The Allergic Diseases:

That group of diseases thatis relatively unimportant…

The Allergic Diseases:

TO THOSE

THAT

DON’T HAVE THEM!

Immunological Mechanisms Involved Immunological Mechanisms Involved in Allergic Diseasein Allergic Disease

Allergen

Environment

Submucosa

Th2-cellTh2-cell B-cellB-cell

Production of antigen-

specific IgE

Sensitization Re-exposureAllergen

Antigen presenting cell

MHC class II protein andepitope

asthma, hayfever, urticaria

Clinicaleffects

Mediators

Mast celldegranulation

+

YYY

Y

YY

Y

Y

Allergen

Antigen presentingcell

T cell

B cell

IgE

Plasma cell

Hyperreactivity Late phase

Early Allergic Reaction

Ongoing Inflammatory Reaction

Mast cellY Y

YY

Y

>

CNS

Gland

>>

>

Blood vessel

Nerve ending

Epithelial cell

<

Busse WW, Holgate ST. Asthma and Rhinits. Boston: Blackwell Science, 1995

The Course of Events Leading to the Immediate Allergic Response and the Ongoing Inflammatory Response

IgEIgE--Dependent Release of Dependent Release of Inflammatory MediatorsInflammatory Mediators

Immediate ReleaseGranule contents:Histamine, TNF-α, Proteases, Heparin

Over HoursCytokine production:Specifically IL-4, IL-13

IgEAllergens

FcεRI

FcεRIbinding site

Sneezing Nasal congestionItchy, runny noseWatery eyes

Over MinutesLipid mediators: ProstaglandinsLeukotrienes

WheezingBronchoconstriction

Mucus productionEosinophil recruitment

Burden of Allergic Rhinitis• Prevalence

– Affects over 50 million Americans (17-20%)– Most prevalent chronic condition in patients under

18 years of age• Socioeconomic impact

– Physical, social, and mental health status adversely affected– Accounts for > 8 million office visits annually– Accounts for > 4 million days of reduced activity annually– 3.5 million lost work days annually– >2 million school days missed annually

Dykewicz M, et al. Ann Allergy Asthma Immunol. 1998;81:478-518.Public Health Service. US Dept of Health and Human Services publication (PHS) 93-1522. 1997.

Stempel: Rhinitis: What it Means and Why it Matters. Am J Managed Care. 1997;8(suppl).

Allergic Rhinitis: Diagnosis

• History– Symptoms– Quality of life– Comorbidities

• Physical examination– Allergic “shiners”– Allergic crease– Pale, boggy, watery mucosa, clear

secretions

• Diagnostic tests– Skin tests for specific IgE– RAST– Nasal cytology for

eosinophils and/or basophils

Symptoms Associated with the Most Common Types of Rhinitis

• Classic symptoms associated with allergic rhinitis– Seasonal Allergic Rhinitis

• Sneezing• Itchy nose / throat• Anterior rhinorrhea / post-nasal drip• Nasal congestion / stuffiness• Itchy, watery eyes

– Perennial Allergic Rhinitis & Non-allergic Rhinitis• Nasal congestion / stuffiness• Anterior rhinorrhea• Post-nasal drip / cough

Dykewicz M, et al. Ann Allergy Asthma Immunol. 1998;81:478-518.Settipane et al. In: Kaliner, ed. Current Review of Allergic Diseases. 2000.

• Perennial Allergic Rhinitis– Dust mites, insects– Animal dander / saliva– Mold spores

Triggers Associated with the Most Common Types of Rhinitis

• Seasonal Allergic Rhinitis– Pollen

• Trees• Grasses• Weeds

– Mold spores• Non-allergic Rhinitis

– Strong odors– Stress– Weather changes

• Temperature• Barometric pressure• Humidity

Dykewicz M, et al. Ann Allergy Asthma Immunol. 1998;81:478-518. Settipane et al. In: Kaliner, ed. Current Review of Allergic Diseases. 2000.

