This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moazzam, N. Articles by Potti, A. Search for Related Content PubMed PubMed Citation Articles by Moazzam, N. Articles by Potti, A. Social Bookmarking                            What's this?

Treatment Side Effects

Case 3. Fluorouracil-Induced Exacerbation of Systemic Lupus Erythematosus

University of North Dakota School of Medicine and Health Sciences, Fargo, ND

A 55-year-old white man with a past medical history of systemic lupus erythematosus (SLE) since 1992 was diagnosed with T4N0M0 (direct hepatic invasion) colon cancer. SLE was in remission at the time of presentation. He was treated with adjuvant chemotherapy with fluorouracil and leucovorin. Initially, he tolerated the chemotherapy well. However, during the third cycle, he developed an erythematous rash on the face that worsened with subsequent doses of fluorouracil therapy. The lesion extended to his neck, thorax, and, finally, his abdomen and legs (Fig 1). Skin biopsy specimens showed atrophic epithelium with perivascular lymphocytes and basilar vacuolar changes, findings suggestive of cutaneous exacerbation of SLE (Fig 2). Because of the latter, fluorouracil therapy was discontinued, which led to resolution of his symptoms. Within 2 weeks, the lesions healed and disappeared (Fig 3).

View larger version (89K): [in this window] [in a new window]   Fig 1.

View larger version (119K): [in this window] [in a new window]   Fig 2.

View larger version (136K): [in this window] [in a new window]   Fig 3.

Fluorouracil is a prodrug, which is subject to both anabolism and catabolism. The cytotoxic activity depends on its anabolism to nucleotides. The toxicity of fluorouracil is related to products of its catabolism. The toxicity results from inhibition of rapidly dividing tissues, such as bone marrow hematopoietic cells and gastrointestinal mucosal cells, with well-established common adverse effects of diarrhea, nausea, vomiting, mucositis,² stomatitis,^2,3 small bowl toxicty,⁴ neutropenia,² myelosuppression,² cardiotoxicity,⁴ and photosensitivity.⁵

SLE-like skin lesions are uncommon in patients receiving fluorouracil. To our knowledge, there are only a few reported cases of lupus-like erythematous eruptions caused by fluorouracil.⁶ In 2001, 17 cases of discoid lupus-like eruptions induced by fluorouracil agents were reported, of which only one case was caused by fluorouracil.⁷ In none of the above-mentioned cases was there a past history of SLE. The exact pathogenesis of fluorouracil precipitating a lupus flare is unknown but may be due to immunologic mechanisms. This is contrary to the fact that antimetabolites and cytotoxic drugs can be used for the treatment of rheumatic diseases.⁸

The clinical scenario in our patient suggests that fluorouracil induced a flare-up of SLE, with lesions present on unexposed areas (such as the chest and abdomen); a skin biopsy showed the cutaneous manifestations of lupus. There are no published data about the effect of fluorouracil on rechallenge in such cases.

REFERENCES

1. Marsoni S: Efficacy of adjuvant fluorouracil and leucovorin in stage B2 and C colon cancer: International Multicenter Pooled Analysis of Colon Cancer Trials Investigators. Semin Oncol 28: 14-19, 2001 (1 suppl 1)[Medline]

2. Kuhn JG: Fluorouracil and new oral fluorinated pyrimidines. Ann Pharmacother 35: 217-227, 2001[Abstract]

3. Spiegel RJ: Acute toxicities of chemotherapy. Cancer Treat Rev 8: 197-207, 1981[CrossRef][Medline]

4. Fata F, Ron IG, Kemeny N, et al: 5-Flurouracil induced small bowl toxicity in patients with colorectal carcinoma. Cancer 86: 1129-1134, 1999[CrossRef][Medline]

5. Horio T, Murai T, Ikai K: Photosensitivity due to a fluorouracil derivative. Arch Dermatol 114: 1498-1500, 1978[Abstract/Free Full Text]

6. Dudley K, Micetich K, Massa MC: Erythema with features of seborrheic dermatitis and lupus erythematosus associated with 5-fluorouracil. Cutis 39: 64-66, 1987[Medline]

7. Yoshimasu T, Hiroi A, Uede K: Discoid lupus erythematosus (DLE)-like lesions induced by uracil-tegafur (UFT). Eur J Dermatol 11: 54-57, 2001[Medline]

8. McCune WJ, Friedman AW: Immunosuppressive drug therapy for rheumatic disease. Curr Opin Rheumatol 4: 314-321, 1992[Medline]

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Moazzam, N. Articles by Potti, A. Search for Related Content PubMed PubMed Citation Articles by Moazzam, N. Articles by Potti, A. Social Bookmarking                            What's this?