Treatment of striae distensae with microdermabrasion: a clinical and molecular study Amany M. Abdel-LatiJ; M.D. * and Amal S. Elbendary, M.D. f *Departments of Dermatology and Venereology, ?clinical Pathology, Faculty of Medicine, Tanta University. Background. Striae distensae are dermal scars associated with epidermal atrophy whose treatment options are unsatisfactory. Although microdermabrasion has become a popular method for superficial skin resurfacing, studies examining its usefulness in treatment of striae are laclung. Objective. To evaluate the efficacy of rnicrodermabrasion in treatment of striae and to test its effect on mRNA expression of type I procollagen. Methods. Each of 20 patients with striae underwent a series of 5 rnicrodermabrasion treatments at weekly intervals to their striae on one half of the body with matched striae on the other half serving as control. From each patient, skin biopsy specimens were obtained 2 weeks after the last microdermabrasion treatment from both treated and untreated control striae. Samples were subjected to real time RT-PCR for assay of type I procollagen -1 mRNA levels. Results. There was good to excellent (more than 50%) improvement in the appearance of striae in 50% of cases 12 weeks after starting 5 rnicrodermabrasion treatments compared to control. The remaining 50% showed mild to moderate (up to 50%) improvement. More improvement was obtained in striae rubra than striae alba. Upregulated type I procollagen a1 mRNA expression was found in the rnicrodermabrasion treated compared to non treated striae. Conclusion. Microderrnabrasion can be a useful therapeutic option in treatment of striae with a possible stimulatory effect on type I procollagen formation. Key words. Striae distensae, microdermabrasion, type I procollagen rnRNA, real time RT-PCR. Striae are visible linear scars which form in areas of dermal damage produced by stretching of the skin.(') The factors which govern the development of striae are poorly understood. It was suggested that striae develop as a result of stress rupture of conpective tissue framework. They are common during adolescence and they seem to be associated with rapid increase in size of a particular regi0n.e) Striae are very common over the abdomen and breast in and may develop on pregnancy "1, shoulders in young male weight lifters when their muscle mass rapidly increases.(5) They are a feature of Cushing' s disease, and may be induced by local or systemic steroid therapy.c2) The importance of genetic factors in determining susceptibility of connective tissue is emphasized by absence of striae in pregnancy in Ehler Danlos syndrome but they are present as one of the minor diagnostic criteria for Marfan's syndrome. The histology is that of scar. In the early stages, inflammatory changes may be conspicuous but later the epidermis is thin and flattened. The dermal collagen bundles are arranged in straight lines parallel to the surface in the direction of presumed stress with abundant clumped elastic fibers.(@ The commonest sites are the outer aspects of the thighs and the lumbosacral region in boys and the thighs, upper arms, buttocks and breasts in girls. In the early stages, striae may appear pink to red (striae rubra), which over time become atrophic and attain a white colour (striae alba). Recently, high-resolution epiluminescence colorimetric assessment of J Egypt worn Dermatol Soc. Vol. 5, No. I , 2008 Amany M. Abdel-Lcctif M.D. and Amal S. Elbenda1?1, M. D. striae distensae distinguished four distinct types, namely striae alba, striae rubra, striae caerulea and striae nigra.The direct and/or indirect influences of melanocyte mechanobiology appear to have a prominent effect on the various colours of striae di~tensae.'~) Multiple treatment modalities have been tried with variable results. These included tretinoin,c8)glycolic acid9c9)pulsed dye laser, (lO.ll) C 0 2 laser,(12)intense pulsed light.(I3)the excimer laser<14-16) and non ablative 1,450-nm diode laser.(17) Aluminum oxide crystal rnicrodermabrasion has become a popular method of superficial skin resurfacing. Microdermabrasion may improve many skin problems including acne scars,(18) acne?