Photosensitive lichenoid drug eruption to capecitabine
Authors: Greg Walker, Natalie Lane, Palak Parekh
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: A 75-year-old Caucasian woman undergoing capecitabine treatment for metastatic breast cancer presented to the dermatology clinic for evaluation of a pruritic eruption on the sun-exposed areas of her body that began 2 months after initiation of capecitabine treatment. The patient reported receiving ample sun exposure during the summer months when she noted the onset of the eruption. She also noted fingernail changes over the same time frame. Her other medications included prochlorperazine maleate 10 mg, hydrocodone/acetaminophen 5 mg/325 mg, and denosumab 120 mg subcutaneously every 4 weeks. Examination revealed numerous violaceous, flat-topped papules on extensor forearms, dorsal hands, and anterior legs (Fig 1). Scaling and erythema was observed in the periungual areas with marked subungual hyperkeratosis. Diffuse erythema was also noted of the palmar and plantar surfaces. Examination of the oral cavity was unremarkable. Fingernail clipping for histopathologic and microbiologic evaluation of fungus was negative. Punch biopsy of the skin of her right dorsal hand demonstrated a lichenoid interface dermatitis with compact orthokeratosis of the stratum corneum, multiple scattered melanophages, and a few eosinophils in the dermis. The clinical and histologic features were consistent with a diagnosis of photosensitive lichenoid drug eruption secondary to capecitabine treatment. The patient was prescribed topical clobetasol propionate 0.05% ointment and systemic hydroxyzine, and was recommended adherence to sun protection strategies. With these measures, she noted a marked improvement in her eruption without any changes in her chemotherapeutic regimen. Capecitabine (Xeloda) is an oral prodrug of fluorouracil (5-FU) used in the treatment of advanced colorectal, esophageal, laryngeal, and metastatic breast cancer.1Mignogna M.D. Fortuna G. Falleti J. Leuci S. Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis.Eur J Clin Pharmacol. 2009; 65: 1057-1059Crossref PubMed Scopus (9) Google Scholar While 5-FU has been used in the past for many solid tumors, it must be administered intravenously. As an oral prodrug of 5-FU, capecitabine is easier to administer and more convenient for the patient; as such, its use has increased in treating these patients.2Weger W. Kränke B. Gerger A. Salmhofer W. Aberer E. Occurrence of subacute cutaneous lupus erythematosus after treatment with fluorouracil and capecitabine.J Am Acad Dermatol. 2008; 59: S4-S6Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar Some reports have suggested a link between capecitabine use and the development of a lichenoid photosensitive eruption.3Hague J.S. Ilchyshyn A. Lichenoid photosensitive eruption due to capecitabine chemotherapy for metastatic breast cancer.Clin Exp Dermatol. 2007; 32: 102-103Crossref PubMed Scopus (1) Google Scholar Other cutaneous side effects have also been reported, the most common of which is palmar-plantar erythrodysesthesia, or hand-foot syndrome, which occurs in as many as 50% of those treated with capecitabine.4Vaccaro M. Barbuzza O. Guarneri F. Guarneri B. Nail and periungual toxicity following capecitabine therapy.Br J Clin Pharmacol. 2008; 66: 325-326Crossref PubMed Scopus (11) Google Scholar This condition causes tingling in the palms and soles that may progress to burning pain 3 to 4 days later with swelling, erythema, and possible skin ulceration.3Hague J.S. Ilchyshyn A. Lichenoid photosensitive eruption due to capecitabine chemotherapy for metastatic breast cancer.Clin Exp Dermatol. 2007; 32: 102-103Crossref PubMed Scopus (1) Google Scholar In addition, reports have linked the use of capecitabine to other cutaneous presentations, including oral lichenoid stomatitis,1Mignogna M.D. Fortuna G. Falleti J. Leuci S. Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis.Eur J Clin Pharmacol. 2009; 65: 1057-1059Crossref PubMed Scopus (9) Google Scholar subacute cutaneous lupus erythematosus,2Weger W. Kränke B. Gerger A. Salmhofer W. Aberer E. Occurrence of subacute cutaneous lupus erythematosus after treatment with fluorouracil and capecitabine.J Am Acad Dermatol. 2008; 59: S4-S6Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar and other dermatologic conditions (Table I).Table ICutaneous side effects of capecitabineLichenoid stomatitisLichenoid lesions associated with bullous areas on anterior tongue and erythema on bilateral buccal cheeks.4Vaccaro M. Barbuzza O. Guarneri F. Guarneri B. Nail and periungual toxicity following capecitabine therapy.Br J Clin Pharmacol. 2008; 66: 325-326Crossref PubMed Scopus (11) Google ScholarNail and periungual toxicityChanges may affect the nail matrix, nail bed, and proximal nail fold – subungual hyperkeratosis, onycholysis, onychomadesis,1Mignogna M.D. Fortuna G. Falleti J. Leuci S. Capecitabine-induced stomatitis: a likely pathogenetic mechanism of oral lichenoid mucositis.Eur J Clin Pharmacol. 2009; 65: 1057-1059Crossref PubMed Scopus (9) Google Scholar acute paronychia, exudative discharge from nails, and erythematous papular, and vascular lesions in nail folds.5Chen G.Y. Chen Y.H. Hsu M.M. Tsao C.J. Chen W.C. Onychomadesis and onycholysis associated with capecitabine.Br J Dermatol. 2001; 145: 521-522Crossref PubMed Scopus (39) Google ScholarPalmar-plantar erythrodysesthesia (hand-foot syndrome)Most common cutaneous reaction to capecitabine, resulting in tingling sensation of palms and soles, followed by burning 3 to 4 days later with swelling and erythema, possibly leading to ulceration of the skin.2Weger W. Kränke B. Gerger A. Salmhofer W. Aberer E. Occurrence of subacute cutaneous lupus erythematosus after treatment with fluorouracil and capecitabine.J Am Acad Dermatol. 2008; 59: S4-S6Abstract Full Text Full Text PDF PubMed Scopus (42) Google ScholarSubacute cutaneous lupus erythematosusErythematous, nonscarring papulosquamous or annular lesions distributed over photosensitive areas.Other common dermatologic conditionsCan induce dermatitis with pruritus, bullous eruptions, xerosis, and alopecia. It may also cause inflammation of preexisting actinic keratosis.3Hague J.S. Ilchyshyn A. Lichenoid photosensitive eruption due to capecitabine chemotherapy for metastatic breast cancer.Clin Exp Dermatol. 2007; 32: 102-103Crossref PubMed Scopus (1) Google Scholar Open table in a new tab The reaction in our patient was unique because of the simultaneous presentation of a photosensitive lichenoid eruption, diffuse palmoplantar erythema, and ungual toxicity, as evidenced by the periungual erythema and subungual hyperkeratosis. With the increasing use of capecitabine in chemotherapeutic treatment for cancer, dermatologists should be aware of its potential cutaneous side effects.