Allergic Reactions & Anaphylaxis Barry Barkinsky EMS-I, Paramedic

Sections Path physiology Assessment findings in anaphylaxis Management Basement findings in Allergic Reaction Patient Education

https://www.youtube.com/watch?v=G9D- Vfmbt4s overview https://www.youtube.com/watch?v=G9D- Vfmbt4s

Incidence In USA - 400 to 800 deaths/year Parenterally administered penicillin accounts for 100 to 500 deaths per year Hymenoptera stings account for 40 to 100 deaths per year Risk factors: beta-blockers, adrenal insufficiency

Why do they die?

Causes of Deaths Laryngeal edema and acute bronchospasm with respiratory failure account for >70% Circulatory collapse accounts for 25% Other <5% - ?brain ?MI

bronchospasm Bronchospasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release (degranulation) of substances from mast cells or basophils under the influence of anaphylatoxins.

Laryngeal edema The acute laryngeal edema seen here that killed the patient was due to an anaphylactic reaction to penicillin. Such an allergy is a form of type I hypersensitivity reaction in which there is preformed IgE antibody on mast cells that quickly reacts with an antigen. The mast cells release histamine and other mediators that lead to the edema.

Allergic Reaction é Physiologic response to antigens Oversensitive response = allergic Occurs after sensitization to antigen Antigen binds with Antibody Less severe result in inflammatory response Type I reaction involves antibodies attached to mast cells or basophils = most severe form

Define some terms Antigen: any substance capable of inducing an immune response Most antigens are proteins Following exposure to an antigen the body releases antibodies

Define some terms Antibodies Substances produced by B lymphocytes in response to the presence of a foreign antigen that will combine with and control or destroy the antigen, thus preventing infection

Define some terms Mast cells Specialized cell of the immune system which contains chemicals that assist in the immune response Systemic mastocytosis

Define some terms Sensitized The initial exposure to an antigen that results in an immune response

Allergic Reaction - definition An exaggerated response by the immune system to a foreign substance

Allergic Reaction é Physiologic response to antigens Oversensitive response = allergic Occurs after sensitization to antigen Antibody binds with Antigen Less severe result in inflammatory response Type I reaction involves antibodies attached to mast cells or basophils = most severe form

Primary response Initial response to an antigen – on 1st time exposure several day response by immune system Generalized antibodies IgG, IgM are released

Secondary response Specialized antibodies with memory now created Specific to the antigen

The speed of the reaction is a good predictor of the severity of the reaction

Anaphylaxis Systemic reaction of multiple organ systems to antigen-induced IgE-mediated immunulogic mediator release in previously sensitized individual

IgE mediated reactions IgE-mediated hypersensitive reactions (allergic rhinitis, asthma,           atopic dermatitis)

Type 1 - immediate (or atopic, or anaphylactic) Symptoms vary from mild irritation to sudden death from anaphylactic shock Allergic asthma Allergic conjunctivitis Allergic rhinitis ("hay fever") Anaphylaxis Angioedema Urticaria (hives) Eosinophilia Penicillin Cephalosporin

Allergic Reaction Antigen Induces antibody formation Examples Drugs (antibiotics) Foods (nuts, shellfish) Insect venoms Animal serum Incompatible blood types

Allergic reaction / Anaphylaxis Antigens enter body by: Injection Ingestion Inhalation Absorption

Mast Cells and the Allergic Response

Mast Cells and the Allergic Response

Mitigating factors? Route of administration And??????????????? IMMUNITY

immunity

Pathophysiology- IMMUNITY Immune Response Exposure to antigen produces primary response with general antibodies Immune system develops antigen-specific antibodies and memory – secondary response Natural and acquired Immunity Induced Active Immunity Active and Passive Immunity

The immune system Natural immunity - OEM Acquired immunity Naturally acquired immunity

Natural immunity Also called: innate immunity Genetically predetermined Not related to previous exposures Everyone has “some” natural immunities

Naturally Acquired immunity Results from exposure to antigens Is enhanced by continued exposures Is believed to be lifelong in duration

Induced active immunity Also called artificially acquired immunity Designed to protect from a future exposure to an antigen Achieved through vaccination Provides relative protection Creates antibodies

Induced passive immunity Same as induced active immunity but includes injection of antibodies Tetanus is an induced passive immunity example Duration is largely unknown and is estimated. Sometimes can be titered

