Hypersensitivity DisordersAllergic Emergencies

Jim Holliman, M.D., F.A.C.E.P.Professor of Military and Emergency MedicineUniformed Services University of the Health SciencesClinical Professor of Emergency MedicineGeorge Washington UniversityBethesda, Maryland, U.S.A.

Hypersensitivity Disorders & AllergicEmergencies : Lecture Objectives

ƒ Describe & compare :–Anaphylaxis & anaphylactoid reactions–Angioneurotic edema–Drug allergies

ƒ Describe emergent Rx & followup outpatient Rx for anaphylactic & other allergic reactions

Allergic ReactionsDefinitions of Terms

ƒ Anaphylaxis (Greek = "backward protection")–Rapid generalized immunologic reaction after exposure to antigens in a sensitized person, with at least 2 of :ƒ resp. or airway compromise from swelling or wheezing

ƒ hypotension or cardiovascular collapseƒ diffuse cutaneous findings (urticaria, angioedema, +/- erythroderma)

Allergic ReactionsDefinitions of Terms (cont.)

ƒ 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

ƒ Urticaria :–Diffuse patchy erythematous pruritic rash with raised borders

ƒ Angioedema :–Non-pitting subcutaneous tissue swelling–Often of the face, mouth, or peri-airway tissue

Pathophysiology of Allergic Reactions

ƒ Mast cell–Final common pathway of all allergic reactions–Present in most tissues–When activated, release (from cell granules) :ƒ Histamineƒ Bradykininsƒ Prostaglandinsƒ Leukotrienes–Clinical effects are due to these above mediators

Four Mechanisms that Lead to Mast Cell Degranulation (Release of Mediators)

ƒ Immunoglobulin E (IgE) mediated hypersensitivity

ƒ Complement cascade activationƒ Direct stimulation of mast cell by

anaphylactoid substancesƒ Inhibition of arachidonic acid pathway

Sequence of Events in IgE Mediated Hypersensitivity Reactions

ƒ 1. Initial exposure to allergenƒ 2. IgE antibody produced in reponse

to allergenƒ 3. Re-exposure of patient to same

allergenƒ 4. Preformed IgE cross links on mast

cell surfaceƒ 5. Mediators (esp. histamine) released

by mast cell

Histamine Receptorsƒ 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

General Clinical Effects of Release of Allergic Mediatorsƒ Mucocutaneous :

–pruritis, flushing, erythema, urticaria, angioedemaƒ Respiratory :

–upper airway angioedema–bronchoconstriction–pulmonary hyperinflation +/- pulm. edema

ƒ Cardiovascular :–vasodilatation, increased vascular permeability, intravascular volume depletion, vasogenic shock, myocardial contractile dysfunction

ƒ Gastrointestinal :–cramping, vomiting, diarrhea

Causes of Anaphylactic and Anaphylactoid Reactions

ƒ IgE mediated allergies :–Beta lactams, hymenoptera stings, food, latex

ƒ Direct mast cell degranulation :–Xray contrast media, opiates, mannitol, neuromuscular blockers

ƒ Altering bradykinin metabolism :–angiotensin converting enzyme (ACE) inhibitors

ƒ Affecting metabolism of arachidonic acid :–aspirin, NSAID's

Considerations About Beta Lactam Antibiotic Allergies

ƒ Penicillin is most common causeƒ Incidence of hypersensitivity about 4 %ƒ Anaphylaxis in 1 per 10,000 administrationsƒ 100 to 500 deaths per year in U.S.ƒ Co-reactivity with cephalosporins < 5%ƒ Can undergo desensitization process but risky

and many alternative antibiotics now availableƒ Can occur from topical exposure (mother preparing

antibiotic suspension for child)

Considerations About Allergy to Hymenoptera Stings

ƒ Hymenoptera include bees, wasps, antsƒ Mostly cause local allergic reactionsƒ 10 % have regional swellingƒ 1 % have anaphylaxis

–Causes 40 to 50 deaths per year in U.S.

