Atopic and allergic conditions: causes, symptoms, diagnosis, treatment

Hypersensitivity reactions of type I include atonic and many allergic disorders. The terms "atopy" and "allergy" are often used as synonyms, but in reality these are different concepts. Atopy is an excessive IgE-mediated immune response; all atonic disorders refer to hypersensitivity reactions of type I. Allergy is any, regardless of the mechanism, an excessive immune response to an external antigen. Thus, all atopy is based on an allergic reaction, but many allergic reactions (eg, hypersensitivity pneumonitis) are not atopic disorders. Allergic diseases are the most common diseases in a person.

Atopy most often affects the nasal cavity, eyes, skin and lungs. These disorders include atopic dermatitis, contact dermatitis, urticaria, and angioedema (which can primarily manifest as skin lesions or symptoms of systemic disease), latex allergy, allergic lung diseases (eg, asthma, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis) and allergic reactions to bites stinging insects.

[1], [2], [3], [4], [5], [6]

Causes of Atopic States

The complex of genetic factors, environmental factors and local factors leads to the development of allergies. The role of genetic factors is the presence of a hereditary predisposition to diseases associated with atopy and specific HLA-loci, and the polymorphism of genes responsible for high affinity, the lgE receptor tnf-chain, IL-4nCD14.

Environmental factors interact with genetic factors at the level of maintenance of the immune response of Th2, which activate eosinophils and IgE production and are pro-allergic. Normally, a primary encounter with bacterial and viral infections and endotoxins (lipopolysaccharides) in early childhood shifts the response from natural Th2 to TM, which suppresses Th2 and induces tolerance towards foreign antigens; this mechanism can be mediated by the Toll-like receptor-4 and is realized by developing a population of regulatory T-lymphocytes (CD4 +, CD25 +) that suppress the Th2 response. Currently, there is a tendency in developed countries to form small families with a small number of children, a cleaner home environment, early vaccination and antibiotic therapy, which deprives children of such a meeting with antigens and suppresses suppression of Th2; such behavioral changes may explain the widespread occurrence of certain allergic conditions. Other factors contributing to the spread of allergic conditions include chronic contact with the allergen and sensitization, diet, physical activity.

Local factors include adhesion molecules of the epithelium of the bronchi, skin, GIT, which direct Th2 to the target tissues.

Thus, the allergen induces an IgE-mediated and Th2-cell immune response. Allergens almost always represent low molecular weight proteins, many of which can be found among air particles. Allergens, including home dust, house dust mite excrement, livestock products, pollen of plants (trees, grasses, weeds) and mold, are often responsible for the development of acute and chronic allergic reactions.

[7], [8], [9]

Pathological physiology of atopic and allergic conditions

After the allergen is combined with IgE, histamine is released from intracellular mast cell granules; these cells are found in the body everywhere, but their greatest concentration is noted in the skin, lungs, mucous GIT; histamine enhances the activation of immune cells and is the primary mediator of the clinical manifestation of atopy. Impaired tissue integrity and various chemical agents (eg, irritants, opioids, surfactants) can cause the release of histamine directly, without the involvement of IgE.

Histamine causes local vasodilation (erythema), which increases the permeability of the capillaries and causes swelling (blisters), surrounding arteriolar vasodilation is mediated by a neuronal reflex mechanism (hyperemia) and stimulation of sensitive ends (itching). Histamine causes contraction of smooth airway myocytes (bronchoconstriction) and gastrointestinal tract (strengthening of the peristalsis of the gastrointestinal tract), increases the secretion of salivary and bronchial glands. When histamine release occurs systematically, it becomes an effective dilator of arterioles and can cause widespread peripheral blood stasis and hypotension; Cerebral vasodilation can be a factor in the development of headache of vascular genesis. Histamine increases the permeability of capillaries; as a result, the loss of plasma and plasma proteins from the vascular bed can cause circulatory shock. This causes a compensatory rise in the level of catecholamines, the source of which are the chromaffin cells.

