Allergic Rhinitis: Clinical Guidelines

List of Abbreviations

ARIA – Allergic Rhinitis and its Impact on Asthma

EAACI – European Academy of Allergy and Clinical Immunology

FcεRI – high-affinity IgE Fc receptor

FDA – Food and Drug Administration

IgE – immunoglobulin E

MS (medical score) – mean summary score of medication requirement

TNSS (Total Nasal Symptom Score) – total nasal symptom score

TNSS + MS – adjusted nasal symptom score taking into account medication requirement

REM (rapid eye movement) – rapid eye movement sleep

Th2 – T-helper type 2 cells

AH – antihistamines (R06: Antihistamines for systemic use)

BP — blood pressure

AD – allergic diseases

AC – allergic conjunctivitis

LTRAs – leukotriene receptor antagonists (R03DC: Leukotriene receptor antagonists)

ACE – angiotensin-converting enzyme

AR – allergic respiratory disease / allergic rhinitis

AIT – allergen-specific immunotherapy

ATC – Anatomical Therapeutic Chemical Classification System

BA – bronchial asthma

VAS – visual analogue scale

IL – interleukin

INCS – intranasal glucocorticosteroids (corticosteroids for topical nasal use) (R01AD: Corticosteroids)

PAR – perennial allergic rhinitis

CG – clinical guidelines

CT — computed tomography

ICD-10 – International Statistical Classification of Diseases and Related Health Problems, 10th Revision

NAR – non-allergic rhinitis

NSAIDs – non-steroidal anti-inflammatory drugs (M01A: Anti-inflammatory and antirheumatic products, non-steroids)

nsH1-AH – non-sedating systemic antihistamines (latest generation)

AE – adverse events

OAS – oral allergy syndrome

FEV1 – forced expiratory volume in 1 second

SCIT – subcutaneous immunotherapy

PEF – peak expiratory flow

RAACI – Russian Association of Allergologists and Clinical Immunologists

RCTs – randomized clinical trials

SAR – seasonal allergic rhinitis

SLIT – sublingual immunotherapy

Level of Reliability of Evidence (LRE) scale

Level of Convincingness of Recommendations (LCR) scale

FVC – forced vital capacity

HR – heart rate

Terms and Definitions

Sensitization is an increased sensitivity to a specific allergen/type of allergen, determined by skin testing and/or elevated levels of specific IgE. Clinically significant and latent sensitization are distinguished.

Clinically significant sensitization (allergy) is the presence of clinical manifestations corresponding to the identified sensitization.

Latent sensitization is the presence of sensitization in the absence of clinical manifestations.

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Allergic rhinitis (AR) is a disease characterized by IgE-mediated inflammation of the nasal mucosa (developing under the action of allergens) and the presence of daily symptoms lasting for an hour or more, including at least two of the following: nasal congestion (obstruction), nasal discharge (rhinorrhea), sneezing, and nasal itching. AR is often combined with other allergic diseases, such as allergic conjunctivitis, atopic dermatitis, and bronchial asthma (BA) [1-7].

AR is considered a risk factor for the development of BA [4-7]. Uncontrolled moderate-to-severe AR leads to a loss of control over BA symptoms [5-8].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

The main etiological factors of AR are:

• Plant pollen. AR caused by sensitization (hypersensitivity) to allergens of wind-pollinated plants is called pollinosis or hay fever. Each region has its own plant pollination (blossoming) calendar, which depends on climate and geographic features. For central Russia, three main periods of blooming of allergenic plants are distinguished: spring (April–May) – associated with the pollination of trees (birch, alder, hazel, oak, etc.); early summer (June – mid-July) – associated with the blooming of grasses or meadow grasses (timothy, fescue, orchard grass, ryegrass, brome, bluegrass, etc.); late summer–autumn (mid-July–September) – associated with the blooming of weeds: composites (sunflower, wormwood, ragweed, marsh elder), nettles (nettle), and goosefoots (saltbush).

• House dust mite allergens (species Dermatophagoides pteronyssinus and Dermatophagoides farinae).

• Epidermal allergens (cats, dogs, horses, etc.).

• Fungal allergens (molds).

• Other house dust allergens (library dust, cockroaches).

Although fungal spores and house dust mite allergens are perennial allergens, their amount in the ambient air also depends on the season. Thus, persistent AR may have a wave-like course and be accompanied by seasonal flares.

• Occupational AR is observed in individuals who, due to their occupation, are in constant contact with various allergens, such as flour, medications, down, feathers, animals, latex, and other allergens (found in livestock breeders, veterinarians, bakery workers, pharmacists, medical personnel, etc.).

• Food allergens. Food allergy is rare in patients with AR without other symptoms. On the other hand, rhinitis is a frequent symptom of food allergy in patients with lesions of various organs. Patients with pollinosis often develop adverse reactions after consuming plant foods. These are due to the fact that pollen and food allergens share common epitopes that cross-react with IgE. The severity of symptoms of such pollen-food allergy varies from local reactions in the form of oral allergy syndrome (tingling in the mouth and pharynx, local edema in the oral cavity) to severe systemic anaphylaxis.

According to its development mechanism, AR belongs to immediate-type allergic reactions (IgE-mediated reaction) [9].

Upon entering the body, the allergen is fragmented in antigen-presenting cells into simpler peptides, which are then presented via the major histocompatibility complex proteins of these cells to T-helper cells (Th2 cells). Th2 cells, in turn, upon activation, produce a number of cytokines, in particular interleukin-4 (IL-4) (and/or an alternative molecule, IL-13), IL-5, -6, -10, and also express the ligand for CD40 (CD40L or CD154) on their surface, which provides the necessary signal for the B cell to induce IgE synthesis. The formed allergen-specific IgE binds to specialized FcεRI receptors with very high affinity, located on mucosal and connective tissue mast cells and basophils, as well as low-affinity FcεRII expressed on the surface of B lymphocytes, monocytes, eosinophils, and possibly T lymphocytes. Upon re-exposure, the allergen binds to IgE antibodies, triggering a cascade of biochemical transformations of membrane lipids (pathochemical phase), the consequence of which is the secretion of mediators such as histamine, arachidonic acid metabolites (prostaglandin D2, sulfidopeptide leukotrienes C4, D4, E4), platelet-activating factor, and activation of plasma kinins [2, 9].

Mediators, by stimulating target organ receptors, induce the pathophysiological phase of the atopic reaction: increased vascular permeability and tissue edema, smooth muscle contraction, hypersecretion of mucous glands, and irritation of peripheral nerve endings. These changes form the basis of the rapid (early) phase of the allergic reaction, developing within the first minutes after allergen exposure (symptoms: itching, sneezing, watery nasal discharge). Preparation for cell migration from vessels to tissue is ensured by altered microvascular blood flow and the expression of cell adhesion molecules on the endothelium and leukocytes. The sequential involvement of adhesion molecules and chemokines leads to tissue infiltration by basophils, eosinophils, T lymphocytes, mast cells, and Langerhans cells. Upon activation, they also secrete pro-allergic (pro-inflammatory) mediators, forming the late (or delayed) phase of the allergic reaction (after 4–6 hours, symptoms: nasal congestion, nasal hyperreactivity, anosmia) [2, 9].

Since lymphocyte accumulation in tissue takes a considerable amount of time, T-lymphocyte cytokines (Th2 profile) are involved in maintaining allergic inflammation only at the final stages. It is generally accepted that changes in cellular composition due to the influx of eosinophils, basophils, Th2 cells, and the maintenance of mast cell activity during the late phase of the allergic response are related to a shift in the overall reactivity of the nasal mucosa. Against this altered background, subsequent allergen exposures provoke more pronounced clinical symptoms (priming effect). Nonspecific hyperreactivity of the nasal mucosa in patients with allergic rhinitis (AR) is manifested by increased sensitivity to various nonspecific irritant stimuli (sharp odors, changes in ambient temperature, etc.). Nonspecific tissue hyperreactivity may also be based on constitutional features, altered receptor sensitivity to mediators and irritants, impaired reflex responses, and vascular and microcirculatory changes [2, 9].

1.3 Epidemiology of the Disease or Condition

The prevalence of AR ranges from 4% to 32% worldwide and from 10% to 24% in Russia [1-8, 10-16]. Noteworthy are the low rate of healthcare-seeking behavior among AR patients in the early stages of the disease and delayed diagnosis. The disease most commonly debuts in the first half of life—during preschool or adolescence.

According to the International Study of Asthma and Allergy in Childhood (ISAAC), the average prevalence of AR symptoms is 8.5% (1.8–20.4%) among 6–7-year-old children and 14.6% (1.4–33.3%) among 13–14-year-old adolescents [17].

According to a study conducted in accordance with the protocol of the Global Allergy and Asthma European Network (GA2LEN) with the participation of Russia in 2008–2009, the prevalence of AR symptoms among adolescents aged 15–18 years was 34.2%. Upon detailed examination, an AR diagnosis was confirmed in 10.4% of cases: in 10.8% of children who reported symptoms according to the questionnaire and in 9.7% of adolescents who did not indicate these manifestations [18, 19]. At the same time, according to data from the Russian Ministry of Health in 2008, the overall incidence of AR in adolescents aged 15–17 years was 0.6%; however, even to date (2021), this figure is 0.86%, which, despite a certain increase, indicates a persistent trend toward underdiagnosis of the disease [19].

AR is frequently associated with asthma, which is detected in 15–38% of patients with AR [1-2, 4-8, 11-25]. At the same time, 55–85% of patients with asthma report symptoms of AR [1-8, 11-25].

1.4 Features of Coding the Disease or Condition

J30.1 – Allergic rhinitis due to pollen

J30.2 – Other seasonal allergic rhinitis

J30.3 – Other allergic rhinitis

J30.4 – Allergic rhinitis, unspecified

1.5 Classification of the disease or condition

Depending on the etiological factor, seasonal AR (SAR), perennial / indoor AR (PAR), or occupational AR are distinguished.

According to the nature of the course, there are:

• intermittent AR – symptoms occur less than 4 days a week or less than 4 weeks per year;

• persistent AR – symptoms occur more than 4 days a week and more than 4 weeks per year.

By severity:

• mild – the patient has mild symptoms of rhinitis that do not disrupt daytime activity and sleep;

• moderate – rhinitis symptoms interfere with work, study, sports, and disrupt the patient's sleep;

• severe – symptoms significantly impair the patient's quality of life; without therapy, the patient cannot normally work, study, or play sports; nighttime sleep is significantly disturbed.

By disease stage: exacerbation, remission.

The formulation of the diagnosis includes indicating the spectrum of allergens to which hypersensitivity has been detected.

