Anaphylaxis Jay Prochnau, MD Indiana University Health Arnett Allergy/Asthma Lafayette, IN.

Anaphylaxis

Jay Prochnau, MD

Indiana University Health Arnett

Allergy/Asthma

Lafayette, IN

Disclosures

• Conduct research in COPD and asthma for GSK and Genentech/Roche

• No conflicts of interest

Anaphylaxis

• Definition• Symptoms• Mechanisms• Causes• Treatment• Workup/prevention

Definitions

• “Ana” = against, “phylaxis” = protection

• Coin termed in 1902 by Portier and Richet

• Attempts to vaccinate dogs against the toxin of sea anemones led to death at much lower doses

Definitions

• “I know it when I see it”– Potter Stewart

• World Allergy Organization: “A severe, life threatening, generalized or systemic hypersensitivity reaction”

• NIAID/FAAN: “A serious allergic reaction that is rapid in onset and may cause death”

Criteria• Criterion 1 – acute onset (minutes to hours) of an illness involving

the skin, mucosal tissue or both (eg hives, pruritus, flushing, swollen tongue/lips/uvula) and at least one of the following:

– Respiratory compromise (dyspnea, wheeze, stridor, hypoxemia, reduced peak flow)

– Reduced blood pressure or associated signs/symptoms (hypotonia, syncope)

• Criterion 2 – 2 or more of the following that occur rapidly (minutes to hours) after exposure to a likely allergen:

– Skin involvement– Respiratory compromise– Reduced BP– Persistent GI symptoms (abdominal cramping, vomiting)

• Criterion 3 – reduced BP after known allergen (minutes to hours)– Systolic <90mmHg (<70 in children), or 30% decrease is SBP

Working definition

• An potentially fatal reaction that involves more than one organ system

Definitions

• Anaphylaxis can be immunologic or non-immunologic, IgE mediated or non-IgE mediated

• Non-IgE mediated anaphylaxis used to be called “anaphylactoid”

Signs and symptoms

• Cutaneous >90%– Urticaria and angioedema 85-90%– Flushing 50%– Pruritus, no rash 2-5%

• Respiratory 40-60%– Dyspnea, wheeze 45-50%– Upper airway swelling 50-60%– Rhinitis 15-20%

Signs and symptoms

• Circulatory– Dizziness, syncope, hypotension, tachycardia 30-35%

• GI– Nausea, vomiting, diarrhea, cramping 25-30%

• Miscellaneous– Headache 5-8%– Chest pain 4-6%– Seizures 1-2%

Signs and symptoms

Mechanisms of anaphylaxis

• Main mediator of anaphylaxis is histamine• Histamine released from mast cells• Mast cell degranulation triggered by cross linking of IgE

antibodies bound to IgE receptors

Mechanisms of anaphylaxis

Effects of histamine

• Activation of itch receptors Pruritus, urticaria

• Vasodilation Urticaria, edema

• Smooth muscle contraction Wheezing

• Increased vascular permeability edema, ↓ BP

Other mast cell mediators

• Neutral proteases– Tryptase, chymase, carboxypeptidase

• Proteoglycans– Heparin, chondroitin sulfate

• Leukotrienes

• Prostoglandins

• Platelet activating factor

Causes of anaphylaxis

• Medications– Most common cause of anaphylaxis (inpatient)– Drug reactions responsible for 230,000 hospital admissions in the US

annually

• Foods– Food allergy affects 6-8% of children, 3-4% of adults– Most common cause of anaphylaxis at home

• Insect stings– 40 deaths/year estimated due to Hymenoptera stings

• Blood products– Anti-IgA antibodies in an IgA deficient patient

Causes of anaphylaxis

• Exercise– May be food dependent

• Vaccines– Gelatin, ovalbumin

• Human seminal plasma anaphylaxis

• Aeroallergens – uncommon cause of anaphylaxis (horse)

Anaphylaxis to medications

• Antibiotics– Most common medication class associated with anaphylaxis– Penicillin, sulfonamides– Vancomycin – usually non IgE mediated/direct mast cell

activation

• NSAIDs– Second most common– Most probably not IgE mediated

• Radiocontrast media– Usually not IgE mediated– Incidence appears to be diminishing

Anaphylaxis to medications

• Perioperative anaphylaxis– Most common neuromuscular blocking agents (62%)– Natural rubber latex (16%)– Intraoperative antibiotics– Protamine use to reverse heparin

• Opioid analgesics– Non IgE mediated– Directly activate mast cells

Anaphylaxis to foods

Anaphylaxis to foods

• Any food can cause anaphylaxis• Most common peanut and tree nuts• “Big 6” foods

