Transcript Slide 1

Allergy : An Overview
Alyson W. Smith, M.D.
Department of Allergy and Immunology
St. Barnabas Hospital
Allergy
• Allergy refers to certain diseases in which immune
responses to environmental antigens cause tissue
inflammation and organ dysfunction. Hypersensitivity
and sensitivity are synonyms for allergy.
• Allergen is any antigen that causes allergy. The
allergen is processed by the dendritic cell, an antigenpresenting cell. It can be complete protein antigens or
low molecular weight proteins capable of eliciting an
IgE response.
• Atopy is the inherited propensity to respond
immunologically to such common naturally occurring
allergens with continuous production of IgE
antibodies. It affects a significant portion of the
general population, estimated at 10%-30% in
developed countries.
Allergic Reaction
The body’s overreaction to a harmless substance (an allergen)
The harmless substance may contacted through the skin,
inhaled into the lungs, swallowed, or injected.
Types of Hypersensitivity Reactions
• Hypersensitivity reactions require a presensitized (immune) state of the host.
• Hypersensitivity reactions can be divided into
four types: type I, type II, type III and type IV,
based on the mechanisms involved and time
taken for the reaction.
• Frequently, a particular clinical condition
(disease) may involve more than one type of
reaction.
Type I hypersensitivity
• Also known as immediate or anaphylactic
hypersensitivity. The reaction may involve skin
(urticaria and eczema), eyes (conjunctivitis),
nasopharynx (rhinorrhea, rhinitis),
bronchopulmonary tissues (asthma) and
gastrointestinal tract (gastroenteritis).
• The reaction may cause a range of symptoms
from minor to death.
• The reaction usually takes 15 - 30 minutes
from the time of exposure to the antigen,
although sometimes it may have a delayed
onset (10 - 12 hours).
• Immediate hypersensitivity is mediated by IgE .
• The primary cellular component in this
hypersensitivity is the mast cell or basophil.
Type IV hypersensitivity
• Also known as cell mediated or
delayed type hypersensitivity .
• e.g. Tuberculin reaction which
peaks 48 hours after the injection of
antigen (PPD)
• The lesion is characterized by
induration and erythema.
• Type IV hypersensitivity is involved
in the pathogenesis of many
autoimmune and infectious diseases
(tuberculosis, leprosy,
blastomycosis, histoplasmosis,
toxoplasmosis) and granulomas due
to infections and foreign antigens.
• Another form of delayed
hypersensitivity is contact dermatitis
(poison ivy , chemicals, heavy
metals, etc.) in which the lesions are
more papular.
Etiology of Atopy
• Etiology is unknown but there is strong evidence for a
complex of genes that can influence the propensity for
atopy through the regulation of total IgE production
and specific IgE antibodies to allergen.
• Environmental factors play a role in etiology. The
initial age of exposure to a particular food or pollen
determine the intensity of the subsequent IgE
antibody response. A coexisting viral respiratory
infection during allergen exposure may have an
adjuvant effect on both specific and total IgE
production. Tobacco smoking have similar effect.
Immunopathogenesis
The major mediators
Histamine: This mediator acts on histamine 1 (H1) and histamine 2
(H2) receptors to cause: contraction of smooth muscles of the airway
and GI tract, increased vasopermeability and vasodilation, nasal
mucus production, airway mucus production, pruritus, cutaneous
vasodilation, and gastric acid secretion.
Tryptase: Tryptase is a major protease released by mast cells; its
exact role is uncertain, but it can cleave C3 and C3a. Tryptase is
found in all human mast cells but in few other cells and thus is a
good marker of mast cell activation.
Proteoglycans: heparin seems to be important in storing the
preformed proteases and may play a role in the production of alphatryptase.
Chemotactic factors: An eosinophilic chemotactic factor of
anaphylaxis
causes eosinophil chemotaxis; an inflammatory factor of anaphylaxis
results in neutrophil chemotaxis. Eosinophils release major basic
protein and, together with the activity of neutrophils, cause significant
tissue damage in the later phases of allergic reactions.
Common Allergens
Mechanism
• Repeated exposures to an allergen may lead to more
serious reactions. Once a person is sensitized (has had a
previous sensitivity reaction), even a very limited
exposure to a very small amount of allergen can trigger a
severe reaction.
• Allergic reactions vary. They can be mild or serious. They
can be confined to a small area of the body or may affect
the entire body.
• Most occur within seconds or minutes after exposure to
the allergen, but some can occur after several hours,
particularly if the allergen causes a reaction after it is
partially digested. In very rare cases, reactions develop
after 24 hours.
