Facilitated delivery of topical steroids after fractional ablative carbon dioxide laser benefits postthyroidectomy hypertrophic scar



    Table of Contents ORIGINAL ARTICLE Year : 2022  |  Volume : 40  |  Issue : 1  |  Page : 3-8

Facilitated delivery of topical steroids after fractional ablative carbon dioxide laser benefits postthyroidectomy hypertrophic scar

Cen-Hung Lin1, Yueh-Ju Tsai1, Shun-Yu Chi2, Mu-Han Hsieh1, Ko-Chien Lin1, Hui-Ping Lin1, Shiun-Yuan Hsu3, Hui-Hong Tsai4, Ching-Hua Hsieh1
1 Department of Plastic Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University and College of Medicine, Kaohsiung, Taiwan
2 Department of General Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University and College of Medicine, Kaohsiung, Taiwan
3 Department of Trauma Surgery, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University and College of Medicine, Kaohsiung, Taiwan
4 An Hsiang Dermatologic Clinic, Kaohsiung, Taiwan

Date of Submission17-Aug-2021Date of Decision02-Dec-2021Date of Acceptance07-Dec-2021Date of Web Publication10-Mar-2022

Correspondence Address:
Dr. Ching-Hua Hsieh
No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung City 833
Taiwan
Dr. Hui-Hong Tsai
No. 123, Ta-Pei Road, Niao-Song District, Kaohsiung City 833
Taiwan
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ds.ds_54_21

Rights and Permissions


Background: Thyroidectomy results in unsightly scarring at the anterior neck of the patient. Objectives: This prospective clinical study aimed to assess the effectiveness of laser assisted drug delivery (LADD) of topical steroid ointment for the treatment of postthyroidectomy hypertrophic scars. Methods: Five courses of a fractional ablative carbon dioxide laser combined with topical 0.05% clobetasol propionate were applied every 4 weeks to treat postthyroidectomy hypertrophic scars in ten adult female patients. The effectiveness was assessed by the patient themselves according to the Patient and Observer Scar Assessment Scale (POSAS) and by three different doctors according to photography evaluations before and 1 year after the first treatment. Results: Assessments of the scars by POSAS revealed significant improvements in terms of itchiness, color, softness, thickness, irregularity, and distorted appearance of the scars, albeit without any significant pain relief. In addition, all indicative characteristics of the scar, namely, vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion, as assessed by the treating doctor and based on photographic evaluations by three different doctors, revealed significant improvements in the scars after treatment. Conclusion: In this study, we demonstrated that the topical delivery of steroids after fractional ablative carbon dioxide laser treatment showed an encouraging outcome in postthyroidectomy hypertrophic scarring.

Keywords: Fractional ablative carbon dioxide laser, hypertrophic scar, laser-assisted drug delivery, steroids, thyroidectomy


How to cite this article:
Lin CH, Tsai YJ, Chi SY, Hsieh MH, Lin KC, Lin HP, Hsu SY, Tsai HH, Hsieh CH. Facilitated delivery of topical steroids after fractional ablative carbon dioxide laser benefits postthyroidectomy hypertrophic scar. Dermatol Sin 2022;40:3-8
How to cite this URL:
Lin CH, Tsai YJ, Chi SY, Hsieh MH, Lin KC, Lin HP, Hsu SY, Tsai HH, Hsieh CH. Facilitated delivery of topical steroids after fractional ablative carbon dioxide laser benefits postthyroidectomy hypertrophic scar. Dermatol Sin [serial online] 2022 [cited 2022 Mar 31];40:3-8. Available from: https://www.dermsinica.org/text.asp?2022/40/1/3/339330   Introduction Top

Thyroidectomy results in inevitable scarring of the anterior neck of the patient. The perception of a poor postthyroidectomy scar is not only associated with poor body image and quality of life but also a higher prevalence of body dysmorphic disorder (an overemphasis on the scar, causing unhappiness) when compared with the general population.[1] Intralesional injection of steroids has been widely used as a treatment for hypertrophic scars with well-known side effects, including pain, erythema, telangiectasia, dermal and fat atrophy, and hypopigmentation.[2],[3],[4],[5] In addition, as previous studies have indicated, laser therapies for hypertrophic scars have shown beneficial effects; for example, fractional ablative carbon dioxide laser has been the most popular laser treatment for hypertrophic scars.[6],[7],[8],[9],[10],[11] This method works on the fibrotic tissues by promoting fibroblast apoptosis and collagen degradation and therefore helps to resurface and reduce the size of the hypertrophic scar.[2],[3],[9]

