Hypersensitivity disorders cld

Immune system Disorders 1

M A R I A C A R M E L A L . D O M O C M A T, R N , M S N

I N S T R U C T O R , C U R A A N D R E H A B N R G I I

S C H O O L O F N U R S I N G

N O R T H E R N L U Z O N A D V E N T I S T C O L L E G E

� Inflammatory and immunologic response

� is normally helpful and protect against infection and can development

� These responses also stimulates tissue growth and repair after injury

� But if prolonged and excessive or occur at inappropriate time

� Effect: normal cells, tissues or organs are damaged

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� Effect: normal cells, tissues or organs are damaged

Maria Carmela L.Domocmat, RN, MSN

W H A T H A P P E N S W H E N T H E I M M U N E S Y S T E M

D O E S N ’ T W O R K T H E W A Y I T S H O U L D ? ?

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� Overreaction

� Hypersensitivity

� Overreactions to invaders and foreign antigens

� Autoimmune response

� Underreaction

� Immunodeficiency

� Congenital

� Acquired

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� Autoimmune response

� When it fails to recognize self-cells and attack normal body tissues


Hypersensitivity Reaction

Hypersensitivity Reaction or Allergic Reaction

� an immune malfunction whereby a person's body is hypersensitized to

react immunologically to typically non-immunogenic substances.

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Definition of terms

� Atopy: the tendency to develop allergies for which there is a genetic disposition and that involve immunoglobulin E (IgE) antibody formation � AKA – atopic, allergic, hypersensitive

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� AKA – atopic, allergic, hypersensitive

� Allergy: describes the increased immune response to the presence of an allergen (i.e., antigen)


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� People must progress through two-step process to become allergic

� 1) sensitization

� 2) reexposure to the allergen

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� 2) reexposure to the allergen

�


General categories of hypersensitivity reactions

� Immediate

� humoral or antigen-antibody

� Delayed

� cell-mediated

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I M M E D I A T E

Type I: Immediate hypersensitivity

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Types of Hypersensitivity


Type II: Cytotoxic hypersensitivity

Type III: Immune complex-mediated

hypersensitivity

D E L A Y E D

Type IV: Delayed Hypersensitivity


Hypersensitivity

There are four different types of hypersensitivities that result from different responses of the immune system:


- onset within minutes of antigen challenge

- examples are allergies to molds, insect bites

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- examples are allergies to molds, insect bites

Type II: Cytotoxic hypersensitivity

- onset within minutes or a few hours of antigen challenge

- examples are adult hemolytic anemia and drug allergies


Hypersensitivity

There are four different types of hypersensitivities that result from different responses of the immune system:

Type III: Immune complex-mediated hypersensitivity- onset usually within 2-6 hours

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- onset usually within 2-6 hours

- examples include serum sickness and systemic lupus

erythematosus

Type IV: Delayed Hypersensitivity- inflammation by 2-6 hours; peaks by 24-48 hours

- examples include poison ivy and chronic asthma


�A T O P I C A L L E R G I E S

�Allergic rhinitis or hay fever�Allergic rhinitis or hay fever

�Urticaria or Hives �A L L E R G I C A S T H M A

�A N A P H Y L A X I S

�A L L E R G Y T O S P E C I F I C A L L E R G E N

�Latex allergy

�bee venom, peanut, iodine, shellfish, drugs


� This is the type of hypersensitivity usually referred to as

“allergy”.

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Type I:

Immediate hypersensitivity

� occurs when an IgE antibody response is mounted against

an antigen in the environment that is usually harmless

� A single exposure to antigen isn’t enough to trigger

hypersensitivity, but the immune response may become

more severe with repeated exposure.

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more severe with repeated exposure.


Type I hypersensitivity – sensitization to an inhaled allergen

or bee sting17

Mast cell

cytokines

→→→→ →→→→


Antigens (red dots) from inhaled pollen are ingested and presented by macrophages to T cells. Activated T cells produce cytokines leading to the production of IgE, which binds to receptors on mast cells and causes the release of histamine, which is responsible for allergy symptoms. Onset is usually within minutes of contact with antigen.

� When the antigen enters through a respiratory mucosal

surface, it is taken up, processed and displayed by antigen-

presenting cells.

� When the presented fragments “lock on” to helper T cell

receptors, the T cells become activated, secreting

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receptors, the T cells become activated, secreting

cytokines.

� The cytokines, in turn, stimulate IgE-producing B cells.

