AllergyAllergy

Hippokrates (460 – 370 BC) – asthma, eczemaHippokrates (460 – 370 BC) – asthma, eczema Botallo (1565) – pollen allergyBotallo (1565) – pollen allergy Pirquet (1910) – Pirquet (1910) – „„allergy“allergy“ Coca a Cooke (1923) – „Coca a Cooke (1923) – „atopy“atopy“ (heredity) (heredity) Coombs a Gell (1963) – 4 types of Coombs a Gell (1963) – 4 types of

hypersensitivity reactions hypersensitivity reactions Dr Dr Kimishige "Kimi" IshizakaKimishige "Kimi" Ishizaka

discovered the antibody class discovered the antibody class IgEIgE in 1966 in 1966

Treg in allergy

flow cytometry CD4+CD25+CD127- population of lymphocytes

AtopyAtopy

famillial history of allergy disease famillial history of allergy disease

production of IgE antibodies againstproduction of IgE antibodies against

inhalant and some food allergensinhalant and some food allergens

skin, nose, conjunctival, bronchial, intestinal skin, nose, conjunctival, bronchial, intestinal

hyperreactivity hyperreactivity

clinical symptoms of clinical symptoms of atopyatopy

skin – angioedema, urticaria, atopic dermatitisskin – angioedema, urticaria, atopic dermatitis allergic rhinoconjunctivitisallergic rhinoconjunctivitis bronchial asthmabronchial asthma

Epidemiology Epidemiology

atopy 30 – 40 % of population atopy 30 – 40 % of population

clinical manifestation 25 – 30 %clinical manifestation 25 – 30 %

influence of heredity and influence of heredity and environmentenvironment

sensitizationsensitization

Allergens Allergens Allergen:Allergen: A substance that is foreign A substance that is foreign

to the body and can cause an to the body and can cause an allergic reaction (type I reacion) in (type I reacion) in certain people. certain people.

isolation and analysis of structureisolation and analysis of structure recombinant synthesisrecombinant synthesis specispecialal nomen nomenclature: first 3 letters genus, next clature: first 3 letters genus, next

letter species druh a number menas sequence of letter species druh a number menas sequence of isolation isolation

E.g. E.g. Betula verrucosa (birch) Bet v1, Bet v2...Betula verrucosa (birch) Bet v1, Bet v2... Artemisia vulgaris (mugwort) Art v1, Art v2 a Artemisia vulgaris (mugwort) Art v1, Art v2 a

Art v3Art v3

Cross reactivtiy, co-Cross reactivtiy, co-recogniotionrecogniotion

cross-reactivity cross-reactivity - IgE for one allergen - IgE for one allergen recognise similar allergen of the another recognise similar allergen of the another originorigin

identity of sequences identity of sequences >>70 %70 % co-recognition –co-recognition – recognition of higher recognition of higher

amount of epitopes, is not possible to amount of epitopes, is not possible to realise the primary sensitiser realise the primary sensitiser

3-D structure of 3-D structure of cross reactive cross reactive

allergensallergens

Allergen Function

Pollens

Fruits and

vegetables

Legumes, nuts and

seeds

TreesGrasses

Weeds

Fagales, group 1

Plant steroid hormone transporter, PR-10

Aln g 1*

    Api g 1*

Cor a 1.04*

Bet v 1*    

Dau c 1*

Gly m 4*

Car b 1*    

Mal d 1*  

Cas s 1*    

Pru ar 1*  

Cor a 1*    

Pru av 1*  

Fag s 1    

Pyr c 1*  

Que a 1*        

Ferreira F, Allergy, 2004Ferreira F, Allergy, 2004

inhalant allergensinhalant allergens

Diagnosis in allergy diseases Diagnosis in allergy diseases

history – familial occurrencehistory – familial occurrence triggers according to environment and seasontriggers according to environment and season clinical evaluationclinical evaluation