In 2013, Waibel et al. first published a study on the laser-assisted delivery of topical steroids using a fractional ablative carbon dioxide laser for hypertrophic scarring and found promising results while decreasing the adverse effects caused by intralesional steroid injection.[12] With such laser-assisted drug delivery (LADD), the epidermal barrier is destroyed after tissue vaporization by a fractional laser, and the infiltration and distribution of the drug into the dermis are enhanced.[13] For example, an ablative carbon dioxide laser can break the epidermis and create exposed spots within the dermis at a depth of 0.5–1 mm, thereby helping deliver the applied drug into the dermis.[13],[14] Animal and clinical studies also applied LADD by combining a fractional ablative carbon dioxide laser with follow-up topical medical agents, including a steroid, 5-fluorouracil, and verapamil hydrochloride, showing favorable outcomes.[2],[3],[13],[15],[16],[17] Therefore, this clinical study was conducted to assess the effects of LADD combined with a fractional ablative carbon dioxide laser and a topical steroid for the treatment of postthyroidectomy hypertrophic scars.

  Materials and Methods Top

This study was conducted beginning on March 1, 2018, with a protocol conforming to the ethical guidelines of the 1975 Declaration of Helsinki, as reflected by the approval of the Institutional Review Board of Chang Gung Memorial Hospital (Reference Number 201800241A3). Informed consent was obtained from all participants included in the study. A total of ten adult female patients who underwent thyroidectomy through a transcervical incision by the same surgeon at our hospital were enrolled in this study [Table 1]. All patients presented with a persistent hypertrophic scar in the neck region for more than 1 year after thyroidectomy. The patients had no systemic chronic disease, history of autoimmune disease, or human immunodeficiency virus infections. No patients had received intralesional steroid injections or laser treatment during this period.

Protocol using fractional ablative carbon dioxide laser with topical steroid

All patients received treatment using the same protocol with the same fractional ablative carbon dioxide laser (eCO2 Plus™, Lutronic, South Korea). Each patient was administered Lidopin 5% cream (Panion & BF Biotech Inc.), which remained on the scar for 30 min for pain relief before each laser course. Later, the Lidopin 5% cream was gently removed using a normal saline-rinsed gauze, and the scar was treated with a fractional ablative carbon dioxide laser with two passes under a 10,600-nm wavelength, 120-mm spot size, pulse energy of 50 mJ, 30 W of power, and a density of 200. A topical steroid cream (clobetasol propionate, 0.05%) was evenly applied to the scar gently back and forth using a cotton swab immediately after the laser treatment. No further routine use of steroid ointment for the scar was prescribed. Postoperatively, neomycin ointment was used for the wound care daily for 3–5 days. The patients underwent five full courses by the same doctor according to the same protocol, with each course given 4 weeks apart.

Self-assessment by patients

For each patient's self-assessment before the first treatment and 1 year after the first treatment, we adopted the Patient and Observer Scar Assessment Scale (POSAS),[18] with a range of 1–10 to represent the severity of the itchiness, pain, color, softness, thickness, irregularity, and distorted appearance of the scar.

Doctor evaluations

Four doctors participated as observers of the clinical outcomes. One of the doctors carried out all treatments and evaluated seven parameters, namely, vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion based on the POSAS using a scoring range of 1–10, from normal to worst conditions, before the first treatment, and 1 year later. The remaining three doctors acted as observers to evaluate the general appearance of the scars based on photographs captured by the same photographer with the same camera before treatment and 1 year after the first treatment. They then rated the scar on a scale of 1–10.

Statistical analysis

The scales and scores before and after treatment from the self-assessments and evaluations were calculated and presented as average values, and subsequently compared using a Kruskal–Wallis one-way ANOVA test (Windows version 23.0; SPSS, Inc., Chicago, USA). Statistical significance was set at P < 0.05.

  Results Top

A total of ten adult female patients with an average age of 37.7 years (range, 21–54 years) were enrolled in this study. They all accepted the same protocol of a fractional ablative carbon dioxide laser application five times, followed by a standard topical steroid immediately applied by the treating doctor. There was no evidence of either local or systemic complications in these patients during follow-up. All the wounds healed smoothly without signs of infection or delayed healing. The postthyroidectomy hypertrophic scars of two patients before and 1 year after the first treatment with fractional ablative carbon dioxide laser with delivery of topical 0.05% clobetasol propionate are shown in [Figure 1].

