Abbreviations used:
AIT: Allergen immunotherapy
AR: Allergic rhinitis
IgE: Immunoglobulin E
INS: Intranasal corticosteroid
LTRA: Leukotriene receptor antagonist
RAST: Radioallergosorbent test
SCIT: Subcutaneous immunotherapy
SLI: Sublingual immunotherapy
Introduction
Up to 20% of the population suffers from allergic rhinitis (AR) and many fail to recognize that the effects of AR reach far beyond the nose. The total direct and indirect costs of AR in the United States exceed $15 billion dollars annually, indicating that the condition affects the entire economy, not just the individual.
In addition to its well-known co-morbidities of recurrent otitis media, sinusitis, cough, and asthma, AR has a tremendous impact on the quality of life including school absence and poor performance. As a result, it is often necessary to treat AR as a chronic, not an episodic disease.
What is allergic rhinitis and how is it diagnosed?
Allergic rhinitis is “a symptomatic disorder of the nose induced by an IgE-mediated inflammation after allergen exposure of the membranes lining the nose” (J Allergy Clin Immunol. 2001;108:S147). What does that mean? If symptoms are present without the presence of allergen-specific IgE or there is allergen-specific IgE without symptoms, technically the patient should not be diagnosed with allergic rhinitis. Of course, the presence of specific IgE is often assumed based on history.
When assessing a patient for allergic rhinitis and before formulating a treatment plan, I consider several key points:
- What are the symptoms?
- What is the timing of the symptoms in relation to exposure to aeroallergens?
- Other than the obvious nasal symptoms, is there coughing, need for antibiotics, or other systemic complaints or concerns?
- The physical exam.
- What treatments have already been used and how effective were they?
- And finally, testing for specific IgE is performed.
The symptoms and signs of AR include itchy nose, throat/palate, eyes (allergic conjunctivitis), and pruritus inside the ears. There is frequently nasal congestion, sneezing, and clear, watery nasal discharge. Some patients also demonstrate an allergic salute, in which they use the palm of the hand to push the nose upward, an allergic “grimace,” and a “clucking sound”.
Triggers of AR are either seasonal or perennial, although many patients have perennial AR with seasonal worsening. Aerobiology varies by geographic region. Most perennial allergens are indoors although outdoor molds (fungi) may be present year-round. Indoor (perennial) allergens include dust mites, molds, animal dander especially from house pets, cockroaches, and rodents. Although there is some seasonality in the level of outdoor molds, most seasonal allergens are pollen, the presence of which depends on the flora of your region.
Allergens as triggers to AR are called “specific” and are related to the presence of IgE (the “allergy” antibody) with an affinity for that allergen. That is, if you are allergic to cats but not dogs, exposure to cats but not to dogs will trigger symptoms. In contrast, there are also “non-specific” triggers to AR that can elicit worsening symptoms in anyone already affected, independent of what he or she is allergic to. Non-specific triggers of AR are considered irritants and include strong odors (such as from cleaning supplies, paint, industrial odors), outdoor and indoor air pollution (such as cigarette smoke, fireplaces, wood-burning or kerosene stoves), and irritant dust as may be found with home construction or just very dusty areas. Control of the symptoms triggered by specific allergens usually helps mitigate the effects of irritant, non-specific triggers of AR.
Treatment of allergic rhinitis
The management of AR is analogous to that of asthma with education (trigger avoidance), symptom reliever medications (“rescue”), preventive medications (“controllers”), and immunotherapy (“immune deviation”). In addition, a similar stepwise approach and appropriate medication adjustment are essential (J Allergy Clin Immunol. 2001;108:S147. and Ann Allergy Asthma Immunol. 2011;1062:S17-19).
Everyone should make an attempt to decrease exposure to his or her triggers of allergic rhinitis. When I speak of allergen avoidance, I speak of decreasing not eliminating exposure, as the latter is virtually impossible. Because of the ubiquity of perennial aeroallergens (dust mites, mold, and animal dander) even in schools, public transportation, and work environments, efforts for avoidance should first be directed at the home environment. Practitioners should become familiar with methods of allergen avoidance to make appropriate recommendations after testing for specific IgE is completed.
