Combined Treatment with Electrocauterization,Carbon Dioxide Laser,and Microneedle Fractional Radiofrequency for Facial Angiofibromas in Tuberous Sclerosis Complex:A Case Report and Literature Review

Jiying DONG,Shen WANG,Min YAN,Jing MI,Ying ZENG,Huyan LIN,Yiqiu ZHANG,Min YAO

ABSTRACT Tuberous sclerosis complex is a type of genetic multisystem disease that causes hamartomas in various organs.Facial angiofibromas commonly occur in 80% of patients and are prominently distributed over the cheek,chin,and nasolabial folds with severe disfigurement and emotional distress.Recently,photoelectric devices have been identified for the treatment of angiofibromas with great efficacy and fewer side effects.We report a case of a 42-year-old man with facial angiofibromas,who was treated with a combination of high-frequency electrocauterization,Ultrapulse CO2laser,and microneedle fractional radiofrequency with 7 sessions and a 6-month follow-up.The patient showed great improvement in relation to the elevated lesions and nodules.A low recurrence rate was observed.This is the first study to investigate the efficacy of high-frequency electrocauterization and microneedle fractional radiofrequency in angiofibromas.It may provide an optimal approach for clinicians wherein a combined treatment of various lasers and electric devices is effective for complicated,protuberant,and firm angiofibromas of specific patients.

KEY WORDS Electrocauterization;CO2laser;Radiofrequency;Angiofibromas;Tuberous sclerosis

INTRODUCTION

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disease caused byTSC1andTSC2tumor-suppressor gene mutations,with a prevalence of 1:6 000 to 1:12 000 births[1].However,70% of the cases are sporadic mutations that lack a family history[2].The two genes and protein products (TSC1or hamartin andTSC2or tuberin) are significant inhibitors of the mammalian target of rapamycin (mTOR) pathway,which regulates cell growth,proliferation,and protein synthesis.Mutations inTSC1andTSC2result in the uncontrolled subsequent production of proteins and hamartomas in all organs,such as cortical tubers in the brain,cardiac rhabdomyoma in the heart,renal angiomyolipomas in the kidneys,and lymphangioleiomyomatosis in the lungs and skin[3-5].Cutaneous manifestations appear early after birth and are primary in 96% of patients with TSC[6].Facial angiofibromas are usually located on the cheek,nasolabial folds,and chin and gradually worsen,leading to inevitable disfigurement,self-contempt,and even functional disorders[7].Skin lesions are treated with various methods of surgical excision,photoelectric equipment,and topical mTOR inhibitors[8].Of these,photoelectric devices,such as CO2laser,pulsed dye laser (PDL),and radiofrequency,are evidently optimal choices due to minimal damage,few side effects,and excellent efficacy,especially for fibrotic lesions.In this study,we report a TSC patient with severe facial angiofibromas who experienced great improvements in fibrous nodules via a combined treatment of high-frequency electrocauterization,Ultrapulse CO2laser,and microneedle fractional radiofrequency.

CASE PRESENTATION

A 42-year-old man presented to our plastic and laser clinic because of multiple facial angiofibromas and severe aesthetic disfigurements for almost 36 years.The patient explained that he noticed erythema around his nose and mouth at six years of age,and the symptoms gradually worsened along with skin paresthesia in the legs and arms.He also presented intellectual developmental delay,learning difficulties,and slow-paced speech and suffered from hearing impairment assisted by hearing aids since childhood.The patient was diagnosed with TSC and facial angiofibromas 15 years ago and was treated with ablation therapy of drugs followed by recurrence after 3 months.Epilepsy was not observed.None of his family members were diagnosed with TSC,but his brothers and sisters also presented learning difficulties.

Physical examination revealed that the angiofibromas were mainly distributed on the nose,nasolabial folds,cheek,and chin and developed into many severe solid nodules measuring up to 0.4 cm in diameter.The patient had several irregular hypomelanotic macules on his limbs and large shagreen patches on the right thigh and knee.Periungual fibromas were found on the feet rather than on the hands.Computed tomography of the head revealed multiple calcified tubers,and ultrasonography of the kidneys showed bilateral renal cysts.The patient’s clinical manifestations fully accorded with the major and minor features of the TSC diagnostic criteria[9](Table 1).

