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Hypersensitivity Disorders Allergic Emergencies

Hypersensitivity Disorders Allergic Emergencies. Jim Holliman, M.D., F.A.C.E.P. Professor of Military and Emergency Medicine Uniformed Services University of the Health Sciences Clinical Professor of Emergency Medicine George Washington University Bethesda, Maryland, U.S.A.

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Hypersensitivity Disorders Allergic Emergencies

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  1. Hypersensitivity Disorders Allergic Emergencies Jim Holliman, M.D., F.A.C.E.P. Professor of Military and Emergency Medicine Uniformed Services University of the Health Sciences Clinical Professor of Emergency Medicine George Washington University Bethesda, Maryland, U.S.A.

  2. Hypersensitivity Disorders & Allergic Emergencies : Lecture Objectives • Describe & compare : • Anaphylaxis & anaphylactoid reactions • Angioneurotic edema • Drug allergies • Describe emergent Rx & followup outpatient Rx for anaphylactic & other allergic reactions

  3. Allergic Reactions Definitions of Terms • Anaphylaxis (Greek = "backward protection") • Rapid generalized immunologic reaction after exposure to antigens in a sensitized person, with at least 2 of : • resp. or airway compromise from swelling or wheezing • hypotension or cardiovascular collapse • diffuse cutaneous findings (urticaria, angioedema, +/- erythroderma)

  4. Allergic Reactions Definitions of Terms (cont.) • Anaphylactoid reaction : • Syndrome presenting similar to anaphylaxis, expressed by similar mediators, but not triggered by IgE & not necessarily due to prior exposure to the inciting agent • Urticaria : • Diffuse patchy erythematous pruritic rash with raised borders • Angioedema : • Non-pitting subcutaneous tissue swelling • Often of the face, mouth, or peri-airway tissue

  5. Pathophysiology of Allergic Reactions • Mast cell • Final common pathway of all allergic reactions • Present in most tissues • When activated, release (from cell granules) : • Histamine • Bradykinins • Prostaglandins • Leukotrienes • Clinical effects are due to these above mediators

  6. Four Mechanisms that Lead to Mast Cell Degranulation (Release of Mediators) • Immunoglobulin E (IgE) mediated hypersensitivity • Complement cascade activation • Direct stimulation of mast cell by anaphylactoid substances • Inhibition of arachidonic acid pathway

  7. Sequence of Events in IgE Mediated Hypersensitivity Reactions • 1. Initial exposure to allergen • 2. IgE antibody produced in reponse to allergen • 3. Re-exposure of patient to same allergen • 4. Preformed IgE cross links on mast cell surface • 5. Mediators (esp. histamine) released by mast cell

  8. Histamine Receptors • 3 types with the following effects when stimulated : • H1 : brochoconstriction, vascular permeability, smooth muscle contraction • H2 : gastric acid secretion, cardiac chronotropy & inotropy • H3 : inhibition of histamine formation & release

  9. General Clinical Effects of Release of Allergic Mediators • Mucocutaneous : • pruritis, flushing, erythema, urticaria, angioedema • Respiratory : • upper airway angioedema • bronchoconstriction • pulmonary hyperinflation +/- pulm. edema • Cardiovascular : • vasodilatation, increased vascular permeability, intravascular volume depletion, vasogenic shock, myocardial contractile dysfunction • Gastrointestinal : • cramping, vomiting, diarrhea

  10. Causes of Anaphylactic and Anaphylactoid Reactions • IgE mediated allergies : • Beta lactams, hymenoptera stings, food, latex • Direct mast cell degranulation : • Xray contrast media, opiates, mannitol, neuromuscular blockers • Altering bradykinin metabolism : • angiotensin converting enzyme (ACE) inhibitors • Affecting metabolism of arachidonic acid : • aspirin, NSAID's

  11. Considerations About Beta Lactam Antibiotic Allergies • Penicillin is most common cause • Incidence of hypersensitivity about 4 % • Anaphylaxis in 1 per 10,000 administrations • 100 to 500 deaths per year in U.S. • Co-reactivity with cephalosporins < 5% • Can undergo desensitization process but risky and many alternative antibiotics now available • Can occur from topical exposure (mother preparing antibiotic suspension for child)

  12. Considerations About Allergy to Hymenoptera Stings • Hymenoptera include bees, wasps, ants • Mostly cause local allergic reactions • 10 % have regional swelling • 1 % have anaphylaxis • Causes 40 to 50 deaths per year in U.S. • Content of venom variable so re-sting may not cause same reaction as before • F/U with allergist for desensitization Rx always recommended for systemic reaction

