FOOD  ALLERGY      JACEK  GOCKI  

FOOD  HYPERSENSITIVITY  

Objectively  reproducible  symptoms  or  signs  initiated  by  exposure  to  a  food  at  a  dose  tolerated  by  healthy  persons  

Food  hypersensitivity  

Immunological  mediated  (Allergy)  

Non  immunological  mediated  

IgE  mediated   Non  IgE  mediated  

Toxic   Metabolic  Pharmacologic  

toxic  contaminants  (e.g.,  histamine  in  scombroid  fish  poisoning,  toxins  secreted  by  Salmonella,  Shigella,  and  Campylobacter)  pharmacologic    properties  of  the  food  (e.g.,  caffeine  in  coffee,  tyramine  in  aged  cheeses)    metabolic  disorders    (e.g.,  lactase  deficiency)    

FOOD  ALLERGY  

Hypersensitivity  reaction  to  a  food,  initiated  by  specific  immunologic  mechanisms  

PREVALENCE  

Food  allergy  affects  about  6%  of  the  US  population  less  than  5  years  of  age  and  about  3.5 4%  of  the  general  population    Most  important  food  allergens  in  Europe:  Children:  cow  milk,  egg,  wheat,  soy,  fish,  peanut  Adults:  hazelnut,  apple,  peach,  kiwi,  carrot  

When  sensitized  person  eat  a  simple  meal,  in  fact  they  eat  a  mixture  of  several  allergens.  Some  of  them  can  be  hidden  allergens,  and  some  could  be  cross  reactive.  It  is  difficult  sometimes  to  recognize  wchich  allergen  provoced  symtoms  

FOOD  ALLERGEN  

Food  allergens  are  proteins  (15-40  kDa)  or    glikoproteins  (10-70  kDa),  wchich  are  good  tolerated  by  helthy  person,  in  atopic  patients  provoke  allergic  disorders  

SOURCE  OF  ALLERGENS  

ANIMAL  ALLERGENS  Most  important  in  childrens  

PLANT  ALLERGENS  Most  importants  in  adults  

A. Cod  

B. Milk  ( -laktoglogulin)  

C. Corn  

D. Birch  

TERMINOLOGY  OF  FOOD  ALLERGENS  

Most  fruts,  vegetables,  milk,  eg,  fish    has  a  several  allergens  For  example:  apple  has  a  3  main  allergens:  Mal  d  1,  Mal  d  2,  Mal  d  3  International  names  of  this  proteins  is  made  by  using  the  latin  name  of  their  sourse  (e.g.  apple    Malus  domestica  )  The  international  names  consist  of  3  parts  First:  3  letters  of  genus  (e.g.  Malus    Mal)  Second:  one  or  two  letters  of  species  (e.g.  domestica    d)  Third:  numeral  (e.g.  1  )    Example:  main  allergen  of  apple:  Mal  d  1  

FEATURE  OF  FOOD  ALLERGENS  (Clinical  important)  

Resistance  to  heating,  chemical  and  enzymatic  proteolysis  Cross  reactive  with  other  allergens    This  features  are  important  for  division  all  food  allergens  in  two  clasess:  

Class 1 C lass 2

Cow milk Caseins (Bos d 8) Whey - -laktoglobulin (Bos d 5) Egg Owoalbumin (Gal d 2) Owomukoid (Gal d 1) Peanuts Vicilin (Ara h 1) Conglutin (Ara h 2) Glicinin (Ara h 3) F ish Parvalbumin (Gad c 1) L ipid transfer proteins (PR-14) Apple (Mal d 3) Corn (Zea m 14)

C ross reactive proteins latex-fruits PR-2 proteins Latex (Hev b 2) Banana Kiwi PR-3 proteins Latex (Hev b 6.02) Avocado (Pers a 1) PR-5 proteins Apple (Mal d 2) Cherry (Pru av 2) Birch (Bet v 1) homologus allergens (PR-10) Apple (Mal d 1) Carrot (Dau c 1) Celery (Api g 1) Birch (Bet v 2) homologus proteins Latex (Hev b 8) Celery (Api g 4)