Table 1 Diagnostic criteria for tuberous sclerosis

Based on the characteristics of multiple fibrosis nodules and mild erythema,we performed a combined treatment of high-frequency electrocauterization (Wuhan Spring Scenery Medical Instrument LTD,China),Ultrapulse CO2laser (Lumenis,Israel),and microneedle fractional radiofrequency (Peninsula,China).Anesthesia was administered using the topical compound lidocaine-prilocaine cream (Bejing Ziguang,China) for 1 h and by injecting 2%lidocaine for the infraorbital nerve block after cleaning the treatment area.

Fibrosis nodules were treated with high-frequency electrocauterization equipped with the monopolar mode and a highly precise metal needle to remove and vaporize large lesions in the deep dermis,including full-thickness skin.The single zone was confined within a 2-5 mm diameter.Due to the rich blood supply around the nose,we simultaneously used Ultrapulse CO2laser for blood coagulation to stop the bleeding and remove mild nodules.The main parameters are as follows:1 mm handtool;pulse energy:2-6 w;pulse duration:10 ms;and pulse interval time:0.1-0.3 s.After the treatment,the wound was cleaned with 0.9% saline solution and cooled with ice packs for 30 min.A small amount of antibiotic ointment was administered.The patient was advised to keep the wound clean and avoid contact with water for one week.The patient had a total of 7 treatment sessions with more than 3 months of interval and a 6-month follow-up.Noticeably,in the fourth session,we chose a microneedle fractional radiofrequency device with 1.2-2.0 mm depth,400-600 ms pulse duration,8-10w pulse energy,and 2-3 passes.Side effects were recorded,such as abnormal erythema,infection,wound impairment,scarring,and pigment abnormalities.Eventually,the patient showed great improvements in facial angiofibromas after 6 months from baseline with 7 sessions (Fig.1).The lesions were almost completely removed,and the patient’s skin was flat without scarring or hyperpigmentation.The overall treatment was tolerated by the patient.Early erythema gradually faded within 1-3 months.However,a percentage of recurrence still existed.

Fig.1 Facial angiofibromas before and after 6 months of 7 treatment sessions with electrocauterization,Ultrapulse CO2laser,and microneedle fractional radiofrequency. (A,C,E)Baseline;(B,D,F) 6 months after the 7 sessions.

DISCUSSION

Facial angiofibromas are a common manifestation of TSC,which are characterized by red to pink papules appearing in the centrofacial areas,especially the cheek,chin,and nasolabial folds.The lesions are made up of dermal connective tissue and blood vessels.Histologically,sebaceous glands are usually atrophic and elastic fibers are absent.Angiofibromas are small and mild at first and gradually become prominent,accompanied by cosmetic disfigurement and emotional distress[10-11].Treatment methods are available and essential,including surgery,dermabrasion,laser therapy,electrocoagulation,and topical rapamycin.

Cryosurgery may cause pain,uncontrolled wound depth,and hypopigmented scar,although it is easy to perform[12].It is a good option to smoothen the skin surface using a combination of dermabrasion and shave excision.However,postoperative hypopigmentation is also worthy of attention[13].According to Capurro et al.[14],treatment by electrosurgery to smoothen multiple pink papules has proven to be efficacious without post-treatment scarring or hypopigmentation during the 3-year follow-up.Electrosurgery is a diathermic apparatus with precise control that delivers energy to the local tissue without overdestruction.Currently,photoelectric methods have become popular for facial angiofibroma treatment.These devices have been reported to improve cutaneous lesions in TSC by selective photothermolysis and fractional photothermolysis to focus on target tissues with minimal damage to the surrounding area.

A CO2laser (10 600 nm) is strongly absorbed by water,which can precisely destroy and flatten the protuberant lesions by heating and vaporizing the tissues.Specifically,Ultrapulse CO2fractional laser has an extremely high peak power to vaporize lesions,a fractional mode to reduce damage to surrounding tissues,and a short pulse duration to decrease heating injuries[15].Ali and colleagues chose CO2laser as monotherapy for nine angiofibroma patients,which showed great improvement in appearance in a retrospective study.The only complication was transient post-treatment hyperpigmentation[16].The CO2laser is a common approach to treat angiofibromas and is usually combined with other techniques to speed up tissue ablation and avoid significant morbidity.

