Клиническая аллергология для обучающихся на английском языке (Clinical Allergology for Learners in English)

МИНИСТЕРСТВО ЗДРАВООХРАНЕНИЯ РЕСПУБЛИКИ БЕЛАРУСЬ

УЧРЕЖДЕНИЕ ОБРАЗОВАНИЯ

«ГОМЕЛЬСКИЙ ГОСУДАРСТВЕННЫЙ МЕДИЦИНСКИЙ УНИВЕРСИТЕТ»

КАФЕДРА КЛИНИЧЕСКОЙ ЛАБОРАТОРНОЙ ДИАГНОСТИКИ,

АЛЛЕРГОЛОГИИ И ИММУНОЛОГИИ

К.С. МАКЕЕВА

КЛИНИЧЕСКАЯ АЛЛЕРГОЛОГИЯ 

ДЛЯ ОБУЧАЮЩИХСЯ НА 

АНГЛИЙСКОМ ЯЗЫКЕ

CLINICAL ALLERGOLOGY FOR 

LEARNERS IN ENGLISH

УЧЕБНОЕ ПОСОБИЕ

Москва

ИНФРА-М

2024

УДК 616(075.8)
ББК 53/57я73

М15

Р е ц е н з е н т ы:

Кафедра клинической лабораторной диагностики и иммунологии

Гродненского государственного медицинского университета;

Романива О.А., кандидат медицинских наук, врач аллерголог-иммунолог

отделения аллергологии и иммунопатологии Республиканского научнопрактического центра радиационной медицины и экологии человека

Макеева К.С.

М15 
Клиническая аллергология для обучающихся на английском языке 

(Clinical Allergology for Learners in English) : учебное пособие / К.С. Макеева. — Москва : ИНФРА-М, 2024. — 84 с.

ISBN 978-5-16-112683-7 (online)

В учебном пособии по дисциплине «Клиническая иммунология и 

аллергология» в краткой и доступной форме представлены современные 
сведения о механизмах этиопатогенеза, специфических методах диагностики и 
лечения аллергических заболеваний. Для контроля и обобщения материала 
после каждого раздела приведены тестовые задания, предложены 
ситуационные задачи для формирования клинического мышления.

Предназначено для студентов пятого курса учреждений высшего 

образования, обучающихся на английском языке по специальности 
«Лечебное дело».

УДК 616(075.8)
ББК 53/57я73

ISBN 978-5-16-112683-7 (online)                  © Учреждение образования

«Гомельский государственный 
медицинский университет», 2024

ФЗ

№ 436-ФЗ

Издание не подлежит 

маркировке в соответствии 

с п. 1 ч. 2 ст. 1

TABLE OF CONTENTS

Introduction ............................................................................................4

Chapter 1. Immunology of allergy ........................................................5

1.1. Factors contributing to allergies ...................................................5
1.2. Allergens. Characteristic and classification ..................................7
1.3. Mechanisms and classification of hypersensitivity reactions ........8
1.4. Review questions to chapter 1 ...................................................18

Chapter 2. Diagnosis of allergy ..........................................................22

2.1. Medical history ...........................................................................22
2.2. Physical examination ..................................................................24
2.3. Allergological examination methods ...........................................28
2.4. Review questions to chapter 2 ...................................................42

Chapter 3. The general principles of treating allergic diseases ......46

3.1. Non-medication therapy .............................................................46
3.2. Medication therapy .....................................................................49
3.3. Allergen-specific immunotherapy ...............................................52
3.4. Review questions to chapter 3 ...................................................54

Chapter 4. Allergopathology ...............................................................58

4.1. Drug allergy ................................................................................58
4.2. Anaphylaxis ................................................................................64
4.3. Emergency treatment for anaphylaxis ........................................67
4.4. Review questions to chapter 4 ...................................................69

Chapter 5. Clinical cases .....................................................................73

Answers to test tasks and clinical cases...........................................77

References ............................................................................................79

Appendix A. Allergic anamnesis card ................................................81

INTRODUCTION

This course material aid covers current issues in clinical allergology. 