HOW LONG IS Induced immunity is good for? Until its not

Anaphylaxis Path physiology Antigen enters body (primary response) Antibodies produced Attach to surface of mast or basophil cells Mast cells become sensitized

Anaphylaxis Path physiology behind the scenes Mast cells Specialized cell which contains chemicals that assist in the immune response In all subcutaneous/submucosal tissues, Including conjunctiva, upper/lower respiratory tracts, and gut Basophils white blood cell which participates in allergic response Circulate in blood

Anaphylaxis Pathophysiology Antigen reenters body (secondary response) Attaches to antibodies on mast or basophil cells Mast cell degranulates, releases Histamine Leukotrienes Slow reacting substance of anaphylaxis (SRS-A) Eosinophil chemotactic factor (ECF)

Histamine Product of mast cells and basophils that causes: Vasodilatation Capillary permeability - angioedema Bronchoconstriction Contraction of the gut

Histamine in detail Three histamine receptor types: H1 H2 H3

Histamine Acts on H1 receptors to cause Smooth muscle contraction Increased vascular permeability Prostaglandin generation (mediators)

Histamine * Release of more histamine from mast cells and basophils Acts on H2 receptors to cause * Increased vascular permeability Gastric acid secretion Stimulation of suppressor lymphocytes Decreased PMN enzyme release * Release of more histamine from mast cells and basophils

Histamine Acts on H3 receptors to cause Inhibition of central, peripheral nervous system neurotransmitter release Inhibition of further histamine formation, release

Decreased peripheral vascular resistance CAUSES Vasodilatation Decreased peripheral vascular resistance CAUSES Hypotension Tachycardia Peripheral Hypoperfusion

Increased Capillary Permeability Tissue edema, urticaria (hives), itching Laryngeal edema Airway obstruction Respiratory distress Stridor Angioedema Fluid leakage from vascular space Hypovolemic shock

Anaphylaxis Path physiology Antigen reenters body (secondary response) Attaches to antibodies on mast or basophil cells Mast cell degranulates, releases Histamine Leukotrienes Slow reacting substance of anaphylaxis (SRS-A) Eosinophil chemotactic factor (ECF)

Leukotrienes Potent bronchoconstrictors, é vascular permeability & possibly coronary vasoconstriction Slower onset than histamine Effects last longer than histamine

Anaphylaxis Path physiology Antigen reenters body (secondary response) Attaches to antibodies on mast or basophil cells Mast cell degranulates, releases Histamine Leukotrienes Slow reacting substance of anaphylaxis (SRS-A) Eosinophil chemotactic factor (ECF)

SRS-A Potent bronchoconstrictor and inflammatory agent released by mast cells; an important mediator of allergic bronchial asthma.

Anaphylaxis Path physiology Antigen reenters body (secondary response) Attaches to antibodies on mast or basophil cells Mast cell degranulates, releases Histamine Leukotrienes Slow reacting substance of anaphylaxis (SRS-A) Eosinophil chemotactic factor (ECF)

ECF Eosinophil chemotactic factor (ECF) A substrate released from mast cells and basophils during anaphylaxis which attracts eosinophils . A tetrapeptide mediator of Immediate Hypersensitivity .

Eosinophil One of the five different types of white blood cell (WBC) belonging to the subgroup of WBCs called Polymorphonuclear Leukocytes . Characterized by large red (i.e. eosinophilic) cytoplasmic granules. Eosinophil function is incompletely understood. They are prominent at sites of allergic reactions and with parasitic larvae infections ( helminths ). Eosinophil secretory products inactivate many of the chemical mediators of inflammation and destroy cancer cells. This phenomenon is most obvious with mast cell-derived mediators. Mast cells produce a chemotactic factor for eosinophils. Produced in the bone marrow, eosinophils then migrate to tissues throughout the body. When a foreign substance enters the body, lymphocytes and neutrophils release certain substances to attract eosinophils which release toxic substances to kill the invader.

In plain English When a foreign substance enters the body, lymphocytes and neutrophils release certain substances to attract eosinophils which release toxic substances to kill the invader.