COW  MILK    (Bos  d)  

Cow's  milk  generally  represents  the  first  foreign  proteins  introduced  into  an  infant's  diet.  It  is  the  most  common  food  allergy  in  young  children.  Cow's  milk  contains  at  least  20  protein  components,  which  may  lead  to  antibody  production  in  humans.  The  milk  protein  fractions  are  subdivided  into  casein  and  whey  proteins.  The  caseins  constitute  76 86%  of  the  protein  in  cow's  milk.  The  casein  fraction  is  composed  of  four  basic  caseins  ( s1,  s2,   ,  and   ).  The  non-casein  fraction,  or  whey,  consists  of   -lactoglobulin,   -lactalbumin,  bovine  immunoglobulins,  and  bovine  serum  albumin.  Extensive  heating  will  destroy  several  of  the  whey  proteins  (bovine  serum  albumin,  bovine   -globulin,  and   -lactalbumin).  However,  routine  pasteurization  is  not  sufficient  to  denature  these  proteins,  but  may  increase  the  allergenicity  of  some  milk  proteins,  such  as   -lactoglobulin.    

HEN  EGG(Gal  d)  

Hen  egg  is  the  most  common  IgE-mediated  food  allergy  in  children.  The  yolk  is  considered  less  allergenic  than  the  white,  although  IgE  antibodies  to  chicken  gamma  globulin,  apovitellenin  I,  and  contaminating  egg  white  proteins  can  be  demonstrated.  The  egg  white  contains  23  different  glycoproteins;;  however,  ovomucoid,  ovalbumin,  and  ovotransferin  have  been  identified  as  the  major  allergens.    Although  ovalbumin  comprises  the  majority  of  the  protein  in  egg  white,  ovomucoid  has  been  shown  to  be  the  dominant  allergen  when  highly  purified  egg  white  proteins  are  utilized.  Ovomucoid  is  responsible  for  clinical  reactivity  in  the  vast  majority  of  egg  allergic  children.  In  addition,  it  was  shown  that  about  70%  of  egg  allergic  children  may  be  able  to  ingest  small  amounts  of  egg  protein  in  extensively  heated  (baked)  products,  e.g.,  breads,  cakes,  and  cookies.      

FISH  

Fish  are  one  of  the  most  common  causes  of  food  allergic  reactions  in  adults,  and  a  common  cause  in  children  as  well.  The  major  allergen  in  cod,  Gad  c  1,  is  a  parvalbumin  that  has  been  isolated  from  the  myogen  fraction  of  the  white  meat.  A  similar  protein,  Sal  s  1,  has  been  isolated  from  salmon.  It  is  heat-stable  and  resistant  to  proteolytic  digestion,  has  a  molecular  weight  of  12  kDa.  Immunoblot  analyses,  10  common  fish  species  were  shown  to  have  a  protein  that  is  similar  to  Gad  c  1.  Unlike  many  other  food  allergens,  the  fish  protein  fraction(s)  responsible  for  clinical  symptoms  in  some  patients  appear  to  be  more  susceptible  to  manipulation  (e.g.,  heating,  lyophilization)  than  other  foods.  Furthermore,  it  was  found  that  most  patients  allergic  to  fresh  cooked  salmon  or  tuna  could  ingest  canned  salmon  or  tuna  without  difficulty,  indicating  that  preparation  led  to  destruction  of  the  major  allergens.  Nevertheless,  allergic  reactions  following  exposure  to  airborne  allergen  emitted  during  cooking  are  not  uncommon.    

