Comprehensive Strategy for Keloid Treatment:Experience at Shanghai Ninth People's Hospital

Xiaoli WU ,Yating YANG ,Wei LIU,Wenbo WANG,Lingling XIA,Xiaoqing WANG,Qiong ZHAO,Zhen GAO

Department of Plastic and Reconstructive Surgery,Shanghai 9th People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,P.R.China

ABSTRACT Keloids are a notorious fibroproliferative disorder that may cause cosmetic concerns and life inconvenience.Various methods such as surgery,injection,and laser have been used;however,single treatments are at risk of recurrence; therefore,comprehensive therapy is the better solution.Here,we focused on the management of different medical interventions according to subjective and objective conditions of keloid patients and summarized several clinical comprehensive strategies based on our clinical experience.One original concept of laser combined with radiotherapy was also introduced as a promising method,especially for wide-based pathological scars.

KEY WORDS keloids,hypertrophic scar,comprehensive treatment,laser,radiotherapy,injection,surgery

INTRODUCTION

Keloids are a notorious fibroproliferative disorder characterized by extra collagen deposition and fibroblast hyperproliferation.Cosmetic concerns and discomfort,such as pain and pruritus,are the most common complaints; however,devastating keloids may significantly ruin the social contact and daily activities of patients and bring about physical and psychological burdens.

Although specific mechanisms remain unclear,several important risk factors have been identified.Race and heredity are critical genetic factors as the African decent has a prevalence rate of 3.5%[1],which is almost 40 times that of Caucasians (0.09% in England)[2].The Asian group is also sensitive to keloids with a risk rate of approximately 0.15%[3].Moreover,studies on inheritance within families revealed that specific genetic and epigenetic alterations are also involved[4-5].Hormones are also suspected as keloids boom during puberty and pregnancy,parallel with fluctuation in sex hormone concentration[6-7].Other systemic risk elements that have been studied include blood tension and diet.As for the local elements,external mechanical forces and chronic inflammation have been demonstrated to be associated with keloid development and recurrence[8-9].Clinically,one or multiple risk factors may coexist and jointly contribute to the development of a keloid scar.Therefore,hereditary factor,inflammation,endocrine element,treatment history,and other associated information should be collected and considered in advance to provide a comprehensive assessment of the severity and degree of risk of development of keloid scars among individuals.

Based on the proportion of inflammation and hyperproliferation,keloids have different manifestations,including inflammatory keloid (characterized by scarlet but relatively flat outlook,with prominent pain and pruritus),nodular keloid (nodular mass with rather dark color) and hybrid-type (with mixed characteristics or non-classical outlook).However,this morphological classification of keloids is inclusive in our institutions,and no general consensus has been reached worldwide.

Due to the complicated mechanisms and morphological features involved,various treatments have emerged,none of which achieved satisfactory outcomes without recurrence when used alone.Steroid injection is the most widely applied method; however,its side effects are considerable and some patients may have resistance.Surgery is frequently used to remove the lesions but may incur new pathological scars.Radiotherapy is regularly practiced as an adjuvant therapy to reduce the recurrence,and laser therapy is also helpful to improve the color or texture.Other possible treatments include Chinese traditional treatment and cryotherapy.Therefore,existing therapies for keloids and hypertrophic scars should be comprehensively combined for better treatment outcomes.

PURPOSES AND INFLUENTIAL FACTORS FOR KELOID TREATMENT

Keloid is mainly treated due to the following three purposes:First,the devastating appearance is the primary concern in most patients,i.e.,the stiff texture and protruding mass are expected to be softened and flattened; therefore,the erythema should fade.Second,discomforting symptoms accompanied with pathological scars such as itching and pain should be relieved in order to improve patients' quality of life.Lastly,recurrence prevention should be highly considered.Scar maturation management and proper post-treatment care should be strictly followed,especially for patients with a history of keloid scars.

