Allergy

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Allergy

• Chapter 20

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• Immediate hypersensitivity because it begins
  rapidly, within minutes of antigen challenge
  (immediate), and has major pathologic
  consequences (hypersensitivity)
• In clinical medicine, these reactions are called
  allergy or atopy, and the associated diseases are
  called allergic, atopic, or immediate
  hypersensitivity diseases
• A variety of human diseases are caused by immune
  responses to nonmicrobial environmental antigens
  that involve TH2 cells, immunoglobulin E (IgE),
  mast cells, and eosinophils
• Allergy is the most common disorder of immunity
  and affects 20 of all individuals in the United
  States

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General Features of Immediate Hypersensitivity
Reaction

• Hallmarks of allergic diseases are the activation
  of Th2 cells and the production of IgE antibody
• Strong genetic predisposition
• Allergens, are usually common environmental
  proteins and chemicals
• Cytokines produced by Th2 cells
• Clinical and pathologic manifestations consist of
  the vascular and smooth muscle reaction that
  develops rapidly after repeated exposure to the
  allergen (the immediate reaction) and a delayed
  late-phase reaction consisting mainly of
  inflammation

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• Allergic reactions are manifested in different
  ways, depending on the tissues affected,
  including skin rashes, sinus congestion,
  bronchial constriction, abdominal pain, diarrhea,
  and systemic shock (Anaphylaxis)

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PRODUCTION OF IGE

• IgE antibody is responsible for sensitizing mast
  cells and provides recognition of antigen for
  immediate hypersensitivity reactions
• Atopic individuals produce high levels of IgE in
  response to environmental allergens, whereas
  normal individuals generally synthesize other Ig
  isotypes, such as IgM and IgG, and only small
  amounts of lgE

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The Nature of Allergens

• Antigens that elicit immediate hypersensitivity
  reactions (allergens) are proteins or chemicals
  bound to proteins to which the atopic individual
  is chronically exposed
• Typical allergens include proteins in pollen,
  house dust mites, animal dander, foods, and
  chemicals like the antibiotic penicillin
• Two important characteristics of allergens are
  that individuals are exposed to them repeatedly
  and, unlike microbes, they do not generally
  stimulate the innate immune responses that are
  associated with macrophage and dendritic cell
  secretion of TH1- and TH17-inducing cytokines
• Chronic or repeated T cell activation in the
  absence of strong innate immunity may drive CD4
  T cells toward the TH2 pathway, as the T cells
  themselves make IL-4,

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• These features include low to medium molecular
  weight (5 to 70 kD), stability, glycosylation,
  and high solubility in body fluids
• Many allergens, such as the cysteine protease of
  the house dust mite Dermatophagoides
  pteronyssinus and phospholipase A2 in bee venom,
  are enzymes, but the importance of the enzymatic
  activity
• Polysaccharides cannot elicit these reactions
  unless they become attached to proteins, and
  penicillin react chemically with amino acid
  residues in self proteins to form hapten-carrier
  conjugates
• Specific IgE antibodies

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Aero-allergens
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Food allergens
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• Allergic Reaction

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Skin Prick Test (SPT)
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THE PROTECTIVE ROLES OF IgE- AND MAST
CELLMEDIATED IMMUNE REACTIONS
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Immunotherapy for Allergic Diseases

• Several empirical protocols have been developed
  to diminish specific IgE synthesis called
  desensitization, small quantities of antigen are
  repeatedly administered subcutaneously
• IgG titers often rise, perhaps further inhibiting
  IgE production by neutralizing the antigen and by
  antibody feedback, and induction of Treg to
  iduce tolerance
• Changing the predominant phenotype of
  antigen-specific T cells from TH2 to TH1
• Other approaches being used to reduce IgE levels
  include systemic administration of humanized
  monoclonal anti-IgE antibodies mentioned earlier

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Allergic Diseases
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Allergic Rhinitis
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Allergic Rhinitis

• AR is the most common form of perennial rhinitis
  ( 43 77 )
• AR is the most common form of allergy (
  500,000,000 )

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Risk factors

• 1 - positive family history of AR
• 2 high socio-economic class
• 3 total IgE gt 100 before 6 year
• 4 passive smoking especially before 1 yr
• 5 feeding start before 6 month
• 6 heavy contact with indoor allergens (esp.
  mite)
• 7 male gender ?
• 8 birth in pollination season ?
• 9 first baby ( single baby ) ?

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AR classification

• Allergic Rhinitis

seasonal
perennial
intermittent
persistent
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AR classification

• 1 seasonal allergic rhinitis ( SAR )
• - often related with outdoor allergens
• - tree pollens in early spring
• - grass pollens in spring summer
• - weed pollens in summer autumn
• 2 perennial allergic rhinitis ( PAR )
• - often related with indoor allergens
• - mite , cockroach , danders , mold

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Inflammatory cells in allergic rhinitis

• 1 mast cell
• 2 eosinophils
• 3 T lymphocyte
• 4 dendritic cells macrophages
• 5 epithelial cell

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Clinical manifestations

• Classic symptoms of allergic rhinitis are
• 1 sneezing
• 2 itching ( itchy nose )
• 3 rhinorrhea ( runny nose )
• 4 blockade ( congestion )