� IgE binds to IgE-receptors on the surfaces of mast cells,

sensitizing them.


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Maria Carmela L.Domocmat, RN, MSN 20

histamine

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� Allergens can be contacted in the ff ways

� Inhaled

� Ingested

� Injected

� contacted

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� contacted


Atopic allergy

� Inhaled

� Plant pollens

� Fungal spores

� Animal dander

� House dust

� Grass

� Injected

� Bee venom

� Drugs

� Biologic subtances(ex: contrast dyes, Adenocotricotropic hormone)

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� Grass

� Ragweed

� Ingested

� Foods

� Food additives

� Drugs

Adenocotricotropic hormone)

� Contacted

� Pollens

� Foods

� Envt proteins


25Maria Carmela L.Domocmat, RN, MSN

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Common Causes of Allergy

What are common allergenic foods?

� Legumes (Peanuts and Soybeans)

� Mollusks (snails, mussels, oysters, scallops, clams, squid)

� Milk

� Eggs

� Fish (cod, salmon, haddock, etc.)� Fish (cod, salmon, haddock, etc.)

� Crustacea (shrimp, crawfish, lobster. etc.)

� Wheat

� Tree nuts (almonds, walnuts, Brazil nuts, etc.)

� Selected food additives

M O S T C O M M O N T Y P E

I N C L U D E S :

Allergic rhinitis or hay fever

Atopic allergy 30

Allergic rhinitis or hay fever

Urticaria or hay fever


A K A : H A Y F E V E R

Allergic Rhinitis 31


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Allergic Rhinitis

� Triggered by reactions to airborne allergens

� Types:

� Seasonal: recur to same time of each of the year

� Often coincide with timing of large environmental exposure

� Chronic: or perennial rhinitis

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� Chronic: or perennial rhinitis

� Occur intermittently or continuous when exposed to allergen

� Non-allergic rhinitis

� Same manifestations are present

� Although no allergic cause is identified immune system does not appear to be involved


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Urticaria 36


� Urticaria may be acute (lasting less than 6 wk) or chronic

(lasting more than 6 wk).

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� Many substances can trigger hives, including:� Animal dander (especially cats)

� Insect bites

� Medications

� Pollen

Shellfish, fish, nuts, eggs, milk, and other foods

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� Shellfish, fish, nuts, eggs, milk, and other foods

� Hives may also develop as a result of:� Emotional stress

� Extreme cold or sun exposure

� Excessive perspiration

� Illness (including lupus, other autoimmune diseases, and leukemia

� Infections such as mononucleosis


Symptoms

� Itching

� Swelling of the surface of the skin into red- or skin-colored

welts (called wheals) with clearly defined edges

� The welts may get bigger, spread, and join together to form larger areas

of flat, raised skin.

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� They can also change shape, disappear, and reappear within minutes or

hours.

� The welts tend to start suddenly and go away quickly. When you press

the center of a red welt, it turns white. This is called blanching.


Hives or urticaria

Hives (urticaria) on the back and buttocks

� These are hives (urticaria) with the typical slightly-raised red

appearance, and are accompanied by itching. These are

located on the buttocks. Hives can be generalized over the

entire body or may be localized, and usually result from an

allergic reaction.

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allergic reaction.

Hives (urticaria) - close-up

� Hives (urticaria) are raised,

red, itchy welts. The

majority of urticaria

develop as a result of

allergic reactions.

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allergic reactions.

Occasionally, they may be

associated with

autoimmune diseases,

infections (parasitosis),

drugs, malignancy, or

other causes.


Hives (urticaria) on the chest

� Hives develop when histamine is

released into the small blood vessels

(capillaries). The capillaries dilate which

causes a welt, and fluid oozes into the

surrounding tissue, causing swelling.

Histamine also causes intense itching.

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� Latex is a milky fluid that comes from the tropical rubber

tree,Hevea brasiliensis.

� Hundreds of everyday products contain latex. Some

common ones are

Gloves

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� Gloves

� Condoms

� Balloons

� Rubber bands

� Shoe soles

� Pacifiers

Maria Carmela L.Domocmat, RN, MSN http://www.nlm.nih.gov/medlineplus/latexallergy.html

Latex exposure is associated with 3 clinical

syndromes

� first syndrome - irritant dermatitis.

� It is a result of mechanical disruption of the skin due to the rubbing of gloves and accounts for the majority of latex-induced local skin rashes. It is not immune mediated, is not associated with allergic complications

� second syndrome - delayed (type IV) hypersensitivity reaction

Result in a typical contact dermatitis.