Symptoms of atopic and allergic conditions

The most common symptoms include rhinorrhea, sneezing, nasal congestion (upper respiratory tract infection), dyspnea and dyspnea (lesion of the lower respiratory tract) and itching (eyes, skin). Among the symptoms there is edema of the nasal concha, pain in the area of additional nasal sinuses during palpation, dyspnea, congestion hyperemia and edema, skin lichenification. Stridor, shortness of breath and sometimes hypotension are life-threatening signs of anaphylaxis. Some children talk about chronic allergic lesions with a narrow and highly arched palate, a narrow chin, an elongated upper jaw with a deep bite (allergic face).

Diagnosis of atopic and allergic conditions

Careful collection of an anamnesis is usually a more reliable method than conducting tests and screening. Anamnesis includes information on the frequency and duration of seizures, changes that occur over time, provoking factors, if known, associated with seasons or a particular situation (eg, a predictable onset of seizures during the flowering season, after contact with animals, hay, dust; time of training, in certain places), family history of such symptoms or atopic disorders; reaction to the treatment. The age at which the disease begins can be important in the diagnosis of asthma, since childhood asthma is atonic in nature, and asthma, beginning after age 30, is not.

[10], [11], [12], [13], [14], [15], [16]

Nonspecific tests

Certain tests can confirm or disprove the allergic nature of the symptoms.

A general blood test is performed to detect eosinophilia in all patients, except for those who receive glucocorticoids; these drugs reduce the level of eosinophils. When detecting 5-15% of eosinophils in the leukocyte formula, an atopy is assumed, but its specificity is not revealed; 16-40% of eosinophils can reflect both atopy and other conditions (eg, drug hypersensitivity, cancer, autoimmune conditions, parasitic infections); 50-90% of eosinophils are a sign of non-atopic disorders, but rather of a hypereosinophilic syndrome or the presence of migrating larvae of helminths of internal organs. The total number of white blood cells is usually normal.

Conjunctival, nasal secretion or saliva can be examined for leukocyte count; the detection of any number of eosinophils presupposes Th2-mediated allergic inflammation.

The level of serum IgE is elevated in atopic states, but this is not a serious diagnostic sign, as it can be increased in parasitic infections, infectious mononucleosis, autoimmune conditions, drug allergies, immunodeficiency states (IgE hyperproduction syndrome, Wiskott-Aldrich syndrome), and some forms multiple myeloma. The determination of the level of IgE is useful for the appointment of subsequent therapy in the case of allergic bronchopulmonary aspergillosis.

Specific samples

In skin tests, a standardized antigen concentration is used, which is injected directly into the skin; Special tests are performed in the case when carefully collected history and general examination did not reveal the cause of the symptoms. Skin tests are more informative in the diagnosis of rhinosinusitis and conjunctivitis than in the diagnosis of allergic asthma or food allergies; The negative response for food allergy is very high. The most commonly used pollen antigens (trees, grasses, weeds), mold, home dust mites, animal products and animal sera, poison stinging insects, food products, p-lactam antibiotics. The choice of the antigen administered is based on the history and geographical position. Two technologies can be used: subcutaneous injection (injection) and intradermal. The first method allows you to identify a greater number of allergens. The intradermal test is more sensitive, but less specific; it can be used in assessing the sensitivity to an allergen with negative or questionable results of a subcutaneous test.

With a subcutaneous test, a drop of the antigen extract is applied to the skin, then the skin is stretched, pierced, or punctured through the extract drop by the tip of needle No. 27 at an angle of 20 ° or with an approved device. With the intradermal technique, the extract is injected intradermally with a 0,5- or 1-mm syringe with a No. 27 needle with a short bevel to form a 1- or 2-mm blister (usually about 0.02 ml). Both subcutaneous and intradermal tests should include the addition of another solution as a negative control and histamine (10 mg / ml with a subcutaneous test, 0.01 ml in a 1: 1000 solution with an intradermal test) as a positive control. For patients with a rare generalized reaction (less than 1 time per year) per test antigen, the study begins with a standard reagent diluted 100-fold, then 10-fold, and finally, standard concentration. The test is considered positive with the appearance of a blister and hyperemia, with a blister diameter 3-5 mm larger than in the negative control after 15-20 minutes. False positive response occurs with dermographism (blisters and hyperemia are provoked by stroking or scarification of the skin). False negative response occurs when improper storage or violation of the shelf life of the allergen extract or when taking some (for example, antihistamine) drugs that suppress reactivity.