Figure 1: Photographs of postthyroidectomy hypertrophic scars of two patients (patient no. 5 and no. 10) before and 1 year after the first treatment applying fractional ablative carbon dioxide laser with delivery of topical 0.05% clobetasol propionate (upper and lower rows present two different patients: left, before treatment; right, 1 year after first treatment).

Click here to view

Patient self-assessment

Assessments of the scars by the patients themselves before and 1 year after the first treatment revealed that despite no significant pain relief [Figure 2], significant improvements in terms of itchiness, color, softness, thickness, irregularity, and distorted appearance of the scars were achieved (P < 0.05) [Figure 2] and [Figure 3].

Figure 2: Differences in pain and itchiness during the last past 2 weeks by self-assessments of the patients before and 1 year after the first treatment (Tx = treatment; score ranging from 1 to 10 representing the severity).

Click here to view

Figure 3: Differences in indicative characteristics of the scars before and 1 year after the first treatment assessed by the patients using the Patient and Observer Scar Assessment Scale (Tx = treatment; score ranging from 1 to 10 representing the severity).

Click here to view

Doctor evaluations

According to the evaluation using POSAS, the vascularity, pigmentation, thickness, relief, pliability, surface area, and overall opinion of the scars before and 1 year after the first treatment showed significant improvements in all indicative characteristics (P < 0.05) [Figure 4]. In addition, photographic evaluations by the three doctors showed significant improvements in the general appearance of the scars at 1 year after the first treatment in comparison with that before the treatment (P < 0.05) [Figure 5].

Figure 4: Differences in indicative characteristics of the scars before and 1 year after the first treatment assessed by the treating doctor using the Patient and Observer Scar Assessment Scale (Tx = treatment; score ranging from 1 to 10, indicating normal to worst appearance).

Click here to view

Figure 5: General appearance of scars evaluated by the observers according to the photograph before and 1 year after the first treatment (Tx = treatment; score ranging from 1 to 10, indicating normal to worst appearance).

Click here to view

  Discussion Top

Intralesional steroid injection is often recommended as a nonsurgical method for treating hypertrophic scars.[19],[20] Some side effects may complicate the intralesional injection of steroids, including pain, erythema, telangiectasia, dermal and fat atrophy, and hypopigmentation.[2],[3],[4],[5] In addition, laser therapies have gained increasing popularity owing to their low rates of complications in the treatment of hypertrophic scars.[4],[14],[21],[22] Various laser therapies have been adopted for improvements in hypertrophic scars with satisfactory results.[6],[8],[9] With the introduction of the LADD concept,[12] the delivery of 0.05% clobetasol propionate following the application of a fractional ablative carbon dioxide laser presents beneficial effects in the treatment of hypertrophic scars. In this study, we demonstrated significant improvements in terms of itchiness, indicative characteristics, and general appearance of hypertrophic scarring after thyroidectomy. Moreover, no adverse effects accompanied by intralesional steroid injections during follow-up were noted. In two other studies using triamcinolone with varying dosages of between 10 and 40 mg/ml, significant improvements in postburn hypertrophic scars based on the Vancouver Scar Scale were also reported using the fractional ablative carbon dioxide laser-assisted delivery of a topical steroid.[2],[16] It was further reported that refractory keloids can be treated using LADD with a fractional ablative laser followed by a combined topical application and intralesional injection of the steroid suspension.[23]

LADD is a newly evolving treatment modality with many possible applications that have thus far been used with various topical products, such as corticosteroids, immunotherapy agents (e.g., 5-fluorouracil or imiquimod), and photosensitizers for treating numerous skin conditions. For example, an ablative fractional CO2 laser alone or combined with minoxidil may serve as an additional treatment for androgenetic alopecia.[24] A fractional 2940-nm LADD of timolol maleate 0.5% is safe and effective for treating deep infantile hemangiomas.[25] Treatment with a 2940-nm erbium-doped yttrium aluminum garnet (Er: YAG) laser followed by topical application of cidofovir significantly reduced the lesion size and improved the symptoms of plantar warts.[26] Fractional Er: YAG lasers have also been used as an assistive drug delivery method to enhance topical hydroquinone permeation in the treatment of melisma.[27] In this study, although we demonstrated that the topical delivery of steroids after a fractional ablative carbon dioxide laser significantly improved postthyroidectomy hypertrophic scarring, such benefits may not be limited to a fractional ablative carbon dioxide laser or the delivery of topical clobetasol propionate. It has further been reported that a 50-mg/mL application of 5-fluorouracil for the treatment of hypertrophic scars demonstrated good results without any evident adverse effects.[3],[17] However, the parameters in LADD must be adjusted based on the type of laser, skin condition of the patient, and drug used for delivery.

