Corticosteroid Atrophy Plaque on the Scalp Treated with 5-Fluourouracil and Bleomycin Infusion in the MMP Technique

Abstract

Alopecia areata (AA) is a disease with a great impact on quality of life of patients. Among several treatment modalities, intralesional injectable corticosteroid therapy is the first option, with corticosteroid-induced cutaneous atrophy as a common adverse event. We describe a case of plaque AA in the frontal region of the scalp that evolved with cutaneous atrophy induced by the application of intralesional corticosteroids but presented complete and sustained repilation after being treated with 5-Fluorouracil and Bleomycin using the technique of MMP (Microinfusion of Medicines into the Skin).

Established Facts

• 5-Fluorouracil (5-FU) is a fluorinated pyrimidine analogue with antimetabolic activity, inhibiting the proliferation of fibroblasts in vitro and in vivo and the gene expression of type I collagen induced by TGF-β8. The antifibrotic property of 5-FU reduces fibrosis in the papillary dermis by stimulating melanogenesis.

• Bleomycin is a cytotoxic antibiotic derived from Streptomyces verticillus. It has antineoplastic, antibacterial, and antiviral properties. It has been shown that cultured human dermal fibroblasts treated with bleomycin have decreased collagen synthesis even when TGF-β1 is applied.

Novel Insights

• A case of alopecia areata in plaque in the frontal region of the scalp that evolved with atrophy induced by the application of intralesional corticosteroids, but when treated with 5-Fluorouracil and Bleomycin using the MMP technique (Microinfusion of Medicines into the Skin, in Portuguese, Microinfusão de Medicamentos na Pele) it presented total response and resolution of the condition.

Introduction

Alopecia areata (AA) affects 1–2% of the general population, being more prevalent among the age of 10–25 years [1], with an impact on quality of life and several treatment options with varying effectiveness [2]. In adults with localized plaques (<30% of involvement), intralesional corticosteroid therapy is one of the main treatments, as it has fewer side effects when compared to systemic corticosteroids and greater penetration when compared to the topical route. However, cutaneous atrophy induced by corticosteroids is a relatively common adverse effect, especially when applied to the deep dermis in high concentrations and in the form of triamcinolone hexacetonide [3]. This article reports a case of AA in plaque in the frontal region of the scalp that evolved with atrophy induced by the application of intralesional corticosteroids, but when treated with 5-Fluorouracil (5-FU) and Bleomycin using the MMP technique (Microinfusion of Medicines into the Skin, in Portuguese, Microinfusão de Medicamentos na Pele) it presented total response and resolution of the condition.

Case Report

V.M.C.F, 31 years old, female, presented with an area of alopecia in the frontal region of the scalp for more than 2 years. During this period, she underwent several treatments, such as topical application of clobetasol 0.05% and minoxidil 5%, 4 infiltration sessions with triamcinolone hexacetonide 5 mg/mL, and application of 2% diphencyprone. On clinical examination, there was a plaque of erythematous-atrophic alopecia with a shiny and hardened background in the frontal region of the scalp measuring approximately 3 × 8 cm (Fig. 1), the hair pull test was negative at the edges. Trichoscopy showed telangiectasia, dystrophic hair, black dots, white dots, yellow dots, and exclamation mark hair (Fig. 2), suggesting the hypothesis of AA associated with atrophy.

Fig. 1.

Plaque of erythematous-atrophic alopecia with a shiny and hardened background in the frontal region of the scalp measuring approximately 3 × 8 cm.

Fig. 2.

Trichoscopy showed telangiectasia, dystrophic hair, black dots, white dots, yellow dots, and exclamation mark hair.

An anatomopathological examination was performed, which showed epidermal atrophy, dermal fibrosis, and reduction of hair follicles, thus suggesting a condition of cicatricial alopecia. However, a new biopsy of the edge of the scalp lesion was performed, which showed findings compatible with non-scarring and non-inflammatory alopecia, corresponding to the non-inflammatory phase of AA (Fig. 3). Then, confirmed the diagnosis of AA with atrophy due to corticoid deposits.

Fig. 3.

Non-scarring alopecia without inflammatory activity with a proportional numerical increase in miniaturized hairs and several follicles in the terminal phase of catagen.

