A characteristic eruption associated with ifosfamide, carboplatin, and etoposide chemotherapy after pretreatment with recombinant interleukin-1 alpha.
BACKGROUND
Patients who received recombinant interleukin-1 alpha (IL-1 alpha) before chemotherapy followed by autologous bone marrow transplantation had a characteristic intertriginous cutaneous eruption that has not previously been described.


OBJECTIVE
Our aim was to document these skin changes and to determine whether IL-1 alpha as a sole agent caused recognizable changes in the skin.


METHODS
A prospective study of the skin changes in eight patients was performed. We characterized the clinical, histologic, and immunohistochemical features of the patient's skin after IL-1 alpha infusions and after chemotherapy.


RESULTS
No specific clinical or histologic changes were seen immediately after IL-1 alpha infusions. Immunohistochemical studies showed significant upregulation of endothelial leukocyte adhesion molecule-1 (ELAM-1) expression. Within 1 day of the initiation of chemotherapy (ifosfamide, carboplatin, and etoposide), a cutaneous eruption consisting of mucositis and varying degrees of erythema progressing to painful erosions in body folds and under adhesive tape developed in all patients. Histologic features were consistent with a chemotherapeutic effect on the epidermis as well as eccrine and apocrine glands. Expression of keratinocyte intercellular adhesion molecule-1 and HLA-DR as well as of ELAM-1 on dermal endothelial cells was increased. The perivascular lymphocytic infiltrate consisted mainly of CD4+ T cells.


CONCLUSIONS
High-dose chemotherapy with ifosfamide, carboplatin, and etoposide resulted in a characteristic cutaneous eruption that is consistent with a toxic reaction to chemotherapeutic agents. Its accentuation in skin folds and under taped areas suggests that eccrine excretion of the drugs or a toxic metabolite is an important contributing factor. IL-1 alpha may induce the expression of ELAM-1 but does not cause a cutaneous eruption.
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
R
R
Prussick
T D
TD
Horn
W H
WH
Wilson
M C
MC
Turner
D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D016190:Carboplatin / Q000009:adverse effects; D003875:Drug Eruptions / Q000209:etiology*; D005047:Etoposide / Q000009:adverse effects; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects; D007375:Interleukin-1 / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011292:Premedication; D011446:Prospective Studies
D000970:Antineoplastic Agents; D007375:Interleukin-1; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide