Transcript 03. Allergic diseases

Common Food Allergens
Food
Infants/Young Older Children Anaphylaxis
children
And Adults
Milk (cow/goat)
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Chicken egg
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Soy
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Peanut
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Tree nuts (walnut, hazel/filbert, cashew,
pistachio, Brazil , pine nut, almond)
Wheat
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Fish
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Shellfish (shrimp, crab, lobster, oyster,
scallops)
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Fruit
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Vegetables
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Seeds (cotton, sesame, psyllium, mustard)
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Spices
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Typical cross reactivity associations include:
Inhalant Allergen
Food Allergens
Birch pollen
Apple, raw potato, carrot, celery, hazelnut, pear,
peach, plum, cherry
Mugwort pollen
Celery, apple, peanut, kiwi fruit, carrot, parsley,
spices (fennel, coriander, aniseed, cumin)
Ragweed pollen
Melons, e.g., watermelon, cantaloupe, and
honeydew, bananas
Latex
Avocado, kiwi fruit, chestnut
Chironomidae
Crustaceans (shellfish)
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Allergic disease is the 5th leading chronic
disease among all ages
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3rd common chronic disease among
children under 18 years old; up to one
child in three is affected
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Trends indicate that by 2015, half of all
Europeans may be suffering from an
allergy
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Allergies affect people from the early
stages of their life and continue until
their late adult ages
The history. Evaluation begins with a careful
allergy/environmental history to identify exposures
and triggers. The clinical history should include
(1) the nature of the illness/symptoms;
(2) precipitators and eleviators of symptoms;
(3) the frequency and duration of attacks;
(4) time lost from school or work;
(5) prior evaluation and treatment;
(6) medical history;
(7) family history;
(8) past and current medications;
(9) occupation and hobbies.
Nose
Oesophagus
Pharynx
Allergic rhinitis
Asthma
Lungs
Stomach
Food allergy
Skin
Eczema
Urticaria
Allergic dermatitis
“Global diseases” – due to the large
spectrum of symptoms affecting the
whole body
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B lymphocyte needs 2 signals to mature to
IgE producing plasma cell.
› IL-4 secreted by Th2 cells
› Interaction of CD40 ligand on the surface of T-
cell with the CD40 receptor on the B cell
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IgE antibody
› Unbounded IgE with half life of 2-3 days
› Bound to receptor on the surface of mast cell,
basophil, dendritic cell, and eosinophil with half
life of several weeks
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Performed mediators:
› Vascular permeability factor (VPF) / vascular
endothelial cell growth factor – enhancing vascular
permeability
› Histamine, proteoglycan, chymase, tryptase,
carboxypeptidase A. heparin
› TNF-alpha, IL-2,3,4,13, CSF, chemokine
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Product inflammatory mediators:
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prostaglandin D2
leukotriene C4, D4, B4
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Developed in bone marrow under
stimulation of IL3,IL5, CSF
 Half life of 8-18 hours in the blood, half life of
several days in the peripheral tissue
 Eosinophil migration ( into peripheral tissue)
 Toxic inflammatory mediators in eosinophil:
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› major basic protein, eosinophil peroxidase,
eosinophil cationic protein,
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Synthesize lipid mediators:
› leukotriene C4
I. Allergic anamnesis. A detailed anamnesis
is a basic information source, necessary for
diagnostics and treatment of the allergic
diseases. While examining patients with the
allergic diseases special attention should be
paid to:
 1. variability of the symptoms (they develop
and disappear rapidly, they develop in the
specific place or in the specific season)
 2. individual allergic anamnesis
 3. family allergic anamnesis
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The organs and the systems, which are most
frequently affected with the allergic
diseases: the skin, eye, respiratory organs
are examined especially attentively.
 Basic principles:
 1. Not to fail to note the affection of the
skin, it is necessary to investigate the entire
skin. A patient can not mention about the
skin manifestations, considering them
insignificant, not related to the disease or
feeling shy of them.
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1) An increase in the number of the
eosinophils up to 5-15%.
 2) Absolute and relative lymphocytosis. A
substantial change in the relationship of
neutrophils/leukocytes
 In exacerbation of the allergic diseases
eosinophils predominate among the
cells in the smears of the phlegm,
discharge from the nose or eyes, in the
concomitant infection there are
neutrophils
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An increase in the total level of IgE in the
serum confirms the diagnosis of the
allergic disease, although the normal
level of IgE does not exclude it.
 4. Determination of the levels of specific
IgE in blood serum (IFA diagnostics, ELISA
and immunoblotting) to different
allergens.
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Polycheck- Panel (BioСheck GmbH, Germany)
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The signs of the allergic diseases:
- Absolute and relative lymphocytosis;
- Eosinophilia;
- An increase (more than 2.8) in the index of
immunoregulation (Tx/Tc) (CD4/CD8):
- An increase in the absolute and relative quantity
of the B-lymphocytes;
- A reduction of the complement content;
- An increase in the levels of the circulating
immune complexes;
- An increase in the autoantibodies to the tissues of
the organs - targets (the skin, mucous membrane
of the nose, bronchi, lungs)
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There are cutaneous – puncture and
scarification and intracutaneous tests.
The positive results of skin tests (erythema
and blister at the site of the allergen
introduction) are of a diagnostic value
only in combination with the data of the
anamnesis, physical and laboratory
investigations.

Skin-prick testing remain the "gold
standard" for identifying clinically
relevant allergens.
Grading of Patch Tests
Grade
Criteria
Significance
+/-
Mild erythema and
no edema
Doubtful
1+
Erythema, edema
and induration
Positive
2+
Erythema, edema
Positive
and isolated vesicles
3+
Erythema, edema
and confluent
vesicles
Positive
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The allergen extracts in the dilution of 1:
100 are used for the intracutaneous tests.
When less than five puncture or
scarification tests are positive,
intracutaneous tests can be carried out
immediately. If the positive puncture or
scarification tests are more,
intracutaneous tests are carried out next
day. Intracutaneous tests with the food
allergens are not made.
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1) Impairment of the technology of skin
tests, the use of the allergen preparations
with expired date, the tests made against
the background of treatment with drugs
decreasing skin sensitivity lead to the
pseudonegative results. The intake of H1blockers is withdrawn for 48 hr, hydroxizine,
terfenadine, loratadin and tricyclic
antidepressants – for 96 hr and astemizole 4 weeks prior to the study. Theophylline,
adrenostimulators (inhalation and for the
internal administration) and cromolin do not
influence the skin sensitivity.
2) Introduction of the incorrectly prepared
solutions of the allergens (incorrect
selection of osmolarity and pH, presence of
the irritating substances), impairment of the
technology of making skin tests, for
example, intracutaneous introduction of
more than 0.02 ml of the allergen solution,
urticate dermographism, introduction of the
substances, which cause the release of
histamine (for example, the extracts of food
allergens), leads to the pseudopositive
results.
 3) Results of the skin tests are compulsorily
compared with the data of anamnesis,
physical and laboratory investigations.
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is a method of development of
sensitization, based on the introduction
of the allergen in the target organ. There
are sublingual, endonasal and inhalation
provocation tests.
› Type I: anaphylactic reaction:
mediated by IgE antibodies,
which trigger the mast cells and
basophils to release
pharmacologically active
agents.
Urticaria
Quinke Oedema
› Type II: cytotoxic reaction: IgM
or IgG antibodies bind to
antigen on the surface of cells
and activate complement
cascade.
1)Transfusion reaction
 2) Hemolytic disease of newborn
 3) Autoimmune hemolytic anemia and
type II drug reaction
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Type III: Immune complex reaction:
complexes of antigen and IgM or IgG
antibodies accumulate in the circulation
or in tissue and activate the complement
cascade. Granulocytes are attracted to
the site of activation and release lytic
enzymes
 1. Local immune complex disease
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2. Acute systemic immune complex disease
3. Chronic immune complex disease
Type IV hypersensitivity
mediated by T cells, which release cytokines
upon activation to cause accumulation and
activation of macrophages.