Allergy Testing for IgE mediated diseases
• Skin testing:
– Indicates presence of IgE
antibody NOT clinical reactivity
– ~90% sensitivity
– ~50% specificity
– ~50% false positives
– Larger skin tests/higher IgE
correlates with likelihood of
reaction but not severity
• Negative prick test or specific IgE
– Essentially excludes IgE
antibody (>95% specific)
Immunocap (blood) testing:
quantifies amount of IgE to
specific allergens
• Immunocap blood testing (previously
known as RAST)
Allergy Testing for non IgE mediated diseases (type 4
hypersensitivity)
• Patch testing for foods or other allergens
(nickel, cosmetics, shampoos)
Allergic
Rhinitis/Conjunctivitis
Most common clinical expression of atopic
hypersensitivity. IgE mediated allergy
localized in the nasal mucosa and
conjunctiva.
Pollens and fungal spores, dust and animal
danders can all trigger this response.
Allergic Rhinitis Diagnosis
Allergic Rhinitis Treatment
Medications: Intranasal steroids, oral
antihistamines (diphenhydramine and
hydroxyzine (short acting) and
fexofenadine, cetirizine, loratadine (long
acting)), intranasal and ocular
antihistamine/mast cell stabilizers
Environmental controls
Urticaria
• Diffuse hives or wheals occur and cause significant
pruritus (itching)
• Individual wheals resolve after minutes to hours, but new
wheals can continue to form.
• Acute Urticaria: (Lasting <6 wk) can be caused by
infections, foods, drugs, or contact allergens. Usually
treat symptomatically.
• Chronic Urticaria: (Lasting > 6 weeks) can be idiopathic,
autoimmune, or a sign of an underlying illness. Very
unlikely to be caused by allergies!
Chronic Urticaria
• In approximately 80% of cases there is no
cause found!
• 25-45% autoimmune
• An autoantibody to the IgE receptor has
been recently discovered as a cause of
chronic urticaria.
Angioedema
• Angioedema is localized tissue swelling that can occur in
soft tissues throughout the body, which may account for
a substantial volume of fluid loss from the intravascular
compartment. Patients may report pain at the site of
swelling instead of pruritus, which occurs with urticaria.
• Angioedema can occur with or without urticaria.
• Angioedema of the laryngopharynx can obstruct the
airway, and patients may report difficulty breathing.
Stridor or hoarseness may be present. It can be life
threatening requiring rapid intubation or even
cricothyroidotomy.
• Causes are similar to urticaria but there is a disease of
hereditary angioedema (episodes of severe angioedema
without urticaria)
Angioedema
Atopic Dermatitis (eczema)
• Atopic Dermatitis is a chronic, relapsing, itchy skin
disease.
• Clinical features:
• Chronic relapsing disease
• Dry, itchy, flaky skin
• Oozing, weeping and fissuring
• Erythema
• Excoriation
• Edema
• Lichenification
– Moderate-severe AD ( up to 33%) have clinically
significant food allergy
Atopic Dermatitis
Evaluation and Treatment
Skin testing, Immunocap testing, Food
avoidance for moderate-severe atopic dermatitis
Moisturization (ointments>creams>lotions)
Antihistamines
Hypoallergenic soaps, detergents, etc
Environmental, occupational, and
temperature control
Topical steroids
Antibiotics for superinfection
Anaphylaxis
Anaphylaxis is highly likely when any one of the following
three criteria are fulfilled:
1.
Acute onset of an illness (minutes to hours) with
involvement of the skin and/or mucosal tissue and
respiratory compromise and/or reduced blood pressure.
2.
Symptoms involving two or more organ systems( skin
/mucosal, respiratory, cardiovascular, GI) that occur rapidly
after exposure to a likely allergen for that patient.
3.
Reduced BP following exposure to a known allergen for that
patient.
The causes of anaphylaxis are divided into two major groups :
• IgE mediated :This form is the true anaphylaxis
that requires an initial sensitizing exposure, the
coating of mast cells and basophils by IgE, and
the explosive release of chemical mediators upon
re–exposure. Ex: foods, venom
• Non–IgE mediated :These reactions, the so
called "anaphylactoid" reactions, are similar to
those of true anaphylaxis, but do not require an
IgE immune reaction. They are usually caused by
the direct stimulation of the mast cells and
basophils. The same mediators as occur with
true anaphylaxis are released and the same
effects are produced. Ex: vancomycin (red man
syndrome)
• The most commonly identified triggers are:
–
Food
–
Insect bites
–
Medications
Symptoms
– Patients may report dizziness, faintness, diaphoresis,
and pruritus. Difficulty breathing can result from
angioedema of the pharyngeal tissue and from
bronchoconstriction.
