A 12 year old girl presents with a chief complaint of year-round nasal stuffiness and itching eyes for the last 2 years. Her complaints include eyes which are red, watery and itchy; nasal drip (runny nose), congestion, itching, and a poor sense of smell; and sneezing. Her nasal stuffiness bothers her most. Her symptoms disrupt her daily activities and her sleep. Most of these symptoms improve slightly when she takes diphenhydramine and when she is away from home. However, her nasal stuffiness does not change with taking the medication. She has a cat which sleeps in her bed room.
Past history: As an infant she developed egg allergy and an eczematous rash on her face, trunk and extremities. She has no history of asthma. Family history: Both her mother and brother have asthma and hay fever.
Exam: VS are normal. Her height and weight are at the 50th percentile. She has bilateral conjunctival inflammation (redness) with mild chemosis (edema), dusky discoloration of the skin under the eyelids, marked pale swelling of the nasal mucosa which almost completely occludes the nasal airways without evidence of nasal polyps or masses. Both eyes and her nose have whitish clear exudates. Otoscopic examination shows fluid behind both tympanic membranes. She has generalized dry skin with a scatter of hyperkeratotic plaque on both extremities and pityriasis alba of her face.
She is diagnosed with severe persistent allergic rhinoconjunctivitis and otitis media with effusion (OME) with a history of atopic dermatitis and egg allergy. She is treated with a non-sedating antihistamine without significant improvement. Intranasal corticosteroids are added next with minimal improvement. She is then referred to an allergist for evaluation and further treatment. Her skin allergy test is positive to dust mite and cat dander. Her family follows the allergist's recommendations which include: encasing the mattress and pillows in a plastic bag wrap, removing the cat from the house, using an antihistamine with mast cell stabilizing activity (olopatadine) eye drops and allergen immunotherapy. All of her symptoms have gradually decreased with these recommendations. She has currently discontinued all of her medications; except when she exposes herself to cats or house dust (she may require antihistamines as needed).
Symptoms due to allergy commonly occur in children. Atopy refers to a tendency of exaggerated IgE antibody production and is defined by the presence of specific IgE in vivo (skin prick test) or in vitro (RAST test). Atopy represents a predisposition to atopic or allergic diseases including allergic rhinitis, asthma, eczema and food allergy. Scientific evidence of the systemic link between all of the atopic diseases has been increasing recently.
The atopy march starts early in life and most believe that the fetal environment may already be important for both the development of subsequent sensitization and disease manifestation. Early events under the influence of a variety of environmental factors, such as exposure to environmental endotoxin, allergens, infections, and variations in nutrient intake, affect the expression of the atopy genotype. Age of onset of each atopic disease is unique and may be influenced by the mentioned factors. Typically, both atopic dermatitis and food allergy are commonly seen in young infants; while asthma usually starts after 3 years of age, and allergic rhinitis develops in later childhood.
By definition allergic rhinoconjunctivitis is a symptomatic disorder of the nose (allergic rhinitis) and eyes (allergic conjunctivitis) resulting from an IgE-mediated immunological reaction following exposure to allergens. Rhinoconjunctivitis is a combined term of rhinitis and conjunctivitis because conjunctivitis is usually accompanied with rhinitis in allergic conditions.
Allergic rhinitis (AR) is extremely common in the general population. The prevalence of AR in the US is about 10-20%. An international study shows that the prevalence of allergic rhinitis varies in different parts of the world from 1%-15% in the 6-7 year-olds and 1%-40% in the 13-14 year-olds. Allergic conjunctivitis (AC), the most common form of ocular allergies, is a self-limited, bilateral inflammation of the eyes.
The nose is a specialized structure with 5 important functions: smelling, resonating for phonation, filtration, heating, and humidification of inhaled air. As a filter for inhaled particles, the nose receives an allergen burden, which per square centimeter is considerably higher than in the lower airways. Its function seems to be the price to be paid for the higher prevalence of AR than other atopic diseases. When airborne allergens come in contact with surface fluid on the nasal mucosa, allergenic molecules are removed within seconds by mucociliary transport and only a small fraction of the allergen molecules will penetrate the epithelial lining since proteins of this size are not easily absorbed from the nasal mucosa. The allergens initiate an allergic reaction when they bind with cell-attached IgE molecules. Mast cells, basophils and Langerhans cells are responsible for the interaction and releasing inflammatory mediators.
Human conjunctiva consist of a nonkeratinized, stratified squamous cell epithelium. The conjunctiva includes goblet cells within the epithelium and overlies the substantia propria, which is composed of connective tissue with cellular elements including mast cells, lymphocytes, macrophages and fibroblasts. One of the highest concentrations of mast cells is at the limbus (the junction of the conjunctiva/sclera and the cornea). The mast cells in the human conjunctiva tend to be centered just beneath the basal epithelial cell layer and around blood vessels. AC is caused by direct exposure of the ocular mucosal surfaces to environmental allergens. The allergic inflammation starts the same as in the nose when allergens bind to the cell-attached IgE molecules and then mediators are released from the cells. Histamine is the principal mediator involved in ocular allergy and inflammation. Most of the allergic reactions are mediated through the effects of histamine on H1 receptors which are found the conjunctiva, cornea, and ophthalmic arteries.