SHELLFISH  

Shellfish  allergens  are  considered  a  major  cause  of  food  allergic  reactions  in  adults,  affecting  up  to  2.3%  of  the  US  adult  population.  This  group  consists  of  a  wide  variety  of  mollusks  (snails,  mussels,  oysters,  scallops,  clams,  squid,  and  octopus)  and  crustacea  (lobsters,  crabs,  prawns,  crawfish,  and  shrimp).  Shrimp  allergens  have  been  most  extensively  studied.  Eighteen  precipitating  antigens  have  been  detected.  Tropomyosin,  a  protein  found  both  in  muscle  and  elsewhere,  has  been  identified  as  the  major  allergen  in  shrimp.  Considerable  cross-reactivity  among  crustacea  has  been  demonstrated  by  skin  test  Invertebrate  tropomyosins  are  highly  homologous  and  tend  to  be  allergenic    those  from  crustaceans  (e.g.,  shrimp,  crab,  crawfish,  and  lobster),  arachnids  (house  dust  mites),  insects  (cockroaches),  and  mollusks  (squid,  snails)    whereas  vertebrate  tropomyosin  tends  to  be  non-allergenic.    

PEANUTS  (Ara  h)  

Peanuts  are  the  most  common  food  allergy  in  the  pediatric  population  beyond  the  age  of  4  years.  Peanut  proteins  are  traditionally  classified  as  albumins  (water-soluble)  and  globulins.  Thirty-two  protein  bands  have  been  identified,    however,  three  with  molecular  weights  of  63.5  kDa  (Ara  h  1),  17  kDa  (Ara  h  2),  and  64  kDa  (Ara  h  3)  have  been  identified  as  major  allergens.  Ara  h  4  through  8  have  been  identified.  A  wide  variety  of  peanut  products  including  flour  and  reprocessed  peanuts  have  been  shown  to  retain  their  allergenicity.  

 

SOYBEANS  

Soybeans  are  a  second  member  of  the  legume  family  that  provokes  a  significant  number  of  hypersensitivity  reactions,  predominantly  in  infants  and  young  children.  Since  soybeans  provide  an  inexpensive  source  of  high-quality  protein,  soybean  protein  is  used  in  many  commercial  foods.  Approximately  10%  of  the  seed  proteins  are  water-soluble  albumins  and  the  remainder  are  salt-soluble  globulins.  Four  major  protein  fractions  have  been  separated  

TREE  NUTS  

Tree  nut  allergies  affect  about  0.6%  of  the  American  population.    Walnuts  were  the  nut  provoking  the  most  allergic  reactions  (34%),  followed  by  cashews  (20%),  almonds  (15%),  pecan  (9%),  pistachio  (7%),  and  hazel  nut,  Brazil  nut,  pine  nut,  and  macadamia  nut,  all  less  than  5%.  I  Europe  most  allergic  reactions  are  provoking  by  hazel  nut  (4,8%  of  overall  population),  and  it  is  a  major  food  allergen  in  adults.    Skin  testing  reveals  extensive  cross-reactivity  among  tree  nuts.    

PROFILINS  

Profilin  is  an  actin-binding  protein  that  was  first  identified  in  birch  pollen  (Bet  v  2)  and  is  now  recognized  as  an  allergenic  protein  in  a  number  of  fruits  and  vegetables.  Profilins  are  responsible  for  the  celery-mugwort-spice  syndrome  and  are  responsible  for  oral  allergy  syndrome  (OAS)  to  apple,  pear,  carrot,  celery  (Api  g  4),  and  potato  in  birch  pollen-allergic  patients.  Profilins  have  also  been  identified  in  tomato,  peanut  (Ara  h  5),  and  soybean  (Gly  m  3),  but  whether  these  proteins  cause  allergic  reactions  remains  to  be  established  

PRs  

Pathogen-related  proteins  (PRs)  have  been  shown  to  comprise  a  large  number  of  class  2  allergenic  proteins  found  in  various  vegetables  and  fruits.  These  proteins  are  induced  when  pathogens,  wounding  or  certain  environmental  stresses,  such  as  drought,  heat,  etc.,  stress  the  plant.  PRs  have  been  classified  into  14  families,  although  six  PR  families  account  for  the  majority  of  cross-reactivity  among  plant  proteins.  

