Type I Hypersensitivty

What antibody do type I hypersensitivity reactions require?

IgE specific for the allergen's antigenic determinant

Are type I hypersensitivity reactions immediate or delayed?

Immediate

What allows early recognition of the immunogen on repeat exposure in type I reactions?

Memory B cells

What is released during cellular activation in type I reactions?

Granules with preformed inflammatory mediators, including histamine

What is the main preformed inflammatory mediator released in type I reactions?

Histamine

What newly formed mediators are generated in type I reactions?

Leukotrienes (LTs), prostaglandins (PGs), thromboxane, and platelet-activating factor (PAF)

What does LT stand for?

Leukotriene

What does PG stand for?

Prostaglandin

What does PAF stand for?

Platelet-activating factor

What is the onset of a type I hypersensitivity reaction?

Generally within 1 hour of exposure

What single organs can type I reactions be limited to?

Nasal mucosa (rhinitis), respiratory tract (acute asthma), skin (urticaria), or GI tract

What type I reaction affects the nasal mucosa?

Rhinitis

What type I reaction affects the respiratory tract?

Acute asthma

What type I reaction affects the skin?

Urticaria

What is a type I reaction involving multiple organs simultaneously called?

Anaphylaxis

Which mediators cause bronchospasm in type I reactions?

Histamine, prostaglandins, leukotrienes, bradykinin, and PAF

Which mediators cause mucosal edema in type I reactions?

Histamine, prostaglandins, leukotrienes, bradykinin, and PAF

Which mediators cause mucus secretion in type I reactions?

Histamine, prostaglandins, leukotrienes, and PAF

Which mediators cause airway inflammation in type I reactions?

ECF-A (eosinophil) and leukotrienes

What does ECF-A stand for?

Eosinophil chemotactic factor of anaphylaxis

What are the 4 manifestations of type I mediators in the airway?

Bronchospasm, mucosal edema, mucus secretion, and airway inflammation

Which type I mediator is involved in all 4 manifestations (bronchospasm, mucosal edema, mucus secretion, and airway inflammation)?

Leukotrienes

Which mediator is involved in bronchospasm and mucosal edema but NOT mucus secretion?

Bradykinin

What is atopy?

A genetic tendency to develop allergic conditions

What are examples of type I allergic diseases?

Food allergies and drug allergies

What are examples of type I atopic diseases?

Asthma, indoor/seasonal allergies, and atopic dermatitis

What are the acute manifestations of food allergies?

Hives, anaphylaxis, flushing, angioedema, and oral itching

What are the chronic manifestations of food allergies?

Eczema, asthma, diarrhea, and vomiting

What is an example of a type I drug allergy?

Beta-lactam-induced urticaria or anaphylaxis

What drug class is a classic example of type I drug allergy?

Beta-lactams

What is allergic asthma?

Asthma worsened or triggered by allergens

What are the symptoms of allergic asthma?

Wheezing, cough, and chest tightness

How is allergic asthma typically managed?

Beta agonists (e.g., albuterol)

What is an example of a beta agonist used for allergic asthma?

Albuterol

What conditions are associated with indoor/seasonal allergies?

Conjunctivitis and rhinitis

What are the symptoms of indoor/seasonal allergies?

Red, watery eyes, runny, itchy nose, and sneezing

What is atopic dermatitis?

Dry, itchy skin (eczema)

What is anaphylaxis?

An acute, life-threatening immune reaction mediated primarily by IgE that involves multiple organ systems

What antibody primarily mediates anaphylaxis?

IgE

How many organ systems does anaphylaxis involve?

Multiple organ systems

What is the increase in anaphylaxis most notably associated with?

Increased use of biologic agents and food allergies in the younger age group

Why is anaphylaxis increasing in the younger age group?

Food allergies

Which drugs are most commonly reported to cause anaphylaxis?

Penicillins, aspirin and other NSAIDs, and insulins

Where do the initial signs and symptoms of anaphylaxis occur?

The skin

What are the initial skin symptoms of anaphylaxis?

Flushing, pruritus, urticaria, and angioedema

What are the respiratory symptoms of anaphylaxis?

Tightness of the throat and chest, dysphagia, dysphonia and hoarseness, cough, stridor, shortness of breath, dyspnea, congestion, rhinorrhea, and sneezing

What are the GI symptoms of anaphylaxis?

Nausea, cramping abdominal pain, vomiting, and diarrhea

Besides GI symptoms, what other general symptoms can occur in anaphylaxis?

Dizziness and hypotension

What are the additional cardiovascular effects of anaphylaxis?

Syncope, altered mental status, chest pain, and dysrhythmia

What are the causes of fatal anaphylaxis?

