Atopy: what is it, causes, symptoms, treatment, prognosis

What is atopy?

Atopy Is a predisposition to an immunological response to various antigens/allergens, leading to CD4 + Th2 differentiation and overproduction of immunoglobulin E (IgE). The clinical consequence of this is a tendency to develop hypersensitivity reactions to allergens. Allergic bronchial asthma and allergic rhinitis are the most common manifestations of atopy, followed by atopic dermatitis and food allergy. Two or more clinical diseases can coexist in a person at the same time or at different times.

Other diseases described as atopic include allergic conjunctivitis, IgE-mediated drug allergy, insect bites, hives and angioedema, as well as anaphylactic shock.

Causes and risk factors

The etiology of atopy is unknown. Twin and epidemiological studies, as well as experiments in families and animals provide strong evidence that genetic factors play a decisive role in the predisposition to atopy, regulating the total synthesis of IgE and the production of IgE antibodies to specific epitopes. The inheritance of multiple genes influences the tendency to overproduction of IgE, and this spreads to families, which is clearly shown in the autosomal transmission of allergies, but the complete inheritance pattern is considered multigenic.

The theory explaining the genesis of atopy suggests that it may arise from abnormal regulation Helper T-cells and suppressor T-lymphocytes, which should aid in the production of IgE by plasma cells.

Examples of chromosomal positions and genes associated with atopy are 5q associated with the cytokine gene cluster (Interleukin (IL) -3, IL-4, IL-5, IL-13, CD14, beta-2-adrenergic receptor and granulocyte-macrophage colony-stimulating factor (GM-CSF)). IL-4 and IL-13 promote IgE switching, and IL-5 stimulates the growth and activation of eosinophils. Beta-2-adrenergic receptors regulate the contraction of bronchial smooth muscles. Chromosome 6p contains a class II major histocompatibility complex (MHC), and some of the alleles regulate T cell responses to environmental antigens or allergens. Gene for chromosome 11q (beta subunit of the high-affinity IgE receptor), which mediates the activation of mast cells. Chromosome 12q contains genes for stem cell factor (involved in the growth and differentiation of mast cells), IFN-gamma (inhibits IL-4 synthesis) and STAT6 (mediates IL-4 signaling). Other genes associated with atopy are the alpha chain of the IL-4 receptor, DPP10 (a protein that regulates the activity of chemokines and cytokines), ADAM33 metalloproteinase, which is involved in airway remodeling, and CD80 / CD86 located at 3q and RANTES at 17q are genes believed to be involved in atopy. Finally, PHF11 at 13q encodes a transcriptional regulator involved in B cell clonal expansion and immunoglobulin expression.

Nonspecific triggers asthma include infections (viral respiratory infections), climatic factors (ozone, cold air and SO2), physiological factors (exercise, hyperventilation, psychological factors) and medication (aspirin and non-steroidal anti-inflammatory drugs).

There is a list of occupational allergens that cause IgE-mediated allergic asthma, which includes animal products (cows, pigs, mice, dogs, cats and horses), insect dust (mealworms, mites, cockroaches, bees and flies), vegetable products origin. (dust, flour, grain and cotton dust), fruits, seeds, leaves and pollen (castor bean, tobacco and weeping figs), vegetables, dust, gums and extracts (western red, California red wood, exotic tree species), microbial agents (fungal allergens, alginates, protozoa, bacteria and fungi), enzymes (papain, pig trypsin, extracts pancreas, subtilisin and pineapple bromelain), therapeutic agents (penicillins, tetracycline, cephalosporins, sulfonamides and spiramycin), sterilizing agents (chloramycin), inorganic chemicals (vapors and salts of metals, aluminum, cobalt, fluorine, nickel, platinum, vanadium and zinc) and organic chemicals (amines, anhydrides and azodicarbonamide).

Epidemiology

Atopy affects a large proportion of the general population, usually 10 to 30% in developed countries. About 80% of people with atopy have a family history of allergies, compared with only 20% of the average population. In monozygous twins, concordance is only 50%. Susceptibility to atopic disease is genetic, but evidence suggests one or two dominant genes are likely to indicate that there are many genes with moderate effects.