Allergic diseases are a serious problem of public health affecting a large 
part of the population. The incidence of allergic diseases continuously 
increases every year, both among adults and children. Allergopathology  
is encountered not only in the practice of allergologists and immunologists, 
but also in the practice of doctors of other specialties. These diseases 
require  comprehensive understanding of the underlying immunological 
mechanisms for their effective diagnosis and treatment. 

This course material aid is intended for students who are studying 

medicine at a medical university. The current manuals and textbooks 
on immunology and allergology are too voluminous and complex, which 
causes certain difficulties for students; the main task of this course 
material aid is to present the basics of clinical allergology in an accessible 
and brief form. The material is divided into 5 parts. The first part provides 
general information about allergic diseases, risk factors, allergens, and 
immunological mechanisms. The second part deals with current issues  
in the diagnosis of allergic diseases. Part 3 contains treatment guidelines 
for allergic diseases. Part 4 provides information on the most topical issues 
of private allergology – drug allergy and anaphylaxis, as well as emergency 
treatment for anaphylaxis. At the end of chapters 1–4 is a number of test 
tasks which students will need to answer in order to check knowledge of 
the subject. The fifth chapter contains situational exercises to develop the 
students’ clinical thinking.

CHAPTER 1

IMMUNOLOGY OF ALLERGY

Von Pirquet, who recognized that in both protective immunity and 

hypersensitivity reactions antigens had induced changes in reactivity, 
introduced the term “allergy” in 1906. Allergy is now used to describe 
a hypersensitivity reaction initiated by immunologic mechanism [7].

Allergies are a number of conditions caused by hypersensitivity of 

the immune system to something in the environment that usually causes 
little or no problem in most people.

Allergic diseases are common, and their prevalence is increasing to 

epidemic proportions. In both industrialized and industrializing countries, 
they affect between 10–50% of the world’s population, having a noticeable 
impact on patients’ quality of life and incurring significant costs.

Allergic diseases can occur at almost any age, some allergies are most 

likely to develop for the first time in particular age groups. The prevalence 
of childhood allergic diseases, such as allergic asthma, allergic rhinitis, 
and atopic dermatitis, has increased exponentially [10, 15, 16].

Atopic march, sometime called allergic march, refers to the natural 

history or typical progression of allergic diseases that often begins early in 
life. As the child grows, so also their atopy, for example – eczema, is most 
likely to occur between birth and 3 months of age. Food allergy is most 
common in second year of life, nasal allergy manifests itself between ages 
of 3 and 7 years. Asthma onset most likely to occur when a youngster is 
between 7 to 14 years [19].

1.1. Factors contributing to allergies

Among them are:
– Genetics.
Hereditary predisposition to allergies is reflected in the term “atopy,” 

introduced to refer to “allergic constitution” – a genetically mediated 
predisposition to allergic reactions. Familial predisposition to allergies is 
associated with polygenic inheritance. Different genes provide: the ability 
of the immune system to develop a primary immune response with the 
production of IgE to a particular allergen; the ability of the immune system 

to “build up” a high level of specific IgE; high functional activity of T-helper 
type II in the production of IL-4 and IL-5; high reactivity of the bronchi and 
skin [8, 10, 16].

– Allergens exposure.
The likelihood of developing allergies could potentially be decreased 

through exposure to microbes in the early stages of childhood. A plausible 
reason for the higher occurrence of asthma and other atopic diseases in 
industrialized nations is the relatively lower rate of infections or exposure 
to microbial products in these countries. A variety of epidemiologic data 
demonstrate that being exposed to environmental microbes during early 
childhood, particularly those found on farms and not in cities, is linked to a 
lower occurrence of allergic disease. The hygiene hypothesis was formulated 
based on this evidence, proposing that exposure to environmental and 
commensal microbes and infections during early-life and even perinatal 
stages encourages a regulated immune system maturation, possibly leading 
to the early development of regulatory T cells. Consequently, individuals who 
experience early-life exposure to environmental and commensal microbes 
and infections are less inclined to develop Th2 responses to noninfectious 
environmental antigens, and therefore, less prone to developing allergic 
diseases later in life.

