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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 25  |  Issue : 2  |  Page : 124-128

Microneedling with topical 5-fluorouracil in the localized stable vitiligo – Is this the way out? – Our experience: A hospital-based study


1 Sparsh Skin Clinic, Jaipur, Rajasthan, India
2 Department of Skin and V.D., Sardar Patel Medical College, Bikaner, Rajasthan, India
3 Gheesibai Memorial Mittal Hospital and Research Centre, Ajmer, Rajasthan, India
4 Department of Skin and V.D., Dr. Sampurnanand Medical College, Jodhpur, Rajasthan, India
5 Department of Health and Family Welfare, Bengaluru, Karnataka, India

Date of Submission27-Mar-2021
Date of Acceptance24-Aug-2021
Date of Web Publication29-Mar-2022

Correspondence Address:
Dr. Paras Choudhary
9/20, Vidyadhar Nagar, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jdds.jdds_35_21

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  Abstract 


Background: Vitiligo is a dermatological challenge with a major socio-psychological concern. Despite the availability of numerous medical and surgical treatment options, a single universally reliable therapeutic modality is yet to emerge due to the variability of response rate in different patients. Purpose: The objective of this study was to assess the safety and efficacy of microneedling along with topical 5-fluorouracil (5-FU) solution application in localized stable vitiligo. Methods: This open, nonrandomized, single-arm study was enrolled with 100 patients with localized stable vitiligo. Microneedling with topical 5-FU solution application was performed on 204 patches. The procedure was performed fortnightly for maximum 6 months. Results: At the end of 3 months, good to excellent (Grade IV) repigmentation was noted in 106 patches (51.96%) and Grade I to Grade II repigmentation was seen in 56 (27.45%) patches whereas at the end of follow-up, 128 (62.74%) patches showed good to excellent response. Conclusion: In conclusion, the results of this study showed that needling with 5-FU is a simple, cost-effective, and well-tolerated procedure which can be used as an alternative or additive modality in the treatment of localized stable vitiligo.

Keywords: 5-fluorouracil, microneedling, vitiligo


How to cite this article:
Singrodia AK, Mehta RD, Sharma D, Choudhary P, Ghiya BC, Bai S J. Microneedling with topical 5-fluorouracil in the localized stable vitiligo – Is this the way out? – Our experience: A hospital-based study. J Dermatol Dermatol Surg 2021;25:124-8

How to cite this URL:
Singrodia AK, Mehta RD, Sharma D, Choudhary P, Ghiya BC, Bai S J. Microneedling with topical 5-fluorouracil in the localized stable vitiligo – Is this the way out? – Our experience: A hospital-based study. J Dermatol Dermatol Surg [serial online] 2021 [cited 2022 Jul 2];25:124-8. Available from: https://www.jddsjournal.org/text.asp?2021/25/2/124/341206




  Introduction Top


Vitiligo is an acquired depigmentary disorder, which is characterized by depigmented macules due to the selective destruction of melanocytes.[1] It causes great social and cosmetic concerns. The prevalence of vitiligo in India varies from 0.1% to 8.8%.[2]

A variety of therapeutic alternatives are available for the treatment of vitiligo, both nonsurgical and surgical. Nonsurgical options are topical corticosteroid, topical calcipotriol, tacrolimus, psoralen and ultraviolet A, narrow-band ultraviolet B, and immunosuppressants.[3] Surgical methods include skin grafting, autologous cultured melanocyte, or epidermal suspension transplantations.[4] Despite the availability of numerous treatment options, a single reliable therapeutic modality is yet to emerge due to the variability of response rate in different patients.

Needling followed by topical application of 5% 5-fluorouracil (5-FU) is a recent advancement to the treatment modality of vitiligo. There are successful reports of dermabrasion and topical 5% 5-FU alone or in combination for the treatment of vitiligo.[5],[6],[7],[8],[9],[10]

Hence to assess the efficacy and safety of microneedling with 5% 5-FU solution in localized stable vitiligo, we conducted this study.