Local AR is a distinct form. In local AR, characteristic symptoms of AR are present, with a clear association between disease exacerbation and contact with an allergen, while standard allergy diagnostic tests (skin prick tests and serum specific IgE) yield negative results. In local AR, specific IgE to the causative allergen is detected in nasal secretions (not available in Russia); positive nasal provocation tests with the causative allergen are also observed [26].

1.6 Clinical presentation of the disease or condition

AR manifests with the following main symptoms:

• nasal congestion (obstruction), characteristic mouth breathing, snorting, snoring, voice changes;

• rhinorrhea (watery nasal discharge);

• sneezing (often paroxysmal, most frequently in the morning; sneezing paroxysms may occur spontaneously);

• itching, less commonly a burning sensation in the nose (sometimes accompanied by itching of the palate and pharynx); nasal itching may manifest as the characteristic "allergic salute" sign (constantly rubbing the tip of the nose with the palm in an upward motion), resulting in some patients developing a transverse nasal crease, excoriations, and scratches on the nose;

• decreased sense of smell (in the late stages of rhinitis).

Additional symptoms of AR develop due to abundant nasal secretion, impaired drainage of the paranasal sinuses, and Eustachian tube dysfunction:

• irritation, edema, hyperemia of the skin over the upper lip and around the alae nasi;

• epistaxis due to forced nose-blowing and traumatic nasal care;

• sore throat, throat clearing (manifestations of concomitant allergic pharyngitis and laryngitis);

• ear pain and crackling sounds, especially during swallowing; hearing impairment (manifestations of allergic tubotympanitis).

General nonspecific symptoms observed in AR:

• fatigue, malaise, irritability;

• headache, increased fatigue, impaired concentration;

• sleep disturbance, depressed mood;

• rarely—fever.

AR is frequently combined with other allergic diseases, such as allergic conjunctivitis, atopic dermatitis, and atopic asthma [1-8, 11-25, 27].

AR symptoms are variable in timing and intensity, showing a clear relationship between exposure to the causative allergen and the onset of symptoms (seasonal exacerbations caused by plant pollination, or exacerbation after contact with pets), as well as an elimination effect—a reduction and complete disappearance of symptoms in the absence of allergen exposure.

Patients with SAR often experience cross-food intolerance syndrome (oral allergy syndrome, OAS – occurring mainly upon consumption of fresh fruits, vegetables, nuts, and seeds), the symptoms of which have varied clinical manifestations ranging from mild oral itching to anaphylaxis.

AR is a risk factor for the development of asthma (level of recommendation validity A; level of evidence reliability – 1) [4-7, 11-25, 28]. Facts indicating the interconnection between AR and asthma have been established:

• high frequency of occurrence (in 15–60% of cases) of both asthma and AR in the same patients [11-25, 28];

• increased bronchial reactivity to acetylcholine and its derivatives as well as to the causative allergen during inhalation provocation tests, which is observed in patients with AR presenting without asphyxiating attacks [29-30];

• during periods of AR exacerbation, patients exhibit a decrease in bronchial patency parameters [29-30];

• increased levels of allergen-specific IgE antibodies in nasal washes in asthma patients who have no clinical signs of AR [26, 30];

• administration of the causative allergen and inflammatory mediators into the nasal cavity induces impaired bronchial patency in patients suffering from asthma [4, 29-30];

• patients with a long-standing history of nasal and paranasal sinus pathology frequently develop asthma later in life [4-30].

The existence of the link between AR and asthma is a crucial rationale for the timely and rational therapy of patients with AR, particularly allergen-specific immunotherapy. It has been shown that the risk of developing asthma in patients with AR is significantly reduced with long-term allergen-specific immunotherapy [31-38].

2. Diagnostics, medical indications and contraindications for diagnostic methods

The diagnosis of allergic rhinitis is established based on the analysis of the allergic history, the nature of clinical symptoms, and the results of a specific allergological examination of the patient [1-7].

Criteria for establishing the diagnosis/condition:

• presence of characteristic complaints: daily manifesting for an hour or more at least two of the following symptoms: nasal congestion (obstruction), nasal discharge (rhinorrhea), sneezing, itching in the nasal cavity;

• presence of anamnestic data indicating a link between the onset of complaints and contact with a suspected causative allergen; presence of other allergic diseases (allergic conjunctivitis, bronchial asthma, cross-food intolerance syndrome, atopic dermatitis);

• presence of positive results from an allergological examination.

Comments: according to the requirements for the development of clinical guidelines, it is necessary to indicate the strength of recommendations and the evidence base in accordance with the grading scales for the levels of evidence (LoE) and grades of recommendation (GoR). For many recommendations, this will be low due to the lack of clinical studies dedicated to them. Despite this, they are necessary elements of patient examination to establish a diagnosis and choose treatment tactics. The presence of characteristic complaints, anamnesis data indicating the onset of complaints after contact with a presumed causative allergen, and matching positive results of an allergological examination are a prerequisite for establishing a diagnosis, as derived from the very definition of allergic rhinitis.

Examination, treatment, and follow-up of a patient with AR should be carried out in parallel by physicians of two specialties: otorhinolaryngologists and allergist-immunologists, which ensures an optimal comprehensive approach to AR therapy.

The otorhinolaryngologist performs a visual assessment of the nasal cavity, anterior rhinoscopy, endoscopic examination of the nasal cavity and nasopharynx, carries out differential diagnosis of AR with other diseases of the nasal cavity and paranasal sinuses, identifies complicated forms of AR, detects anatomical abnormalities in the nasal cavity, and determines indications for surgical treatment in such patients.

The allergist-immunologist determines the allergy testing strategy, performs skin and provocation tests, interprets the results of the allergy examination, rules out or confirms the presence of asthma, determines the feasibility of allergen-specific immunotherapy, and performs allergen-specific immunotherapy.

2.1 Complaints and Anamnesis

Comments: characteristic features include daily manifestations lasting for an hour or more of at least two of the following symptoms: nasal congestion (obstruction), nasal discharge (rhinorrhea), sneezing, and nasal itching. The presence of all symptoms is not mandatory. In patients with PAR, the leading symptoms are nasal congestion, pronounced difficulty in nasal breathing, and mucinous nasal discharge. In patients with SAR, the most frequent symptoms are paroxysmal sneezing, nasal itching, and rhinorrhea. In addition to the classic symptoms of AR, general malaise, headache, earache, hearing loss, olfactory impairment, epistaxis, sore throat, cough, and ocular symptoms are often noted. The most important diagnostic factor is a thorough history taking, which will indicate the causes, duration, and resolution of symptoms, the presence of allergic diseases (allergic conjunctivitis, asthma, atopic dermatitis) in the patient and their blood relatives, and the cause-and-effect features of the onset of disease signs and its exacerbations.

2.2 Physical Examination

Comments: external signs of rhinitis are characteristic: difficulty in nasal breathing; slightly open mouth; dark circles under the eyes. Mucous or mucopurulent nasal discharge (in case of secondary infection), maceration of the skin above the upper lip and in the area of the nasal alae, facial puffiness, and the "allergic salute" (rubbing the tip of the nose with the palm) may be observed.

2.3 Laboratory Diagnostics

Comments: An increase in eosinophil levels is possible during an AR exacerbation. At the same time, peripheral blood eosinophilia may have other causes (parasitic infestations, fungal infections, etc.). A normal peripheral blood eosinophil level does not prove the absence of an allergic disease. It must also be taken into account that this parameter is affected by the intake of certain medications (systemic antihistamines, leukotriene receptor antagonists, and systemic glucocorticoids can lead to a decrease in peripheral blood eosinophilia).

An increase in markers of bacterial inflammation (leukocytosis, left shift in the leukocyte formula) is a reason to search for a focus of infectious inflammation, primarily acute rhinosinusitis [7].

• In patients with pronounced symptoms during an AR exacerbation, it is recommended to consider performing a cytological examination of upper respiratory tract lavages to detect nasal secretion eosinophilia during the initial diagnosis of AR, including for differential diagnosis with other chronic rhinitis and to monitor therapy efficacy [7, 45–48].

GoR BLoE 3Grade of recommendation - B (level of evidence - 3)

Comments: Characteristically, there is an increase in the relative number of eosinophils to 10% or more. At the same time, eosinophilia in nasal secretion cytology may have other causes (NARES, polypoid rhinosinusitis, etc.). It must also be taken into account that this parameter is affected by the use of certain medications (the use of systemic and topical antihistamines, leukotriene receptor antagonists, systemic glucocorticoids, and topical nasal corticosteroids can lead to a decrease in nasal secretion eosinophilia). Seasonal changes in nasal secretion cytology are also possible in patients [7, 45-48].

Comments: A normal or elevated serum total IgE level does not prove the absence or presence of an allergic disease, including AR [49-52]. A normal total IgE level may be combined with an elevated level of specific IgE to clinically significant allergens, while an elevated total IgE level may be observed in the absence of sensitization and atopy (other causes of elevated total IgE may include parasitic infestation, fungal infection, oncopathology, hyper-IgE syndrome, etc.).

Comments: the dose-dependent effect of omalizumab** is achieved at maximum binding of free IgE. The calculation of the omalizumab** dose and determination of the treatment regimen are carried out individually, depending on body weight and baseline total IgE level (prior to the first administration of omalizumab**).

2.4 Instrumental Diagnostics

Comments: Characteristics include: nasal turbinate edema, significant watery secretions, bright red mucosal coloration during SAR exacerbations, cyanotic or gray mucosa in PAR, mucosal mottling ("marbling", Voyachek's sign); polyps may be detected.

Comments: Endoscopic examination allows the detection of anatomical abnormalities of the nasal cavity and paranasal sinuses, as well as other pathologies. A topical decongestant challenge (adrenomimetic solution test) can be used to assess the reversibility of nasal obstruction.

Comments: Indications for X-ray examination of the nasal cavity and paranasal sinuses include:

- presence of rhinosinusitis symptoms (purulent nasal discharge, pain over the sinus projections, headache, fever);

- presence of markers of bacterial inflammation: leukocytosis, neutrophil shift in the complete blood count.

Comments: Computed tomography is performed for the differential diagnosis of AR, identification of other causes of nasal obstruction, or in complicated forms of AR, primarily polyposis rhinosinusitis.

Comments: Allergic rhinitis is a risk factor for the development of bronchial asthma. During exacerbation periods, patients with allergic rhinitis may exhibit reduced expiratory flows on pulmonary function testing, which can be a predictor of bronchial asthma development. Attention is drawn to the decrease in flow rate parameters—FEV1; when this parameter is reduced, a bronchodilator test is performed to detect latent bronchospasm [2, 10, 29]. One of the contraindications for AIT is an FEV1 decrease below 70% of predicted values [44].

