Comprehensive pathogenesis and clinical therapy in striae distensae: An overview and current perspective

Yichen Shen ,Qinqin Png ,Jinghong Xu,*

a Department of Plastic Surgery,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,Zhejiang,China

b Department of Plastic Surgery,Hwa Mei Hospital,University of Chinese Academy of Sciences,Ningbo 315010,Zhejiang,China

Keywords:Striae distensae Pathogenesis Clinical therapy

ABSTRACT The pathogenesis of striae distensae(SD)is complicated and has not yet been fully elucidated.Hormonal changes,overstretched skin,and structural and functional changes in the skin may be crucial factors in the development of SD.Therapy aims to stimulate dermal collagen synthesis and improve skin texture.Mainstream treatments include topical medications,chemical peeling,laser and radiofrequency therapy,microdermabrasion,microneedle therapy,and filler injection therapy.In the present review,we summarize current perspectives on the pathogenesis and clinical therapy of SD.

1.Introduction

Striae distensae (SD) or stretch marks are common scars that impair skin aesthetics.They may affect the abdomen,breasts,upper arms,hips,waist,and thighs.1According to its appearance,SD could be categorized as striae rubrae (red,SR) and striae albae (white,SA).2The initial manifestation of SD is characterized by slightly raised pink or purple linear marks (SR).After months to years,SR gradually fades to hypopigmented atrophic scars(SA).3

SD shows clear sex predilection with low incidence in males but an incidence as high as 88% in females.4,5SD is a common skin condition whose lesions may be asymptomatic or accompanied by mild pruritus and pain.6,7However,it often affects appearance and causes psychological distress,especially in young women.8Therefore,there is increasing demand for treatment of SD.

2.Risk factors

Several risk factors are associated with development of SD including race,age,family history,skin type,body mass index (BMI),and weight,9,10although the association between race and the risk of SD development remains unclear.11Nonwhite women have been reported to have a higher association with SD than white women,12but other researchers have found that women with lighter skin are susceptible to SD.3In addition,sex and age influence disease site.Young men’s lower back and knees,as well as women’s thighs and calves are more vulnerable to SD.1BMI and obesity are two important risk factors in young people.13Pregnancy SD(striae gravidarum,SG)is more common in women with a family history of SD,multiple pregnancies,polyhydramnios,and higher gestational age,pre-pregnancy BMI,and fetal birth weight.9,14In addition,monozygotic twins,family history,and Marfan syndrome are associated with the development of striae,suggesting genetic predisposition may be one of the risk factor of SD.15

3.Pathogenesis

The exact pathogenic mechanism of SD has not been fully elucidated.Previous studies have reported the following pathogenic factors: excessive mechanical stretch of the skin,structural and functional alterations of skin,and hormonal changes.

SD usually occurs in the following situations: rapid growth of abdominal circumference during pregnancy,weight gain,puberty,and exercise-induced muscle hypertrophy.16,17This suggests that mechanical stress plays an important role in the occurrence of SD.Other researchers have considered that structural and functional alterations of the skin might be another factor in the occurrence of SD.Wang et al.18found decreased procollagen and fibronectin,and marked disruption and aberrant regulation of elastic fibers in the skin with SD.In addition,migration and proliferation of fibroblasts were suppressed in SD.Using genome sequencing,Tung et al.19hypothesized that the expression of mutated genes may lead to changes in the composition of skin elastic fibers,thereby promoting the occurrence of SD.

It is well known that hormones,including estrogen,androgen,cortisol,and relaxin,are closely related to the occurrence of SD.20Several studies have demonstrated an increased expression of estrogen receptors,androgen receptors,and glucocorticoid receptors in the SD skin compared to normal skin.21-23For instance,patients with Cushing syndrome have higher incidence of SD.In Cushing syndrome,corticotrophin-releasing hormone and adrenocorticotropic hormone(ACTH)levels are constantly higher than normal,followed by extensive protein degradation,resulting in skin and muscle atrophy.24Relaxin,a hormone that reduces collagen production,is inversely correlated with the incidence of SD in pregnant women.25,26Lower serum relaxin levels decrease elasticity of the connective tissue,therefore contributing to the occurrence of SD during pregnancy.26In addition,SD was also reported to be associated with certain diseases,including Marfan syndrome,rheumatic fever,typhoid,and chronic liver disease.23,27