Infections caused by respiratory viruses and bacteria can contribute 

to the development of asthma and can worsen pre-existing asthma. Up 
to 80% of asthma attacks in children are believed to occur following 
respiratory viral infections. Although it may appear inconsistent with the 
hygiene hypothesis, the infections linked to asthma are caused by human 
pathogens that can potentially harm pulmonary mucosal barriers. The 
evidence that supports the hygiene hypothesis concentrates on exposure 
to various environmental bacteria that may not necessarily cause tissue 
damage. Some epidemiologic studies indicate that a failure to colonize the 
respiratory or gastrointestinal tract early in life by particular commensal 
microbes can increase the risk for respiratory viral infections that induce 
asthma [8, 10].

– Environmental pollution. Urbanization.
Normally, the bronchial epithelium produces mediators that reduce 

the bronchoconstrictor effect. Under the influence of pollutants (NO2, SO2), 
the airway epithelium is damaged and neuropeptides are released, 
which triggers the neurogenic component of inflammation. Pollutants 
also contribute to the activation of arachidonic acid metabolism and 
suppression of antioxidant defenses. Pollutants activate bronchial 
epithelial cells with formation and secretion of pro-inflammatory cytokines 

(IL-8, tumor-necrotizing factor). Exhaust particles also activate airway 
epithelial cells with release of pro-inflammatory cytokines. Tobacco smoke 
is not only a respiratory irritant. It weakens the protective functions of 
the mucous membranes of the respiratory tract, contributes to easier 
penetration of allergens, and contributes to the development of bronchial 
hyperresponsiveness. Tobacco smoke has cross-allergenic properties 
with plant pollen [10, 13, 16].

To this, one can add the following factors:
– The peculiarities of infant nutrition, in particular early transfer to 

artificial feeding.

– Eating disorders in adults (irregular intake of food, violation of the 

ratio between the amount of food products, abuse of one type of food)  
[13 15, 16, 17].

1.2. Allergens. Characteristic and classification

An allergen is a type of harmless antigen that causes an abnormally 

elevated immune response in the sensitized body and to which most 
healthy people are tolerant. 

Properties of the allergens:
– Relatively small molecular mass.
– Capacity of sorption and aggregation in small particles thus diffusing 

mucous secrets and integumentary tissues without evident defects of the 
latter.

– High solubility and easy elution in liquid media of organism.
– In vivo chemical stability (allergens do not metabolize easily at least).
– Among proteins the most frequent allergens are enzymes, proteases. 

Non-protein allergens are distinguished by their capacity to join protein 
compounds of own organism (haptens) [15, 16, 17].

Allergens are able to produce a small effect. For instance, significant 

pathogenic total dosing of ambrosia allergen is 1 mcg per year.

The broadest definition of an allergen is that it is any molecule that 

binds IgE antibodies.

– A major allergen is an allergen that is recognized by IgE antibodies  

of >50% of patients allergic to the allergen source.

– A minor allergen is recognized by <50% of the allergic population 

[7, 17].

All allergens fall into two large groups:
– endoallergens formed within the body (they can be cells damaged 

by infection, chemical, physical or other influences);

– exoallergens – substances that affect a person from the outside. In 

turn, exoallergens are divided into two large groups: infectious and noninfectious nature [15, 17].

Infectious allergens include antigens of bacterial, viral, fungal, proto
zoan and helminth antigens. Allergic reactions mainly occur upon contact 
with opportunistic and non-pathogenic microorganisms, less often with 
pathogens [17].

Non-infectious allergens include pollen, food, household, epidermal, 

insect, medicinal and industrial allergens.

Allergens are divided by the way they enter the body – inhalation 

(aeroallergens), ingestion, injection, skin contact.

Allergens are classified according to their origin:
– Animal products (Fel d 1 (allergy to cats), fur and dander, cockroach 

calyx, wool, dust mite excretion).

– Foods (celery and celeriac, corn or maize, eggs (typically albumen, 

the white), fruit, pumpkin, eggplant, legumes, beans, peas, peanuts, 
soybeans, milk, seafood, sesame, soy, tree nuts, pecans, almonds, wheat).

