Anaphylaxis

Introduction

Anaphylaxis is an acute, potentially life-threatening allergic systemic reaction. The mechanisms and clinical presentations are varied. It results from the sudden systemic release of mediators from mast cells and basophils. Most are due to IgE-mediated allergic reactions to foods (30% of fatal cases of anaphylaxis), drugs, and insects. 

Pathogenesis

• Most commonly, anaphylaxis occurs due to IgE mediated reactions when allergens interact with allergen-specific IgE antibodies (formed from previous exposure) bound to FcE receptors on mast cells and basophils.
          
  • Cross-linking of IgE receptors and cell activation cause mediators (e.g., histamine, platelet-activating factor), enzymes (e.g., tryptase) and cytokines (e.g., tumor necrosis factor, IL-4) to be released from mast cells and basophils, which result in vasodilatation, increased vascular permeability (resulting in massive fluid shifts), smooth muscle contraction, and mucus secretion
  • Released cytokines attract and activate other cells which produce an inflammatory response that is more prolonged.
  • Multiple systems are affected during an acute IgE mediated reaction including skin, GI tract, respiratory tract and cardiovascular system, explaining the widely variable clinical presentation of anaphylaxis 
• Alternative mechanisms for anaphylaxis include immune complex/complement-mediated and direct mast cell stimulation (e.g., vancomycin resulting in "red man syndrome", opiate medications, radiocontrast media)

Systemic clinical manifestations

1. Skin and mucosal: Flushing, pruritis, uticaria, angioedema of the eyelids, lips, uvula, glottis, tongue, tearing or itching of eyes (90% of anaphylaxis cases involve the skin)
2. Respiratory: Sensation of throat closure or choking, upper airway edema, cough, stridor, wheezing, shortness of breath, nasal discharge and congestion (70%)
3. Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain (45%)
4. Cardiovascular: Hypotension, arrhythmia, syncope, dizziness (45%)

Angioedema. http://en.wikipedia.org/wiki/Anaphylaxis#mediaviewer/File:Angioedema2010...

The reaction may be immediate within seconds, delayed for hours, or be biphasic with recurrence of symptoms or new symptoms.

• Injected/IV allergens tend to cause symptoms more rapidly than ingested allergens (seconds to minutes vs. minutes to 1-2 hours, respectively). Though there are exceptions.
• There may be a prodrome such as a rash around the mouth, itchy tongue, lips, or mouth, that may cause the individual to seek attention prior to the development of more serious symptoms.
• At different times, patients will have a different reaction with the same contact. May be dose related.

Common precipitators of anaphylactic reaction

Foods

• Additives are not common causes of anaphylaxis
• Nuts, fish, shellfish

• ​Often there is cross reactivity among different foods within groups. It is advisable to avoid all nuts if you are allergic to peanuts unless oral challenges are negative. Avoidance is often difficult. Some foods are labeled under different names and may not be noticed. Also, certain foods have ingredients added that the patient is unaware of. This is especially common in baked goods that contain nuts
• ​Eggs, milk, soy - allergies to these foods are often outgrown

Insect stings: bees, wasps, fire ants. Must differentiate from localized reaction because if it is true anaphylaxis, immunotherapy may be indicated. 

Pharmaceuticals

• Penicillin- most skin testing is ineffective because test material does not contain material that allergic reaction is against. 
• Aspirin, NSAIDs, sulfonamides
• Vaccines-All vaccines have been reported to cause anaphylaxis but most discussion is about MMR because it is made with egg products and the high incidence of egg allergies in children. The MMR can be given to individuals sensitive to eggs if you watch them after the shot for 30 minutes and are prepared to give epinephrine. There is no reason to skin test first or give in small doses
• Contrast media
• Allergy shots- have patient wait after you give the shot to make sure there is no reaction
• IVIG

Latex: 

• Common in spina bifida and patients with GU anomalies

Exercise: 

• Different from exercise induced bronchospasm. May be sporadic and related to something the person ate prior to exercise. Food alone doesn't cause the reaction

Idiopathic: 

• Recurrent anaphylaxis without apparent external cause

Acute diagnosis

Anaphylaxis is highly likely when any ONE of the following 3 criteria is fulfilled:

CRITERION 1. Acute onset of an illness with the involvement of the skin, mucosal tissue, or both 
AND AT LEAST ONE OF THE FOLLOWING
 A. Respiratory compromise
 B. Reduced BP or associated sympotms of end-organ dysfunction