  13. Treatment of Allergic Reactions from Hymenoptera Stings • If local reaction only : • Ice pack, pain med, diphenhydramine PO • Watch at least 30 minutes to be sure systemic reaction does not occur • If systemic reaction : • O2, epi, IV fluid bolus, IV diphenhydramine, IV steroids, observe at least 4 hours • For both types : • Check sting site & remove stinger if imbedded (scrape, don't squeeze), update tetanus, consider antibiotic if ? cellulitis

  14. Considerations About Allergic Reactions to Foods • Most commonly due to : • legume vegetables (peanuts, soybeans, peas, beans) • crustaceans • mollusks • cow's milk • eggs (may also react to MMR vaccine) • nitrites or sulfite preservatives in foods • Must differentiate seafood allergy from scombroid poisoning (due to ingestion of spoiled fish containing histamine)

  15. Considerations About Latex Allergy • An increasingly recognized recent problem • Can result in fatal anaphylaxis • High incidence in pts. with spina bifida & congenital urologic problems • Be careful to select non-latex gloves & catheters for pts. with this allergy

  16. Allergic Reactions to Radiocontrast Media • Occur in 1 % of cases • 10 % of occurences are severe • About 500 ( ? ) fatal reactions in U.S. annually • Risk factors : • prior reaction (30 % recurrence rate) • advanced age • renal or hepatic dysfunction • asthma

  17. Allergic Reactions to Radiocontrast Agents (cont.) • High osmolarity agents (Hypaque, Renografin, Conray) • Tri-iodinated, ionic • Low osmolarity agents : • non-ionic dimers • produce less histamine release & less vascular endothelial irritation • Much more expensive (5 X) • Recent reports show reduction in complications of contrast studies using these agents, but reactions still occur in 30%

  18. Allergic Reaction Prophylaxis for Radiocontrast Agent Use • Pretreatment reduces recurrent allergic reaction rate to 1% • One suggested regimen : • Hydrocortisone 200 mg IV just prior to & 4 hours after contrast, & cimetidine 300 mg IV & diphenhydramine 50 mg IV just prior to contrast • Should have epi & resus. equipment available • Pre-Rx indicated for pt. requiring a contrast study with prior Hx of reaction or renal dysfunction

  19. Angioedema Due to ACE Inhibitors • Occurs in 0.2 % of pts. on ACE inhibitors • Can occur even after prolonged use of ACE inhibitors without a prior reaction • Predeliction for head & neck angioedema so airway compromise possible • Rx by stopping the ACE inhibitor, epi, steroids, diphenhydramine, +/- airway management

  20. Severe angioedema

  21. Same patient on prior slide after treatment

  22. Spectrum of Presentations of Allergic Reactions • Time to onset, intensity, & duration of reaction vary, depending on : • degree of sensitivity of pt. • route of exposure • amount ("dose") of antigen • Rarely pts. may have "biphasic" reaction with reexacerbation of Sx 4 to 8 hours after the initial reaction

  23. Clinical Manifestations of Systemic Allergic Reactions • Diffuse pruritis, urticaria, angioedema, erythroderma • Anxiety, dizziness, sense of doom, altered mental status • Dyspnea, stridor, wheezing • Dysphagia, dysarthria, drooling • Vomiting, diarrhea, abd. cramps • Urinary incontinence • Hypotension +/- bradycardia

  24. Differential Dx of Severe Allergic Reaction • Sudden loss of consciousness : • vasovagal syncope, seizures, dysrhythmias, CVA • Acute respiratory distress : • status asthmaticus, upper airway infection, foreign body aspiration, pulm. embolus • Cardiovascular collapse : • intraabdominal bleed, acute MI • Systemic disorders : • mastocytosis, hereditary angioedema (C1 esterase deficiency syndrome) , carcinoid syndrome, scromboid poisoning, MSG syndrome

  25. E.D. Management of Systemic Allergic Reactions • Since may progress rapidly & unpredictably, all pts. with possible systemic reaction should be rapidly triaged to acute care room & continuously monitored • Suggested initial sequence : • O2 / airway management • SQ or IM epi (0.01 mg/kg or max. 0.3 mg in adults) • IV placement ; IV fluid bolus (NS) if hypotensive • IV diphenhydramine & IV steroids • Beta 2 aerosol if wheezing • Secondary meds ; consider repeat epi doses • Remove source of reaction if possible • Give IV fresh frozen plasma if hereditary angioedema from C1 esterase deficiency