ƒ Content of venom variable so re-sting may not cause same reaction as before

ƒ F/U with allergist for desensitization Rx always recommended for systemic reaction

Treatment of Allergic Reactions from Hymenoptera Stings

ƒ If local reaction only :–Ice pack, pain med, diphenhydramine PO–Watch at least 30 minutes to be sure systemic reaction does not occur

ƒ If systemic reaction :–O2, epi, IV fluid bolus, IV diphenhydramine, IV steroids, observe at least 4 hours

ƒ For both types :–Check sting site & remove stinger if imbedded (scrape, don't squeeze), update tetanus, consider antibiotic if ? cellulitis

Considerations About Allergic Reactions to Foods

ƒ 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

ƒ Must differentiate seafood allergy from scombroid poisoning (due to ingestion of spoiled fish containing histamine)

Considerations About Latex Allergy

ƒ An increasingly recognized recent problem

ƒ Can result in fatal anaphylaxisƒ High incidence in pts. with spina bifida

& congenital urologic problemsƒ Be careful to select non-latex gloves &

catheters for pts. with this allergy

Allergic Reactions to Radiocontrast Media

ƒ Occur in 1 % of casesƒ 10 % of occurences are severeƒ About 500 ( ? ) fatal reactions in U.S.

annuallyƒ Risk factors :

–prior reaction (30 % recurrence rate)–advanced age–renal or hepatic dysfunction–asthma

Allergic Reactions to Radiocontrast Agents (cont.)

ƒ High osmolarity agents (Hypaque, Renografin, Conray)–Tri-iodinated, ionic

ƒ 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%

Allergic Reaction Prophylaxis for Radiocontrast Agent Use

ƒ Pretreatment reduces recurrent allergic reaction rate to 1%

ƒ 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

ƒ Pre-Rx indicated for pt. requiring a contrast study with prior Hx of reaction or renal dysfunction

Angioedema Due to ACE Inhibitors

ƒ Occurs in 0.2 % of pts. on ACE inhibitorsƒ Can occur even after prolonged use of ACE

inhibitors without a prior reactionƒ Predeliction for head & neck angioedema so

airway compromise possibleƒ Rx by stopping the ACE inhibitor, epi,

steroids, diphenhydramine, +/- airway management

Severe angioedema

Same patient on prior slide after treatment

Spectrum of Presentations of Allergic Reactions

ƒ Time to onset, intensity, & duration of reaction vary, depending on :–degree of sensitivity of pt.–route of exposure–amount ("dose") of antigen

ƒ Rarely pts. may have "biphasic" reaction with reexacerbation of Sx 4 to 8 hours after the initial reaction

Clinical Manifestations of Systemic Allergic Reactions

ƒ Diffuse pruritis, urticaria, angioedema, erythroderma

ƒ Anxiety, dizziness, sense of doom, altered mental status

ƒ Dyspnea, stridor, wheezingƒ Dysphagia, dysarthria, droolingƒ Vomiting, diarrhea, abd. crampsƒ Urinary incontinenceƒ Hypotension +/- bradycardia

Differential Dx of Severe Allergic Reaction

ƒ Sudden loss of consciousness :–vasovagal syncope, seizures, dysrhythmias, CVA

ƒ Acute respiratory distress :–status asthmaticus, upper airway infection, foreign body aspiration, pulm. embolus

ƒ Cardiovascular collapse :–intraabdominal bleed, acute MI

ƒ Systemic disorders :–mastocytosis, hereditary angioedema (C1 esterase deficiency syndrome) , carcinoid syndrome, scromboid poisoning, MSG syndrome

E.D. Management of Systemic Allergic Reactions

ƒ Since may progress rapidly & unpredictably, all pts. with possible systemic reaction should be rapidly triaged to acute care room & continuously monitored

