ALLERGIES & BIOLOGICS Colleen Cole, DNP, MSN, MBA, FNP, - - PowerPoint PPT Presentation

ALLERGIES & BIOLOGICS

Colleen Cole, DNP, MSN, MBA, FNP, APRN-BC

Objectives

• To increase understanding allergens
• Understand different types of immunotherapy
• Become aware of why patients may benefit from immunotherapy
• Be aware of which patients may benefit from immunotherapy
• Have a basic understanding of biologics and their use

What is an Allergy?

• An allergic reaction begins in the immune system. If you have an

allergy, your immune system mistakes an otherwise harmless substance as an invader known as an allergen. The immune system

• verreacts to the allergen by producing Immunoglobulin E (IgE)
• antibodies. These antibodies travel to cells starting the reaction that

releases histamine and other chemicals, causing an allergic reaction.

Types of Allergy

Airborne allergy Food allergy Drug allergy Stinging insect allergy Latex allergy

Allergy Facts

Estimated 50 million Americans suffer from nasal allergies Antigens stimulate an abnormal response when entering the body by inhalation, ingestion, or contact Typically develops early in life

80% before age of 20

Factors that determine susceptibility

Genetic background Exposure to allergens Exposure to certain toxins (example: air pollution)

Development

• f Allergies

Step 1

Sensitization – exposure to allergen results àof allergen specific Immunoglobulin (IgE) antibodies. These adhere to circulating basophils or mast cells located in the mucosal surface of the skin, GI tract, or respiratory tract.

Development of allergen hypersensitivity is a two-step process

• The release of mediators from activated mast cells and basophils are

responsible for allergic symptoms in sensitive individuals.

Development

• f Allergies

Step 2

• Allergic reaction that occurs with additional

exposure to the allergen. Allergen reacts with the cell-bound specific IgE, causing chemical mediators such as histamine, leukotrienes, and prostaglandins to be released.

The release of mediators from activated mast cells and basophils are responsible for allergic symptoms in sensitive individuals.

What Intensifies Allergen Reactions?

• Clinical response intensified by several factors:
• Length of time exposed to an allergen
• Exposure to an allergen through the mouth
• Exposure to an allergen after ingesting alcohol
• Exposure to an allergen after strenuous activity
• Exposure to multiple allergens on the same day

GETTING A DIAGNOSIS

Clinical history Physical examination Confirmatory lab & skin testing

Testing

• Skin test preferred over Radioallergosorbent testing, or RAST testing,
• RAST test were formerly the go-to blood test for helping to diagnose an allergy. However,

newer allergy blood tests are now available.

• ImmunoCAP testing is a more common allergy blood testing specific IgE
• Typically wait for full aeroallergy panel skin testing until individual is 6 years of age
• Blood work CBC with diff, IgE, IgG, IgA, IgM
• Prior to skin testing patient must be off certain medications (if possible) that could

potentially lead to false negative results – histamines, steroids, leukotriene inhibitors.

• If unable to stop testing proceed with above blood test (RAST/ImmunoCAP) preference.

IgA, IgG, IgM, IgE

• IgA. IgA antibodies are found in areas of the body such the nose, breathing passages, digestive tract, ears, eyes,

and vagina. IgA antibodies protect body surfaces that are exposed to outside foreign substances. This type of antibody is also found in saliva, tears, and blood. About 10% to 15% of the antibodies present in the body are IgA

• antibodies. A small number of people do not make IgA antibodies.
• IgG. IgG antibodies are found in all body fluids. They are the smallest but most common antibody (75% to 80%)
• f all the antibodies in the body. IgG antibodies are very important in fighting bacterial and viral infections. IgG

antibodies are the only type of antibody that can cross the placenta in a pregnant woman to help protect her baby (fetus).

• IgM. IgM antibodies are the largest antibody. They are found in blood and lymph fluid and are the first type of

antibody made in response to an infection. They also cause other immune system cells to destroy foreign

• substances. IgM antibodies are about 5% to 10% of all the antibodies in the body.
• IgE. IgE antibodies are found in the lungs, skin, and mucous membranes. They cause the body to react against

foreign substances such as pollen, fungus spores, and animal dander. They are involved in allergic reactions to milk, some medicines, and some poisons. IgE antibody levels are often high in people with allergies.

