Allergic rhinosinusitis is a disorder expressed in the tissues of the nares and upper airway, manifested by local edema and inflammatory infiltration of the submucosa and mucosa, and associated with increased secretion of mucoid materials with accompanying inflammatory leukocytes. These processes lead to obstruction of airflow and of mucus drainage, and, therefore, may be complicated by postobstructive infectious complications.
By definition, allergic disease is dependent on the host generation of allergen-specific IgE antibodies.
Allergic rhinosinusitis is a diagnosis made clinically, as there are no definitive objective tests available for routine clinical use to confirm this entity. There are two major forms of this disorder: seasonal and perennial. Thus, it is a diagnosis based on history (often by questionnaire) and physical examination. In some epidemiological studies, the presence of allergy is confirmed by results of skin prick tests or in vitro allergy testing. The prevalence of this disorder varies widely in the literature, based upon the different sources of the data (i.e., questionnaires, phone interviews, and direct examination), but the majority of the literature suggests that 20% to 25% of children and about 15% of adults suffer from this condition (1). Peak prevalence is between 10 and 30 years in most countries (2). Atopic individuals are at much increased risk for this disorder and there is a significant correlation between the report of nasal symptoms and the prevalence of allergen-specific IgE. There is a strong genetic component to allergic rhinosinusitis, and children whose parents are both allergic have a high likelihood (>50%) of manifesting allergic rhinosinusitis before school age. Also, the presence of other allergic manifestations (e.g., eczema) foreshadows the presentation of allergic rhinosinusitis. Allergic disease must be differentiated from other causes of rhinitis, including infection, genetic disorders (cystic fibrosis and ciliary defects), and drug-induced, hormonal, occupational, anatomic, neoplastic, and irritant causes.
The fundamental cause of allergic rhinosinusitis is the generation of allergen-specific IgE antibodies to inhalant materials normally immunologically ignored. The presence of allergen-specific IgE can be determined either by prick puncture skin testing or by in vitro testing. Recent work indicates that intradermal skin testing does not add to the diagnostic armamentarium for this problem, and in the face of a negative prick puncture skin test, intradermal testing adds nothing to the diagnosis (3). The specific allergen to which an individual is sensitized is based, to some degree, on genetics, and, to a larger degree, on environment. The most important allergens for perennial symptoms are house dust mites, furred animals, and cockroaches. Seasonal allergens include molds and the pollens of grasses, trees, and weeds.
The generation of IgE is regulated by the interaction of T-lymphocytes and antigen-presenting cells and is facilitated by the cytokines Interleukin (IL)-4 and IL-13. Complex interactions between allergen-specific T-lymphocytes and B-lymphocytes, including binding of CD40/CD40 ligand, eventuate in the immunoglobulin gene switch/recombination to IgE (4). IgE may be synthesized locally within the nasal mucosa as well as systemically, although the importance of local IgE production is uncertain. Secreted IgE is then bound tightly to high-affinity receptors on the surface of tissue mast cells and circulating peripheral blood basophils. These cells possess, preformed, a number of inflammatory mediators exemplified by histamine, and upon activation, generate and release a variety of vasoactive and inflammatory molecules including leukotrienes (LTs), chemoattractants, and active enzymes. Activation occurs when an allergen cross-links two adjacent IgE molecules on the surface of mast cells or basophils, and this causes release of preformed mediators and the generation and release of unstored ones. These mediators alter the control of the nasal vasculature and activate nasal neuronal reflexes to induce airflow obstruction, nasal itch/sneezing, and vasodilatation. In addition, they augment nasal mucus secretion, stimulate vascular leakage, and promote plasma protein transudation. In addition to these direct effects, inflammatory mediators generated by the IgE-allergen interaction support eosinophilic polymorphonuclear leukocyte migration and survival and activate endothelial cells to express adhesion molecules relevant to the local influx of eosinophils and basophils to generate a characteristic allergic inflammatory state. Much of this cascade has been verified in human studies of allergen deposition into the nasal cavity followed by measurement of physiologic changes accompanied by histopathological analysis of the nasal tissue and the direct measurement of inflammatory mediators and cytokines in nasal tissue and secretions (5).
