Recommendations

Key Recommendations

A life-threatening, rapid hypersensitivity reaction, requiring immediate medical attention, anaphylaxis is characterized by rapidly progressive upper airway obstruction, rash, bronchospasm, and hypotension or cardiovascular collapse. The diagnosis is largely clinical, based on history and examination findings.[6]

History

Clues from the clinical history should point to the allergen exposure. Clinicians should gather details about similar reactions in the past as well as known allergies and hypersensitivities. A determination of potential causes includes inquiry about food or medication consumed before the event and possible insect stings or bites. It is important to gather information about the location where the event occurred, outdoors versus indoors, at home, work, or school, or in a restaurant. Triggers for anaphylactic reactions may include heat, cold, or exercise.[1]

Biphasic reactions or symptom recurrence after resolution of the initial presentation

Can be identified by defining onset and clinical course, including recurrence of symptoms after resolution of the initial reaction.[46][47][48]

There are limited data to predict the risk of biphasic or protracted anaphylaxis. Based on very low-certainty evidence, the following factors are associated with an increased risk of biphasic anaphylaxis: anaphylaxis caused by any drug in patients ages <18 years; anaphylaxis caused by an unknown trigger; anaphylaxis symptoms with cutaneous manifestations; wide pulse pressures during initial reaction; severe initial anaphylaxis symptoms; anaphylaxis in patients ages <18 years treated with corticosteroids; and patients requiring >1 dose of epinephrine (adrenaline).[12]

Clinical presentation

There are a wide variety of signs and symptoms; therefore, a clinical evaluation should include all organ systems. Many patients describe a sense of impending doom (angor animi). The patient appears agitated, confused, and either flushed or pale.[49] Neurologic manifestations also include dizziness, visual disturbances, tremor, disorientation, syncope, and seizures. Rhinitis together with bilateral conjunctivitis is often an early sign of progressive respiratory involvement. Inspiratory stridor is an ominous sign often quickly leading to fatal laryngeal obstruction.[49] Wheezing, an overinflated chest, the use of accessory muscles, and preference for the forward-leaning position point to bronchoconstriction. Cardiovascular collapse may occur in addition to hypotension.[50] Nearly all adults will show skin manifestations of systemic mediator release, such as rash, erythema, or urticaria.[16][51] These features might be overshadowed by the more dramatic respiratory and cardiovascular symptoms.[52] Abdominal pain, nausea, vomiting, and diarrhea are common symptoms.

Stridor
Stridor

Auscultation sounds: Stridor

Laboratory evaluation in acute setting

No laboratory test in the acute setting should delay urgent management of the patient.

Serum total tryptase measurements are not helpful for confirmation of the diagnosis of anaphylaxis at the time of the episode because the assay takes several hours to perform; however, they can be useful later.[53] Serum or plasma for tryptase should be obtained as soon as possible after emergency treatment has started and a second sample ideally within 1 to 2 hours (but no later than 4 hours) from the onset of symptoms.[54][55][Evidence C]​ Large elevations, however, may persist for hours. To determine the baseline level of tryptase, an additional sample should be collected at least 24 hours after all symptoms have resolved. Serum tryptase levels are normally undetectable (<1 nanogram/mL) in healthy individuals who have not had anaphylaxis in the preceding hours. In anaphylaxis, elevations can range from insignificant to levels above 100 nanograms/mL. For example, high levels have been seen following severe anaphylaxis induced by medications; however, in clinically obvious food-induced anaphylaxis, tryptase levels may not be elevated, even if serum was collected in a timely manner.[56][57] Hence, normal levels do not exclude anaphylaxis. Elevated levels of total tryptase implicate mast cell involvement and correlate with hypotension. The sensitivity and specificity of tryptase elevation have not been determined.[58]

Plasma histamine levels and urinary histamine metabolites can be measured but are rarely used in clinical practice. Elevated histamine levels correlate with anaphylaxis severity, but histamine has a very short half-life. N-methyl-histamine levels are elevated when compared with baseline.[59][60] Histamine and histamine metabolite levels may be affected by dietary factors.

Laboratory testing to prevent recurrence

Testing for the precipitating allergen after the acute episode is recommended to ensure allergen avoidance and to reduce the risk of recurrence. A referral to an allergist is always recommended.

Challenge test

Skin testing (with commercially available allergen extracts) is recommended to assess the likelihood of a reaction prior to considering oral food challenge. Skin testing with commercial extracts, or fresh fruit, has a high sensitivity and a negative predictive value of >90%.[61]

In food allergy, oral challenge with the suspected allergen remains the definitive test; however, this test may subject the patient to a risk of reaction recurrence of unpredictable severity.

In vitro IgE testing

The measurement of food-specific immunoglobulin E (IgE) antibodies directed against the food protein, is a robust test to assess for the presence of allergic antibodies.

Positive skin and in vitro IgE tests do not confirm the clinical relevance of the sensitization; clinical history and oral food challenge are required to make a diagnosis. Studies have been performed to define clinical decision points of skin test size or IgE level to help decide on thresholds at which a clinical reaction is expected.[61]

Other laboratory tests

Basophil activation tests have been described as a supplemental tool in diagnosing severe peanut allergy in adults.[62]

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