 

CLINICAL  MANIFESTATIONS    -  IgE  mediated  -  Non  IgE  mediated  -  Mixed,  IgE  and  non  IgE  mediated    

IgE  mediated  diorders  

Skin:  Urticaria,  angioedema,  flushing,  acute  morbilliform  rash,  acute  contact  urticaria  

 Gastrointestinal:Oral  allergy  syndrome,  gastrointestinal  anaphylaxis  

 Respiratory:Acute  rhinoconjunctivitis,  acute  bronchospasm  

 Generalized:  Anaphylaxis,  food-dependent  exercise-induced  anaphylaxis  

Non  IgE  mediated  disorders  

Skin  :  Contact  dermatitis,dermatitis  herpetiformis    Gastrointestinal:  Allergic  proctocolitis,  food  protein-induced  enterocolitis  syndrome,  celiac  disease,  infantile  colic  

Mixed,  IgE  and  non  IgE  mediated  

Skin:  Atopic  dermatitis,  contact  dermatitis    Gastrointestinal:  Allergic  eosinophilic  esophagitis,  allergic  eosinophilic  gastroenteritis  

 Respiratory:  Asthma  

Oral  allergy  syndrome  (OAS)    

Pollen-food  allergy  syndrome  (oral  allergy  syndrome  [OAS])  is  elicited  by  a  variety  of  plant  proteins,  especially  PRs,    cross-reacting  with  airborne  allergens.  Symptoms  are  provoked  almost  exclusively  in  the  oropharynx  and  rarely  involve  other  target  organs.  It  is  estimated  that  OAS  affects  up  to  50 70%  of  adults  suffering  from  pollen  allergy,  especially  to  birch,  ragweed,  and  mugwort  pollens.    Local  IgE-mediated  mast  cell  activation  provokes  the  rapid  onset  of  pruritus,  tingling,  and  angioedema  of  the  lips,  tongue,  palate,  and  throat,  and  occasionally  a  sensation  of  pruritus  in  the  ears  and/or  tightness  in  the  throat.  Symptoms  are  generally  short-lived  and  are  most  commonly  associated  with  the  ingestion  of  various  fresh  fruits  and  vegetables.  

   

DIAGNOSIS  

Medical  history    Diet  diaries    Elimination  diets    Prick  skin  tests    In  vitro  allergen-specific  IgE  tests    Intragastral  provocation  under  endoscopy    Oral  food  challenges    

OPEN  SINGLE  BLIND  DOUBLE  BLIND  

The  double-blind,  placebo-controlled  food  challenge  (DBPCFC)    

DBPCFC  

The  double-blind,  placebo-controlled  food  challenge  (DBPCFC)  has  been  labeled  the   for  the  diagnosis  of  food  allergies.  Many  investigators  have  utilized  DBPCFCs  successfully  in  children  and  adults  to  examine  a  variety  of  food-related  complaints.  The  selection  of  foods  to  be  tested  in  DBPCFCs  is  generally  based  upon  history,  skin  test,  and/or  in  vitro  IgE  results.  Foods  unlikely  to  provoke  food  allergic  reactions  may  be  screened  by  open  or  single-blind  challenges.  However,  for  research  studies  positive  reactions  by  these  methods  should  be  confirmed  by  DBPCFC,  except  perhaps  in  very  young  infants.    

DBPCFC  

Prior  to  undertaking  DBPCFC,  several  factors  need  to  be  taken  into  consideration.  Suspect  foods  should  be  eliminated  for  714  days  prior  to  challenge,  longer  in  some  non-IgE-mediated  gastrointestinal  disorders.  Antihistamines  should  be  discontinued  long  enough  to  establish  a  normal  histamine  skin  test,  and  other  medications  should  be  minimized  to  levels  sufficient  to  prevent  breakthrough  of  acute  symptoms.  In  some  asthmatic  patients,  short  bursts  of  corticosteroids  may  be  necessary  to  insure  adequate  pulmonary  reserve  for  testing  (FEV1  >70%  predicted).    