– Insect stings (bee sting venom, wasp sting venom, mosquito stings).
– Mold spores.
– Metals (nickel, chromium).
– Plant pollens (grass – ryegrass, Timothy grass; weeds – ragweed, 

plantago, nettle, Artemisia vulgaris, Chenopodium album; sorrel, trees –  
birch, alder, hazel, hornbeam, Aesculus, willow, poplar, Platanus, Tilia, 
Olea, Ashe juniper, Alstonia scholaris).

– Drugs (penicillin, sulfonamides).
– Other (latex, wood) [15, 17, 19].

1.3. Mechanisms and classification of hypersensitivity 

reactions

Adaptive immunity serves the important function of host defense 

against microbial infections, but immune responses are also capable of 
causing tissue injury and disease.

Disorders caused by immune responses are called hypersensitivity 

diseases. This term arose from the clinical definition of immunity as 
“sensitivity,” which is based on the observation that an individual who has 
been exposed to an antigen exhibits a detectable reaction or is “sensitive” 
to subsequent encounters with that antigen.

Hypersensitivity is exaggerated immune responses of detriment to 

the host. They are classified according to the system devised by Gell and 
Coombs. Hypersensitivity diseases are commonly classified according to 
the type of immune response and the effector mechanism responsible for 
cell and tissue injury (Figure 1):

– type I immediate hypersensitivity;
– type II antibody-mediated hypersensitivity;
– type III immune complex-mediated hypersensitivity;
– type IV cell-mediated hypersensitivity [1, 10, 16].
Regardless of the immune mechanisms involved, hypersensitivity 

reactions can be divided into two phases: a sensitization phase and a 
detrimental effector phase.

Depending on the length of time between the beginning of contact 

of the sensitized organism with the antigen and the occurrence of clinical 
manifestations, allergic reactions are divided:

– immediate type – develops within 15–20 min or sooner);
– late (postponed) allergic reactions – develop within 4–6 hrs;
– delayed allergic reactions – develop within 48–72 hrs [10, 12, 11].

Hypersensitivity type I

Immediate hypersensitivity is an IgE antibody – and mast cell-mediated 

reaction to certain antigens that causes rapid vascular leakage and 
mucosal secretions, often followed by inflammation (Figure 2). Disorders 
in which IgE-mediated immediate hypersensitivity is prominent are also 
called allergy, or atopy, and individuals with a propensity to develop these 
reactions are said to be atopic. Immediate hypersensitivity may affect 
various tissues and may be of varying severity in different individuals.

Sensitization phase
The sensitization phase of type I immediate hypersensitivity reactions 

occurs when antigen exposure induces IgE production with IgE binding to 
FcεR on mast cells and basophils. 

Figure 1 ‒ Types of hypersensitivity reactions [1]

Note. In the four major types of hypersensitivity reactions, different immune  

effector mechanisms cause tissue injury and disease. CTLs – cytotoxic T-lymphocytes;  
Ig – immunoglobulin.

Antibodies IgE, rather than 

other isotypes, are produced 
depending 
on 
the 
CD4+  

T-cell-derived 
cytokines 

present 
in 
the 
B-cell 

microenvironment 
during 

its activation. T-cell clones, 
specific for defined allergens 
and 
isolated 
from 
atopic 

individuals, are predominantly 
a Th2 phenotype associated 
with production of the cytokines 
IL-4 and IL-10, rather than IL-2 
and IFNγ. The presence of 
IL-4/IL-10 during T-dependent 
B-cell 
activation 
induces 

isotype switching to IgE. 

Antibodies IgE bind to high 

affinity Fcε receptors present 
on mast cells and basophils, 
“awaiting” re-exposure to the 
initiating antigen.

Effector phase
Tissue damage is caused 

by inflammatory mediators (histamine, prostaglandins, leukotrienes, and platelet activating 
factor) released from mast cells 
and basophils following antigen 
binding to cell bound IgE.

These 
substances 

induce 
increased 
vascular 

permeability, vasodilatation, and smooth muscle contraction, either locally 
or systemically, depending on the site of antigen exposure.

Latephase
The immediate wheal and flare reaction is followed 2 to 4 hrs later 

by a late phase reaction consisting of the accumulation of inflammatory 
leukocytes, including neutrophils, eosinophils, basophils, and Th2 cells.

Figure 2 ‒ The sequence of events

in immediate hypersensitivity [1]