– Patients may also report GI symptoms, including
nausea, vomiting, diarrhea, and abdominal cramping.
– Patients may experience uterine cramping or urinary
urgency.
– Patients can have a sudden onset of respiratory
and/or circulatory collapse and go into anaphylactic
shock.
Anaphylaxis Treatment
• Epinephrine: drug of choice
– Self-administered epinephrine readily available at all
times
– If administered, seek medical care IMMEDIATELY
– Train patients, parents, contacts: indications/technique
• Antihistamines: secondary therapy only: WILL NOT
STOP ANAPHYLXAXIS
• Corticosteroids
• IV fluids
Food Allergy
Food Allergy may be defined as a complex of clinical
syndromes resulting from the sensitization of the patient
to one or more foods, in which symptoms manifest locally
in the GI tract. This can result in reactions from hives to
anaphylaxis.
Some reactions are classically allergic (immediate
reactions alone), or may reflect non IgE-mediated
mechanisms.
Food allergy is different than food intolerance. Ex: Lack
of digesting enzymes (lactose intolerance)
Food Allergy
• Proteins or glycoproteins (not fat or carbohydrate)
• Major allergenic foods (>85% of food allergy)
– Children: milk, egg, soy, wheat, peanut, tree nuts
– Adults: peanut, tree nuts, shellfish, fish, fruits and vegetables
• Allergies to peanuts, tree nuts, seafoods, and seeds typically persist
• ~20% of cases of peanut allergy resolve by age 5 years.
Prognostic factors favoring loss of allergy include:
– PST <6mm
– ≥2 years avoidance
– History of mild reaction
– Few other atopic diseases
– Low levels of peanut-specific IgE
Pollen-Food Syndrome or
Oral Allergy Syndrome
•
•
•
•
Clinical features: rapid onset oral pruritus, rarely progressive
Epidemiology: prior sensitization to pollens
Key foods: raw fruits and vegetables
Allergens: Profilins and pathogenesis–related proteins
– Heat labile (cooked food usually OK)
• Cause: cross reactive proteins pollen/food
• Some studies have shown that up to 9 percent of people with OAS
may experience more severe symptoms of food allergy, and up to 2
percent may experience anaphylaxis.
Birch
Ragweed
Grass
Mugwort
Apple, carrot, celery, cherry, pear, hazelnut
Banana, cucumber, melons
Melon, tomato, orange
Melon, apple, peach, cherry
Latex-Fruit Syndrome
• It is estimated that 50-70 % of latex-allergic people have IgE
antibodies cross-reactive to the antigens coming from some
vegetable foods
• Avocado
• Banana
• Chestnut
• Potato
• Tomato
• Kiwi
• Pineapple
• Papaya
• Eggplant
• Melon
• Passion Fruit
• Mango
• Wheat
• Cherimoya
Pediatric Gastrointestinal Syndromes
Age Onset:
Duration:
Characteristics:
Enterocolitis
Enteropathy
Proctitis
Infant
Infant/Toddler
Newborn
12-24 mo
? 12-24 mo
9 mo-12 mo
Failure to thrive Malabsorption Bloody stools
Shock Villous atrophy
No systemic sx
Lethargy
Diarrhea
Eosinophilic
Vomit
Diarrhea
Non-IgE-mediated, typically milk and soy induced
\
 Spectrum may include colic, constipation and occult GI blood loss

Evaluation
• Prick skin testing and/or Immunocap blood
testing
• Elimination diets (1 - 6 weeks) most useful for
chronic disease (eg. AD, GI syndromes)
– Eliminate suspected food(s) or
– Prescribe limited “eat only” diet or
– Elemental diet
• Oral challenge testing (MD supervised,
emergency meds available)
– Open
– Single-blind
– Double-blind, placebo-controlled (DBPCFC)
Food Allergy: Treatment
• Complete avoidance of
specific food trigger
• Ensure nutritional needs
are being met
• Education
• Anaphylaxis Emergency
Action Plan if applicable
– most accidental exposures
occur away from home
Prevention
• Avoid triggers such as foods and medications
that have caused an allergic reaction, even a
mild one. This includes detailed questioning
about ingredients when eating away from home.
Ingredient labels should also be carefully
examined.
• A medical ID tag should be worn by people who
know that they have serious allergic reaction.
