1. Allergic Rhinitis in Children
Dr. KANUPRIYA CHATURVEDI

2. Outline of Presentation
What is allergic rhinitis?
Epidemiology
Pathophysiology
Diagnosis and differential diagnosis
Assessment and classification of AR
Health effects of AR
Management of AR

3. What is Allergic Rhinitis
Allergic rhinitis involves inflammation of the mucous membranes of the nose, eyes, eustachian tubes, middle ear, sinuses, and pharynx.
The nose invariably is involved, and the other organs are affected in certain individuals.
Inflammation of the mucous membranes is characterized by a complex interaction of inflammatory mediators but ultimately is triggered by an immunoglobulin E (IgE)–mediated response to an extrinsic protein

4. IgE mediated Rhinorhoea Nasal blockage Postnasal drip Itchiness
Sneezing
Associated health effects
IgE mediated
Allergic rhinitis is associated with a symptom complex characterized by paroxysms of sneezing, rhinorrhea, nasal obstruction, and itching of the eyes, nose, and palate. It is also frequently associated with postnasal drip, cough, irritability, and fatigue [1-3].
The pathogenesis of allergic rhinitis is presented in this topic review. The clinical manifestations, diagnosis, and treatment of this condition are discussed separately. (See "Clinical manifestations and epidemiology of allergic rhinitis (rhinosinusitis)" and "Diagnosis of allergic rhinitis (rhinosinusitis)" and "Pharmacotherapy of allergic rhinitis".)

5. Pathophysiology
The tendency to develop allergic, or IgE-mediated, reactions to extrinsic allergens has a genetic component.
In susceptible individuals, exposure to certain foreign proteins leads to allergic sensitization, which is characterized by the production of specific IgE directed against these proteins.
This specific IgE coats the surface of mast cells, which are present in the nasal mucosa.
When the specific protein is inhaled into the nose, it can bind to the IgE on the mast cells, leading to immediate and delayed release of a number of mediators.

6. Pathophysiology
The mediators that are immediately released include histamine, tryptase, chymase, kinins, and heparin.
The mast cells quickly synthesize other mediators, including leukotrienes and prostaglandin D2.
These mediators, via various interactions, ultimately lead to the symptoms of rhinorrhea (ie, nasal congestion, sneezing, itching, redness, tearing, swelling, ear pressure, postnasal drip).
Mucous glands are stimulated, leading to increased secretions. Vascular permeability is increased, leading to plasma exudation.
Vasodilation occurs, leading to congestion and pressure. Sensory nerves are stimulated, leading to sneezing and itching. All of these events can occur in minutes; hence, this reaction is called the early, or immediate, phase of the reaction

7. Pathophysiology
Over 4-8 hours, these mediators, through a complex interplay of events, lead to the recruitment of other inflammatory cells to the mucosa, such as neutrophils, eosinophils, lymphocytes, and macrophages.
This results in continued inflammation, termed the late-phase response.
The symptoms of the late-phase response are similar to those of the early phase, but less sneezing and itching and more congestion and mucus production tend to occur.[13]
The late phase may persist for hours or days.

8. Epidemiology
Frequency: Allergic rhinitis affects approximately 40 million people in the United States. Recent US figures suggest a 20% cumulative prevalence rate. Scandinavian studies have demonstrated a cumulative prevalence rate of 15% in men and 14% in women.[17] The prevalence of allergic rhinitis may vary within and among countries. This may be due to geographic differences in the types and potency of different allergens and the overall aeroallergen burden.
Mortality/Morbidity- While allergic rhinitis itself is not life-threatening (unless accompanied by severe asthma or anaphylaxis), morbidity from the condition can be significant. Allergic rhinitis often coexists with other disorders, such as asthma, and may be associated with asthma exacerbations.

9. Epidemiology
Race: Allergic rhinitis occurs in persons of all races. Prevalence of allergic rhinitis seems to vary among different populations and cultures, which may be due to genetic differences, geographic factors or environmental differences, or other population-based factors.
Sex: In childhood, allergic rhinitis is more common in boys than in girls, but in adulthood, the prevalence is approximately equal between men and women.
Age: Onset of allergic rhinitis is common in childhood, adolescence, and early adult years, with a mean age of onset 8-11 years, but allergic rhinitis may occur in persons of any age. In 80% of cases, allergic rhinitis develops by age 20 years.

