Luz Fonacier MD, FACAAI, FAAAAISection Head of Allergy

Program Director, Allergy and ImmunologyWinthrop University HospitalProfessor of Clinical Medicine

SUNY at Stony Brook

APPA 41st Annual Convention and Scientific Seminar Newark, New Jersey

August 3, 2013

Drug Allergy and Anaphylaxis:

Conflict of Interest

No conflicts of interest to disclose relevant to this presentation

Educational Objectives:

1.Define and recognize the signs and symptoms of drug allergy and anaphylaxis2.2. Discuss office preparedness and treatment of anaphylaxis in an out-patient practice

Adverse Drug Reaction

Accounts for 2-5% of hospitalized admissions 30% of medical in-patients develop ADR

6-8% of ADRs are allergic

Penicillin Allergy

~ 10% of patients report PCN allergy but after complete evaluation, up to 90% are able to tolerate PCN

Use of alternate broad-spectrum antibiotics in assumed PCN allergic patients may lead to multiple drug-resistant organisms, higher costs, & increased toxic effects

Skin testing patients with PCN allergy leads to reduction in the use of broad-spectrum antibiotics & may decrease costs

PCN skin testing is the most reliable method for evaluating IgE-mediated PCN allergy

The negative predictive value of PCN skin test (major & minor determinants) for immediate reactions approaches 100%

The positive predictive value is between 40% & 100%

Solensk R and. Khan D. Drug Allergy: An Updated Practice Parameter. Annals of Allergy 2010

Cephalosporin in patients with aHistory of penicillin allergy

If PCN (major & minor determinants) skin test negative, patients with possible IgE-mediated reaction (regardless of severity) may receive cephalosporins with minimal concern about an immediate reaction

IF PCN skin test positive (1) administer alternate (non–-lactam) antibiotic (2) administer cephalosporin via graded challenge (3) administer cephalosporin via rapid induction of tolerance

Without PCN skin testing, cephalosporin treatment in patients with a history of penicillin allergy, (selecting out those with severe reaction), show a reaction rate of 0.1%

Solensk R and. Khan D. Drug Allergy: An Updated Practice Parameter. Annals of Allergy 2010

Identical R-group side chains

Patients allergic to amoxicillin should avoid cephalosporins with identical R-group side chains

Cefadroxil Cefprozil Cefatrizine

Patients allergic to ampicillin should avoid cephalosporins & carbacephems with identical R-group side chains

Cephalexin Cefaclor Cephradine Cephaloglycin Loracarbef

Monobactam (aztreonam) does not cross react with other beta-lactams except ceftazidine (identical R-group side chain)

Solensk R and. Khan D. Drug Allergy: An Updated Practice Parameter. Annals of Allergy 2010

Radiocontrast Media Reaction

No association with shellfish allergy Premedication :

Prednisone 50mg 13,7 &1 hour before Diphenhydramine 50 mg PO or IM +/- H2 blockers

High osmolar RCM with premedication Reaction rate decrease from 33% to 4-9%

Low osmolar RCM with premedication Reaction rate decrease to 0.7%

Pseudoallergic and allergic reactions to Aspirin and NSAIDs

(Aspirin Exacerbated Respiratory Disease)

ACE Inhibitors

Cough: ~25% Usually disappear 1-2 weeks after d/c Rare in Angiotensin II receptor inhibitors

Angioedema: 0.1-0.7% (more common in African-Americans)

Most occur > 1 mo. after initiation; Mean (1.8 yrs) Unpredictable recurrences with patterns of relapse &

remissions atypical intubation more likely in relapse

May persist for several weeks after discontinuation

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What Is Anaphylaxis?