There are two phases of the allergic response in allergic rhinoconjunctivitis: the early phase (minutes to hours) and late phase (6 hours to days). The early phase is induced by mediators such as histamine, prostaglandin, neuropeptides and leukotrienes released by the mast cells. Histamine directly stimulates sensory neurons, inducing pruritus and sneezing, and in concert with the leukotrienes, stimulates the vascular endothelium, inducing vasodilation and increased vascular permeability. Histamine also induces cholinergically mediated reflex glandular secretions, which can be inhibited by atropine or ipratropium. The early phase results in itchy eyes and nose, sneezing, watery eyes, rhinorrhea, edematous conjunctiva and nasal mucosa. After several hours of allergen exposure, other inflammatory cells including eosinophils, neutrophils and activated lymphocytes are demonstrable in the last phase response. The late phase or cellular phase leads to a recrudescence of nasal or eye symptoms associated with a second rise in histamine occurring in some affected persons. Basophils are felt to be responsible for the late-phase histamine peak. Eosinophil activation and accumulation with the release of eosinophilic proteins and mediators are the cause of increasing nasal blockage and hypersensitivity. It results in increasing sensitivity when repeatedly exposed to the same allergens (called the priming phenomenon).
The major symptoms of AR are sneezing, rhinorrhea, nasal pruritus and nasal congestion. There are two common presentations, seasonal and perennial allergic rhinitis. Seasonal allergic rhinitis is characterized mainly by periodic symptoms of the nose, ears, and throat with watery rhinorrhea, nasal congestion, sneezing, and pruritus occurring during the pollination season of the plants (typically, trees in spring, grass in summer and weeds in fall) to which the patient is sensitive. The sneezing, pruritus and rhinorrhea are a main complaint in the seasonal type. Perennial allergic rhinitis is characterized by intermittent or continuous nasal symptoms resulting from indoor allergen exposure (house dust mites, animal fur) without seasonal variation. Nasal obstruction may be the major or sole complaint of the perennial type, particularly in children, in whom the nasal passage is relatively small. Lacrimation, sneezing, clear rhinorrhea and itching of the nose, ears and throat may also occur. The symptoms are less severe than seasonal allergic rhinitis. The decreased severity of the symptoms seen in these patients may lead them to interpret their symptoms as resulting form "sinus trouble" or "frequent colds". In reality, the differentiation of seasonal and perennial types may not be clearly defined. Physical findings of AR often reveal changes in the eyes, nose, ears and throat. A horizontal nasal crease, caused by upward rubbing of the nose due to itching (allergic salute), is usually seen in children. The pale or bluish nasal mucosa with variable degrees of swelling and nasal blockage, and clear watery or yellow nasal secretions may be seen. The appearance of dark circles under the eyes (allergic shiners) is due to venous engorgement secondary to nasal congestion. Periorbital eczema, erythematous conjunctiva with papillary hypertrophy, and gelatinous secretions may appear. Posterior pharyngeal lymphoid hyperplasia secondary to postnasal drip is also noted. Middle ear fluid (otitis media with effusion or serous otitis media) is commonly noted. In some patients, however, the above findings are absent. All of the symptoms may be associated with recurrent sinusitis, asthma or eczema.
The symptoms of AC are watery, itchy, red, sore, swollen, stinging and burning eyes. Corneal symptoms, including photophobia and blurring of vision, are reported in rare cases. The ocular symptoms are frequently associated with nasal and/or pharyngeal symptoms. AC is seldom followed by permanent visual impairment. The presentation can be varied from mild to very severe and can be categorized into seasonal and perennial type. Seasonal allergic conjunctivitis (SAC) is more common and more severe. The onset of symptoms is seasonally related to specific circulating aeroallergens. Grass pollens are more commonly thought to be associated with more ocular symptoms than other aeroallergens. Ragweed is the most common cause of AC accompanying AR. Perennial allergic conjunctivitis (PAC) has symptoms throughout the year. PAC patients may have seasonal exacerbations. Dust mites, animal dander, and feathers are the most common airborne allergens implicated in PAC, which is more likely than SAC to be associated with perennial rhinitis. Both PAC and SAC patients are similar in distribution of age, sex, and associated symptoms of AR, asthma or eczema. Clinical findings of AC include: milky or pale pink conjunctiva with vascular congestion that may progress to conjunctiva swelling (chemosis), a white exudate during the acute state that becomes stringy in the chronic form. The conjunctiva surfaces are mildly injected with various degrees of chemosis. Lid edema sometimes occurs, as well as papillary hypertrophy along the tarsal conjunctival surface (the palpebral surface may appear bumpy). The clinical signs and symptoms are usually bilateral, although the degree of involvement may not be symmetrical.