• https://www.uofmhealth.org/health-library/hw41342

Diagnosis IgE Mediated Disorders

Allergic rhinoconjunctivitis Urticaria Angioedema Asthma Gastrointestinal allergies –Eosinophilic esophagitis Atopic dermatitis Oral allergy syndrome Anaphylaxis

Atopic Dermatitis

• Atopic dermatitis is an eczematous eruption

associated with asthma and allergic rhinitis

• Occurs in 10% to 20% of children and 1% to 3%
• f adults
• Est. 50% and 80% of children who have atopic

dermatitis later develop asthma and/or allergic rhinitis as a progression known as the atopic march

• Immunotherapy has proven to be beneficial in

these patients

Atopic Dermatitis

• Several features suggests classification as an

atopic disorder including the following:

• Family history of allergic rhinitis and asthma
• Elevated levels of serum IgE
• Eosinophilia
• Frequent hypersensitivity to environmental

allergens

Airborne Allergy

• Indoor Allergens
• House Dust mites
• Cockroaches
• Molds
• Rodents
• Animal Dander
• Outdoor Allergens
• Pollens
• Molds

Food Allergy

Tree nuts Peanuts Wheat Soy Eggs Fish, shellfish Fruit Vegetables spices

Food Allergy vs. Food Intolerance

• Food allergy is NOT the same as food intolerance.
• Food allergy occurs in susceptible person who was previously sensitive to a particular food
• allergen. Symptoms may include pruritis, urticaria, angioedema, wheezing, airway obstruction,

nauseas, vomiting, abdominal cramping, diarrhea, nasal congestion, and in severe cases anaphylaxis.

• Food intolerance may be an adverse response to food that is NOT based on immunologic
• mechanisms. For example milk “allergy” or intolerance can exist because of immunologic reaction

to a protein in milk where the person lacks an enzyme that digest lactose.

• Non-allergic food-induced disorders such as celiac disease and lactose intolerance have

significantly different pathophysiology mechanisms

Oral Allergy Syndrome

Symptoms of the mouth and throat Symptoms include difficulty swallowing comment and/or an itchy or burning sensation of the tongue or throat Persons who are allergic to certain pollens may experience this syndrome when they consume certain raw fruits or vegetables Example individual may be allergic to Birch and experience symptoms when they eat apples from their cherries, celery, peaches, pears, or hazelnuts

Oral Pollen Allergy Syndrome

Drug Allergy

Occur between 8 – 15 per 100 hospital admissions annually Antibiotics & anti-inflammatory drugs most common

Stinging Insect Allergy

Vespids (yellow jacket, hornet, wasp) Apids (honeybee, bumblebee) Formicidae (fire ant) Affects 0.3% to 3% of people in US Causes 40 deaths per year

Latex Allergy

Symptoms from minor dermatitis to anaphylaxis Demonstration of IgE sensitivity confirms dx BUT lack of IgE does NOT rule it out Symptoms may occur on skin, resp, eyes, GI & GU.

Latex Allergy Cross- Reactivity

Allergy Treatment

Avoidance Pharmacotherapy Allergy immunotherapy

Immunotherapy History

• Various forms of allergy treatments have been tried over last century from
• ral drops, nasal inhalations, powders, tablets, to injections
• Early 20th century – allergy drops
• 1911 Leonard Noon and John Freeman discovered hypodermic inoculations
• Second ½ of 20th century SCIT became widely utilized in the world
• 1970 Hymenoptera venom therapy proven safe & effective
• 2014 SLIT – Difficult to obtain insurance coverage at this time

What About Immunotherapy?

• Raises the patient's tolerance to specific

allergens

• Vials are made specific to the allergens that

the patient tests positive

• Immunotherapy is typically given over 3-5

years

• Goal is to halt or minimize allergic disease

symptoms

• Patient receives 1st dose from each new vial

in the allergist office. May receive following doses from that vial at PCP IF PCP agrees and is prepared to administer care for potential anaphylaxis post injection and follows administration protocols for potential injection site reactions

Summary of Safety SCIT vs SLIT

• SCIT
• Rare systemic reactions (3/1000 injections)
• Rare fatalities (1/2.5M injections- declining)
• Frequent local reactions
• Erythema/pruritus/swelling- injection site
• SLIT
• Rare systemic reactions
• Specific administration on taking medication sublingal
• No known fatalities
• Frequent local reactions
• Erythema/Pruritus/edema- mouth, lips, tongue, upper airway

FDA Approved SLIT Products (Sublingual Tablets)

Product Dose (daily) Schedule Age Ragwitek MSD 4/17/14 Ragweed 12 Amb a 1 Units 12wks pre/co-seasonal 18-65 Grastek MSD 4/11/14 Timothy 2800 BAU 12wks pre/co-seasonal 5-65 Oralair Stallergenes 4/1/14 Sweet Vernal, Orchard, Perennial Rye, Timothy, and Kentucky Blue 300 IR (~9000 BAU) 16wks pre/co-seasonal (10-17yo 3d build to 300IR) 10-65 Odactra MSD 12 Dustmite Daily year round 18-65

Subcutaneous Immunotherapy

Why Immunotherapy?

• Failed traditional avoidance & RX management
• Poor symptom control
• Goal Long-term, permanent/reduction of

symptoms through direct action on the immune system.

• Decreased levels of specific IgE antibodies
• Increased levels of regulatory T cells
• Decreased histamine release
• Decreased release from basophils

Allergen Immunotherapy Indications

• Indicated for management of IgE

mediated disorders:

• Allergic rhinoconjunctivitis/Rhinitis
• Allergen-induced asthma
• Atopic dermatitis
• Hymenoptera and fire ant

hypersensitivity

Allergen Immunotherapy in Special Populations

• Effective and often well tolerated
• Should be considered along with

pharmacotherapy and allergen avoidance for AR, asthma & insect allergy Children

• Allergen immunotherapy can be continued
• Doses are not increased and sometimes

reduced

• Usually not initiated in the pregnant patient

Pregnant patients

Adapted from Cox L, Li JT. Nelson H and Lockey R. Allergen Immunotherapy. A Practice Parameter Second Update. J Allergy Clin Immunology. 2007; 120 (3): S25-85.

Contraindications

Comorbid conditions

• uncontrolled asthma
• markedly compromised lung function (chronic or acute)
• unstable angina or recent MI
• significant arrhythmia
• uncontrolled hypertension
• failure of a major organ system

Concomitant medications (considerations > contraindications)

• Beta blockers (relative for AIT, less so for needed VIT)
• Possibly ACE Inhibitors

**Need for individualized risk/benefit analysis (i.e. VIT vs AIT)

Immunotherapy: Treatment Schedules

• Although there are different

schedules which may include “rush” schedules, the typical build up schedule is immunotherapy

• nce to twice per week.
• Maintenance is once per week à
• nce every other weekà and finally
• nce per month.

Discontinuing Immunotherapy

• No specific tests to determine when SCIT should be

discontinued

• Response to SCIT should be evaluated periodically and

discontinuation should be considered after 3-5 years

• Discontinuing venom immunotherapy is based on severity of

initial reaction, reactions during therapy, and duration of treatment

Cox L et al. Allergen immunotherapy: A practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1-55.

Education

• If the patient has a “knot” type reaction or swelling 24 hours after injection it is important

to notify or follow the allergist protocol. A reduction in dose may be necessary.

• Patient education is very important!
• Example:
• Number to call for problems
• Reporting adverse reactions
• What is anaphylaxis
• No upper body or vigorous exercise day of injection
• How to use EpiPen or Auvi Q or similar epinephrine device

Fatal Reactions (FR) from Immunotherapy

• 24 FRs between 1945 - 1984 in retrospective review
• 15 immunotherapy-related FRs between 1985 and 1989 and

estimated 1 fatality in every 2.0 million injections

• Recently, immunotherapy fatality survey documented 41 FRs between

1990 and 2001

• Collectively, 1 FR in approx. 2.5 million injections (.0004%) prior to

2002; rates may be lower in recent years4

1. Bernstein DI, Wanner M, Borish L, Liss GM. J Allergy Clin Immunol 2004;113:1129-36. 2. Amin HS, Liss GM, Bernstein DI. J Allergy Clin Immunol 2006; 117:169-75. 3. Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC. J Allergy Clin Immunol 79:660 677, 1987. 4. Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. Ann Allergy Asthma Immunol. 2016 Apr;116(4):354-359.e2