10. Diagnosis of Allergic Rhinitis
History & symptoms of recurrent or persistent rhinitis and/or associated health effects
Signs of atopy and recurrent or persistent rhinitis
Demonstration of IgE allergy
Exclusion of other causes of rhinitis
— The diagnosis of allergic rhinitis is made on clinical grounds based upon the characteristic history (including presence of risk factors), symptoms and signs on physical examination, and (if indicated) the confirmed presence of allergen-specific IgE. Symptoms should also be reproducible on exposure to allergens to which the patient has been sensitized. (See "Clinical manifestations and epidemiology of allergic rhinitis (rhinosinusitis)".)
A positive response to a therapeutic trial of either topical nasal steroids or topical antihistamines does not establish a diagnosis of allergic rhinitis [6]. These two therapies, which are often useful in the treatment of allergic rhinitis, are also effective in the treatment of perennial nonallergic rhinitis [7].

11. Diagnosis of Allergic Rhinitis
History & clinical symptoms of recurrent or persistent rhinitis and/or associated health effects
Rhinorhoea
Nasal blockage
Postnasal drip
Itchiness
Sneezing
Others: conjunctivitis, eczema, asthma, chronic rhinosinusitis, otitis media with effusion, sleep obstruction…

12. History
Important elements in history include an evaluation of the nature, duration, and time course of symptoms; possible triggers for symptoms; response to medications; comorbid conditions; family history of allergic diseases; environmental exposures; occupational exposures; and effects on quality of life.
Symptoms that can be associated with allergic rhinitis include sneezing, itching (of nose, eyes, ears, palate), rhinorrhea, postnasal drip, congestion, headache, earache, tearing, red eyes, eye swelling, fatigue, drowsiness, and malaise.
Some forms of allergic rhinitis can be readily diagnosed by history alone. Seasonal allergic rhinitis caused by tree and grass pollen typically occurs in the spring (rose fever), and symptoms caused by ragweed pollen exposure in the fall (hay fever), although there are regional variations (figure 1). Symptoms of seasonal allergic rhinitis are predictable and reproducible from year to year.
By comparison, classic perennial allergic rhinitis is associated with nasal symptoms which occur for more than two hours per day and for more than nine months of the year. Perennial allergic rhinitis usually reflects allergy to indoor allergens like dust mites, cockroaches, or animal dander, although aeroallergens may cause perennial rhinitis in tropical or subtropical climates.
The presence of consensus risk factors for atopy provides additional support for the diagnosis of allergic disease. This is particularly true for those with a personal or family history of atopic disease, as well as a clear history of animal and pollen triggers of allergic rhinitis symptoms. A review of multiple studies proposed symptomatic classification of allergic rhinosinusitis by frequency ("intermittent" or "persistent") and severity ("mild" or "moderate-severe"). The WHO had targeted allergic rhinitis because of its impact on asthma, and the classification is strikingly similar to consensus asthma guidelines .

13. Symptoms and chronicity
Determine the age of onset of symptoms and whether symptoms have been present continuously since onset.
Determine the time pattern of symptoms and whether symptoms occur at a consistent level throughout the year (ie, perennial rhinitis), only occur in specific seasons (ie, seasonal rhinitis), or a combination of the two.
During periods of exacerbation, determine whether symptoms occur on a daily basis or only on an episodic basis. Determine whether the symptoms are present all day or only at specific times during the day.
Determine which organ systems are affected and the specific symptoms.

14. Trigger factors
Determine whether symptoms are related temporally to specific trigger factors. This might include exposure to pollens outdoors, mold spores, specific animals, or dust while cleaning the house.
Irritant triggers such as smoke, pollution, and strong smells can aggravate symptoms in a patient with allergic rhinitis. These are also common triggers of vasomotor rhinitis.
Other patients may describe year-round symptoms that do not appear to be associated with specific triggers. This could be consistent with nonallergic rhinitis, but perennial allergens, such as dust mite or animal exposure, should also be considered in this situation.