(l9) skin texture irregularities, mottled pigmentation(20) and fine wrinkles-c21) In addition, Karimipour et al, (2005) (22) reported that microdermabrasion induces epidermal signal transduction pathways associated with remodeling of the dermal matrix. However, studies documenting the efficacy of rnicrodermabrasion in treatment of striae are lacking. This study was performed to evaluate clinically the efficacy of microdermabrasion in treatment of striae and to investigate at the molecular level its stimulatory effect on type I procollagen formation. PATIENTS AND METHODS Twenty patients with striae distensae collected from the Out-Patient clinic of Dermatology and Venereology department of Tanta University hospital were included in this study. Informed consent was obtained from each patient. They included 14 (70%) females and 6 (30%) males. Their ages ranged from 18 to 35 years (mean; 26 year). Twelve patients had striae rubra and 8 patients had striae alba. The duration of the disease ranged from 3 months to 2 years (mean; 9 months). The treated striae were present on the thighs [6 (30%) cases], abdomen [5 (25%) cases], upper arms [5 J Egypt worn Dermatol Soc. Vol. 5, No. 1, 2008 (25%) cases] and back [4 (20%) cases]. Five (25%) patients have Fitzpatrick's skin type 11, eight (40%) have type 111, and seven (35%) have Fitzpatrick's skin type IV. Each patient underwent a series of 5 microdermabrasion treatments at weekly intervals to his or her striae on one half of the body with matched striae on the other half serving as control. The basic aluminum oxide/sodium chloride-based rnicrodermabrasion system is a closed loop consisting of the following: vacuum suction distributed through a hand piece that sucks the skin into the hand piece, a compression system that propels crystals (corundum) at a programmable pressure when the skin is sucked into the hand piece, a reservoir for unused corundum, and a waste receptacle which contains used corundum and skin debris that have been aspirated back through the vacuum. Multiple passes with the microdermabrasion hand piece on the striae were performed until a strong erythema was visible. Photographs were taken before microdermabrasion treatment, 2 and 8 weeks after the last treatment. All photographs were taken with the same Nikon coolpix-4500 digital camera (4.0 mega pixels), under similar background, light intensity and positioning.. Three blinded observers were asked to grade the degree of clinical improvement based on photographic assessment for the change in width, colour mismatch and skin atrophy comparing treated striae with untreated matched control 8 weeks after the last treatment (12 weeks following the onset of microdermabrasion treatment). The degree of improvement was graded by 4 point grading scale as follows; mild (< 25%), moderate (25-50%), good (>50%-75%) and excellent (>75%) improvement. Patient satisfaction was graded by 3 point grading scale; A (not satisfied), B (somewhat satisfied) and C (highly satisfied). From each patient, 3 mm punch biopsy specimens were obtained 2 weeks after the last (6 weeks following the first) microdermabrasion treatment, one from treated striae and the other from matched Trecrtment of striae distensae with microdermclbrusion: a clitzical and moleculur study untreated control striae. Skin s p e @ - m s were frozen at -70 oC until assay of type I procollgen a1 mRNA levels using real time reverse transcriptional polymerase chain reaction (RT-PCR). Real time RT-PCR for assay of type I procollagen mRNA: Total RNA extraction was performed after sample homogenization using extraction kit QIAGEN (QIA amp RNA mini kit Inc USA) according to the manufacturer's instructions. 2 mg of total RNA were reverse-transcripted using standard reagents (Gibco, USA). The cDNA corresponding to 20 ng of RNA served as a template in a reaction containing 4 mmol/L MgC12, 0.5 mmol/L of each primer and DNA Master SYBR (Roche Molecular Green mixture Biochemicals, USA), under the following conditions; denaturation at 95 oC for 10 min, followed by 45 cycles, each cycle consisting of 95 oC for 15 seconds, 60 oC for 5 seconds and 72 oC for 10 seconds. Fluorescence emission readings were monitored at 72 oC at the end of each cycle and analyzed using Light Cycler Soft ware (Roche Molecular Biochemicals USA). Relative amounts of type I procollagen a1 transcript levels were normalized to glyceraldehyde-3 phosphate dehydrogenase (GAPDH) levels. Melting curves were generated after each run to confirm amplification of specific transcripts. The sequence of primers used for real time RT-PCR assay was: GA1, 5'CCAGCCGAGCCACATCGCTC- 3', GA2, 5'- ATGAGCCCCAGCCTTCTCCAT- 3' (for GAPDH) and 5'-GTCTTCCTGGCCCCTCTGGTG-3', 5'-TCGCCCTGTTCGCCTGTCTCA-3' (for type I procollagen a 1).cu) Statistical analysis: Data were analyzed with statistical package for social science (SPSS) version 11, statistical soft ware (USA). Chi square test and student (t) -test were utilized. Significance was established at P value <0.05. RESULTS Twelve weeks following the start of 5 microdermabrasion treatments at weekly intervals, 4 (20%) patients showed mild (<25%) improvement, 6 (30%) got moderate (25-50%) improvement, 6 (30%) got good ( 250%-75%) improvement and 4 (20%) got excellent (>75%) improvement (table 1). More improvement was noted in striae