The pathophysiology and molecular mechanisms of SD remain unclear.The recombination of extracellular matrix (ECM),including fibronectin,collagen,elastin,and fibrillin,has been reported to play a key role in SD pathogenesis.28,29Schuck et al.30used microarray analysis to detect differentially expressed genes between SD and normal skin samples and compiled a list of 22 down-regulated and 4 up-regulated genes.In addition,the enrichment analysis showed that the main biological process is ECM disassembly,and the main genes responsible for this modulation are elastin and MMP7.30Due to the lack of reliable cell and animal models,our understanding of the key pathophysiology of SD and the ability to evaluate different treatment modalities have been greatly hindered.Borrelli et al.31reported up-regulated CD26 and down-regulated CD74 in SD fibroblasts and then developed a mouse model that recapitulates human SD formation.These results suggest new strategies and opportunities to understand and treat SD.

4.Clinical and histological manifestations

SD generally appears as an edematous skin at first,and then the skin turns red,purple,or atrophic flat,referred to as SR.After 6-10 months,the red striae eventually progress to SA,appearing as persistent hypopigmented scar-like depressions with fine wrinkles.In dark-skinned patients,SD can be striae nigrae (black) or striae caerulea (bluish).SD usually appears in a symmetrical distribution and commonly affects the abdomen,waist,breasts,inner upper arms,thighs,and buttocks.1,32

SR and SA show differences in histological manifestations.SR is characterized by a flat epidermis and an inflammatory dermis.In the early stage,collagen,elastin,and fibrillin are reduced in the central region of the dermis,while the outer periphery is composed of thick and tortuous elastic fibers.33Light and electron microscopy revealed mast cell degranulation,phagocytic activation,and elastolysis in the mid-dermis of the lesion area.34Meanwhile,SA is similar to an atrophic scar,characterized by epidermal atrophy,loss of rete ridges,and thin dermal collagen bundles aligned parallel to the skin surface.35

5.Treatment

The treatment of SD is usually selected according to the striae type and Fitzpatrick classification.The therapeutic purpose of SR is to reduce erythema and hyperpigmentation,as well as skin itching.36For SA,treatment focuses on reducing the surface area and hypopigmentation to improve the clinical appearance.20The Fitzpatrick classification reflects skin phototype,which might be beneficial to the clinician’s decision making.12,37

5.1.Topical medication

Medications,including retinoids,silicone gel,and centella asiatica,are commonly used for topical therapies of SD.38However,such therapy requires several weeks of treatment,and outcomes are highly dependent on patient compliance.2Retinoic acid has fibroblastic affinity and can induce collagen synthesis.39It is mainly used for the treatment of SR,but the benefit is limited with SA.40,41Typically,initial improvement may be seen with daily application of 0.1% tretinoin cream for 2 months.Post-inflammatory hyperpigmentation may be a possible side effect,especially in patients with skin phototypes IV-VI.Silicone gel can increase skin collagen content and reduce hyperpigmentation.42A randomized controlled trial evaluated the treatment effect of onion extract cream with centella asiatica and reported that the color,texture,softness,and overall appearance of SR in women had significantly improved.43

5.2.Chemical peeling

Chemical peeling is the application of a chemical agent to make the affected skin necrotic and peel off and thus be replaced by new epidermis.44Commonly used agents for skin peeling include carbolic acid,glycolic acid,trichloroacetic acid,and alpha hydroxy acids.45,46For instance,a prospective,non-randomized study using 70% glycolic acid for SD treatment of 40 patients found a significant reduction in the width of striae,as well as decreased hemoglobin in SR patients and increased melanin in SA patients.47Caution is important when using high concentrations of agents for chemical peeling,and the potential side effects of chemical peeling include erythema,scale,and hyperpigmentation.

