Allergic Rhinitis

Definition, Etiology, PathogenesisTop

Allergic rhinitis (AR) is an inflammation of the nasal mucosa related to an allergy, most frequently IgE-dependent.

1. Classification:

1) Based on the duration of signs and symptoms:

a) Intermittent AR, lasting <4 days a week or <4 weeks.

b) Persistent AR, lasting >4 days a week and >4 weeks.

2) Based on the severity of signs and symptoms:

a) Mild AR, in which none of the following criteria are met.

b) Moderate or severe AR, in which ≥1 of the following criteria are met: sleep disturbance; impairment of daily activities, leisure, and sport; impairment of school or work; troublesome symptoms.

3) Based on causative allergens:

a) Seasonal AR, caused by seasonal allergens.

b) Perennial AR, caused by allergens present in the environment throughout the year.

2. Etiologic factors:

1) Inhaled allergens:

a) Pollens (particularly of anemophilous plants): Most frequently pollens from trees such as birch or Ficus benjamina (the weeping fig), grasses and weeds such as ragweed, and other plants such as mugwort.

b) House dust mites, cockroaches.

c) Dander, epidermis, and secretions (saliva, urine) of cats, dogs, rodents (eg, rabbits, guinea pigs, hamsters, rats, mice), horses, and cattle.

d) Molds (eg, Alternaria spp, Cladosporium spp) and yeasts (eg, Candida albicans, Saccharomyces cerevisiae, Saccharomyces minor, Pityrosporum spp).

2) Food allergens: Nasal symptoms may accompany anaphylaxis caused by food allergens; cross-reactivity may occur between foods and inhaled allergens (oral allergy syndrome; see Food Hypersensitivity). In addition, if foods are crushed or boiled and then aerosolized, they may cause respiratory symptoms if the patient is allergic to the food (eg, when shrimp is boiled, it may cause respiratory symptoms in individuals allergic to shrimp; when large loads of soybeans are dumped off a ship in a harbor, the resulting aerosolized soybean powder may cause respiratory symptoms).

3) Occupational allergens: Latex (most frequently from latex gloves); high-molecular-weight substances, including plant and animal proteins (eg, allergens of laboratory and farm animals, grain dust, tobacco, red pepper, tea, coffee, cocoa, dried fruit, enzymes present in cleaning products or used in pharmaceutical manufacturing, fish, shellfish); low-molecular-weight substances (eg, nickel and platinum salts, dyes, acid anhydrides); bacterial enzymes used industrially for manufacturing soaps and detergents.

Clinical Features and Natural HistoryTop

Typical manifestations: Watery nasal discharge (rhinorrhea); sneezing, frequently paroxysmal; nasal congestion and thick mucous discharge; nasal itching, frequently also conjunctival itching (and injection), itching of the ears, palate, or throat; partial loss of smell (hyposmia); dry oral mucosa; sometimes systemic signs and symptoms, including sleep disturbance, impaired concentration and learning abilities, low-grade fever, headache, and depressed mood. Rhinorrhea and sneezing as dominant symptoms suggest seasonal AR, while nasal congestion is usually a dominant feature of perennial AR. In 70% of patients symptoms worsen at night and in the early hours of the morning.

Symptoms are present during exposure to a particular allergen and may be seasonal (eg, during a pollination season in patients with pollen allergy) or perennial (eg, in patients with house dust mite allergy). In both situations symptoms may be persistent or intermittent.

In some patients with AR signs and symptoms improve or resolve spontaneously after several years.

AR, particularly when chronic, may block sinus ostia, result in inflammation in the sinus, or both; the inflammation increases the risk of bacterial sinusitis. AR is also associated with a 3- to 8-fold increase in the risk of asthma development and with worsening of preexisting asthma control.

The following signs and symptoms are usually associated with a condition other than AR (seek an alternative diagnosis): unilateral symptoms, nasal congestion without other accompanying symptoms, mucopurulent nasal discharge, postnasal drip (with thick mucus, without rhinorrhea, or both), facial pain, recurrent epistaxis, and complete loss of smell (anosmia).