In this study, we chose a CO2 laser in place of any type of ablative laser such as Er: YAG[28] for LADD. The Er: YAG laser has a mechanism of action similar to that of traditional CO2 lasers but also has the advantages of a shorter recovery period and less postoperative edema and adverse effects than the CO2 laser.[29] However, the CO2 laser produces a deeper depth of vaporization (20–60 um vs. 3–5 um, respectively)[30] and thermal damage depth (100–150 um vs. 10–40 um)[31] than the Er: YAG laser. In addition, studies have demonstrated improved clinical outcomes and greater dermal collagen remodeling with CO2 lasers compared with the Er: YAG laser on the basis of per laser pass.[32] Because this study focused on the effect of drug delivery, the effective depth of the laser was a major concern in choosing the type of ablative laser. In this regard, whether there is a similar effect of LADD by Er: YAG laser for postthyroidectomy scars would be an interesting issue to be addressed. Furthermore, based on our experience in dealing with postthyroidectomy scars with LADD, we believe that, because of the limited penetration depth of the CO2 laser, the use of LADD may fit with different indications with intralesional steroid injection. Intralesional steroid injection is indicated for keloid or thick hypertrophic scars following thyroidectomy, but LADD is more suitable for thin and wide scars. The use of intralesional steroid injection for thin and wide scars may be associated with complications such as skin atrophy and telangiectasia of the surrounding normal skin; however, such complications were not seen in LADD in our limited cases. However, because clobetasol propionate, an ultra-high potency topical steroid, had been applied on the skin with disrupted barrier by the laser, postoperative wound care of laser-treated area should be careful to avoid any risk for infection.

This study has several limitations. First, the number of recruited patients was relatively small, and further studies using a large group of patients may help confirm and clarify the findings. Second, the patients enrolled in the study all lived in Southern Taiwan and might not represent patients in other regions. Further, as a technique for enhancing the absorption of a topical steroid following the use of a fractional ablative carbon dioxide laser, it is unknown whether the contributing effect in treating hypertrophic scars is from the laser or steroid or if a synergic effect of both modalities occurs. Finally, whether there is a combined effect in LADD than the use of topical steroid or laser treatment only was addressed and should be investigated in future work.

  Conclusions Top

In this study, we demonstrated that, with significant improvements in terms of itchiness, indicative characteristics, and general appearance, the topical delivery of steroids after a fractional ablative carbon dioxide laser application showed an encouraging outcome in treating postthyroidectomy hypertrophic scarring.

Acknowledgments

We would like to thank the statistical analyses assisted by Biostatistics Center, Kaohsiung Chang Gung Memorial Hospital.

Financial support and sponsorship

This research was supported by a grant from Chang Gung Memorial Hospital (CDRPG8H0013).

Conflicts of interest

There are no conflicts of interest.

 