5.3.Laser and radiofrequency therapy

5.3.1.Pulsed dye lasers

Pulsed dye lasers (PDL) are beneficial for the treatment of SR by targeting hemoglobin and stimulating the synthesis of dermal collagen and elastin.48However,PDL is not suitable for the treatment of SA.49By applying hematoxylin and eosin stains and skin biopsies,McDaniel et al.50found that treatment with the 585-nm PDL increased dermal elastin,thus improving the appearance of lesions in 39 patients with SD.Meanwhile,a clinical trial on 20 SD patients(including 9 SR and 11 SA)reported that there was no apparent clinical alteration in SA after treatment with the 585-nm PDL.51The most common side effects of PDL include purpura,localized pigmentation,and blisters.

5.3.2.Carbon dioxide fractional lasers

Carbon dioxide(CO2)fractional lasers can remove the surface layer of skin,thus rejuvenating the whole skin and improving the appearance of SD.52A prospective randomized study with 64 subjects used global aesthetic improvement scale scores on a standard 5-point scale,and histological analysis to evaluate the appearance,degree,and collagen remodeling of SD.The results showed that a 1 565-nm non-ablative fractional laser was more effective for SD treatment than the topical β-glucan regimen.53Despite the effectiveness of these clinical trials,the disadvantages of fractional laser treatment include higher complications and longer recovery periods,which need to be monitored by physicians.

5.3.3.Non-ablative fractional lasers

Non-ablative fractional lasers (NAFLs) mainly include Nd:YAG,Er:glass,Er-doped fiber lasers,Thulium fiber lasers,and 694-nm fractional Q-switched ruby lasers.54,55Different NAFLs have been used in studies to treat SD.56-59In a study including 30 women conducted by Hendawy et al.57comparing the efficacy of Nd:YAG and CO2fractional lasers in the treatment of SD,it was reported that the patient satisfaction score and clinical efficacy of Nd:YAG laser exceeded those of CO2fractional lasers.A comparison study of the 1 565-nm Er:glass and the 1 064/532-nm Nd:YAG lasers demonstrated that both were effective and safe for the treatment of SA.58Another clinical study involving 51 SD patients evaluated the clinical efficacy of treatment with 1 540-nm Er:glass lasers,which were applied in 2-4 total treatments at 4-to 6-week intervals.59The results showed a 50%or greater overall improvement in all patients at least 6 months after Er:glass treatment as well as no recurrence of striae at 18 or 24 months.

5.3.4.Excimer lasers

Excimer laser treatment can improve the appearance of SA.Goldberg et al.60found that 308-nm excimer lasers were effective in increasing pigmentation in mature hypopigmented striae in 80%of subjects,but the treatment effect was not durable.Another clinical trial involving 31 adult subjects assessed the pigmentation of SA by visual and colorimetric assessments compared with that in control groups and concluded that to sustain the cosmetic benefit for SA,a 308-nm excimer laser should be applied every 1-4 months.61Potential complications arising from this treatment could be transient erythema and the splaying of pigment.

5.3.5.Intense pulsed light

Intense pulsed light (IPL) devices employ xenon flash lamps to emit high-intensity polychromatic light to target various chromophores in the skin.62IPL therapy is applied in many dermatological diseases,especially pigmented lesions.63Several studies demonstrated significant clinical and microscopic improvements in SD after IPL treatment,indicating that the treatment was effective.64,65A prospective study of 15 women with late stage SD of the abdomen demonstrated that all patients showed both clinical (total length,discolorations,and general appearance of striae)and microscopic (elastosis,edema,inflammation,and quality of the collagen fibers) improvement.65High-energy IPL may easily cause post-inflammatory hyperpigmentation.Therefore,low-energy IPL therapy may be a substitute for SR.

5.3.6.Radiofrequency

Exposure to radiofrequencies can improve the appearance of SD through induction of inflammation,denaturalization of elastic and collagen fibers,followed by production of new collagen.66A clinical study on 16 subjects reported that using radiofrequency for the treatment of pregnancy related SD resulted in significant reduction in both the length and width of striae bands and a high degree of patient satisfaction(up to 87.5%).67Several studies compared the efficacy of radiofrequency and other therapies,including pulsed dye laser,fractional laser,and platelet-rich plasma injection and demonstrated that a combination of both therapies can significantly enhance the efficacy of SD treatment.68-70In addition,radiofrequency therapy combined with growth factors has been reported to add to the effect of monotherapy.Afify et al.71found that the combination of fractional microneedling radiofrequency and lyophilized growth factors significantly improved SA outcomes and patient satisfaction.

