Capecitabine‐induced hand–foot syndrome and cutaneous hyperpigmentation in an elderly vitiligo patient

Abstract

EditorCapecitabine is a non-cytotoxic oral fluoropyrimidine carbamate agent that acts as a prodrug of 5-FU. 1 After oral administration, capecitabine is rapidly absorbed and further activated, through several enzymatic steps, to its main metabolites. Both the mode of administration (oral route) and the nature of the agent (prodrug) make it a more suitable and safer option, when compared to 5-FU. Capecitabine is prescribed in 21-day cycles, comprising 14 days of continuous administration, followed by a 7-day rest period 2 either as a monotherapy regimen for advanced colorectal cancer, or in conjunction with docetaxel for advanced chemotherapy-refractory breast carcinoma.Its main cutaneous side-effect is undoubtedly the handfoot syndrome (HFS), also known as palmar-plantar erythrodysesthesia, although several cases of skin discoloration, alopecia, nail changes, photosensitivity and radiation recall reactions have also been reported. 1 An 82-year-old Caucasian man was started on capecitabine after undergoing a right haemicolectomy for stage III adenocarcinoma of the ascending colon. Skin complaints started on the second 14-day course of chemotherapy, with extensive hyperpigmentation of the normal, photo-exposed non-vitiliginous skin, along with painful palmar and plantar erythema, oedema and desquamation. There had been no previous or concurrent sun exposure, the patient having strictly complied with medical recommendations concerning photoprotection and the avoidance of any drug known to be photosensitizer or otherwise to interact with capecitabine.Upon examination the palms and soles were erythematous, oedematous and warm and tender upon palpation; hyperpigmentation of the malar and ear areas of the patient's face was also evident in overt contrast to the adjacent vitiliginous facial skin areas ( fig. 1).The use of tacrolimus 0.1% ointment, b.i.d., under occlusion, along with regular emollients, was started on the hands and feet, with prompt and significant relief 1 week upon initiation. As far as the hyperpigmentation, however, the asymptomatic hyperpigmentation only resolved about 6 months after the completion of the nine courses of chemotherapy.The capecitabine-induced HFS is not a rare event, as it has been reported to occur in up to 68% of patients. That is not at all surprising bearing in mind the long known association of 5-FU with this particular skin side-effect, mostly seen when administered by continuous infusion. 3The pathophysiology of HFS is largely unknown. It is nevertheless known to be aggravated by strenuous exercise and manual labour, as well as to be clearly dose related, as such seriously affecting the outcome of the chemotherapeutic regimen.Thus, HFS treatment consists of discontinuation of the drug, emollient local therapy and, probably (still deserving clarification), pyridoxine (vitamin B 6 ). We are not aware of the previous use of tacrolimus ointment in this setting; however, its barrier-restoring properties along with its immunomodulatory, anti-inflammatory profile led us to successfu...

Possible Mechanisms by Which Topical 5-Fluorouracil and Dermabrasion Could Induce Pigment Spread in Vitiligo Skin: An Experimental Study

“…In the same way in human skin, normal and intact skin did not show any clinical alteration following application of 5-FU cream during topical treatment of many cutaneous disorders (actinic keratosis, psoriasis, and epithelial neoplasms) [10]. Localized hyperpigmentations located in the normally pigmented extremities (hands and feet) and tongue have been reported mainly during systemic treatment of various cancers by 5-FU [14–20] but only occasionally during topical treatment [29, 30]. In vitiligo skin with black or white hairs, no improvement or any pigment spread was observed after the exclusive topical use of 5-FU cream [2].…”

“…Usually, these hyperpigmented lesions are located on the normally pigmented extremities (hands and feet) and tongue. It has been postulated that these hyperpigmentations could be considered as postinflammatory hyperpigmentations on sites submitted to repeated friction [14–20]. …”

Disorders of pigmentation

“…120 Vitiligo has also followed the use of interferon-α therapy for hepatitis B infection. 123 Many cases of depigmentation, some resembling vitiligo, have been reported following the use of the tyrosine kinase inhibitor imatinib, used in the treatment of chronic myeloid leukemia. 123 Many cases of depigmentation, some resembling vitiligo, have been reported following the use of the tyrosine kinase inhibitor imatinib, used in the treatment of chronic myeloid leukemia.…”

Unconventional Treatments for Vitiligo: Are They (Un) Satisfactory?

“…Capecitabine is an oral prodrug of 5-FU, used in the treatment of metastatic colon and breast cancers. It has been observed how its use cause cutaneous hyperpigmentation [ 11 ][ 12 ]. At the moment, more studies have to be conducted to evaluate the potential use of the drug in the treatment of vitiligo.…”