Comments: Injection allergen-specific immunotherapy is associated with the risk of systemic reactions, the most severe of which is anaphylactic shock. In the event of severe systemic reactions, treatment requires the administration of epinephrine, which is contraindicated in significant cardiac rhythm disturbances (tachyarrhythmia, ventricular fibrillation, stage IIB–III chronic heart failure). Detecting these conditions is necessary prior to starting allergen-specific immunotherapy, as they constitute a contraindication to the injection method of allergen-specific immunotherapy [44].

2.5 Other Procedures

Allergy testing is necessary to confirm the allergic nature of rhinitis, identify causal allergens in order to formulate lifestyle and dietary recommendations, and determine the feasibility of allergen-specific immunotherapy. Allergy testing can be performed via skin testing with non-bacterial allergens (skin prick tests), determination of specific IgE levels in blood serum, and provocation tests.

The choice of allergy testing method is determined by the availability and equipment of the allergy clinic and the presence/absence of contraindications to skin testing.

Comments: Skin tests are performed in an allergy clinic setting by a specially trained nurse or allergist-immunologist. Prick tests or scratch tests are most commonly used. The results of allergen testing are correlated with negative and positive control test results. Skin test results are very important for diagnosing atopic diseases, but they are not absolute and have contraindications [1, 2, 7]. Test reliability may be affected by early childhood (under 5 years) or, conversely, advanced age (over 60 years), use of systemic glucocorticoids, systemic antihistamines, psychotropic drugs (which reduce skin sensitivity), dermographism (false-positive result), a short period following an acute allergic reaction (false-negative result), etc. During annual follow-up, the test may be repeated if the appearance of a new clinically significant sensitization is suspected.

Comments: Determining the level of allergen-specific IgE antibodies in serum is especially important when skin test results are inconclusive or when testing cannot be performed (e.g., during an acute exacerbation of an allergic disease or in the presence of other contraindications), or when necessary diagnostic allergens are lacking (e.g., mold allergens). Reliability of the result is affected by the test system used, which may have low sensitivity and specificity, reflected in both false-positive and false-negative results. The gold standard for laboratory allergy diagnostics is solid-phase immunofluorescence, for example, using the automated ImmunoCAP instrument, which has high sensitivity for detecting specific IgE at ultra-low concentrations and, according to independent studies, is the most accurate and stable. The test report is presented as a quantitative result and is considered positive at values > 0.70 kU/l [2, 7].

Component-resolved (molecular) diagnostics belongs to the third level of allergy diagnostics and is used to map a patient's allergic sensitization at the molecular level using purified natural or recombinant allergen molecules instead of allergen extracts [72-73]. Molecular diagnostics is not recommended for all patients with AR. This method may be used in case of discrepancies between anamnestic data and the results of first-line allergy testing (skin tests, determination of specific IgE), in case of AIT failure, or when prescribing AIT with recombinant allergens.

During annual follow-up, repeat testing may be performed if there is a suspicion of new clinically relevant sensitization.

Determining the total serum IgE level in a patient with suspected AR is impractical because it does not provide the necessary diagnostic information, has no value in differential diagnosis, and does not affect treatment selection in any way (see above, section 2.3) [7].

Nasal allergen provocation tests are performed in adult patients with AR to clarify the diagnosis when discrepancies arise between medical history data and the results of other diagnostic methods, as well as in cases of multiple sensitization to various allergens and the need to select a clinically significant allergen for AIT. All provocation tests may only be performed by an allergist-immunologist trained in this procedure within a specialized allergy room or hospital setting.

Interpretation of the obtained allergy test results is performed in conjunction with the medical history. Clinically significant and latent sensitization are determined.

Differential diagnosis of AR should be carried out with such conditions as: infectious rhinitis; rhinitis caused by intranasal anatomical abnormalities, including adenoids (in children) and chronic rhinosinusitis with nasal polyps; non-infectious non-allergic rhinitis (NAR) and its phenotypes/subphenotypes: non-allergic eosinophilic rhinitis; drug-induced NAR (due to nonsteroidal anti-inflammatory drugs, mediated by vascular effects of alpha-blockers and beta-blockers, caused by ACE (angiotensin-converting enzyme) inhibitors, reserpine, or prolonged use of adrenomimetics (alpha-1 adrenoceptor stimulants, decongestants); hormonal NAR (associated with pregnancy, puberty, menstrual cycle, systemic hormonal contraceptives, acromegaly, hypothyroidism); non-allergic occupational rhinitis (induced by low-molecular-weight chemical compounds/irritants), rhinitis of the elderly (atrophic); food/alcohol-induced rhinitis; idiopathic NAR; primary ciliary dyskinesia, cystic fibrosis.

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

Achievement of complete control of AR symptoms is necessary. If trigger factors persist (ongoing exposure to the causative allergen, tobacco smoke, or other irritants), one can only speak of a reduction in the severity of AR symptoms.

The main principles of AR treatment include (Table 1):

• pharmacotherapy

• avoidance (elimination) measures

• allergen-specific immunotherapy (AIT)

Table 1. Stepwise approach to AR therapy

nsH1-AHs – non-sedating systemic antihistamines (latest generation); intranasal AHs – anti-allergic agents other than corticosteroids (ATC code R01AC); LRA – leukotriene receptor antagonists (ATC code R03DC); INCS – intranasal glucocorticosteroids – local, nasal corticosteroids (ATC code R01AD).

¹ administration of omalizumab** is possible for patients aged 12 years and older when previous therapy is insufficiently effective, detailed explanation in the text in section 3.1

3.1 Pharmacotherapy

Comments: It is advisable to use non-sedating systemic antihistamines (nsH₁-AHs) with the following preferred characteristics: selective action on H₁-receptors, rapid onset of clinical effect, efficacy lasting 24 hours or more, absence of tachyphylaxis (tolerance), high safety profile, lack of sedative effect, absence of clinically significant interactions with food or drugs, they should not be substrates for transport proteins, and lack of interaction with the cytochrome P4503A (CYP3A) system and cardiotoxicity [1-5, 7, 74-92]. Individual nsH₁-AHs differ in pharmacodynamics and pharmacokinetics, their ability to cross the blood-brain barrier and cause sedation (more pronounced with cetirizine**, depending on the dose), and possibly in their ability to suppress pro-inflammatory mediators involved in the development of allergic reactions [74-92].

Desloratadine (ATC code: R06AX27) for children aged 6 to 12 months: 1 mg once daily; for children aged 1 to 5 years: 1.25 mg once daily; for children aged 6 to 11 years: 2.5 mg once daily; for adults and adolescents aged 12 years and older: 5 mg once daily.

Levocetirizine (ATC code: R06AE09) for children aged 2 to 6 years: 1.25 mg twice daily; for adults and children older than 6 years: 5 mg once daily.

Loratadine** (ATC code: R06AX13) for children aged 2 to 12 years with a body weight of 30 kg or less: 5 mg once daily, with a body weight greater than 30 kg: 10 mg once daily; for adults and adolescents older than 12 years: 10 mg once daily.

Fexofenadine (ATC code: R06AX26) for children aged 6 to 11 years: 30 mg twice daily; for adults and adolescents older than 12 years: 120 mg once daily.

Cetirizine** (ATC code: R06AE07) for children aged 6 to 12 months: 2.5 mg once daily; for children aged 1 to 2 years: 2.5 mg twice daily; for children aged 2 to 6 years: 2.5 mg twice daily or 5 mg once daily; for adults and children older than 6 years: 5–10 mg once daily.

Ebastine (ATC code: R06AX22) for adults and adolescents older than 12 years: 10–20 mg once daily (a sublingual rapidly dispersing form is available).

Rupatadine (ATC code: R06AX28) for adults and adolescents older than 12 years: 10 mg once daily.

Bilastine (ATC code: R06AX29) for adults and adolescents older than 12 years: 20 mg once daily.

Comments: Despite recommendations to use non-sedating systemic antihistamines (latest generation) for the treatment of patients with AR, cases of sedating systemic antihistamine (first-generation) use still occur in practice. Almost all first-generation AHs, in addition to their antagonistic action on H1-receptors, also block other receptors, in particular muscarinic, serotonergic, and dopaminergic receptors, which leads to a number of adverse effects [9, 58-59]. The most frequently recorded adverse effects are sedation, drowsiness, and dizziness due to the drugs crossing the blood-brain barrier and binding to histamine receptors there [9, 93, 94]. Histamine is an important mediator in brain tissue, participating in the regulation of the sleep-wake cycle, general brain activity, mental functions, and appetite. Sedating systemic antihistamines (with the exception of doxylamine) suppress the REM (rapid eye movement) phase of sleep, after which they cause a pronounced REM-rebound syndrome—an increase in its quantity and intensity. As a result, sleep becomes fragmented (sleep fragmentation), heart rhythm is disturbed, and tissue hypoxia and sleep-related breathing disorders (apnea) develop [93-94]. This leads to daytime sleepiness, reduced daytime activity, and impaired cognitive function. Sleep apnea increases the risk of sudden death [93-94].

Comments: Intranasal antihistamines can be prescribed as monotherapy and in combination with other drugs. This class of drugs is characterized by a rapid onset of action (within the first 30 minutes) and a high safety profile. Side effects include mucosal dryness [2, 4, 6, 7, 82, 95, 96].

Azelastine (ATC code: R01AC03) nasal spray, metered: for adults and children over 6 years of age, 1 metered dose (0.14 mg/0.14 ml) in each nostril twice daily. If necessary, adults and children over 12 years of age may use 2 metered doses (0.28 mg/0.28 ml) in each nostril twice daily. It is used until symptoms resolve and is suitable for prolonged use, but for no more than 6 months.

Levocabastine (ATC code: R01AC02) nasal spray, metered: for adults and children over 6 years of age, 2 doses (100 mcg) in each nostril twice daily; in case of more pronounced symptoms, use 3–4 times daily is possible. If there is no clinical effect after 3 days, the drug is discontinued. If a clinical effect is present, it is used until symptoms resolve.

Comments: Intranasal glucocorticosteroids (INGCS) are superior in potency to systemic antihistamines and cromoglicic acid** (nasal preparation), and effectively reduce symptoms such as nasal congestion, itching, sneezing, and rhinorrhea due to their pronounced anti-allergic, anti-inflammatory, and vasoconstrictive effects [1-7, 76, 82, 97-104].

It has also been noted that INGCS have a positive effect on ocular symptoms in patients with AR combined with allergic conjunctivitis due to the suppression of the naso-ocular reflex [105, 106].

Side effects of INGCS include mucosal dryness, epistaxis, and rarely, nasal septum perforation. To prevent adverse reactions, patient training in the proper technique of INGCS administration is necessary.