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Treatment

• 1 Environment control
• aeroallergen food allergen
• irritants
• 2 pharmacotherapy
• intermittent ----- anti-H /- decongestant
• persistent ------- INCS
• 3 Immunotherapy

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ASTHMA
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• Asthma is one of the most common chronic
  diseases, with an estimated 300 million
  individuals affected worldwide. Its prevalence is
  increasing, especially among children
• Asthma is a chronic inflammatory disorder of the
  airways
• Asthma is not a cause for shame. Olympic
  athletes, famous leaders, other celebrities, and
  ordinary people live successful lives with asthma
  

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Prevalence data for childhood asthma

• Male gt female ( prepubertal )
• Female gt male ( postpubertal )
• Urban gt rural
• Developed (western) gt undeveloped countries
• Slack gt white ( minimal different )
• School age gt preschool age ( prevalence )
• Preschool age gt School age ( incidence )

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Allergy asthma ?
80 allergic
Childhood asthma
Adult asthma
50 allergic
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Risk factors for asthma

• atopy
• allergy to house dust mite
• allergen exposure
• family history of asthma
• early viral RTI
• passive smoking
• cigarette smoking
• maternal smoking
• prematurity
• male gender
• length of breast feeding
• food intolerance hypersensitivity
• high dietary intake of sodium
• air pollution
• urban living

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• Hygiene hypothesis

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Pathogenesis
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Clinical manifestation

• The classic symptoms of asthma

cough
wheez
Chest Thightness
chest pain
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Treatment
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Atopic dermatitis (atopic eczema)
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Age-specific lesions of AD

• - in infants cheek
  , scalp , extensors surface
• - in older children adult flexors
  (politeal fossa, antecubital
• 
  fossa )

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Environment factors

• 1 allergens ( aeroallergen food allergen )
• 2 irritants ( detergent-soaps-low humidity-
• high humidity-hot air-cold air-, )
• 3 infections ( S.A , HSV , malsseziafurfur )
• 4 emotional stress
• 5 endocrine factors

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Vicious cycle of skin infection and AD
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Triggers of atopic dermatitis
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Anaphylaxis
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Etiology

• Foods 36
• Drug 17
• Insect sting 15
• others 32
• ( latex exercise cold- idiopathic)

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The most common causes of anaphylaxis

• Foods Drugs
• Peanut Antibiotics
  
• Tree nut Aspirin
• Fish NSAIDs
• Shellfish Anesthetic
  agents
• Egg Opioids
• Cows milk RCM
• wheat

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Clinical manifestation

• Cutaneous 80-90
• flushing, urticaria angioedema
• Respiratory 50-60
• hoarseness, nasal congestion, sneezing,
  dyspnea, cough, wheezing and laryngeal edema
• Cardiovascular 30-35
• hypotension,dysrrhytmia, arrhythmia,
  myocardial ischemia
• Gastrointestinal 20-25
• nausea, abdominal cramping, vomiting, and
  diarrhea
• Miscellaneous
• headache 5-8, Substernal pain 4-6,
  Seizure 1-2

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Treatment

• Epinephrine ( Adrenaline )
• H1 blocker ( Diphenhydramine )
• H2 blocker ( Ranitidine )
• Corticosteroid ( Hydrocortisone )
• B2 agonist ( Ventolin )

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• Urticaria / Angioedema

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• Episodes of hives that continue for lt 6 week are
  considered acute, and
• Those that persist for gt 6 week are designated
  chronic

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Etiology

• Foods food additives
• Drugs
• Insect bite insect sting
• Latex other contactants
• Physical agents
• Infections
• Transfusion reactions
• CVD
• Malignancy
• Complement disorders
• Hereditary disease ( HAE , muckle-well , )
• Systemic disease ( PV , systemic mastocytosis
  ,.. )
• Idiopathic

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Acute urticaria
IgE - mediated
Foods , drugs , insect sting , latex ,
Non-IgE-mediated
Directly morphine, exercise, cold, sunlight
Leukotrienes change aspirin NSAIDS
Alternative pathway activation RCM
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Acute urticaria
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Cold urticaria
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Dermatographism
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Solar Urticaria
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Chronic urticaria

• Chronic urticaria is reported to be more common
  in adults, while acute urticaria is more common
  in children
• Both sexes are affected however, chronic
  urticaria is more common in women, especially in
  middle-aged women
• CIU occurs twice as often in women as in men

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Urticaria

• Male female
• More common in children and adolescent
• peak 20 30 year
• Often due to foods drugs
• 15 20 of GP

Acute urticaria
chronic urticaria

• female gt male
• More common in middle age
• peak 30 50 year
• Often idiopathic ( CIU )
• Approximately 1

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Etiology of Chronic urticaria
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Idiopathic ( CIU )
Physical agents
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Autoimmunity , malignancy , complement
disorder , occult infections , systemic disease ,

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Antihistamines urticaria
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Classification of angioedema without urticaria
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ACE - inhibitor angioedema
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HAE ( treatment )

• Treatment of HAE is difficult
• For acute attacks, C1 INH concentrate or FFP
  should be administered
• Intubation or tracheotomy may be necessary
• Corticosteroids and antihistamines are not
  helpful
• Subcutaneous adrenaline ( 0.01 ml / kg ,
  epinephrine 1 1000,
• max 0.3 ml ) may be tried

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