15. Co-morbid conditions
Patients with allergic rhinitis may have other atopic conditions such as asthma or atopic dermatitis.
Look for conditions that can occur as complications of allergic rhinitis. Sinusitis occurs quite frequently
Other possible complications include otitis media, sleep disturbance or apnea, dental problems (overbite), and palatal abnormalities.
Nasal polyps occur in association with allergic rhinitis, although whether allergic rhinitis actually causes polyps remains unclear.
Investigate past medical history, including other current medical conditions. Diseases such as hypothyroidism or sarcoidosis can cause nonallergic rhinitis.

16. Family history
Because allergic rhinitis has a significant genetic component, a positive family history for atopy makes the diagnosis more likely.
A greater risk of allergic rhinitis exists if both parents are atopic than if one parent is atopic.
However, the cause of allergic rhinitis appears to be multifactorial, and a person with no family history of allergic rhinitis can develop allergic rhinitis.

17. Environmental exposure
A thorough history of environmental exposures helps to identify specific allergic triggers.
This should include investigation of risk factors for exposure to perennial allergens (eg, dust mites, mold, pets).
Risk factors for dust mite exposure include carpeting, heat, humidity, and bedding that does not have dust mite–proof covers.
Chronic dampness is a risk factor for mold exposure.
A history of hobbies and recreational activities helps determine risk and a time pattern of pollen exposure.

18. Diagnosis of Allergic Rhinitis
Signs of atopy and recurrent or persistent rhinitis
Atopic individuals respond to allergen exposure by producing allergen-specific IgE. IgE antibodies bind to IgE receptors on mast cells throughout the respiratory mucosa and to basophils in the peripheral blood. When the same allergen is subsequently inhaled, the allergen binds to and crosslinks IgE on the mast cell surface, resulting in activation and release of inflammatory mediators.
Nasal mast cells release histamine, prostaglandins, leukotrienes, PAF, and bradykinin, among other mediators. These result in the signs and symptoms of allergic rhinitis. Tissue eosinophilia is also a feature of allergic rhinitis, and eosinophil-derived mediators are associated with nasal epithelial injury and desquamation, subepithelial fibrosis, and hyperresponsiveness.
The allergic nasal response consists of an immediate phase, which peaks at 15 to 30 minutes after allergen exposure and corresponds to mast cell degranulation and mediator release, and a late phase, which peaks at 6 to 12 hours after exposure and corresponds to infiltration of the nasal tissues by eosinophils, basophils, and other inflammatory cells. Patients with allergic rhinitis usually have similar inflammatory changes in the linings of the paranasal sinuses.

19. Diagnosis in Primary Care Setting

20. Diagnosis of Allergic Rhinitis
Demonstration of IgE allergy
Allergic rhinitis is associated with a symptom complex characterized by paroxysms of sneezing, rhinorrhea, nasal obstruction, post nasal drainage, and itching of the eyes, nose, and palate. (See 'Introduction' above.)
Identification of the specific allergens to which the patient is sensitive is not necessary for successful treatment in many cases. However, patients whose symptoms are severe or refractory to therapy should be referred to an allergy specialist for a more definitive evaluation. Properly performed skin testing is the best method for determining allergic sensitization.
The differential diagnosis of allergic rhinitis includes acute and chronic rhinosinusitis, chronic nonallergic rhinitis, rhinitis medicamentosa, atrophic rhinitis, and rhinitis due to systemic medications.

21. Immunoassay vs Skin Test for Diagnosis of Allergy
Not influenced by medication
Not influenced by skin disease
Does not require expertise
Quality control possible
Expensive
Skin test
Higher sensitivity
Immediate results
Requires expertise
Cheaper
Serum tests for allergy — Immunoassays to detect allergen-specific IgE antibodies in the serum have limited utility in the diagnosis of allergic rhinitis. (These tests are sometimes referred to as radioallergosorbent tests, or RASTs, because earlier methods utilized radioactive reagents. The methods currently in use are more correctly referred to as immunoassays for allergen-specific IgE).
Skin testing — Carefully performed immediate hypersensitivity skin testing (prick skin tests) is a quick, relatively inexpensive, and safe way to identify the presence of allergen specific IgE. These tests are usually performed by allergy specialists. In sensitive patients, testing with selected diagnostic vaccines of tree, grass, or weed pollen, mold, house dust mite, and/or animal allergens results in a wheal and flare reaction at the skin test site within 20 minutes.
Skin testing is particularly useful among patients with:
An unclear diagnosis based upon the history and physical examination
Poorly controlled symptoms, such as persistent nasal symptoms and/or an inadequate clinical response to nasal glucocorticoids
Coexisting persistent asthma and/or recurrent sinusitis/otitis