DiagnosisTop

Diagnostic Tests

1. Studies confirming the diagnosis of allergy: Positive skin prick tests with inhaled allergens (the most sensitive, quickest, and cheapest diagnostic tests in AR), increased serum levels of specific IgE levels (not recommended as screening, as it is more expensive and less sensitive). In exceptional cases of conflicting results and unclear diagnosis, nasal challenge may be performed.

2. Anterior rhinoscopy and nasal endoscopy reveal bilateral (although not always symmetric) mucosal edema with watery discharge covering the mucosa (in patients with chronic AR the discharge is thick). The mucosa is pale or bluish but may also be hyperemic. Sometimes polyps are present.

3. Cytology of nasal smear reveals an increased percentage of eosinophils (≥2%, usually during exacerbations), mast cells or basophils, and goblet cells (>50%). However, these results are not specific for AR and are similar in patients with nonallergic rhinitis.

4. Computed tomography (CT) of the nose and sinuses is indicated in selected cases where surgery is being considered. It allows for reliable assessment of sinusitis that may coexist with AR.

Diagnostic Criteria

In most cases the diagnosis of AR can be established on the basis of typical symptoms and signs from the patient’s history and physical examination, which may be aided as needed by skin prick tests and specific IgE measurements.

Differential Diagnosis

1. Other types of rhinitis:

1) Infectious rhinitis: Caused by viruses (differential diagnosis with common cold: Table 1), bacteria, or fungi.

2) Drug-induced rhinitis: Edema of the nasal mucosa, most frequently caused by the overuse of topical sympathomimetics, or less frequently by acetylsalicylic acid, other nonsteroidal anti-inflammatory drugs (NSAIDs), pyrazolones, angiotensin-converting enzyme inhibitors, antidepressants, reserpine, methyldopa, alpha-adrenergic antagonists, phosphodiesterase inhibitors, and chlorpromazine.

3) Hormonal rhinitis: This may occur during the menstrual cycle, puberty, pregnancy, in patients using oral contraceptives or hormone replacement therapy, and in those with hypothyroidism.

4) Atrophic rhinitis: Progressive atrophy of the nasal mucosa and underlying bone with widening of nasal cavities, which are filled with crusts. The disease leads to nasal obstruction, hyposmia, and a constant sensation of bad taste in the mouth. It usually occurs in elderly patients.

5) Idiopathic rhinitis (formerly known as vasomotor rhinitis): Caused by an exaggerated response to chemical and physical factors (eg, dry and cold air or concentrated chemicals). Hot spicy foods may cause rhinorrhea (gustatory rhinitis), probably because of stimulation of sensory nerves and vagal nerve reflex, whereas foods, dyes, and preservatives may cause rhinitis mediated by unknown nonallergic mechanisms. Alcohol may cause nasal congestion by directly degranulating mast cells.

6) Eosinophilic rhinitis with or without NSAID hypersensitivity (nonallergic rhinitis with eosinophilia syndrome [NARES]): Characterized by the presence of eosinophils in the nasal mucosa, perennial symptoms, and absence of features of atopy (although atopy may also be present).

7) Rhinitis caused by intranasal cocaine use: This may cause rhinorrhea, hyposmia, and perforation of the nasal septum.

2. Other conditions: Nasal polyps; polyps of the sinuses; sinusitis; nasal septal deviation; turbinate, tonsillar, or (usually) adenoid hypertrophy; nasal foreign body; nasal neoplasms; abnormalities of the ciliary structure or function; cerebrospinal fluid leakage; granulomatosis with polyangiitis (Wegener granulomatosis) and eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss syndrome).

TreatmentTop

General Measures

1. Avoiding allergens: This may involve, for instance, limiting open air exercise during pollen seasons of suspected plants, keeping windows closed or using window filters, and removing pets from home. Combining these with techniques of house dust mite control may be beneficial. Consider using websites or mobile apps providing pollen calendars.

2. Rinsing the nose with sterilized isotonic or hypertonic saline or sea water.

3. Indications for referral to an ear, nose, and throat (ENT) specialist: Suspected complications or chronic sinusitis not responding to empiric treatment, recurrent otitis media, unilateral or treatment-resistant symptoms, recurrent epistaxis, nasal septal deviation and other anatomical abnormalities, nasal polyps.

4. Indications for considering surgical treatment: Lower turbinate hypertrophy resistant to pharmacologic treatment, nasal septal deviation affecting nasal function, complications of AR.

