Hypersensitivity - Emergency Room Treatment


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Diagnosis and treatment of hypersensitivity in emergency medicine.

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  • Hypersensitivity refers to the undesirable sometimes fatal reactions produced by the normal immune system.
  • Gell and Coombs proposed a classification system in 1963? Mnemonic: ACIDS
  • Exposure may be by ingestion, inhalation, injection or direct contact. The reaction is mediated by IgE antibodies and produced by the immediate release from mast cells of histamine, cytokines, interleukins, leukotrienes and prostaglandins.
  • - Immediate inflammatory response within seconds to minutes - Biphasic - Symptoms vary from mild irritation to sudden death from anaphylactic shock
  • IgG + IgM antibodies bind to these antigens to form complexes that activate classical pathway of complement, generating mediators of acute inflammation at the site and membrane attack complexes cause cell lysis and death
  • Soluble immune complexes form in the blood and deposit in various tissues ( typically the skin, kidney and joints) The antigen may be exogenous (chronic bacterial, viral or parasitic infections) or endogenous like in SLE The soluble immune complex trigger an immune response via classical pathway of complement activation
  • - Is not antibody mediated but rather cell mediated, specifically T-lymphocytes recognise specific antigens, causing a delayed immune reaction
  • Bacitracin Poison ivy Staples cream
  • These reactions occur when IgG antibodies directed towards cell surface antigens have a stimulatory effect on target. Ligand is an extracellular substance that binds to receptors Apoptosis is programmed cell death-deliberate suicide -
  • In short “ a severe allergic reaction”
  • An inflammatory response but not IgE mediated Direct histamine release from mast cells Same manifestations as anaphylaxis and treatment is same RadioContrast Media Opiates: morphine and codeine Red man syndrome after Vancomycin
  • Laryngeal edema and acute bronchospam with respiratory failure account for >70%
  • -Many preformed mediators are released in blood stream: Histamine, ECF-A, HMW-NCF, tryptase, kallikrein and newly formed mediators such as PAF, arachidonic acid metabolites, prostaglandins - There are 3 histamine receptors: H1, H2, H3. Histamine acts on H1 receptors to cause:
  • Clinical expression of anaphylaxis depends on: There will be a difference if one ingests 250mg of Pen VK vs. getting an IM/IV injection of 1 million units of Benzathine Penicillin
  • The first clinical manifestations involve the skin: warmth and tingling of the face, mouth, upper chest, palms and soles or site of exposure, itching, urticaria and angioedema Respiratory symptoms soon follow: cough, chest tightness, SOB, wheezing, throat tightness, odynophagia, hoarsness
  • May also complain of: Caused by hypotension or dysrhythmia
  • May reveal: Blanching, raised, palpable wheals Swellling of the superficial dermal layers
  • Swelling of the deeper dermal layers and subcutaneous tissues, nonpruritic
  • Optimal Management requires
  • Must suspect and treat within moments of presentation
  • - Although the exact benefit of corticosteroids has not been established, most experts advocate their administration. Their benefit is not realized for 6 to 12 hours after administration so their primary role may be in prevention of recurrent or protracted anaphylaxis.
  • Epinephrine should be used with caution in the elderly
  • It should be noted that Epi has been given for years SQ but recent studies have shown that the speed of absorption is unsatisfactory when given SQ. Peak levels may take 25 min to occur following SQ administration of Epi while peak levels may be obtained within 5-6 minutes when Epi injected IM
  • Heliox has been found to be helpful in a variety of airway obstruction including asthma, COPD and upper airway obstruction, helium decreased force necessary to move the gas thru the airways & decreases the mechanical work of the respiratory muscles
  • Bronchospasm refractory to epinephrine may respond to: The use of anticholinergic therapy with atrovent decrease c GMP levels, therefore decreasing mediator release and reversing the action of mediators on target tissue cells.