(1) Acute onset (min to hours) with involvement of:

Skin/mucosal tissue :hives, generalized itch/flush, swollen lips/tongue/uvula

AND

Airway compromise:dyspnea, wheeze/bronchospasm, stridor, reduced PEF

OR

Reduced BP or associated symptoms collapse, syncope

Sampson HA et al. J Allergy Clin Immunol 2006;117:391-7

Definition of Anaphylaxis

Anaphylaxis is likely when any 1 of 3 criteria are fulfilled

Definition of Anaphylaxis

(2) After exposure to a likely allergen (minutes to hours)

Two or more of the following

• Skin/mucosal tissue (e.g., hives, generalized itch/flush, swollen lips/tongue/uvula)

• Respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, reduced PEF)

• Reduced BP or associated symptoms (e.g., hypotonia, syncope)

• Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting)

Sampson HA et al. J Allergy Clin Immunol 2006;117:391-7.

Definition of Anaphylaxis

(3) After exposure to known allergen for that patient (minutes to hours)

Hypotension• Infants and children: low systolic BP

(age-specific) or >30% drop in systolic BP

• Adults: systolic BP <90 mm Hg or >30% drop from their baseline

Sampson HA et al. J Allergy Clin Immunol 2006;117:391-7.

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Clinical Features of Anaphylaxis

Signs & Symptoms in Anaphylaxis

Webb LM, Lieberman P. Ann Allergy Asthma Immunol 2006;97:39-43

Uniphasic Anaphylaxis

Antigen Exposure

Treatment

Initial Symptoms

0 Time

Biphasic Anaphylaxis

Antigen Exposure

Treatment

Initial Symptom

s

0

Second-Phase

Symptoms

Treatment

1-8 hours

1-72 hours

Time

2nd events• Incidence:1-20%• Onset 1-78 hrs • Most occur w/in 8 hrs• May be fatal• Severity variable• Corticosteroids do not reliably prevent

Protracted Anaphylaxis

Antigen Exposure

Initial Symptoms

0

Possibly >24 hours

Time

How Long To Observe After Anaphylaxis?

8 hr observation would cover most (not all reactions)

Consider 24 hr observation for: Oral administration of antigen Hypotension or laryngeal edema Onset of symptoms > 30 min after antigen Requirement for high doses of epinephrine

All patients discharged should have prescription and education for self-injectable epinephrine

Lieberman P. Ann Allergy Asthma Immunol 2005;95:217-26

“Burden” of Using Self-injectable Epinephrine

Examined possible negative aspects of EpiPen vs. VIT in insect allergic patients

In patients who were positive about EpiPen 59% inconvenient 64% troublesome to carry

22% afraid of side effects of EpiPen 18% “would not dare” use the EpiPen

Elberink JNGO et al. J Allergy Clin Immunol 2006;118:699-704.

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Causes of Anaphylaxis

Idiopathic Anaphylaxis is a Common Cause

Webb LM, Lieberman P. Ann Allergy Asthma Immunol 2006;97:39-43.

Foods Causing Anaphylaxis

Egg Cow's milk Peanuts

Less commonly other legumes soybeans, pinto beans, peas,

green beans, garbanzo Tree nuts

hazelnuts, walnuts, cashews, almonds, pistachios

Fish cod or whitefish

Shellfish shrimp, lobster, crab, scallops,

or oysters Wheat Soy

Fruits banana or kiwi

Seeds cotton seed , sunflower

seed

Burks AW et al. Immunol Allergy Clin N Am 1999;19:533-52.

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Treatment of Anaphylaxis

Key Features of Therapy

• Rapid and aggressive administration with IM epinephrine

• Maintenance of adequate intravascular volume with early and aggressive administration of intravenous fluids

• Other elements of optimal therapy: Delivery of 100% oxygen Rapid transport to a hospital

Acute Treatment Of Anaphylaxis

Early recognition and treatment delays in therapy are associated with fatalities

Assessing the nature and severity of the reaction

Brief history identify allergen if possible

initiate steps to reduce further absorption medications (especially -blockers)

