Medline ® Abstracts for References 49,50

BACKGROUND: Drugs have occasionally been implicated in dermatomyositis (DM) onset.

OBJECTIVE: We sought to review case reports of drug-induced DM.

METHODS: Articles were gathered from MEDLINE and bibliographies of acquired reports. Causality was assessed using World Health Organization criteria. Clinical characteristics, management, and resolution were examined.

RESULTS: In 70 reported cases, 50% of patients were female and the median age was 57 years. Hydroxyurea was implicated in 51% of cases. All cases had pathognomonic (76%) or compatible (24%) cutaneous findings. Hydroxyurea cases lacked myositis, but myositis was described in 79.4% of nonhydroxyurea cases. Drug causality was probable (25.7%) or possible (74.3%), but not certain in any case. Most patients had underlying pathology associated with DM (44% had malignancy; 16% had rheumatoid arthritis). Of the sample, 84.3% had improvement of DM after discontinuation of the drug.

LIMITATIONS: Case reports may emphasize unusual findings.

CONCLUSIONS: Further work is needed to differentiate drug effects from underlying, predisposing factors.

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.

OBSERVATIONS: 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 thelower 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.