  • - If responsive to Naloxone start IV drip
  • Positive inotropic and chronotropic cardiac effects mediated independently of alpha and beta receptors Pregnant women ( category B drug) Usefulness is anecdotal only-no controlled trials Dose is 1mg for adults and 0.5mg for children SQ, IM or IV- may require a glucagon infusion SE of glucagon: nausea, vomiting, hypokalemia, hyperglycemia
  • Regardless of response to therapy, all patients with systemic features must be observed for 6-8 hours There is no accurate way to predict which patients will experience a biphasic reaction Admission mandatory for anyone with moderate to severe reaction, this includes anyone who showed signs of upper airway obstruction or hypotension.
  • Avoid food/ for insect bites, venom immunotherapy helps Aerosol spray containing Epi indicated for patients who developed throat swelling All patients with peanut or nut allergy should carry one, less for milk and eggs since reactions usually milder
  • Hypersensitivity - Emergency Room Treatment

    1. 1. Hypersensitivity Josyann Abisaab, MD Department of Emergency Medicine New York Presbyterian Hospital- Weill Cornell Medical Center
    2. 2. Outline <ul><li>Types of Hypersensitivity </li></ul><ul><li>Anaphylaxis </li></ul><ul><li>Disposition </li></ul><ul><li>Prevention </li></ul>
    3. 3. Definition of Hypersensitivity <ul><li>Undesirable reactions produced by the normal immune system. </li></ul>
    4. 4. Classification of Hypersensitivity <ul><li>Type I: Immediate/ A naphylactic </li></ul><ul><li>Type II: C ytotoxic Antibody Reaction </li></ul><ul><li>Type III: I mmune Complex Reaction </li></ul><ul><li>Type IV: D elayed-Type Hypersensitivity </li></ul><ul><li>Type V: S timulatory Hypersensitivity </li></ul>
    5. 5. Type I- Immediate hypersensitivity <ul><li>Provoked by reexposure to a specific antigen. </li></ul><ul><li>IgE mediated </li></ul><ul><li>Mast cells and Basophils stimulation </li></ul><ul><li>Release of Histamine and other chemicals </li></ul><ul><li>Vasodilation, mucous secretion, bronchospasm </li></ul>
    6. 6. Type I- Immediate <ul><li>Acute response within 1 hour </li></ul><ul><li>Late-phase response 4-6 hours after original reaction, can last 1-2 days </li></ul><ul><li>Local vs. systemic </li></ul>
    7. 7. Type I- Immediate <ul><li>Urticaria (hives) </li></ul><ul><li>Angioedema </li></ul><ul><li>Allergic conjunctivitis </li></ul><ul><li>Allergic Rhinitis </li></ul><ul><li>Allergic Asthma </li></ul><ul><li>Anaphylaxis </li></ul>
    8. 8. Type II- Cytotoxic Antibody Reaction <ul><li>Antigen is on the patient’s own cell surfaces </li></ul><ul><li>Mediated by IgG and IgM </li></ul><ul><li>Complement activation </li></ul><ul><li>Cell lysis and death </li></ul><ul><li>Reaction takes hours to a day </li></ul>
    9. 9. Type II- Cytotoxic <ul><li>Transfusion reactions </li></ul><ul><li>Rh incompatibility </li></ul><ul><li>Autoimmune hemolytic anemia </li></ul><ul><li>Goodpasture’s syndrome </li></ul><ul><li>Pemphigus </li></ul><ul><li>ITP </li></ul><ul><li>Rx: anti-inflammatory + immunosuppressive agents </li></ul>
    10. 10. Type III- Immune Complex Hypersensitivity <ul><li>Antigen-antibody complexes deposit in tissue </li></ul><ul><li>Antigen is soluble- not attached to organ involved </li></ul><ul><li>Classical pathway of complement activation </li></ul><ul><li>Takes hours to days to develop </li></ul>