Mometasone (ATC code: R01AD09) nasal spray, metered: for adults and children over 12 years of age, 2 doses (100 mcg) in each nostril once daily (200 mcg/day). Once the desired therapeutic effect is achieved, for maintenance therapy, it is advisable to reduce the dose to 1 dose (50 mcg) in each nostril once daily (100 mcg/day). If necessary, the daily dose can be increased to 4 doses (200 mcg) in each nostril once daily (400 mcg/day). After symptom reduction, dose reduction is recommended. For children aged 2 to 12 years, 1 dose (50 mcg) in each nostril once daily (100 mcg/day).

Fluticasone furoate (ATC code: R01AD12) nasal spray, metered: for adults and children over 12 years of age, 2 doses (55 mcg) in each nostril once daily (110 mcg/day). Once the desired therapeutic effect is achieved, for maintenance therapy, it is advisable to reduce the dose to 1 dose (27.5 mcg) in each nostril once daily (55 mcg/day). For children aged 2 to 12 years, 1 dose (27.5 mcg) in each nostril once daily (55 mcg/day). If necessary, the dose may be increased to 2 doses (55 mcg) once daily (110 mcg/day). Once the desired therapeutic effect is achieved for maintenance therapy, it is advisable to reduce the dose to 1 dose (27.5 mcg) in each nostril once daily (55 mcg/day).

Fluticasone (fluticasone propionate) (ATC code: R01AD08) nasal spray, metered: for adults and children over 12 years of age, 2 doses (100 mcg) in each nostril once daily (200 mcg/day). Once the desired therapeutic effect is achieved, for maintenance therapy, it is advisable to reduce the dose to 1 dose (50 mcg) in each nostril once daily (100 mcg/day). For children aged 4 to 12 years, 1 dose (50 mcg) in each nostril once daily (100 mcg/day).

Budesonide** (ATC code: R01AD05) nasal spray, metered: for adults and children over 6 years of age, 2 doses (100 mcg) in each nostril twice daily (400 mcg/day). Once the desired therapeutic effect is achieved, for maintenance therapy, it is advisable to reduce the dose to 1 dose (50 mcg) in each nostril twice daily or 2 doses (100 mcg) in each nostril once daily (200 mcg/day). Duration of use should not exceed 3 months.

Beclometasone** (ATC code: R01AD01) nasal spray, metered: for adults and children over 6 years of age, 2 doses (100 mcg) in each nostril twice daily (400 mcg/day). The maximum daily dose is 400 mcg/day. Once the desired therapeutic effect is achieved, for maintenance therapy, it is advisable to reduce the dose to 1 dose (50 mcg) in each nostril twice daily.

Comments: Combined intranasal antihistamines and intranasal glucocorticosteroids (INGS) combine the effects of both drug classes: a rapid onset of action and a pronounced anti-inflammatory effect. Accordingly, side effects characteristic of both combined drug classes may develop [2, 6, 7, 76, 82, 107-116].

Azelastine + Fluticasone (ATX code: R01AD58) nasal spray, metered, for adults and children over 12 years of age: 1 dose (50 mcg fluticasone / 137 mcg azelastine) into each nasal nostril 2 times a day.

Azelastine + Mometasone (ATX code: R01A) nasal spray, metered, for adults (aged 18 and older): 1 dose (50 mcg mometasone / 140 mcg azelastine) into each nasal nostril 2 times a day. The duration of treatment is 2 weeks.

Mometasone + Olopatadine (ATX code: R01AD59) nasal spray, metered, for seasonal and perennial allergic rhinitis in adults and children over 12 years of age: 2 doses (50 mcg mometasone / 1200 mcg olopatadine) into each nasal nostril 2 times a day; for seasonal allergic rhinitis in children aged 6 to 11 years: 1 dose (25 mcg mometasone / 600 mcg olopatadine) into each nasal nostril 2 times a day.

Comments: Through specific binding to cysteinyl leukotriene receptors, montelukast suppresses inflammation of the nasal mucosa and bronchi triggered by allergens and nonspecific triggers; it possesses pronounced anti-allergic and anti-inflammatory effects and is effective both in suppressing symptoms and for the prevention of AR symptoms. Leukotriene receptor antagonists (LTRAs) are inferior in efficacy to corticosteroids (topical, nasal use). They can be used both as monotherapy and in combination therapy for AR [1-7, 76, 117-122].

Montelukast (ATX code: R03DC03) for children aged 2 to 6 years: 4 mg (1 chewable tablet) once daily; for children aged 6 to 15 years: 5 mg (1 chewable tablet) once daily; for adults and children over 15 years: 10 mg once daily.

Comments: prescribing montelukast when AR is combined with bronchial asthma allows for the control of symptoms of both allergic rhinitis and bronchial asthma while avoiding polypharmacy [2, 6, 123-125]. The duration of the treatment course ranges from 1 to 3 months or more. According to the medical product instructions for use of montelukast, there are no limitations on the duration of AR therapy.

Comments: Combination products combine the mechanisms of action of both drug classes. Accordingly, adverse effects characteristic of both combined drug classes may occur.

Levocetirizine + Montelukast (ATC code: R03DC53) for adults and children over 15 years old, 1 tablet (10 mg montelukast / 5 mg levocetirizine) once daily.

Comments: cromoglicic acid** (nasal preparation) has a mast cell membrane-stabilizing effect; its efficacy is lower than that of systemic antihistamines, leukotriene receptor antagonists, and corticosteroids (topical, nasal), and it has a high safety profile.

Cromoglicic acid**, metered nasal spray, for adults and children over 5 years old, 1 dose (2.8 mcg) in each nostril 4 times daily (22.4 mcg daily). If necessary, 1 dose (2.8 mcg) in each nostril 6 times daily (33.6 mcg/day). Once the therapeutic effect is achieved, the frequency of application can be reduced and used only upon contact with the allergen. Treatment course is 4 weeks.

Comments: They affect the sympathetic regulation of blood vessel tone by acting on adrenergic receptors. Short-term use of topical preparations does not lead to functional or morphological changes.

Oxymetazoline (ATC code: R01AA05) metered nasal spray or nasal drops, for adults and children over 6 years old, 1-2 doses of 0.05% solution in each nostril 2-3 times daily. For children aged 1 year to 6 years, 1-2 drops of 0.025% solution in each nostril 2-3 times daily. For infants under 4 weeks, 1 drop of 0.01% solution in each nostril 2-3 times daily; from the 5th week of life up to 1 year, 1-2 drops of 0.01% solution in each nostril 2-3 times daily. The drug is used for 3-4 days.

Xylometazoline** (ATC code: R01AA07) metered nasal spray or nasal drops, for adults and children over 6 years old, 1 dose of 0.1% solution in each nostril 1-3 times daily. For children aged 2 to 6 years, 1 dose of 0.05% solution in each nostril 1-2 times daily. The drug is used for no more than 5-7 days.

Comments: Prolonged use (more than 10 days) of such drugs may be accompanied by tachyphylaxis, nasal mucosal edema, and the development of rhinitis medicamentosa.

Comments: used as symptomatic therapy for the rapid relief of nasal congestion

Dimetindene + Phenylephrine (ATC code: R01AB01) metered nasal spray or nasal drops. For adults and children over 6 years old, 1-2 doses of spray or 3-4 drops in each nostril 3-4 times daily. For children aged 1 year to 6 years, only as nasal drops, 1-2 drops in each nostril 3-4 times daily.

Comments: A short course of systemic glucocorticoids is proposed as fourth-line therapy or treatment for severe exacerbation. Given the extensive list of side effects and contraindications for systemic glucocorticoids, it is advisable to limit the course of therapy. Intranasal injections of systemic glucocorticoid solutions and depot preparations in the treatment of AR are unacceptable as they may lead to severe complications (blindness, etc.).

Prednisolone** (ATC code: H02AB06) dose and duration of treatment are determined by the physician individually based on indications and disease severity. Contraindicated in tablets for children under 3 years of age.

Methylprednisolone** (ATC code: H02AB04) dose and duration of treatment are determined by the physician individually based on indications and disease severity

Dexamethasone** (ATC code: H02AB02) dose and duration of treatment are determined by the physician individually based on indications and disease severity

Comments: The use of depot forms of systemic glucocorticoids in AR can lead to the rapid development of adverse effects, including secondary adrenal insufficiency.

Comments: omalizumab** is effectively used in the therapy of severe allergic asthma, but the results of several double-blind placebo-controlled clinical trials using omalizumab** for the treatment of allergic rhinitis have demonstrated its high efficacy in reducing the severity of all AR symptoms and lowering the need for symptomatic medications. The prescription of omalizumab** for AR is possible for patients aged 12 years and older and is proposed as fourth-line therapy when prior therapy is insufficiently effective. The duration of therapy is determined depending on the form of the disease. In the protocols of 11 previously conducted RCTs and a phase III study, the duration of drug administration was at least 3 months [7, 54-55, 131-132]. A recent limited open-label observational non-comparative prospective study on the use of omalizumab** in patients with severe exacerbations of seasonal AR caused by birch pollen showed that the onset of omalizumab's effect occurs within 3 to 7 days; with a short season duration (1 month), complete symptom control can be achieved with a low frequency of injections (1-2). Considering its mechanism of action, omalizumab** should be administered at least a week before the expected pollination season of causal plants in patients with severe AR (according to anamnestic data from previous seasons) who have not timely undergone allergen-specific immunotherapy, and treatment should be continued until the end of the pollination season of causal allergens [56].

Omalizumab** (ATC code: R03DX05) for adults and adolescents over 12 years old as subcutaneous injections once every 2 or 4 weeks. The dose of the drug (from 75 to 600 mg) must be selected in accordance with the Omalizumab dosing table**.

3.2 Allergen Avoidance Measures

Elimination or removal of causal allergens refers to etiopathogenetic methods of allergy treatment. In most cases, completely avoiding contact with the allergen is impossible.

Comments: Even partial implementation of allergen-avoidance measures facilitates the course of the disease, reduces the need for medications, including potent ones. Special attention is recommended to be paid to these measures when there are serious restrictions on the use of many pharmacological drugs (pregnancy, early age, presence of comorbid pathology) and in the presence of sensitization to epidermal allergens [7, 133, 134].

In addition to well-known avoidance measures (use of special filters, daily wet cleaning, avoidance of contact with pets, moving to another climatic zone during the flowering season of causally significant plants, etc.), irrigation procedures with products for moisturizing, cleansing, and protecting the nasal mucosa – isotonic saline solutions – are of certain importance.

Comments: The use of isotonic saline solution, including sea water-based products, helps to liquefy viscous mucus, improve ciliary epithelial function, reduce the exposure of dust particles, allergens, and haptens on the surface of the nasal mucosa, and has a moisturizing effect [7, 135-138].

3.3 Allergen-Specific Immunotherapy

Allergen-specific immunotherapy (AIT) is the main method of pathogenetic treatment of allergic diseases associated with an IgE-mediated mechanism, consisting in the administration of increasing doses of the allergen responsible for the clinical manifestations of the disease in a given patient [44].