http://jan.ucc.nau.edu/~daa/heartlung/breathsounds/WINAUS/Audio/WHEEZE_4.WAV

http://jan.ucc.nau.edu/~daa/heartlung/breathsounds/WINAUS/Audio/ASTHMAWHEEZE.WAV

skin prick testskin prick test laboratory tests – allergen specific IgElaboratory tests – allergen specific IgE

lab test for allergen-lab test for allergen-specific IgEspecific IgE

Allergic rhinitisAllergic rhinitis

IgE mediated inflammation of nasal mucosa IgE mediated inflammation of nasal mucosa induced by inhalant allergensinduced by inhalant allergens

symptoms: running nose (serous secretion), symptoms: running nose (serous secretion), itching, sneezing itching, sneezing

Seasonal x perenialSeasonal x perenial Therapy: allergens avoidanceTherapy: allergens avoidance pharmacotherapy: antihistamine, mast cell pharmacotherapy: antihistamine, mast cell

blocking agents, topical steroidsblocking agents, topical steroids allergen immunotherapyallergen immunotherapy

allergen immunotherapyallergen immunotherapy

identification of responsible allergenidentification of responsible allergen for allergic rhinoconjunctivitis, bronchial for allergic rhinoconjunctivitis, bronchial

asthma, insect venom allergy, latexasthma, insect venom allergy, latex s.l., s.c. for 3 - 5 yearss.l., s.c. for 3 - 5 years induction of Treg induction of Treg CD4+CD25+127-CD4+CD25+127-

FOXP3(forkhead box FOXP3(forkhead box p3)p3)

antiinflammatory cytokines antiinflammatory cytokines TGFTGFββ a IL-10 a IL-10

Balance between Treg and Th2 reacitvity is diferent in sensitised Balance between Treg and Th2 reacitvity is diferent in sensitised and healthy and healthy

TTrreg eg produce suppressor factors - produce suppressor factors - IL-10 a TGF- IL-10 a TGF- ββAkdis M, 2006Akdis M, 2006

Atopic dermatitisAtopic dermatitis

Prevalence in Europe 10%Prevalence in Europe 10% Unknown etiology and pathogenesis Unknown etiology and pathogenesis

usually worst in childhood: usually worst in childhood:

80% improoving with age80% improoving with age

but 20-50% developing of asthma but 20-50% developing of asthma

and/or allergic rhinitis and/or allergic rhinitis

atopic marchatopic march

Atopic dermatitis - Atopic dermatitis - pathogenesis pathogenesis

skin barrier disorderskin barrier disorder: mutation of : mutation of gen for fillagrin (aggregation of gen for fillagrin (aggregation of filaments of keratinocytes), disorder filaments of keratinocytes), disorder of keratinization of keratinization

loss of water and penetration of loss of water and penetration of allergens into the skinallergens into the skin

starting of sensitization, atopic starting of sensitization, atopic march? march?

Localisation of singns in Localisation of singns in atopic deramtitis in atopic deramtitis in

differnt agediffernt age

SCORADSCORADindexindex

SSeverity everity ScoScoring of ring of AAtopic topic DDermatitisermatitis

AA Extent criteriaExtent criteria BB Intensity criteriaIntensity criteria CC Subjective symptomsSubjective symptoms

SCORAD index :SCORAD index : AA/5 + 7x/5 + 7xBB/2 + /2 + C C ==

SCORADSCORAD Objektivní kritériaObjektivní kritéria Rozsah Rozsah Intenzita 6 kritérií erytém Intenzita 6 kritérií erytém

edém / papulyedém / papuly

mokvání / krustymokvání / krusty

exkoriaceexkoriace

lichenifikacelichenifikace

suchostsuchost

Subjektivní kritériaSubjektivní kritéria svědění svědění

poruchy spánkuporuchy spánku

SCORADSCORAD Extent criteriaExtent criteria

The The rule of 9 before the age of 2 : cervical : cervical preponderance preponderance

The The rule of 9 in adults and older children Grading in practice :Grading in practice :

It is advisable to draw lesion spread directly on the It is advisable to draw lesion spread directly on the evaluation sheet and then perform the calculation. evaluation sheet and then perform the calculation.

