A multimodal approach to the treatment of extensive burn scars: a modified subcision technique for intralesional delivery of corticosteroid and 5-fluorouracil in combination with several procedural laser therapies; a case report (2024)

Abstract

Keywords: Burn, scar, corticosteroid, laser, 5-fluorouracil, subcision

Lay Summary

Introduction

Hypertrophic and keloidal scarring secondary to thermal injury frequently causessignificant functional, cosmetic and psychosocial morbidity. Patients commonlycomplain of pain, itching, impaired mobility, depression and poor self-esteem. Whilethere is no uniform treatment algorithm, a wide range of therapeutic procedures havebeen employed with variable degrees of success. The exact mechanism of keloid andhypertrophic scar formation is not fully defined, yet studies have shown that excesscollagen production, which is due to abnormal fibroblast activity in response totransforming growth factor-ß stimulation and increased vascularity are typicallyseen in involved tissue.^1,2Treatments include, but are not limited to, intralesional injections, topicalagents, pressure therapy, silicone gel sheeting, cryotherapy, laser treatments andreconstructive surgery. Our case report reflects a multimodal approach to treatinghypertrophic facial and neck scarring complicated by hair entrapment in a patientwith significant associated pain, discomfort and psychosocial impairment.

Case

A 55-year-old Hispanic man, with a history of generalised seizure disorder, presentedwith complaints of extensive scarring involving the entire trunk, neck and face (35%body surface area) following a burn injury three years before presentation. He wasinterested in pursuing treatment for disfiguring symptomatic scarring on his faceand neck, which was causing him significant psychological distress. The burns were aresult of water heater explosion that ensued after the patient experienced a grandmal seizure while fixing the stated appliance. The patient’s initial injuries weretreated at an outside hospital burn unit where he received aggressive wound care andextensive skin grafting procedures. He complained of persistent and, often,incapacitating pruritus, pain, tightness and progressive immobility of his skin.Emotionally, the patient displayed an altered sense of self, lack of self-esteem andhad a documented history of depression due to the injuries he had sustained.

On physical examination, extensive pink to brown firm, hypertrophic rope-like plaquesand associated contractures were noted on the upper and lower cutaneous lip, chin,lower mandible, neck, trunk and bilateral upper extremities, including the hands.All scars were tender on palpation (Figure 1a; Figure2a). Amputation of the distal digits on the left hand was alsoappreciated.

One firm tender nodule containing numerous terminal hairs on the left submental chinwas biopsied. Histopathologic examination of the tissue revealed cicatricialfibrosis and a dilated follicular cyst with associated keratin. Granuloma formationwas noted to be consistent with a ruptured follicle. No foreign body was seen onpolarisation.

To ameliorate symptoms and improve the appearance and functional status of hisextensive hypertrophic and keloidal burn scars on his face and neck, an aggressive,non-surgical course of treatment consisting of nine monthly interventions wasdeveloped. In effort to maximise patient comfort, medical modalities (intralesionalinjections) were alternated with procedural laser therapies (epilatory, vascular andfractional laser treatments).

At eight-week intervals, five concurrent sessions of high-dose intralesionaltriamcinolone acetonide (40 mg/mL, total 6 cc) injections and 5-fluorouracil (5-FU;50 mg/mL, total 2 cc) injections were administered via a modified subcisionaltechnique. All injections were delivered using a 25-gauge needle (1.5-in. length)into the deep dermis as to avoid inducing superficial atrophy. After an initiallinear ‘tunnel’ was established within the scar by advancement of the needle,medication was injected in retrograde fashion. From single points of entry, theneedle was reintroduced several times in a fanning pattern to maximize the totaltreated area using the fewest number of access sites.

Additionally, he underwent four combination laser sessions with the pulsed dye laser(PDL) (595 nm [VBeam Perfecta, Syneron-Candela Inc, Irvine, CA, USA], spot size 5mm, energy 10J, pulse duration 5 ms, cooling setting 2) and Alexandrite laser (755nm [GentleLase, Syneron-Candela Inc, Irvine, CA, USA], spot size 8 mm, energy 35 J,cooling setting 30/20/0) to the upper cutaneous lip, chin, jawline and neck. Onefractional laser (1550 nm [Fraxel Dual, Solta Medical Inc, Hayward, CA, USA], energy50 mJ, treatment level 5, passes 8) treatment was performed after topical (topicallidocaine and prilocaine 2.5% cream) and local anaesthetic (1% lidocaine with1:100,000 epinephrine, total 3 cc) administration at month 3. While he reportedimprovement in the appearance of his scar after fractional resurfacing, hecomplained of temporary isolated altered mental status, which he attributed to theadministration of the anaesthetics. In accordance with his preference to eschewfurther usage of topical or local anaesthetics, only PDL and Alexandrite lasers werecontinued.

