|Ahead of print publication
Microneedle-assisted steroid delivery therapy in the management of hypertrophic scars: A split-lesion study
Guruswamy Vishwanath1, Jandhyala Sridhar2
1 Consultant Reconstructive Surgery & Ex Additional Director General Medical Services (Navy), IHQ of MoD (Navy), New Delhi, India
2 Department of Dermatology, INHS Asvini, Mumbai, India
|Date of Submission||06-Aug-2020|
|Date of Decision||18-Aug-2020|
|Date of Acceptance||21-Aug-2020|
|Date of Web Publication||09-Dec-2020|
INHS Asvini, Colaba, Mumbai - 400 005, Maharashtra
Source of Support: None, Conflict of Interest: None
Introduction: Microneedle assisted transdermal delivery is an emerging technique of drug delivery on the horizon with exciting potential therapeutic applications. Aims and Objectives: To study the role of microneedling assisted steroid therapy in the management of hypertrophic scars and make suitable recommendations on employability of the procedure as a treatment modality. Materials and Methods: Twenty six consecutive patients with hypertrophic burn scars were studied. Each scar was divided into two halves–control and test. Both halves received topical fluticasone propionate cream 0.05% once daily, silicone gel sheet and a pressure garment. In addition, the test half received microneedling therapy followed by fluticasone propionate cream 0.05% application twice weekly for twelve sittings. The two halves were evaluated for response using the Vancouver Scar Scale (VSS) at the beginning and end of therapy. Results: Twenty patients completed the study. No statistically significant difference was noted in the VSS scores of the two halves. Subjective relief of pruritus was found to be statistically significant in the test half. Conclusion: This study found that percutaneous microneedling assisted steroid therapy as per the the regimen used in this study produced no objectively assessed benefit in the management of hypertrophic scars. Relief of pruritus was noted.
Keywords: Derma roller, microneedling, scars, steroid therapy
| Introduction|| |
Normal wound healing is a complex event which involves hemostasis, a period of inflammation, followed by waning of the inflammatory process, restoration of epithelial integrity, deposition and remodeling of collagen. The end product of the wound healing process is a scar. The events occur in a regulated and time bound manner, thus there is a fairly predictable march of events in wound healing and scar formation.
In certain clinical situations, however, the regulation of the wound healing processes goes awry. There is a prolonged phase of inflammation with attendant hyperemia, excessive and in some cases progressive deposition of collagen and delay or failure of maturation of collagen resulting in an imperfect, “overhealed” scar. This is referred to as a hypertrophic scar and in certain cases a keloid.
The factors that cause hypertrophic scar formation are yet not fully understood. Predisposing factors include race, age, location of the scar on the body (some areas such as the presternal region and over the deltoid being more predisposed), type of skin (thick, sebaceous gland bearing skin being more predisposed), a familial tendency to hypertrophic scarring, and time period to wound closure. Obviously, this has considerable surgical significance since scar formation prejudices the strength of the healed wound, thus predisposing to wound dehiscence, occurrence of a hernia, burst abdomen, etc. Overhealing with fibrosis can have equally damaging effects like tethering of a repaired tendon hampering its function, dense scar at nerve repair sites causing blockage of tubules preventing nerve regeneration, hypertrophy of a postoperative skin scar causing discomfort, and esthetic considerations.
Thus, effective measures are required to control or prevent hypertrophic scarring and to deal with it when it occurs. Measures that have been used to control hypertrophic scarring include: Pressure, silicone gel application, intralesional steroid therapy, drugs such as tacrolimus, lathyrogens such as beta N oxylamino L alanine, radiotherapy, proprietary preparations containing cepae extract, heparin, and allantoin (Contractubex®, Hexilak®).
Combination of modalities of treatment may be required, steroid therapy is usually the sheet anchor of treatment in established hypertrophic scarring in clinical practice. Intralesional triamcinolone acetonide in two strengths of 10 mg/mL and 40 mg/mL are used. Intralesional injection is both difficult and painful. Injection with considerable pressure is required to deliver the drug into an area of dense scarring. Blockage of the fine needle by the triamcinolone suspension is frequent. The distension caused by the injection in dense scar tissue can produce high local pressure and considerable pain. The injection may be required to be repeated fortnightly and repeated at multiple sites in case of large hypertrophic scars.
Transdermal drug delivery would appear optimal but has not been effective owing to poor penetration of the drug into the lesion due to the barrier posed by the stratum corneum; the large majority of drugs unable to cross the skin at therapeutic rates.