– Peanut/tree nuts– Shellfish/fish– Cow’s milk– Egg– Soy– Wheat

Anaphylaxis to insect stings

• Hymenoptera venoms most common• Hymenoptera = “membrane winged” insects

– Yellow jacket, yellow hornet, white faced hornet, paper wasp, honeybee, imported fire ant (in the south)

• Anaphylaxis reported to multicolored asian lady beetles

Causes of anaphylaxis

• Up to 60% of cases of anaphylaxis referred to allergy specialty clinics have no apparent trigger = “idiopathic anaphylaxis”

Differential diagnosis of anaphylaxis

• ACE inhibitor mediated angioedema– Mediated by bradykinin, not histamine– May affect up to 2.2% of patients on ACE inhibitors

• Restaurant syndromes– Scombroid fish poisoning– Anisakiasis– MSG– Sulfites

• Mastocytosis– Systemic mastocytosis, mast cell activation syndrome

Differential diagnosis of anaphylaxis

• Nonorganic disease– Vocal cord dysfunction, globus hystericus, panic attack

• Vasovagal syncope– Pallor as opposed to flushing– Bradycardia as opposed to tachycardia

• Myocardial infarction or stroke

• Flushing disorders– Menopause– Medications that cause flushing (niacin)– Alcohol

Differential diagnosis of anaphylaxis

• Tumors– Carcinoid– Pheochromocytoma– GI tumors: VIPoma– Medullary carinoma of the thyroid

• Idiopathic capillary leak syndrome– Rare, can be fatal

• Undifferentiated somatoform anaphylaxis

Diagnosis of anaphylaxis

• Diagnosis of anaphylaxis is primarily clinical

• Laboratory workup may be helpful– Histamine

• Stays elevated for 30-60 minutes• Urinary metabolites may stay elevated for 24 hours

– Tryptase• Stays elevated for 4-6 hours• May not be elevated in anaphylaxis due to food allergy

– Platelet activating factor (PAF)• “BNP” of anaphylaxis• Increasing levels of PAF may indicate greater severity

Tryptase in anaphylaxis

PAF in anaphylaxis

• N Engl J Med 2008 Jan 3;358(1):28-35N

Treatment of anaphylaxis

• ABCs• Protection of airway crucial, early intubation if

necessary– Laryngeal edema most common cause of death from

anaphylaxis– Supplemental oxygen

• Pressure support– Place patient in recumbent position, elevate lower

extremities– IV fluids, pressors if necessary

Treatment of anaphylaxis

• “EASI”• Epinephrine 1:1000

– First line therapy for anaphylaxis– Should be given IM (as opposed to SC or IV), lateral thigh

(vastus lateralis muscle) for optimal absorption– Dose 0.3 to 0.5ml for adults, 0.01ml/kg for children– Can be repeated every 5-15 minutes as needed

• Antihistamines– Diphenhydramine or hydroxyzine 50mg every 6 hours

• Steroids– Methylprednisolone or prednisone to prevent biphasic

reaction

• Inhaled beta-agonists (e.g., albuterol)

Absorption by administration site

Prevention of anaphylaxis

• Allergy referral

• Careful history and directed testing to identify trigger of anaphylaxis– Skin testing vs RAST testing– Skin testing to medications is of limited utility with the

exception of penicillin

• Patients should have access to an epinephrine autoinjector

Prevention of anaphylaxis

Prevention of anaphylaxis

Prevention of anaphylaxis

• Medication allergy– Avoidance– Desensitization if necessary

• Food allergy– Avoidance– Trials with oral immunotherapy look promising

• Hymenoptera allergy– Venom immunotherapy 98% curative, 100% effective

Prevention of anaphylaxis

• Radiocontrast media allergy– Use of lower osmolar or nonionic contrast media– Pretreatment with steroids and antihistamines

• Prednisone 50mg 12h, 6h and 1h and diphenhydramine 50mg 1h prior to RCM administration

• Hydrocortisone 200mg and diphenhydramine 50mg pre-procedure

– Risk of reaction 60% if high osmolar contrast is used again, 6% with either low osmolar contrast media or with pretreatment, 0.6% with low osmolar contrast media and pretreatment

Mast cell activation disorders

• Primary mast cell disorders– Mastocytosis– Monoconal mast cell activation disorder (MMAD)

• Secondary mast cell disorders– Allergic disorders (IgE mediated urticaria/anaphylaxis)– Chronic autoimmune urticaria/angioedema

• Idiopathic mast cell disorders– Idiopathic anaphylaxis– Idiopathic urticaria/angioedema– Idiopathic mast cell activation syndrome (MCAS)

Questions