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� Result in a typical contact dermatitis.

� Symptoms usually develop within 24-48 hours of cutaneous or mucous membrane exposure to latex in a sensitized person.

� Third syndrome - immediate (type I) hypersensitivity

� most serious, and least common

� mediated by an immunoglobulin E (IgE) response specific for latex proteins.


See http://emedicine.medscape.com/article/756632-overview#showall for more information

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Maria Carmela L.Domocmat, RN, MSN http://www.mountnittany.org/assets/images/krames/7596.jpg

Allergic asthma48


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� See link: http://emedicine.medscape.com/article/137501-overview#showall for additional information

Maria Carmela L.Domocmat, RN, MSN http://cureasthmaguide.com/wp-content/uploads/2010/02/inflammed-airways-complex.jpg

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Maria Carmela L.Domocmat, RN, MSN http://www.dentalgentlecare.com/images/lungs-asthma.gif

Clinical

Manifestations

of Immediate

HypersensitivityHypersensitivity

ASTHMA

Anaphylaxis54


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Maria Carmela L.Domocmat, RN, MSN http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001847/bin/19320.jpg

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H X : A C C U R A T E A N D D E TA I L E D H X

Describe onset and duration of problems

Nursing assessment 57

Ask abt work, school, home, environment, possible exposures

through hobbies, leisure time or sports activities

Ask presence of allergies among relatives

P H Y S I C A L A S S E S S M E N T


Clinical Manifestations of

Immediate Hypersensitivity

Allergy is characterized by a local or systemic

inflammatory response to allergens

Local symptoms:� Nose: swelling of the nasal mucosa, rhinorrhea

� Eyes: redness and itching of the conjunctiva (allergic conjunctivitis)

� Airways: bronchoconstriction, wheezing, sometimes

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� Airways: bronchoconstriction, wheezing, sometimes outright attacks of asthma

� Ears: feeling of fullness, possibly pain, and impaired hearing due to the lack of eustachian tube drainage.

� Skin: various rashes, such as eczema, hives and contact dermatitis.

� Head: while not as common, headaches are seen in some with environmental or chemical allergies.


Allergy is characterized by a local or systemic inflammatory response to allergens

Systemic allergic response � Is also called anaphylaxis

� Depending of the rate of severity, it can cause cutaneous reactions, bronchoconstriction, edema, hypotension, coma and even death.

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reactions, bronchoconstriction, edema, hypotension, coma and even death.


Hives Symptoms

� Itching

� Swelling of the surface of the skin into red- or skin-colored

welts (called wheals) with clearly defined edges

� The welts may get bigger, spread, and join together to form larger areas


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� They can also change shape, disappear, and reappear within minutes or

hours.

� The welts tend to start suddenly and go away quickly. When you press

the center of a red welt, it turns white. This is called blanching.


http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001848/

Food allergies

� The body's immune system normally

reacts to the presence of toxins, bacteria

or viruses by producing a chemical

reaction to fight these invaders.

However, sometimes the immune

system reacts to ordinarily benign

substances such as food or pollen, to

which it has become sensitive. This

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which it has become sensitive. This

overreaction can cause symptoms from

the mild (hives) to the severe

(anaphylactic shock) upon subsequent

exposure to the substance. An actual

food allergy, as opposed to simple

intolerance due to the lack of digesting

enzymes, is indicated by the production

of antibodies to the food allergen, and

by the release of histamines and other

chemicals into the blood.


Food Allergy - Symptoms

� Nausea

� Diarrhea

� Abdominal cramps

� Pruritic rashes

� AngioedemaAngioedema

� Asthma/rhinitis

� Vomiting

� Hives

� Laryngeal edema

� Anaphylaxis

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S K I N T E S T S

• Scratch or prick test

Allergy tests 65

• Intradermal test

•O R A L F O O D C H A L L E N G E O R E L I M I N A T I O N D I E T

•L A B O R A T O RY T E S T S

CBC

Increased serum IgE

RAST (radioallergosorbent test)


� Skin Tests

� Individual is inoculated with allergen by scraping or injection

� Fast: results within 30’

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� Prep

� Discontinue Glucocorticoids and antihistamine 5 days b4 test (to avoid

suppressing allergic response during the test)

� Nasal sprays to reduce mucous membrane swelling can be continued

but shld be discontinued if with antihistamine

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but shld be discontinued if with antihistamine


Skin Tests: ID

Skin Tests: Intradermal or Scratch test

• The allergens are either injected intradermally or into small scratchings made into the patient's skin

• If the patient is allergic to the substance, then a visible inflammatory reaction will usually occur within 30 minutes.