Microneedling assisted delivery is a method that uses a dermaroller [Figure 1] and [Figure 2]. Microneedling assisted therapy may hold potential as a means of transdermal drug delivery. However, scant data exist on the modality, more so in Indian patients. Further, intralesional steroid therapy is not acceptable to many patients due to pain considerations. This study was undertaken to improve the existing knowledge and to assess whether there is a role for the microneedling assisted therapy as a treatment modality in hypertrophic scars, in lieu of conventional intralesional and topical? steroids.
|Figure 2: Close up view of head of the dermaroller showing array of spikes|
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| Materials and Methods|| |
The study was a prospective trial carried out at the Reconstructive Surgery Centre of a tertiary care hospital. Based on the incidence of scars among patients seeking treatment and the proportion being treated with intralesional steroid, a sample size of 26 was arrived at. Approval was obtained for the study from the Institutional Ethical Committee. Patients reporting or referred to the Reconstructive Surgery Centre were enrolled in the study with informed consent.
Inclusion and exclusion criteria
Patients with hypertrophic burn scars that would otherwise have been? managed with intralesional steroid injection were included [Figure 3]. Patients unwilling for the treatment, those with contraindications to steroid therapy, and those already treated with intralesional steroids, scars of duration <6 months and >1 year, infected scars, and those with sinus formation were excluded. For practical reasons, patients with hepatitis and HIV infection, and those with hypertrophic scars of the head and neck region, and age <10 years were also excluded from the study.
Demographic data, details pertaining to the scar such as size, location of scar, duration of scar and previous treatment were recorded. Photographs were taken before and after completion of the study period.
Test and control halves
Each scar was divided into two halves – control and test [Figure 4]. Both halves received topical fluticasone propionate cream 0.05% once daily, silicone gel sheet and a pressure garment.
A eutectic mixture of local anesthetics (EMLA) 2.5% lignocaine and 2.5% prilocaine was applied over the test half of the scar and covered with an occlusive dressing for 90 min for achieving topical anesthesia [Figure 5].
|Figure 5: The entire lesion is covered with eutectic mixture of local anesthetics cream and an occlusive drape for 90 min|
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Microneedling and treatment
After removal of the EMLA cream, under aseptic condition, the test half underwent dermaroller therapy. Dermaroller with microneedles of 1.5 mm size was used [Figure 6] with 4 strokes each in four directions, along the long, short and both oblique axes of the lesion. Thereafter, a thin layer of fluticasone propionate cream 0.05% ? was applied over the procedure site [Figure 7] and covered with an occlusive dressing for 24 h. The procedure was done twice weekly for a total of twelve sittings.
The Vancouver Scar Scale (VSS) was used for objective assessment or scar improvement. The VSS includes vascularity (3 points), pigmentation (2 points), pliability (5 points), and height (3 points), making a maximum of 13 points. The scar was evaluated by VSS at the start and after 6 weeks of treatment. The 10 point visual analog scale (VAS) for pruritus was used to assess change if any in pruritus as a scar symptom over the control and test areas. VAS is a 10 cm long line (oriented horizontally or vertically), on which patients indicated the intensity of pruritus by crossing the line at the point that corresponded to their pruritus severity, being informed that the beginning of the scale refers to no pruritus (0 points) and the end to the most severe pruritus they can imagine (10 points).
Pre and post treatment (in the control and test areas) values of VSS were used for analysis. Chi square test for r * c table and paired t test were carried out, depending on the groups compared, to estimate the differences in proportion of patients responding to the two treatment modalities. Fixing the significance level and difference in proportions at 0.05 and 0 respectively, two tailed P value was computed using the? Microsoft Office Excel 2010, Redmond, Washington, USA.
| Results|| |
The study was carried out on 26 subjects who fulfilled the inclusion criteria. Of these, six subjects were either lost to follow up or could not complete the study. Hence, for the purpose of statistical analysis, data on 20 patients were analyzed.
The mean age of the study population was 36. Half of the patients were from the age group 30 to 35 years. Sixty eight percent were males.
Upper and lower extremities were the most frequent location of hypertrophic scars in this study (60%). Chest and abdomen accounted for the remaining patients (40%). Mean duration of scars was 8.26 months (standard deviation 9.35). All patients reported varying degrees of pruritus over the scar at presentation.
Comparison of effect of microneedling assisted steroid therapy is shown in [Table 1]. It was found that microneedle assisted steroid therapy had no statistically significant effect on hypertrophic scar as compared to the adjacent control area.