Comments: The efficacy of AIT in AR is manifested by a reduction or complete absence of clinical symptoms upon natural allergen exposure. Following AIT, there is a decrease in the duration of exacerbation and a reduction in the need for both baseline and symptomatic medications. AIT helps prevent the transformation of AR into asthma and prevents the expansion of the spectrum of allergens to which the patient develops hypersensitivity. AIT acts on both the early and late phases of the allergic response, leading not only to the inhibition of the allergen-specific reaction but also to the suppression of tissue hyperreactivity, manifested by increased sensitivity to the allergy mediator – histamine. Under the action of AIT, the migration of effector cells into the zone of allergic inflammation is suppressed, and regulatory T lymphocytes are generated, contributing to the induction of immunological tolerance, which is characterized by the suppression of the proliferative and cytokine response to the causative allergens (see methodological recommendations for AIT) [31-38, 44, 139-150].

There are subcutaneous and sublingual methods of AIT.

Main therapeutic forms of allergens registered in the Russian Federation (V01AA: Allergen extracts):

• aqueous-saline extracts of allergens of tree pollen, grass pollen, weed pollen, house dust, Dermatophagoides mites for subcutaneous AIT;

• allergoids obtained by polymerizing the allergen with formaldehyde or carbamylation;

• allergens of tree pollen, grasses, house dust mites adsorbed on calcium phosphate or aluminum hydroxide suspension for subcutaneous AIT;

• allergens of birch pollen, grass pollen, ragweed, house dust mites for sublingual use.

AIT protocols/regimens are not universal – they are unique for each method and drug. Differences in regimens are due to differences in the chemical and therapeutic properties of the drug. As a rule, the AIT protocol includes two stages: Stage 1 – the phase of reaching the maximum therapeutic dose (buildup phase); Stage 2 – the maintenance therapy phase (main therapy phase). Protocols of some modern therapeutic allergens do not provide for a dose-buildup phase; treatment starts immediately with the maintenance dose of the allergen [44].

Depending on the duration of the protocol, AIT can be: pre-seasonal, pre-seasonal-seasonal, and year-round.

The presence of indications and contraindications for AIT, the choice of therapeutic allergen, and the prescription of AIT are carried out by an allergist-immunologist in accordance with the instructions for the selected therapeutic allergen and the methodological recommendations for AIT [2, 44]. To assess efficacy, symptom severity and medication requirements are evaluated at baseline and after AIT using the Total Nasal Symptom Score (TNSS) taking into account medication use [151].

3.4 Surgical treatment

Surgical intervention for AR is performed if the patient has a comorbid pathology. Indications for surgical intervention in patients with AR with nasal obstruction are determined by an otolaryngologist based on the results of clinical (including endoscopic examination of the nasal cavity and nasopharynx) and radiological examination of the patient [2, 4, 7, 152, 153].

The decision on the necessity of surgical intervention, preoperative preparation, and postoperative management is made by the otolaryngologist based on clinical guidelines for the management of the respective disease/condition. Scheduled surgical treatment is not recommended during the pollination season of causally significant allergens.

3.5 Methods of Traditional and Alternative Medicine

Due to the lack of evidence of a positive clinical effect on the course of AR, methods such as homeopathy, herbal medicine, hypnosis, relaxation techniques, air ionizers, and physical therapy are not recommended [2, 4, 7].

Comments: A systematic review and meta-analysis of 13 randomized clinical trials involving 2,365 patients, including 1,265 individuals in the active treatment group, demonstrated a reduction in the severity of nasal symptoms and an improvement in quality of life with this type of therapy [7, 154, 155].

3.6 Special Aspects of AR Treatment in Children

AR is most common in school-age children. In pediatric practice, it is suggested to adhere to the same treatment approaches for AR as in adults [2, 4, 7, 35-37, 57, 97, 115, 125, 133, 156-160]; however, physiological and anatomical characteristics of childhood must be considered in diagnosis and therapy.

When choosing therapy, one must be guided by safety principles, current legislation, and approved instructions for use. Special attention should be paid to allergen-avoidance measures (where indicated – the use of products for moisturizing, cleansing, and protecting the nasal mucosa (other nasal preparations, ATX code R01AX10) – isotonic saline solutions or barrier agents based on microcrystalline cellulose – topical sorbents), minimizing drug exposure [137]. Due to the lack of clinical trials in younger age groups, there are certain restrictions on the prescription of certain drugs.

Systemic antihistamines. In children, the symptoms of allergic rhinitis (AR) can affect cognitive function and academic performance, which may be further impaired by sedating systemic antihistamines (first-generation drugs). The adverse event (AE) profile of these drugs is characterized by a negative impact on the cognitive sphere—perception, attention, figurative thinking, memory, analytical and synthetic processes, psychomotor activity, probabilistic forecasting, fine motor skills, and overall quality of life. In addition, such AEs as altered sleep architecture (suppression of the REM sleep phase), the development of obstructive sleep apnea, and daytime drowsiness can also lead to a decrease in learning capacity, social maladaptation, and impaired cognitive development [93–94].

Drug registration particulars have limited the availability of the latest-generation systemic antihistamines for use in pediatric practice: thus, cetirizine** and desloratadine are approved from the age of 6 months, while loratadine** is approved from 2 years of age, whereas first-generation systemic antihistamines—chloropyramine** and dimetindene—are approved from 1 month of age. When choosing a systemic antihistamine, one should be guided by current legislation and approved instructions for use; once the patient reaches the appropriate age, preference should be given to second-generation (non-sedating) systemic antihistamines [2, 93–94, 158–160].

Cromoglicic acid** has a favorable safety profile and is effective for AR symptoms such as nasal pruritus, sneezing, and rhinorrhea; however, the use of this drug is limited by the need for frequent administration, lower efficacy compared to intranasal corticosteroids, and a lack of effect on nasal congestion [2, 7, 159–161].

Corticosteroids for local (nasal) use—intranasal glucocorticosteroids (INGCS) are effective treatments for AR. The use of INGCS in children with AR not only reduces the severity of nasal obstruction and other rhinitis symptoms, but also decreases the degree of adenoid hypertrophy and, consequently, the need for surgical treatment. Combination drugs—intranasal antihistamines and intranasal corticosteroids (INGCS)— combine the action of both drug classes: a rapid onset of action and a pronounced anti-inflammatory effect.

Numerous studies conducted in children have shown that the use of modern INGCS at therapeutic doses does not affect growth or the hypothalamic-pituitary-adrenal axis. Nevertheless, topical (nasal) corticosteroids should be prescribed at the minimum therapeutic daily doses, and for long-term use, the child's growth should be monitored. The safety profile of INGCS and the likelihood of adverse effects are determined by their systemic bioavailability and the level of corticosteroid inactivation during first-pass hepatic metabolism. The following INGCS are registered and approved for pediatric practice in the Russian Federation: fluticasone furoate and mometasone (used in children from 2 years of age), fluticasone (fluticasone propionate, used from 4 years of age), beclometasone**, and budesonide** (from 6 years of age). Among modern INGCS, the lowest systemic bioavailability (from 0.1% to 1–2%) is characteristic of: fluticasone furoate, mometasone, and fluticasone (fluticasone propionate). The minimum sufficient doses should be used, limiting the use of INGCS with high bioavailability, such as budesonide** (30–40%) and beclometasone** (40–50%) [162–163]. When prescribing therapy, one must account for the high systemic bioavailability of dexamethasone (over 80%), which is a component of many topical combination products frequently used to treat acute and chronic inflammatory diseases of the nasopharynx [2, 4, 7, 97, 157–163].

Leukotriene receptor antagonists. In pediatric practice, AR may manifest as part of allergic multimorbidity, preceding or accompanying bronchial asthma (BA) [164]. In children with AR suffering from BA, the administration of leukotriene receptor antagonists helps avoid polypharmacy and may also provide a steroid-sparing effect. Montelukast at a dose of 4 mg is approved for use in children from 2 years of age, and at a dose of 5 mg, from 6 years of age [2, 4, 7, 125, 159–160].

According to official drug labeling, allergen-specific immunotherapy (AIT) can be performed in children older than 5 years. AIT in children with AR helps prevent the progression of AR to BA and the expansion of the spectrum of causative allergens [2, 4, 35–37, 44, 159–160]. The availability of therapeutic allergens for sublingual AIT significantly expands the feasibility of this method in pediatric practice (high safety profile, no need for injections, and no requirement for frequent doctor visits). When prescribing sublingual AIT to children, parents or legal representatives must be informed of the importance of strictly following the physician's instructions and treatment regimen, while warning against intentional or unintentional non-compliance and uncontrolled treatment.

3.7 Special Aspects of AR Treatment in Pregnant and Lactating Women

When diagnosing AR in pregnant women, it is necessary to account for the possible presence of such a common condition as rhinitis of pregnancy, caused by physiological changes during gestation (elevated estrogen and placental growth hormone levels). Rhinitis of pregnancy is nasal congestion occurring during pregnancy, not accompanied by signs of respiratory infection or allergy, and resolving completely within 2 weeks postpartum [164–165]. The identification of sensitization to specific respiratory allergens will point toward AR. Skin testing during pregnancy and lactation is not performed due to the potential, albeit minimal, risk of anaphylaxis. For allergy testing during pregnancy and lactation, serum-specific IgE levels are measured [166].

In the treatment of AR in pregnant and breastfeeding women, preference is given to avoidance measures, including saline irrigation therapy [2, 4, 7, 164–168]. If avoidance approaches are insufficiently effective, pharmacotherapy is prescribed taking into account potential risks to the course of pregnancy, maternal health, and the unborn child [2, 4, 7, 164–168].

For ethical reasons, controlled clinical trials of drugs used for AR have not been conducted in pregnant women. Accordingly, there are no data for these drugs demonstrating an absence of risk to the fetus in any trimester of pregnancy (FDA Pregnancy Category A). Several medications used to treat AR belong to Category B (no risk demonstrated in animal reproduction studies, and systematic reviews of case-control studies in pregnant women show no evidence of human risk): loratadine**, cetirizine**, budesonide** [2, 4, 7, 164–171].

Most drugs used for AR belong to Category C (there is a potential for fetal harm, but the potential benefit may outweigh the potential risk).

The prescription of medications during the first trimester of pregnancy (the period of embryogenesis) is undesirable, except in cases of vital necessity.

When prescribing therapy during breastfeeding, one should limit treatment to topical medications with minimal systemic bioavailability whenever possible. All systemic drugs used to treat AR pass into breast milk; therefore, if their administration is necessary, discontinuation of breastfeeding should be considered.

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Comments: The education program for patients (or their legal representatives) with AR should include providing information about the disease, formulating an individualized treatment plan, and teaching self-management techniques.

