ALLERGIC MARCH

Literature reading
Wahyu murtiono.H
Department of Otorhinolaryngology-Head & Neck Surgery Faculty of Medicine Padjadjaran University Hasan Sadikin General Hospital Bandung 2011

The ``allergic march':

The natural history of atopic diseases. Characterized a typical sequence of sensitization and manifestation of symptoms Certain age period, persist over years or decades, tendency for spontaneous remission with age.
U. Wahn in:What drives the allergic march? Curr Opin Allergy Clin Immunol, 2002; 2: 55560.
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The Allergic March

EUGENE G WEINBERG, MB ChB, FCPaed, FAAAAIThe allergic march

Prenatal sensitization
Multifactorial cause of allergy
Genetic constitutionEnvironmental Factors * Still in debate.

Andrew H. Liu, MDThe Allergic March of Childhood

 Immune response start in week 20th of pregnancy. Amniotic fluid(+) house dust mite allergen Transplacental transport mechanism of different allergen.
Andrew H. Liu, MDThe Allergic March of Childhood

Proposed mechanisms by which maternal exposure to bacteria protects against allergies in offspring.

Holt P G , Strickland D H J Exp Med 2009;206:2861-2864

2009 Holt and Strickland

Postnatal beginning
Inhaled allergen and food allergen. Exposure to allergen in early life in genetically predisposed individual. Airways allergic diseases (allergic rhinitis and asthma) increased steadily in prevalence to age 7years.

Andrew H. Liu, MDThe Allergic March of Childhood

Early atopic signs

Dermatitis, Gastroesophageal reflux, Chronic rhinorrhea Recurrent wheezing

Lawrence D. Rosen, M.D. An Integrative Approach to Atopic Disorders in Children DOI: 10.1089/act.2007.13201
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U. Wahn - Curr Opin Allergy Clin Immunol,9 2002; 2: 55-560

 There may be areverse allergic march where some atopic children first present with asthma and only later on develop eczema.

EUGENE G WEINBERG, MB ChB, FCPaed, FAAAAIThe allergic march

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Root of the Problem

The development of atopy early in childhood is linked with the later development of airways allergic disease. The problem of atopy begins when the nascent immune system develops aberrant immune responses to common ubiquitous, and unavoidable exposures.
Andrew H. Liu, MDThe Allergic March of Childhood
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 Chronic ongoing exposures fuel inappropriate prolonged injury and inflammation to the airways aberrant repair of injured tissues.

Aberrant processes through critical periods of postnatal lung growth and differentiation fully developed lung may differ from the normal lung.
This may underlie the persistent asthma phenotype.
Andrew H. Liu, MDThe Allergic March of Childhood
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The Iceberg Model

Understanding a new paradigm of care in children with atopic disorders. The tip:
The visible phenomena in atopic children (skin rashes, vomiting, runny noses, and coughing).

Beneath:
Genomic predisposition (familial and individual tendency to develop immune dysregulation under certain environmental circumstances).
Lawrence D. Rosen, M.D. An Integrative Approach to Atopic Disorders in Children DOI: 10.1089/act.2007.13201 13

Lawrence D. Rosen, M.D. An Integrative Approach to Atopic Disorders in Children DOI: 10.1089/act.2007.13201

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Genetic factors:
During the first twenty years of life The risk of developing atopic symptoms correlated to the existence of atopic disease in parents and siblings.

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Allergens:
Food allergens Respiratory inhaled allergens (pollen, moulds, animal dander, mites).

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The environment:
Insufficient exposure to certain infectious agents in early childhood increase the risk of developing allergy by disturbing the TH1/TH2 balance and favouring the TH2 allergic mechanism. Improved hygiene could be partly responsible for this phenomenon.
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The hygiene theory

Nature may immunize
Against the development of allergic diseases and asthma through : infections and microbial exposures of the 1. Respiratory
2. Gastrointestinal tracts 3. The skin in early life.

U. Wahn - Curr Opin Allergy Clin Immunol, 2002; 2: 55-560

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 Skin sensitization lead to airway sensitization. Disturb balance between Th1 and Th2 greater expression of Th2 and production of cytokines. * Induced IgE production and activate Eosinophil.

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The hygiene theory

Andrew H. Liu, MDThe Allergic March of Childhood

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The hygiene theory

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 Protective Th1 immune responses to microbial exposures that begin immediately after birth and after leaving the sterile environment of the mothers womb.
When this process goes well, Th1-based immune development prevents pro-allergic Th2 immune development and atopy, thereby keeping environmental exposures from becoming allergens.
Andrew H. Liu, MDThe Allergic March of Childhood

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Th1 immune :
Improve host defense by inducing antiviral mechanisms that keep respiratory viruses from proliferating in respiratory epithelium and spreading down the airways.

Responses during airways injury and inflammation also inhibit aberrant repair processes that underlie pathologic tissue changes in asthma.

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 Leading to greater expression of the TH2 features resulting from the secretion of the cytokines IL-4, IL-5,IL-10 and IL-14. These cytokines: Induce IgE production activate eosinophils leading to allergic inflammation.
Eugene G Weinberg, MB ChB, FCPaedTHE ATOPIC MARCH
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Intervention and Prevention

The basis for a stratified approach to early interventions. Allergy testing is now recommended from infancy If food allergies are suspected to cows milk, hens egg,peanut allergens should be tested for specific allergies irrespective of their age
Adrian Morris, MBChB, DCH, MFGPIS ALLERGY TESTING COST EFFECTIVE? Current Allergy & Clinical Immunology, March 2006 Vol 19, No.1 28

Prevention of atopy
Primary prevention :
The avoidance of early allergen exposure to certain foods and inhalantsfrom birth.

The ETAC (Early Treatment of the Atopic Child):

The role of cetirizine in delaying the atopic march.

Eugene G Weinberg, MB ChB, FCPaedTHE ATOPIC MARCH

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The use of probiotics

Cultures of beneficial bacteria : Enhancing the microbial balance Restore normal intestinal permeability and gut microecology. Improve the immunological barrier function of the intestine. Reduce the generation of proinflammatory cytokines characteristic of allergic inflammation.

In the future may be used in the primary prevention of the allergic march and asthma.
Eugene G Weinberg, MB ChB, FCPaedTHE ATOPIC MARCH
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CONCLUSIONS
Allergic diseases have now become the most common group of diseases among children.Treatment is mainly based on preventing and/or controlling symptoms

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 New promising treatments, such as the administration of sublingual immunotherapy.

In the future, it is anticipated that therapies that modify the severity of atopic eczema in infants and young children will decrease the risk for the eventual development of allergic disease and thus prevent the consequences of the allergic march.
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 Intensive research is still required before a potential cure for all allergic children may eventually be developed.

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THANK YOU
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