Intensity criteriaIntensity criteria ErythemaErythema : : stage 1 / / stage 2 / / stage 3 Edema / papulationEdema / papulation : : stage 1 / / stage 2 / / stage 3 Oozing / crustingOozing / crusting : : stage 1 / stage 2 / stage 3 / stage 2 / stage 3 ExcoriationExcoriation : stage 1 / stage 2 / stage 3 : stage 1 / stage 2 / stage 3 LichenificationLichenification : stage 1 / stage 2 / stage 3 : stage 1 / stage 2 / stage 3

Subjective symptomsSubjective symptomsThe two most representative items concerning the quality The two most representative items concerning the quality of life of patients are : Pruritus of life of patients are : Pruritus and and Insomnia Insomnia

SCORADSCORADeryterythemahema

0 0 withoutwithout 1 m1 mildild

2 2 moderate moderate

3 3 severesevere

SCORADSCORADededemaema / papul / papulationation

0 0 withoutwithout

1 m1 mildild

2 2 moderatemoderate

3 3 severesevere

SCORADSCORAD Oozing / crusting Oozing / crusting

00 withoutwithout 1 m1 mildild

2 2 modrate modrate

3 3 severesevere

SCORADSCORAD Excoriation Excoriation

0 0 withoutwithout

1 m1 mildild

2 2 moderate moderate

3 3 severesevere

SCORADSCORAD Lichenification Lichenification

0 0 withoutwithout

1 m1 mildild

2 2 moderate moderate

3 3 severesevere

SCORADSCORAD

Atopic dermatitisAtopic dermatitis abnormalities of lipids of the skin - abnormalities of lipids of the skin -

xerodermaxeroderma autonomic nervous abnormalities autonomic nervous abnormalities white dermografismwhite dermografism itching → excoriationitching → excoriation

Staphylococcal, mycotic, herpes infectionStaphylococcal, mycotic, herpes infection = impetigo = impetigo

xerosis, xerosis, lichenification, lichenification, excoriationexcoriation

cheilitischeilitis

Atopic dermatitis- therapyAtopic dermatitis- therapy

allerges avoidance, elimination diet, cotton allerges avoidance, elimination diet, cotton dress, stress avoidancedress, stress avoidance

UV therapy, balneothrapy, psychotherapyUV therapy, balneothrapy, psychotherapy rehydratation: emolients rehydratation: emolients topical steroidstopical steroids topical tacrolimus,primecrolimus topical tacrolimus,primecrolimus antihistaminesantihistamines immunosupressive th (steroids, cyklosporin A)immunosupressive th (steroids, cyklosporin A)

bronchial asthmabronchial asthma

chronic inflammatory disease :chronic inflammatory disease : bronchial hyperreactivity, bronchospasm bronchial hyperreactivity, bronchospasm eosinophils and mast cellseosinophils and mast cells neutrophils ??neutrophils ?? Th2 lymphocytes Th2 lymphocytes

reversible bronchial obstructionreversible bronchial obstruction

AB, epidemiology AB, epidemiology

Prevalence 6-8%Prevalence 6-8%

world: 300. 000. 000 cases world: 300. 000. 000 cases

in ČR 99 deaths/ yearin ČR 99 deaths/ year

Etiolgy, pathogenesis of Etiolgy, pathogenesis of BA ??BA ??

Genetic backgroundGenetic background Environmental factors:Environmental factors: allergens, occupational exposures allergens, occupational exposures smokingsmoking RS (respiratory syncytial) virus RS (respiratory syncytial) virus

infection in early childhood – infection in early childhood – wheezing wheezing

Pathologic changes in asthmaPathologic changes in asthmaInfalmmatory cells in bronchial mucosaInfalmmatory cells in bronchial mucosa eosinophils: MBP, ECP, EDN, EPOeosinophils: MBP, ECP, EDN, EPO mast cells: IgE, histamine, LTmast cells: IgE, histamine, LT neutrophils?neutrophils? lymphyocytes cytokines secretion lymphyocytes cytokines secretion Remodelling of bronchial wallRemodelling of bronchial wallepithelium desquamation epithelium desquamation thickeness of basal membrane thickeness of basal membrane hypertrophy of smooth muscleshypertrophy of smooth muscleshyperplasia of mucus glandshyperplasia of mucus glands

