Clinical Challenges in Recognizing, Diagnosing and Treating Anaphylaxis

1. Clinical Challenges in Recognizing, Diagnosing and Treating Anaphylaxis David Elkayam, MD Bellingham Asthma, Allergy & Immunology Bellingham, Washington SNOW Conference, 10 March 2007

2. Goals • Recognize the newer definition of anaphyalxis. • Recognize the difference / similarity between anaphylaxis and anaphylactoid reactions. • Recognize biphasic anaphylaxis. • Optimize treatment: • Initiate tx early • IM v. SC Epi

3. Case Presentation • CK is a 10 yo male who presents to the school nurse’s office. • Onset of sx: ~5-10 mins ago during recess after lunch. • Sx: oropharyngeal and palmar itching  progresses to generalized itching, visible hives and a sensation of mild throat swelling, w/o wheezing, coughing, or obvious respiratory distress. • Pt has Medic Alert Bracelet that identifies him as peanut allergic.

4. Case Presentation • CK : is he in trouble? • What else do you need to know? • VS, PE, PHx: severity of prior rxn? does he have asthma? • What do you do? • Administer Benadryl? • Administer Epi? • How much? • Call 911? • What are the consequences of intervention v. monitoring?

5. Anaphylaxis: Defined • Anaphylaxis is a potentially life-threatening allergic or allergic-like (anaphylactoid) reaction resulting from exposure to a substance to which an individual has become sensitized • Most typically, an immediate systemic reaction caused by rapid, IgE-mediated immune release of potent mediators from mast cells and peripheral blood basophils Lieberman PL. Anaphylaxis. MedGenMed 1(1), 1999 [formerly published in Medscape Pulmonary Medicine eJournal 1(4), 1997]. Available at: http://www.medscape.com/viewarticle/408706.  Accessed July 8, 2005.

6. Anaphylactoid Reaction • Anaphylactoid rxn: non-IgE, otherwise the same pathophysiology/ potential severity. • ASA • Radiocontrast Dye • Some drug reactions

7. Causes of Anaphylaxis www.emnet-usa.org

8. Anaphylaxis – Operational Definition • Two or more organ systems • skin (e.g., hives) • respiratory (e.g., swelling of the lips, tongue, or throat; trouble breathing or shortness of breath; stridor, wheezing) • cardiovascular (e.g., hypotension, dizziness or fainting, altered mental status) • gastrointestinal (e.g., trouble swallowing, abdominal pain) • …or… Hypotension (SBP <100 mmHg) www.emnet-usa.org

9. Incidence of Anaphylaxis Increase between 1991 and 1995 Cause of anaphylaxis 12 Other N=876 Insect venom Food 10 Therapeutic drugs N=671 Unspecified 8 No. of discharges with diagnosis of anaphylaxis/ N=462 100,000 discharges N=415 6 4 2 0 1991-2 1992-3 1993-4 1994-5 Year Sheikh and Alves, BMJ, 2000

10. Incidence of Anaphylaxis Continues to Increase: 1995-1999 Wilson, comment on Sheikh and Alves, BMJ, 2000

11. Anaphylactic Reaction Allergen IgE antibody Mast cell granules Mast Cell Immediate reaction Wheeze Urticaria Hypotension Abdominal cramping Late-phase reaction Phil Lieberman: Anaphylaxis,a clinicians manual

12. Most Frequent Signs and Symptoms of Anaphylaxis ManifestationPercent Urticaria/angioedema 88 Upper airway edema 56 Dyspnea/wheeze 47 Flush 46 Hypotension 33 Gastrointestinal 30 Tang AW. Am Fam Physician 2003

13. Clinical Course of Anaphylaxis

14. Patterns of Anaphylaxis • Uniphasic • Symptoms resolve within hours of treatment • Biphasic • Symptoms resolve after treatment but return between 1 and 72 hours later (usually 1-3 hours) • Protracted • Symptoms do not resolve with treatment and may last >24 hours Lieberman, 2004

15. Uniphasic Anaphylaxis Treatment Initial Symptoms Time 0 Antigen Exposure

16. Biphasic Anaphylaxis Treatment Treatment Second-Phase Symptoms Initial Symptoms 1-8 hours Time 0 Classic Model 1-72 hours Antigen Exposure New Evidence