CRITERION 2. TWO OR MORE OF THE FOLLOWING that occur rapidly after exposure to a likely allergen for that patient:
A. Involvement of the skin-mucosal tissue
B. Respiratory compromise
C. Reduced BP or associated sympotms
D. Persistent Gastrointesinal sympotms

CRITERION 3. Reduced BP after exposure to know allergen for a patient

Clinical criteria for diagnosing anaphylaxis. Second symposium on the definition and management of anaphylaxis: Summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium

Emergency treatment

Epinephrine is the treatment of choice for anaphylaxis and should be given immediately. Epinephrine saves lives!

• Assess airway, breathing, and circulation
• IM Epinephrine (1 mg/mL preparation) - 0.01mg/kg (max dose 0.5 mg) administered intramuscularly (anterior-lateral thigh, preferred) every 5-15 min.
  • ​IV epinephrine is an option for patients with severe hypotension or cardiac arrest unresponsive to IM epi and fluid resuscitation
• Place patient in the recumbent position with legs elevated (increase stroke volume, cardiac output)
• Administer oxygen by non-rebreather mask or endotracheal tube, if needed 
• Aggressive IV fluid resuscitation for hypotension unresponsive to epinephrine (up to 35% of the blood volume may shift to extravascular space in the first 10 minutes due to increased vascular permeability)
• Other vasopressors (norepinephrine, vasopressin) may be required if SBP < 90 after epinephrine and fluid resuscitation
• H1 and H2 antihistamines (e.g., diphenyhydramine, ranitidine) IM or IV (or oral with mild sx) may be given for symptomatic treatment of uticaria/angioedema/pruritis but ineffective for raising blood pressure
• Steroids - slower to act, may be helpful in preventing protracted/recurrent symptoms, though no clinical evidence to support this
• If severe bronchospasm, may give nebulized albuterol
• If stridor, may try epinephrine by nebulizer
• If on beta-blocker, may try glucagon
• Careful observation after initiating treatment. Decision on admitting child to hospital is dependent on condition after therapy.

Follow up after anaphylaxis

• Patients who have experienced anaphylaxis due to an exposure encountered outside of a medical setting should carry self-injectible epinephrine (e.g., EpiPen, AUVI-Q) in case anaphylaxis develops
• Child should have Medic-Alert bracelet
• Family, school, camp, baby-sitter, etc. should be aware of the condition and know what to avoid. Also they should be familiar with reaction and have an Epinephrine "kit" available and know how to use it.
• Patient Counseling
  • Seek support
  • Allergen identification and avoidance
  • Follow up with Allergist
  • Epinephrine for emergencies

    

CLICK HERE for a video on how to use the injectible EPI PEN.

References

1. Lieberman P. Kemp S. etal. The diagnosis and management of anaphylaxis: an updated practice parameter.  J Allergy Clin Immunol 2005 Suppl: S 483
2. Waibel KH. Anaphylaxis. Pediatr Rev. 2008;29(8):255-263. doi:10.1542/pir.29-8-255
3. Pathophysiology of anaphylaxis - UpToDate
4. Pichichero M. A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Pencillin-Allergic Patients. Pediatrics April 2005 pg 1048
5. Gruchalla R. Pirmohamed M. Antibiotic Allergy NEJM Feb 9, 2006
6. Lack G. Food Allergy.  NEJM Sept 18, 2008
7. Sampson HA, Munoz-Furlong A.Second Symposium on the definition and management of anaphylaxis: summary report.  Second National Institute of Allergy abd Infectious Diseasae/Food Allergy and Anaphylaxis Newtowrk Symposium.  J. Allergy Clin Immunol 2006 Feb;117(2):391-7.
8. National Institue of Allergy and Infectious Disease.Guidelines for the Diagnosis and Management of Food Allergy in the United States Dec 2010
9. Caubet J. et al.The role of penicillin in benign skin rashes in childhood: A prospective study based on drug rechallenge. J of Allergy and Clinical Immunology 2011
10. Burkes A. et al.  NAID-Sponsored 2010 Guidelines for Managing Food Allergy: Applications for Pediatric Population.  Pediatrics Nov 2011
11. Burks A et al.  Oral Immunotherapy for Treatment of Egg Allergy in Children.  NeJM July 19, 2012
12. Emergency management of anaphylaxis in infants and children - UpToDate.