22. Other Causes of Rhinitis in Children
Infection
Viral, bacterial,
Rhinosinusitis
Foreign body in the nose
Rhinitis associated with physical or chemical factors
Drug, food induced rhinitis
NARES, aspirin sensitivity
Vasomotor rhinitis
Underlying causes of nonallergic rhinitis include vasomotor rhinitis, rhinitis medicamentosa, nonallergic rhinitis with nasal eosinophilia syndrome, and miscellaneous other disorders. Additional diseases to consider include acute infectious rhinitis, atrophic rhinitis, and rhinitis that occurs in association with systemic diseases.
Except for patients with mixed rhinitis, all nonallergic syndromes are distinguished from allergic rhinitis by negative skin tests, and a history that supports the alternative diagnosis
— Symptoms of the common cold vary from patient to patient, with rhinitis and nasal congestion being the most common. Nasal obstruction, rhinorrhea, and sneezing are usually present early in the course of the cold, although a sore or "scratchy" throat is frequently the most bothersome symptom on the first day of illness. The sore throat is usually short lived, and nasal symptoms predominate by the second and third day. Cough typically becomes troublesome on the fourth or fifth day of illness, by which time the nasal symptoms are less severe.
Chronic nonallergic rhinitis — Chronic nonallergic rhinitis is characterized by perennial symptoms, an older average age than in patients with allergic rhinitis, and mild or absent nasal itching and sneezing. Patients with this disorder complain of chronic nasal congestion intensified by rapid changes in temperature and relative humidity, odors, or alcohol. They have little nasal itching or sneezing; however, headaches, anosmia, and sinusitis are common. A family history of allergy or allergic symptom triggers is uncommon. Negative skin tests to inhalant allergens are essentially diagnostic for a nonallergic rhinitis syndrome. Vasomotor rhinitis is sometimes considered a subset of chronic nonallergic rhinitis. The various clinical syndromes that can be included under the more general term chronic nonallergic rhinitis are reviewed separately.

23. Health Effects of Allergic Rhinitis
Social inconvenience
Sleep disturbances/obstruction
Learning difficulties
Impaired maxillary growth
Dental problems
Infection: nose and sinuses
Co-morbidities: conjunctivitis, asthma, rhinosinusitis, otitis media

25. Looking for asthma…

26. In Patients with Rhinitis:
Routinely ask for symptoms suggestive of asthma
Perform chest examination
Consider lung function testing
Consider tests for bronchial hyperresponsiveness in selected cases

27. AR Classification Intermittent Persistent
. < 4 days per week
. or < 4 weeks
Persistent
. > 4 days per week
. and > 4 weeks
Mild
normal sleep
& no impairment of daily activities, sport, leisure
& normal work and school
& no troublesome symptoms
Moderate-severe
one or more items
. abnormal sleep
. impairment of daily activities, sport, leisure
. abnormal work and school
. troublesome symptoms
in untreated patients

29. Management of allergic rhinitis
The management of allergic rhinitis involves the following
components:
Allergen avoidance
Pharmacotherapy.
Allergen immunotherapy. Of note, immunotherapy helps prevent the development of asthma in children with allergic rhinitis, and thus should be given special consideration in the pediatric population.

30. Medications for Allergic Rhinitis - ARIA
sneezing rhinorrhea nasal nasal eye obstruction itch symptoms
H1-antihistamines
oral to
intranasal
intraocular
Corticosteroids
Cromones
intranasal
intraocular
Decongestants
intranasal
oral
Anti-cholinergics
Anti-leukotrienes
Management combines allergen avoidance and pharmacologic therapy, with allergen immunotherapy added for refractory or severe cases.
Intranasal glucocorticoids (INGCs) are the most effective single therapy for allergic rhinitis in most patients with significant or persistent symptoms.
With this in mind, we favor the following approaches for specific patient groups:
Children <3 years — For children <3 years, initial treatment depends upon both of the child's symptoms and the concerns of the parents/caregivers.
For children <3 years with mild symptoms, we suggest a second generation antihistamines (Grade 2B). Cetirizine (approved for children ≥6 months), loratadine, and fexofenadine (both approved for children ≥2 years) are similarly efficacious and are available in syrups.
If this is not effective or the child has prominent congestion, we suggest changing to an INGC with minimal systemic bioavailability and once-daily dosing (Grade 2B). Mometasone furoate and fluticasone furoate are approved for children ≥2 years of age.
Intranasal cromolyn may be helpful for children with mild or episodic symptoms, whose parents are especially concerned about possible side effects, although the need for frequent dosing (one to two sprays three to four times daily) limits compliance.