Radioallergosorbent testing (RASD - radioallergosorbent testing) determines the presence of allergen-specific serum IgE and is performed with contraindications to skin tests, for example, with generalized dermatitis, dermographism, anamyloid anaphylactic reaction to an allergen or the need for taking antihistamines. A known allergen in the form of an insoluble polymer allergen conjugate is mixed with serum and detected with ¹²⁵ 1-labeled anti-1gE antibodies. Any allergen-specific IgE of the serum binds to the conjugate and is determined by measuring the amount of ¹²⁵ 1-labeled antibodies.

In provocative tests, there is a direct contact of the mucous membranes with the allergen and is used in patients who need to document the reaction (for example, the establishment of occupational hazard or disability) and sometimes for the diagnosis of food allergies. Ophthalmic examination has no advantages over skin tests and is rarely performed. Nasal or bronchial administration of a provoking agent is also a possible method of investigation, but a bronchial provocation test is only used if the clinical significance of a positive skin test is not clear or no antigen extracts are available (for example, occupational asthma).

Treatment of atopic and allergic conditions

Control over the environment

Removing or preventing contact with an allergen is the basis of allergy treatment.

Therefore, preference should be given to cushions with synthetic fibers and a dense coating on mattresses; it is often necessary to wash bed linens in hot water; To exclude soft upholstery of furniture, soft toys, carpets, communication with domestic animals; to tackle the struggle against cockroaches; It is also recommended to use desiccants in the toilet rooms, basement floors and other poorly ventilated, damp areas. Other measures may include the treatment of residences by vacuum cleaners and filters using high-efficiency particulate air, the elimination of food allergens, restriction of visiting certain rooms by pets, frequent wet cleaning of furniture and carpets. Additional non-allergenic triggers of allergic reactions (cigarette smoke, sharp smells, irritating smoke, air pollution, low temperatures, high humidity) should be excluded or strictly controlled.

[17], [18], [19], [20], [21], [22], [23]

Antihistamines

Antihistamines do not affect the production or metabolism of histamine, but block its receptors. H2-blockers are the main element of therapy for allergic diseases. H2-blockers are used primarily to suppress the secretion of hydrochloric acid in the stomach and are of limited importance in the treatment of allergies; they can be used for certain atopic disorders, especially with chronic urticaria.

Oral H2 blockers provide symptomatic treatment of various atopic and allergic disorders (seasonal hay fever, allergic rhinitis, conjunctivitis, urticaria, other dermatoses, minor reactions in the transfusion of incompatible blood and the introduction of radiopaque substances); they are less effective in allergic bronchoconstriction and vasodilation. The onset of action is usually observed after 15-30 minutes of peak reaches after 1 hour, the duration of the action is usually 3-6 hours.

Among oral H2-blockers, drugs with sedative effect or without it are isolated (preference should be given to drugs with less sedation). Sedative antihistamines are widely available, purchased without a prescription. All these drugs have a significant sedative and anticholinergic effect; but they also have certain limitations in the appointment of elderly patients, patients with glaucoma, starting hyperplasia of the prostate, constipation, dementia. Non-active (non-anticholinergic) antihistamines are preferred, except when a sedative effect is needed (for example, nighttime treatment of an allergic disease or short-term treatment of insomnia in adults or nausea in younger patients). Anticholinergic effects may also partially justify the use of sedative antihistamines for the symptomatic treatment of rhinorrhea in ARI.

Antihistamine solutions can be applied intranasally (azelastine for the treatment of rhinitis) or in the form of droplets for instillation into the eyes (azelastine, emedastin, ketotifen, levocabastine, olopatadine for the treatment of conjunctivitis). Diphenhydramine is also available for topical application, but it is not recommended for use; its effectiveness is not proven, it can cause drug allergy in young children who simultaneously use oral H2-blockers; can develop anticholinergic intoxication.