The diagnosis of allergic rhinoconjunctivitis is based on a detailed history and physical findings as mentioned. Many allergic patients do not report the ocular or nasal symptoms unless they are asked directly about them during a medical examination. When evaluating patients who present with significant nasal symptoms, the following questions should be asked:
1. Is the nasal congestion or sneezing/itching/runny nose a main concern? Are there eye symptoms?
2. Does an activity or allergen exposure or a specific environment contribute to the symptoms? Seasonal or year-round symptoms? What are the clinically relevant allergens?
3. Are there other atopic diseases in the patient or the family?
4. Were any medications including topical OTC preparations (nasal and eye drops) used in the past?
5. Do the symptoms cause a major impact on lifestyle such as school activity or sleeping?
Typically, patients with classic symptoms do not require any tests. Slightly elevated serum IgE, mild peripheral blood eosinophils and eosinophilia of the nasal secretions are common findings; but these results are not diagnostic. Allergy testing including skin testing or radioallergosorbent test (RAST) may be required for the diagnosis and guidance of environmental avoidance in some patients with uncontrollable disease or atypical presentations. The allergy tests in young children are limited because positive specific IgE or skin prick tests to inhaled allergens usually develop after the second year of life.
Skin testing is the most common test for the diagnosis of allergy because of its simplicity, high sensitivity, low cost and rapidity of the result. Prick testing is widely used by allergists since the test is quick, not painful, inexpensive, highly specific with a low risk of systemic reaction. Prick testing requires: 1) devices such as metal needles or lancets or commercial test devices, 2) allergen extracts, 3) positive controls (histamine) and negative controls (glycerin or saline). A physician and equipment for treating anaphylaxis reaction should be readily available while performing the test. Patients should be instructed to discontinue some medications inhibiting skin response for a period of time including tricyclic antidepressants (5 days), hydroxyzine (3 days), astemizole (60 days), and other antihistamines (3 days). Contraindications for skin tests are generalized skin disease, inability to discontinue antihistamines, history of severe reactions or anaphylaxis to previous skin testing, pregnancy, dermatographism, unstable angina and beta-adrenergic receptor agent therapy (beta blockers, beta agonists or both). A response to an allergen with a wheal size greater than 3 mm in diameter indicates a positive result and having a specific IgE to the allergen. If the skin prick result is negative, an intradermal skin test may be considered in a highly suspected patient since the intradermal skin test is more sensitive.
RAST is an in vitro test for specific IgE antibodies based on the principle of immunoabsorption . This in vitro test for allergy is a convenient allergy test for non-allergist physicians or for patients who have contraindications for skin testing. RAST is not as sensitive as the skin test in most instances. Appropriate in vitro tests correlate up to 70-80% of the time with prick skin tests. CAP-RAST testing (a type of RAST test) is preferred over other RAST tests because of better standardization.
The differential diagnosis of allergic rhinoconjunctivitis includes infectious rhinoconjunctivitis, which includes the common cold, usually caused by rhinovirus, RSV, parainfluenza virus, influenza virus and adenovirus. Fever, sore throat, thick purulent rhinorrhea or eye discharge, erythematous nasal mucosa, and the presence of cervical lymphadenopathy are helpful differential findings in infectious rhinitis. Common diseases that may be confused with perennial allergic rhinitis are recurrent infectious rhinitis, chronic sinusitis, and vasomotor rhinitis. Structural and mechanical conditions that may mimic perennial allergic rhinitis include a deviated nasal septum, hypertrophic turbinates, adenoid hypertrophy, foreign bodies and tumors. Inflammatory and immunologic diseases such as Wegener's granulomatosis and sarcoidosis may present with rhinitis symptoms. Nasal polyposis, an uncommon condition causing nasal congestion in children, is usually associated with cystic fibrosis, asthma and aspirin intolerance and predisposes to sinusitis.
Nonallergic rhinitis with eosinophilia (NARES) may be misdiagnosed as allergic rhinitis. NARES is not IgE dependent and is not associated with high IgE levels or positive skin tests. Symptoms in NARES are more likely to be induced by exposure to irritants, strong odors, cold air, and cigarette smoke. Drug-induced rhinitis is associated with use of various oral agents, especially certain classes of antihypertensive beta- blockers, oral contraceptives, chlorpromazine, aspirin and overuse of topical (nasal drops and sprays) sympathomimetics (rhinitis medicamentosa). Other less-common causes of rhinitis include occupational exposure, hormones, food and alcohol.
Several eye diseases need to be differentiated in patients with allergy and ocular symptoms. Irritative and chemical conjunctivitis is commonly confused with AC. The main symptom caused by environmental pollutants and smoke is conjunctival hyperemia. Atopic keratoconjunctivitis typically occurs in patients with atopic dermatitis. It is a bilateral, sight-threatening disease and symptoms are much more severe than SAC and PAC. The symptoms include significant itching, burning and redness, eventual fibrosis, decreased keratinization of conjunctival surfaces, cataract formation and lid malposition. Vernal keratoconjunctivitis is a chronic form of allergic conjunctivitis characterized by large "cobblestone" papillae on the underside of the eyelid. The symptoms are intensely pruritic and sight-threatening. Giant papillary conjunctivitis, a non-allergic condition, may be confused with ocular allergy. Giant papillae on underside of eyelid and non itching are distinguishing symptoms.