    11. 11. Type III- Immune Complex <ul><li>Serum sickness </li></ul><ul><li>SLE </li></ul><ul><li>Rheumatoid arthritis </li></ul><ul><li>Erythema nodosum </li></ul><ul><li>Arthus reaction (Farmer’s Lung) </li></ul><ul><li>Immune complex glomerulonephritis </li></ul><ul><li>Rx: anti-inflammatory agents </li></ul>
    12. 12. Type IV- Delayed-Type Hypersensitivity <ul><li>Mediated by T-Lymphocytes </li></ul><ul><li>Takes 2-3 days </li></ul><ul><li>Contact dermatitis (poison ivy, nickel) </li></ul><ul><li>PPD </li></ul><ul><li>Transplant rejection (GVHD) </li></ul><ul><li>Rx: corticosteroids + other immunosuppressive agents </li></ul>
    13. 13. Contact Dermatitis
    14. 14. Delayed Hypersensitivity Reactions TB, leprosy Foreign body presence Hardening 21-28 days Granuloma Tuberculin Intradermal Local induration 48-72 hr PPD Poison ivy, heavy metals Epidermal Eczema 48-72 hr Contact Antigen Site Clinical Appearance Reaction time Type
    15. 15. Type V- Stimulatory Hypersensitivity <ul><li>IgG stimulate their target </li></ul><ul><ul><li>Graves Disease </li></ul></ul><ul><ul><li>Myasthenia Gravis </li></ul></ul><ul><li>Ligand induced apoptosis </li></ul><ul><ul><li>Stevens Johnson Syndrome/Toxic Epidermal Necrolysis (TENS) </li></ul></ul>
    16. 16. Type V- Stimulatory <ul><li>Stevens Johnson Syndrome </li></ul><ul><li> TENS </li></ul>
    17. 17. Anaphylaxis <ul><li>Case Presentation: </li></ul><ul><li>39 y.o male BIBA in respiratory distress with agonal pulse. </li></ul><ul><li>Paramedics report patient was helping a friend paint when he was stung by a bee. He walked into the house, saying:”I don’t feel good” and collapsed. </li></ul><ul><li>Intubated at scene, en route given endotracheal and IV Epi, IV Benadryl </li></ul>
    18. 18. Anaphylaxis <ul><li>Case Presentation: </li></ul><ul><li>On arrival in ED, patient intubated, cyanotic from neck up, CPR in progress </li></ul><ul><li>2 nd Large bore IV, wide open fluids </li></ul><ul><li>Dopamine drip </li></ul><ul><li>Epnephrine drip </li></ul><ul><li>Central line </li></ul><ul><li>Isuprel drip, Levophed drip </li></ul><ul><li>Monitor: agonal wide-complex </li></ul>
    19. 19. Anaphylaxis <ul><li>Case presentation: </li></ul><ul><li>TVP failed to capture </li></ul><ul><li>After 20 min prehospital and 30 min hospital resuscitation, no response. </li></ul><ul><li>Patient died. </li></ul><ul><li>Cause: “Fatal Anaphylactic Reaction” </li></ul>
    20. 20. What is Anaphylaxis? <ul><li>“ A systemic reaction of multiple organ systems to an antigen-induced IgE-mediated immunologic mediator release in a previously sensitized individual” </li></ul>
    21. 21. What does the word mean? <ul><li>“ ana” means against or backwards </li></ul><ul><li>“ phylaxis” means guard or protect </li></ul><ul><li>Anaphylaxis= “without protection” </li></ul><ul><li>Prophylaxis= “for protection” </li></ul>
    22. 22. What is Anaphylactoid? <ul><li>A nonimmunologic reaction </li></ul><ul><li>Not mediated by IgE </li></ul><ul><li>Direct histamine release </li></ul><ul><li>Same manifestations & treatment as anaphylaxis </li></ul><ul><li>Causes: RCM, opiates, ACEI, exercise, blood products, gammaglobulin, NSAIDs, ASA </li></ul>