Following two sets of injections and one laser session, the hypertrophic scars becamemore supple and scattered, allowing entrapped, horizontally growing terminal hairs(~1 cm in length) to be visualised within the scars located on the neck. In order todecrease the suspected inflammation stimulated by this hair trapping, theAlexandrite laser was added to the patient’s therapy regimen. At the completion oftreatment, the patient reported significant improvement in pain, itch, physicalmobility and self-esteem. Clinically, he displayed a remarkable decrease in scarthickness and improvement in the parameters of erythema, dyschromia, texture andrange of motion (Figure 1b;Figure 2b). Results weremaintained at 15 months after presentation.

Discussion

Anti-inflammatory and anti-metabolite therapies such as intralesional steroid and5-FU injections, respectively, have been shown to improve symptoms and cosmesis inboth hypertrophic scars and keloids.³ Steroid injections are proposed to work via inhibition of the mitoticactivity of fibroblasts and keratinocytes, inflammatory blockade and vasoconstriction.⁴ While steroid injections have been recommended as first-line therapy fortreating hypertrophic and keloidal scars, there is a relatively high recurrencerate, especially for large and chronic scars. Furthermore, many treatment sessionsare often required.^3,5Fluorouracil is a pyrimidine analogue and chemotherapeutic agent that has been shownto inhibit myofibroblast and fibroblast activity and collagen synthesis.^4,6 Flurouracil injections havetypically been combined with low concentrations of corticosteroid (9:1 ratio of 5-FUto triamcinolone) to decrease the adverse effect of erythema. This smallconcentration of steroid, however, does not seem to contribute an additivetherapeutic effect.^7,8

A recent study by Lee et al. retrospectively examined the safety and efficacy ofcombination therapy involving three monthly sessions of subcision followed bylow-dose intralesional corticosteroid (triamcinolone acetonide 5 mg/mL) injectionfor treatment of postoperative adherent linear thyroidectomy scars. Significantclinical improvement was seen in 15 of the 16 patients reviewed. Another recentstudy found excision and intralesional 5-FU and corticosteroid treatment(triamcinolone acetonide 5 mg/mL) to be superior to excision and radiation therapyin reducing size and recurrence of ear keloids.⁹ Additionally, when compared with intralesional verapamil injections,triamcinolone remains superior in reducing size, pigmentation, height, pliabilityand vascularity of keloids and hypertrophic scars.¹⁰ Subcision is a technique introduced by Orentreich,¹¹ in which a sharp needle (usually 16 or 18 gauge) is introduced into the skinbeneath a depressed scar and is able to act like a scalpel to incise and releasetethered fibrous attachments causing the scar to lift. This dermal injury responseand subsequent connective tissue generation following subcision can be modified byintralesional corticosteroid injection.^11,12

Laser therapy is another effective means of treating hypertrophic scars. PDL has beenshown to improve burn scar texture and pliability as well as to decrease erythemaand associated symptoms from burn scars resulting from chemical peels, carbondioxide laser procedures and accidental thermal injury.¹³ In 2012, a systematic review of eight randomised controlled trials found thatthree or more treatment sessions with PDL led to significant improvement inVancouver scar scale scores (objective changes in pigmentation, vascularity,pliability, scar height) and global assessment as compared to no treatment orconventional treatments including varied combinations of intralesional triamcinoloneacetonide, intralesional 5-FU, pressure garments and silicone gel sheeting or otherlaser treatments.¹⁴ PDL was found to be superior to conventional treatment modalities inimproving the associated symptoms and overall appearance of the scar.¹⁴

Burn scars have also been variably responsive to non-ablative, fractional andablative laser therapies. While fractional resurfacing with a 1550-nm erbium laserhas been traditionally used in the management of photodamaged facial skin, producingsignificant improvement in rhytides, skin texture, dyschromia and acne scarring, ithas also been shown to improve dyschromia,^15,16 skin texture, hypertrophy oratrophy, and self-reported self-esteem in patients with burn scars.¹⁶

