Clinical review: Advances in allergic rhinitis research in children
Allergic rhinitis is a common pediatric disease. The prevalence of allergic rhinitis in adolescents aged 13-14 years is 14.6%, with more than 1 million worldwide. Allergic rhinitis usually presents with symptoms such as runny nose, nasal congestion, tearing, nasal itching and sleep disturbances. These symptoms can occur year-round and have a serious impact on the quality of life of children.
Advances in drug therapy and new specific immunotherapy have relieved symptoms in many patients with allergic rhinitis. The investigators reviewed and summarized the available literature, particularly the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, and published their findings in the BMJ.
Allergic rhinitis is a non-infectious inflammatory disease of the nasal mucosa in atopic individuals exposed to allergens mediated primarily by IgE release and involving multiple immunoreactive cells and cytokines.
Epidemiology
In recent years, the incidence of allergic rhinitis in children has been increasing. An international study of asthma and allergic rhinitis involved 1,200,000 children from 98 countries. The study found that 8.8%, 13.1%, and 8.3% of children aged 6-7 years in North America, South America, and Western Europe, respectively, had allergic rhinitis. 80% of patients with allergic rhinitis symptoms were diagnosed with allergic rhinitis before the age of 20. And 80-90% of these allergic rhinitis will persist into adulthood.
Classification
Allergic rhinitis is classified as intermittent or persistent, depending on the frequency of symptoms. Intermittent allergic rhinitis is usually associated with rare allergens (e.g., animal dander), while persistent allergic rhinitis is associated with common allergens (e.g., dust mites). Intermittent allergic rhinitis is diagnosed if symptom episodes occur less than 4 days per week or last less than 4 weeks. Persistent allergic rhinitis was diagnosed if the episodes were more than 4 days per week or lasted for more than 4 weeks.
The duration of the immune response triggered by exposure to different allergens varies in children. The classification of seasonal and perennial allergic rhinitis is gradually replacing the previous classification. In an observation of the outcome of 2347 children with allergic rhinitis, 72% were sensitized to seasonal or perennial allergens. In a cross-sectional study evaluating 6533 children with the new classification, more than 50% of the children with seasonal allergen sensitivity had persistent allergic rhinitis.
Allergic rhinitis can be classified as mild, moderate or severe depending on the severity of the disease and its impact on quality of life. Mild allergic rhinitis is diagnosed if the symptoms are mild and tolerable, and if sleep and daytime activities are not affected. If the child has two or more of the four symptoms of sneezing, nasal itching, nasal discharge and nasal congestion, the symptoms are unbearable and sleep and daytime activities are affected, the child is diagnosed with moderate to severe allergic rhinitis.
Causes
Allergic rhinitis is a multifactorial disease that is triggered by a combination of genes and the environment. Risk factors for allergic rhinitis may be present in all age groups. A longitudinal cohort study of 8,176 families found that children with a personal or parental history of allergy were at significantly increased risk of developing allergic rhinitis.
Common allergens included dust mites, animal hair dander, fungi and pollen. In a study of 3034 adults and children from 14 European countries, 33.4% of patients were allergic to grass, 26.5% to dust mites, and 19.4% to cat dander.
Allergens stimulate mast cells to release mediators that cause the initial allergic symptoms. Histamine, however, is a key mediator in the early reaction phase and can cause typical symptoms such as runny nose, itchy nose and sneezing. Other inflammatory cells cause delayed reactions.
Allergic rhinitis and asthma
The close relationship between allergic rhinitis and asthma has received extensive clinical attention. Treatment of allergic rhinitis can control asthma. Allergic rhinitis is a high risk factor for asthma, and rhinitis can exacerbate asthma attacks and increase the risk of asthma development.
Conversely, if effective control measures for allergic rhinitis are taken early in the course of the attack, the recurrence of asthma can be reduced or even avoided.
Diagnostic criteria for allergic rhinitis
Children with allergic rhinitis usually have symptoms such as sneezing, nasal congestion and nasal itching, which may be accompanied by eye symptoms such as itchy eyes and conjunctival congestion. Children can be tested by allergen skin prick test and serum specific IgE test, and nasal provocation test if necessary.
Anterior rhinoscopy is the best test for diagnosis in young children. The parent or guardian can sit next to the child and hold the child’s head and arm on one side and insert the rhinoscope in the upper posterior direction of the patient’s nose. The normal nasal mucosa is pink, but in allergic rhinitis the nasal mucosa appears typically swollen and gray.
Nasal polyps and turbinate hypertrophy are difficult to differentiate. Bacterial culture of nasal swabs is not diagnostic. Symptoms of allergic rhinitis in children include unilateral nasal congestion, recurrent bloody runny nose, and pain. Cranial nerve examination is used to evaluate rare nasal sinus tumors resulting in visual disturbances, diplopia, and sensory abnormalities. Children who present with these symptoms should be further evaluated by an ear, nose, and throat specialist.
Indications for allergen testing
Clinicians may perform allergen testing in children with allergic rhinitis if they are resistant to medications or have concurrent asthma. In a cross-sectional study of 784 children with allergic rhinitis, 89% tested positive for IgE. Allergen testing can find the true cause of allergies, avoid allergens, and achieve targeted prevention and treatment.
Allergen testing can be analyzed by skin prick test and serum specific IgE antibody test in children. The skin prick test uses 0.1% histamine and saline as positive and negative control tests, respectively, to determine negative or positive results and the intensity of the positivity. 15-minute air masses larger than 3 mm in diameter are considered positive.
Figure 3 Positive skin prick test
The radioallergen adsorption test is used to measure the level of IgE specific to the allergic animal and to identify the specific allergen. Compared to the radioallergen adsorption test, the skin prick test has a better positive predictive value and is easy to detect. However, the results of the skin prick test can be influenced by recent antihistamines taken. The clinician can choose the test according to the local situation.