  Methods Top


This hospital-based, open, nonrandomized, single-arm study was conducted in the department of dermatology over 1 year from July 2016 to June 2017, after obtaining the approval of the institutional ethical and research board. (Approval number No: S. No.-F ([Acad]) SPMC/2015/2976 Dated-01/9/15). The sample size was calculated at 80% study power, α error of 0.05, and expected deviation of 2.

Hundred patients with a total of 204 patches were enrolled in the study. A written consent form was obtained from each participant before the study initiation. The inclusion criteria were as follows: patients should have a maximum of five patches of vitiligo; the patches should be stable, i.e. should not have shown any increase or decrease in pigmentation or size over the past 6 months; the size of individual patch should be <10 cm in diameter; no local and systemic therapy for at least 6 months before inclusion in the study; and no active infection should be present on the patches or on the body. Patients with vitiligo on mucosae, pregnant, and lactating women, patients with active infections, keloidal tendency, history of koebnerization, bleeding disorders, and other uncontrolled systemic illnesses were excluded from the study.

All patients were subjected to full history taking, including personal history, history of onset, course, duration, and site of present dermatological disease; family history of vitiligo; past history of previous treatments taken, previous episodes of repigmentation, koebnerization, and disease stability. General examination and detailed dermatological examination to detect the type, and sites of vitiligo were done. Laboratory investigations as complete blood count, coagulation profile, and glycemic status were performed for every patient.

Steps of the procedure

The patch was surgically cleansed meticulously with betadine, and half an hour before the procedure, the topical anesthetic cream (lidocaine/prilocaine 2.5%/2.5%) was applied on the patch to anesthetize it. Microneedling of the vitiligo patch was performed with a 26-gauge needle with punctures made close to each other as much as possible. To keep the uniformity and calibrate the depth of the puncture, the needle was entered only up to the diesel end. This resulted in multiple tiny, punctate, and bleeding points. Homeostasis was achieved by compressing a normal saline-soaked piece of gauge on the vitiligo patch. This was followed by topical application of 5-FU solution and rubbing it for about 2 min. About 1 ml of 5-FU solution (250 mg/5 ml) available in the form of ampules was applied over 1 cm2 area of the patch. The occlusive dressing was then done and kept for 1 day. A second-generation cephalosporin (cefuroxime) and anti-inflammatory drugs (nonsteroidal anti-inflammatory drugs) with topical fusidic acid were given for 5–7 days postoperatively. All procedures were done by the senior author.

Follow-up

This procedure was repeated every fortnightly for maximum 6 months (12 sessions). After the last session, patients were followed up monthly up to 3 months for the appearance of pigmentation and complications if any. A total of 12 sittings were done and if pigmentation occurred earlier, treatment was stopped, and the patient was followed every month up to 9 months.

Assessment

Evaluation was done by the same operator

Clinical photographs were taken before treatment and at each subsequent follow-up. At the end of the study, depending on the percentage of repigmentation, the final outcome was recorded as: Grade I (G1) <25% repigmentation (poor), Grade II (G2) 25%-50% repigmentation (fair), Grade III (G3) 50%–75% repigmentation (good), and Grade IV (G4) >75% repigmentation (excellent). The evaluation of the result was done by the whole team in consensus at every follow-up visit.

Statistical analysis

Data were statistically analyzed using the Statistical Package for Social Sciences (SPSS) software 22 (IBM Corp., Armonk, New York, USA). Quantitative variables were represented as means and standard deviation and categorical variables were analyzed in the form of frequency and percentage.