• If any history of a serious allergic reactions, carry
emergency medications (such as
diphenihydramine and injectable epinephrine
A 10 yo boy presents for evaluation of hives of 4 months duration. His parents are
frustrated by the lack of change in their son’s symptoms despite changes in soaps,
detergents, and fabric softener. They would like their son to be seen by a specialist for
evaluation. They describe the hives as raised, erythematous, pruritic, 1-2 cm lesions that
involve the trunk and extremities. The hives resolve spontaneously in a few hours and
occur in the day and at night. The child is otherwise healthy and only taking an
antihistamine for pruritus. Of the following, the most likely cause of the hives are:
1.
2.
3.
4.
5.
Allergy to a food
additive or preservative
Allergy to dust mites
Autoantibody to the IgE
receptor
Autoimmune thyroid
disease
Systemic mastocytosis
20%
20%
20%
20%
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4
20%
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Countdown
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In early May, a 12-year-old girl comes to your office with symptoms of rhinitis,
congestion, and fatigue most mornings, but she says she is well by mid-day. The
symptoms have been occurring for the past 3 weeks, which coincides with the start of
tree pollen season. An oral antihistamine and intranasal steroid are being used
appropriately and have provided incomplete benefit. She wants to do something now
that can improve her symptoms for this season. Of the following, your BEST option is to:
1.
2.
3.
4.
5.
Begin allergy immunotherapy
(allergy shots)
Begin antileukotriene
monotherapy
Change her intranasal
steroid
Change her oral
antihistamine
Recommend she close her
bedroom windows.
20%
20%
20%
20%
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4
20%
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You are evaluating a 14 year old female for allergic rhinitis. Despite a regimen of multiple
allergy medications, she continues to have sneezing, rhinorrhea, and nasal congestion.
You decide to consult an allergist for further evaluation, specifically aeroallergen skin
testing and evaluation for allergy shots. Of the following, the most likely medication to
alter the results of skin testing is:
1. Corticosteroid
nasal spray
2. Inhaled beta 2
agonist
3. Low dose inhaled
corticosteroid
4. Oral antihistamine
5. Oral leukotriene
antagonist
20%
20%
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You are evaluating a 3-year-old boy who is new to your practice. His mother states that he is allergic
to the following foods: eggs, peanuts, fish sticks, pancakes, cake, Raisinettes, M&Ms, tuna fish salad,
macaroni salad, and ice cream from an ice cream store. He can eat Spaghetti, macaroni and cheese,
and chocolate ice cream from a carton. When he reacts, he immediately breaks out in hives, vomits,
and sometimes wheezes. He has injectable epinephrine, but has not used it because his symptoms
do not seem bad enough. The mother has brought him to you because she feels she needs more
guidance with his food allergies. Of the following, your BEST advice is that:
1.
2.
3.
4.
5.
Allergy shots should be started
immediately for his food allergies
Daily oral antihistamine should be
started to prevent anaphylaxis
He is not really allergic to
macaroni salad because he can
spaghetti
It is unlikely he is allergic to all
these foods and further
evaluation is needed
The treatment of choice for
anaphylactic reactions is an oral
antihistamine
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A 5-year-old girl presents with rhinitis, congestion, and sneezing of several months’
duration. Antihistamine therapy has been somewhat helpful, but the girl still has
symptoms. You have recommended removing the stuffed animals from her bed and
closing the bedroom windows. There are no animals in the home, but some relatives do
have pets. Of the following, the BEST next step is to:
1.
2.
3.
4.
5.
Add an intranasal
steroid to her regimen
Begin antileukotriene
therapy
Change the type of
antihistamine
Not allow the child to
visit her relatives
Order immediate-type
skin testing
10
20%
20%
20%
20%
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4
20%
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5
A father brings in his 7-year-old daughter to be evaluated for a rash and swelling on her
entire body. These symptoms have been present for about 2 weeks. After obtaining a
careful history and performing a physical examination, you determine that the child has
urticaria. Of the following, the MOST likely cause is
1. artificial food coloring
2. milk
3. new laundry
detergent
4. shrimp
5. upper respiratory
tract viral infection
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A 12-year-old boy presents with a 6-month history of a raised erythematous rash
involving the trunk, arms, and legs that recurs daily. The rash is pruritic but resolves
within 1 hour without bruising or discoloration. Despite trying various food elimination
diets, his parents have seen no change in his symptoms. The rash resolves within 15
minutes after taking diphenhydramine, but he is so sedated from the medication that
he misses school. He is otherwise healthy, but his parents are frustrated. Of the
following, the MOST appropriate initial long-term treatment for this boy's rash is:
1.
2.
3.
4.
5.
Fexofenadine
Hydroxyzine
Ranitidine
Prednisone
Montelukast
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10 yo boy comes to clinic complaining of tongue and mouth itching a
few minutes after eating fresh apples. The oral symptoms resolve in a
few minutes. Other than allergic rhinitis in the Spring months, he is
healthy. Of the following, you are MOST likely to recommend:
1.
