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Luz Fonacier MD, FACAAI, FAAAAI Section Head of Allergy Program Director, Allergy and Immunology

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

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Luz Fonacier MD, FACAAI, FAAAAI Section Head of Allergy Program Director, Allergy and Immunology

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  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

  2. Conflict of Interest • No conflicts of interest to disclose relevant to this presentation

  3. Educational Objectives: • Define and recognize the signs and symptoms of drug allergy and anaphylaxis • 2. Discuss office preparedness and treatment of anaphylaxis in an out-patient practice

  4. Adverse Drug Reaction • Accounts for 2-5% of hospitalized admissions • 30% of medical in-patients develop ADR • 6-8% of ADRs are allergic

  5. 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

  6. 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

  7. 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

  8. 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%

  9. Pseudoallergic and allergic reactions to Aspirin and NSAIDs (Aspirin Exacerbated Respiratory Disease)

  10. 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

  11. What Is Anaphylaxis?

  12. Definition of Anaphylaxis Anaphylaxis is likely when any 1 of 3 criteria are fulfilled Sampson HA et al. J Allergy Clin Immunol 2006;117:391-7

  13. 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.

  14. Definition of Anaphylaxis (3) After exposure to known allergenfor 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.

  15. Clinical Features of Anaphylaxis

  16. Signs & Symptoms in Anaphylaxis Webb LM, Lieberman P. Ann Allergy Asthma Immunol 2006;97:39-43

  17. Uniphasic Anaphylaxis Treatment Initial Symptoms Time 0 Antigen Exposure

  18. Biphasic Anaphylaxis • 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 Treatment Treatment Second-Phase Symptoms Initial Symptoms 1-8 hours Time 0 1-72 hours Antigen Exposure

  19. Protracted Anaphylaxis Initial Symptoms 0 Time Possibly >24 hours Antigen Exposure

  20. 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

  21. “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.

  22. Causes of Anaphylaxis

  23. Idiopathic Anaphylaxis is a Common Cause Webb LM, Lieberman P. Ann Allergy Asthma Immunol 2006;97:39-43.

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

  25. Treatment of Anaphylaxis

  26. 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

  27. 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

  28. 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

  29. 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

  30. Epinephrine self Injectable

  31. 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.

  32. 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

  33. 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

  34.  -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

  35. 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.

  36. Office Preparedness for Anaphylaxis

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

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

  39. 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

  40. 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

  41. 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

  42. 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

  43. 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

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