Diagnosis of BADiagnosis of BA

historyhistory examination – wheezing , cough examination – wheezing , cough spirometry spirometry challenge tests with metacholinchallenge tests with metacholin PEF monitoring PEF monitoring eNO in exhaled aireNO in exhaled air ECP in the serum ECP in the serum Bronchoscopy: lavage, biopsyBronchoscopy: lavage, biopsy

triggerstriggers inhalant allergensinhalant allergens occupational exposuresoccupational exposures drugs (aspirin sensitive asthma)drugs (aspirin sensitive asthma) wheather, climate factorswheather, climate factors exerciseexercise smoking, smogsmoking, smog virus infectionvirus infection stress, emotionstress, emotion gastrooesphageal refluxgastrooesphageal reflux

BA classificationBA classification

IntermittentIntermittent Mild persistent Mild persistent Moderate persistent Moderate persistent Severe peristent Severe peristent

Efficacy of therapy: Efficacy of therapy: Controlled, partially controlled, Controlled, partially controlled,

uncontrolled uncontrolled

Classification of Classification of bronchial asthma bronchial asthma

according to severityaccording to severity (GINA)(GINA)BA type Asthma crises Nocturnal

attacksPEF or FEV1PEFvariability

Intermittent < 1/weekNormal asymptomatic PEF betweencrises

≤ 2/month ≥ 80%<20%

Mild persistent

> 1/week, but < 1/dayCrises can affect activity

> 2/month ≥ 80%20-30%

Moderate persistent

DailyCrises affect activity

> 1/week 60-80%>30%

Severe persistent

Permanently Frequently ≤60%

changes changes in in

bronchial bronchial asthamaasthamaremodelliremodelli

ng ng

PatPathhologology of asthmatic airwayy of asthmatic airway

© Current Medicine, Inc© Current Medicine, Inc

a a mucus plug mucus plug containing containing cells and cells and debris; debris;

b b mooth mooth muscle muscle hypertrophy hypertrophy and and hyperplasia;hyperplasia;

cc thickening thickening of basement of basement membrane membrane and and subepithelial subepithelial fibrosis; fibrosis;

d d damaged damaged epithelium; epithelium;

e e hhypertrophieypertrophied mucous d mucous gland.gland.

Bronchomotor testingBronchomotor testing

Obstruction Obstruction Completly reversibleCompletly reversibleImcompletly reversible Imcompletly reversible Irreversible Irreversible

therapy of BAtherapy of BA

inhaled bronchodilatators SABA, LABAinhaled bronchodilatators SABA, LABA inhaled corticosteroidsinhaled corticosteroids antileucotriensantileucotriens theopyhllines theopyhllines oral steroidsoral steroids immunosupression (immunosupression (cyclosporine, cyclosporine,

methotrexatemethotrexate)) anti IgE monoclonal antibody anti IgE monoclonal antibody

omalizumab omalizumab

case report 1case report 1 girl, 10 years oldgirl, 10 years old history: atopic dermatitis history: atopic dermatitis

in early childhood in early childhood

running nose, sneezing, running nose, sneezing, itching of eyesitching of eyes

breathlessnessbreathlessness with with wheezingwheezing also during also during nigths nigths

in the last 5 years, in in the last 5 years, in MMarch and arch and AprilApril

What diagnostic test are What diagnostic test are useful? useful?

What therapy would you What therapy would you recommend? recommend?

allergensallergens

Case report 2Case report 2

Man 45 years old Man 45 years old From 15 years BA, From 15 years BA,

few times at few times at intensive care unit intensive care unit with intubation with intubation and mechanical and mechanical ventilation ventilation

Diagnostic test and Diagnostic test and therapy plann? therapy plann?