Treatment of allergic rhinitis
In recent years, the treatment of allergic rhinitis includes allergen avoidance, nasal irrigation, medication, and specific immunotherapy.
1.Avoidance of allergen contact
The main modality of allergen control is to reduce the exposure of affected children to dust mites. However, a multicenter randomized controlled trial of 696 children found no significant difference between different preventive measures. Therefore, the guidelines for allergic rhinitis and its impact on asthma do not recommend any chemical or physical methods to reduce dust mite exposure.
In another randomized controlled trial, allergic rhinitis symptoms were significantly reduced after environmental control in children with cat dander allergy, and the new 2010 edition of the guidelines for allergic rhinitis and its effects on asthma recommends that patients with such allergies should avoid exposure to animal dander and fungi.
2. Nasal rinses
Nasal rinsing with saline is an inexpensive and effective method of treating allergic rhinitis. In a randomized controlled trial of 20 children with allergic rhinitis, two weeks of hypertonic saline rinsing of the nasal cavity significantly reduced symptoms such as nasal itching, congestion, runny nose, sneezing, and reduced the use of antihistamines.
Saline irrigation enhances mucociliary transport, reduces mucosal edema, decreases inflammatory mediators, effectively removes nasal bacteria, and mechanically clears concentrated mucus from the nasal cavity. Because of the preference for fine sprays in children, saline rinses are a better option. Ideally, nasal rinses can also be incorporated into the daily bathing regimen for children whose symptoms persist for more than 1 month.
3. Medication
Medications for allergic rhinitis in children include oral or nasal antihistamines, nasal corticosteroids, and leukotriene receptor antagonists. Guidelines for allergic rhinitis and its effect on asthma suggest that nasal steroids should be used preferentially for moderate to severe persistent allergic rhinitis.
4.Antihistamines
Currently, antihistamines are divided into first-generation antihistamines (e.g. paracetamol) and second-generation antihistamines (e.g. cetirizine). The first generation antihistamines are being phased out because they tend to cause suppression of the central system and affect the normal life of children. Second-generation antihistamines have a rapid onset of action, strong anti-sensitizing effect, high efficacy, few side effects, long duration of efficacy, and can significantly reduce nasal allergy symptom scores.
For children with mild to moderate intermittent or mild persistent allergic rhinitis, the guidelines for allergic rhinitis and its effects on asthma recommend that anti-sensitization therapy should be continued for one month if there is a response to antihistamines. If there is no improvement, the treatment medication should be reselected. Studies have found that oral and nasal preparations are equally effective, but that nasal preparations work faster.
In the meantime, parents and children should first learn about the possible side effects of antihistamines (including drowsiness, headache, gastrointestinal upset, etc.). Of these, headache is the most common side effect. Studies have found that cetirizine and loratadine can be used in children older than 2 years of age. However, levocetirizine hydrochloride can only be used in children over 6 years of age.
5. Nasal corticosteroids
Glucocorticoids play a key role in suppressing allergic reactions. Researchers found that the mometasone furoate group could significantly reduce nasal allergy symptom scores compared to the placebo group. Nasal corticosteroids were significantly more effective than antihistamines in combating allergy, and were also effective in treating intranasal congestion.
Both mometasone furoate and fluticasone propionate are approved for use in children over 6 years of age. However, the European Academy of Allergy and Clinical Immunology considers both drugs equally acceptable for use in children 2 years of age.
Before using nasal corticosteroids, parents and children should first learn about the side effects of the drug, including rhinorrhea, headache, and abnormal sense of smell. Studies have shown that nasal steroids have similar side effects to placebo.
6.Other drug treatment
Leukotrienes are inflammatory mediators produced by inflammatory cells such as mast cells and eosinophils. Studies have found that anti-leukotriene drugs are as effective as antihistamines, but not as effective as nasal glucocorticoids in improving nasal allergy symptom scores and improving patients’ quality of life.
Anti-leukotriene drugs (e.g., montelukast) are indicated for intermittent and persistent allergic rhinitis and are third-line therapeutic agents for the treatment of allergic rhinitis, especially in children with allergic rhinitis combined with asthma.
Anti-leukotriene drugs reduce bronchospasm and reduce the inflammatory response. And montelukast, as a long-acting anti-leukotriene drug, is indicated for children over 6 years of age.
Nasal decongestants can relieve nasal congestion but do not help other symptoms. However, long-term use tends to produce rebound nasal congestion. Guidelines for allergic rhinitis and its effect on asthma do not recommend the use of nasal decongestants for allergic rhinitis in children.
7. Immunotherapy
Immunotherapy, or desensitization, can induce immune tolerance to allergens in children and prevent further development of allergic rhinitis while improving their quality of life.
Immunotherapy can be administered subcutaneously or sublingually. Sublingual immunotherapy is more suitable for children. A meta-analysis of 22 double-blind randomized controlled trials found that immunotherapy significantly reduced nasal allergy symptom scores in children and adolescents aged 3 to 18 years.
Side effects of sublingual immunotherapy include local itching, mild asthma, and allergic reactions. Evidence-based medicine shows that the treatment rarely has serious side effects. The frequency and severity of side effects can be reduced by taking antihistamines prior to immunotherapy.
Immunotherapy is usually used in children over 5 years of age. In addition, specific immunotherapy may reduce the risk of asthma in patients with allergic rhinitis. Therefore, immunotherapy may reduce the burden and risk of asthma in patients with allergic rhinitis when maximum drug doses are not effective in controlling allergic rhinitis symptoms.
Figure 1 Nasal turbinate hypertrophy
Figure 2 Nasal polyp
Figure 3 Positive skin prick test