    23. 23. Anaphylaxis: How does it manifest? <ul><li>Clinical severity varies from mild to fatal </li></ul><ul><li>Majority of reactions are respiratory and dermatologic </li></ul><ul><li>Innocent early findings may progress to lethal over a short time </li></ul>
    24. 24. What causes the deaths? <ul><li>Laryngeal edema and acute bronchospasm >70% </li></ul><ul><li>Circulatory collapse >25% </li></ul><ul><li>other <5% - ?brain ?MI </li></ul>
    25. 25. In USA <ul><li>30,000 emergency room visits each year </li></ul><ul><li>400 to 800 deaths/year </li></ul><ul><li>IV penicillin accounts for 100 to 500 deaths per year </li></ul><ul><li>Hymenoptera stings account for 40 to 100 deaths per year </li></ul><ul><li>Risk factors: protracted course, betablockers, adrenal insufficiency </li></ul>
    26. 26. Histamine <ul><li>Prime mediator of both local and systemic effects </li></ul><ul><li>H1: smooth muscle contraction,  vascular permeablility </li></ul><ul><li>H2: gastric acid secretion, release of more histamine,  vascular permeability </li></ul><ul><li>H3: inhibition of central and peripheral neurotransmitter release, inhibition of further histamine </li></ul>
    27. 27. Clinical expression depends on: <ul><li>Degree of hypersensitivity </li></ul><ul><li>Quantity, route, rate of antigen exposure </li></ul><ul><li>Pattern of mediator release </li></ul><ul><li>Target organ sensitivity and responsiveness </li></ul>
    28. 28. Timing <ul><li>Uniphasic </li></ul><ul><li>Biphasic </li></ul><ul><li>Protracted </li></ul><ul><li>Laryngeal edema more common in biphasic (40%) or protracted (57%) cases </li></ul>
    29. 29. Usual culprits
    30. 30. Clinical manifestations <ul><li>Skin: urticaria and angioedema </li></ul><ul><li>Respiratory: cough, dyspnea, wheezing, hoarseness </li></ul>
    31. 31. Clinical manifestations <ul><li>Lightheadedness or syncope </li></ul><ul><li>Nasal congestion and sneezing </li></ul><ul><li>Ocular itching and tearing </li></ul><ul><li>Cramping abdominal pain with N/V/D </li></ul><ul><li>Headache </li></ul><ul><li>Sense of impending doom </li></ul><ul><li>↓ level of consciousness </li></ul>
    32. 32. Examination <ul><li>Urticaria </li></ul>
    33. 33. Examination <ul><li>Angioedema </li></ul>
    34. 34. Examination <ul><li>Angioedema of </li></ul><ul><li>oropharynx </li></ul>
    35. 35. Examination <ul><li>Conjunctivitis, rhinitis </li></ul><ul><li>Tachypnea, tachycardia, hypotension </li></ul><ul><li>Laryngeal stridor, hoarseness </li></ul><ul><li>Wheezing, ronchi, diminished air flow </li></ul>
    36. 36. Optimal Management <ul><li>High index of suspicion </li></ul><ul><li>Early diagnosis </li></ul><ul><li>Pharmaceutical intervention </li></ul><ul><li>Observation </li></ul><ul><li>Disposition </li></ul>
    37. 37. Index of suspicion <ul><li>The motto of Emergency Medicine: </li></ul><ul><ul><li>TREAT FIRST </li></ul></ul><ul><ul><li>ASK QUESTIONS LATER </li></ul></ul>
    38. 38. Treating mild anaphylaxis <ul><li>Urticaria, rhinitis, conjunctivitis, mild bronchospasm </li></ul><ul><li>Epinephrine 1:1000 </li></ul><ul><ul><li>0.3cc IM may repeat every 5-20min prn </li></ul></ul><ul><ul><li>0.01mg per kg in children </li></ul></ul><ul><li>Benadryl 50 mg po or IM </li></ul><ul><li>Consider: H2-blocker, prednisone, inhaled beta-agonists </li></ul>
