Immunohistochemical characterization of cutaneous drug eruptions by STI571.

BACKGROUND

STI571, a selective BCR-ABL tyrosine kinase inhibitor, is a promising new drug for chronic myelogenous leukemia (CML). However, the drug has been reported to be associated with adverse cutaneous drug eruptions with high frequency.

OBJECTIVE

In this study, the characteristics of the cutaneous drug eruptions by STI571 were investigated.

METHODS

The clinical records of 10 patients diagnosed with drug eruption by STI571 were reviewed. We obtained 10 skin biopsy specimens from patients with drug eruption by STI571, 6 from the antibiotics-induced drug eruption group, and 5 from normal skin (control). Immunohistochemical analysis was performed to detect CD4, CD8, CD56, IL-18, IL-1beta and ICAM-1 expression in the cutaneous drug eruption.

RESULTS

Seven out of 10 patients had maculopapular exanthema, 2/10 erythema multiforme, 1/10 urticaria. We analyzed the composition of T-lymphocyte subsets from the infiltrates at the STI571-induced drug eruption site in eight patients. Unlike other drug eruptions, the increase in the CD8 expression was statistically significant, especially in the dermoepidermal junction and the upper dermis (P < 0.01). The enhanced expression of IL-18 and IL-1beta was observed as well. In contrast, ICAM-1 was either weakly positive or negative.

CONCLUSIONS

Drug eruption caused by STI571 was mostly expressed as a maculopapular exanthema. The histopathological findings were similar in drug eruption by antibiotics or STI571. Unlike the drug eruptions caused by antibiotics, where the expression of CD4 was dominant, CD8 was dominant in drug eruptions by STI571. The expression of IL-18 and IL-1beta was increased in both groups. This elevation of IL-18 and IL-1beta may assist in understanding the pathogenesis of cutaneous drug eruption.