  Results Top


Clinical data of the study participants

The present study was carried out on 100 vitiligo patients, and their ages ranged from 5 to 60 years with the mean age of 26.93 ± 8.50 years. Male patients represented 42% of the studied participants, while females represented 58% with a female-to-male ratio of 1.38:1. Only 6% of the cases had a positive family history of vitiligo. The duration of the disease ranged from 1 to 13 years with the mean duration of 5.48 ± 2.25 years. Duration of stability ranged from 6 months to 9 years with the mean duration of 2.325 ± 1.15 years. The most common morphological type in our study was vitiligo vulgaris (60 of 100, 60%) followed by focal vitiligo (36 of 100, 36%). About 92% of the patients received previous treatment for vitiligo but not in the past 6 months. Of the 204 patches, 100 were on the trunk/abdomen, 74 on the limbs, 24 on the face, and 6 were on the scalp. Of 100 cases, only two had associated autoimmune disease (hypothyroidism), whereas the family history of autoimmunity was not noted [Table 1].
Table 1: Clinical data of cases

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Repigmentation data in the study participants

After 4 weeks of treatment (2 weeks after the second treatment session), 82 (40.19%) lesions showed G1 repigmentation, and 6 (2.94%) lesions showed G2 repigmentation. After 12 weeks of treatment, 20 (9.80%) lesions showed G1 repigmentation, 36 (17.64%) lesions showed G2 repigmentation, 56 (27.45%) lesions showed G3 repigmentation, while 50 (24.50%) lesions achieved excellent G4 repigmentation. At the end of the study, i.e. after 3 months of follow-up, 12 (5.88%) lesions showed G1 repigmentation, 20 (9.80%) lesions showed G2 repigmentation, 64 (31.37%) lesions showed G3 repigmentation, while 64 (31.37%) lesions achieved G4 repigmentation [Table 2]. Forty-four lesions did not show any repigmentation after follow-up of 3 months, while 2 lesions showed relapse at the end of 3 months which achieved G1 repigmentation while on treatment [Figure 1] and [Figure 2].
Table 2: Grades of repigmentation after treatment with microneedling and 5-fluorouracil

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Figure 1: Grade 4 response (>75% repigmentation) in a vitiligo patch over the lateral side of the abdomen: (a) At baseline; (b) at 8 weeks; (c) at 12 weeks

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Figure 2: Grade 3 repigmentation in a vitiligo patch at preauricular area: (a) At baseline; (b) at 10 weeks

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On analyzing the site-wise response, G4 response was most often observed in patches over the trunk (40 of 100, 40%) followed by face (8 of 24, 33.33%), and limbs (15 of 74, 20.27%) [Table 3].
Table 3: Depicting site-wise lesions (%) showing Grade 4 response at the end of therapy

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Side effects

Of 204 patches, 12 (5.88%) showed inflammation, 2 (0.98%) patches showed hypertrophic scar formation at 6 weeks whereas 24 (11.76%) patches showed hyperpigmentation. Of these 24 patches, hyperpigmentation returned to normal skin color in 16 patches during the follow-up period. Postprocedure, erythema, and mild pain were observed in 20 and 15 patients, respectively. Ulceration, itching, and koebnerization were not seen in any patient. No systemic side effects were observed.


  Discussion Top


Microneedling is turning popular as a treatment option in dermatology, which dramatically increases the bioavailability of topical treatments and further enhances their transcutaneous absorption. In the present study, we tried microneedling with a 26-gauge needle as a simple, inexpensive, and quick procedure that can be used as a transdermal drug delivery modality. Hyperpigmentation, the known side effects of 5-FU treatment is observed during the treatment of skin tumors and psoriasis, and it was the basis of this study.[11],[12]

Needling induces a strong trauma-induced inflammatory response inciting migration of keratinocyte along with melanocyte. The inflammatory mediators such as leukotrienes C4 and D4 and matrix metalloproteinases from keratinocytes help in melanocyte migration and proliferation.[8],[9],[10],[13]

The better therapeutic effect of microneedling with 5-FU can be explained by several mechanisms first, after epidermal abrasion, the 5-FU penetrates easily and deeply and stimulates the migration of active melanocytes from the pigmented to the achromic epidermis through enlarged intercellular spaces produced due to local edema.[9],[10],[11]

