The correct answer is:

After resolution of symptoms, observe the asymptomatic patient for at least 6 hours; antihistamines and glucocorticoids do not reliably decrease risk of biphasic anaphylaxis and are not recommended for this purpose.

Key Point:

The AAAAI and ACAAI jointly emphasize that importance of:

1. identifying patients at increased risk for a recurrence of anaphylaxis within 1-72 hours (biphasic anaphylaxis), and secondly

2. understanding that neither antihistamines nor glucocorticoids ameliorate that risk.
They recommend an extended observation period for those at risk for biphasic anaphylaxis, with a suggestion that 6 hours observation of the asymptomatic patient may be sufficient, depending on the patient’s co-morbidities. The threshold for admission should be low in older patients and those with cardiovascular or other chronic disease (increased risk of fatal anaphylaxis also during the recurrence).

Explanation:

The AAAAI and ACAAI endorse a 3-category definition of anaphylaxis from 2006 that captures the full range of anaphylaxis presentations - from milder cases to those that lack classic features such as skin manifestations or hypotension. They state:

Anaphylaxis is likely when 1 of the following 3 categories applies:

a) Assumes rash, but not hypotension; 2 symptoms required: acute onset of an illness (minutes to hours) with involvement of the skin, mucosal tissue, or both with either respiratory involvement or reduced blood pressure and/or associated symptoms of end-organ dysfunction; or

b) Most flexible definition designed to capture milder cases, eg urticaria plus GI symptoms – 2 symptoms required: two or more of the following that occur rapidly after exposure to a likely allergen for the patient, including:

i. involvement of skin-mucosal tissue,
ii. respiratory involvement,
iii. reduced blood pressure or associated symptoms, or
iv. gastrointestinal symptoms; or i. involvement of skin-mucosal tissue,

c) Assumes hypotension, but not rash - 1 symptom required: reduced blood pressure as a result of exposure to a known allergen trigger.

In a patient who falls into one of the above categories for anaphylaxis, epinephrine is the first drug to be given, something that one study found to only occurs in 8% of patients due to the administration of antihistamines and glucocorticoids prior to epinephrine. Studies show that the delay of epinephrine is associated with increased fatality.

Antihistamines and glucocorticoids also do not reliably decrease the risk of biphasic anaphylaxis. It is estimated that at a 5% incidence rate of biphasic anaphylaxis, 72 patients would need to be treated with antihistamine and 161 patients with glucocorticoids, respectively, to possibly prevent one case of biphasic anaphylaxis. However, both agents can be given as secondary treatment to increase patient comfort. This is not to be confused with patients who have an allergic reaction without anaphylaxis, who do not require epinephrine and are routinely treated with antihistamines and glucocorticoids.

Finally, a 1-hour observation period of the ASYMPTOMATIC patient after resolution of anaphylaxis is sufficient in most non-severe cases of anaphylaxis (negative predictive value of 95% for occurrence of biphasic anaphylaxis) as long as the patient also does not have co-morbidities that increase the risk of a fatal outcome.

In patients with either a severe case of anaphylaxis or e.g. cardiovascular or other chronic morbidities, the optimal observation period is unknown. The authors suggest a minimum of a 6-hour observation period of the asymptomatic patient AFTER resolution of anaphylaxis (97.3% negative predictive value for occurrence of biphasic anaphylaxis). This extended observation period has been calculated to be cost-effective, based on an estimate that the extended observation period leads to an estimated 76% reduction in mortality.

Signs of increased risk of biphasic anaphylaxis (requires extended observation:

1. Severe symptoms at presentation (no odds ratio provided)

2 doses of epinephrine are necessary (odds ratio 4.82)

3. cutaneous signs and symptoms (odds ratio 2.54)

4. drug trigger in children (odds ratio 2.35)

5. wide pulse pressure (odds ratio 2.11)

6. unknown trigger (odds ratio 1.63)