2.
3.
4.
5.
Allergy skin testing to fresh
apples probably will have
negative results
Cooking the apple will not
alter its allergenicity
Her son should avoid eating
all fruits
Her son should avoid milk
products
Her son’s symptoms are
related to his allergic rhinitis
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The mother of a 14 yo girl with asthma is concerned that her daughter’s
recent exacerbation is due to mold exposure. Their home sustained
flood damage earlier this year. The mother provides you with a list of
diagnostic tests she found on the internet. Of the following, the MOST
appropriate testing to evaluate the girl for possible mold allergy is:
1. Allergy skin
testing
2. Applied
kinesiology
3. Cytotoxic testing
4. Provocationneutralization
5. Pulse test
10
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A patient with a latex allergy may
react to what food?
1.
2.
3.
4.
Apple
Banana
Peach
Soy
25%
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25%
2
3
25%
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A 12 month old female presents with a 3 month history of a pruritic rash
that involves her cheeks, neck, anterior trunk, and antecubital areas.
The rash improves with OTC corticosteroid cream but returns upon
stopping. On PE, you observe a raised erythematous rash that has
areas of lichenification. Of the following, the MOST helpful intervention
is:
1.
2.
3.
4.
Eliminate milk, soy,
eggs, and wheat from
diet
Perform food skin
testing
Perform aeroallergen
skin testing
Recommend a skin
biopsy
25%
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25%
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3
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A mother brings in her 12 month old son who broke out in hives after
eating breakfast. Immediately after eating eggs, he developed a
diffuse, erythematous, pruritic rash. She is concerned about an egg
allergy. Of the following, the BEST statement regarding IgE mediated
•
A. cooking the egg egg allergy:
•
•
•
•
eliminates its allergic
potential
B. egg is the most
common food allergy in
the 1st year of life
C. egg white is more
allergenic than egg yolk
D. Most children do not
outgrow their egg allergy
E. The MMR vaccine is
contraindicated in patients
with an egg allergy
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References & Online Further Reading
• Atopic diseases: in Medical Immunology .eds ( Tristram G.Parslow, Daniel P. A Stites, Abba
I.Terr.and John B. Imboden), tenth edition.
• Anaphylaxis and Urticaria: in Medical Immunology .eds ( Tristram G.Parslow, Daniel P. A
Stites, Abba I.Terr.and John B. Imboden), tenth edition.
• Brostoff J and Challacombe, S. Food Allergy and Intolerance. Bailliere Tindall, London.
1987. pp 431-794
Shapiro, RS, Isenberg, BC. Allergic Headache. Annals of Allergy. 23 (3): 1965
Monroe J, Brostoff, J. Food Allergy and Migraine. Lancet. July 5, 1980
Egger J, Will J, Carter CM. Is Migraine Food Allergy? A Double-Blind Control Trial of
Oligoantigenic Diet Treatment. Lancet. 865, 1983
Mansfield L, Vaughn R, et al. Food Allergy and Adult Migraine: Double-Blind Mediator
Confirmation of an Allergic Etiology. Annals of Allergy. 55:126-129, . Nsouli TM, et al.
Serous Otitis Media and Food Allergy. Annals of Allergy, 73:215-219
Sandberg, DH. Gastrointestinal complaints related to diet. Intern Pediatrics, 5(1):23-29,
1990
Hill, DJ. A low allergy diet is a significant intervention in infantile colic: results of a
community based study. J of Allergy and Clinical Immunology, 1995 (Dec): 886-890
Randolph TG. Allergy as a Causative Factor of Fatigue, Irritability, and Behavioral
Problems of Children J Pediatrics. 31:560-572, 1947
. Boris M and Mandel FS. Foods and additives are common causes of the attention deficit
hyperactive disorder in children. Annals of Allergy. 72(5):462-468, 1994
• Adkinson NF Jr. Middleton’s Allergy: Principles and Practice. 6th ed. Philadelphia, Pa:
Mosby; 2003.
• Rakel RE. Textbook of Family Medicine. 7th ed. Philadelphia, Pa: WB Saunders; 2007.
• American Gastroenterological Association medical position statement: guidelines for the
evaluation of food allergies .Gastroenterology 2001 .Mar;120(4):1023-5.
• American College of Allergy, Asthma, & Immunology. Food allergy: a practice parameter .
Ann Allergy Asthma Immunol 2006 .Mar;96(3 Suppl 2):S1-68.
• Adkinson NF Jr .Middleton’s Allergy: Principles and Practice6 .th ed. Philadelphia, Pa:
Mosby; 2003