Hydroxyurea-associated dermatomyositis-like eruption demonstrating abnormal epidermal p53 expression: a potential premalignant manifestation of chronic hydroxyurea and UV radiation exposure.
BACKGROUND
Chronic hydroxyurea therapy is associated with numerous cutaneous adverse effects. While hydroxyurea-associated nonmelanoma skin cancers are known to be associated with significant morbidity and occasional mortality, to date, dermatomyositis-like eruption has been considered a benign entity, other than its ability to mimic true dermatomyositis leading to inappropriate immunosuppression. More recently, hydroxyurea-associated squamous dysplasia has been characterized as a premalignant precursor to hydroxyurea-associated nonmelanoma skin cancers and shown to manifest abnormal p53 expression.


METHODS
An elderly woman receiving chronic hydroxyurea therapy for myelodysplasia developed a dermatomyositis-like eruption that was misdiagnosed as true dermatomyositis, leading to continuation of hydroxyurea. Years later she developed severe hydroxyurea-associated nonmelanoma skin cancers resulting in discontinuation of hydroxyurea, poor control of her myelodysplasia, and death. Re-evaluation with immunohistochemical analysis of tissue from her original dermatomyositis-like eruption revealed focal confluent nuclear expression of p53 along the lower layers of the epidermis, suggestive of a premalignant state.


CONCLUSIONS
We suggest that dermatomyositis-like eruption and hydroxyurea-associated squamous dysplasia represent similar clinical manifestations of a common underlying chronic phototoxic process involving aberrant keratinocyte p53 expression mediated by hydroxyurea's antimetabolite properties and UV radiation exposure. Accordingly, we suggest that dermatomyositis-like eruption, previously considered a benign entity, may represent a premalignant precursor of hydroxyurea-associated nonmelanoma skin cancers warranting discontinuation of hydroxyurea therapy.
Division of Dermatology, University of Louisville, 310 E Broadway, Louisville, KY 40202, USA. akalajian@yahoo.com
Andrew H
AH
Kalajian
Sarah Josephson
SJ
Cely
Janine C
JC
Malone
Jyoti B
JB
Burruss
Jeffrey P
JP
Callen
D000369:Aged, 80 and over; D004273:DNA, Neoplasm / Q000235:genetics; D003882:Dermatomyositis / Q000139:chemically induced* / Q000473:pathology; D003937:Diagnosis, Differential; D003875:Drug Eruptions / Q000209:etiology / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006229:Hand Dermatoses / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects*; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000209:etiology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000009:adverse effects; D011230:Precancerous Conditions / Q000175:diagnosis / Q000209:etiology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
D004273:DNA, Neoplasm; D019384:Nucleic Acid Synthesis Inhibitors; D006918:Hydroxyurea