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Indian Journal of Dermatology, Venereology, Leprology, Vol. 70, No. 1, January-February, 2004, pp. 46-47 Letter To Editor Flagellate hyperpigmentation from bleomycin Pavithran K, Doval DC, Talwar V, Vaid AK Department of Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi Code Number: dv04014 Sir, Mucocutaneous side effects associated with bleomycin are stomatitis, ulcers, scaly erythematous and bullous lesions, sclerosis, nail changes, digital gangrene and pigmentary alterations.[1] Hyperpigmentation occurring mainly on the pressure areas of the skin as well as in areas of scratch marks is seen in approximately 30% of patients. Flagellate hyperpigmentation is very characteristic of bleomycin. A 42-year-old woman was diagnosed to have granulosa cell tumor of the ovary stage IV (multiple lung metastasis). After debulking surgery she was given combination chemotherapy with bleomycin, etoposide, and cisplatin. After 2 cycles (180 mg of bleomycin), she noted hyperpigmentation of the hands and linear pigmented lesions over the anterior abdominal wall, shoulder region and back [Figure - 1]. She denied permission for biopsy of the lesions. She was continued on chemotherapy and she attained complete remission after 3 cycles. Chemotherapy was discontinued after one more cycle due to poor tolerance. The hyperpigmented lesions resolved completely over a period of 3 months after the discontinuation of chemotherapy. Bleomycin is an antineoplastic antibiotic derived from Streptomyces verticillius. After intravenous administration it is widely distributed throughout the body. It is rapidly inactivated in all organs by bleomycin hydrolase except in the lungs and skin where it is deficient. This results in primarily cutaneous and pulmonary toxicities. Flagellate linear hyperpigmentation is the characteristic lesion associated with bleomycin and is seen in about 20-30% of cases, primarily on the upper trunk and limbs.[2] It is dose dependent, occurring after a cumulative dose of 90 and 285 mg, but some cases have been reported with doses as low as 15 mg given parenterally. It follows the administration of bleomycin by a duration ranging from 1 day to 9 weeks[2] and may persist for up to 6 months.[3] The exact pathogenesis of these lesions is not known. Some authors consider that the linear lesions result from increased leakage of the drug from dilated vessels after rubbing or scratching the skin, but others have been unable to reproduce linear hyperpigmentation by these means.[1] It is also speculated that scratching induces subclinical local vasodilatation by a dermographic mechanism resulting in an excessive in situ accumulation of bleomycin.[4] The reason for the increased pigmentation is thought to be due to increased melanocyte stimulation by melanocyte stimulating hormone, inflammatory oncotaxis and stimulation of melanocytes by adrenocorticotrophic hormone.[5] Further studies are needed to determine the cause of the pruritus and to explain the linear pattern of the skin lesions following bleomycin therapy. REFERENCES
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