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Intralesional Treatment With 5-Fluorouracil and Steroid Improves Allergic Contact Dermatitis Without Causing Skin Atrophy and Rebound Lesions

Chen, Xiangming BS; Wang, Guojiang MS; Zeng, Qingwen MD; Zhang, Haiqing BS; Hu, Yang BS; Yu, Aihua MS; Li, Ting MS

doi: 10.1097/DER.0000000000000270
Letters

Department of Dermatology, Shanghai Jiading Nanxiang Hospital, Shanghai, China, School of Life Sciences, Shanghai University China;

Department of Dermatology, Shanghai Pudong New District Zhoupu Hospital, Shanghai, China;

Department of Pediatric Endocrinology/Genetics, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, Institute for Pediatric Research, China;

Department of Dermatology, Shanghai Jiading Nanxiang Hospital, Shanghai, China.

This study was supported by a grant from Shanghai City Key Medical Specialties in B Construction Projects (number ZK2012B18).

Address reprint requests to Ting Li, MS, Department of Dermatology, Nanxiang Hospital of Jiading, 495, Zhongren Road, Jiading District, Shanghai, China. E-mail: kety5288@163.com.

The authors have no conflicts of interest to declare.

X.C. and G.W. contributed equally to this study.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

To the Editor:

Intralesional triamcinolone acetonide (TA) injections can rapidly and effectively treat severe localized dermatitis. However, these treatments are associated with adverse effects such as dermal atrophy, hypopigmentation, capillary dilation, and Cushing syndrome.1,2 These adverse effects may be attributable, in part, to the large doses of TA required to obtain the desired outcome.3 The combination of 5-fluorouracil (5-FU) and TA has been shown to be superior to TA monotherapy in patients with keloids and hypertrophic scars.4 Furthermore, combination therapy reduces the required dosage of both drugs. However, limited data are available on the use of intralesional TA injections along with 5-FU for the treatment of allergic contact dermatitis (ACD).

We therefore examined the effects of 5-FU plus TA on 2,4-dinitrofluorobenzene–induced ACD in BALB/c mice. In our study, ACD mice were randomly allocated to the following 4 groups (9 mice per group): ACD control group, 5-FU group, TA group, and 5-FU/TA group. The mice in the 5-FU, TA, and 5-FU/TA groups received intralesional injections of 1 mg 5-FU, 0.4 mg TA, and a mixture of 0.5 mg 5-FU + 0.2 mg TA, respectively. The control group received intralesional injections of 1 mL normal saline. Another 9 healthy mice were assigned to a nontreatment group and left untreated. We analyzed the clinical and histopathological features in all groups and measured the serum cytokine levels (interleukin [IL] 4, interferon γ, tumor necrosis factor [TNF] α, and IL-17) at different time points (1, 7, and 15 days after treatment).

Intralesional injection of 0.4 mg TA alone showed significant anti-inflammatory activity but also led to obvious skin atrophy and a rebound phenomenon. In contrast, both combined therapy with half-dose 5-FU and TA and treatment with TA alone reduced lesion severity (Fig. 1). This finding is in line with our previously published clinical results.5 This effect was also supported by the results of the histopathological analysis. The intralesional injection of 0.4 mg TA inhibited the increase in epidermal thickness and capillary caliber within 7 days, but a rebound phenomenon was observed on day 15. The administration of 1 mg 5-FU significantly decreased epidermal thickness at a later time point and decreased the capillary caliber and increased the skin thickness at all time points, as compared with TA treatment. In addition, the serum cytokine measurements showed that the 5-FU–mediated inhibition of TNF-α was persistent, and the combination of TA with 5-FU could offset the weakened inhibition of TNF-α by TA alone at later stages.

Figure 1

Figure 1

In conclusion, our experiment revealed the effects of TA alone, 5-FU alone, and 5-FU/TA in a mouse model of 2,4-dinitrofluorobenzene–induced ACD. The intralesional injection of TA alone reduced inflammatory reaction and cytokine levels in the early stage but induced significant skin atrophy, rebound lesions, and elevated cytokine levels in later stages. Our results give an insight into the potential advantages of combined treatments with low-dose 5-FU/TA. Such a treatment may improve inflammatory lesions without producing skin atrophy or rebound lesions and could lower serum TNF-α and IFN-γ levels in vivo.

Xiangming Chen, BS

Department of Dermatology

Shanghai Jiading Nanxiang Hospital

Shanghai, China

School of Life Sciences

Shanghai University China

Guojiang Wang, MS

Department of Dermatology

Shanghai Pudong New District Zhoupu Hospital

Shanghai, China

Qingwen Zeng, MD

Department of Pediatric Endocrinology/Genetics

Xinhua Hospital, Shanghai Jiao Tong University

School of Medicine, Shanghai

Institute for Pediatric Research, China

Haiqing Zhang, BS

Yang Hu, BS

Aihua Yu, MS

Ting Li, MS

Department of Dermatology

Shanghai Jiading Nanxiang Hospital

Shanghai, China

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REFERENCES

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2. Jang WS, Park J, Yoo KH, et al. Branch-shaped cutaneous hypopigmentation and atrophy after intralesional triamcinolone injection. Ann Dermatol 2011;23(1):111–114.
3. Zimmermann GR, Avery W, Finelli AL, et al. Selective amplification of glucocorticoid anti-inflammatory activity through synergistic multi-target action of a combination drug. Arthritis Res Ther 2009;11(1):R12.
4. Trisliana Perdanasari A, Lazzeri D, Su W, et al. Recent developments in the use of intralesional injections keloid treatment. Arch Plast Surg 2014;41(6):620–629.
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