Urticaria

Angioedema Swelling in mouth or throat Less often the sheer amount of swelling means that so much fluid has moved out of your blood circulation that your blood pressure drops dangerously

Angioedema

Smooth Muscle Spasm Bronchospasm GI Tract Spasm Bladder Spasm Respiratory distress “Tight Chest” Wheezing GI Tract Spasm Nausea, vomiting Cramping, diarrhea Bladder Spasm Urinary urgency Urinary incontinence

Classification Mild allergic reaction Moderate allergic reaction Severe allergic reaction (anaphylaxis)

Mild Allergic Reaction Characteristics Urticaria (hives), itchy Erythema (redness) Rhinitis Conjunctivitis Mild bronchoconstriction Usually localized (look on abdomen, chest, back) No SOB or hypotension/hypoperfusion Often self-treated at home

Erythema

Pruritus

urticaria

wheals

Conjunctivitis

Moderate Allergic Reaction Characteristics Mild signs/symptoms with any of following: Dyspnea, possibly with wheezes Angioneurotic edema Systemic, not localized No hypotension/hypoperfusion

Severe Allergic Reaction (Anaphylaxis) Characteristics Mild and/or moderate signs/symptoms plus Shock / hypoperfusion

Clinical Manifestation Dependent on: Degree of hypersensitivity Quantity, route, rate of antigen exposure Pattern of mediator release Target organ sensitivity and responsiveness

Assessment findings in anaphylaxis Focused History and Physical Exam Focused History Sample and OPQRST history Rapid onset usually 30-60 seconds following exposure Speed of reaction is indicative of severity Previous allergies and reactions

Assessment findings in anaphylaxis Physical Exam Presence of severe respiratory difficulty / hypotension is key to differentiating anaphylaxis from allergic reaction

Clinical Manifestation Severity varies from mild to fatal Most reactions are respiratory, dermatologic Less severe early findings may progress to life- threatening over a short time Initial signs/symptoms do NOT necessarily correlate with severity, progression, duration of response Generally, quicker symptoms = more severe reactions

Clinical Manifestation First manifestations involve skin Warmth and tingling of the face, mouth, upper chest, palms and/or soles, or site of exposure Erythema Pruritus is universal feature, erythema May be accompanied by generalized flushing, urticaria, nonpruritic angioedema

Erythema Erythema exsudativum multiform majus presents with typical or atypical targets mainly localized on the limbs and hemorrhagic erosions of at least one mucosal site. The skin detachment is below 10% of the body surface area.

Clinical Manifestation May progress to involvement of respiratory system cough chest tightness dyspnea wheezing throat tightness dysphagia hoarseness

Clinical Manifestation Other Signs and Symptoms lightheadedness or syncope caused by hypotension or dysrhythmia nasal congestion and sneezing ocular itching and tearing cramping abdominal pain with nausea,vomiting, or diarrhea bowel or bladder incontinence decreased level of consciousness

Clinical Manifestation Physical Exam findings may include urticaria, angioedema, rhinitis, conjunctivitis tachypnea, tachycardia, hypotension laryngeal stridor, hypersalivation, hoarseness, angioedema

Insect Sting Hypersensitivity Hymenoptera - yellow jackets, honeybees, hornets, wasps, bumble bees 90%: Local hives, Pruritus 10%: Massive local reaction, including swelling beyond two joints of extremity 1%: Systemic reaction 10%: have worse reaction on second sting 28%: have recurrent systemic reaction

Management Treatment depends upon severity of reaction and signs/symptoms of its presentation

Management Optimal management requires High index of suspicion (suspect, treat within minutes) Early diagnosis Pharmaceutical intervention Observation Disposition

Management of Anaphylaxis Scene safety Consider the Possibility of Trauma Protect the Airway Use Airway Adjuncts with care Intubate early in severe cases to prevent total occlusion of the airway Be prepared to place a surgical airway

Management of Anaphylaxis Support breathing High flow oxygen or assisted ventilation if indicated Establish IV access Patient may be volume depleted due to “third spacing” of fluid Administer crystalloid solution at appropriate rate. Place a second IV if indicated

Patient Self-Management Benadryl 50 mg p.o. At any sign of anaphylaxis, self-administer IM epinephrine (Epi-Pen®, Ana-Kit®) If short of breath or wheezing, use aerosolized epinephrine (Primatene Mist, Medihaler-Epi)

Mild Allergic Reaction Often self-treated at home Diphenhydramine 25 - 50mg IV or deep IM IV is acceptable FOR LAST RESORT – HEROIC MEASURES If stinger present, flick it away with credit card or fingernail May consider (if available and indicated): cimetidine or ranitidine prednisone inhaled beta-agonists