Asphyxia caused by airway obstruction and cardiovascular collapse

What causes asphyxia in fatal anaphylaxis?

Airway obstruction

What does dysphagia mean?

Difficulty swallowing

What does dysphonia mean?

Difficulty speaking or hoarse voice

What is stridor?

A high-pitched breathing sound caused by upper airway obstruction

What does rhinorrhea mean?

Runny nose

What is syncope?

Fainting

What is another name for a pseudoallergic reaction?

Anaphylactoid reaction

What are anaphylactoid reactions?

Immediate systemic reactions that mimic anaphylaxis but are not caused by IgE-mediated immune responses

Do anaphylactoid reactions involve IgE?

No

How do drugs cause anaphylactoid reactions?

By causing degranulation (release of histamine) without involving IgE

What is an example of a drug that causes an anaphylactoid reaction?

Opioids

How do opioids cause an anaphylactoid reaction?

They directly activate mast cells and cause histamine release

What symptoms can opioids cause through histamine release?

Flushing or pruritus

What is the difference between anaphylaxis and an anaphylactoid reaction?

Anaphylaxis is IgE-mediated; an anaphylactoid reaction mimics it but does not involve IgE

Why does anaphylaxis require prompt treatment?

To minimize the risk of serious morbidity or death

What is the first-line therapy for anaphylaxis?

Epinephrine intramuscular (IM) injection, given without delay

What route is epinephrine given for anaphylaxis?

Intramuscular (IM)

What follows epinephrine in the treatment of anaphylaxis?

Adjunctive therapy for symptom control

What should patients be assessed for after anaphylaxis treatment?

Possible recurrence

Which patients should be prescribed auto-injectable epinephrine?

Patients who may reencounter the allergic trigger (e.g., peanuts, shellfish, and medications)

What is the epinephrine auto-injector dose for adults?

0.3 mg

What is the epinephrine auto-injector dose for children?

0.15 mg

How many epinephrine auto-injectors should patients carry at all times?

Two

What is the first step in managing allergic rhinitis?

Implement appropriate environmental controls

If environmental controls are not totally effective, how should allergic rhinitis drug treatment be started?

Select a single drug based on symptoms

Which symptoms do antihistamines treat in allergic rhinitis?

Sneezing, itching, rhinorrhea, and ocular symptoms

Which symptom do systemic decongestants treat in allergic rhinitis?

Nasal congestion

Which symptoms do intranasal steroids treat in allergic rhinitis?

Sneezing, itching, rhinorrhea, and nasal congestion

What should be done if allergic rhinitis symptoms are not controlled with one agent?

Switch to or add another agent from a different drug class

What should be considered if allergic rhinitis symptoms are still not controlled after trying different drug classes?

Montelukast

For prevention, when must allergic rhinitis therapy be continued?

Prior to and during allergen exposure/season

Which symptom do antihistamines NOT help with?

Nasal congestion

Which allergic rhinitis symptoms do corticosteroids help with?

All symptoms

Which enzyme do corticosteroids inhibit?

Phospholipase A2

What is the result of corticosteroids inhibiting phospholipase A2?

Decreased arachidonic acid

Corticosteroids decrease which mediators made from arachidonic acid?

Leukotrienes, prostaglandins, and thromboxanes

Corticosteroids inhibit the influx of which cells into local sites?

Eosinophils, basophils, and TH2 lymphocytes

What effect do corticosteroids have on eosinophil production?

Prevent eosinophil production in the bone marrow and rapidly decrease circulating eosinophils

Which cytokines do corticosteroids inhibit?

TNFα, IL-1, and IL-6 (among many others)

What type of drug is cromolyn?

Mast cell stabilizer

How does cromolyn work?

Prevents mast cell release of histamine and leukotrienes

What conditions is cromolyn used to manage?

Bronchial asthma, allergic rhinitis, and certain allergic eye conditions (vernal conjunctivitis, keratitis, and keratoconjunctivitis)

Which allergic eye conditions can cromolyn be used for?

Vernal conjunctivitis, keratitis, and keratoconjunctivitis

What are the adverse effects of oral antihistamines?

Sedation (1st generation), dry mouth/eyes, dizziness, blurred vision, confusion, and hypotension

Which generation of oral antihistamines causes sedation?

1st generation

What are the adverse effects of intranasal products?

Nasal irritation, throat irritation, headaches, and nosebleeds

How long do intranasal steroids take to start working?

More than 1 week

How should allergy therapies be taken to be effective?

Regularly

When are allergy therapies most effective if started?

Just prior to the start of allergy season

What is the most common kind of eczema?

Atopic dermatitis