luz fonacier md, facaai, faaaai section head of allergy program director, allergy and immunology
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APPA 41 st 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 - PowerPoint PPT PresentationTRANSCRIPT
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