Delayed Reactions to Contrast Agents
Delayed reactions to contrast agents are those that occur at least 1 hour after but within 1 week of receiving an ICA. Typical delayed reactions can manifest with signs and symptoms similar to an acute reaction, such as rash, pruritus, nausea, vomiting, diarrhea, and, occasionally, hypotension; however, reactions with cutaneous manifestations are most common. These cutaneous manifestations can be diverse in nature but typically occur as a pruritic maculopapular rash or urticaria.40 Severe skin reactions, such as toxic epidermal necrolysis and Stevens-Johnson syndrome, have also been reported.41, 42 Delayed reactions tend to be milder in nature than acute reactions. The overall incidence of delayed reactions after the administration of an ICA can be as high as 14%.40 Iso-osmolar agents (ie, nonionic dimers) are associated with the highest risk of causing a delayed reaction. Specifically, the incidence of a delayed cutaneous reaction after a nonionic dimer is 3 times greater than after the use of a nonionic monomer or an ionic dimer.43 Some data suggest an association between sun exposure and the risk of developing a delayed cutaneous reaction to ICAs, due to a possible photosensitizing effect by ICAs.44
Cutaneous delayed reactions are thought to be due to a T-cell–mediated type IV hypersensitivity reaction and are believed to be a reaction generated against the ICA molecule itself, not iodine.45 Delayed reactions are more common in patients treated with interleukin 2 because interleukin 2 is a potent stimulator of T lymphocytes.46 As with acute reactions, the management goal for delayed reactions is to identify patients at risk and minimize the risk of a reaction. Patients at greater risk for a delayed reaction to ICAs are those who had a prior reaction to an ICA agent, who are to receive a nonionic dimeric ICA, and who are being treated with interleukin 2. Although skin testing may be used to confirm a reaction to an ICA, the sensitivity of the test may depend on the duration of the administration of the test compared with the timing of initial ICA exposure.47 Furthermore, a negative predictive value of 97% suggests that skin testing may be more useful to rule out a reaction to ICAs.48 In patients with a prior reaction, ICAs should be avoided, if possible. However, in those with a prior reaction who still require the use of ICAs, nonionic dimeric ICAs should be avoided and corticosteroid prophylaxis should be considered.49 In those who develop a reaction, treatment is usually based on symptoms. For cutaneous reactions, treatment with corticosteroids can be helpful. For severe cutaneous reactions or those that do not resolve quickly, consultation with a dermatologist should be considered.
Cutaneous delayed reactions are thought to be due to a T-cell–mediated type IV hypersensitivity reaction and are believed to be a reaction generated against the ICA molecule itself, not iodine.45 Delayed reactions are more common in patients treated with interleukin 2 because interleukin 2 is a potent stimulator of T lymphocytes.46 As with acute reactions, the management goal for delayed reactions is to identify patients at risk and minimize the risk of a reaction. Patients at greater risk for a delayed reaction to ICAs are those who had a prior reaction to an ICA agent, who are to receive a nonionic dimeric ICA, and who are being treated with interleukin 2. Although skin testing may be used to confirm a reaction to an ICA, the sensitivity of the test may depend on the duration of the administration of the test compared with the timing of initial ICA exposure.47 Furthermore, a negative predictive value of 97% suggests that skin testing may be more useful to rule out a reaction to ICAs.48 In patients with a prior reaction, ICAs should be avoided, if possible. However, in those with a prior reaction who still require the use of ICAs, nonionic dimeric ICAs should be avoided and corticosteroid prophylaxis should be considered.49 In those who develop a reaction, treatment is usually based on symptoms. For cutaneous reactions, treatment with corticosteroids can be helpful. For severe cutaneous reactions or those that do not resolve quickly, consultation with a dermatologist should be considered.
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