Allergen Immunotherapy: Systemic Reactions

• Temporally related signs and symptoms can include:
• Skin reactions including itch, hives, swelling, flushing
• Constriction of airways (upper or lower airways)
• Nasal and ocular pruritis and injection
• Feeling of warmth or impending doom
• Swelling of tongue or throat
• Nausea, vomiting, diarrhea, or abdominal symptoms
• Dizziness, fainting, weak and rapid pulse
• Onset usually rapid, with majority occurring within 30 minutes, although

delayed reactions can occur (14-50% of reactions)1

• Incidence (< .05% to 3.5% of injections)

1Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. Annals Allergy Asthma Clin Immunol. 2011 Nov; 107(5);

426-431.e1

Allergen Immunotherapy: Local Reactions

• Local reactions: redness, swelling and heat at injection site
• Not uncommon occurrence
• Large local reactions are not necessarily predictive of future

systemic allergic reactions

• If persistent large local reaction, consider:
• Cool compress, pre-medication with H1 blockers, temporary dose

adjustment especially if frequent large local reactions

Roy SR. et. al. Ann Allergy Asthma Immunol. 2007 Jul;99(1):82-6.

Adverse Event Reduction Measures

• Pre-injection assessment
• Asthma (Resp symptoms

check, Peak Flow)

• Other medical conditions
• Appropriate 1st dose for

increased sensitivity

• 30-minute wait
• Educate patient on S/S of

systemic reactions

• Report immediately
• Report delayed sx’s
• Procedures to avoid

clerical/nursing errors

• Vial & patient identifiers
• Color-coded vials
• Reduced dose
• New vials
• Schedule interruptions
• Understand Protocol

from Allergist office

Adapted from Cox L et al. Allergen immunotherapy: A practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1-55.

• Epinephrine is your #1 go to drug for anaphylaxis
• H1 antihistamines: diphenhydramine IM or IV
• Adults: 25 to 50 mg
• Children: 1-2 mg/kg
• H2 blockers PO or IV
• (cimetidine, ranitidine, famotidine)
• Oxygen and bronchodilators
• Possible Glucagon in those on betablockers
• Intravenous fluids or vasopressors as needed for vascular collapse
• Depending on reaction, consider PO or IV steroids

Medications for Treatment of Anaphylaxis

Allergen Extract Dilutions

Immunotherapy Summary

• Takes 3-5 years for effective results
• Immunotherapy typically is given twice a

week initially.

• After 6-8 months may be reduced to once a

week ->once every other week -> once monthly.

• Patients encouraged to continue

antihistamines and/or Singulair

• Must observe patient for 30 minutes

following injection(s)

• Patients should know how to administer

epinephrine/Auvi-Q for anaphylaxis.

Summary Risks of Immunotherapy

• Local reactions, which can involve redness, swelling or irritation at the

injection site. These common reactions typically begin within a few hours of the injection and clear up soon after.

• Systemic reactions, which are less common — but potentially more
• serious. You may develop sneezing, nasal congestion or hives. More-severe

reactions may include throat swelling, wheezing or chest tightness.

• Anaphylaxis is a rare life-threatening reaction to allergy shots. It can cause

low blood pressure and trouble breathing. Anaphylaxis often begins within 30 minutes of the injection, but sometimes starts later than that. **Individuals who receive injections routinely (weekly-monthly) are less likely to have a reaction

BIOLOGICS

Biologics

• Dupixent-Dupilumab
• Fasenra-Benralizumab
• Nucala-Mepolizumab
• Cinqair-Resilzumab
• Xolair- Omalizumab – Only Anti-IgE

Biologics/Immunomodulators

• These treatments include a variety of vaccines, blood components and

proteins that are either derived from natural sources or are synthesized in the laboratory.

• Treatment options for respiratory and dermatologic diseases have

considerably improved over the last 10 years

• Most promising biologic therapies target IgE, Interleukin (IL)-4, IL-5, &

IL-13

• This review will focus on monoclonal antibodies for asthma comment

nasal polyps, urticaria, reduce IgE, & atopic dermatitis

Purpose

• EOSINOPHILIC ASTHMA- Xolair, Nucala, Cinqair, Fasenra, and Dupixent –

with several others currently in development.