Allergic rhinitis occurs on average in 12.7% -24% of the population of Russia. The prevalence and incidence are due to the geographic distribution of common allergens, including dust mites and allergenic plants. Both sexes are equally affected. The prevalence of bronchial asthma varies worldwide. It is a common disease that affects 5% of the population in Western countries. It causes over 3,000 deaths in the United States each year. Despite significant advances in immunotherapy, there has been an increase in mortality and morbidity rates. There were 8.4 million children with asthma in the US in 2014, of which 11.1% lived in poor urban areas

Pathophysiology

The pathophysiology of atopy usually demonstrates mast cell activation. Antigen binding to IgE binds Fc-epsilon RI proteins on mast cells. It activates protein tyrosine kinases (Lyn and Syk), which in turn activate the MAP kinase cascade and phosphatidylinositol-specific phospholipase C, which catalyzes the release of the following molecules: IP3 and DAG from membranes PIP2. Inositol triphosphate (IP3) causes the release of intracellular calcium from the endoplasmic reticulum. DAG and calcium activate PKC, which phosphorylates substrates such as the myosin light chain molecule, and thus leads to the degradation and release of preformed mediators. MAP kinases and calcium react by activating the enzyme cytosolic phospholipase A2, which stimulates the synthesis of lipid mediators, including PGD2, LTC4, LTD4, and LTE4. Ras / MAP kinases in the presence of calcium and PKC induce the expression of cytokine genes that release TNF and other cytokines (IL-4, IL-5, IL-6, IL-13, among others). Lipid neurotransmitters, cytokines and histamine induce an inflammatory response.

Basophils and mast cell mediators include biogenic amines and enzymes stored in pre- formed granules, cytokines and lipid mediators, which are mainly synthesized again upon activation cells. Histamine and other biogenic amines, as well as lipid mediators, cause vascular leakage and increased intestinal motility, which are components of immediate allergic reactions. Cytokines and lipid mediators increase inflammation, which is part of the late-stage response. Enzymes are thought to contribute to tissue damage. Activated eosinophils release enzymes as well as cationic proteins that are toxic to parasites and host cells. Several enzymes in eosinophil granules are thought to be involved in tissue damage in chronic allergic disorders.

Dysregulation of lymphocytes is a possible explanation for allergic dermatitis. It has been reported that a delayed hypersensitivity reaction of skin tests to allergens, a reaction lymphocytes in vitro to mitogens or allergens and autologous mixed lymphocyte responses are defective. It has been reported that with atopic dermatitis, increased susceptibility to vaccinia virus, molluscum contagiosum, warts, herpes simplex virus and skin infections caused by dermatophytes is in harmony with a defect in the effector mechanism of T-lymphocytes. It has been suggested that an abnormal or defective population of CD4 + helper T cells may explain the inability of CD8 + T cells to function as immunosuppressants of IgE production.

Histopathology

Atopy is manifested by a histopathologically characteristic reaction in the form of small nodules with vesicles and redness of the skin, which occurs in response to stimulated allergen release of mediators from mast cells, local blood vessels, which expand and become permeable to proteins and fluids, which causes local edema and redness.

The histological characteristics of bronchial asthma show an affected bronchus with excessive mucus production, many inflammatory cells of the submucosa, including lymphocytes and eosinophils, thickening of the basement membrane, and hypertrophy smooth muscles.

Diagnostics

Signs and symptoms

The following atopic diseases have a history of atopy (hypersensitivity to many allergens and elevated serum IgE levels). In the absence of contact, patients have no symptoms.

Atopic rhinitis:

• nasal congestion;
• rhinorrhea;
• sneezing;
• itchy nose;
• upper respiratory tract cough syndrome;
• dry cough;
• eye symptoms;

Rhinoscopy often shows a pale, swollen nasal mucosa with watery discharge. The conjunctiva is also hyperemic and edematous.

Allergic asthma symptoms:

• asthma can start at any age;
• frequent attacks of wheezing and dyspneaassociated with chest tightness and coughing (often nocturnal in children), sometimes with the release of thick and viscous sputum;
• fatigue;
• general malaise;
• extended expiratory phases.

In severe attacks, breathing, sounds and wheezing may be absent.

Symptoms of atopic dermatitis:

• the disease almost always begins in infancy;
• itching that is worse at night and often from irritants such as hair
• have a strong family history of atopy;
• scratching and rubbing will exacerbate the typical eczematous skin rash;
• ingestion of allergenic food can cause an exacerbation;
• the skin is usually dry and scaly;
• the presence of active skin lesions with pruritus and erythema;
• chronic lesions thicken and lose.

