The 2022 edition of the Chinese Guidelines for the Diagnosis and Treatment of Allergic Rhinitis (which can be read for free at the end of the article) has updated more content in the epidemiology, pathogenesis, diagnosis and treatment of allergic rhinitis, especially adding environmental control, anti-IgE treatment, and combination drug therapy strategies, expanding the relevant content of immunotherapy in detail, and closely integrating with the current research hotspots and clinical key difficulties of allergic rhinitis.
Combined with the data, the author combed and summarized the knowledge of the treatment drugs and stepwise use of allergic rhinitis in detail.
The basics
Allergic rhinitis (allergic rhinitis, AR) is a noninfectious inflammatory disease of the nasal mucosa mediated primarily by immunoglobulin E (IgE) after exposure of atopic individuals to allergens (allergens) [1-2]. In addition to AR allergen-specific IgE-mediated type I allergies, non-IgE-mediated inflammatory reactions and neuroimmune disorders are also involved in the development of AR.
Category [1-2]:
Classification according to the time of onset of symptoms:
Intermittent AR (episodes of symptoms
Persistent AR (symptom onset ≥ 4d/week and ≥ 4 weeks).
Classification according to disease severity: mild AR, moderate-severe AR.
Classification according to allergen type:
Seasonal AR (symptoms are seasonal, and the common allergens are seasonal inhalation allergens such as pollen and fungi);
Perennial AR (symptoms are perennial, common allergens are dust mites, cockroaches, animal dander and other indoor perennial inhalation allergens and some occupational allergens).
Typical symptoms: clear watery nose, itchy nose, paroxysmal sneezing, nasal congestion, can be accompanied by ocular symptoms (such as allergic conjunctivitis) including tearing, itchy eyes, redness and burning sensation, etc., more common in pollen allergy, while 40% of AR patients can have asthma, nasal symptoms can also be accompanied by cough, stridor, shortness of breath, chest tightness and other pulmonary symptoms, but also accompanied by eczema, chronic sinusitis, upper airway cough syndrome, secretory otitis media, atopic dermatitis, sleep disorders, eosinophilic esophagitis, etc. [1-3].
Treatment: including environmental control, drug therapy, immunotherapy, etc., of which the main therapeutic drugs are glucocorticoids, antihistamine drugs, leukotriene receptor antagonists (LTRA), mast cell membrane stabilizers, decongestants, anticholine drugs, etc. [1-3].
First, the treatment of AR drugs
Allergic rhinitis (allergic rhinitis, AR) commonly used treatment drug guidelines are recommended as such [1-2]
Differences in the improvement of symptoms of allergic rhinitis (allergic rhinitis, AR) with commonly used drugs [1-3,7,13,15]
1. Glucocorticoids
It is significantly anti-inflammatory, anti-allergic, and antiedematous, and its anti-inflammatory effect is non-specific, effective in various inflammatory diseases, can control acute inflammation and relieve symptoms for a short period of time, and can continuously control inflammatory reaction states [1-3]. Intramuscular, intravenous, or intranasal corticosteroids are not recommended [1-2].
Nasal glucocorticoids
It additionally improves asthma control levels and lung function in patients with concomitant asthma and is superior to antihistamines in controlling nasal symptoms, including nasal congestion [1-3]. Patients with asthmatic AR are often treated with inhaled, oral, or nebulized glucocorticoids [1-2].
Fat-soluble nasal glucocorticoids are more easily absorbed by the nasal mucosa and can remain longer, entering target cells to bind to glucocorticoid receptors (GR) and functioning [1,4-5].
Common nasal glucocorticoid fat solubility from high to low [1,4-5]:
Mometasone furoate> fluticasone propionate> budesonide> triamcinolone acetonide
Compared with the first generation of nasal glucocorticoids, the second generation of nasal glucocorticoids has the characteristics of high lipophilicity, strong binding to receptors, stronger anti-inflammatory activity, and low bioavailability[1].
Systemic adverse effects of nasal glucocorticoids are rare, and it is recommended to prioritize drugs with low systemic bioavailability when long-term use, refer to the age limits and recommended dosages of the instructions, and regularly monitor the height of children [1,4-5].
Mild and moderate-severe intermittent AR courses: not less than 2 weeks, moderate-severe sustained AR courses: more than 4 weeks.
Due to the presence of the mildest inflammatory state of inflammation in the mucosa in AR, continuous treatment or the lowest maintenance dose of continuous therapy is significantly better than intermittent treatment [1-2].
Adverse reactions Source: Medication Assistant app "Rational Medication"
Oral glucocorticoids
Short-term use may be considered in arria with severe symptoms that are difficult to control, and in patients with moderate-to-severe persistent AR who cannot control severe nasal congestion symptoms with other treatments [1-2]. Prednisone 0.5 to 1.0 mg/kg is recommended for morning treatment for 4 to 7 days [1-2].
2. Antihistamine drugs (H1 receptor antagonists)
Anti-allergic, anti-inflammatory, nasal and oral administration [1-2,6-7].