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

18. Fatal Anaphylactic Reactions Are Often Associated With: • Delay between time of symptom onset and administration of treatment • Adverse therapeutic event • History of asthma • However, most fatal reactions are unpredictable • Appropriate management after recovery from a severe reaction may be protective against a fatal recurrence Pumphrey, Curr Opin Allergy Clin Immunol 2004; Sampson et al, N Engl J Med, 1992; Pumphrey, Clin Exp Allergy, 2000

19. Subsequent Reactions May Increase in Severity with Time % of reactions Proportion of reactions rated severe Simons et al, J Allergy Clin Immunol, 2004

20. Anaphylaxis : Acute Management Overview of the most important aspects of in-office and in-the-field treatments

21. Treatment • Epinephrine is the drug of choice for all anaphylactic episodes • Flexibility in dosing needed to treat effectively • Some patients require more than a single injection • Different doses for pediatrics and adults • Early and aggressive use to maintain airway, blood pressure, and cardiac output

22. Medical Clinic Treatment • Epinephrine • Up to 35% of patents may need a second dose • Antihistamines • Corticosteroids • Oxygen • Impair further absorption • Local epinephrine, tourniquet • Supine, elevate legs • ER, ICU monitor/support (fluids, pressors, etc.) Lieberman PL. Anaphylaxis. MedGenMed 1(1), 1999 [formerly published in Medscape Pulmonary Medicine eJournal 1(4), 1997]. Available at: http://www.medscape.com/viewarticle/408706.  Accessed July 8, 2005.

23. Epinephrine • The most important single medication in the treatment of acute systemic allergic / anaphylactic events. • No strict contraindications • (including metabisulfite sensitivity). • Reverses airway edema and spasm, slows/stops the release of potent vasoactive mediators • (e.g., histamine, etc.), • Potent inotropic and chronotropic cardiac effects • (ie., supports / restores perfusion and BP). • Frequently underutilized.

24. Epinephrine Dosing • Intramuscular injection in lateral thigh produces most rapid rise in blood level • 0.01mg/kg in children, 0.3-0.5mg in adults • Data suggest that as many as 30-35% of patients require more than a single epinephrine injection Korenblat and Day, Allergy Asthma Proc, 1999; Webb et al, J Allergy Clin Immunol, 2004

25. Epinephrine Injection: Route and Site Do Matter Injection route Injection site C-max: mean ± SEM (pg/mL) EpiPen IM Thigh 12,222* ± 3,829 Epinephrine IM Thigh 9,722* ± 4,801 Epinephrine IM Arm 1,821 ± 426 Epinephrine SQ Arm 2,877 ± 567 Saline IM Arm 1,458† ± 444 Saline SQ Arm 1,495† ± 524 *P < .01 from all arm values. †Endogenous epinephrine Simons, et al. JACI 2001;108:871-873.

26. Epinephrine Injection: IM vs. SQ Simons et al.: Prospective, randomized, blinded study in children T-max was 8 ± 2 minutes after injection of epinephrine 0.3 mg from an EpiPen IM in the vastus lateralis vs. 34 ± 14 minutes (range, 5 to 120) after injection of epinephrine 0.01 mg/kg SQ in the deltoid region.

27. Acute Management: Epinephrine Autoinjector

28. Overview of Available Auto-Injectors

29. Overview of Available Auto-Injectors

30. Epinephrine content vs. Time past expiration

31. Case Presentation: CK • Peanut Allergy • Dangerous: most common cause of food allergy related deaths in US. • Added risk factors: • severity of prior event • level of anti peanut sIgE • Presence of asthma • In this setting, treat early, aggressively (injected Epi + other tx’s)

32. Inadequate Management Post ER for Food Anaphylaxis Clark et al, J Allergy Clin Immunol, 2004

33. Anaphylaxis Conclusions • Anaphylaxis is a life-threatening acute reaction which is under-reported, frequently misdiagnosed and under-treated • More common than previously thought; increasing incidence and prevalence • Rapid and proper administration of epinephrine is the standard of treatment • Many patients require a second epinephrine injection to treat anaphylaxis • Patients education needed – delays in treatment, improper administration and outdated epinephrine • Written Action Plan • Medical Alert Bracelet

34. Anaphylaxis: Conclusions & Questions • Prior to this presentation, how aware were you • Of the new practice parameters? • Difference/similarity b/w anaphylaxis and anaphylactoid reactions. • Uniphasic, protracted & biphasic anaphylaxis? • Underutilization of epinephrine in fatal attacks? • 35% of patients may need a second dose?

35. Thank You ! • Questions? • Please feel free to write me at: • David Elkayam, MD • ddelkayam@hinet.org