The effect of microneedling assisted steroid therapy pruritus over the test area is summarized in [Table 2]. The reduction in VAS pruritus scores over the test area after 3 months of treatment was found to be statistically significant as compared to control.
|Table 2: Comparison of effect microneedling-assisted steroid therapy on pruritus|
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| Discussion|| |
Until recently, the only means of delivering molecules through the skin was either by hypodermic needles or transdermal patches. Hypodermic needles effectively deliver almost any drug at almost any rate across the skin but are limited by pain, need for medical expertise, and difficulty to have controlled delivery over long periods of time. In contrast, transdermal patches largely eliminate these limitations, but suffer from an inability to deliver most drugs across skin at useful rates since they have molecular size >500 Daltons.,
Microneedling assisted delivery comprises the use of a dermaroller having a 12 cm handle at the end of which lies a cylinder of 2 cm diameter and 2 cm length. On the surface of the cylinder, 24 circular arrays of 8 microneedles each (total 192 needles) are present, with needle lengths of 0.5–1.5 mm and base diameter of 35–70 microns depending on the model used. Rolling the cylinder on the skin surface creates microchannels on the stratum corneum, through which any kind of substance applied on the skin will gain access to the deeper and viable skin layers. The size is of the needles is more than enough to pierce the stratum corneum and allow increase in absorption of almost 10,000 fold compared to simple application to skin, but are small enough to be painless. Microneedles thus fall between transdermal patches and hypodermic needles in attempting to gain the advantages and eliminate the disadvantages of each one.
A regime of using dermaroller for the scars twice a week for 6 weeks was adopted. In the absence of guidelines regarding the frequency and duration of treatment sessions for effective therapy, a biweekly regimen was arrived at by considering the factors of patient convenience and office routine. Treatment was assessed at the end of 6 weeks as this is about the time at which the effects of microneedle steroid therapy become apparent in clinical practice. Steroid ointment was used with occlusive dressing for 24 h after the micropunctures were made. Since it is known that micropunctures remain open for up to 24 h after their production, this practice is considered rational.
Meseci studied 61 patients of post-caesarean section scars with the treatment group receiving corticosteroid cream every other day for 3 months, starting on postoperative day 10. The modified VSS was calculated at regular intervals. At the end of 6 months, significant improvement in all four components of the VSS was found. Lower age of scars may have accounted for the favorable response in this study, unlike in our study where older and more mature scars were enrolled.
This study failed to show any statistically significant improvement in hypertrophic scars when microneedling assisted steroid therapy was added to other therapeutic modalities in the management of hypertrophic scars. In a study to assess the microneedling devices as transepidermal drug delivering system for corticosteroid in the treatment of hypertrophic scars, Zidan et al. used a Dermapen® microneedling device to create micropunctures in skin followed by application of 40 mg/ml triamcinolone acetonide solution. The procedure was repeated for 3 times at 3 weekly intervals. The results showed considerable improvement in all four parameters of VSS score at 3 months. Triamcinolone acetonide has a molecular weight of 434.5 g/mol, while fluticasone propionate used in our study has a molecular weight of 500.6 g/mol. Higher molecular weight of fluticasone propionate may have impeded its penetration. Lack of efficacy of the studied technique may also be related to the type and frequency of roller application and the resultant density and depth of micropunctures produced.
A reduction in VAS pruritus scores over the test area after 6 weeks of treatment was found to be statistically significant as compared to control, applying a cut off score of 4. Clinically also, a significant relationship was found to exist between microneedling assisted steroid therapy and relief of pruritus. Improvement of pruritus symptom was noted in another similar study using microneedling assisted steroid therapy.
There were other limitations of our study. The choice of fluticasone propionate (a potent halogenated topical steroid) may be debated. Since the micropuncture facilitated transdermal delivery was expected to replicate the effects of intralesional steroid injection, it could be argued that the logical choice of applied topical steroid should have been triamcinolone acetonide, the agent used for intralesional steroid injection. However, occlusive effect of a cream base was preferred, and since triamcinolone acetonide cream was not available, fluticasone propionate was substituted.
| Conclusion|| |
This study found that percutaneous microneedling assisted steroid therapy in the regimen used in this study produced no objectively assessed benefit in the management of hypertrophic scars. Significant relief of pruritus was however noted. Microneedling assisted percutaneous therapy is in its infancy and is likely to find wide application in therapeutic use in the times to come. Further studies exploring the potential use of this modality of therapy are therefore urged.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
[Table 1], [Table 2]