• This response will range from slight reddening of the skin to full-blown hives in extremely sensitive patients.

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hives in extremely sensitive patients.

• Problems: some people may display a delayed-type hypersensitivity (DTH) reaction which can occur as far as 6 hours after application of the allergen and last up to 24 hours. This can also cause serious long-lasting tissue damage to the affected area. These types of serious reactions are quite rare.



http://www.allergyclinic.co.uk/images/pricktest.jpg

Oral Food Challenge

� Used to identify specific allergen if skin testing is not

conclusive and if keeping a food diary has failed to

determine the offending food items

� Prep - eliminate suspected foods 7-14 days b4 test

Eat defined suspected allergen for at least 1 day

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� Eat defined suspected allergen for at least 1 day

� Monitor s/s of allergy

� If with many food allergies – eat only 1 food type/day of

testing


� Laboratory tests

� CBC

� Increased eosinophils 12% (normal 1-2%)

� Increased WBC count, but percentage of neutrophils is normal (55-70%)

� Note: if acute infection occurs with rhinitis – both WBC and neutrophils

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� Note: if acute infection occurs with rhinitis – both WBC and neutrophils are increased)

� Increased serum IgE

� Only confirms the presence of infection

� But does not indicate specific allergen

� RAST (radioallergosorbent test)

� Shows blood level of IgE directed against a specific antigen

� Can determine specific allergies

� Expensive Maria Carmela L.Domocmat, RN, MSN

Management of Type I

Hypersensitivity Reaction74


Allergy management

1. Avoidance therapy - identify and prevent exposure to

allergen, control of environment

2. Symptomatic therapy

1. Teach how to use Epi-pen

Desensitization therapy

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3. Desensitization therapy


1. Avoidance therapy

� Avoid direct contact with allergen

� Airborne allergen

� Air-conditioning and air cleaning units

� Remove cloth drapes, upholstered furniture, carpet

Cover mattress and pillows with plastic or cotton fine mesh

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� Cover mattress and pillows with plastic or cotton fine mesh

� Pet-induced allergy

� Keep pet out of bedroom

� Thoroughly clean room to remove hair and dander

� Frequent bathing of pet


1. Avoidance therapy

� Avoid direct contact with allergen

� Latex allergy

� Avoid products with latex;

� use synthetic substances that do not contain latex protein

� Ex: Elastylite glove

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� Ex: Elastylite glove

� Note: always use latex-free products in the care of client

with known latex allergy



� Drug therapy or Pharmaceutical approaches to allergy

treatment involve

� Decongestants

� Antihistamine

� Corticosteroids

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� Corticosteroids

� Mast cell stabilizers

� Leukotrine Antagonists

� Complementary and alternative Therapies

� Aromatherapy

� Eat unprocessed honey



� Nasal Decongestants

� Action: prevent release of mediators such as histamine but do not clear the allergen

� Have similar action to adrenergic agents - cause vasoconstriction in inflamed tissues

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inflamed tissues

� Often contain ephedrine, phenylephrine, or pseudoephedrine

� Phenylephrine – 1 spray/nostril 4-6x/day ; Oxymetazoline -1 spray/nostril 2x/day ; pseudoephedrine (Sudafed)

� Note: caution not to use more frequently than directed or for longer than 4 days (overuse or continued use causes a rebound nasal congestion or rebound rhinitis and worsens the symptoms)

� S/E: dry mouth, increased BP, sleep difficulties


Nasal Spray 80


Nasal Decongestants:

Nursing Implications

� Decongestants may cause hypertension, palpitations, and

CNS stimulation—avoid in patients with these conditions

� Patients on medication therapy for hypertension should

check with their physician before taking OTC

decongestants

Mosby items and derived items © 2005, 2002 by Mosby, Inc.

decongestants

� Assess for drug allergies

Nasal Decongestants:


� Patients should avoid caffeine and caffeine-containing

products

� Report a fever, cough, or other symptoms lasting longer

than a week

Monitor for intended therapeutic effects


� Monitor for intended therapeutic effects


� Antihistamine

� Compete with histamine at receptor site and block histamine from binding to the receptor –prevents vasodilation and capillary leak

� first generation antihistamines

� diphenhydramine (Benadryl) and chlorpheniramine (Chloratrimeton)

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� diphenhydramine (Benadryl) and chlorpheniramine (Chloratrimeton)

� common side effect : sedation, drowsiness, and dry mouth

� Use at night before bedtime to avoid feeling tired the next day.

� second-generation antihistamines

� loratadine (Claritin), fexofenadine (Allegra), and certirizine (Zyrtec)

� less likely to cause drowsiness and can be taken during the daytime.


Antihistamines:


� Gather data about the condition or allergic reaction that required treatment; also assess for drug allergies

� Contraindicated in the presence of acute asthma attacks and lower respiratory diseases

� Use with caution in increased intraocular pressure, cardiac


� Use with caution in increased intraocular pressure, cardiac or renal disease, hypertension, asthma, COPD, peptic ulcer disease, BPH, or pregnancy

http://www.chipola.edu/instruct/health-sciences/PowerPointPresentations/Pharmacology/Chapter_035.ppt

Antihistamines:


� Instruct patients to report excessive sedation, confusion, or

hypotension

� Avoid driving or operating heavy machinery, and do not

consume alcohol or other CNS depressants

Do not take these medications with other prescribed or


� Do not take these medications with other prescribed or

OTC medications without checking with prescriber


Antihistamines:


� Best tolerated when taken with meals—reduces GI upset

� If dry mouth occurs, teach patient to perform frequent

mouth care, chew gum, or suck on hard candy (preferably

sugarless) to ease discomfort

Monitor for intended therapeutic effects


� Monitor for intended therapeutic effects


� Combined products

� Claritin-D.

� loratadine (Claritin) and pseudoephedrine (Sudafed) are combined in the over-the-counter product

� This allergy relief medicine gives the benefit of the antihistamine to

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prevent nasal allergies and the decongestant to open swollen nasal passages.



� Corticosteroids

� Decreased inflam and immune response in many ways

� One way – prevent synthesis of mediators

� Nasal spray – prevent symtpoms of rhinitis

Systemic – can produce severe S/E; avoised for rhinites; used inly

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� Systemic – can produce severe S/E; avoised for rhinites; used inly

in short-term basis for other probmels assoc wth type I hypersen.

� Beclomethasone (Beconase) –

� 1-2 metered spray /nostril ; 1-2x/day

� fluticasone (Flovent, Flonase)

� 2 metered spray /nostril/day


Inhaled Corticosteroids:


� Contraindicated in patients with psychosis, fungal

infections, AIDS, TB

� Cautious use in patients with diabetes, glaucoma,

osteoporosis, PUD, renal disease, HF, edema


� Teach patients to gargle and rinse the mouth with water

afterward to prevent the development of oral fungal

infections


Inhaled Corticosteroids:


� Abruptly discontinuing these medications can lead to

serious problems

� If discontinuing, should be weaned for 1 to 2 weeks, only

if recommended by physician


� Report any weight gain of more than 5 pounds a week or

the occurrence of chest pain

http://www.chipola.edu/instruct/health-sciences/PowerPointPresentations/Pharmacology/Chapter_036.p


� Mast cell stabilizers

� Prevent mast cell membranes from opening when allergen bnds to the IgE

� Prevent symptomes of rhinits but not useful during acute episodes

� cromolyn (NasalCrom, Intal)

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� cromolyn (NasalCrom, Intal)

� 1 spray/nostril/4-6x/day

� Use as directed (effectiveness depends on regular use)

� Start therapy 2-4 weeks b4 expected allergy season


Mast Cell Stabilizers:


� For prophylactic use only

� Contraindicated for acute exacerbations

� Not recommended for children younger than age 5

� Therapeutic effects may not be seen for up to 4 weeks


� Teach patients to gargle and rinse the mouth with water afterward to minimize irritation to the throat and oral mucosa




� or Antileukotrienes

� Also called leukotriene receptor antagonists (LRTAs)

� Currently available agents

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� montelukast (Singulair)

� zafirlukast (Accolate)

� zileuton (Zyflo)

� 600mg 4x/day

� Do not take with terfenadine or theophylline – Zyflo increases plasma concentrations of these drugs




� Leukotrine

� Substances in the body that cause inflammation, bronchoconstriction,

and mucus production

� Result: coughing, wheezing, shortness of breath

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� Result: coughing, wheezing, shortness of breath

� Includes:







� 600mg 4x/day

� Do not take with terfenadine or theophylline – Zyflo increases plasma concentrations of these drugs

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concentrations of these drugs


