Anaphylaxis Q & A

Lee Herold, DVM, DACVECC, defines anaphylaxis in cats and dogs and discusses potential causes, diagnosis, and treatment for this potentially fatal emergency.

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Q: What is anaphylaxis?
A: Anaphylaxis is a type I hypersensitivity reaction. In type I hypersensitivity reactions antigens bind to preformed IgE present on mast cells and stimulate mast cell degranulation. Anaphylactic reactions are differentiated from simple allergic reactions by the severe systemic manifestation of mast cell degranulation including hypotension, respiratory distress and cardiovascular collapse that occur after exposure to the antigen. Anaphylactoid reactions do not require preformed IgE and therefore are not technically type I hypersensitivities but are clinically indistinguishable. Therefore both anaphylactic and anaphylactoid reactions should be approached in the same manner clinically. The antigens that can trigger these systemic reactions are wide-ranging and include foods, biological products (e.g., blood or plasma transfusions, intravenous immunoglobulin), vaccines, medications, insect bites or other envenomations, contact (e.g., latex) or inhaled allergens (e.g., pollen). Whatever the inciting cause of anaphylaxis, an important note is that anaphylaxis is a severe, systemic and a potentially life-threatening result of antigen exposure.

Q: What are the target organs of anaphylaxis in dogs and cats?
A: The target organ of anaphylaxis in dogs is the gastrointestinal tract, specifically the liver. The target organ of anaphylaxis in the cat is the respiratory tract. Species differences in the concentration and location of mast cells within the body determine the target organ of anaphylaxis and also contribute to which clinical signs are observed in patients with anaphylaxis. For this reason dogs that present with anaphylaxis are more likely to have collapse associated with vomiting and diarrhea, which can progress to hemorrhagic diarrhea. Dogs with anaphylaxis may or may not have cutaneous signs (figures 1 and 2) associated with allergic reaction. In a comparison of anaphylaxis with simple allergic reaction in a series of dogs, cutaneous signs were significantly associated with only allergic reactions, while when observed in anaphylaxis the skin signs were often subtle. It is less common for dogs to have respiratory distress associated with anaphylaxis unless facial and laryngeal edema are severe. This occurs more commonly in brachycephalic breeds that are anatomically less capable of compensating for even small amounts of facial or laryngeal edema. With the target organ of anaphylaxis in cats being the respiratory tract, cats are more likely to present with collapse and respiratory distress manifests as open mouth breathing, tachypnea, dyspnea, and hypoxemia.

Q: Are there any lab or diagnostic tests for anaphylaxis?

A: Unfortunately anaphylaxis in veterinary and human medicine remains a diagnosis largely based on history and clinical presentation. The World Allergy Organization has published guidelines for the clinical diagnosis of anaphylaxis in humans. Figure 3 provides the human diagnostic criteria for anaphylaxis. In this diagnostic tree, the suspicion for anaphylaxis relies heavily on potential or known exposure to an inciting antigen; however, criterion for the diagnosis of anaphylaxis when there is no known antigen exposure is also given. When a patient presents with no antigen exposure and cutaneous signs of allergic reaction, they need to have either respiratory signs or collapse to meet the criterion for diagnosis of anaphylaxis. This column of the human diagnostic criteria is the most common scenario that we encounter in veterinary medicine, as most of our patients are unable to voice the exposure to potential antigens. Biomarkers of mast cell degranulation, including measurement of serum tryptases and histamine, have been used in human medicine to support the clinical diagnosis of anaphylaxis.  These tests, however, are not routinely available even in human hospitals, and not specific for anaphylactic reactions rendering them relatively useless for clinical decision-making. Because the liver is a target organ of anaphylaxis in dogs, elevations in alanine transaminase (ALT) have been evaluated as a biomarker of anaphylaxis. ALT elevation has an 85% sensitivity and 98% specificity in differentiating anaphylaxis from simple allergic reaction. Ultrasounds of the gall bladder wall demonstrating either thickened gall bladder wall at >3mm or striated appearance of the gall bladder wall , when  evaluated between patients with simple allergic reaction and anaphylaxis, had a 93% sensitivity and 98% specificity for anaphylaxis.[NP1] Because diagnosis of anaphylaxis remains dependent on history and clinical signs, a complete differential list should be always be considered. Common emergency problems that may have similar presentations to anaphylaxis include acute hemorrhage, addisonian crisis, pericardial effusion, heat stroke, severe hemorrhagic gastroenteritis, and acute decompensation of allergic or reactive airway disease.