[24], [25], [26], [27]

Mast cell stabilizers

Examples of this group of drugs are cromolyn and nedocromil. These drugs block the release of mediators from mast cells; they are used in the case when other drugs (antihistamines, local glucocorticoids) are ineffective or little tolerant. Also used are eye forms (for example, lodoxamid, olopatadin, pemirolast).

Anti-inflammatory drugs.

NSAIDs are ineffective. Glucocorticoids can be administered intranasally or orally. Oral glucocorticoid drugs are used for systemic severe but self-stopping allergic disorders (eg, seasonal asthma outbreaks, severe widespread contact dermatitis) and for treatment of conditions refractory to the therapy used.

Antileukotriene drugs are used to treat mild forms of persistent bronchial asthma and seasonal allergic rhinitis.

Anti-1gE antibodies (omalizumab) are used to treat moderate to severe or persistent, or severe bronchial asthma, refractory to standard therapy; this drug can be used in the treatment of refractory allergic rhinitis.

[28], [29], [30], [31], [32], [33], [34], [35]

Immunotherapy

Contact with the allergen in gradually increasing doses (hypo- or desensitization) by injection or in large doses sublingually can induce tolerance and is used if contact with the allergen can not be prevented and drug therapy does not give the desired results. The mechanism is unknown, but may be associated with the induction of IgG, which competes with IgE for the allergen and blocks the binding of IgE to their receptors on mast cells; and may be associated with the induction of interferon y, IL-12 and cytokines secreted by TM-lymphocytes or by induction of regulatory T lymphocytes.

To achieve the full effect, injections should be carried out monthly. Usually begin with a dose of from 0.1 to 1.0 active units (LAE, BAU - biologically active units) depending upon the initial sensitivity and then increased weekly or biweekly in minutes 2 times per injection to a maximum tolerable concentration . Patients should be monitored for 30 minutes at each dose increase because of the risk of anaphylaxis following injection. The maximum dose should be administered every 4-6 weeks throughout the year; this treatment is better than the preseason or seasonal treatment, even with seasonal allergies. In this treatment, allergens are used, contact with which usually can not be ruled out: pollen, house dust mite, mold, poison of stinging insects. The insect venom is standardized by weight, the usual initial dose is 0.01 μg and the usual maintenance dose is 100 to 200 μg. Desensitization to livestock products of domestic animals is usually used for patients who can not avoid contact with the allergen (veterinarians, laboratory workers), but data on the benefits of such treatment are not enough. Food desensitization is not indicated.

Inhalational nasal glucocorticoids and stabilizers of mast cell membranes

A drug	Dosage with one injection	Initial dose	The number of doses in the can (one nostril)
Inhaled nasal glucocorticoids
Beclomethasone dipropionate	42μg	> 12 years: 1 injection 2 to 4 times a day. 6-12 years: 1 injection 2 times a day	200
Budesonide	32μg	6 years: 2 injections 2 or 4 times a day
Flunisolide	50μg	6-14 years: 1 injection into each nostril 3 times a day or 2 injections into each nostril 2 or 3 times a day	125
Fluticasone	50μg	4-12 years: 1 injection into each nostril 1 time per day. > 12 years: 2 injections into each nostril 1 time per day	120
Triamcinolone acetonide	55mkg	> 6 years: 2 injections 1 time per day	100
Systemic glucocorticoids
Dexamethasone	84μg	6-12 years: 1-2 injections 2 times a day. > 12 years: 2 injections 2 or 4 times a day	170
Mast cell stabilizers
Kromolin	5.2 mg	6 years: 1 injection 3 or 4 times a day
Nedocromil	1.3 mg	6 years: 1 injection into each nostril 2 times a day

Desensitization to penicillin and foreign (xenogeneic) serum can be performed.

Side effects are usually associated with overdose, sometimes with a malaise administration of the drug intramuscularly or intravenously, and are manifested by a variety of symptoms from mild cough or sneezing to generalized urticaria, severe asthma, anaphylactic shock, and sometimes death. They can be prevented by a very small increase in dose, repeat or decrease in dose if the local response to the previous injection was excessive (2.5 cm in diameter), lowering the dose with fresh extracts. It is recommended to reduce the dose of pollen preparations during the flowering period.