5. Prevention and Dispensary Observation

Prevention aims to maintain long-term disease control and prevent exacerbations, and includes avoidance measures: eliminating or limiting exposure to allergens or other AR triggers, and excluding (limiting) cross-reactive foods and herbal medicinal products (for patients with pollen sensitization) [2, 7].

Dispanserization (clinical follow-up) aims to improve adherence to prescribed therapy to prevent the progression of the pathological process and the development of complications, as well as to correct risk factors for the development of bronchial asthma.

Comments: The minimum frequency of follow-up visits (consultations) is at least once a year for adults and at least twice a year for children. The duration of dispensary observation is lifelong or until the following conditions are met: achieving stable compensation of physiological functions or stable remission of the chronic disease (allergic rhinitis) for 3 years or more.

An important part in the management of patients with allergic diseases is guiding patients on the need for competent and timely treatment, familiarizing them with modern methods of specific and nonspecific therapy, teaching them how to use medications correctly, various measures for preventing exacerbations, psychological rehabilitation, self-monitoring, and introducing them to the latest scientific achievements in the fields of allergology and immunology.

6. Organization of Medical Care

Treatment of allergic rhinitis is, in most cases, carried out on an outpatient basis. When clinically indicated, medical care can be provided in any form and under conditions stipulated by the legislation of the Russian Federation.

Indications for hospital admission to a medical organization:

1) extremely severe and/or complicated course of the disease (emergency/urgent);

2) in children, a severe exacerbation with pronounced nasal obstruction (emergency/urgent);

3) the need for an accelerated course of allergen-specific immunotherapy under allergen avoidance conditions (elective)

Indications for patient discharge from a medical organization

1) achieving control over allergic rhinitis symptoms, normalization of laboratory parameters;

2) completion of the course of allergen-specific immunotherapy.

The approval for prescribing targeted therapy for patients with allergic rhinitis is carried out by a medical board (consilium of physicians).

7. Additional Information

Allergic rhinitis, as a rule, does not require hospitalization and does not lead to disability or death of the patient. However, like any chronic pathology, it tends to worsen—symptoms become more pronounced over time, some patients develop bronchial asthma, the spectrum of causal allergens expands, and the effectiveness of standard therapy decreases [2, 4-7, 22-25]. Of note is the low rate of early-stage medical seeking among patients with allergic rhinitis and their late referral to an allergist (6 to 13 years after disease onset) [2, 10, 12]. Delayed diagnosis of allergic rhinitis leads many patients to self-medicate for a long time, typically involving the excessive use of adrenomimetics (decongestants) and sedating systemic antihistamines [12]. The physical discomfort caused by the main symptoms of allergic rhinitis has an undesirable effect on the psychological state and social life of individuals, limiting their professional activity [2, 10, 12]. Inadequate therapy, especially with drugs having prominent side effects (such as sedation, cardiotoxicity, etc.), can affect the general condition, thereby worsening the patient's quality of life, reducing labor productivity, and increasing indirect treatment costs. A comprehensive approach, including rational pharmacotherapy, allergen avoidance measures, and allergen-specific immunotherapy, generally leads to a reduction in clinical manifestations, improves the patient's quality of life, and helps achieve long-term remission [32-36].

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Astafyeva Natalia Grigoryevna, Head of the Department of Clinical Immunology and Allergology, Saratov State Medical University named after V.I. Razumovsky of the Russian Ministry of Health, Professor, Doctor of Medical Sciences, Member of the Russian Association of Allergologists and Clinical Immunologists.

2. Baranov Alexander Alexandrovich, Academician of the Russian Academy of Sciences, Honorary President of the Union of Pedians of Russia, Advisor to the Head of the Research Institute of Pediatrics and Child Health of the National Medical Research Center of Children's Health, Petrovsky National Research Center of Surgery, Professor at the Department of Pediatrics and Pediatric Rheumatology, Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University), Chief freelance pediatric specialist of the Russian Ministry of Health.

3. Vishneva Elena Alexandrovna, Professor of the Russian Academy of Sciences, Press Secretary of the Union of Pedians of Russia, Deputy Head for Science at the Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Doctor of Medical Sciences, Member of the Russian Association of Allergologists and Clinical Immunologists.

4. Daykhes Nikolai Arkadyevich, Corresponding Member of the Russian Academy of Sciences, Director of the National Medical Research Center for Otorhinolaryngology of the Federal Medical-Biological Agency of Russia, Chief freelance otorhinolaryngologist of the Russian Ministry of Health, Vice-President of the National Medical Association of Otorhinolaryngologists, Professor, Doctor of Medical Sciences.

5. Zhestkov Alexander Viktorovich, Head of the Department of General and Clinical Microbiology, Immunology and Allergology, Samara State Medical University of the Russian Ministry of Health, Professor, Doctor of Medical Sciences, Member of the Russian Association of Allergologists and Clinical Immunologists, Russian Respiratory Society.

6. Ilyina Natalia Ivanovna, Vice-President of the Russian Association of Allergologists and Clinical Immunologists, Deputy Director for Clinical Work – Chief Physician of the National Research Center "Institute of Immunology" of the Federal Medical-Biological Agency of Russia, Professor, Doctor of Medical Sciences.

7. Korneeva Olga Vitalievna, Deputy Director for Scientific Work of the National Medical Research Center for Otorhinolaryngology of the Federal Medical-Biological Agency of Russia, Associate Professor, Professor at the Department of Otorhinolaryngology, Faculty of Additional Professional Education, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Doctor of Medical Sciences, Member of the National Medical Association of Otorhinolaryngologists.

8. Karpova Elena Petrovna, Head of the Department of Pediatric Otorhinolaryngology, Russian Medical Academy of Continuous Professional Education, Professor, Doctor of Medical Sciences, Member of the National Medical Association of Otorhinolaryngologists.

9. Kim Irina Anatolyevna, Head of the Department of Science and Education, National Medical Research Center for Otorhinolaryngology of the Federal Medical-Biological Agency of Russia, Professor of the Department of Otorhinolaryngology, Faculty of Additional Professional Education, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Doctor of Medical Sciences, Member of the National Medical Association of Otorhinolaryngologists.

10. Kryukov Andrei Ivanovich, Corresponding Member of the Russian Academy of Sciences, Director of the Sverdhevsky Research Clinical Institute of Otorhinolaryngology, Chief freelance otorhinolaryngologist of the Moscow Healthcare Department, Head of the Department of Otorhinolaryngology, Faculty of General Medicine, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Professor, Doctor of Medical Sciences, Member of the National Medical Association of Otorhinolaryngologists.

11. Kurbacheva Oksana Mikhailovna, Chief freelance allergist-immunologist of the Central Federal District of Russia; Professor at the Department of Clinical Allergology and Immunology, Faculty of General Medicine, Yevdokimov Moscow State University of Medicine and Dentistry, Head of the Department of Bronchial Asthma, National Research Center "Institute of Immunology" of the Federal Medical-Biological Agency of Russia, Professor, Doctor of Medical Sciences, Member of the Presidium of the Russian Association of Allergologists and Clinical Immunologists.

12. Meshkova Raisa Yakovlevna, Chief freelance allergist-immunologist of the Smolensk Region, Head of the Department of Allergology and Immunology, Smolensk State Medical Academy, Professor, Doctor of Medical Sciences, Member of the Russian Association of Allergologists and Clinical Immunologists.

13. Namazova-Baranova Leila Seymurovna, Academician of the Russian Academy of Sciences, President of the Union of Pedians of Russia, Head of the Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Head of the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Chief freelance pediatric specialist in preventive medicine of the Russian Ministry of Health, Professor, Doctor of Medical Sciences, Member of the Russian Association of Allergologists and Clinical Immunologists.

14. Nenasheva Natalia Mikhailovna, Head of the Department of Clinical Allergology, Russian Medical Academy of Continuous Professional Education, Professor, Doctor of Medical Sciences, Member of the Presidium of the Russian Association of Allergologists and Clinical Immunologists, Member of the Russian Respiratory Society.

15. Novik Gennady Aizikovich, Deputy Chairman of the Executive Committee of the Union of Pedians of Russia, Head of the Vorontsov Department of Pediatrics, Faculty of Pediatrics and Continuing Professional Education, Saint Petersburg State Pediatric Medical University of the Russian Ministry of Health, Professor, Doctor of Medical Sciences, Member of the Russian Association of Allergologists and Clinical Immunologists.

16. Nosulya Evgeny Mikhailovich, Head of the Educational and Clinical Department of the Sverdhevsky Research Clinical Institute of Otorhinolaryngology, Professor, Doctor of Medical Sciences, Member of the National Medical Association of Otorhinolaryngologists.

17. Pavlova Ksenia Sergeevna, Leading Researcher at the Department of Bronchial Asthma, National Research Center "Institute of Immunology" of the Federal Medical-Biological Agency of Russia, Candidate of Medical Sciences, Member of the Russian Association of Allergologists and Clinical Immunologists.

18. Pampura Alexander Nikolaevich, Chief freelance pediatric allergist-immunologist of Moscow, Head of the Department of Allergology and Clinical Immunology of the Veltischev Research Clinical Institute of Pediatrics of the Pirogov Russian National Research Medical University of the Russian Ministry of Health, Professor, Doctor of Medical Sciences, Member of the Russian Association of Allergologists and Clinical Immunologists, Member of the Union of Pedians of Russia.

19. Svistushkin Valery Mikhailovich, Chief freelance otorhinolaryngologist of the Central Federal District of Russia, Director of the Clinic and Head of the Department of Ear, Nose and Throat Diseases, Sechenov First Moscow State Medical University, Professor, Doctor of Medical Sciences, Member of the National Medical Association of Otorhinolaryngologists.

20. Selimzyanova Lilia Robertovna, Leading Researcher at the Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Associate Professor at the Department of Pediatrics and Pediatric Rheumatology, Sechenov First Moscow State Medical University of the Russian Ministry of Health (Sechenov University), Associate Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Member of the Union of Pedians of Russia, Candidate of Medical Sciences.

21. Khaitov Musa Rahimovich, Corresponding Member of the Russian Academy of Sciences, Director of the National Research Center "Institute of Immunology" of the Federal Medical-Biological Agency of Russia, Chief freelance specialist in allergology and immunology of the Federal Medical-Biological Agency of Russia, President of the Russian Association of Allergologists and Clinical Immunologists, Professor, Doctor of Medical Sciences.

22. Efendieva Kamilla Evgenyevna, Executive Secretary of the Union of Pedians of Russia, Deputy Head for Educational and International Activities of the Research Institute of Pediatrics and Child Health, Petrovsky National Research Center of Surgery, Associate Professor at the Department of Faculty Pediatrics, Pediatric Faculty, Pirogov Russian National Research Medical University of the Russian Ministry of Health, Candidate of Medical Sciences.