    39. 39. Steroids <ul><li>Benefit 6-12 hrs after administration </li></ul><ul><li>May prevent biphasic or protracted reaction </li></ul>
    40. 40. Myth: Epi is dangerous <ul><li>Reality: </li></ul><ul><li>Risks of anaphylaxis far outweigh risks of Epi administration </li></ul><ul><li>Minimal cardiovascular effects in children (Simons et al, 1998) </li></ul><ul><li>Caution in: elderly, known cardiac disease and tachyarrythmias </li></ul>
    41. 41. Treating moderate anaphylaxis <ul><li>Angioedema or hypotension with BP>80mmHg </li></ul><ul><li>Epinephrine 1:1000- 0.3 cc IM </li></ul><ul><li>Benadryl 50mg IM or IV </li></ul><ul><li>Pepcid IV </li></ul><ul><li>Solumedrol 40-125mg IV </li></ul><ul><li>Oxygen, IVF, cardiac monitor </li></ul>
    42. 42. Treating severe anaphylaxis <ul><li>Laryngeal edema, respiratory failure, shock </li></ul><ul><li>Epinephrine 1:10,000- 1cc IV over 5 min, repeat every 3-5 min prn </li></ul><ul><li>Benadryl 50-100mg IV over 3 min </li></ul><ul><li>H2 blockers </li></ul><ul><li>Solumedrol </li></ul><ul><li>Nebulizers: racemic epi, albuterol </li></ul>
    43. 43. Laryngeal edema <ul><li>Chin lift, jaw thrust </li></ul><ul><li>Naso-or oropharyngeal airway </li></ul><ul><li>Racemic epi 0.5 cc neb </li></ul><ul><li>Heliox (Boorstein et al, AEM, 1989) </li></ul><ul><li>Tracheal intubation prn </li></ul><ul><li>Surgical airway prn </li></ul>
    44. 44. Persistent bronchospasm <ul><li>Albuterol by continuous nebulization </li></ul><ul><li>Aminophylline 5.6 mg/kg IV over 20-30 min </li></ul><ul><li>Atrovent by nebulization </li></ul><ul><li>Heliox </li></ul><ul><li>Steroids </li></ul><ul><li>Intubation </li></ul>
    45. 45. Persistent hypotension <ul><li>Trendelenberg </li></ul><ul><li>2 largebore IV’s infusing crystalloid </li></ul><ul><li>Monitor urine output and CVP </li></ul><ul><li>PASG </li></ul><ul><li>Consider: Naloxone 0.4-0.8mg IV </li></ul><ul><li>Vasopressors: dopamine, isoproterenol, levophed </li></ul>
    46. 46. What about Glucagon? <ul><li>When epi contraindicated, may be an option </li></ul><ul><li>Positive inotropic and chronotropic cardiac effects </li></ul><ul><li>Consider in patients: </li></ul><ul><ul><li>On beta blockers </li></ul></ul><ul><ul><li>With known CAD </li></ul></ul><ul><ul><li>Pregnant women </li></ul></ul><ul><ul><li>No response to other drugs </li></ul></ul>
    47. 47. Disposition <ul><li>Systemic features: observe for 6-8 hours </li></ul><ul><li>Cannot predict biphasic reaction </li></ul><ul><li>Admission mandatory for: </li></ul><ul><ul><li>Moderate to severe reaction, even if they respond rapidly to Rx </li></ul></ul><ul><li>Consider admission for: </li></ul><ul><ul><li>Elderly </li></ul></ul><ul><ul><li>CAD </li></ul></ul><ul><ul><li>Asthma </li></ul></ul><ul><ul><li>On beta blocker </li></ul></ul>
    48. 48. May be discharged home if <ul><li>Mild anaphylaxis </li></ul><ul><li>No hypotension </li></ul><ul><li>No signs of airway obstruction </li></ul><ul><li>Rapid response to ED therapy </li></ul><ul><li>Observed for 6 hours without recurrence </li></ul><ul><li>Safe discharge to care of responsible adult </li></ul>
    49. 49. Outpatient management <ul><li>4 day course of Benadryl Q6h </li></ul><ul><li>4 day course of Pepcid BID </li></ul><ul><li>4 day course of Prednisone 50mg/day </li></ul><ul><li>(Ellis et al, CMAJ, 2003) </li></ul><ul><li>Referral to an Allergist </li></ul>