General Therapy supplemental oxygen, IVF, vital signs, cardiac

monitoring Goals of therapy

ABC’s

Body Position in Anaphylaxis

Patients with anaphylactic shock should be kept lying down Legs raised - vena cava is the lowest part of the body Patients already supine should use their epinephrine while

supine

Epinephrine in Anaphylaxis Epinephrine

Drug of choice Best location is IM in the thigh

Adult dose 0.3-0.5 ml (0.3-0.5 mg) of a 1:1,000 dilution IM in

lateral thigh prn q 5-15 min Mechanisms of action

agonist increase BP by peripheral vasoconstriction

-agonist reverse bronchoconstriction positive inotropic & chronotropic activity increases cyclic AMP levels

inhibit further mediator release from mast cells and basophils

Epinephrine self Injectable

Volume Resuscitation

During anaphylaxis 35% of intravascular volume may transfer to extra vascular space in 10 minutes

Saline preferred crystalloid Stays intravascular longer than dextrose No lactate (potentially worsen lactic acidosis)

Adults 5-10 ml/kg in 1st 5-10 minutes

Caution if have CHF Children

Up to 30 ml/kg in 1st hr

Anaphylaxis Practice Parameters J Allergy Clin Immunol 2005;115:S463-518.

Antihistamines In Anaphylaxis

Not a substitute for epinephrine H1-antagonists

useful for cutaneous symptoms H2-antagonists (Ranitidine: 1mg/kg IV

(maximum dose 50mg) evidence favor combination of H1 & H2-

antagonists especially in the presence of hypotension

Secondary Anaphylaxis Therapy

• Glucagon• For refractory hypotension in patients on Beta-Blockers

• Atropine sulfate• Also for patients who are beta blocked• Consider for severe bradycardia

• Albuterol nebulization

• Solumedrol• No role for acute anaphylaxis• May help with concomitant asthma

-Blocked Anaphylaxis

Beta blockade increase release of mediators enhance responsiveness of pulmonary,

cardiovascular, and cutaneous systems to mediators

paradoxical responses to epinephrine bronchoconstriction and bradycardia

unopposed alpha-adrenergic and reflex vagotonic effects

Treatment of Near Fatal Reactions to IT

Delay (or no administration) of epinephrine associated with higher risk of fatal vs. non-fatal reactions (OR 7.3)

Clinical outcomes of subcutaneous vs. intramuscular epinephrine similar

37% non-fatal reactions to IT did not receive systemic steroids or antihistamines without difference in outcome

Amin HS et al. J Allergy Clin Immunol 2006;117:169-75.

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Office Preparedness for Anaphylaxis

Recommended Equipment

Anaphylaxis Practice Parameters J Allergy Clin Immunol 2005;115:S483-523.

Recommended Equipment

Anaphylaxis Practice Parameters J Allergy Clin Immunol 2005;115:S483-523.

Office Preparedness

Develop an emergency plan Practice it regularly

Mock anaphylaxis drills are very helpful After anaphylaxis treatment

Review with staff what went right and wrong Review regularly with staff (especially

new staff) signs and symptoms of anaphylaxis Post warning symptoms for shot patients

Office Preparedness

“Shoot epinephrine first…ask questions later” policy Staff should be comfortable

administering epinephrine prior to your arrival and approval

Rule of thumb: if you would feel hesitant about administering epinephrine to a patient, reconsider giving shots in the office

Office Preparedness

Be familiar with medications and doses

Attach anaphylaxis flow sheets with proper doses to areas where injections given

Assign staff to check crash cart and supplies routinely

Conclusions

Defining anaphylaxis is complex Idiopathic anaphylaxis is the most

common cause History is key to determining an etiology Intramuscular epinephrine in the thigh

treatment of choice Office preparedness requires routine

practice

Myths in Anaphylaxis

Anaphylaxis is always preceded by mild symptoms

There is no need to rush because there is always time to get to a medical facility

Epinephrine is always effective A mild reaction will not progress and will go away Antihistamines are effective by themselves in the

treatment of anaphylaxis