The management of allergic rhinoconjunctivitis in children includes allergen avoidance and education, medications and allergen immunotherapy as in adults. Allergen avoidance and environmental control are the main stay of treatment in all age groups.
Allergen avoidance and environmental control:
A wide range of allergens have been associated with allergic rhinoconjunctivitis, of which house dust mites are clearly the most important. The single most effective strategy for reduction of dust mite exposure involves bed-covering systems, which separate the mite allergens from the allergic individual by encasing mattress, pillows and blankets with mite allergen impermeable covers. Other recommendations for dust mite control are: 1) Washing the blankets, bed linen or other washable material such as curtains and toys in hot water over 55 degrees C regularly once a week. 2) Removing children's soft toys or washing/freezing the toys once a week. 3) Removing and replacing carpet in the house with vinyl or polished wooden floor boards. If it is impossible to remove the carpet, the carpet can be completely covered by polyethylene sheeting. 4) Mite control (acaricide) sprays have demonstrated some effects in reducing mite numbers and allergen levels. However, the clinical efficacy demonstrates only reducing symptom scores but not medication use. 5) High efficiency particulate air (HEPA) vacuum cleaners can reduce allergen load but no trial has demonstrated that this will improve symptoms.
Cat and dog fur is one of major allergens implicated in causing the perennial type. The allergens are not the dander itself but are contained in the saliva and in sebaceous secretions, which can flake off in small particles and remain airborne for considerable periods of time. This results in a ubiquitous allergen that can be found in many public places, even in a cat-free or dog-free buildings and schools. It makes avoidance much more difficult. The only effective measure for avoiding the allergens in the home is to remove the pets, carefully vacuum and clean all carpets, mattresses and upholstered furniture. Frequent washing of cats may reduce allergen exposure. However, clinical studies have not shown a clear benefit from this procedure when carried out once a week. A placebo-controlled trial of a HEPA air cleaner in the treatment of cat allergy did not find a significant effect on rhinitis.
Indoor molds can be removed with a bleach solution and can be followed by measures to reduce local moisture or humidity such as using a dehumidifier. Outdoor allergens, such as pollens, grass and fungal spores, are difficult to avoid. Outdoor exercising in the morning for sufferers with pollen allergy is recommended. These sufferers should be reminded to keep their bedroom window closed during the daytime and open windows only at night when the pollen count is low.
Medical treatment for allergic rhinitis:
It should be noted that there are only a few medications that have been tested in children under the age of two years. In young children under the age of four, use of nasal saline drops or spray can simply comfort them and help to clear their nose before eating or sleeping. Several concerns of medical treatment in children have been raised. The most important aspects are the antihistamine side effects on the cognitive functions of pre-school and school children. The use of systemic corticosteroids such as oral or depot-preparations should be deferred due to their systemic adverse effects. Children with allergic rhinitis who are athletes should be advised about the medications used since some of these medications are prohibited by various sports organization. Alpha-adrenergic agonists and systemic decongestants (both often combined with H1-antihistamines) are often prohibited in organized youth sports since they have a central stimulant effect. For intranasal corticosteroid use, a medical certificate documenting medical necessity should be issued. However, the regulations vary between countries, so physicians treating the athletes should be aware of these regulations.
All H1 antihistamines are competitive antagonists of histamine and are rapidly absorbed from the gastrointestinal tract. Antihistamines are most effective for sneezing, pruritus and rhinorrhea. They exert little effect on nasal congestion. Therefore, as a rule, they are more effective in acute, seasonal allergic rhinitis than in the perennial form in which congestion or stuffiness is usually more prominent. The use of H1-antihistamines is important for the treatment of rhinitis in children. The response to different antihistamines may differ from patient to patient, but it has been demonstrated that children not responding to one antihistamine may respond to another.
Antihistamines have been classified into first and second generation families. Some of the commonly used first generation antihistamines are triprolidine, diphenhydramine, chlorpheniramine, azatadine and hydroxyzine. All of them except hydroxyzine are over-the-counter medications (OTC). The first-generation antihistamines cause drowsiness, reducing one's ability to concentrate, blunting cognitive functions to some extent, and have varying anti-muscarinic effects such as dry mouth, constipation, blurring of vision, urinary retention. Their adverse effects limit their utility. Their use should be restricted to two relatively uncommon situations: 1) Children with urticaria or atopic dermatitis whose pruritus is so severe that the sedation produced by an old H1-antagonist, such as diphenhydramine or hydroxyzine, is a benefit rather than a risk. 2) Children with anaphylaxis who require intravenous diphenhydramine as adjunctive treatment to epinephrine and other medications.
Second-generation antihistamines are recommended for seasonal AR. Currently available forms include:
. . . . . azelastine (Astelin): nasal spray, BID.
. . . . . cetirizine (Zyrtec): low sedating, PO, once daily.