The comprehensive treatment strategy should be flexibly regulated according to clinical symptoms,patients'expectations,and available methods at the medical institutions.Based on the clinical type,inflammatory keloids are characterized by a red appearance and prominent pain or pruritus,preferably managed with nonsurgical methods and use of topical medicine,laser,or radiation to relieve the symptoms and promote maturation,whereas nodular keloids with or without infection are managed with operation-dominant strategy to directly remove the lesion (including infection tissues).Our experience indicates that patients' general conditions are influential for the treatment outcomes and should be considered when planning an individualized treatment strategy.Age and sex matter because steroid and radiation therapies are contraindicated for young women who may be pregnant or are planning to get pregnant.For patients from remote areas or those who are too busy to attend frequent follow-up sessions,medical convenience and flexible visit are crucial for their compliance.As for patients with systemic disease,such as diabetes or polycystic ovary syndrome,side effects of certain therapies should be cautiously considered.Another decisive practical element is the availability of certain medical devices,especially for radiotherapy.Moreover,qualified treatment practiced by professional staff is essential for the overall treatment success.Finally,as the symptoms of pain and itching are subjective and the expectation to aesthetic improvement varies from individuals and sites,thorough communications and adjustments should be practiced to reach a consensus about the endpoint of medical intervention.Furthermore,any unrealistic pursuit is a potential hazard for both patients and institutions.

OUR EXPERIENCES IN COMPREHENSIVE TREATMENT STRATEGIES

Here,we summarized several comprehensive strategies for keloid treatment that have been widely applied in our institutions and introduced one concept of laser combined with radiotherapy (LCR) as our original therapeutic innovation.

Comprehensive surgical treatment

Comprehensive surgical treatment refers to surgical removal of lesions using tension-reduction,radiotherapy,or other methods.Surgeries can significantly improve the appearance and increase the local radio-sensitivity,and thereby reduce the dosage and side effects of radiation.The indications of comprehensive surgical treatment roughly include nodular keloids,multiple keloids,and keloids with chronic infection; other keloid lesions such as elbow or neck keloids that may interfere with normal functions are also recommended.However,the surgical risk should be cautiously considered for elderly patients,patients with systemic diseases,and young kids.Large areas of inflammatory keloids are also contraindications as the high-tensioned incision due to skin scarcity may further increase the cutaneous inflammation and incur recurrence.Because the postoperative care is important for the recurrence prevention,patients with mental disorders,those with poor compliance,or those who are unable to return for regular follow-ups are also considered.We also summarized six key points for the surgical repair:1) thoroughly remove the infection;2) practice tension-reduction suture; 3) avoid creating extra wounds; 4) stanch bleeding; 5) close cavity; and 6)promote primary healing.Figure 1 shows a young male patient with chest keloid treated with comprehensive surgical therapy.The lesion was surgically removed under the assistance of barbered suture and local flap.Regular postoperative radiotherapy and tension-reduction devices were also applied to prevent recurrence.Significant improvements and no signs of recurrence were observed 12 months postoperatively.

Comprehensive injection treatment

Steroid injection is one of the most frequently used nonsurgical keloid treatments,characterized by low expanse and exact effect as glucocorticoids can relieve chronic inflammation and suppress immune cell proliferation[10],and is particularly suitable for new lesion,inflammatory keloids,keloids small in size or quantity,and keloids at important aesthetic areas.Although topical steroid injection or application is relatively safe compared to systemic steroid treatment,side effects remain a major long-term problem,including acnes and hyperglycemia.Combined with 5-fluorouracil (5-FU),triamcinolone acetonide (TCA) injection has been proven to have better performance to reduce scar height,lower recurrence risk,and patient satisfaction as well as fewer side effects[11].Assisted with laser therapy,the general appearance of the lesion (hyperpigmentation,stiffness,etc.) could achieve better improvements.Apart from the allergic population,children,elderly individuals,and pregnant population (including planned parenthood) should be avoided as steroid hormones are involved in multiple physiological procedures and may interfere with the normal functions.Moreover,the anti-inflammation effect of steroids may be dangerous for patients with infection or other major systemic disease.Giant,cauliflower-shaped keloids and densedistributed keloids are less recommended as the drug may be poorly distributed and the injection process may cause extraordinary pain.Here are five tips for injection:1) multi-point injection; 2) moderate depth; 3) pay attention to pulling back; 4) regular review; and 5) be careful with the endpoint.Figure 2 shows a male patient with chest keloid with red and flat lesions,covering large areas; therefore,we chose a comprehensive injection therapy.Monthly TCA and 5-FU injections were administered at the beginning,and the interval was gradually prolonged according to the treatment response.The appearance of keloids significantly improved at 12 months postoperatively.