The spread of rashes in atopic dermatitis depends on age - in childhood, the forehead and cheeks are more often affected.

Food allergies can manifest as:

• rhinoconjunctivitis;
• asthma;
• hypotension;
• arrhythmias;
• nausea and vomiting;
• abdominal cramps or diarrhea.

Respiratory symptoms alone are rare. Food allergies are usually part of systemic anaphylaxis.

Analyzes and visualization

Evaluation of immediate hypersensitivity includes a complete blood count, an IgE immunoglobulin assessment, and a prick test.

Quantitative serum immunoglobulins:

• IgM, IgG and IgA.

Total white blood cell count and differential:

• Hb (decreases with autoimmune hemolytic anemia).
• Eosinophilia.
• Lymphocyte tests (CD4 / CD8 counts and suppressor T-cell counts that may be below standard).

Allergic test:

• Prik tests using a variety of allergens from animals, plants, food, pathogens and environmental pollutants.
• Radioallergosorbent test (RAST): used to detect specific IgE antibodies.

Other research methods:

• Whey protein electrophoresis (to exclude IgE myeloma).
• Stool examination (for intestinal parasites).
• Appropriate elimination diet and blind provocation (to clarify the diagnosis of food allergy).
• Chest X-ray (for bronchial asthma).

Differential diagnosis

Atopy should be differentiated from diseases associated with elevated serum total IgE levels, which include:

• allergic bronchopulmonary aspergillosis;
• parasitic diseases;
• immunodeficiency with ataxia-telangiectasia;
• hyper-IgE syndrome;
• Wiskott-Aldrich syndrome;
• IgE myeloma;
• thymic alimphoplasia;
• graft versus host disease.

Differential diagnosis of atopic rhinitis:

• chronic non-allergic (vasomotor) rhinitis;
• medication rhinitis;
• infectious rhinitis;
• vernal keratoconjunctivitis.

Differential diagnosis of allergic bronchial asthma:

• pulmonary emphysema;
• acute bronchiolitis;
• cystic fibrosis;
• aspiration of a foreign body;
• airway obstruction caused by a congenital vascular anomaly;
• cardiac asthma caused by left ventricular failure;
• carcinoid tumors.

Differential diagnosis of atopic dermatitis:

• localized neurodermatitis (simple chronic lichen);
• allergic or irritating contact dermatitis;
• seborrhea and dermatophytosis;
• pomfolix (dyshidrosis).

Treatment

- Allergic rhinitis.

Treatment for allergic rhinitis consists of environmental measures to prevent exposure to allergens, drugs, and desensitization. As an allergic disease, preventive treatment by avoiding allergens is the most effective treatment. However, it is not always possible to avoid this due to the need for medications to control symptoms or the use of desensitization.

Environmental measures include prevention of allergen occurrence based on clinical history allergies, and not only on the basis of a positive skin test result or only radioallergosorbent test. Environmental controls include removing pets, cleaning house dust by frequent cleaning, and avoiding toys and other items. The use of air purification devices may be helpful. Outdoor pollen and mold growth must be prevented.

Antihistamines are the most commonly used medications for allergic rhinitis and should be administered with caution to avoid side effects, although new non-sedating antihistamines are available that control the most common side effects effects. Oral nasal decongestants may be helpful in combination with antihistamines. For the treatment of allergic eye conjunctivitis, antihistamine drops are critical. Treatment with cromolyn with a nasal spray four times a day is beneficial and does not cause immediate or long-term toxicity. Systemic corticosteroids are extremely effective in reducing the symptoms of allergic rhinitis, but since it is a chronic and benign condition, they should be used with great caution. Desensitization (allergen injection therapy) should be given to patients whose symptoms are not controlled despite appropriate previous therapeutic measures.

- Allergic asthma.

This is a manifestation of atopy localized in the bronchi. Critical mediators are released, including histamine, leukotrienes and cytokines, including IL-4, IL-5, IL-13, TNF, and eosinophil chemotactic factor. The goal of symptomatic asthma is to control the hyper-irritating bronchial mucosa through environmental measures, medications, and other treatments.