. . . . . loratadine (Claritin): non-sedating, PO, once daily.
. . . . . fexofenadine (Allegra): non-sedating, PO, BID.
. . . . . desloratadine (Clarinex): non-sedating, once daily.
Only cetirizine and desloratadine are approved by FDA for perennial allergic rhinitis. Loratadine and fexofenadine are less sedating (minimal or no drowsiness). The above oral antihistamines are available as a combination medication with pseudoephedrine (Zyrtec-D, Claritin-D, Allegra-D) since antihistamines have little effect on congestion. However, the use of an antihistamine with decongestant is limited to children older than 12 years. Desloratadine (Clarinex) is a non-racemic form of loratadine.
Intranasal corticosteroids ("steroids" for short) have proved to be the most effective class of drugs in reducing the symptoms of allergic rhinitis. This clinical response reflects the broad anti-inflammatory activity and multiple pharmacologic actions of corticosteroids. They have demonstrated specific effects on decreasing the activity of inflammatory cells such as mast cells, basophils, eosinophils, Langerhans' cells and decreasing the levels of chemical mediators including histamine, Th2 cytokines, chemokine and adhesion molecules. A single dose of intranasal steroid administration blocks the late-phase response; whereas repeated dosing blocks both early and late response, as well as the priming phenomenon. Intranasal steroids reduce the specific IgE production in seasonal allergic rhinitis and decrease nasal hyperresponsiveness or the priming phenomenon.
Intranasal steroids have been considered as second line agents after antihistamines by many physicians; however, first-line use of intranasal steroids is becoming increasingly common, especially for patients with moderate to severe symptoms. Intranasal steroids are more efficacious in chronic symptom relief than oral antihistamines, decongestants and cromolyn except for eye symptoms. Regular use of intranasal steroids is more effective than intermittent p.r.n. use, but p.r.n. use does have some efficacy in many patients. Although no well controlled study of a combination use of steroids and other medications is published, in clinical practice, intranasal steroids can be used in combination with other therapies to achieve optimal improvement in overall symptoms.
Several intranasal steroids are available including beclomethasone (Beconase, Vancenase), flunisolide (Nasarel), triamcinolone (Nasacort), budesonide (Rhinocort), fluticasone (Flonase) and mometasone (Nasonex). After using the recommended dosage for 2 weeks, the patient should be reevaluated, and the dosage can be adjusted based on the clinical response. The goal of therapy should be to use the lowest dosage that provides effective relief of symptoms. With proper use of intranasal steroids, 60-90% of patients may have nearly complete relief of rhinitis symptoms.
The most frequently observed adverse effect with intranasal steroids is local irritation. Approximately 10% of patients have some form of nasal irritation, nasal burning or sneezing after administration. Bloody nasal discharge occurs in approximately 2% and a few cases of septal perforation were reported due to improper techniques of administration. Long-term use of intranasal steroids does not appear to cause a significant risk of adverse morphologic effects on the nasal mucosa. Systemic side effects of intranasal steroid are rare, such as growth suppression due to low systemic absorption. Generally, the systemic absorption can occur through direct intranasal absorption or through gastrointestinal absorption of the swallowed fraction of the administered dose. It is likely that approximately 80% of the administered intranasal dose is swallowed resulting in systemic absorption. Mild growth suppression may result from chronic use of beclomethasone since it is metabolized to another active steroid compound.
Cromolyn sodium (Nasalcrom) has been one of the common drugs used for AR in children. It inhibits mast cell mediator release, and may inhibit C-type sensory nerve fiber transmission which modulates vascular and glandular responses. The drug is effective only when applied topically to the mucosal surface of the allergic end organ. It cannot be used orally for allergic disease. Cromolyn has been shown in numerous studies to be effective for both types of AR. It has a greater benefit in seasonal type symptoms and in highly allergic persons.
The major advantage of cromolyn is its safety, since there are no significant side effects of this drug. Its major drawback is the Q.I.D dose. In addition, it must be used on a regular basis to be effective, and ideally should be started before the onset of the symptoms. In patients with the seasonal type, cromolyn is best initiated just before the season starts at a dose of one spray in each nostril four times daily, and is continued throughout the season. In patients with perennial type, it can be started at any time, but it may take a few to several days to be effective. The recommended dose is one to two sprays in each nostril four times daily. After a patient's symptoms have stabilized, the dose may be decreased to three times daily, with increases to four times daily if symptoms worsen. Patients who are allergic to known triggers, such as animals, can use two sprays of cromolyn in each nostril 30 minutes before allergen exposure to prevent an allergic reaction.
Montelukast (Singulair), a leukotriene receptor antagonist given orally, has a new indication to be used for seasonal allergic rhinitis. Its efficacy might be equal to oral antihistamines (more data are needed), but it is less effective than intranasal corticosteroids and more expensive than both.
