Pseudoallergy, sometimes known as nonallergic hypersensitivity, is a clinical mimic of immediate-type allergic reactions that lacks underlying immunological mechanisms.^[1]

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), along with certain food ingredients and additives like tartrazine, benzoates, and salicylates, are the most common causes of pseudoallergic reactions. Since these reactions don't require IgE sensitization, they may manifest themselves after only one exposure. Doses-dependent, pseudoallergic reactions typically involve substances that are chemically unrelated.^[2]

The lack of information in skin tests and serology makes the diagnosis challenging. Nonallergic hypersensitivity is diagnosed on the basis of a unique clinical pattern, clinical signs, time course, and response to cause elimination. Oral challenge tests can be used to confirm pseudoallergy in the proper clinical setting.^[3]

Signs and symptoms

Clinically, pseudoallergy and anaphylaxis are identical.^[4] Pseudoallergy symptoms include gastrointestinal symptoms, urticaria, bronchospasm, and angioedema,^[5] along with headache, edema, skin flushing, hypotension, and shock.^[6]

Causes

Although they are commonly used to treat pain related to fractures, opioid medications have well-known side effects.^[7] Almost all opioids have the ability to directly induce mast cell degranulation, which in turn can result in pseudoallergy.^[8] Opioid medications, including morphine, codeine, and meperidine, have been known to cause pseudoallergy.^[9] By directly activating mast cells, opioids cause histamine release, which results in flushing or pruritus that is almost always mistaken for allergy symptoms.^[10] Compared to other opioids, codeine and morphine have been shown to be more likely to cause mast cell degranulation. By using a non-immunologic mechanism that is not dependent on IgE or the high-affinity IgE receptor FcεRI, codeine causes pseudoallergy.^[11] This suggests that codeine may activate mast cell degranulation by acting on the opioid receptor.^[12]

Mechanism

While pseudoallergy and IgE-mediated allergy share some similarities in their clinical manifestations,^[13] pseudoallergy is not the same as common allergy or type 1 reactions.^[14] Pseudoallergy can be caused by a variety of medications through various pathways. For example, taxol can cause pseudoallergy by stimulating the complement system. The reaction occurs for the first time without any prior sensitization.^[15]