PDL and Nd:YAG lasers are effective for erythematous angiofibromas because they can selectively target cutaneous hemoglobin and coagulate microvessels[17-18].In a retrospective study of 29 TSC patients,Papadavid et al.investigated the specific application of different lasers(CO2laser and PDL) based on the clinical manifestations of the vascular,fibrous,and protuberant types of angiofibromas.Excellent outcomes were achieved in most cases of vascular types after treatment with PDL,10 of 13(77%) cases of a fibrous or protuberant type after treatment with Ultrapulse or continuous CO2laser,and 3 of 4(75%) cases of mixed types after treatment of both lasers.However,post-inflammatory hyperpigmentation and persistent hypertrophic scarring were observed in patients treated with a continuous CO2laser[19].Such findings warn us of the depth and size of vaporization as well as the side effects of scarring and dyspigmentation,particularly in a continuous CO2laser,despite its high efficacy for flattening lesions.Gang Ma et al.demonstrated that Nd:YAG laser treatment of facial angiofibromas with pink to red smooth telangiectatic papules showed excellent improvement in 10 patients and good improvement in two patients.Hematoxylin and eosin staining showed decreased dermal fibrosis and vasodilatation after the last follow-up[20].In another group,Fioramonti reported that all 13 patients showed great improvement of elevated angiofibromas by a combined treatment of erbium:YAG laser (2 940 nm),PDL,and CO2laser through evaluation of a visual analog scale (VAS) after a 6-month follow-up[9].The erbium:YAG laser with a wavelength of 2 940 nm is absorbed by the superficial skin layer at a depth of 1 μm to achieve tissue ablation.In addition,the use of radiofrequency for facial angiofibromas was first reported in 2008[21].Radiofrequency generates energy that causes tissue cutting or coagulation by an electric current.In a case report,a 30-year-old woman with disfiguring angiofibromas on the nose,malar,lower lip,chin,and forehead region was treated with a high radiofrequency device.It was a successful process,and the patient returned to normal life and showed good improvement without scars or hyperpigmentation[22].Finally,we should realize that multiple treatments are essential,and dermatologists and plastic surgeons reasonably utilize the right devices for different types of angiofibromas of TSC.

In this study,the patient had clinical features of prominent,firm,and severe protuberant fibrous nodules and minimal erythema in the midface.For this reason,we chose a combined treatment of high-frequency electrocauterization,Ultrapulse CO2laser,and microneedle fractional radiofrequency device instead of a PDL.In our experience,electrocauterization is highly suitable for large and elevated fibrosis tubers owing to the preciseness of metal needles,controllability of depth,and operational convenience.However,the disadvantage of electrocauterization equipment is the poor efficacy of coagulation.Ultrapulse CO2laser was used to coagulate bleeding tissues and mild lesions.To avoid dyspigmentation and scarring,the size of a single therapy site was approximately limited to 2-5 mm diameter.Radiofrequency is employed for darker skin types owing to the absence of epidermal chromophores.Radiotherapy is frequently used in cosmetic therapy for skin laxity,enlarged pores,and scarring through fibrous stimulation and collagen remodeling[23-24].After three sessions,we selected microneedle fractional radiofrequency to heat fibrous tissues and scars of both dermal and epidermal layers without epidermal damage or hyperpigmentation.In consideration of his financial burden,radiofrequency was used in only one session.Through 7 treatment sessions,facial angiofibromas showed great improvement in the flatness of lesions,number of nodules,and hardness of the texture.

In recent years,topical rapamycin,an inhibitor of mammalian target of the mTOR pathway,has been found to be effective in reducing erythema and size of angiofibromas by downregulating angiogenesis and growth[25].Some studies have reported that the application of topical 1%-2% rapamycin ointment and ablative CO2laser treatment resulted in excellent outcomes and high satisfaction with large papular lesions[26-27].Therefore,it is a good option for the combined treatment of topical rapamycin and various photoelectric devices when facial angiofibromoas of TSC patients are large,multiple,and elevated,as in the present case.Importantly,the therapy should always be treated case by case,based on the individual situation.

ETHICS DECLARATIONS

Ethics Approval and Consent to Participate

Ethical approval was waived as this is a case report.The participant provided written informed consent before study enrollment.

Consent for Publication

All the authors have consented to the publication of this article.

Competing Interests

The authors declare no conflicts of interest.The authors state that the views expressed in the article are their own and not the official position of the institution or funder.

AUTHORS’ CONTRIBUTIONS

JY D designed and drafted the manuscript and S W and M Y collected and assembled the data.J M,Y Z,HY L,and YQ Z analyzed the data and drew the figures.M Y supervised and revised the study.All authors have read and approved the final manuscript.