rubra than striae alba (table 2, fig.1). In striae rubra, 1 (8.4%) patient got mild improvement, 3 (25%) got moderate improvement, 4 (33.3%) got good improvement, and 4 (33.3%) got excellent improvement (fig. 2). In contrast, patients with striae alba got mild improvement in 3 (37.5%) cases, moderate improvement in 3 (37.5%) cases and good improvement in 2 (25%) cases and no excellent improvement was obtained. The difference was statistically significant (table 2). No significant differences in the degree of improvement were observed in different (11-IV) skin types (table 3). Side effects were minimal and limited to post inflammatory hyper pigmentation in 4 (20%) cases and transient erythema in 5 (25%) patients. Patient satisfaction scores revealed that 8 (40%) patients were highly (C) satisfied and 8 (40%) were somewhat (B) satisfied while 4 (20%) were not (A) satisfied. There was a highly significant increase in relative amounts of type-I procollagen a 1 mRNA in treated (0.55kO. 12) compared to non treated control (0.18k0.04) striae 6 weeks following the start of 5 microdermabrasion treatments. El Mild IModerate @ Good EI Excellent g 1 40 35 30 25 :: 10 t 5 0 Striae rubra striae alba Degree of improvement Fig. 1. More improvement was found in striae rubra compared to striae alba 12 weeks following the start of 5 microderrnabrasion treatments. J Egypt worn Dermutol Soc. Vol. 5, No. 1, 2008 Amany M. Abdel-Latif M.D. and Amal S. Elbendary, M.D. Table 1. Improvement of striae distensae 12 weeks after starting 5 microdermabrasion treatments. Degree of improvement Number Percentage Mild (~25%) 4 20% Moderate(25%-50%) 6 30% Good (>50%-75%) C 30% Excellent ( >75%) 4 20% IStriae rubra (N=12) No % improvement 1 Mild (~25%) Moderate(25%-50%) 3 IStriae alba (N=8) No % Mean f SD Significant*: P. value < 0.05 Chisquare X2 P. value 8.4 3 37.5 25 3 37.5 Good (>50%-75%) 4 33.3 2 25 4 33.3 0 0 Excellent(>75%) I - 1 mRNA relative amounts Range Table 2. Improvement of striae rubra compared to striae alba 12 weeks following the start of 5 microdermabrasion treatments. Degree of Table 4. Relative amounts of type-I procollagen -1 mRNA in skin lesions of treated compared to non treated control striae 6 weeks following the start of 5 microdermabrasion treatments. 5.07 0.041* Significant*: P. value c 0.05 Fig. 2(A). Striae rubra on the right upper arm before treatment Table 3. Improvement of striae distensae 12 weeks following the start of 5 microdermabrasion treatments by Fitzpatrick's skin type. I Chisquare Fitzpatrick's skin type X2 1.26 P. value 0.974 Non significant: P. value >0.05 J Egypt wom Dermatol Soc. Vol. 5, No. I , 2008 Fig. 2(B). Striae rubra showing typical erythema immediately following microdermabrasion treatment. Treatment of striae distewith microdemuzbrasion: a clinical and.qolecular study , I L I A Fig. Z(C). Treated striae 6 weeks after brdting rnicrodermabrasion. DISCUSSION controlled study, 0.025% tretinoin cream was ineffective in the treatment of striae rubra and alba. (8) However, topical 0.1% tretinoin was found to improve the clinical appearance of early erythematous striae. ("J5) In addition, striae alba were improved with topical therapy with 20% glycolic acid combined with either 0.05% tretinoin or 10% L- ascorbic acid, 2% Zinc sulfate and 0.5% tyr~sine.(~) Various lasers have recently been reported as effective treatment modalities for striae distensae, but pigmentary alterations are a major concern to the darker skin type. Jimenez et al, reported that the 585- nm pulsed dye laser might help to improve striae rubra but had no effect on striae alba. (I1) Moreover, post inflammatory hyperpigmentation was a significant side effect in dark (IV-VI) skin types. (l1~l2)In a recent study, the thermage (a radiofrequency device for the lifting of the face and neck) combined with pulsed dye laser appeared to be an effective treatment for striae distansae. (26) On the other hand, Tay et al, (2006) found that the non ablative 1,450-nm diode laser was not useful in the treatment of striae in patients with skin types IV-VI. (I7) However, Intense- pulsed light has been shown to improve striae alba but PIH occurred in 40% of patients.(13) In addition, the 308-nm excimer laser has been shown to temporarily repigment striae by increasing the number of melanocytes but without improving the atrophy. 