Immunohistochemical characterization of cutaneous drug eruptions by STI571

• Published in: Journal of dermatological science Vol. 38; no. 1; pp. 9 - 15
• Main Authors: Park, Hyun Jeong, Kim, Hei Sung, Kim, Hee Jung, Lee, Jun Young, Cho, Baik Kee, Lee, Ah Won, Yoon, Do Young, Cho, Dae Ho
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 01-04-2005
• Subjects: Adult; Anti-Bacterial Agents - adverse effects; Benzamides; Case-Control Studies; Child; CML; Drug eruption; Drug Eruptions - metabolism; Drug Eruptions - pathology; Female; Humans; ICAM-1; IL-18; IL-1β; Imatinib Mesylate; Immunohistochemistry; Immunophenotyping; Interleukin-1 - metabolism; Interleukin-18 - metabolism; Male; Middle Aged; Piperazines; Pyrimidines - adverse effects; Skin - metabolism; Skin - pathology; STI571; Drug eruption; ICAM-1; CML; STI571; IL-1β; IL-18
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2004.12.002

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.
In this study, the characteristics of the cutaneous drug eruptions by STI571 were investigated.
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-1β and ICAM-1 expression in the cutaneous drug eruption.
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-1β was observed as well. In contrast, ICAM-1 was either weakly positive or negative.
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-1β was increased in both groups. This elevation of IL-18 and IL-1β may assist in understanding the pathogenesis of cutaneous drug eruption.