Pharmacologic Treatment

According to the 2016 Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, intranasal glucocorticoids may be used to treat seasonal AR, either alone or in combination with an oral or nasal antihistamine. In perennial AR, treatment with an intranasal glucocorticoid alone is suggested, without the addition of an antihistamine (oral or nasal).

1. Glucocorticoids:

1) Intranasal glucocorticoids: Beclomethasone, budesonide, ciclesonide, fluticasone furoate, mometasone furoate, fluticasone propionate: One to 2 doses are administered to each nostril once daily or bid. These are the most effective agents in AR that improve all signs and symptoms (including ocular manifestations). The onset of action is 7 to 12 hours after administration, and the maximum effect is observed after 2 weeks of treatment. Long-term treatment with intranasal glucocorticoids appears to be safe. The main adverse effects are mucosal dryness and minor bleeding from the nasal mucosa.

2) Oral glucocorticoids: For instance, prednisone 0.5 mg/kg once daily in the morning may be used for a few days in severe AR when treatment with intranasal glucocorticoids and antihistamine drugs has been ineffective.

2. Antihistamines (H1 antagonists):

1) Oral antihistamines (agents and dosage: Table 2): Particularly beneficial in patients with conjunctivitis. The preferred antihistamines are agents that cause less sedation and concentration impairment, are not cardiotoxic, and cause fewer interactions with other drugs or with foods.

2) Intranasal antihistamines: Azelastine, levocabastine. These have only topical effects on the nose and are indicated in mild AR. One to 2 doses are administered to each nostril bid. The onset of action is 15 to 20 minutes after administration.

3) Intraocular antihistamines: Azelastine, emedastine, epinastine, ketotifen, olopatadine.

4) Combination intranasal glucocorticoids and intranasal antihistamines are also available. Fluticasone propionate and azelastine have been combined in one nasal spray to be given bid.

3. Antileukotrienes: Oral montelukast (10 mg once daily), pranlukast, or zafirlukast may be used in patients with seasonal AR, but intranasal glucocorticoids and antihistamines are more effective.

4. Cromones: Intranasal cromolyn (INN cromoglicic acid) qid, and 1 to 2 drops intraocularly 4 to 6 times a day in case of ophthalmic symptoms. It is less effective than intranasal glucocorticoids and antihistamines but safe.

5. Decongestants may be used for quick relief of nasal congestion. They are administered intranasally (ephedrine, phenylephrine, naphazoline, xylometazoline, oxymetazoline, tetrahydrozoline [INN tetryzoline], tymazoline; use ≤5 days because of the risk of drug-induced rhinitis) or orally (ephedrine, phenylephrine, pseudoephedrine; do not use in pregnancy, in patients with hypertension, cardiovascular disease, thyrotoxicosis, prostatic hypertrophy, glaucoma, psychiatric disorders, and in patients treated with beta-blockers or monoamine oxidase inhibitor inhibitors; in many patients these agents cause insomnia).

6. Anticholinergic agents administered intranasally reduce nasal secretions. They are beneficial in idiopathic rhinitis.

7. Specific allergen immunotherapy is the most effective treatment of AR caused by inhaled allergens. It reduces or eliminates signs and symptoms of the disease, reduces medication use, prevents sensitization to other allergens, and reduces the risk of asthma by two-thirds. It is available for subcutaneous injection or as sublingual tablets. The beneficial effects of therapy may persist for some time after its completion.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to heterogeneity. Durham SR, Emminger W, Kapp A, et al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. J Allergy Clin Immunol. 2010 Jan;125(1):131-8.e1-7. doi: 10.1016/j.jaci.2009.10.035. PubMed PMID: 20109743. Scadding GW, Calderon MA, Shamji MH, et al; Immune Tolerance Network GRASS Study Team. Effect of 2 Years of Treatment With Sublingual Grass Pollen Immunotherapy on Nasal Response to Allergen Challenge at 3 Years Among Patients With Moderate to Severe Seasonal Allergic Rhinitis: The GRASS Randomized Clinical Trial. JAMA. 2017 Feb 14;317(6):615-625. doi: 10.1001/jama.2016.21040. PubMed PMID: 28196255; PubMed Central PMCID: PMC5479315.

TablesTop