Hydroxyurea associated with concomitant occurrence of diffuse longitudinal melanonychia and multiple squamous cell carcinomas in an elderly subject.
BACKGROUND
Hydroxyurea is a cytostatic agent used to treat myeloproliferative disorders and long-term treatment is associated with mucocutaneous adverse events and nail hyperpigmentation.


OBJECTIVE
The purpose of this study was to report the concomitant occurrence of multiple squamous cell carcinomas and diffuse nail hyperpigmentation associated with hydroxyurea treatment, and to describe a successful therapeutic approach using imiquimod 5%.


METHODS
We report the case of an 81-year-old white man (weight, 82 kg; height, 173 cm; photodamaged type II skin) affected with cirrhosis of the liver, chronic idiopathic myelofibrosis, and a 3-year history of longitudinal melanonychia and periungual hyperpigmentation. His current medication regimen was hydroxyurea (500 mg BID), iron (525 mg QD), and folic acid (15 mg QD) for the myeloproliferative disease and the associated anemia; spironolactone (25 mg BID) and furosemide (20 mg BID) for the complications of cirrhosis; allopurinol (100 mg QD) to treat gout; and theophylline (250 mg QD) for chronic bronchitis. The patient presented with several actinic keratoses, squamous cell carcinomas, and multiple keratoacanthomas, one of which was pigmented. Both the longitudinal melanonychia and the multiple skin cancers first appeared after approximately 6 months of hydroxyurea treatment. A correlation between dose and manifestation was investigated but none was found. Based on the Naranjo algorithm, the adverse reaction observed was probably related to the hydroxyurea treatment (score = 6); however, the hydroxyurea chemotherapy could not be discontinued because of the myeloproliferative disorder. Complete remission was observed after 6 to 10 weeks of imiquimod 5% (10 mg/cm of skin cancer) treatment. The patient completed a 10-month follow-up, maintaining a complete resolution of the treated skin lesions; however, the development of a painful hand ulcer, possibly associated with the hydroxyurea, and new skin cancers were observed at the last follow-up visit.


CONCLUSIONS
We report this case of the concomitant appearance of multiple skin cancers and nail changes associated with hydroxyurea use. The progressive appearance of squamous epitheliomas and other cutaneous adverse events, such as the ulcer, suggests that alternative chemotherapies should be considered for the treatment of myeloproliferative diseases.
Saraceno
Rosita
R
Department of Dermatology, University of Rome Tor Vergata, Rome, Italy. rositasaraceno@yahoo.it
Teoli
Miriam
M
Chimenti
Sergio
S
D000369:Aged, 80 and over; D000634:Aminoquinolines / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000188:drug therapy; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects*; D017495:Hyperpigmentation / Q000139:chemically induced* / Q000188:drug therapy; D000077271:Imiquimod; D008297:Male; D009196:Myeloproliferative Disorders / Q000188:drug therapy; D009260:Nail Diseases / Q000139:chemically induced* / Q000188:drug therapy; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000188:drug therapy
D000634:Aminoquinolines; D000970:Antineoplastic Agents; D000077271:Imiquimod; D006918:Hydroxyurea