    50. 50. Prevention <ul><li>Avoid the food </li></ul><ul><li>Aerosol spray containing Epi-Primatene or Medihaler-Epi </li></ul><ul><li>Epi-Pen </li></ul><ul><li>Medic Alert bracelet </li></ul>
    51. 51. Board Type Questions <ul><li>A 27 year old man presents after a syncopal event following a long run. He c/o lightheadedness and itching, along with swelling of his hands and feet. His BP is 68/36 mmHg and pulse is 160. Lung examination shows he has diffuse wheezing. His blood glucose is 95 mg/dl. The most important initial IV therapy would be: </li></ul><ul><ul><li>Epinephrine </li></ul></ul><ul><ul><li>Diphenhydramine </li></ul></ul><ul><ul><li>Methylprednisolone </li></ul></ul><ul><ul><li>Normal Saline </li></ul></ul><ul><ul><li>Pepcid </li></ul></ul>
    52. 52. Board Type Questions <ul><li>Type I Hypersensitivity: </li></ul><ul><li>occurs 24 hours after the initial stimulus </li></ul><ul><li>is produced by IgE antibodies </li></ul><ul><li>is cell mediated </li></ul><ul><li>is best treated with steroids </li></ul><ul><li>is diagnosed by measuring serum histamine levels </li></ul>
    53. 53. Board Type Questions <ul><li>A 45 year old man with no PMH was playing golf when he complained of a sting on his hand, followed by shortness of breath and loss of consciousness. EMS at scene report a BP 70/40, HR 140 and bilateral wheezing. The most likely diagnosis is: </li></ul><ul><ul><li>Vasovagal syncope </li></ul></ul><ul><ul><li>Asthma </li></ul></ul><ul><ul><li>Psychogenic syncope related to bad golfing day </li></ul></ul><ul><ul><li>Anaphylactic shock </li></ul></ul><ul><ul><li>Myocardial Infarction </li></ul></ul>
    54. 54. Board Type Questions <ul><li>A 19-year-old woman with a past history of seasonal allergic rhinitis is referred to the ED from her family doctor’s office. She had received her routine injection of allergen immunotherapy (ragweed). Twenty minutes later, she began to notice itching in the palms of her hands, followed by shortness of breath and a sensation of throat swelling. In the ED, patient is noted to be flushed, sweating and in moderate distress. Her BP is 110/60 and her HR is 120. She is speaking in full sentences. The most appropriate initial emergency treatment would be: </li></ul><ul><li>Epinephrine 1:10,000- 1cc IV </li></ul><ul><li>Racemic Epi 0.5 cc neb </li></ul><ul><li>Epinephrine 1:1000- 0.3 cc IM </li></ul><ul><li>Albuterol neb </li></ul><ul><li>Benadryl 50mg po </li></ul>
    55. 55. Board Type Questions <ul><li>A 40 year old woman presents to the ED 30 minutes after eating chicken with cashews at a chinese restaurant. Patient complains of hives, itchy eyes, throat tightness as well as mild shortness of breath. The astute ED intern makes the diagnosis of urticaria and mild anaphylaxis. She administers IM Epi and Benadryl with immediate resolution of symptoms. Patient now feels well and wants to go home. </li></ul><ul><li>You agree with patient and write discharge order </li></ul><ul><li>You give her steroids first then discharge her </li></ul><ul><li>You recommend observation in the ED for at least 6 hours </li></ul><ul><li>You recommend discharge home under the care of an adult after 2 hours </li></ul><ul><li>You recommend admission to the hospital </li></ul>
    56. 56. Any questions?