Medical treatment of AR requires follow-up visits, reassessment, and dose adjustments. The “best” regimen for a patient is the one that is most effective, best tolerated, and uses the least amount of medication necessary to accomplish those goals No single plan works best for everyone.
Second-generation antihistamines (loratadine, desloratadine, fexofenadine, cetirizine, and levocetirizine) are the treatment of choice for relief of sneezing, rhinorrhea, and nasal, palatal, and ocular itch. Because these are large lipophilic molecules that do not easily cross the blood-brain barrier, second-generation antihistamines are less likely to be sedating and have fewer anticholinergic side effects than the first-generation antihistamines such as diphenhydramine and hydroxyzine. They are also are longer acting. Antihistamines may not have a tremendous effect on nasal congestion for which oral decongestants (e.g., pseudoephedrine) may be necessary. Intranasal antihistamine sprays (azelastine, olopatadine) may also help relieve congestion, but some patients find the after taste unpleasant. Intranasal decongestant sprays should be used sparingly because of the risk of rhinitis medicamentosa.
Patients with mild AR may not require anything more than adequate symptom relievers. However, patients with symptoms more often than 4 days per week, for more than 4 weeks, and/or whose symptoms interfere with their quality of life (i.e., moderate or severe AR) require daily controller medications. The gold standard for preventive medications for AR are the low-dose intranasal corticosteroid sprays (INS). This large class of medications effectively manages all the symptoms of AR except palatal and ear itch, for which antihistamines might still be necessary. INS use prevents the release of mediators of allergic inflammation (except leukotrienes) thereby preventing symptoms. Furthermore, they reduce nasal hyper-reactivity (analogous to bronchial hyper-reactivity of asthma) and reduce the priming effect caused after allergen exposure. By attenuating the naso-ocular reflex, INS might also contribute to the control of allergic conjunctivitis.
The INS are intended for regular/daily use and are extraordinarily safe. They have negligible if any of systemic side effects. The most common adverse effects are local drying, irritation, and epistaxis that are reduced by aiming the spray laterally, not medially during application. Nonetheless, many patients do not prefer this useful class of medications because of intolerable side effects, aversion to nasal sprays, or steroid phobias.
The leukotriene receptor antagonists (LTRAs) are an alternative to INS for symptom prevention, especially in those resistant to use or intolerant of INS or for whom the INS are ineffective. Although montelukast and related medications generally do not work as well in as many people as the INS, there are patients for whom LTRAs provide outstanding or even complete relief of symptoms by blocking the leukotriene pathway. One can only speculate that in those patients, the leukotriene mediators are a primary cause of allergic inflammation. The LTRAs are well tolerated and with the exception of the previous adverse reactions, there is no contraindication to their use.
The medical regimen should be stepped up or down as indicated depending on the degree of control. Patients with seasonal worsening may need annual seasonal adjustments.
Allergen immunotherapy (AIT) is a highly effective and potentially curative treatment option for AR. By altering the immune response to aeroallergens from a TH2 to a TH0 or T reg response, most patients achieve tolerance to allergens and ultimately require little or no daily controller medications.
All patients with moderate or severe AR should be considered for AIT as long as they have allergen-specific IgE that correlates with their symptom pattern. Of great importance, those with poor symptom control despite using controller medications and who are trying to avoid their triggers should be encouraged to start AIT. I also think patient preference must be considered. Even those with easily controlled symptoms may prefer AIT to the use of medications.
The natural history of the patient’s disease should also be considered when discussing AIT. Is the patient improving or worsening over time? Patients with AR are at risk of progression of the disease with the development of new sensitivities and the development of asthma. AIT is known to decrease the likelihood of progression of the disease by at least 50%. Certainly, those who have started to worsen should consider AIT. Patients with intense occupational exposures to indoor or outdoor allergens should also consider AIT.
