Iodinated radiocontrast media are associated with non-IgE-mediated activation of mast cells and basophils. Prior exposure (sensitization), therefore, is not required. Aggregated immunoglobulin comprises a significant proportion of immunoglobulin in gamma globulin which is used for passive immunization for various conditions. While these aggregates cause mild reactions, anti-IgA antibodies may cause anaphylactoid reactions when intravenous immunoglobulin is administered to a patient with selective IgA deficiency. Similarly, blood or plasma transfused into an IgA deficient patient who possess anti-IgA antibodies of the IgG class may form circulating immune complexes, activate complement, and cause an anaphylactoid reaction.

Several diagnostic and therapeutic agents have been shown to induce histamine release from mast cells or basophils from normal individuals, although the incidence of these reactions and their clinical severity vary widely. Reactions to these agents do not require prior exposure and sensitization, although patients with a history of a previous radiocontrast medium reactions demonstrate a markedly increased risk of anaphylaxis upon subsequent exposure.

The approximately 1% incidence of untoward reactions to aspirin and nonsteroidal anti-inflammatory drugs (NSAID) has been attributed to alterations of arachidonic acid metabolism, as these agents block the cyclooxygenase enzyme. No role for IgE can be found in these reactions. Aspirin intolerance may be present in up to 20% of asthmatics, and its clinical manifestations may be more slowly progressive and protracted than those of classical, IgE-mediated anaphylaxis.