Four general principles of allergy management

The Allergy Report. Am Acad Allergy Asthma Immunol. 2000.

1. Education and monitoring

2. Avoidance of trigger factors

3. Pharmacotherapy

4. Immunotherapy

Managing Patients with Allergic Rhinitis

Environmental ControlStrategies for Dust Avoidance

• Encase mattress, box spring, and pillow in mite-proof, impermeable covers

• Decrease household humidity (40-50%)• Remove carpeting from bedroom• Wash bed sheets and blankets in hot water (at least 130˚F)

at least once a week• Remove all feather pillows and comforters • Minimize dust-collecting surfaces (e.g., shelves, stuffed animals, books)• Remove venetian blinds from the bedroom, use washable

curtains with shades• Avoid vacuuming when dust-sensitive patients are home,

use vacuum cleaners with HEPA filtering devices• Remove upholstered furniture from the bedroom

The Allergy Report. Am Acad Allergy Asthma Immunol. 2000.Dykewicz M, et al. Ann Allergy Asthma Immunol. 1998;81:478-518.

Therapeutic Options in the Management of Allergic Rhinitis

• Antihistamines– Oral– Intranasal

• Decongestants– Oral– Topical

• Anticholinergics– Oral– Intranasal

• Antihistamine-decongestant combinations

• Corticosteroids• Intranasal• Systemic

• Cromolyn sodium • Leukotriene antagonists• Immunotherapy

What is Allergen Immunotherapy?

• Desensitization process that includes the administration of increasing doses of a specific allergen, over time, to a sensitive individual– Increases tolerance for the particular allergen– Decreases symptoms when patient comes in

contact with particular allergen

“Anaphylaxis is the opposite condition to protection (phylaxis). I coined the word in 1902 to describe the peculiar attribute which certain poisons possess of increasing instead of diminishing the sensitivity of an organism to their action…

Charles Richet, Anaphylaxis (translated by Murray Bligh)

The University Press, Liverpool, 1913

Precipitants of Precipitants of IgEIgE--Mediated AnaphylaxisMediated Anaphylaxis

• Antibiotics: penicillins, cephalosporins

• Allergenic extracts

• Anesthetics/muscle relaxants

• Foods: shellfish, nuts, eggs

• Foreign proteins and venoms: hymenoptera, fire ant, triatoma

• Latex

Most Frequent Signs and Symptoms Most Frequent Signs and Symptoms of Anaphylaxisof Anaphylaxis

30Gastrointestinal

33Hypotension

46Flush

47Dyspnea/Wheeze

56Upper Airway Edema

88Urticaria Angioedema

PercentManifestation

Diagnosis: Diagnosis: PositivePositive

• Avoid Insects

• Carry Emergency Kit

• Immunotherapy

Time from sting to beginning of Time from sting to beginning of treatmenttreatment

10%66%18%6%0%0%50

fatal

1%8%4%50%22%15%100

nonfatal

No info

No Rx

>60 min

30-60 min

10-30 min

0-10 minCases

Case StudiesCase Studies1979 - 16 years old• Asthma• Peanut butter hives. Also, aromas

1987 - in Chicago, ingested cookie• Severe wheezing, angioedema, intubation• Did not use Epi-pen

1995 - hospitalized at St. Mary’s, cookie1997 - Mexican restaurant• tracheostomy in St. Luke’s parking lot• ICU for 3 days

Peanut AllergyPeanut Allergy

1.5 million Americans at risk

50-100 deaths per year

clinical reaction every 3-5 years

The Allergic Cascade is Interrupted by The Allergic Cascade is Interrupted by OmalizumabOmalizumab

B-cellB-cell

IgEIgE

omalizumab complexeswith free IgE

omalizumab complexeswith free IgE

omalizumabomalizumabMast cellMast cell

Allergen-driven B-cell secretes IgE

Allergen-driven B-cell secretes IgE

FcεRIFcεRI