Oral antihistamines
The second generation of such drugs includes cetirizine, levocetirizine, loratadine, desloratadine, deferratadine citrate and the like.
Its onset of action is rapid, the duration of action is long, can significantly alleviate nasal symptoms, especially nasal itching, sneezing and runny nose, although the efficacy of nasal symptoms is not as good as nasal glucocorticoids, but it can effectively control mild and most of the moderate-severe AR, but also effective for combined ocular symptoms, but the effect of improving nasal congestion is limited, can be routinely used in elderly AR patients [1-2,6-7]. For patients with pollen allergies, prophylactic therapy is recommended before the spread of allergenic pollen, which is beneficial for symptom control [1-2].
It is usually given once a day for a course of at least 2 weeks. For people who are allergic to pollen, the course of treatment is determined based on the time of pollen spread and the effect on symptoms [1-2].
The permeability of the blood-brain barrier of the second-generation oral antihistamine drugs is low, reducing the inhibitory effect on the central nervous system, so sedation and drowsiness adverse reactions are less common. Severe arrhythmias such as prolongation of the QT interval and torsades de pointes and ventricular tachycardia are rare [1-2,6-7].
Nasal antihistamines
These include levocapbastine nasal preparations, azelastine nasal preparations, orotadine nasal preparations.
Its efficacy ≥ second-generation oral antihistamines, particularly in the relief of nasal congestion symptoms [1-3,6-7]. Nasal antihistamines take effect faster than oral antihistamines, usually 15 to 30 minutes after administration [1-3].
It is usually given twice a day for no less than 2 weeks [1-2].
The main adverse effects are bitter taste, and nasal burning sensation, nosebleeds, drowsiness, and headache are rare [1-3].
3. Leukotriene receptor antagonist (LTRA)
Leukotriene can stimulate vascular smooth muscle dilation, increase vascular permeability, make the mucous membrane hyperemic and swollen, and stimulate epithelial cup cells and glands to secrete mucus, which is one of the main inflammatory mediators causing nasal congestion, rhinorrhoea and other nasal symptoms in AR patients [1-3,9].
Leukotriene receptor antagonists (LTRA), such as montelukast, are anti-allergic and anti-inflammatory and are used in the treatment of AR or asthmatics [1-2].
Montelukast is taken orally every night before bedtime, recommended for 8 to 12 weeks, which significantly improves AR nasal and eye symptoms and quality of life, improves nasal congestion symptoms better than second-generation oral antihistamines, and is effective in relieving sneezing and runny nose symptoms, and can be used in AR with or without asthma [1-2,9].
Oral LTRA alone is less effective than nasal corticosteroids alone [1-2]. Oral LTRA can be used alone, but is more recommended in combination with second-generation antihistamines and/or nasal corticosteroids [1-2].
4. Mast cell membrane stabilizer (chromosteroids)
It is anti-allergic and includes sodium cromoglycate, nedromide, sodium nitrate, tetrazoserone, pyripramine potassium and trinilox.
Among them, cromoglobinate sodium and trinistide are more commonly used. It has a certain effect on alleviating the symptoms of sneezing, runny nose and itchy nose in AR, but it does not improve nasal congestion significantly, and can also be used as a preventive treatment drug about 2 weeks before pollen spread, which has a relieving effect on the onset of symptoms caused by pollen allergy in seasonal AR patients [1-2].
Due to slower onset and short duration of action, it is usually required to do so 3 to 4 times a day, orally or intranasally for more than 2 weeks, and sustained treatment is better [1-2].
Sodium cromoglycate occasionally has irritation and allergic reactions, and trinist may see gastrointestinal discomfort, headache, palpitations, bladder irritation, and rash [1-2].
5. Decongestant
Decongestants are α receptor agonists that promote vascular smooth muscle contraction, reduce local tissue fluid production, reduce nasal mucosal congestion and swelling when used locally in the nasal cavity, quickly relieve nasal congestion, and at the same time use before nasal glucocorticoids can expand their distribution in the nasal cavity and enhance their anti-inflammatory effects, and are recommended as ar second-line treatment drugs [1-3].
Common adverse reactions of nasal decongestants include dry nasal cavity, burning sensation and needle prickling, and some headaches, dizziness, and increased heart rate can be seen.
Excessive concentration, prolonged treatment or excessive frequency of medication can cause rebound nasal mucosal congestion, predisposing to drug-induced rhinitis. It is not recommended for patients with dry nasal passages, atrophic rhinitis, hypertension, coronary heart disease, diabetes mellitus, hyperthyroidism, angle-closure glaucoma, and those receiving monoamine oxidase inhibitors or tricyclic antidepressants [1-2,8,14].
6. Anticholine drugs
May reduce glandular secretion and relax airway smooth muscles, and may also inhibit airway inflammation and remodeling. Among them, benzycloquine ammonium bromide, ipratropium bromide, etc. can control rhinorrhoea symptoms [1-2].