5-FU also induces the repigmentation of vitiligo may be by the overstimulation of follicular melanocytes, which migrate to the surface during epithelialization, resulting in hyperpigmentation.[6],[14]

Finally, 5-FU competes with deoxyuridine and its derivatives for the enzyme thymidylate synthase and damages some inhibitory agents or cells within the epidermis or dermis that may be responsible for the destruction of pigment cells producing vitiligo.[10],[15]

The present study constituted patients of age varying from 5 to 60 years, with the mean age of 26.93 ± 8.50 years. The female-to-male ratio was 1.38:1 in our study showing female preponderance similarly showed by other studies.[16],[17],[18],[19] This probably reflects the increased social stigma of vitiligo in female patients and thus early treatment-seeking behavior.

Vitiligo vulgaris (60%) was the most common morphological pattern, followed by focal vitiligo (36%) in our study; these findings were consistent with the study conducted by George et al., Zahra et al. and Shashikiran et al.[16],[19],[20]

At 4 weeks of treatment, G1 repigmentation was noted in 82 (40.19%) patches and 6 (2.94%) lesions showed G2 repigmentation. However, Zahra et al. reported initiation of repigmentation in 76 patches (65%) at the end of 4 weeks, and Mina et al. reported in 44% of the patches at the end of 6 weeks, treated with 5-FU combined with microneedling.[19],[21]

At the end of 3 months, good to excellent G4 repigmentation was noted in 106 patches (51.96%) whereas G1 to G2 repigmentation was seen in 56 (27.45%) patches. At the end of follow-up (9 months), 128 (62.74%) patches showed good to excellent response, and 32 (15.68%) patches showed poor to good repigmentation.

The results of our study were comparable to a study conducted by Shashikiran et al. in which more than 75% repigmentation was reported in 49% of the patches.[20] Zahra et al. and Mina et al. noted excellent repigmentation in 47% of the patches and 48% of the patches, respectively, treated with combined microneedling and 5-FU.[19],[21]

Ghiya et al. used microneedling with 5-FU, and the repigmentation percentage was 67.24%, but their study included only children aged from 5 to 14 years old.[7] Vedamurthy et al. conducted a trial on 3 cases of vitiligo using needling and 5-FU, and the cases showed >75% repigmentation, but it included only 3 cases.[8] Santosh et al. found that approximately 60% of the patients (30) had hyperpigmentation in the vitiligo lesions after 3 months of treatment with 5-FU after microneedling.[9] Khater et al. showed excellent response in 18% of the patients by intradermal 5-FU injection in nonsegmental vitiligo.[22]

We found that the maximum number of truncal patches (40%) showed G4 response at the end of the study followed by face (33.33%) and limb patches (20.27%). These findings were in concordance with the study by Zahra et al. and Shashikiran et al.[19],[20]

In this study, the reported side effects were few, and all patients well tolerated the procedure. Hyperpigmentation occurred in 11.76% of the patches which improved during the follow-up period. Inflammation occurred in 5.88% of the patches and two patients showed hypertrophic scar formation (chest and arm). There were no systemic side effects in any patient. A better response was seen on the patches of trunk area similar to Zahra et al. study.

This may indicate that the combination of 5-FU with microneedling could be considered a safe and tolerable technique for the treatment of localized stable vitiligo. The 5-FU solution and 26-gauge needle are readily available everywhere, and the procedure does not require much expertise or expense, providing the patient a clinically efficacious, and cost-effective treatment modality.

The limitations of the study were the small sample size and the short follow-up period of the study. However, much more studies are still needed to find the exact mechanism of action, the possible side effects of 5-FU, and stability of repigmentation by longer follow-up of the patients. To assess the exact cause and mechanism of site-wise variations in pigmentation further studies are also needed.


  Conclusion Top


We can say that needling with topical application of the 5-FU solution is a simple, cost-effective, and safe modality without the need of extensive surgical instruments and minimal side effects. It can be used as an alternative or additive method before, or in combination with other approved methods for stable vitiligo.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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