No conflicts of interest.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Allergist-immunologist

2. Otorhinolaryngologist

3. General practitioner / Physician

4. Pediatrician

5. General practitioner

Methods used for evidence collection/selection:

• electronic database searching.

Description of methods used for evidence collection/selection:

• the evidence base for the recommendations includes publications from the Cochrane Library, EMBASE, and MEDLINE databases. The search depth was 15 years.

Table 1.Levels of Evidence (LoE) grading scale for diagnostic methods (diagnostic interventions)

Table 2.Levels of Evidence (LoE) grading scale for prevention, treatment and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table 3. Scale for grading levels of recommendation certainty (LRC) for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Economic analysis:

Cost analysis was not performed, and pharmacoeconomic publications were not analyzed.

Method of recommendation validation:

• External peer review;

• Internal expert review.

Description of the guideline validation method:

The preliminary version of these guidelines was reviewed by independent experts, who were asked to comment primarily on how accessible the interpretation of the evidence underlying the recommendations is for understanding.

Feedback was obtained from primary care physicians and district therapists regarding the clarity of the recommendations and their assessment of the recommendations as a practical tool for daily practice.

The preliminary version was also sent to a non-medical reviewer for comments from the patients' perspective.

Comments received from experts were carefully systematized and discussed by the chair and members of the working group. Each point was discussed, and the resulting changes made to the recommendations were logged. If no changes were made, the reasons for refusing to make changes were logged.

Consultation and peer review:

The draft version was posted for broad discussion on the website of the Russian Association of Allergologists and Clinical Immunologists so that all interested parties could participate in discussing and improving the recommendations.

The draft recommendations were also reviewed by independent experts who were asked to comment primarily on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.

Working Group:

For the final revision and quality control, the recommendations were re-evaluated by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account and the risk of bias in the development of the recommendations was minimized.

Procedure for updating clinical guidelines.

The mechanism for updating clinical guidelines provides for their systematic revision at least once every three years, as well as upon the emergence of new evidence-based medicine data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to previously approved clinical guidelines, but no more frequently than once every 6 months.

Appendix A3. Reference Materials

1. Order of the Ministry of Health of the Russian Federation No. 606n dated November 7, 2012, "On Approval of the Procedure for Providing Medical Care to the Population in the Profile 'Allergology and Immunology'" Registered with the Ministry of Justice of the Russian Federation on January 28, 2013. Registration No. 26732

2. Order of the Ministry of Health of the Russian Federation No. 103n dated February 28, 2019, "On Approval of the Procedure and Deadlines for the Development of Clinical Guidelines, Their Revision, Standard Form of Clinical Guidelines and Requirements for Their Structure, Composition and Scientific Validity of Information Included in Clinical Guidelines" Registered with the Ministry of Justice of the Russian Federation on May 8, 2019. Registration No. 54588

3. Guidelines for the development of physician action algorithms. Ministry of Health of the Russian Federation, 2016.

Appendix B. Physician Action Algorithms

Appendix C. Patient Information

Allergic rhinitis is an inflammatory disease of the nasal mucosa caused by exposure to an allergen. Characteristic symptoms (manifestations) of allergic rhinitis include:

- sneezing,

- nasal congestion,

- watery nasal discharge,

- nasal itching.

Allergic rhinitis is often combined with other allergic diseases: allergic conjunctivitis (eyelid itching, eye redness, lacrimation), bronchial asthma (cough, wheezing, dyspnea, shortness of breath), atopic dermatitis (skin itching, skin redness, skin dryness, rashes), etc.

In allergic rhinitis, symptoms occur under the same conditions, for example:

- upon contact with house dust (during cleaning or in a dusty room);

- upon contact with pets (cats, dogs, guinea pigs, horses, etc.);

- when reading books and magazines, especially old ones;

- in spring, summer, and/or autumn,

The above symptoms of the disease may bother you throughout the year, as in perennial (year-round) allergic rhinitis, or during a specific season (spring, summer, and/or autumn), as in pollinosis.

Household or year-round allergic rhinitis is associated with sensitization (hypersensitivity) to house dust allergens.

House dust includes:

- various fibers (clothing, bed linen, furniture);

- library dust (dust particles from books, magazines);

- epidermal particles (desquamated particles of the surface skin layers) of humans and animals (cats, dogs, rodents), animal dander, bird feathers;

- spores of microscopic mold and yeast fungi;

- cockroach and house dust mite allergens (chitin shell particles and their waste products).

Pollinosis, or hay fever, or seasonal allergic rhinitis is associated with sensitization (hypersensitivity) to the allergens of wind-pollinated plant pollen.

Each region has its own plant pollination (flowering) calendar, which depends on climatic and geographical features.

For Central Russia, three main flowering periods of allergenic plants are distinguished:

- spring (April–May) – associated with the flowering of trees (birch, alder, hazel, oak, etc.);

- early summer (June – mid-July) – associated with the flowering of cereals or meadow grasses (timothy, fescue, orchard grass, ryegrass, brome, rye, bluegrass, etc.);

- late summer - autumn (mid-July – September) – associated with the flowering of weeds: Asteraceae (sunflower, wormwood, ragweed) and Chenopodiaceae (orache).

If you are allergic to plant pollen or mold spores, cross-reactions to food products are often noted. This is due to the similar structure of plant pollen allergens and certain foods. Food intolerance reactions can manifest as the following symptoms: itching or burning of the palate, sore throat, lip swelling, sneezing, nasal congestion, eyelid itching, lacrimation, redness of the skin around the mouth, difficulty breathing, difficulty swallowing, swelling of the soft facial tissues, laryngeal edema, itchy rashes all over the body, nausea, vomiting, abdominal pain, stool disorders. Extremely rarely, such a severe reaction as anaphylactic shock may occur. Sometimes patients with tree pollen allergies note contact dermatitis when peeling new potatoes or carrots.

Some patients note food intolerance reactions only during the pollinosis exacerbation season, while others note them throughout the year (see the cross-reaction table).

Allergic reactions can occur to herbal medicines and cosmetics, and in the case of allergy to fungal allergens, to fungal-derived medicines.

How is allergic rhinitis diagnosed?

Observation and treatment of a patient with allergic rhinitis are carried out jointly by an otorhinolaryngologist and an allergist-immunologist. If the above symptoms are present, it is necessary to consult doctors in both specialties. The otorhinolaryngologist will perform an examination and assess the presence of anatomical features and other pathology. The allergist-immunologist will perform allergy diagnostics to identify clinically significant allergens.

To diagnose (identify) clinically significant allergens (i.e., those allergens that cause your symptoms of allergic rhinitis and conjunctivitis), doctors use two main methods:

Performing skin scarification or prick tests: drops of allergen solutions are applied to the skin of the forearm or back, and then scratches or punctures are made through these drops using a scarifier (a special needle). In addition to allergen solutions, a histamine solution (positive control) and a test control (negative control) are applied. The test takes 15–20 minutes. In all people, the positive control produces redness and swelling (a wheal). There should be no reaction to the negative control. If you are allergic to a substance, redness and a wheal similar to the positive control reaction form at the site of the allergen. Systemic antihistamines must not be taken on the eve of and on the day of the test. The test is not performed:

- during a severe exacerbation of the disease (for example, during the pollination season of causative plants);

- if the skin of both forearms and back is damaged;

- if systemic antihistamines cannot be discontinued;

- during pregnancy and breastfeeding.

If skin provocation tests cannot be performed, determination of specific IgE (class E immunoglobulin) levels in blood serum is carried out.

What is IgE and why does it increase in allergies? For every foreign substance - an antigen (let's call it a "harmful agent") penetrating the body, the immune system produces antibodies ("defenders") that should block and remove the "harmful agents" from the body. The interaction between antigen and antibody is strictly specific; they fit each other like a key in a lock.

In a healthy body, antibodies (immunoglobulins) class G (IgG, let's call them the "active defender army") are produced, which help the body neutralize the enemy in time. In a patient suffering from allergies, the body produces antibodies (immunoglobulins) class E (IgE, let's call them the "alternative army of false defenders") in response to a specific allergen (also known as antigen). Class E immunoglobulins are located on mast cells (found in the skin and mucous membranes of the respiratory and digestive tract) and basophils (found in the blood). These cells contain a large amount of active substances similar to histamine. When an allergen (the "key") enters the body of an allergy sufferer, it opens mast cells and basophils through class E immunoglobulins (IgE, the "lock"), releasing a large amount of active substances similar to histamine, which determines the development of an allergic reaction (redness, swelling, itching, etc.)

Normally, the total IgE level is extremely low (less than 130 IU), and specific IgE (IgE to specific allergens) is practically undetectable (0–1 reaction class). If hypersensitivity to a specific allergen is present, specific IgE (2–4 reaction class) is detected, and an increase in the total IgE level is determined (not always).

Cross-reactive food and drug allergic reactions

What allergy prevention measures exist?

Allergen elimination or reducing contact with the clinically significant allergen is the first and necessary step in allergy treatment. It is especially important to carry out these measures when there are serious restrictions on drug treatment (pregnancy, breastfeeding, early childhood, severe comorbid conditions).

Reducing contact with household allergens:

- try to remove carpets, soft toys, bookcases, boxes, thick fabric curtains, a TV, and a computer from the room where you sleep and spend most of your time (the concentration of dust increases significantly near them);

- replace carpet flooring with easily washable laminate, linoleum, or wooden flooring;

- wall finish: washable wallpaper or painted walls should be preferred;

- replace down, feather, and wool pillows, mattresses, and blankets with synthetic or cotton ones; wash pillows and blankets every month; replace pillows and blankets every year; use protective mattress covers and replace them with new ones at least once every 10 years;

- bedspreads should be made of easily washable, lint-free fabrics;

- perform wet cleaning at least twice a week; use vacuum cleaners with disposable bags and filters or water-reservoir vacuum cleaners;

- install an air conditioner or air filter in the apartment; ensure regular filter replacement;

- maintain indoor humidity at no more than 40% – this reduces the reproduction rate of mites and molds;

- do not keep pets, birds, or fish (even if you do not have increased sensitivity to epidermal allergens);

- do not keep indoor plants;

- do not store items under the bed or on top of cabinets;

- do not smoke;

- do not use perfumes and other strongly scented substances, especially in sprays;

- it is best to clean in the absence of the patient; if you have to clean yourself, wear a respirator capable of trapping fine particles (allergens);

- do not scatter clothing around the room; store clothes in a closed wardrobe; store wool and fur clothing in zippered covers;

- avoid open bookshelves; books should be stored behind glass;

- use acaricides – special agents that destroy mites;

- rinse your nose with isotonic saline nasal products for moisturizing, cleansing, and protecting the nasal mucosa, including seawater-based products.