ƒ 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

Airway Management Considerations for Severe Allergic Reactions

ƒ Swelling impinging the airway may progress rapidly so earlier intubation more likely successful than later

ƒ Consider sedation without paralysis if anticipated difficulty

ƒ Start with ETT size one size smaller than usualƒ Have surgical airway equipment at bedsideƒ Place nasal airway early even if ETT not initially

requiredƒ Consider use of inhaled racemic epi

The Key Med in Rx of Allergic Reactions : Epinephrine (epi)

ƒ Is the most important & effective Rx med

ƒ Alpha agonist effects :–Vasoconstriction, decreased vascular permeability, resolution of angioedema

ƒ Beta agonist effects :–Bronchodilatation, cardiac inotropy, mast cell membrane stabilization

Potential Complications of Use of Epi for Allergic Reactions

ƒ Hypertension (may cause CNS bleed)ƒ Increased myocardial O2 consumptionƒ Coronary vasoconstrictionƒ 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

Epi Doses for Allergic Reactions

ƒ Give IM or SQ if unable to start IV line quicklyƒ Give IV if markedly hypotensiveƒ IM or SQ dose : 0.01 mg/kg

–0.01 ml/kg of 1:1000 ; max. dose 0.3 mg

ƒ IV dose : 0.1 mg (max.)–1 cc of 1:10,000

ƒ Repeat as neededƒ Can also give via MDI (10 to 20 puffs)

Antihistamine Med Rx for Allergic Reactions

ƒ Act by competitively inhibiting H1 & H2 receptorsƒ Diphenhydramine is best single agent against

pruritis, but combo Rx (with H2 blocker) is superiorƒ Give PO for mild & local reactionsƒ Give IM only if airway compromise & unable to start

IVƒ Give IV for severe reactionsƒ Usually give 50 mg diphenhydramine, & 300 mg

cimetidine or 50 mg ranitidine

Steroid Rx for Allergic Reactions

ƒ Have antiinflammatory effects, stabilize mast cell membranes, & may blunt the biphasic response

ƒ Indicated in almost all pts. with systemic reactionsƒ Usually 100 mg hydrocortisone or equivalent is

sufficientƒ May need 1 to 2 days follow-on oral use (prednisone

40 mg/day) depending on source of reactionƒ Give PO if airway & BP not cpmpromised, otherwise

give IV

Use of Glucagon for Allergic Reactions

ƒ 1 mg IV dose (repeated as needed) may be useful for cases refractory to initial Rx with epi & IV fluid & H1/H2 blockers & steroids

ƒ Also useful in pts. on beta blockers, & as "back-up" med to lower dose epi in pts. with CAD or HBP

ƒ Can cause emesis as side effect

Disposition Decisions for Patients with Allergic Reactions

ƒ Mild local reactions should be observed for 30 minutes ; then sent home on PO diphenhydramine if no Sx progression

ƒ Systemic reactions that respond to initial Rx should be observed 2 to 4 hours for recurrence

ƒ Those manifesting airway compromise or hypotension (even if they respond to Rx) probably should be admitted overnight

ƒ Pts. on beta blockers, elderly, asthmatics, or with other comorbid diseases should often be admitted

Discharge Medications for Patients with Allergic Reactions

ƒ 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

Other Discharge Considerations for Patients with Systemic Allergic Reactions

ƒ Education about preventive or avoidance measures

ƒ Get Medic-Alert bracelet or necklaceƒ Consider epi self-injection kitƒ Standby oral diphenhydramineƒ Discontinue beta blockers if possibleƒ Referral to allergist for desensitization

Hypersensitivity Disorders & Allergic Reactions : Summary

ƒ Evaluate all pts. with allergic reactions emergently

ƒ Assess airway & hemodynamics firstƒ Epi is mainstay of Rxƒ Consider use of adjunctive medsƒ Observe to determine if relapse or

need for admissionƒ Discharged pts. should be instructed

carefully about F/U & prevention