Initially, it was decided to infiltrate sterile saline solution (NaCl 0.9%) over the corticoid crystals, with the aim of dissolving them, but there was no response to 4 weekly applications, waiting 2 months with the follow-up [4]. Therefore, it was decided to surgically remove the corticoid crystals. After infiltrative anesthesia with lidocaine with vasoconstrictor, an incision was made with a scalpel and exeresis with curved Kelly tweezers. After removing all the crystals, the fibrosis was treated with the local application of a drug with antifibrous action. There were 3 bimonthly sessions. In the first session, 5-FU was applied and in the subsequent sessions, Bleomycin. The technique used for the application was MMP (Microinfusion of Medication in the Skin), which consists of using a tattoo machine to infuse the medication. There was gradual and complete repilation of the treated area (Fig. 4). The patient received a follow-up for more than 5 years with a good and sustained response (Fig. 5).

Fig. 4.

Complete repilation of the treated area after treatment with 5-FU and Bleomycin in the MMP technique.

Fig. 5.

Complete repilation maintained after more than 5 years of follow-up with post-treatment with 5-FU and Bleomycin in the MMP technique.

Discussion

AA is an autoimmune disease that targets hair follicles in the anagen phase and causes non-scarring alopecia. AA usually manifests before age 40, with no gender or race predilection. The lifetime risk of developing AA is estimated at 2% [5].

Intralesional corticosteroid therapy overcomes the epidermal barrier, delivering the drug directly to the inflamed area [6]. Classically, a concentration of 2.5, 5 and 10 mg/mL of triamcinolone is used for the scalp [3], and the three concentrations have the same effectiveness [3]. Triamcinolone acetonide is a corticosteroid most widely used injectable in the world [7]. In Brazil, triamcinolone acetonide is restricted to intraocular use and, therefore, the most widespread form has become triamcinolone hexacetonide (TH), its less soluble derivative and with a higher risk of skin atrophy [6].

The procedure described here, the Microinfusion of Medicines into the Skin (MMP) was idealized and based to be performed by doctors through the ancient tattooing procedure. In MMP, the infused active principles, after acting in the tissue, would probably be absorbed and eliminated in a variable period of time [8].

Microneedling releases platelet-derived growth factors, epidermal growth factors, by activating regeneration through wounds, activating stem cells in the bulb and leading to overexpression of genes related to hair growth, such as the Wnt3-a, Wnt10-b, and factor of vascular endothelial growth in rats [9].

5-FU is a fluorinated pyrimidine analogue with antimetabolic activity, inhibiting the proliferation of fibroblasts in vitro and in vivo and the gene expression of type I collagen induced by TGF-β8. The antifibrotic property of 5-FU reduces fibrosis in the papillary dermis by stimulating melanogenesis. Furthermore, 5-FU has a direct effect on melanocytes and repigmentation [10].

Bleomycin is a cytotoxic antibiotic derived from Streptomyces verticillus. It has antineoplastic, antibacterial, and antiviral properties. It has been shown that cultured human dermal fibroblasts treated with bleomycin have decreased collagen synthesis even when TGF-β1 is applied [11].

Kabel et al. [12] evaluated the efficacy and safety of intralesional infusion of 5-FU and bleomycin in the treatment of keloids and hypertrophic scars in 120 patients. Patients who used 5-FU alone or combined with triamcinolone (acetonide) showed less improvement than patients who received only bleomycin. Vascularity, pigmentation, elasticity, and height were evaluated. It was concluded, in the study that the injection of bleomycin was more effective when compared to intralesional 5-FU [12].

Although bleomycin has been shown to be superior to 5-FU, the combination of the drugs is justified due to the broad antifibrosant capacity of 5-FU. Therefore, it is concluded that the treatment used with the MMP technique was effective, with a long-lasting and sustained response, and could promote the study of new treatment options for adverse effects and iatrogenic events in the medical field.

Statement of Ethics

This study protocol was reviewed and approved by Universidade de Mogi das Cruzes – UMC/SP – Brazil, approval number 73060623.5.0000.5497. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors did not receive any funding.

Author Contributions

Caio Leal Carvalho, Fernanda Freitas de Brito, Letícia Bortolini, and Raissa Pinheiro Zobiole: critical literature review and manuscript critical review. Vanessa Catalá Casteli Assumpção: preparation and writing of the manuscript. Luciana Gasques de Souza: approval of the final version of the manuscript, data collection, analysis and interpretation, effective participation in research orientation, intellectual participation in propaedeutic and/or therapeutic management of studied case, preparation and writing of the manuscript, study conception, and planning.

Funding Statement

The authors did not receive any funding.

Data Availability Statement

All data generated or analyzed during this study are included in this article. Further enquiries can be directed to the corresponding author.