 |
|
Intralesional Fluorouracil Injection in Infantile Digital Fibromatosis
Chang-Keun Oh, MD, PhD;
Hyo-Sung Son, MD;
Yoo-Wook Kwon, PhD;
Ho-Sun Jang, MD, PhD;
Kyung-Sool Kwon, MD, PhD
From the Department of Dermatology, Pusan National University College of Medicine, Busan, Korea (Drs Oh, Son, Jang, and K.-S. Kwon); and Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md (Dr Y.-W. Kwon).
Arch Dermatol. 2005;141:549-550.
REPORT OF A CASE
A 7-year-old Korean girl presented with an 8-month history of an erythematous hard plaque on her left hand. There was no history of trauma. On physical examination, a 1.4 x 0.8-cm firm plaque was observed on the ulnar surface of the left hand at the metacarpophalangeal level (Figure).
|
|
|
|
Figure. Plaque on the ulnar surface of the left hand. A, Well-defined erythematous firm plaque before treatment. B, One month after first injection. C, One month after second injection. D, Seven months after fifth injection.
|
|
|
Histopathologic examination showed moderately cellular fibroblasts throughout the dermis. Hematoxylin-eosin staining revealed eosinophilic intracytoplasmic inclusion bodies in fibroblasts. The inclusions stained bright red with Masson trichrome and deep purple with phosphotungstic acid–hematoxylin. They were negative for alcian blue and periodic acid–Schiff.
THERAPEUTIC CHALLENGE
In the past, infantile digital fibromatosis (IDF) was considered potentially malignant, leading to amputation of affected digits.1 However, reported cases of spontaneous regression suggest a more benign biologic behavior, and metastases have never been reported.1-3 Therefore, a conservative approach is now advocated. However, deformities of the affected digits have developed in a number of untreated cases, with functional impairment after regression of tumor.1-3 Moreover, up to 60% of cases recurred even after standard wide local excision.1-2 Thus, an effective, nonsurgical treatment with low morbidity is desirable.
SOLUTION
We treated the lesion with 5 monthly intralesional injections of fluorouracil. At each session, undiluted fluorouracil (50 mg/dL) was injected into the lesion using a 30-gauge needle without any local or general anesthesia. At each treatment, the total 10 mg (0.2 mL) of fluorouracil was injected at 2 or 3 sites. Systemic adverse effects were not observed, and local adverse effects included only pain on injection. Partial response was noted after 1 injection, and the lesion regressed with flattening after 5 injections (Figure). No recurrence was noted during a 2-year follow-up period.
COMMENT
Infantile digital fibromatosis is a rare benign fibrous tumor that develops on the fingers and toes of infants and children.4 In this case, intralesional injection of fluorouracil was effective in inducing regression of IDF. Fluorouracil, a pyrimidine analogue with antimetabolite activity, is widely used in cancer chemotherapy. Interestingly, it inhibits dermal fibroblast proliferation and collagen synthesis in cell culture.5-6 Recently Wendling et al7 demonstrated that fluorouracil inhibited transforming growth factor  –induced type I collagen synthesis through the inhibition of transforming growth factor –SMAD–driven COL1A2 transactivation in human fibroblasts.
Fluorouracil has previously been used to reduce scarring. In the early 1980s, it was investigated as an adjunct to glaucoma-filtering surgery, as failure of glaucoma filtration surgery often occurred as a result of scarring at the surgical site.5, 8 In 1999, Fitzpatrick9 reported his 9-year experience with the use of intralesional injection of fluorouracil for the treatment and prevention of inflamed hypertrophic scars and keloids. Favorable responses were noted in most patients. The best responses were obtained with scars that were very red, symptomatic, inflamed, and indurated. Old, uninflamed, asymptomatic scars did not respond very well. Keloids responded, but frequently recurred. Fitzpatrick’s success has been confirmed by others.10-11 Uppal et al10 reported that a single application of fluorouracil solution after extralesional excision of keloids resulted in significant reduction of scar size and recurrence. Gupta and Kalra11 further demonstrated the efficacy of intralesional fluorouracil as an individual therapeutic agent for the treatment of small keloids. They reported that approximately half of the patients showed more than 50% flattening of the treated keloid. Although hypertrophic scars, keloids, and IDF express different clinical phenotypes, they share myofibroblastic features on histologic examination.12-14 These similarities may explain our success with intralesional injections of fluorouracil.
The safety of fluorouracil as an adjunct to glaucoma-filtering surgery in children also has been established.15 We used 10 mg of fluorouracil as an intralesional dosage according to previous keloid therapies.9-11 Although this dosage of fluorouracil is much lower than tolerable intravenous dosages, careful attention needs to be paid to both short- and long-term safety in children.16 The common adverse effects of intralesional fluorouracil treatment were pain, purpura, ulceration, burning sensation, and pigmentary disturbance.9, 11 The main disadvantages of fluorouracil treatment were pain and the need for repeated injection. Therefore, another alternative technique, such as topical fluorouracil application after excision surgery or shave removal, might also be useful to minimize these disadvantages. Nevertherless, intralesional fluorouracil injection appears to be a safe, effective treatment for IDF that warrants further investigation.