Reducing contact with epidermal allergens:

- there are no allergen-free animals;

- it is necessary to part with pets and not acquire new ones;

- if this is not possible, it is essential to thoroughly vacuum rooms and upholstered furniture; prohibit animals from entering the bedroom; wash pets regularly;

- do not visit circuses, zoos, and homes with animals;

- do not use clothing made from animal wool and fur.

Reducing contact with mold allergens:

- maintain indoor humidity at no more than 40%;

- regularly clean and dry areas that promote mold growth (showers, basements);

- ensure regular replacement of filters in air conditioners;

- wipe all wet surfaces dry after using the bathroom; use mold-preventive cleaning solutions (containing chlorine, boric acid, or baking soda);

- if leaks or black spots on walls are present, remediation must be performed using special fungicidal agents (which kill fungi and prevent their growth);

- do not keep aquarium fish or breed indoor plants;

- dry clothes in a ventilated room outside the living area;

- do not participate in gardening work in spring and autumn;

- when planning a vacation, avoid trips to countries with warm, humid climates;

- avoid visiting poorly ventilated areas (cellars, storehouses);

- do not consume foods of fungal origin.

Reducing contact with plant pollen:

- avoid staying outdoors on days with peak pollen concentrations in the air;

- rinse your nose with isotonic saline nasal products for moisturizing, cleansing, and protecting the nasal mucosa, including seawater-based products;

- exclude foods that cause cross-allergic reactions from your diet (see the cross-reactivity table);

- whenever possible, travel to regions where the plants causing allergic pollen bloom at a different time or do not grow there (mountains at an altitude of over 1,500–2,000 meters);

- do not use herbal medicines and cosmetics;

- during the pollination season of plants to whose pollen you are allergic, elective surgical interventions and routine vaccinations are not recommended. These procedures should be performed before the pollination season begins or postponed until it ends.

What to do when symptoms of allergic rhinitis appear?

- To reduce symptom severity, non-sedating systemic antihistamines (latest generation) may be used in dosages according to the product leaflet.

- Do not use decongestants for more than 7 days.

- If symptom control is not achieved, consult a doctor to adjust the therapy.

What is allergen-specific immunotherapy?

None of the medications you use to relieve the symptoms of allergic rhinitis can alter your body's response to the allergen. Unfortunately, allergic diseases tend to snowball: first, mild manifestations of rhinitis and/or conjunctivitis appear, then symptoms become pronounced and the medications that used to work no longer help, a dry cough develops, and some individuals experience choking attacks and develop bronchial asthma. If at the beginning of the disease the season was limited to 2 weeks, later on it lengthens, or, if a house dust allergy has developed, you feel unwell all year round.

The only method available today capable of altering your body's response to the allergen and preventing the further progression of allergy is allergen-specific immunotherapy (AIT). This method has existed for over a century, is widely used worldwide, and has been employed in our country since the 1960s.

The allergen causing your disease (house dust, house dust mite, tree or grass pollen) is diluted a millionfold and administered to your body in gradually increasing doses. As a result of the treatment, your body gets used to this allergen and stops reacting so strongly to it. During this process, complex reactions occur within your immune system, the ultimate outcome of which is a switch from an abnormal (allergic) response to a normal (healthy) response to this allergen.

Following AIT, patients report a reduction in the manifestations of allergic rhinitis and/or conjunctivitis, up to their complete disappearance, a decreased need for medications, and an improved quality of life. The treatment efficacy averages 70% and reaches up to 90% in some patients. The effect is noticeable after the first course of treatment, but at least three full treatment courses are required to achieve the best outcome. Efficacy is higher in patients with shorter disease duration and lower severity.

There are injection and sublingual methods of administering AIT. The presence of indications and contraindications for AIT, the selection of the therapeutic allergen, and the prescription of AIT are performed by an allergist-immunologist.

Considering the general trends in the course of allergic diseases, which "snowball," the efficacy of AIT, the ability to prevent the development of bronchial asthma in patients with allergic rhinitis, and to prevent the expansion of the spectrum of causative allergens (the addition of new allergens triggering reactions), as well as the safety of AIT when correctly performed, AIT can be an excellent treatment method for many patients.

In any case, only your attending physician can determine the treatment tactics, taking into account the individual characteristics of your body, the course of the allergic disease, and comorbid conditions. Do not self-medicate! Timely medical consultation will help select the correct treatment in a timely manner.

Patient Glossary

Allergen – a substance that triggers an allergic reaction

Allergy (atopy) – a disease caused by the action of a specific allergen

Symptoms - manifestations of a disease

Rhinitis - an inflammatory disease of the nasal mucosa

Conjunctivitis is an inflammatory disease of the mucous membrane of the eye

Sensitization is an increased sensitivity to a specific allergen

Indoor (perennial) allergic rhinitis is associated with sensitization to house dust allergens, epidermal allergens, or fungal allergens

Pollinosis (hay fever, seasonal allergic rhinitis) is associated with sensitization to allergens from wind-pollinated plant pollen.

Diagnosis – determination

Causative allergen is the allergen that triggers allergy symptoms

Allergen elimination is the reduction of contact with the causative allergen.

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. Visual analog scale with an algorithm for optimizing the pharmacologic treatment of allergic rhinitis

Russian title: Visual analog scale (VAS) with an algorithm for optimizing the pharmacologic treatment of allergic rhinitis.

Original title: Visual analog scale (VAS) and Step-up algorithm in untreated patients using the VAS.

Source (official developer website, validation publication):

Bousquet P.J., Combescure C., Neukirch F., Klossek J.M., Méchin H., Daures J.P. Visual analog scales can assess the severity of rhinitis graded according to ARIA guidelines. Allergy. 2007; 62 (4): 367–372. DOI: 10.1111/j.1398-9995.2006.01276.x [39].

Bousquet J, Schunemann HJ, Hellings PW, Arnavielhe S, Bachert C, Bedbrook A, et al. MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis. J Allergy Clin Immunol. 2016;138(2):367-74 e2 [40].

Courbis AL, Murray RB, Arnavielhe S, Caimmi D, Bedbrook A, Van Eerd M, et al. Electronic Clinical Decision Support System for allergic rhinitis management: MASK e-CDSS. Clin Exp Allergy. 2018;48(12):1640-53 [41].

Type (underline):

- rating scale

- score

- questionnaire

- other (specify): ______________________

Purpose: Assessment of the severity of allergic rhinitis symptoms during therapy

Content (template):

The visual analog scale (VAS) is a horizontal graduated line 10 cm (100 mm) long (Fig.), on which the patient marks with a vertical line their score of the disease's impact (e.g., allergic rhinitis) on their well-being, expressed in points from 0 (0 mm) to 100 (100 mm), where 0 means no complaints or symptoms, and 100 means maximally severe manifestations of the disease. The distance to the vertical line is then measured in millimeters and expressed in points.

Fig. Visual analog scale

Key (interpretation): Scores from 0 to 50 indicate controlled AR, while scores of 50 and above indicate uncontrolled AR.

Notes: VAS results can be used to select the treatment step according to the proposed algorithm. The proposed algorithm involves step-by-step treatment and takes patient preferences into account, depending on the VAS results. If ocular symptoms persist, the addition of medications for allergic conjunctivitis is recommended.

Step-by-step treatment algorithm for previously treated patients using

the visual analog scale (adolescents and adults) [21].

Appendix G2. Allergic Rhinitis Control Criteria

Russian title: Criteria for allergic rhinitis control

Original title: Practical assessment of rhinitis control

Source (official developer website, publication with validation): Papadopoulos NG, Bernstein JA, Demoly P, Dykewicz M, Fokkens W, Hellings PW, Peters AT, Rondon C, Togias A, Cox LS. Phenotypes and endotypes of rhinitis and their impact on management: a PRACTALL report. Allergy. 2015 May;70(5):474-94. DOI: 10.1111/all.12573. Epub 2015 Feb 19 [43].

Type (underline):

- rating scale

- index

- questionnaire

- other (specify): integral assessment considering subjective and objective parameters

Purpose: Assessment of symptom control in allergic rhinitis

Content (template):

* The patient is asked to close their mouth and breathe exclusively through the nose for 30 seconds

Key (interpretation): Any deviation from these criteria indicates a loss of control, and step-up therapy may be considered. The decision for step-down therapy should be made by evaluating the clinically asymptomatic period (control of rhinitis symptoms) resulting from previous therapy over the past 4 weeks.

Notes -

Appendix G3. Nasal Symptom Scoring Scale Adjusted for Medication Requirements

Russian title: Combined symptom and medication score for rhinitis

Original title: Combined symptom and medication score (CSMS)

Source (official developer website, publication with validation): Pfaar O, Demoly P, Gerth van Wijk R, Bonini S, Bousquet J, Canonica GW, Durham SR, Jacobsen L, Malling HJ, Mosges R, Papadopoulos NG, Rak S, Rodriguez del Rio P, Valovirta E, Wahn U, Calderon MA. Recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic rhinoconjunctivitis: an EAACI Position Paper. Allergy 2014; 69: 854–867 [151]

Type (underline):

- rating scale

- index

- questionnaire

- other (specify): _____________________

Purpose: Assessment of symptom severity and medication requirement; can be used at baseline and to evaluate the efficacy of allergen-specific immunotherapy

Content (template):

Indicate the severity of symptoms on a 3-point scale, where 0 - no symptoms, 1 – mild symptoms, 2 – moderate symptoms, 3 – severe manifestations.

* the physician then calculates the average total nasal symptom score (TNSS) over the past 7 days. The minimum acceptable TNSS value is 0 points, meaning complete absence of symptoms, and the maximum acceptable TNSS value is 12 points.

Indicate all medications you have taken

* the physician then calculates the average medication score (MS) over the past 7 days. The use of local or systemic antihistamines alone is rated as 1 point, the need for topical intranasal corticosteroids is rated as 2 points, and the need for systemic glucocorticoids is rated as 3 points. Scores are not summed; the maximum score is assigned. Thus, the minimum acceptable MS value is 0, indicating no need for medication, and the maximum acceptable MS value is 3, indicating the need for third-line medication.

Key (interpretation): The physician then calculates the combined nasal symptom and medication score over the past 7 days: TNSS + MS (the minimum acceptable value is 0 points, indicating no symptoms and no need for medication, and the maximum acceptable value is 15 points, indicating maximum severity of rhinitis symptoms despite the use of third-line medications)

Notes: The patient fills out this diary during an exacerbation period (seasonal exacerbation and/or period of active contact with the causative allergen) at initial presentation, and in the following season or 6–12 months after allergen-specific immunotherapy (AIT). Based on the dynamics of baseline parameters and those after AIT, a decision is made regarding treatment efficacy, the need for repeated courses, or the possibility of discontinuing therapy.