• ATOPIC DERMATITIS – Dupixent
• CHRONIC IDIOPATHIC URTICARIA – Xolair
• NASAL POLYPOSIS WITH ALLERGIC RHINITIS – Dupixent
• EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA) - Nucala

Eosinophilic Asthma

Eosinophils are white blood cells that are a normal part of the immune system but can also cause lung inflammation. Nearly 7 out of 10 adults with asthma may have elevated eosinophils, which can be a key cause of

• asthma. Active eosinophils in the lungs can inflame the airways.

While not well defined for severe asthma, elevated blood eosinophils were considered 150 cells/μL or more in this analysis of registry data.

Dupixent

• Human monoclonal antibody of the IgG4 subclass
• Inhibits IL-4 and IL-13 signaling
• Atopic Dermatitisà ages 6+
• Moderate-to-severe eosinophilic or oral steroid

dependent asthmaà ages 12+

• Chronic Rhinosinusitis with Nasal Polyposis

(CRSwNP)à ages 18+

Fasenra

• Eosinophilic Asthmaà ages 12+
• Binds to IL-5 alpha on eosinophils
• Within 24 hours à Near complete depletion
• f blood eosinophils

Nucala

EOSINOPHILIC ASTHMA AGES 6+ EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA), ADULTS

Xolair

• Monoclonal antibody
• Anti-IgE - binds to IgE thus preventing IgE from binding to mast

cells and basophils

• Asthmaà IgE level and weight based, Age 6+
• Chronic Idiopathic Urticariaà Not IgE/weight based, Age 12+
• 75 – 375 mg SQ every 2-4 weeks

Xolair

A skin or blood test is performed to test for aeroallergens Added to step 5 of the 2017 global Initiative for Asthma guidelines stepwise approach for asthma therapy in place of or in addition to oral glucocorticoids Currently, there are no definitive recommendations for length of treatment. Revaluation of patient ‘s asthma should be performed around 16 to 24 weeks.

Xolair

The only biologic to have a black box warning Must be given in the office Patients must be monitored an appropriate amount of time in office following injection(s). 1st & 2nd dose 2 hours. Potential evidence of cardiovascular and cerebrovascular risks

Cinqair reslizumab 100mg/10ml

• CINQAIR à18 years of age+
• Typically given outpatient as infusion
• Severe asthma
• Pro – can be given for obese
• Reduces blood eosinophils.

Biologic Adverse Reactions

• Hypersensitivity – generalized urticaria, rash, erythema nodusum and serum

sickness.

• Conjunctivitis and Keratitis – more frequently reported
• Eosinophilic conditions
• Bronchospasms
• Anaphylaxis – Xolair black box warning
• Must test/treat parasitic (Helminth) infections prior to treatment

Biologic Summary

• Biologics play a large role in reduction of eosinophilic asthma, nasal

polyps, chronic idiopathic urticaria, atopic urticaria, and elevated IgE.

• May options for patient to receive in office, at home, or at infusion center

depending on medical illness.

• Have demonstrated to show great improvement in improving quality of

life for patients.

• Acceptable dosing are from age range from 6 years and up depending

upon the drug recommendation

Sources

Amin HS, Liss GM, Bernstein DI. J Allergy Clin Immunol 2006; 117:169-75. Bernstein DI, Wanner M, Borish L, Liss GM. J Allergy Clin Immunol 2004;113:1129-36. Cox L et al. Allergen immunotherapy: A practice parameter third update. J Allergy Clin Immunol. 2011;127(1 Suppl):S1-55. Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. Annals Allergy Asthma Clin Immunol. 2011 Nov; 107(5); 426-431.e1 Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. Ann Allergy Asthma Immunol. 2016 Apr;116(4):354-359.e2 Greineder, D. J Allergy Clin Immunol 1996;98:S330-4 Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC. J Allergy Clin Immunol 79:660 677, 1987. Middleton 8th Edition Practice Parameters 3rd JACI 2011 Roy SR. et. al. Ann Allergy Asthma Immunol. 2007 Jul;99(1):82-6. Stallergenes Greer Allergy Immunotherapy Compendium https://www.uofmhealth.org/health-library/hw41342