Nasal ipratropium (Atrovent), a topical anticholinergic nasal spray, is useful in patients with both allergic and non allergic rhinitis who experience rhinorrhea from various other triggers (e.g., cold air, eating spicy foods, and other irritants), by controlling rhinorrhea induced by nonspecific activation of cholinergic receptors. Its effectiveness is limited in patients with moderate to severe allergic rhinitis because ipratropium has little effect on other symptoms, such as sneezing, pruritus, or congestion. It is commonly used as an adjunct therapy if the rhinorrhea symptoms still persist with the antihistamine or intranasal steroid treatment. It is recommended for use in children older than 6 years. Common adverse effects are drying of the nasal mucosa and mild epistaxis.
Adrenergic nasal decongestants are available in both topical forms (e.g., oxymetazoline, phenylephrine and propylhexedrine) and oral forms (e.g., pseudoephedrine, phenylpropanolamine). The decongestants increase nasal patency by inducing vasoconstriction and reducing tissue swelling and obstruction. Although the decongestants have been used in children for years, there are very few studies in these young patients. The decongestants can be useful initially, often coupled with an antihistamine to control active allergic rhinitis symptoms. Once control is achieved, further symptoms usually can be prevented by the judicious use of antihistamines alone or with a nasal corticosteroid.
Decongestants should be deferred in small children and in patients who currently take MAO inhibitors. The side effects of oral decongestants are nervousness, dizziness, tachycardia, shakiness, urinary retention, insomnia. Its long-term round-the-clock use may increase the risk for hypertension. There is an association of hemorrhagic stoke and phenylpropanolamine (PPA) use in adults. Therefore, PPA was removed from the market by the FDA in November 2000. The major concern of nasal decongestants is the prolonged use which may induce rhinitis medicamentosa (especially with topical decongestants), which is rebound mucosal swelling from withdrawal of the medication. This discomfort may prompt the patient to use the medication frequently to avoid a sense of smothering. Ultimately, this cycle can induce serious irreversible mucosal damage. Therefore, topical preparations should be used for not more than 3 to 5 consecutive days to prevent rhinitis medicamentosa.
A guideline of treatment for allergic rhinitis: Recently, an expert panel in association with the World Health Organization (WHO) has recommended a guideline for the medical treatment of AR based on clinical severity ("mild" or "moderate-severe"). The severity is further subdivided into "intermittent" or "persistent" according to the duration of symptoms. It is necessary to define the severity of the allergic individual, then the choices of medications are based on the severity:
"Mild" means that none of the following items are present: sleep disturbance, impairment of daily activities (leisure and/or sport), impairment of school or work, troublesome symptoms. "Moderate-severe" means that one or more of the above items is present and a disturbance or impairment exists which not found in "mild". "Intermittent" means that the symptoms are present for less than 4 days a week or for less than 4 weeks. "Persistent" means that the symptoms are present more than 4 days a week or for more than 4 weeks. Treatment recommendations are as follows:
For mild intermittent disease: oral or intranasal H1 antihistamines or intranasal decongestants (for less than 10 days and not to be repeated more than twice a month) or decongestants (not recommended in children less than 12 years old).
For moderate-severe intermittent disease: oral or intranasal H1 antihistamines or oral H1-antithistamines or decongestants or intranasal steroids or cromolyn sodium .
For mild persistent disease: Same medications as for moderate-severe intermittent above. The patient should be reassessed after 2 to 4 weeks. A stepwise approach is advised. If the patient has persistent mild symptoms and is on an H1-antihistamine or cromolyn treatment, changing the medication to an intranasal steroid is suggested. The dosage of intranasal steroids may be reduced by half if the patient responds well to the treatment. In seasonal allergy, a shorter course of treatment is required depending on the pollen season. However, long-term treatment may be needed especially in perennial allergy.
For moderate-severe persistent disease: Intranasal steroids are the first line treatment. The patient should be reassessed after 2 to 4 weeks of the treatment. A stepwise approach is advised. If the patient does not improve, consider other reasons for failure to respond to the treatment including heavy persistent allergen exposure (e.g., cat on the bed), inadequate medication compliance, nasal obstruction preventing drug delivery, other additional nasal pathology such as nasal polyps, sinusitis or nasal septal deviation, and a wrong diagnosis. If the major symptom is blockage, doubling the dose of the intranasal steroid is suggested. Add an H1-antihistamine if the symptoms of sneezing, itching or rhinorrhea still exist. Add ipratropium if rhinorrhea is not improved. If the patient's symptoms are less, a step down approach should be used. However, the treatment should last for at least three months or for the duration of the pollen season. In the step down treatment, a low dose of intranasal steroid may be required as a maintenance treatment to control symptoms. Referral to a specialist may be considered if the treatment is not fully effective, or if the duration of the treatment is over 3 months and the medications are not helpful.
Medical treatment of allergic conjunctivitis:
The primary goal of medical treatment is to alleviate the ocular symptoms and signs which disrupt the patient's quality of life. Initial management with allergen avoidance, cold compresses, and lubrication (artificial tears) should be tried before ocular agents are tried. Cold compresses provide considerable symptomatic relief, especially from ocular pruritus and swelling. In fact, all ocular medications provide additional subjective relief when applied immediately after refrigeration. Tear substitutes consisting of saline solution combined with a wetting and viscosity agent, such as methylcellulose or polyvinyl alcohol, can be applied topically 2 to 4 times a day and as needed. It is a soothing, effective, convenient and inexpensive option which directly removes and dilutes allergens that may come in contact with the conjunctiva.
