Specialty Spotlight: Anaphylaxis

Anaphylaxis

Chelsea Zorn, DVM, DACVECC

 

Anaphylaxis

With warmer and nicer weather also comes the increased exposure to allergens for our canine and feline friends, potentially leading to anaphylaxis. Anaphylaxis is a severe, potentially fatal, systemic allergic reaction that occurs suddenly after contact with an allergy-causing substance.

There are anaphylactic and anaphylactoid reactions, which are both systemic, immediate-type hypersensitivity reactions. Anaphylactic reactions are mediated by IgE (i.e., secondary to insect bites, venom, food, and medications), while anaphylactoid reactions are IgE-independent (i.e., transfusion reactions). Clinically, these are indistinguishable, and diagnosis and treatment are identical.

The chemical mediators of anaphylaxis include histamine, heparin, proteases, and proteoglycans. Shock develops as a result of the rapid release of these potent inflammatory and vasoactive mediators, which increase vascular permeability and lead to vasodilation and hypovolemia.

 

Physical Exam Findings and Clinical Signs

The severity of the anaphylactic event is related to the amount of mediators released as well as the rapidity of their degradation. The systemic response progresses rapidly with the release of mediators within seconds to minutes. The onset of clinical signs is usually within 5-30 minutes.

There are well-recognized species differences for acute systemic anaphylaxis in the major organ systems affected and the associated clinical signs. In dogs, the gastrointestinal tract and the liver are the primarily affected organs, and the severity of shock is directly proportional to the degree of congestion to the liver and gallbladder. In the cat, the respiratory tract predominates as the shock organ.

Signs and symptoms can be divided into four major categories: cutaneous, respiratory, cardiovascular, and gastrointestinal.

Cutaneous:

Symptoms are often subtle and short-lived and include:

  • Generalized erythema
  • Urticaria
  • Pruritus
  • Facial angioedema

Respiratory:

These signs are seen more commonly in cats than in dogs:

  • Dyspnea (from laryngeal and pharyngeal edema)
  • Bronchospasm
  • Stridor
  • Tachypnea
  • Cough

Cardiovascular:

Patients with anaphylaxis will often develop distributive-hypovolemic shock characterized by hypotension and increased vascular permeability, leading to massive fluid shifts. As much as 35% of intravascular volume can shift into the extravascular space within 10 minutes, resulting in rapid hemodynamic collapse and the following signs:

  • Pale mucous membranes
  • Prolonged capillary refill time
  • Poor pulse quality
  • Hypothermia
  • Depressed to dull mentation
  • Arrhythmias and myocardial ischemia

Hemoperitoneum development can be seen, though the exact mechanism is not fully understood. In a case report on 11 dogs with concurrent anaphylaxis and hemoperitoneum, 10/11 survived to discharge, and all were medically managed for their hemoabdomen.

Gastrointestinal:

These signs commonly occur with anaphylaxis and include:

  • Nausea
  • Vomiting
  • Diarrhea (+/- hemorrhagic)

Other clinical signs include weakness, syncope, seizures, conjunctival infection, and lacrimation.

 

Diagnostics

Due to the lack of an accepted standard working definition and wide variability of clinical manifestations, anaphylaxis can be difficult to diagnose.

When taking a history on a patient, these questions can increase your suspicion of an anaphylactic reaction:  

  • Previous history of hypersensitivity reactions
  • Recent vaccinations
  • Previous transfusions
  • Exposure to new foods, medications, or insect bites/stings
  • Acute onset of illness (minutes to several hours)

Bloodwork

  • An increase in ALT concentration
  • Other blood work changes can be seen consistent with shock and dependent on the underlying organs affected.

Imaging

  • A thickened, striated gallbladder wall (‘gallbladder halo sign’)
  • If the respiratory tract is affected and there is upper airway obstruction present, non-cardiogenic pulmonary edema can be seen on radiographs.
  • Abdominal ultrasound may reveal free fluid and, when sampled, consistent with a hemoabdomen.

 

Treatment and Monitoring

Anaphylaxis is a true medical emergency. Aggressive treatment should be initiated as soon as possible since there is a high potential for rapid and progressive deterioration. Anaphylaxis can also be “biphasic,” meaning it can recur after several hours. It can also be considered “persistent,” with clinical signs lasting up to 32 hours, but this is uncommon. Ideally, these patients should be monitored in a medical setting for a period of 3 days.

Epinephrine

An essential medication in the treatment of anaphylaxis.

Stimulates both α and β adrenergic receptors. Alpha-1 adrenergic effects result in vasoconstriction to increase peripheral vascular resistance. Beta-1 adrenergic effects result in positive inotropic and chronotropic activity to increase cardiac output. Beta-2 adrenergic effects are the most important in that it suppresses the release of mediators of inflammation from mast cells and basophils.

Doses:

  • mg/kg IM (do not exceed 0.3mg in patients <40kg or 0.5mg in patients >40kg). This dose can be repeated every 5-15min as needed.
  • 05 mcg/kg/min IV CRI titrated to clinical effect for those in significant shock.
  • Subcutaneous injections should be avoided as epinephrine is a powerful vasoconstrictor which will delay its absorption.

Adverse effects of epinephrine include:

Ventricular arrhythmias, hypertension, myocardial infarction, and pulmonary edema.

Antihistamines

Antihistamines should never be substituted for epinephrine in the treatment of anaphylaxis. They should be administered as an ancillary treatment, alone or in combination, to relieve cutaneous signs and symptoms (especially urticaria and pruritus) as well as decrease gastric acid secretion.

H1 antihistamines (e.g., diphenhydramine, cyproheptadine, cetirizine) shift and stabilize H1 receptors but do not prevent ongoing mediator release. H2 antihistamines (e.g., cimetidine, ranitidine) may be more effective in combination with H1 antihistamines.

Glucocorticoids

Downregulate the late-phase eosinophilic inflammatory response, as opposed to the early phase response. The onset of beneficial effects takes 4-6 hours and is not a first-line treatment choice for anaphylaxis.

Fluid Resuscitation

Aggressive fluid resuscitation is recommended for hypotensive patients as well as to help prevent cardiovascular collapse. It should be titrated to clinical response.

 

Prognosis

The prognosis is individualized based on the severity and progression of the anaphylaxis. Most recommendations for preventing recurrences of anaphylaxis are strict avoidance of the specific trigger(s).

– Chelsea Zorn, DVM, DACVECC

 

References

Shmuel, D. L. and Cortes, Y. Clinical Practice Review: Anaphylaxis in dogs and cats. Journal of Veterinary Emergency and Critical Care 23(4) 2013, pp. 377-394.

Hnatusko, A. L., Gicking, J. C., and Lisciandro, G. R. Anaphylaxis-related hemoperitoneum in 11 dogs. Journal of Veterinary Emergency and Critical Care 31(1) 2021, pp. 80-85.

Quantz J. E., Miles, M. S., Reed, A. L., and White, G. A. Elevation of alanine transaminase and gallbladder wall abnormalities as biomarkers of anaphylaxis in canine hypersensitivity patients. Journal of Veterinary Emergency and Critical Care 19(6) 2009, pp. 536-544.