Food  Challange  

Concerns  about  bias  No   Yes  

Objective  symptoms   Subjective  or  difficult  to  interpret  symptoms  or  research  study  

Open  OFC   blinded  OFC  

DBPC  FC  SB  OFC    

With/Without  Placebo  

Patient  and  observer  bias  reduced  

Patient  bias  reduced  

No  symptoms  or  convincing  objective  symptoms  

Subjective    symptoms  

Accurate  diagnosis  food  allergy  

THERAPY  OF  FOOD  ALLERGIC  DISORDERS  

strict  elimination  of  the  offending  allergen  In  accidental  ingestions  and  exposures  will  occur,  so  food-allergic  patients  must  be  educated  and  prepared  to  recognize  symptoms  and  initiate  treatment  of  food  allergic  reactions  should  be  prescribed  an  epinephrine  autoinjector    

THERAPY  OF  FOOD  ALLERGIC  DISORDERS  

Some  medications  such  as  H1  and  H2  antihistamines,  ketotifin,  corticosteroids,  and  leukotriene  inhibitors  have  been  utilized  in  an  attempt  to  modify  symptoms  of  food  allergic  disorders.  Antihistamines  may  partially  mask  symptoms  of  oral  allergy  syndrome  and  IgE-mediated  skin  symptoms,  but  overall  they  have  minimal  efficacy  in  blocking  systemic  reactions.  Oral  corticosteroids  are  generally  effective  in  treating  chronic  IgE-mediated  disorders,  e.g.,  atopic  dermatitis  or  asthma,  or  non-IgE-mediated  gastrointestinal  disorders,  e.g.,  allergic  eosinophilic  esophagitis  or  gastroenteritis,  and  dietary-induced  enteropathy,  but  the  steroid  side  effects  are  generally  unacceptable.  Oral  cromolyn  sodium  has  not  been  shown  to  be  effective  in  preventing  or  treating  IgE-mediated  food  allergies  or  allergic  eosinophilic  gastroenteritis  in  appropriately  controlled  studies.    

THERAPY  OF  FOOD  ALLERGIC  DISORDERS  

Anti-IgE  antibody  in  the  treatment    Chinese  herbal  medication  

recombinant  food  proteins  are  currently  under  development    

SUMMARY  

Food  allergy  affects  about  6%  of  the  US  population  less  than  5  years  of  age  and  about  3.5 4%  of  the  general  population  Sensitization  to  specific  proteins  within  food  allergens  may  occur  in  the  gastrointestinal  tract,  

egg,  milk  or  peanut,  or  as  a  consequence  of  an  allergic  sensitization  to  inhalant  allergens,  considered  class  2  food  allergy,  e.g.,  raw  carrots  and  apples  or  melons,  secondary  to  birch  or  ragweed  pollen  sensitivity,  respectively    

SUMMARY  

Food  reactions  may  be  due  to  IgE-mediated,  non-IgE-mediated,  or  a  combination  of  IgE-  and  non-IgE-mediated  reactions  involving  the  skin,  gastrointestinal  tract,  respiratory  tract,  and/or  cardiovascular  system  Increasing  levels  of  food-specific  serum  IgE  antibodies  or  prick  skin  test  mean  wheal  diameters  correlate  with  increasing  probabilities  of  clinical  reactivity,  although  the  double-blind,  placebo-for  diagnosing  food  allergy  Strict  food  allergen  avoidance  remains  the  only  proven  therapy  for  treating  food  allergy,  although  a  number  of  promising  immunomodulatory  approaches  are  now  in  clinical  trials  

  Thank  you    and  good  appetite