However, AIT is not for everyone. While there is a dearth of head-to-head studies, subcutaneous AIT (SCIT) appears to be more effective than sublingual AIT (SLIT) for seasonal allergens and is comparable to or more effective than SLIT for perennial aeroallergens. SCIT must be administered in a medical setting with the capacity to treat anaphylaxis in the rare event of a significant systemic reaction to the injections. SLIT appears to have less of a risk for systemic reactions, but it is not risk-free. While SLIT is administered at home, SCIT requires many visits to the allergist's office and should not be offered to those who cannot commit the time necessary for it to be effective. In the United States, only grass, ragweed, and dust mites have been approved for SLIT in tablet form.
AIT doses should not be increased during pregnancy but AIT should not be stopped because of pregnancy. Patients with poorly controlled asthma or fragile cardiovascular disease are at greater risk of systemic AIT reactions and those on beta-blockers may not respond as well to epinephrine if it is needed to treat a severe AIT reaction.
Guidelines for the care of AR provide considerations for consultation with an allergist. Patients with moderate-severe AR might benefit from a consultation, but those with an incomplete response to medications or comorbid conditions should be referred. If allergic triggers need to be identified or AIT is a consideration, the allergist will be useful. Patients suspected of having a structural abnormity contributing to symptoms might benefit from ear, nose throat consultation.
Summary
AR is a highly prevalent disease that has a significant impact on the quality of life and negatively affects the daily activities of the majority of patients. It is often under-appreciated as a source of misery for its sufferers and its comorbidities are often not related to the baseline disease.
Many highly effective and inexpensive treatment options are available for AR, giving us the ability to alleviate the misery it causes. Practitioners should be aware of treatment alternatives, adjusting the medical regimen as needed to provide much-needed relief.
Complications and comorbidities of allergic rhinitis
Of great importance, many patients with AR suffer from complications and co-morbidities that are not always recognized as direct effects of nasal disease. AR is a risk factor for recurrent otitis media and sinusitis. Nasal congestion may result in anosmia, altered taste, and decreased appetite. Chronic mouth breathing may result in halitosis, pharyngitis, and in the long-term a high arched palate and orthodontic disturbances. Post-nasal drip is the most common cause of chronic cough, but patients with AR who cough should also be assessed for possible concurrent asthma.
Perhaps the most underappreciated effects of AR lie in its impact on the quality of life. Nasal congestion is the most bothersome symptom of which patients with AR complain, but the disease has more systemic effects. A very high proportion of patients with AR have constitutional symptoms including fatigue, irritability, and difficulty concentrating. Many are embarrassed by their symptoms and some even become depressed.
About a quarter of patients with AR miss school or work because of their symptoms, but AR is an even greater cause of “presenteeism” with the great majority reporting lost productivity at work or school.
The physical exam
Physical findings in AR may include boggy, pale, bluish hued inferior turbinates, infra-orbital darkening (“allergic shiners”), conjunctival redness, and extra folds of the lower eyelids (Dennie-Morgan folds). The allergic salute commonly results in a transverse nasal crease as a result of the tip of the nose constantly being pushed upward. Post-nasal drip may be visible on physical exam and posterior pharyngeal lymphoid hyperplasia (“cobblestoning”) may be the result of post-nasal drip. Because asthma is common in AR, the lungs should also be examined routinely.
Testing for specific IgE
Allergy skin testing is the preferred method for the identification of allergen-specific IgE. It is less expensive and takes less time to get results than in vitro tests (colloquially called “RASTs”) and in many ways is much easier to interpret. However, I recognize that skin testing is not practical in a primary care office, requiring referral to an allergist.
Most in vitro tests today use similar methods as the older paper disk RASTs, but with a different solid medium. They are more sensitive and specific than true RASTs, although they might not quite approach the statistical value of skin tests. One advantage of in vitro tests is that they do not require that oral antihistamines be withheld beforehand.
Whatever method of testing is chosen, it is important to the only test for allergens thought to be relevant to and potential triggers of the symptoms. The choice of tests and their interpretation must be done in the context of history. It is important to understand that a positive test merely indicates sensitization (the presence of allergen-specific IgE). The diagnosis of allergy relies on the presence of specific IgE AND symptoms with exposure. For that reason, tests for irrelevant allergens should not be requested. Flora varies depending on geographic region. The results of testing for allergen-specific IgE allow for focused recommendations for allergen avoidance (see below).