Laser combined radiotherapy

Photoelectric treatment is favored by both keloid patients and operators as they are easily operated and have lesser systemic side effects.The pulsed-dye lasers (PDL) of 585 nm or 595 nm,diode laser of 980 nm,and Nd:YAG laser of 1,064 nm reduce the redness through the laser that break the blood vessels to improve the color of the scar,whereas the Erbium:YAG laser of 2,940 nm and CO2 laser of 10,600 nm reduce the capacity of the laser that shrinks the lesion volume.However,although these lasers have been used for keloid treatment for years,the single treatment is weak in evidence-based medicine research and may stimulate keloid to incur recurrence.Better results and reduced recurrence have been described by combining CO2-pulsed-dye or Nd:YAG laser with topical steroid treatment or interferon[12-14].

Radiotherapy has been reportedly effective to reduce the postoperative recurrence of keloids[15].Electric beam and X-ray are suggested to be practiced 24 hours postoperatively with a total dose of ＜20 Gy.Intensitymodulated radiotherapy can accurately and evenly distribute intensified radiation to the target area,thereby reducing the exposure to the peripheral normal tissue and preventing radiation-associated complications.

To further explore the potential of photoelectric treatment and radiotherapy,we introduced a novel concept of LCR for the comprehensive treatment of keloids and hypertrophic scars.LCR is composed of three steps:volume reduction (intralesional excision or injection),radio-sensitivity enhancement (fractionated CO2laser),and recurrence prevention (radiotherapy).Either injection or intralesional excision is first considered to reduce the thickness of the scar tissue and allow the photoelectric treatment (fractionated CO2laser,1-1.5 cm) and radiotherapy (electric beam,1.5 cm) to penetrate the lesion.The fractionated CO2laser is then applied (48 h within the surgery or 1 month within the last injection)to evenly distribute pores on the epidermis and cause damage beneath,enhancing the radio-sensitivity for the following radiotherapy.Finally,the LCR procedure is completed with the electric beam for the prevention of recurrence.Because of the special distributing characteristics of laser and radiation,LCR is particularly suitable for wide-based keloids or hypertrophic scars with flat conjunction to the normal skin,which used to be a challenge as the surgery may cause serious skin defect and the magnitude volume of the scar tissue limits the efficacy of photoelectric treatment and radiotherapy.Figure 3 shows the success of the LCR in a young female patient with disseminated keloids at both jawlines.On treatment with LCR therapy (steroid injection +fractionated CO2laser+radiotherapy),the general states of both scars significantly improved without recurrence.

CONCLUSION

Keloids are notorious dermal tumors that may cause considerable psychological pressure and inconvenience to patients.As the morphological and pathological characteristics of keloids greatly vary,patients'expectations and available methods are the treatment strategy,and the endpoint should be subtly set according to individual conditions under thorough communications.The complicated mechanisms of keloids lead to multiple treatment methods.However,single therapies are highly at risk of recurrence,thereby making comprehensive treatments essential for satisfactory outcomes.In this report,we summarized several clinical comprehensive strategies from the experience at our institutions and introduced one original concept of LCR as a novel comprehensive treatment for keloids and hypertrophic scars.LCR exerts the potential of radiotherapy and photoelectric treatment,combined with the traditional methods of injection and operation (core dissection),and is a promising solution to the clinical challenge of wide-based pathological scars.In addition,more trusted assessment scales on classifications and risk degree are expected to assist in the clinical treatment of keloids and hypertrophic scars.

Acknowledgement

None

Funding

This study is supported by the National Nature Science Foundation of China (81101432 and 81272036).

Author's contributions

Dr.Xiaoli Wu,Dr.Zhen Gao,and Pro.Wei Liu conceived the concept and revised the manuscript.Ms.Yangting Yang drafted the manuscript.Dr.Wenbo Wang,Dr.Lingling Xia,Ms.Qianyu Ma,and Dr.Xiaoqing Wang collected the clinical data and patient consents.All authors read and approved the submission of the final manuscript.

Ethics approval and consent to participate

Informed consents for publication of photographs wer e obtained from patients.

Competing interests

All authors declared no conflicts or competing interests.