2. Symptomatic therapy; Leukotrine Antagonists


� 20 mg BID

� Take 1 hr b4 or 2 hrs after eating (food

slows absorption of drug)

� There is an increased incidence of URI

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� There is an increased incidence of URI

when co-administered with inhaled

corticosteroids (drug reduced local

inflam and immune response)

� Reduce dose if also taking aspirin

(aspirin increases plasea concentration

of Accolate)


Antileukotrienes: Drug Effects

� Keep bronchial airways relaxed (open)

� Decrease mucus secretion

� Prevent vascular permeability

� Preventing inflammation


� Preventing inflammation


zileuton

Headache

Dyspepsia

Nausea

Dizziness

zafirlukast

Headache

Nausea

Diarrhea

Liver dysfunction

98

Dizziness

Insomnia

Liver dysfunction

• montelukast has fewer side effects

Liver dysfunction



Antileukotrienes:


� Ensure that the drug is being used for chronic management

of asthma, not

acute asthma

� Teach the patient the purpose of the therapy

Improvement should be seen in about


� Improvement should be seen in about

1 week


Antileukotrienes:


� Check with physician before taking any

OTC or prescribed medications—many

drug interactions

� Assess liver function before beginning therapy


� Medications should be taken every night on a continuous

schedule, even if symptoms improve



� Complementary and alternative Therapies

� Aromatherapy

� Possible mechanism of action – competition and desensitization

� Eat unprocessed honey

� Indicated for those who have pollen allergies

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� Indicated for those who have pollen allergies



� AKA:

� Hyposensitization

� Allergy shots

� Indicated when allergens are identified

and cannot be avoided easily

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and cannot be avoided easily

� Immunize with increasing doses of

allergen

� Mechanism of action – competition



� Injection given

� weekly -1st year

� q other week – 2nd year

� q 3-4 wks – 3rd year

� 5 years- recommended course of treatment

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� 5 years- recommended course of treatment

� Or rally

� Sublingual immunotherapy (SLIT)

�


Desensitization or Hyposensitization

�has been effective for a few antigens, particularly bee

venom.

�is designed to cause an IgG response instead of an IgE

response.

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�The allergen is either ingested or injected into the subject

starting in small amounts and increased to larger amounts.


Desensitization or Hyposensitization

�This treatment can have 2 effects:

1. T-helper 1 cells produce more IgG which binds to the

antigen so that it can’t bind to IgE receptors on mast

cells and cause release of histamines. – (Competition)

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2. IgG binds to and removes the antigen before it binds to

T-helper 2 cells. The T- helper 2 cells will then not be

able to produce the B cells that will produce IgE.


Control of Type I Hypersensitivity Reactions

� Epinephrine

� Increases cAMP levels and inhibits degranulation,

� relaxes smooth muscles, increases cardiac output, and decreases

vascular permeability

� Antihistamines

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� Antihistamines

� block the H1 and H2 histamine receptors on cells and

� prevent degranulation


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Type II:

Cytotoxic hypersensitivity

� Antibody-mediated Cytotoxic Hypersensitivity

� Complement-mediated lysis

� Antibody dependent cell-mediated

cytotoxicity (ADCC)

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� cytotoxicity (ADCC)

� Opsonization


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� Hemolytic anemias

� Hemolytic Transfusion Reactions

� Hemolytic Disease of the Newborn

� Drug-Induced Hemolytic Anemia

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� Drug-Induced Hemolytic Anemia


Transfusion Reactions

� Due to antibodies that react with antigens on red blood cells

� Transfused cells are killed by complement-mediated lysis

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ABO Blood Group System

Table 19.2

Hemolytic Disease of the Newborn

Figure 19.4

Hemolytic Disease of the Newborn

� Maternal IgG specific for red blood cell antigens crosses the

placenta and causes lysis.

� The most severe form of the disease, called erythroblastosis

fetalis, develops in an Rh+ fetus carried in an Rh- mother.

Rh is an antigen found on red blood cells.

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� Rh is an antigen found on red blood cells.


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Child with Rh hemolytic disease of the

newborn

� Why is the fetus edematous?

The child has hydrops fetalis. Patients with Rh hemolytic disease have severe anemias, which lead to high output failure and both left and right heart failure, the latter responsible for peripheral edema

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responsible for peripheral edema and ascites. The liver in this fetus had massive hepatomegaly secondary to extramedullary hematopoiesis.


http://www.duke.edu/~ema5/Golian/Slides/5/hematology11_files/Hem282.jpg

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� Brain of the above fetus. What

is causing the yellowish

discoloration?

