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[page 68]                                                            [Dermatology Reports 2011; 3:e30]

Tegafur-induced acral
hyperpigmentation
Vera Teixeira, Ricardo Vieira,
Américo Figueiredo
Department of Dermatology, Coimbra
University Hospital, Portugal

Abstract 

Tegafur is a prodrug of 5-fluorouracil (5-FU)
with a similar spectrum of antitumor activity. It
is used in the treatment of advanced gastroin-
testinal neoplasms. Over 5-FU, tegafur has the
advantage of oral administration and less
hematologic toxicity. Gastrointestinal toxicity is
its main dose-limiting factor. The cutaneous
adverse effects of tegafur include mucositis,
photosensitivity, diffuse or nail-restricted hyper-
pigmentation, palmoplantar erythrodysesthesia
syndrome, palmoplantar keratoderma, sclero-
dactyly and Raynaud phenomenon. We report
here the case of a patient who developed acral
hyperpigmentation during treatment with
tegafur.

Case Report

A 48-year-old woman, phototype V, with an
advanced rectal adenocarcinoma stage C
(Duke’s classification) diagnosed in Decem-
ber 2009, who developed acral hyperpigmenta-
tion during tegafur intake. Radio-therapy and
chemotherapy (including tegafur) were initi-
ated as neoadjuvant agents followed by rectal
anterior resection. Tegafur (500 mg/d) was
reintroduced one month after surgery. Four
months later, the patient appeared with multi-
ple 2-10 mm round and oval-shaped brown
macules on the face (Figure 1), tongue (Figure
2A), hands, soles and nails. Almost all nails
were involved, and longitudinal melano-nychia
was identified in the 2nd e 3rd fingernails of her
right hand (Figure 2B). The skin biopsy
revealed mild basal pigmentation. The diagno-
sis of tegafur-induced hiperpigmentation was
made. One month after discontinuation of
tegafur, the hyperpigmented acral lesions
began to clear. 

Discussion

The cutaneous adverse effects of tegafur
include mucositis, photosensitivity, diffuse or
nail-restricted hyperpigmentation, palmoplan-
tar erythrodysesthesia syndrome, palmoplantar

keratoderma, sclerodactyly and Raynaud phe-
nomenon1-4. Hyperpigmentation of the skin,
mucosa and nails is a side effect associated
with various chemotherapy drugs, including 5-
FU and its prodrugs.5 The time course of tegafur
therapy, the cutaneous reaction and its clear-
ance after discontinuing the treatment suggest
a causal relationship based on chronological cri-
teria. The cause of such pigmentation is
unknown, although there may be a mechanism
common to other chemotherapy drugs. These
substances may increase pigmentation by direct
or MSH-mediated stimulation of melanocytes.6

In 1991, Llistosella et col. proposed a mixed
mechanism involving melanocyte hyperplasia
and a decreased keratinocyte turnover, as basal
pigmentation and dermal melanophages were
observed histologically.1

Clinicians should be aware of this side
effect of tegafur, since it is being increasingly
used in patients with advanced colon cancer.

References

1. Llistosella E, Codina A, Alvarez R, et al.
Tegafur-induced acral hyperpigmentation.
Cutis 1991;48: 205-7.

2. Rios-Buceta L, Buezo GF, Peñas PF, et al.
Palmo-plantar Erythrodysaesthesia Syn-
drome and Other Cutaneous Side-effects
after Treatment with Tegafur. Acta Derm
Venereol 1996;77:80-1.

3. Jucglà A, Sais G, Navarro M, et al. Palmo-
plantar keratoderma secondary to chronic
acral erythema due to tegafur. Arch Der-
matol 1995; 131:364-5.

4. Seishima M, Izumi T, Kanoh H. Raynaud’s
phenomenon possibly induced by a com-
pound drug of tegafur and uracil. Eur J
Dermatol 2000;10:55-8. 

5. Revenga F. Cutaneous side-effects caused by
Tegafur. Int J Dermatology 1999;38: 955-6.

6. Fukushima S, Hatta N. Atypical moles in
patient undergoing chemotherapy with
oral 5-fluorouracil prodrug. Br J Dermatol
2004;151:698-700.

                             Dermatology Reports 2011; volume 3:e30

Correspondence: Vera Teixeira, Serviço de
Dermatologia, Hospitais da Universidade de
Coimbra, Praceta Mota Pinto, 3000-075 Coimbra,
Portugal. E-mail: verafmup@hotmail.com

Key words: tegafur, 5-fluorouracil, acral hyperpig-
mentation.

Received for publication: 23 August 2011.
Accepted for publication: 24 August 2011.

This work is licensed under a Creative Commons
Attribution NonCommercial 3.0 License (CC BY-
NC 3.0).

©Copyright V. Teixeira et al., 2011
Licensee PAGEPress, Italy
Dermatology Reports 2011; 3:e30
doi:10.4081/dr.2011.e30

Figure 1. Brown macules on the face.

Figure 2. Hyperpigmentation on the tongue (A) and longitudinal melanonychia in the 2nd
e 3rd fingernails (B). 

A B

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