragweed. Systemic reactions are less frequent with SLIT, but transient oral pruritus is common. Immunotherapy is contraindicated in patients with significant cardiovascular disease or unstable asthma. Severe cases of anaphylaxis have occurred after allergen immunotherapy when patients were taking a β-adrenergic blocking agent. Thus, immunotherapy should be conducted with caution in any patient requiring β-adrenergic blocking therapy.

Immunotherapy should be reserved for clearly documented seasonal or perennial rhinitis that is clinically related to defined allergen exposure with confirmation by the presence of allergen- specific IgE through skin or serum-specific IgE testing. The response to immunotherapy is associated with a complex of cellular and humoral effects that includes a modulation in T lymphocyte cytokine production and allergen-specific IgG4 expansion. Systemic treatment with omalizumab, an anti-IgE monoclonal antibody, is efficacious for allergic rhinitis and can be used with immunotherapy to enhance safety and efficacy. However, omalizumab is not currently approved for treatment of allergic rhinitis.

A sequence for the management of allergic or perennial rhinitis based on an allergen-specific diagnosis and stepwise management as required for symptom control would include the following: (1) identification of the offending allergen(s) by history with confirmation of the presence of allergen-specific IgE by skin test and/or serum assay; (2) avoidance of the offending allergen if possible; and (3) medical management in a stepwise fashion with treatment stepdown as symptoms permit (Fig. 1). Mild symptoms of allergic rhinitis are treated with oral antihistamines, intranasal antihistamines, intranasal corticosteroids, or intranasal cromolyn (for short-term prevention). Moderate to more severe allergic rhinitis is managed with intranasal glucocorticoids and intranasal antihistamines; additional therapies include oral antihistamines, antihistamine- decongestant combinations, and intranasal anticholinergics. Persistent or seasonal moderate to severe allergic rhinitis that remains uncontrolled with maximal medical therapy or coexisting allergic rhinitis with asthma merit consideration of allergen specific immunotherapy.

Fig1. Algorithm for the diagnosis and management of rhinitis. Persistent is defined as >4 days per week for >4 weeks. Moderate/severe is defined as abnormal sleep, impaired daily activities (school, work, sport, leisure), and/or troublesome symptoms. CysLT, cysteinyl leukotriene; ENT, ear, nose, and throat; IgE, immunoglobulin E.

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الدينية يطلق الدورة التطويرية والفقهية الخامسة لملاكات العتبة العباسية المقدسة

قسم الشؤون الفكرية ينظّم ختمة قرآنية رمضانية لطلبة العلوم الدينية الأفارقة في النجف

شعبة الخطابة تقيم مجلسا للوعظ والإرشاد في الصحن الشريف تزامناً مع حلول شهر رمضان المبارك

قسم التطوير يختتم دورة إعداد المدربين لملاكات مديرية تربية كربلاء

المزيد

الآخبار الصحية

مفاجأة.. تحسين القدرة على التحمل لا يعتمد العضلات فقط

المرتفعات والأكسجين.. دراسة "مبشرة" لمرضى السكري

علماء يبتكرون "آلية" تتوقع موعد ظهور أعراض الزهايمر

ماذا يحدث لجسمك عند التوقف عن تناول الخضراوات والفواكه؟

المزيد

الآخبار التكنلوجية

رصد "القرش النائم" في أحد أقسى الأماكن على وجه الأرض

أسماك أعماق البحر تكشف نظاما بصريا يتجاوز "المألوف"

زوكربيرغ أمام القضاء في قضية إدمان المراهقين

"علي بابا" تكشف عن نموذج جديد للذكاء الاصطناعي

المزيد

مواضيع ذات صلة

Mechanisms of Immune Dysregulation in Autoimmune Disease

Chimeric Antigen Receptor T Cells

Checkpoint Inhibition Therapy for Cancer

Mechanisms of Regulation of T-Cell Activation

Neutrophils & Eosinophils Employ Nets to Entrap Parasites

Immunotherapy

Immune Tolerance and Autoimmunity

Cellular interactions in regulation of normal immune responses

Markers of Granulocytic Maturation

The Complement System Also Protects Against Infection

Monocytopoiesis

Eosinophil Production