Be prepared to recognize and treat anaphylaxis

February 2004

“Personnel administering biologic products or serum should be prepared to recognize and treat systemic anaphylaxis. The medications, equipment and competent staff necessary to maintain the patency of the airway and to manage cardiovascular collapse must be available immediately. Appropriate and timely transfer of a patient with anaphylaxis to a pediatric intensive care unit or a hospital emergency department may be necessary.” — 2003 Red Book

It is estimated that there are between 1,500 and 2,000 deaths in the United States annually as a result of anaphylaxis and many more cases that do not end fatally.

---Philip A. Brunell, MD

Some have estimated that as many as one in 500 individuals experience this type of reaction annually and that millions of individuals may be at risk. Although these reactions are relatively uncommon, it is essential that one be prepared to promptly recognize, manage and, whenever possible, to prevent them.

The risk of anaphylaxis following immunization is said to be about one in 1.5 per million (Pediatrics. 2003;112:815). As multiple vaccines often are given at the same visit, it is difficult to identify specific culprits.

The Institute of Medicine has reported that causal relationships exist for the measles-mumps-rubella (MMR), hepatitis B and diphtheria-tetanus toxoids vaccines.

There has been interest in the relationship between gelatin and vaccines as the cause of anaphylaxis and caution has been urged if someone has a reaction to MMR and one is contemplating giving varicella vaccine or vice versa (Pediatrics. 2004;113:170). Gelatin in MMR and varicella vaccines is suspect and a reaction to either should be a cause of concern. Egg protein in influenza vaccine does not seem to be a major problem (Pediatrics. 2003;112:815) but most people are aware of the danger of giving this vaccine to people with egg allergies.

It is difficult to estimate the risks of anaphylaxis to various agents, as episodes are not usually reported. An estimate to the total population has been made from the number of doses of epinephrine dispensed to Canadians. The highest rates, 1.4 %, were found in males younger than 17 years of age (J Allergy Clin Immunol. 2002;110:647). Some vaccine related anaphylactic reactions are detected by the Vaccine Adverse Event Reporting System (VAERS).

It is also possible that some reactions considered to be anaphylactic are not. When I was on sabbatical at Northwick Park in England, one of our staff was sent to obtain blood for a study. A patient fainted after the needle was inserted into her vein as she screamed “my God.” My colleague, the venipunturist, responded without losing a beat, “No madam, but the closest Northwick Park could provide.” He adroitly recognized this was not an anaphylactic reaction to latex or another substance. The victim recovered uneventfully and my friend went on to become a professor of medicine at Cambridge.

Perhaps, however, my colleague was foolhardy as it is preferable to over treat with adrenaline than to delay therapy of a life-threatening condition. Most would have given adrenaline and then tried to sort out the situation, but others have more conservative recommendations for when adrenaline should be administered (Pediatrics. 2003;11:1601). All agree, however that this should be initial therapy.

Anaphylactic reactions may involve the respiratory, cardiovascular, gastrointestinal, or central nervous systems or the skin. Cutaneous signs are most common. Urticaria and angioedema and flushing are the most frequent signs with pruritus without rash being less common. Respiratory involvement may vary, from nasal symptoms, and throat pruritus and tightness to hoarseness, barky cough, dysphagia, dyspnea wheezing, cyanosis and apnea. Patients may be anxious. Nausea, vomiting, diarrhea and cramping pain may be present in one quarter to one-third of patients. Many patients will rapidly progress to hypotension and shock. The onset is usually within minutes of being challenged but can be delayed particularly in food allergies.

Symptoms are believed primarily to be caused by the release of mediators from mast cells and basophils following binding of multivalent allergens to cross-link the IgE and FcR receptors signaling these cells to release histamine, which is stored in granules. Other substances, including prostaglandins and leukotrienes are believed to participate as well as other types of cells. Symptoms are produced by vasospasm of smooth muscle cells in the respiratory and gastrointestinal tract and relaxation of smooth muscle cells in the vasculature resulting in increased vascular permeability causing edema of tissues.

Adrenaline is the initial drug to be given. Doses should be repeated if there is an inadequate response to a previous dose. About one-third of victims require more than a single dose. In addition, steroids and antihistamines have a role and in severe cases, intravenous fluids, oxygen, inhaled bronchodilators and dopamine may be needed. Patients who are receiving ß blockers will antagonize the action of adrenaline. Patients must be observed following anaphylactic reactions as biphasic reactions may occur. Some believe that prompt administration of adrenaline or steroids decreases the likelihood of these events. Observation from four to 24 hours has been recommended.

Anaphylactoid reactions are associated with similar symptoms but result from direct release of mediators and are not antigen mediated. Reactions to radio contrast media are examples of this type of reaction. Besides vaccines, drugs, stings and foods are common inciting agents. Peanuts, certain tree nuts or seafoods, particularly shellfish, soy, milk and wheat are some of the more common offending foods. Peanut allergy seems to have been on the increase. Many schools prohibit bringing in peanut butter. It is important that patients suspected of having allergies that cause significant clinical symptoms be tested by a qualified individual as I have found that some parents make careers of preparing special diets for their children on the suspicion that they have certain “food allergies.”

Laboratory tests are usually not obtained but ß-tryptase, which is released from mast cells and blood histamine levels or urine metabolites of histamine have been used in the hands of some. These substances tend to be transitory. ß-tryptase is usually not found in food-induced anaphylaxis. A work up by an allergist is indicated for all those who have had an anaphylactic reaction. Confirmation of the inciting factor is important. Very often, no trigger can be found for anaphylactic reactions. For those who are truly allergic and for whom the inciting factor is identified, avoidance and desensitization where possible should be part of their management. Anaphylactic reactions can be mimicked by rare conditions e.g. systemic mastocytosis, and can be mistaken for carcinoid syndrome.

It is important that those who have had anaphylactic reactions or are at increased risk of such reactions be prepared to deal with them by carrying adrenaline, and be instructed on its use. School and day care centers should be prepared for these reactions. Optimal management of patients at risk can prevent fatalities. Places where our children learn or play should be made aware of the need to decrease risks to our children by helping children avoid exposure to potentially harmful foods, insects and other substances that may cause anaphylaxis. Personnel must be trained to deal with this emergency and equipment must be provided for such an event.