Oral antihistamines used for the treatment of systemic or nasal allergy can reduce but do not eliminate the eye symptoms. However, treatment with oral antihistamines, especially the first generation, may cause eye dryness which interferes with the ocular defense mechanism and increases the potential for ocular irritation and sensitivity. The use of a "topical" agent on the affected eyes is the easiest and most direct therapeutic method. An important consideration for effective topical treatment is compliance. Treatments causing ocular irritation are likely to diminish compliance and may lead to a chronic duration of the condition, decreased patient satisfaction, and increased ocular sensitivity. Efficacy of these agents varies from patient to patient, and the choice of agent used will depend on the underlying health of the eye and other variables, such as drug cost, contact lens wear, and compliance. Several topical agents are available for the treatment and the prophylaxis of ocular allergies. These include vasoconstrictors, antihistamines, mast cell stabilizers, and anti-inflammatory agents.
OTC topical antihistamines are widely used in combination with topical vasoconstrictors. The combination is more effective than either agent alone or a systemic antihistamine. Adverse effects of topical vasoconstrictors include burning and stinging on instillation, mydriasis, rebound hyperemia or conjunctivitis medicamentosa with chronic use and drug interaction with MAO inhibitors. Topical vasoconstrictors are contraindicated in patients with narrow angle glaucoma.
Topical prescription antihistamines, including levocabastine, emedastine and azelastine, are a good option for symptomatic relief of an ocular allergy. Since these agents do not provide mast cell stabilization, they do not prevent or treat a significant cause of the allergy. All of the topical antihistamines require dosing as frequently as every 4-6 hours, except azelastine which requires only BID dosing, which may improve compliance.
Topical mast cell stabilizers include cromolyn, nedocromil, lodoxamide and pemirolast. It should be noted that the medications require several days (3-5 days) to start providing symptomatic relief of ocular allergy. The relief reported within 15 minutes probably represents a "washout" effect immediately after contact with the eyes. Long term use of these agents is necessary since they are preventive only. These agents require Q.I.D. administration with the exception of nedocromil which is B.I.D. Topical dual action antihistamine and mast cell stabilizers include ketotifen and olopatadine. Therefore, they have rapid onset and prolonged duration of action. Both of them are approved for twice a day dosing for treating AC in children 3 years and older. Topical ketorolac (a nonsteroidal anti-inflammatory agent) is approved for use in children 12 years and older with acute SAC. It inhibits allergen induced prostaglandin production which diminishes the ocular itching and conjunctival hyperemia. Local administration of topical corticosteroids is associated with localized ocular complications such as viral infection, elevated intraocular pressure and cataract formation. Therefore, routine use is not recommended and their use should be under the close supervision of an ophthalmologist.
Allergen immunotherapy (AIT) is a safe and effective treatment for long-term control of allergic rhinoconjunctivitis. AIT is considered when environmental control is limited, when medications are ineffective or not well tolerated, or when the symptoms are a significant trigger for other chronic problems such as asthma or sinusitis. AIT results in successful treatment of AR in 85%-90% of cases. It is also recommended as a treatment for venom or insect hypersensitivity and selected cases of asthmatics. Patients with chronic urticaria, atopic dermatitis, or food allergy do not benefit from AIT. AIT induces immune tolerance to the specific allergens. In many cases, AIT can prevent clinical progression of allergic disease and may minimize the development of sensitization to multiple allergens in patients who are sensitized to a single allergen. The terms, "allergen vaccination" and "allergen immunotherapy", can be used interchangeably.
Prior to considering AIT, the patient must have evidence of specific IgE sensitivity such as a positive skin test or RAST test. Small doses of allergen extracts to which the patient is sensitized, are administered subcutaneously. The injected dose can be gradually increased as in a conventional AIT or rapidly increased as in a rush AIT until the maintenance dose is reached. The goal is to blunt the immune response with an optimal dose.
The efficacy of AIT for common allergens including house dust mite, cat, cockroach, birch, grass, and ragweed pollens have been well-documented. The efficacy of AIT depends on the quality of the allergen extract, the duration, the frequency of administration, the relevant allergens and the allergen doses. The dose of specific protein delivered in an allergen extract is crucial for induction of immune tolerance. If the extract is highly diluted or there are too many allergens which result in reduction of the relevant allergen dose, it will compromise the efficacy. In low doses, AIT is not effective in most patients. Therefore, a high dose of allergen extract per injection must be achieved as a maintenance dose to provide significant clinical benefit.