The yellow pigment is

unconjugated, lipid soluble


unconjugated, lipid soluble

bilirubin derived from

macrophage destruction of the

Rh-sensitized fetal RBCs. The

condition is called kernicterus.

Kleihauer-Betke test in maternal blood post-

delivery

� The mother is O negative

and the baby is O positive.

Who do the normal

colored RBCs belong to

and what should the

mother be given to

� The normal staining cells

contain Hgb F and represent

fetal RBCs, while the pale

staining cells contain Hgb A

from the mother. She should

be given Rh immune

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mother be given to

prevent sensitization?

be given Rh immune

globulin (anti-D) to prevent

sensitization to the D

antigen.


Drug Induced Hemolytic Anemia

� Antibiotics covalently attach to proteins on red blood cells

� Penicillin, cephalosporin, Streptomycin

� This essentially creates a hapten-carrier complex that can

result in a B cell response to the drug

Red-blood cells bound to the drug are killed by

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� Red-blood cells bound to the drug are killed by

complement-mediated lysis


Drug (p=penicillin) modified red blood cells induce the production of antibodies, because the bound drug makes them look foreign to the

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look foreign to the immune system. When these antibodies are bound to them, the red blood cells are more susceptible to lysis or phagocytosis. Onset is dependent on the presence of specific antibodies.


� Symptoms:

� Fever, chills, nausea, clotting within vessels and lower back pain.

� Treatment:

� Stop the transfusion! Or discontinue offending drug

Plasmapheresis

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� Plasmapheresis

� Filtration of plasam to remove specific subtances to remove antibodies

� Symptomatic treatment

� Provide diuretic to increase urine output and reduce buildup of hemoglobin

� For Rh – mother

� Should be given Rh immune globulin (anti-D) or RhoGam


� If mother has not yet been sensitized or exposed to the

Rh+ fetus,

� She will be given an injection of Rh-immune globulin (Rhogam)at

� about 28 weeks of pregnancy,

� and within 72 hours after a birth, miscarriage, abortion, or amniocentesis.

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� and within 72 hours after a birth, miscarriage, abortion, or amniocentesis.

� If receive injection at 28 weeks and after delivery, sensitization will be

prevented and Rh incompatibility should not be a problem during your

next pregnancy.

�


http://www.pregnancy.org/article/rh-incompatibility-and-why-you-need-rhogam?page=1

� The Rh-immune globulin contains antibodies to the Rh D

factor.

� These antibodies will destroy any red blood cells from the baby that

have entered the mother’s blood.

� The mother will not have a chance to form own antibodies to the Rh D

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� The mother will not have a chance to form own antibodies to the Rh D

factor.



� It is important to receive Rh-immune globulin in all cases

when the baby's blood could leak into the mother’s system,

including:

� All pregnancies including ectopic (tubal) pregnancies

� Early miscarriages

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� Early miscarriages

� After chorionic villus sampling

� After amniocentesis



� How Long Will the Effects Last?

� Sensitization usually doesn't happen until after the birth of an Rh-

positive baby.

� Therefore, in most cases Rh incompatibility is not a problem during

a woman's first pregnancy and delivery of an Rh-positive baby.

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a woman's first pregnancy and delivery of an Rh-positive baby.

� However, later pregnancies and deliveries may be affected unless the

mother is treated with Rh-immune globulin after EVERY birth,

miscarriage, and abortion. Sensitization is permanent and the

effects are usually worse with each subsequent pregnancy.



�S E R U M S I C K N E S S

�S L E

Type III:

Immune complex-mediated

hypersensitivity

�R H E U M A T O I D A R T H R I T I S

�A G E

Type III hypersensitivity

� Involve reactions against soluble antigens circulating in

serum.

� Usually involve IgM, IgG antibodies.

� Antibody-Antigen immune complexes are deposited in

organs, activate complement, and cause inflammatory

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organs, activate complement, and cause inflammatory

damage.

� Glomerulonephritis: Inflammatory kidney damage.

� Occurs with slightly high antigen-antibody ratio is present.


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Type III hypersensitivity – immune complex formation

and deposition

Immune complexes of antigen (red dots) and antibody form in target organ

Immune complexes activate complement (green dots- C3a, C4a, and C5a), and mast cells (yellow cell) degranulate.

Inflammation and edema occur, and organ is damaged


Type III hypersensitivity – immune complex formation and

deposition

� In sensitized individuals, allergen (antigen) combined with

antibody leads to the formation of immune complexes,

which activate complement and the inflammatory

response.