Treatment for bronchial asthma involves environmental management, as in atopic rhinitis. Medication includes the use of sympathomimetic beta-adrenergic bronchodilators, which are useful and used for acute attacks or for long-term treatment. Epinephrine can be successfully administered subcutaneously at a dose of 0.2-0.5 ml. Albuterol, metaproterenol, pirbuterol and isoetharine are selective beta-adrenergic bronchodilators, dosed by inhalation as an aerosol. Theophylline is a potent bronchodilator when used in combination with sympathomimetic drugs. Intravenous theophylline can be used in dosages ranging from 250 to 500 mg and is rapidly administered for acute asthma attacks. Glucocorticoids are extremely effective in treating allergic asthma. Although they should only be used for asthma when other treatment options have failed. A daily dose of 30 to 60 mg prednisone is usually sufficient.

Cromoline sodium (20 mg) can be administered in a metered-dose inhaler and for long-term preventive therapy. It never reverses an acute attack. Antibiotics can be used for allergic asthma if secondary bacterial bronchitis occurs or bronchopneumonia. Hydration and expectorants are effective for thick phlegm. Desensitization in allergic asthma works well for allergic rhinitis. An example is injection treatment for pollen hay fever. Antileukotrienes such as montelukast and zafirlukast can be prescribed for allergic asthma and atopic rhinitis.

- Atopic dermatitis.

Atopic dermatitis is a chronic skin disorder that requires proper skin care, environmental control, medication, and allergen avoidance. The most preventative measure is the use of non-irritating lubricants for itchy skin. Topical steroids are effective when skin lesions are less severe, but systemic eczema requires systemic corticosteroids, often starting at high doses and then gradually tapering off until therapeutic effect. Oral antihistamines can help control itching. Patients should not bathe frequently, use irritating fabrics and harsh detergents. In case of infection, an appropriate antibiotic is required.

- Food allergies.

Treatment for food allergies is the strict elimination of the irritating allergen. It is imperative to have an emergency plan and a written action plan for anaphylaxis. An adrenaline self-injecting form and an alert medical bracelet are critical to letting healthcare providers know what's going on. The most common food allergens in children are cow's milk, soy wheat, eggs and peanuts, which account for 91% of reactions. In adults, the most common allergens are fish, shellfish, peanuts, tree nuts, eggs, fruits and vegetables.

Forecast

Atopic people have a lifelong tendency to develop allergic reactions as they are incurable. However, the manifestations of atopy often change over time. Atopic dermatitis has a better prognosis and can be treated with immunotherapy with some success. Allergic asthma has a prognosis that varies with the persistence of the causing allergen, blood or tissue IgE levels, and genetic makeup.

Systemic anaphylaxis is the occurrence of an immunoglobulin E-mediated response in multiple tissues simultaneously. The causative agent of the allergen is insect poison, food or medicine. The reaction can be fatal and can be caused by a small amount of the allergen. The prognosis for anaphylaxis is very poor and requires immediate medical attention.

Complications

Complications of allergic rhinitis - untreated cases can lead to:

• sinusitis;
• otitis media;
• nasal polyps;
• apnea.

Complications of allergic bronchial asthma:

• pneumothorax;
• subcutaneous emphysema.

Complications of atopic dermatitis:

• secondary infections caused by staphylococcus;
• herpetic eczema;
• secondary contact dermatitis (caused by antibiotics);
• dermatitis hands (with excessive contact with water);
• ophthalmic complications include atopic keratoconjunctivitis, keratoconus and atopic cataract.

Anaphylaxis:

• It can lead to acute, life-threatening respiratory failure.
• A medical emergency is needed and IgE is mediated by the massive and rapid release of histamines and leukotrienes from mast cells.
• In severe cases, there is acute laryngeal edema, bronchospasm, hypotension, cyanosis and shock.
• There is a list of medications and supplements that cause anaphylactoid reactions, including non-steroidal anti-inflammatory drugs such as aspirin, aminopyrine, fenoprofen, flufenamic acid, ibuprofen, indomethacin and naproxen; opiate drugs, including morphine, codeine, and meperidine; mannitol, radiographic iodine-containing contrast agents, dextran, curare and d-tubocurarine.
• Anaphylactoid reactions should be treated in the same way as anaphylaxis.