Allergic rhinoconjunctivitis causes substantial morbidity although the disease is not associated with mortality. Many physicians do not pay attention to the disease because they underestimate the impact of allergic rhinoconjunctivitis on other diseases, quality of life and performance. AR is a common cause of asthma exacerbation or uncontrolled persistent asthma. It is estimated that up to 90% of children with asthma have respiratory allergies, especially to indoor allergens such as house dust mite, Alternaria species, cockroach, or cat. All asthmatics should be evaluated for allergic rhinitis. Untreated or undertreated allergic rhinitis is associated with the development of otitis media with effusion (OME) and sinusitis. The OME may result in hearing impairment, which worsens progressively as the symptoms continue. There is strong evidence that AR and atopic dermatitis are more common in children with OME compared with normal subjects. Therefore, children with OME should be assessed for allergic rhinoconjunctivitis and children with allergic rhinoconjunctivitis should be assessed for OME. Adverse effects of allergic rhinoconjunctivitis in children are school absences, poor performance, poor concentration, headaches, malaise, and lethargy as a consequence of sleep disturbance and therefore reduced ability to learn. Furthermore, many of the antihistamines employed have some sedating effects, thereby aggravating the problem.
Although genetic factors contribute to the risk of allergic disease development, it is likely that environmental factors are partially responsible for the increase in the prevalence of atopic diseases. Therefore, changing the surrounding environment or other factors may decrease or prevent the atopic diseases. The following measures are recommended:
1. Raising children in a smoke-free environment, starting in utero.
2. Breast feeding for 4-6 months, delaying the introduction of solid food until 6 months of age, and withholding highly allergenic foods such as egg and peanut for 2 to 3 years, especially in a highly allergic family.
3. Reducing exposure to environmental allergens, especially in patients who have already developed respiratory allergies.
A hygiene hypothesis is supported by some studies. This hypothesis implies that overcrowding and unhygienic contacts early in life may protect from atopic diseases. The changes of human microbial flora, declining exposure to food-borne and orofecal infections, to helminths and to environmental sources of endotoxin are putative contributors to the rise of allergy cases among populations living with a western lifestyle. Lifestyle or clinical recommendations based on this hygiene hypothesis still remain to be proven.
1. The most prevalent of allergic disease in school-age children is:
. . . . . a. Atopic dermatitis
. . . . . b. Food allergy
. . . . . c. Asthma
. . . . . d. Allergic rhinitis
. . . . . e. Drug allergy
2. A 15 year-old has had persistent year-round nasal itching and stuffiness. What is the most likely allergen responsible for the symptoms?
. . . . . a. Dust mite
. . . . . b. Weed
. . . . . c. Tree
. . . . . d. Grass
. . . . . e. Mold
3. Which one is the most effective method for controlling dust mite exposure?
. . . . . a. Encasing mattresses, pillows and blankets
. . . . . b. Spraying an acaricide agent in the house
. . . . . c. Using HEPA air filter and vacuum
. . . . . d. Removing furniture and carpet in the house
. . . . . e. Washing washable materials in hot water
4. The most effective measure for allergen avoidance in furred animal allergy is:
. . . . . a. Washing the animal twice a week.
. . . . . b. Using HEPA air filter and vacuum in the house.
. . . . . c. Limit areas of the animal in the house.
. . . . . d. Removing furniture and carpet in the house.
. . . . . e. Removing the animal from the house.
5. Which one is the appropriate medical treatment of an 8 year old girl who develops nasal allergy in spring season?
. . . . . a. Diphenhydramine
. . . . . b. Cetirizine
. . . . . c. Fexofenadine with pseudoephedrine
. . . . . d. Nasal decongestant spray
. . . . . e. Beclomethasone nasal spray
6. The most effective and appropriate for a child with chronic allergic rhinitis and nasal stuffiness is:
. . . . . a. Intranasal antihistamine
. . . . . b. Intranasal corticosteroid
. . . . . c. Intranasal decongestant
. . . . . d. Oral antihistamine
. . . . . e. Oral antihistamine and decongestant
7. Which one is the most common adverse effect of intranasal steroids?
. . . . . a. Nasal irritation
. . . . . b. Septal perforation
. . . . . c. Nasal bleeding
. . . . . d. Short stature
. . . . . e. Adrenal suppression
8. Which one of the diseases benefits from allergen immunotherapy?
. . . . . a. Food allergy
. . . . . b. Atopic dermatitis
. . . . . c. Allergic rhinoconjunctivitis
. . . . . d. Latex allergy
. . . . . e. Chronic urticaria
9. Which one of the following eye drops has both antihistamine and mast cell stabilizer properties?
. . . . . a. Naphazoline
. . . . . b. Levocabastine
. . . . . c. Cromolyn
. . . . . d. Olopatadine
. . . . . e. Rimexolone
10. A mother of children with multiple allergic diseases asks you for allergy prevention advice for her next child. What would you recommend?
. . . . . a. Smoking free environment
. . . . . b. Breast feeding at least 4 months
. . . . . c. Diet control during pregnancy
. . . . . d. Using HEPA air filter and vacuum
. . . . . e. Both a and b
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Answer to questions
1.d, 2.a, 3.a, 4.e, 5.b, 6.b, 7.a, 8.c, 9.d, 10.e