14-16 Microdermabrasion, a popular method of superficial skin resurfacing with beneficial effect in scarring(18) and photodamage (27) would also be expected to improve striae being dermal scars associated with epidermal atrophy. In this study, 50% of patients with striae got good to excellent (more than 50%) improvement while the remaining 50% got mild to moderate (up to 50%) improvement compared to untreated controls12 weeks after starting 5 microdermabrasion treatments at weekly intervals. Striae rubra showed more significant improvement than striae alba. There was no significant difference' in the degree of improvement in different (11-IV ) skin types. Complications were minimal and limited to post inflammatory hyperpigmentation that occurred in 20 % and transient erythema in 25% which was well accepted by the patients. Eighty percent of ' the studied patients were satisfied with treatment. Mahuzier in his text book on microdermabrasion(28)stated that 10-20 sessions of microdermabrasion at an interval J Egypt wom Dermatol Soc. Vol. 5, No. 1,2008 Amany M. Abdel-Lltij-M.D. and Amul S. Elbendui-y, M.D. of not less than one month , each session resulting in bleeding points, provide satisfactory improvement in striae distensae. Moreover, histological examination of the striae after microdermabrasion treatment showed epidermal thickening and more collagen and elastic fibers in the dermis.28 In the current study, there was upregulated type I procollagen a 1 mRNA expression in treated striae being measured at 6 weeks after starting microdermabrasion treatment. This might indicate a stimulatory effect of microdermabrasion on collagen formation with subsequent dermal remodeling accounting for the therapeutic benefit. It has been suggested based on histologic studies that the beneficial effects noted with microdermabrasion for scars and photodamage result from new collagen and elastin production in the dermis.(29). Karimipour et al,"" in their study on the molecular alterations in normal skin following rnicrodermabrasion, found that mean increases in the study population of type 1 procollgen mRNA and protein failed to reach statistical significance after a single microdermabrasion treatment (measurements were made on days 1, 2,3,4,7,10,14, and 16, post treatment). However, 2 of 11 subjects studied did demonstrate increased type I procollagen gene expression (2.9-, 3.1-fold) 14 days after a single microdermabrasion treatment. Type I11 procollagen and tropoelstin mRNA and protein levels did not appear to change in that study.(22) We can speculate that repeating microdermabrasion treatment can make the stimulatory effect on type I procollagen gene expression manifest contributing to the increased mean type I procollagen a1 mRNA levels observed in our study. Emerging evidence indicates that internal or externally applied mechanical tension on the skin can substantially alter the activity of key pathways that regulate connective tissue homeostasis.(30)In a recent study,(31) the abrasive component together with the negative pressure of microdermabrasion were necessary for stimulating expression of key genes involved in dermal remodeling. There was J Egypt worn Dermatol Soc. Vol. 5, No. 1, 2008 significant increases in gene expression of the c-Jun component of activator protein- 1, interleukin 1 p, tumor necrosis factor - a, matrix metalloproteinases ( MMP- 1, MMP-3, MMP-9 ) in normal skin treated micr~dermabrasion.(~l) with Microdermabrasion treatment appeared to set in motion a cascade of molecular events capable of causing dermal remodeling and repair.(22) Studies on the use o f rnicrodermabrasion in treatment of striae are lacking. There remains a major disparity between the popularity of microdermabrasion in the public sector and cohesive and comprehensive scientific data documenting the efficacy of the procedure. (32) In conclusion, rnicrodermabrasion is effective, well tolerated, and safe for treating striae distensae having more beneficial effect on striae rubra than striae alba with ability to upregulate type I procollagen mRNA expression involved in dermal matrix remodeling. Reappraisal of this potentially useful procedure points toward a need for well-designed clinical trials and studies with a long follow-up based on objective assessment parameters. A larger study may be needed to demonstrate any additional benefit including the influence of microdermabrasion on different aspects of dermal remodeling and repair. Further studies are also needed to determine the optimum number of treatment sessions and the suitable intervals between treatments beside the possibility of enhancing its effect by combining microdermabrasion with other treatments as topical tretinoin or glycolic acid in treating striae. REFERENCES I . Burrows NP, Love11 CR. Disorders of connective tissue. In: Burns T, Breathnach S, Cox N and Grriffiths C, editors. Rook's text book of Dermatology. Blackwell Science; 2004.p. 46.1-46.7 1. 2. Stevanovic DV. Corticosteroid induced atrophy of the skin with telangiectasia: a clinical and experimental study. Br J Dermatol 1972;87: 548-56. 3. 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