31. Oral Antihistamines Newer agents First generation agents Acrivastine
Chlorpheniramine
Brompheniramine Diphenydramine
Promethazine
Tripolidine
Hydroxyzine
Azatadine
Newer agents
Acrivastine
Azelastine
Cetirizine
Desloratadine Fexofenadine Levocetirizine Loratadine
Mizolastine
First generation agents — First generation antihistamines include diphenhydramine, chlorpheniramine, hydroxyzine, brompheniramine, and others. These are available over-the-counter, both as single agents and in combination with other drugs. They are similarly efficacious compared to each other, with minor differences
Adverse effects and safety — First generation antihistamines cause significant sedation because they are lipophilic and easily cross the blood brain barrier Central nervous system symptoms are reported by 20 percent or more of patients, and adverse effects on intellectual and motor function are well-documented, even in the absence of subjective awareness of sedation
Second and third generation antihistamines — The second generation antihistamines include loratadine, cetirizine, azelastine, and olopatadine. These lipophobic agents were developed primarily to avoid the unwanted central nervous system effects of the first generation drugs Onset of action is within one hour for most agents, and peak serum levels are attained in two to three hours . They are also longer-acting, and are dosed once or twice daily. Like older H1 antihistamines, they have less impact on nasal congestion compared to intranasal glucocorticoids (INGCs). The oral second generation agents appear to be similarly efficacious to each other .

32. Nasal Antihistamines Azelastine Levocabastine Olopatadine
Antihistamine nasal sprays — Azelastine and olopatadine are available as prescription nasal sprays. These agents appear to have some antiinflammatory effect and can improve nasal congestion They are similarly effective . Antihistamine nasal sprays have a rapid onset of action (less than 15 minutes) and can be administered "on demand" [9]. Azelastine has a bitter taste that can be bothersome to some patients, although this has been corrected in newer preparations [93. Azelastine can be sedating if it is inadvertently swallowed.

33. Newer Generation Oral Antihistamines
First line treatment for mild allergic rhinitis
Effective for
Rhinorrhea
Nasal pruritus
Sneezing
Less effective for
Nasal blockage
Possible additional anti-allergic and anti-inflammatory effect
In-vitro effect > in-vivo effect
Minimal or no sedative effects
Once daily administration
Rapid onset and 24 hour duration of action

34. Decongestants: Alpha-2 Adrenergic Agonists
Oral
Pseudoephedrine
Nasal
Phenylephrine
Oxymetazoline
Xylometazoline
Decongestants are relatively contraindicated in patients with hypertension, and contraindicated in those receiving monoamine oxidase therapy, and should be used with caution in patients with closed angle glaucoma, cardiovascular or cerebrovascular disease, hyperthyroidism, or bladder neck obstruction

35. Decongestants EFFICACY: Oral decongestants: moderate
Nasal decongestants: high
ADVERSE EFFECTS:
Oral decongestants: insomnia, tachycardia, hyperkinesia
tremor, increased blood pressure, stroke (?)
Nasal decongestants: tachyphylaxis, rebound congestion, nasal
hyperresponsiveness, rhinitis medicamentosa

36. Anti-Leukotriene Treatment in Allergic Rhinitis
Efficacy
Equipotent to H1 receptor antagonists but with onset of action after 2 days
Reduce nasal and systemic eosinophilia
May be used for simultaneous treatment of allergic rhinitis and asthma
Safety
Dyspepsia (approx. 2%)