5.4.Microdermabrasion

Microdermabrasion is a minimally invasive cosmetic procedure that relies on abrasive components,such as inert crystals,and a vacuum component.72After microdermabrasion treatment,thickening of the epidermis with increasing collagen,less melanization,and regular distribution of melanosomes may occur.73A randomized trial compared the therapeutic effect of microdermabrasion with 0.05% topical tretinoin cream in 32 early SR patients,finding that both treatments were equally effective for SR,and patients were more compliant with microdermabrasion due to fewer side effects.41

5.5.Microneedle therapy

Microneedling therapy has the advantages of minimal invasiveness and less pain,as well as a combination of topical medication.74Consequently,it has been widely used in the treatment of atrophic scars,wrinkles,and a variety of skin diseases.71,75Several studies have compared the efficiency of microdermabrasion through sonophoresis,CO2fractional lasers,and skin microneedling,and it was demonstrated that microneedling was superior to the other two treatments.76,77

5.6.Filler-injection therapy

The use of fillers to treat SD has expanded patient options to achieve therapeutic effects in a clinical setting.Fillers,including platelet-rich plasma (PRP),polycaprolactone-based filler (PCL),poly-L-lactic acid,silicone and succinylated atelocollagen,were reported to be beneficial in the treatment of SD.42,78-81For instance,PRP contains a high concentration of platelets,as well as various growth and bioactive factors,and cytokines,which may stimulate extracellular matrix synthesis and modulate inflammation.82,83Several studies have compared the efficacy of PRP injection and other therapies.When compared to tretinoin cream,PRP injection showed greater improvement and patient satisfaction for the treatment of SA.84Furthermore,PRP injection and CO2fractional lasers did not differ significantly for SA treatment.68,85As a PCL-based dermal filler,DLMR01 has direct and secondary “delayed” volumizing effect,which makes it an excellent candidate for treating intractable SD.79Other fillers containing active ingredients,including growth factors,were also used to treat SD.For instance,Kikuchi et al.86tested the safety and efficacy of a silicon-based scar cream containing recombinant human growth factors,hyaluronic acid,and vitamin C for SD.Twenty-two subjects with SD were recruited,and the results showed improved appearance and texture in 86.4%of patients.However,current data on the effectiveness and safety of these interventions are limited.Further research is necessary to determine the role of these treatments.

5.7.Other therapies

Many pregnant women use topical preparations to prevent SD.87,88However,the relationship between these preventive measures and SD remains unclear.One study reported that 77.6%of Japanese women used cream and/or lotion to prevent SG.87However,the results showed that these preventive steps were not successful.A meta-analysis involving 800 women evaluated the role of Alphastria,Trofolastin,Verum,olive oil,and cocoa butter and concluded that there was no statistically significant difference between the treatment and control groups.89Other studied also came to mixed conclusions.87,90Therefore,evidence for the effectiveness and safety of these interventions remains insufficient.Further research is necessary to determine the role of these treatments.

6.Conclusion

SD is a common disfiguring skin disease that affects a large number of patients,particularly pregnant women.Owing to the development of new technology,more therapeutic methods are expected to emerge.However,satisfactory clinical strategies are still lacking.Multi-center,prospective,randomized,and controlled studies are urgently needed to identify safe and efficient treatment options.In addition,exploring the pathogenesis of SD from a genetic perspective may become a research hotspot in the future,which might be beneficial for formulating an effective clinical strategy.

Ethics approval and consent to participate

Not applicable.

Consent for publication

All the authors have consented for the publication.

Authors’ contributions

Shen Y: Investigation,Visualization,Writing-Original draft.Pang Q:Conceptualization,Writing-Review and editing.Xu J: Funding acquisition,Supervision.

Competing interests

The authors declare that they have no competing interests.

Acknowledgments

This work was supported by the National Natural Science Foundation of China(grant no.81873937).