Q: How do I treat anaphylaxis?
A: Epinephrine remains the mainstay of treatment for any patient with anaphylaxis. Epinephrine increases blood pressure with alpha adrenergic activity and decreases mast cell degranulation. Epinephrine can also promote bronchodilation and relieve airway obstruction. Patients with hypotension refractory to initial epinephrine doses and intra-vascular volume loading can be placed on a continuous rate infusion of epinephrine or other vasopressors. After epinephrine other rationale pharmaceutical interventions include the administration of corticosteroids to reduce formation of inflammatory end products of the arachidonic acid cascade, and antihistamines to reduce edema and vasodilation associated with histamine release. Fluid therapy including colloid and crystalloid fluid therapy is especially important in patients with severe GI fluid losses and hypotension to replenish intravascular volume. Oxygen therapy is indicated to support patients with respiratory distress and hypoxemia particularly cats. The need for intubation and ventilation of a patient because of anaphylaxis is uncommon.

Q: What can we do to prevent anaphylaxis?
A: Antigen avoidance is the only way to prevent anaphylaxis. Avoidance is feasible in instances in which the inciting antigen is known (e.g., vaccinations, known food ingredients, medications). Avoidance is made difficult for many veterinary patients presenting with anaphylaxis because the inciting antigen is unknown or is environmental  consequently rendering avoidance 100% of the time not practical (the case for most insect stings or spider bites).

Q: Is there a role for EpiPens® in veterinary anaphylaxis?
A: EpiPens® are commercially available epinephrine packaged auto-injectors intended for home use and intramuscular injection in humans to treat anaphylaxis. EpiPens come in 0.15mg (EpiPen Jr®) and 0.3mg auto-injectors. There are 2 injectors (2 doses) per package. At the 0.01mg/kg epinephrine dose the 0.15mg injector is an appropriate dose for a 15kg veterinary patient, the 0.3mg injector is appropriate for a 30kg patient. EpiPens® may be cost prohibitive for veterinary species with a cost of about $300-400 for a 2-pack. The cost may change in the next couple of years as EpiPens® are expected to come off patent. In rare instances of patients with repeated presentations of anaphylaxis due to unavoidable antigens, I have dispensed injectable epinephrine in individual dosing syringes for SQ or IM injection. Dispensing epinephrine requires careful client communications about the indications, side effects and administration at home. Dispensing epinephrine in individual dosing syringes is less costly for the client compared to EpiPens®, and the dose can be customized for our veterinary patients. The prescription of epinephrine or EpiPens® is intended to be used for emergency treatment and can be life-saving in anaphylaxis, but it does not preclude the need to seek veterinary care as soon as possible for fluids, oxygen and monitoring. A scenario in which I have dispensed epinephrine that is particularly relevant here in the Pacific Northwest is the dog that experiences anaphylaxis because of insect stings during back country hikes with the owners. In an instance such as this the patient demonstrates a history of anaphylaxis, the antigen is largely unavoidable and the patient would be secluded enough from veterinary clinics so as not to be able to seek veterinary care in an appropriate timeframe for successful treatment of anaphylaxis.

Suggested Readings:
1. Shmuel DL, Cortes Y. Anaphylaxis in dogs and cats. Journal of Veterinary Emergency and Critical Care 2013;23(4): 377-394.
2. Simons FER, Ardusso LRF, Bilo MB, et al. World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis. Journal of Allergy and Clinical Immunology 2011;127(3):587-593. E1-e20.
3. Quantz JE, Miles MS, Reed AL, White GA. Elevation of alanine transaminase and gall bladder wall abnormalities as biomarkers of anaphylaxis in canine hypersensitivity patients. Journal of Veterinary Emergency and Critical Care 2009;19(6):536-544.

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