The location of the inflammation depends on the location

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� The location of the inflammation depends on the location

of the antigen - inhaled, under skin, systemic.

� Onset is usually within 2-6 hours.


Type III (Immune Complex) Reactions

� IgG antibodies and antigens form complexes that lodge in

basement membranes.

Figure 19.6

Serum sickness

� Group of symptoms that occur after receiving serum or

certain drugs

� Most common causes:

� Penicillin

Other antibiotics

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� Other antibiotics

� Some animal-based drugs

� Less common- vaccines


Serum - does not contain white or red blood cells nor a clotting factor

� s/s

� 7-12 days after receiving the causative agent

� Fever arthralgia (achy joints)

� Rash

� Lymphadenopathy

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� Lymphadenopathy

� Malaise

� Polyarthritis and nephritis


SLE

� Caused by immune-complexes lodged in :

� Vessels(vasculitis)

� Glomeruli (nephritis)

� Joints (arthralgia, arthritis)

� Other organs and tissues

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� Other organs and tissues


Rheumatoid arthritis

� Caused by immune-complexes lodged in joint spaces

followed by destruction of tissue , and later, scarring and

fibrous changes

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Management

� Usually self-limiting

� Symptoms subside after several days


� Antihistamine for itching

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� Aspirin for arthralgia

� Prednisone if severe symptoms


�P P D ( P O S I T I V E P R O T E I N D E R I VA T I V E ) T E S T F O R T B

Type IV:

Delayed Hypersensitivity

�C O N TA C T D E R M A T I T I S

�P O I S O N I V Y R A S H E S

�L O C A L R E S P O N S E T O I N S E C T S T I N G S

�T I S S U E T R A N S P L A N T R E J E C T I O N S

139Type IV hypersensitivity – delayed-type or contact

Antigen (red dots) are processed by local APCs

T cells (blue cells) that recognize antigen are activated and release cytokines

Inflammatory response causes tissue injury.


Antigen is presented by APCs to antigen-specific memory T cells that become activated and

produce chemicals that cause inflammatory cells to move into the area, leading to tissue injury.

Inflammation by 2-6 hours; peaks by 24-48 hours.

Type IV hypersensitivity

� the only type that is not antibody-mediated.

� This is the type involved in

� contact hypersensitivity (poison ivy, reactions to metals in jewelry);

� tuberculin-type hypersensitivity (the tuberculosis skin test);

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� and granulomatous hypersensitivity (leprosy, tuberculosis, schistosomiasis and Crohn’s disease).


� It is called delayed because its onset may vary;

� the length of the delay varies from 72 hours in contact and tuberculin-type to 21-28 days in granulomatous hypersensitivity.

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� In Type IV hypersensitivity, antigen presented by APCs

activates antigen-specific memory T cells (which have

been sensitized by prior exposure), causing them to

release cytokines that activate and attract other T cells and

phagocytic cells to the area. Where the source of antigen

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phagocytic cells to the area. Where the source of antigen

is at the skin surface, the APC migrates from the dermis,

through lymphatic vessels to a lymph node in order to

present antigen to a T cell.


� In the TB skin test, a small amount of soluble antigen

(tuberculin) is injected into the skin.

� The T cells that are activated by the antigen secrete

cytokines that draw other cells to the site.

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� Within four hours, neutrophils have arrived, followed by

an influx of monocytes and T cells at about 12 hours.

� The peak of activity is at about 48-72 hours, at which

point the area has become red and swollen.


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Contact Hypersentivity

� History and physical

examination provide

diagnostic clues

Jelly Fish Hypersensitivity

� In this case, the

erythematous reaction

developed one week

after the contact with a after the contact with a

jelly fish

Acute Graft Rejection is a manifestation of Acute Graft Rejection is a manifestation of

delayed hypersensitivitydelayed hypersensitivity

Fluid Accumulation in Delayed Hypersensitivity ReactionsFluid Accumulation in Delayed Hypersensitivity Reactions

Patch test to identify the allergen for contact

eczema 151

Dendritic cell

Management

� Removal of offending allergen

� Reaction is self-limiting – 5-7 days


� Monitor reaction site and sites distal for circulation adequacy

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� Corticosteroids or other anti-inflam

� Benadryl is not recommended – bcoz histamine is not the main

mediator and IgE is not the cause


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Have an allergy-free day!

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Hypersensitivity disorders cld

Health & Medicine

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