1) Infectious delayed type hypersensitivity
OT( Old Tuberculin ) test
2) Contact dermatitis :
3) Acute rejection of allogenic transplantation and
immune response in local tumor mass
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Eczematous skin lesions (age dependent)
Early onset and typical localization of skin
lesions according to age
Pruritis
Stigmata of atopy
Personal or family history of atopy
IgE mediated sensitization (demonstrated
by skin prick test serum IgE measurement
Dry skin
 Hyperlinearity of palms and soles
 Linear grooves of fingertips
 Dennie-Morgan fold (atopy fold, doubled intraorbicular
fold)
 Hertoghe’s sign (hypodense lateral eyebrows)
 Short distance between scalp hair growth in the temporal
hairline and eyebrows
 Periorbital shadow (halo)
 Delayed blanching after intracutaneous
injection of acetylcholine
 White dermatographism
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They are used:
- in acute states - parenterally (prednisolone,
hydrocortisone, dexamethasone)
- systematically - orally and intramuscularly
prolonged forms - drugs- depot – effect for a
month (polcortolon, diprospan)
- locally - inhalation forms, nasal sprays, ointments
and creams.
Antihistamine drugs (blockers of H1
- histamine receptors)
They are effective only upon transfer from
the pathochemical stage to the
pathophysiological one.
Competitive (with histamine) blockade of H1 - receptors –
drugs should be taken frequently (3-4 times in a 24 hour
period), and in the large doses (risk of the toxic action);
 - penetrate through the blood-brain barrier - sedative
side-effect (sleepiness) + potentiate the effect of
analgesics and antipyretics;
 - Irritate the GIT mucosa - the side-effect is diarrhea,
therefore the intake is after meal (adsorption velocity
from the bowels is lowered);
 - In the prolonged intake (more than 10 days)
tachyphylaxis develops (addiction) - effectiveness is
lowered;
 - bind with the blood proteins (risk of the toxic effect
during dehydration, cachexia and secretory dysfunction
of the kidneys);
 - muscarine-like effect (anticholinergic action) - they
decrease the secretion of the mucous glands of the
respiratory system – they are contraindicated in diseases
of the respiration organs in presence of the thick phlegm
in the bronchi (they reduce the drainage function of the
bronchi).
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Hismanal, histalong (Astemizol), Claritin
(Loratadine), Zirtek (Cetirizine), Cestin
(Ebastine), Trexil (terfenadine)
 Peculiarities of pharmacokinetics and the
mechanism of action:
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They are noncompetitive blockade of H1
- histaminic receptors; they do not
penetrate through the blood-brain barrier;
they do not irritate the GIT mucosa;
tachyphylaxis does not develop; do not
bind with the blood proteins;
anticholinergic action is absent.
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Telfast (Fexofenadine), Erius (dezloratadine), Aleron
(levocetirizine)
According to the last recommendations of
allergologists intake of the drugs of the first generation
is indicated in the emergency allergic states, since
they are in the injection forms, and the administration
of the drugs of the second and third generation is
indicated for the course therapy.
At the same time the drugs of the second and
third generation do not exceed those of the first
generation in the manifestation of the antiallergic
effect. Furthermore, many people are noted to have
individual sensitivity (selective) to the antihistamine
drugs. There may be higher efficacy in intake of the
drugs of the first generation and minimum reaction
after the intake of the drug of the second or third
generation.
They are effective at the pathochemical stage
and ketotifen - upon transfer from the
pathochemical stage to the pathophysiological
one.
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Cetotifen, sodium cromolin (intal, cromolin,
cromogexal, cromoglin etc), Nedocromil of sodium
(Tiled).
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Anti-leucotriene drugs (inhibitors of
leucotriene metabolism)
Selectively binds to human
immunoglobulin E (Omalizumab)
Specific immunotherapy
Thank you for your attention!