Moderate Allergic Reaction High flow oxygen IV NS Titrated to systolic BP 90 mm Hg ECG monitor Beta agonists Nebulized albuterol, isoetharine, terbutaline IM terbutaline or epinephrine 1:1000 or IV aminophylline if severe bronchoconstriction Diphenhydramine 25-50 mg IM or IV Methylprednisolone 125 mg IV Transport

Anaphylaxis Airway and Breathing Circulation High concentration oxygen Ventilations, ETT, alternative airway prn Consider inhaled beta agonists Circulation Large bore IV NS X 2 Quickly titrate fluids to perfusion with bolus therapy ECG monitor Treat as pre-arrest patient

Anaphylaxis FOR FAILURE TO RESPOND TO PREVIOUS Epinephrine 0.5 - 1.0 mg 1:10,000 IV prn Hypotension unresponsive to fluids and epinephrine è consider dopamine ~10 mcg/kg/min Bronconstriction unresponsive to Epi è consider aminophylline Diphenhydramine 50 mg IV Methylprednisolone 125 mg IV Rapid transport

Disposition Regardless of response to therapy, all patients with systemic features must be observed for 6 to 8 hours

Latex Allergies Due to a growing number of persons experiencing latex allergies, EMS providers should be prepared to treat patients with such allergies Have latex free equipment Use the patient’s latex free supplies

QUESTIONS?

What specific information would you like at this point? Case Presentation #1 You are dispatched to an electronics manufacturing plant to see a 28-year-old woman. The woman believes she is having an allergic reaction. Security officers will meet you at the front gate and escort you to the patient. What specific information would you like at this point?

Case Presentation #1 You find this patient in an office area sitting at her desk. From a distance, you notice she is awake and speaking clearly. She does not appear to have any breathing difficulty. She states she had just returned from lunch and began to feel hot and light headed. Her friend pointed out that the patient’s arms and neck are very red, and that her face appears “puffy”.

Case Presentation #1 The patient states she is allergic to peanuts but has not eaten any. She went to a health food café where she had grilled chicken and steamed vegetables. She has no other past history and takes no medications. Her last allergic rx was similar to this. Vitals are: BP-116/70; Pulse-100; RR-20; Lung sounds-clear and equal. No difficulty swallowing, redness to her arms, chest, neck and face. Would you like to perform any other procedures/exams/testing or obtain other history before treating?

So, what is your complete treatment plan for this patient? Case Presentation #1 So, what is your complete treatment plan for this patient?

Case Presentation #2 39 year-old male found at home in respiratory arrest with a bradycardic carotid pulse. His wife states he was helping a friend paint when he was apparently stung by a bee. He walked into the house, saying “I don’t feel good,” and collapsed.

Case Presentation #2 PMH: depression, gastritis, seasonal allergies Medications: Ritalin, Zantac, Prozac, Claritin No known drug allergies No prior reactions to hymenoptera What therapies would you like to begin for this man?

Case Presentation #2 You have done the following: intubated orotracheally administered intravenous epinephrine, 0.5 mg & Diphenhydramine 50 mg started 2 large-bore IVs of NS and given 500 cc fluid At this point, the patient no longer has a pulse

Case Presentation #2 You begin CPR and give the following: Dopamine drip at 10 mcg/kg/min Epinephrine, 1:10,000, 1 mg IV q 3-5 min You now note the following: ECG: Idioventricular rhythm Lung Sounds: difficult to hear Obvious facial edema Can you think of any ideas for further treatment?

How to avoid future stings 1. Don’t “smell like a rose” - avoid scented soaps and fragrances 2. Wear garments that fit close to the body. Insects can become trapped in loose-fitting clothing and will sting defensively. 3. Wear shoes outdoors at all times, in addition to long pants and long-sleeved shirts.

How to avoid future stings 4. Wear clothing in colors not attractive to bees: white, red, grey. Avoid floral designs and brown clothing, which may mimic the color of the bee’s natural predator, the brown bear. 5. Wasp or hornet nests or beehives near the home should be destroyed by a professional exterminator.

How to avoid future stings 6. Stay away from insect feeding grounds: flower beds, fields of clover, garbage, orchards with ripe fruit. 7. Avoid outdoor picnics.