Benzycloquine ammonium bromide:
A highly selective M1 and M3 choline receptor antagonist that reduces nasal secretions compared to ipratropium bromide while improving nasal congestion, nasal itching, and sneezing[1].
Ipratropium bromide:
The 4th generation of atropine drugs can inhibit the secretion of serous mucus glands, mainly used to reduce nasal secretions, improve the symptoms of runny nose, can significantly reduce the watery nasal discharge, and also has a curative effect on perennial rhinitis and colds, but has no obvious effect on symptoms such as nasal itching, sneezing, nasal congestion and so on. Generally, it can inhibit hypersecretion of glands 15 to 30 minutes after nasal spraying, and the efficacy is maintained for 4 to 8 hours [1-2].
Two. Stepwise use of AR
According to the treatment effect of AR, a ladder treatment plan can be carried out, and the treatment can be downgraded when the treatment effect is good, and the treatment can be upgraded when the treatment effect is poor. Escalation usually requires the addition of combinations, and de-escalation reduces combinations [1].
Mild AR and moderate-degree intermittent AR, with good efficacy usually achieved with first-line drug monotherapy;
Moderate-to-severe persistent AR, with a combination of second-generation antihistamines and/or leukotriene receptor antagonists (LTRA) based on preferred nasal glucocorticoids[1];
Seasonal AR can be optional with nasal glucocorticoids combined with second-generation oral or nasal antihistamines;
Perennial AR recommends a combination of nasal glucocorticoids and nasal antihistamines [1, 7].
Moderate- to severe AR whose nasal symptoms (predominance is nasal congestion) after nasal corticosteroid therapy may be enhanced with leukotriene receptor antagonists (LDAs) in combination [1-2,13]. The leukotriene receptor antagonist (LTRA) montelukast, in combination with second-generation oral antihistamines, has a more significant effect on the improvement of daytime and nighttime symptoms, including nasal congestion and sleep disturbances, in seasonal AR patients [1-2, 7,13].
In patients with severe symptoms of nasal congestion, the combination of nasal decongestants (short-term, ≤ 3 days) during nasal glucocorticoid therapy can significantly improve efficacy and significantly improve nasal symptoms [1-2,13,15]. Oral antihistamines combined with nasal decongestants can alleviate nasal symptoms in AR patients, especially the improvement of nasal congestion symptoms, and it should be noted that insomnia, headache, dry mouth, hypertension, nervous tension and other adverse reactions may occur [1-2,7,13,15].
Resources:
1 Guidelines for the Diagnosis and Treatment of Allergic Rhinitis in China (2022, Revised Edition)[J].Chinese Journal of Otolaryngology Head and Neck Surgery, 2022,57(2):8-24
2 Guidelines for the diagnosis and treatment of allergic rhinitis (Tianjin, 2015)[J].Chinese Journal of Otolaryngology, Head and Neck Surgery, 2016, 51(1): 6-13
3 Expert consensus on the classification and diagnosis of rhinitis and nasal medication regimen[J].Chinese Journal of Otolaryngology and Skull Base Surgery,2019,25(6):573-577
4 Perioperative Glucocorticoids Medical-Pharmaceutical Expert Consensus (Guangdong Pharmaceutical Association, June 21, 2021)
Expert Consensus on 5 Nasal Glucocorticoids for the Treatment of Allergic Rhinitis (2021, Shanghai)[J].Chinese Journal of Otolaryngology and Skull Base Surgery, 2021,27(4):365-371
6 Oral H1 antihistamines for the treatment of allergic rhinitis 2018 Guangzhou Consensus[J].Chinese Journal of Otorhinolaryngology,2018,18(3):153-154
Expert consensus on the application of 7 antihistamine H1 receptor drugs in common allergic diseases in children[J].Chinese Journal of Practical Pediatrics,2018,33(3):161-168
8 Expert consensus on the diagnosis and treatment of allergic rhinitis in children (Chongqing, 2010)[J].Chinese Journal of Pediatrics,2011,49(2):116-117
Expert consensus on the clinical application of 9 leukotriene receptor antagonists in common respiratory diseases in children[J].Chinese Clinical Journal of Practical Pediatrics,2016,31(13):973-975
10 Pharmacovigilance Alert No. 8,2018 (Issue 184 overall)
11 Australian Medicines Agency (TGA) Alert: New Risk Management Measures for Montelukast (July 2018)
12 UK and Ireland warn of risk of neuropsychiatric reactions in Montelukast (UK MHRA website and Irish HPRA website)
13 Expert consensus on early identification and diagnosis and treatment of common cold and allergic rhinitis in children[J].Journal of Clinical Pediatrics,2017,35(2):143-146
14 Pharmaceutical Expertise (II)[M].Beijing: China Medical Science and Technology Press, 2015:457
15 Li Quansheng et al. Clinical Practice Guidelines for Allergic Rhinitis: Recommended by the American Society of Otolaryngology Head and Neck Surgery[J].Chinese Department of Otolaryngology Head and Neck Surgery, 2015,22(9):482-486
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Guidelines for the Diagnosis and Treatment of Allergic Rhinitis in China