A recent consensus report suggests that fractional ablative laser resurfacing therapydeserves a prominent role in future scar treatment paradigms based on evidence ofimprovement of scar contractures and function (ambulation, improved grip and earliermore aggressive implementation of prosthetic devices). Scar texture and colour aswell as symptomatic relief of burning and itching have also been consistentlydemonstrated with fractional laser.¹⁷ However, recovery time with fractional and ablative lasers is somewhat longerthan that of non-ablative lasers. Similarly, fractional and ablative procedures alsorequire either topical or local anaesthesia application beforehand and can posepotential risks, especially when treating widespread surface areas. Suchafter-effects of fractional and ablative lasers include erythema (persisting up tofour months after treatment) and dyspigmentation.¹⁸

A recent case series by McGoldrick et al. utilised fractional ablative CO2 lasertherapy in treating burn scars in sensitive and functionally mobile areas includingthe breast, face, finger and elbow.¹⁹ While three patients were treated with multiple sessions of variable-depthCO2 fractional ablative therapy (10,600 nm), one patient with a hypertrophic burnscar of the left elbow underwent a combined approach of intralesional 5-FU andcorticosteroids with one session of medium-depth (1.5 mm) CO2 fractional laser treatment.¹⁹ Monotherapy with any one procedure is often ineffective and a combinationapproach of injections and laser treatments such as that utilised by McGoldrick etal. as well as to treat our patient, may provide a more satisfactory outcome.Additionally, in the treatment of our patient, a subcision technique for dermalrelease was utilised.

Many recent reports have found combination treatments to be superior to monotherapy.Intralesional 5-FU in combination with low dose-intralesional triamcinolone (mixtureratio 9:1) for the treatment of keloids and hypertrophic scars was found to besuperior to intralesional triamcinolone (10 mg/mL) treatment alone in more than oneseries.^20,21 Likewise, PDL and fractional lasers may have synergistic rolesin the treatment of burn scars. Erythematous and more acutely inflamed scars aremost amenable to PDL, while pigmentary and textural alterations respond better tofractional laser treatments.¹⁷ A prospective, before and after, single cohort study of 147 burn patientswith hypertrophic scars found that a 12-month treatment course with a combination ofPDL and fractional CO2 laser caused significant improvement in scars.²²

Further improvement may be demonstrated with the addition of intralesionalmedications such as corticosteroids and 5-FU as an adjuvant to lasertherapy.^7,8One blinded clinical trial found that intralesional 5-FU combined with low-dosetriamcinolone (3:1) plus PDL was more efficacious in treating keloids andhypertrophic scars when compared to 5-FU combined with triamcinolone or any of thesetreatments alone.⁷ Steroid tape may also prove an effective adjunct therapy to treatinghypertrophic scars, though safety and absorption data must be further researched,especially with use on the face and neck.²³

A recent case of hypertrophic scarring after deep chemical peel was improved as aresult of multimodal therapy. This 75-year-old woman with a four-month history ofscarring following a phenol peel for perioral rhytides underwent 10 treatments witha 595-nm PDL followed immediately by the 1450-nm diode laser in combination withintralesional triamcinolone and 5-FU. She showed significant overall improvement.⁴ A recent pilot study found that adjuvant intralesional autologousplatelet-rich plasma injections may also hold promise as keloid therapy for patientswho fail conventional treatments.²⁴

Our case is unusual in that the patient had notable trapping of hair where skingrafting was previously performed. We suspect that this complication added to thepatient’s persistent pain and itching. Review of the literature found a singlereport of a painful facial burn scar, which was found to have internal hair growthwithin previously skin grafted sites on excision. These ‘non-emergent’ hairs weresuccessfully removed with Alexandrite laser, which produced temporary symptomatic relief.²⁵

Our selection of targeted, multimodal, minimally invasive therapies focused onremoving the stimulus for continued scar production and inflammation (laser hairremoval of entrapped hairs) while also aggressively normalising dermal thickness(intralesional high-dose steroid and antimetabolite administration delivered via amodified subcision technique) and improving colour and texture (PDL and non-ablativefractional laser therapy).

Conclusion

Our case highlights the success of combination medical and procedural treatment(triamcinolone and 5-FU intralesional injections with a series of vascular,fractional and hair removal lasers) for extensive hypertrophic head and neck burnscars. Triamcinolone and 5-FU intralesional injections normalised dermal thickness,while minimally invasive vascular, fractional and hair removal laser therapytargeted underlying inflammation via laser hair removal of entrapped hairs and PDLand non-ablative fractional laser therapy improved skin colour and texture. Ourconclusions are limited by small sample size in this case report. Future researchshould investigate the role of hair entrapment in inflammatory keloid and scarformation and opportunities for multimodal, minimally invasive treatment.

Acknowledgments

The authors thank Alejandra Higareda, CMA for her help with coordination of care andtranslational assistance.

Footnotes

References

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