37. Nasal Corticosteroids
Beclomethasone dipropionate
Budesonide
Ciclesonide
Flunisolide
Fluticasone propionate
Mometasone furoate
Triamcinolone acetonide
Nasal steroid sprays are highly efficacious in treating allergic rhinitis. They control the 4 major symptoms of rhinitis (ie, sneezing, itching, rhinorrhea, congestion). They are effective as monotherapy, although they do not significantly affect ocular symptoms. Studies have shown nasal steroids to be more effective than monotherapy with nasal cromolyn or antihistamines. Greater benefit may occur when nasal steroids are used with other classes of medication. They are safe to use and not associated with significant systemic adverse effects in adults . Glucocorticoids inhibit allergic inflammation in the nose at many levels. These agents downregulate inflammatory responses by binding to intracellular glucocorticoid receptors in the cytoplasm of inflammatory cells. The receptors undergo conformational changes upon activation, entering the cell nucleus where they bind with glucocorticoid response elements located on antiinflammatory genes. These activated genes transcribe messenger RNA for antiinflammatory proteins. At the same time, activated glucocorticoid receptors suppress the transcription of most cytokine and chemokine genes
* Currently only approved for asthma

38. Nasal Corticosteroids
reduction of
mucosal inflammation
late phase reactions
priming
nasal hyperresponsiveness 1
reduction of
mucosal mast cells
acute allergic reactions 2
suppression of
glandular activity
and vascular leakage
induction of
vasoconstriction 3
reduction of
symptoms and exacerbations

39. Nasal Corticosteroids
Most potent anti-inflammatory agents
Effective in treatment of all nasal symptoms including obstruction
Superior to anti-histamines and anti-leukotienes
First line pharmacotherapy for persistent allergic rhinitis
Intranasal corticosteroids may be divided into first, second, and third generation preparations. These products are equally efficacious, although the total bioavailability (oral and nasal) of second and third generation intranasal steroids is markedly lower than that of first generation agents, resulting in lower risk of systemic effects
First generation: beclomethasone (unknown bioavailability), and flunisolide (40 to 50 percent bioavailability).
Second generation: budesonide (10 to 34 percent).
Third generation: fluticasone propionate (<2 percent), mometasone furoate (undetectable), and fluticasone furoate (<1 percent).
— Glucocorticoids inhibit allergic inflammation in the nose at many levels These agents downregulate inflammatory responses by binding to intracellular glucocorticoid receptors in the cytoplasm of inflammatory cells. The receptors undergo conformational changes upon activation, entering the cell nucleus where they bind with glucocorticoid response elements located on antiinflammatory genes. These activated genes transcribe messenger RNA for antiinflammatory proteins. At the same time, activated glucocorticoid receptors suppress the transcription of most cytokine and chemokine genes.

40. Nasal Corticosteroids
Overall safe to use
Adverse Effects
Nasal irritation
Epistaxis
Septal perforation (extremely rare)
HPA axis suppression
Suppressed growth

41. Other Management Aspects
Manage other co-morbidities:
Allergic conjunctivitis
Asthma
Sinusitis…
Environmental manipulations:
allergen avoidance
Pollution treatment
Nutritional support
Activities and sports

42. Environmental Control
1. Allergens
House dust mites
Pets
Cockroaches
Molds
Pollen
2. Pollutants and Irritants

43. House dust mite allergen avoidance
Provide adequate ventilation to decrease humidity
Wash bedding regularly at 60°C
Encase pillow, mattress and quilt in allergen impermeable covers
Use vacuum cleaner with HEPA filter
Dispose of feather bedding
Remove carpets
Remove curtains, pets and stuffed toys from bedroom

44. Allergen Avoidance Pets
Remove pets from bedrooms and, even better, from the entire home
Vacuum carpets, mattresses and upholstery regularly
Wash pets regularly (±)
Molds
Ensure dry indoor conditions
Use ammonia to remove mold from bathrooms and other wet spaces
Cockroaches
Eradicate cockroaches with appropriate gel-type, non-volatile, insecticides
Eliminate dampness, cracks in floors, ceilings, cover food; wash surfaces, fabrics to remove allergen
Pollen
Remain indoors with windows closed at peak pollen times
Wear sunglasses
Use air-conditioning, where possible
Install car pollen filter

45. To Conclude…
Allergic rhinitis is very common and causes considerable morbidity
Adequate and appropriate treatment leads to significant improvement in quality of life
Co-morbid conditions are common and warrants special attention and treatment for optimal results
Environmental manipulations is also important in the control of disease