T cell-mediated reactions to iodinated contrast media: evaluation by skin and lymphocyte activation tests

In addition to immediate reactions, late adverse reactions to iodinated contrast media (ICM) were reported in 2% to 5% of patients exposed to ICM and, as a consequence, have recently gained more attention. A few well-documented case reports postulate a hypersensitivity mechanism.

The aim of this study is to demonstrate a T cell-mediated mechanism to the ICM by using in vitro and ex vivo tests.

We analyzed 12 patients with 13 adverse ICM reactions, 9 of whom were women. Clinical history suggested an immune reaction to ICM. Skin tests (skin prick, intradermal, and patch tests) were performed with various ICM and read after 15 minutes and 24 and 48 hours. Skin biopsy specimens of positive test sites of 11 patients were evaluated by means of immunohistology. T-cell reactivity to ICM in vitro was analyzed with lymphocyte activation tests.

Seven patients showed generalized maculopapular eruptions, one of them with fever; 4 had a so-called drug hypersensitivity syndrome with exanthema, eosinophilia, and fever; 1 had maculopapular eruptions and fever; 1 had late-onset urticaria with loss of consciousness; and 1 had facial edema and respiratory distress. An immune reaction to ICM was inferred from positive skin prick test (2 patients), positive patch test (10 patients), and positive intradermal test (9 patients) at 24 and 48 hours. Skin biopsy specimens revealed a T-cell infiltrate in the dermis with predominantly CD4 + T cells in 8 patients, CD8 + T cells in 1 patient, and equal numbers in 1 patient. Cross-sensitivities to several ICM were observed (9/12). Other drug allergies were noted in 6 of the 12 patients.

Delayed reactions to ICM are most likely caused by immune reactions to these drugs and can elicit different clinical features. The involvement of T cells is suggested by positive skin test, as well as positive proliferative responses, to the drugs in vitro . A high degree of cross-reactivity with other than the eliciting ICM was observed. Moreover, 50% of these patients reported another drug hypersensitivity, suggesting a predisposition to immune reactivity in some patients.