The most important and prevalent nonrhinitic symptoms expressed by patients with allergic rhinosinusitis are ocular, otic, and respiratory: patients note itchy and watery eyes and manifest injection of the conjunctivae. The palpebral conjunctivae may demonstrate cobblestoning, indicating lymphocytic infiltration. Otic manifestations include patient-reported sensations of fullness or clicking sensations and decreased auditory acuity. Nonnasal respiratory effects are manifest as asthma with cough and wheezing dyspnea. While not all patients with allergic rhinosinusitis have asthma, most asthmatic patients experience rhinitis, and importantly, studies indicate that appropriate management of rhinosinusitis improves the efficacy of asthma treatment. The local head and neck manifestations of allergic rhinosinusitis include pale and boggy nasal mucosae and swollen turbinates, resulting in obstruction of airflow. Additionally, copious nasal secretions, generally described as watery, but often containing mucoid materials and plasma proteins, are present. There may be tenderness over the sinuses and in uncomplicated allergic rhinosinusitis, sinus radiographs may demonstrate mucosal thickening. Some patients may appreciate nasal congestion as headache rather than as facial pressure/pain. Abnormal mobility of the tympanic membrane and the presence of otitis media commonly are noted. Fatigue, perhaps due to sleep disturbances caused by nasal airflow obstruction, commonly accompanies allergic rhinosinusitis (6).
The diagnosis of allergic rhinosinusitis is based first upon clinical presentation. Thus, the presence of itchy/watery eyes, sneezing, palatal itching, clear watery rhinorrhea, and sinus/ facial pressure suggest this disorder. In addition, the presence of other allergic manifestations such as asthma, eczema, or urticaria/angioedema, and a family history of atopic disorders, provide further support. Exacerbation of symptoms during specific seasons of the year (spring = trees, late spring to early summer = grasses, and fall = weeds and molds), or with certain exposures (e.g., cat), is additional evidence of an allergic etiology. Physical examination may be relatively unremarkable or may reveal pale and swollen nasal mucosa, sometimes described as a bluish discoloration, enlarged turbinates, and copious nasal secretions. Profound erythema of the mucosa and/or the presence of purulent nasal discharge should suggest other diagnoses or the presence of complications of underlying allergic disease. Specialized tests of nasal airway resistance, nasal airway caliber, and nasal provocation testing with specific allergens have been used in research settings but are not widely available for clinical use. Supporting laboratory tests include assessment of peripheral blood eosinophilia that may reach 10% to 12%, but may be normal, and the quantitation of total serum IgE. Total IgE may be normal or moderately elevated in allergic rhinosinusitis but is not a conclusive diagnostic test for this disorder. Specific diagnosis is made by the demonstration of elevated amounts of allergen-specific IgE antibody. This may be done by performing allergy prick puncture skin testing, or in vitro, using a modification of the radioallergosorbent technology. There is good correlation between these two testing modalities, and the choice of test is based on availability of the test, the presence or absence of dermatographism, the ability to withhold antihistaminic medications, and the cost. Recent studies indicate that a negative prick puncture skin test essentially rules out allergic nasal disease, and therefore no additional information is to be gained by performing intradermal skin tests for inhalant allergens in this setting (3). A positive reaction to a prick puncture skin test, or an in vitro test, must be correlated with the clinical situation to verify the diagnosis. For example, in a patient with springtime rhinitis, a reaction to ragweed (a fall allergen) is unlikely to be relevant.
Therapy for allergic rhinosinusitis is directed initially at the symptomatic manifestations. Thus, rhinorrhea, sneezing, and nasal obstruction are the targets of therapy, based on the patient's presenting problems.
Histamine is a major contributor to all of these symptoms; therefore, its blockade is the initial treatment of choice (7). Generally an H-1 antagonist, either a first-generation molecule such as chlorpheniramine, or, if soporific effects are a problem, a second-generation antihistaminic such as loratidine, cetirizine, or fexofenadine, is the treatment of choice. Alternatively, an antihistaminic agent (azelastine) can be applied directly to the nasal mucosa via inhalation.