  26. Airway Management Considerations for Severe Allergic Reactions • Swelling impinging the airway may progress rapidly so earlier intubation more likely successful than later • Consider sedation without paralysis if anticipated difficulty • Start with ETT size one size smaller than usual • Have surgical airway equipment at bedside • Place nasal airway early even if ETT not initially required • Consider use of inhaled racemic epi

  27. The Key Med in Rx of Allergic Reactions : Epinephrine (epi) • Is the most important & effective Rx med • Alpha agonist effects : • Vasoconstriction, decreased vascular permeability, resolution of angioedema • Beta agonist effects : • Bronchodilatation, cardiac inotropy, mast cell membrane stabilization

  28. Potential Complications of Use of Epi for Allergic Reactions • Hypertension (may cause CNS bleed) • Increased myocardial O2 consumption • Coronary vasoconstriction • Tachycardia / dysrhythmias In pts. who have HBP, CAD, CVA, or pregnancy, should consider need for epi carefully & may need to decrease dose; should still be given though to these pts. if reaction is severe

  29. Epi Doses for Allergic Reactions • Give IM or SQ if unable to start IV line quickly • Give IV if markedly hypotensive • IM or SQ dose : 0.01 mg/kg • 0.01 ml/kg of 1:1000 ; max. dose 0.3 mg • IV dose : 0.1 mg (max.) • 1 cc of 1:10,000 • Repeat as needed • Can also give via MDI (10 to 20 puffs)

  30. Antihistamine Med Rx for Allergic Reactions • Act by competitively inhibiting H1 & H2 receptors • Diphenhydramine is best single agent against pruritis, but combo Rx (with H2 blocker) is superior • Give PO for mild & local reactions • Give IM only if airway compromise & unable to start IV • Give IV for severe reactions • Usually give 50 mg diphenhydramine, & 300 mg cimetidine or 50 mg ranitidine

  31. Steroid Rx for Allergic Reactions • Have antiinflammatory effects, stabilize mast cell membranes, & may blunt the biphasic response • Indicated in almost all pts. with systemic reactions • Usually 100 mg hydrocortisone or equivalent is sufficient • May need 1 to 2 days follow-on oral use (prednisone 40 mg/day) depending on source of reaction • Give PO if airway & BP not cpmpromised, otherwise give IV

  32. Use of Glucagon for Allergic Reactions • 1 mg IV dose (repeated as needed) may be useful for cases refractory to initial Rx with epi & IV fluid & H1/H2 blockers & steroids • Also useful in pts. on beta blockers, & as "back-up" med to lower dose epi in pts. with CAD or HBP • Can cause emesis as side effect

  33. Disposition Decisions for Patients with Allergic Reactions • Mild local reactions should be observed for 30 minutes ; then sent home on PO diphenhydramine if no Sx progression • Systemic reactions that respond to initial Rx should be observed 2 to 4 hours for recurrence • Those manifesting airway compromise or hypotension (even if they respond to Rx) probably should be admitted overnight • Pts. on beta blockers, elderly, asthmatics, or with other comorbid diseases should often be admitted

  34. Discharge Medications for Patients with Allergic Reactions • Most should receive : • Diphenhydramine 25 to 50 mg PO QID X 2 days • Cimetidine 300 mg PO QID X 2 days • Prednisone 40 to 50 mg PO (1 to 2 mg/kg) QD X 2 days • Consider susphrine (epi tannate in oil) 0.005 cc/kg (max. 0.3 cc) SQ prior to D/C • Consider epi self-injection kit (Epi-Pen or Ana-Kit) • Consider standby albuterol MDI • Consider non-sedating antihistamine

  35. Other Discharge Considerations for Patients with Systemic Allergic Reactions • Education about preventive or avoidance measures • Get Medic-Alert bracelet or necklace • Consider epi self-injection kit • Standby oral diphenhydramine • Discontinue beta blockers if possible • Referral to allergist for desensitization

  36. Hypersensitivity Disorders & Allergic Reactions : Summary • Evaluate all pts. with allergic reactions emergently • Assess airway & hemodynamics first • Epi is mainstay of Rx • Consider use of adjunctive meds • Observe to determine if relapse or need for admission • Discharged pts. should be instructed carefully about F/U & prevention

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