| Submissions
Clinicians, local and regional societies, residents, and fellows are invited to submit cases of challenges in management and therapeutics to this section. Cases should follow the established pattern. Submit 4 double-spaced copies of the manuscript with right margins nonjustified and 4 sets of the illustrations. Photomicrographs and illustrations must be clear and submitted as positive color transparencies (35-mm slides) or black-and-white prints. Do not submit color prints unless accompanied by original transparencies. Electronic submissions must have all figures in TIFF format. Material should be accompanied by the required copyright transfer statement, as noted in "Instructions for Authors." Material for this section should be submitted to George J. Hruza, MD, Laser and Dermatologic Surgery Center, 14377 Woodlake Dr, Suite 111, Town and Country, MO 63017 (cuttingedge{at}lasersurgeryusa.com).
|
|
AUTHOR INFORMATION
Correspondence: Chang-Keun Oh, MD, PhD, Department of Dermatology, Pusan National University, College of Medicine, 1-10 Ami-dong, Seo-gu, Busan 602-739, Korea (ckoh{at}pusan.ac.kr).
Accepted for Publication: July 20, 2004.
Financial Disclosure: None.
Acknowledgment: We thank Christine Ko, MD, Dermatopathology, University of California, Los Angeles, for the revision of the manuscript for this article.
REFERENCES
| |
1. Dabney KW, MacEwen GD, Davis NE. Recurring digital fibrous tumor of childhood: case report with long-term follow-up and review of the literature. J Pediatr Orthop. 1986;6:612-617.
ISI
| PUBMED
2. Beckett JH, Jacobs AH. Recurring digital fibrous tumor of childhood: a review. Pediatrics. 1977;59:401-406.
FREE FULL TEXT
3. Azam SH, Nicholas JL. Recurring infantile digital fibromatosis: report of two cases. J Pediatr Surg. 1995;30:89-90.
FULL TEXT
|
ISI
| PUBMED
4. Reye RDK. Recurring digital fibrous tumors of childhood. Arch Pathol. 1965;80:228-231.
ISI
| PUBMED
5. Blumenkranz MS, Claflin A, Hajek AS. Selection of therapeutic agents for intraocular proliferative disease: cell culture evaluation. Arch Ophthalmol. 1984;102:598-604.
ABSTRACT
6. de Waard JW, de Man BM, Wobbes T, van der Linden CJ, Hendriks T. Inhibition of fibroblast collagen synthesis and proliferation by levamisole and 5-fluorouracil. Eur J Cancer. 1998;34:162-167.
7. Wendling J, Marchand A, Mauviel A, Verrecchia F. 5-Fluorouracil blocks transforming growth factor-beta–induced alpha 2 type I collagen gene (COL1A2) expression in human fibroblasts via c-Jun NH2-terminal kinase/activator protein-1 activation. Mol Pharmacol. 2003;64:707-713.
FREE FULL TEXT
8. Gressel MG, Parrish RK II, Folberg R. 5-Fluorouracil and glaucoma filtering surgery, I: an animal model. Ophthalmology. 1984;91:378-383.
ISI
| PUBMED
9. Fitzpatrick RE. Treatment of inflamed hypertrophic scars using intralesional 5-FU. Dermatol Surg. 1999;25:224-232.
FULL TEXT
|
ISI
| PUBMED
10. Uppal RS, Khan U, Kakar S, Talas G, Chapman P, McGrouther AD. The effects of a single dose of 5-fluorouracil on keloid scars: a clinical trial of timed wound irrigation after extralesional excision. Plast Reconstr Surg. 2001;108:1218-1224.
FULL TEXT
|
ISI
| PUBMED
11. Gupta S, Kalra A. Efficacy and safety of intralesional 5-fluorouracil in the treatment of keloids. Dermatology. 2002;204:130-132.
FULL TEXT
|
ISI
| PUBMED
12. Iwasaki H, Kikuchi M, Mori R, et al. Infantile digital fibromatosis: ultrastructural, histochemical, and tissue culture observations. Cancer. 1980;46:2238-2247.
FULL TEXT
|
ISI
| PUBMED
13. Eyden B. Electron microscopy in the study of myofibroblastic lesions. Semin Diagn Pathol. 2003;20:13-24.
ISI
| PUBMED
14. Chipev CC, Simman R, Hatch G, Katz AE, Siegel DM, Simon M. Myofibroblast phenotype and apoptosis in keloid and palmar fibroblasts in vitro. Cell Death Differ. 2000;7:166-176.
FULL TEXT
|
ISI
| PUBMED
15. Snir M, Lusky M, Shalev B, Gaton D, Weinberger D. Mitomycin C and 5-fluorouracil antimetabolite therapy for pediatric glaucoma filtration surgery. Ophthalmic Surg Lasers. 2000;31:31-37.
ISI
| PUBMED
16. Balis FM, Holcenberg JS, Poplack DG. General principles of chemotherapy. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. Philadelphia, Pa: JB Lippincott Co; 1997:243-244.
SECTION EDITOR: GEORGE J. HRUZA, MD; ASSISTANT SECTION EDITORS: MICHAEL P. HEFFERNAN, MD; ELAINE SIEGFRIED, MD
|
