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Treatment of Palmoplantar Keratoderma With Continuous Infusion 5-Fluorouracil

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A 49-year-old man electively chose to undergo a trial of intravenous chemotherapy with 5-fluorouracil (5-FU) for his inherited punctate palmoplantar keratoderma (PPK). His father also had this skin disorder, which coincidentally cleared after 2 courses of chemotherapy consisting of 5-FU and cisplatin to treat his lung cancer, prompting the patient to undergo this trial of therapy. After the patient's first course of a 5-day continuous infusion (CI) of 5-FU (1000 mg/m2 per day), the lesions on his hands and feet regressed by approximately 80%. However, after completion of each course, the lesions seemed to reappear to some degree. The patient desired to pursue further therapy; therefore, CI 5-FU at a dose of 250 mg/m2 per day (500 mg/d) was instituted, while pyridoxine was avoided in the hope of causing a hand-foot syndrome that may provide some long-term benefit. After receiving a 12-week course of therapy of CI 5-FU at 250 mg/m2 per day, his lesions were approximately 95% improved, with only a few minute punctate keratoses remaining. At follow-up nearly 4 years later, the lesions remain 90% cleared.


 

References

Although, to our knowledge, there has been no literature that associates systemic 5-fluorouracil (5-FU) with the treatment of palmoplantar keratoderma (PPK), we are convinced that systemic 5-FU was responsible for clearing the lesions in a patient—possibly due to the epidermal changes in the palms and soles secondary to hand-foot syndrome induced by 5-FU.

An objective assessment of our patient suggested that systemic 5-FU most likely was the reason for the apparent clearing of his keratoses; however, a randomized controlled trial is needed to determine if systemic 5-FU is applicable in the treatment of PPK. This case brings new light to a disease for which treatment options are limited and no cure exists.

PPK represent a heterogeneous group of disorders most often characterized by a hyperkeratosis of the palms and soles.1,2 PPK may be hereditary, acquired, or an associated feature that is part of a syndrome. Clinically, inherited PPK can be divided into 3 forms: diffuse, striated, and punctate.3

The pathogenesis of PPK remains unknown, and the treatment is purely symptomatic; there is no definitive treatment or cure.4 Treatment modalities have consisted of topical and systemic therapy as well as surgical excision. The literature has indicated no major benefits with the use of topical therapy, including topical retinoids, corticosteroids, calcipotriol, or topical keratolytics such as 5% to 10% salicylic acid ointment, 30% propylene glycol, 20% to 30% lactic acid, and 10% to 12% urea ointment.1,5-7 Keratolytic agents may be useful in reducing the thickness of the keratoderma, but the lesions recur when treatment is stopped.6 Overall, the outcomes of treatment of PPK have been rather disappointing. Superior results from systemic treatment with oral retinoids, specifically isotretinoin, have been reported in some cases of PPK. However, there are significant risks and toxicities associated with long-term oral retinoid therapy; and like keratolytic agents, discontinuance of therapy causes the lesions to recur to their initial severity.1,7

We report a case of inherited punctate PPK treated successfully with systemic 5-FU. Prior to this, the patient had tried treatment with many topical keratolytic agents, including salicylic acid, urea, and topical 5-FU, from which he attained only minimal benefit. The option of therapy with oral isotretinoin was discussed with the patient; however, he did not choose this option because it is not a cure and lifelong treatment would be required for long-term benefits.

Case Report

A 49-year-old man electively chose to undergo a trial of intravenous chemotherapy with 5-FU for his punctate PPK. He had had this dermatologic disorder since he was a teenager. The patient reported that the calluses on his feet were painful and that those on his hands were embarrassing. Differential diagnosis ruled out toxin-induced PPK (ie, arsenic) because of the lack of chemical exposure; he was diagnosed with hereditary punctate PPK, of which his family history is significant (his father also had the disorder). In 1987, his father was diagnosed with lung cancer and received chemotherapy consisting of continuous infusion (CI) 5-FU and cisplatin. Coincidentally, his lesions cleared after 2 treatments and never recurred, though he died of lung cancer 2 years later.

The patient's dermatologist noted that treatments had been unsuccessful thus far and that therapeutic options had been exhausted. The dermatologist was unaware of alternative treatments and thoroughly reinforced to the patient that other than his father's case, there was no evidence to suggest that treatment with 5-FU was effective. The patient was aware that systemic 5-FU was not the standard of care for PPK; however, he was willing to accept all risks associated with treatment.

Prior to initiating therapy, the patient weighed 81 kg and was not taking any medications including topical creams and over-the-counter products. His medical history was significant for back problems and a herniorrhaphy. He smoked three quarters of a pack of cigarettes a day. His mother died of heart disease. His siblings were alive and well.

The patient's laboratory results were acceptable to start treatment. A peripherally inserted central catheter line was placed. Pictures were taken of the lesions before treatment to document possible response. A single course of CI 5-FU was instituted: 1000 mg/m2 per day for 5 days via an infusion pump connected to his catheter line. The patient was instructed to gargle daily with 0.5% hydrogen peroxide solution.

The patient tolerated the first course of 5-FU without incidence. Other than minor fatigue and slight mucositis, he experienced no particular side effects, though he noticed his feet were more painful than usual. Physical examination revealed mild erythema over his hands, and some of the lesions that used to be skin colored were now purplish and erythematous.

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