Download Slide 1

APPA 41st Annual Convention and Scientific Seminar
Newark, New Jersey
August 3, 2013
Drug Allergy and Anaphylaxis:
Luz Fonacier MD, FACAAI, FAAAAI
Section Head of Allergy
Program Director, Allergy and Immunology
Winthrop University Hospital
Professor of Clinical Medicine
SUNY at Stony Brook
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 anaphylaxis
2. 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 IgEmediated 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 a
History 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




Patients allergic to ampicillin should avoid cephalosporins &
carbacephems with identical R-group side chains






Cefadroxil
Cefprozil
Cefatrizine
Cephalexin
Cefaclor
Cephradine
Cephaloglycin
Loracarbef
Monobactam (aztreonam) does not cross react with other betalactams 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 :




High osmolar RCM with premedication


Prednisone 50mg 13,7 &1 hour before
Diphenhydramine 50 mg PO or IM
+/- H2 blockers
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 AfricanAmericans)



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
What Is Anaphylaxis?
14
Definition of Anaphylaxis
Anaphylaxis is likely when any 1 of 3 criteria are fulfilled
(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
(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 (agespecific) 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.
Clinical Features of
Anaphylaxis
18
Signs & Symptoms in Anaphylaxis
Webb LM, Lieberman P. Ann Allergy Asthma Immunol 2006;97:39-43
Uniphasic Anaphylaxis
Treatment
Initial
Symptoms
0
Antigen Exposure
Time
Biphasic Anaphylaxis
Treatment
Initial
Symptoms
Treatment
1-8 hours
SecondPhase
Symptoms
Time
0
Antigen
Exposure
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
1-72 hours
Protracted Anaphylaxis
Initial
Symptoms
0
Antigen
Exposure
Time
Possibly >24 hours
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.
Causes of Anaphylaxis
25
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


Tree nuts



cod or whitefish
Shellfish


hazelnuts, walnuts, cashews,
almonds, pistachios
Fish


Less commonly other legumes
 soybeans, pinto beans, peas,
green beans, garbanzo
shrimp, lobster, crab, scallops, or
oysters
Wheat
Soy
Burks AW et al. Immunol Allergy Clin N Am 1999;19:533-52.

Fruits


banana or kiwi
Seeds

cotton seed , sunflower
seed
Treatment of
Anaphylaxis
29
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



medications (especially -blockers)
General Therapy


initiate steps to reduce further absorption
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



Adults


Stays intravascular longer than dextrose
No lactate (potentially worsen lactic acidosis)
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.
Office Preparedness for
Anaphylaxis
40
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


After anaphylaxis treatment


Mock anaphylaxis drills are very helpful
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