Antihistaminics may help diminish nasal obstruction but are often not fully effective against this symptom.
To decrease congestion, two strategies are available. The one often employed first by patients is the use of vasoconstrictor agents. These may be used topically, with the problem of rhinitis medicamentosa, rebound vasodilatation that is often worse than the presenting problem. Oral use of decongestants may be effective in ameliorating congestion in some patients but their use may be associated with hypertension and sleep disorders.
A more effective approach to nasal congestion and inflammation is the use of a topical nasal corticosteroid spray. This class of agent is the most potent and effective modality for the treatment of allergic rhinitis and is effective against all of the manifestations of this disorder (8). Common side effects include local nasal irritation and occasional thrush. Less common, but possibly important in the case of long-term use, are an increase in incidence of glaucoma, cataracts, and osteoporosis. These drugs diminish the inflammatory influx of cells into the nasal mucosa and diminish the strength of the local allergic response.
An alternative anti-inflammatory agent available for topical nasal usage is cromolyn, a drug that is less potent than inhaled steroids but virtually free of side effects.
The use of an LT receptor antagonist (montelukast and zafirlukast) has been shown to augment the effect of an antihistamine agent in control of nasal obstruction (9); however, those two drugs together are less effective in controlling nasal symptoms than inhaled glucocorticoids.
Another strategy for the control of allergic nasal disease is allergen based. The first is allergen avoidance and is best based on direct knowledge of the specific allergen in question. Removal of furred animals, control of cockroaches or mold, and use of impervious bed covers to diminish mite exposure have all been shown to be effective in controlling allergen-induced symptoms in sensitized patients. Closure of windows and use of air conditioning and air filtration can help decrease pollen exposure during pollination seasons.
The only specific and potentially curative therapy currently available for the treatment of allergic rhinosinusitis is allergen immunotherapy (10). This modality consists of providing incrementally increasing amounts of allergen to which the patient is sensitive, until a fixed maintenance dose is reached. It is essential for high doses of allergen to be provided if a therapeutic immune response is to occur. Successful immunotherapy results in the generation of allergen-specific IgG antibodies and a modified T-lymphocyte response characterized by the generation of regulatory T-lymphocytes. Immunotherapy should be reserved for those patients failing medical therapy.
Generally, allergic rhinosinusitis is a benign condition readily responsive to therapeutic intervention.
The major complications of this disorder are due to inflammatory obstruction of the osteomeatal complex. Such obstruction leads to the prevention of normal clearance of the sinuses, diminishes gas exchange leading to lowered oxygen tension, and predisposes one to sinus infection. In this setting, infection is generally due to aerobic bacteria including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. In some patients, fungal superinfection may also occur, most commonly due to Alternaria or Aspergillus species. In some patients, aberrant allergic or immunologic responses to the fungi have been presumed to contribute to the histopathologic manifestations of the disease. Acute sinusitis is generally manifest by fever, local pain, and purulent nasal drainage. Symptoms in subacute or chronic sinusitis are generally less specific and include nasal obstruction, diminished sense of smell, halitosis, and postnasal discharge.
Although the direct contribution of allergic mechanisms to otitis media remain controversial, it is clear that obstruction to Eustachian tube drainage and resultant dysfunction can result in symptoms of ear fullness and diminished hearing and may contribute to the severity and persistence of otitis media.
Another complication of untreated IgE-mediated nasal disease is the development of nasal polyps. Because they are a characteristic finding in the syndrome of nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity, this topic will be dealt with in that section below.
Allergic rhinosinusitis is generally a benign, albeit chronic, condition that responds well to therapy. Epidemiologic studies suggest that its highest incidence is in young adulthood, suggesting a waning of symptoms as one ages; however, allergic rhinosinusitis can persist for many decades. Some patients with this condition develop asthma; this is particularly true in children (the so-called "allergic march").
Allergic rhinosinusitis is an extremely common disorder. It is generally easily treated but may be complicated by sinusitis (acute or chronic) and otitis. Additionally, as for all allergic diseases, patients must be evaluated for non-head-and-neck manifestations, including ocular and lower respiratory dysfunction.
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If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.