  References Top
1.Sethukumar P, Ly D, Awad Z, Tolley NS. Scar satisfaction and body image in thyroidectomy patients: Prospective study in a tertiary referral centre. J Laryngol Otol 2018;132:60-7.  Back to cited text no. 1
    2.Majid I, Imran S. Fractional carbon dioxide laser resurfacing in combination with potent topical corticosteroids for hypertrophic burn scars in the pediatric age group: An Open Label Study. Dermatol Surg 2018;44:1102-8.  Back to cited text no. 2
    3.Waibel JS, Wulkan AJ, Rudnick A, Daoud A. Treatment of hypertrophic scars using laser-assisted corticosteroid versus laser-assisted 5-fluorouracil delivery. Dermatol Surg 2019;45:423-30.  Back to cited text no. 3
    4.On HR, Lee SH, Lee YS, Chang HS, Park C, Roh MR. Evaluating hypertrophic thyroidectomy scar outcomes after treatment with triamcinolone injections and copper bromide laser therapy. Lasers Surg Med 2015;47:479-84.  Back to cited text no. 4
    5.Kawecki M, Bernad-Wiśniewska T, Sakiel S, Nowak M, Andriessen A. Laser in the treatment of hypertrophic burn scars. Int Wound J 2008;5:87-97.  Back to cited text no. 5
    6.Choi YJ, Kim JY, Nam JH, Lee GY, Kim WS. Clinical outcome of 1064-nm picosecond neodymium-doped yttrium aluminium garnet laser for the treatment of hypertrophic scars. J Cosmet Laser Ther 2019;21:91-8.  Back to cited text no. 6
    7.Lei Y, Li SF, Yu YL, Tan J, Gold MH. Clinical efficacy of utilizing Ultrapulse CO2 combined with fractional CO2 laser for the treatment of hypertrophic scars in Asians – A prospective clinical evaluation. J Cosmet Dermatol 2017;16:210-6.  Back to cited text no. 7
    8.Miletta N, Siwy K, Hivnor C, Clark J, Shofner J, Zurakowski D, et al. Fractional ablative laser therapy is an effective treatment for hypertrophic burn scars: A prospective study of objective and subjective outcomes. Ann Surg 2021;274:e574-80.  Back to cited text no. 8
    9.Ouyang HW, Li GF, Lei Y, Gold MH, Tan J. Comparison of the effectiveness of pulsed dye laser vs. pulsed dye laser combined with ultrapulse fractional CO2 laser in the treatment of immature red hypertrophic scars. J Cosmet Dermatol 2018;17:54-60.  Back to cited text no. 9
    10.Poetschke J, Dornseifer U, Clementoni MT, Reinholz M, Schwaiger H, Steckmeier S, et al. Ultrapulsed fractional ablative carbon dioxide laser treatment of hypertrophic burn scars: Evaluation of an in-patient controlled, standardized treatment approach. Lasers Med Sci 2017;32:1031-40.  Back to cited text no. 10
    11.Żądkowski T, Nachulewicz P, Mazgaj M, Woźniak M, Cielecki C, Wieczorek AP, et al. A new CO2 laser technique for the treatment of pediatric hypertrophic burn scars: An observational study. Medicine (Baltimore) 2016;95:e5168.  Back to cited text no. 11
    12.Waibel JS, Wulkan AJ, Shumaker PR. Treatment of hypertrophic scars using laser and laser assisted corticosteroid delivery. Lasers Surg Med 2013;45:135-40.  Back to cited text no. 12
    13.Issler-Fisher AC, Waibel JS, Donelan MB. Laser modulation of hypertrophic scars: Technique and practice. Clin Plast Surg 2017;44:757-66.  Back to cited text no. 13
    14.Hultman CS, Edkins RE, Wu C, Calvert CT, Cairns BA. Prospective, before-after cohort study to assess the efficacy of laser therapy on hypertrophic burn scars. Ann Plast Surg 2013;70:521-6.  Back to cited text no. 14
    15.Azzam OA, Bassiouny DA, El-Hawary MS, El Maadawi ZM, Sobhi RM, El-Mesidy MS. Treatment of hypertrophic scars and keloids by fractional carbon dioxide laser: A clinical, histological, and immunohistochemical study. Lasers Med Sci 2016;31:9-18.  Back to cited text no. 15
    16.Khandelwal A, Yelvington M, Tang X, Brown S. Ablative fractional photothermolysis for the treatment of hypertrophic burn scars in adult and pediatric patients: A single surgeon's experience. J Burn Care Res 2014;35:455-63.  Back to cited text no. 16
    17.Sabry HH, Abdel Rahman SH, Hussein MS, Sanad RR, Abd El Azez TA. The efficacy of combining fractional carbon dioxide laser with verapamil hydrochloride or 5-fluorouracil in the treatment of hypertrophic scars and keloids: A clinical and immunohistochemical study. Dermatol Surg 2019;45:536-46.  Back to cited text no. 17
    18.Draaijers LJ, Tempelman FR, Botman YA, Tuinebreijer WE, Middelkoop E, Kreis RW, et al. The patient and observer scar assessment scale: A reliable and feasible tool for scar evaluation. Plast Reconstr Surg 2004;113:1960-5.  Back to cited text no. 18
    19.Lee SJ, Yeo IK, Kang JM, Chung WS, Kim YK, Kim BJ, et al. Treatment of hypertrophic burn scars by combination laser-cision and pinhole method using a carbon dioxide laser. Lasers Surg Med 2014;46:380-4.  Back to cited text no. 19
    20.Makboul M, Makboul R, Abdelhafez AH, Hassan SS, Youssif SM. Evaluation of the effect of fractional CO2 laser on histopathological picture and TGF-β1 expression in hypertrophic scar. J Cosmet Dermatol 2014;13:169-79.  Back to cited text no. 20
    21.Clayton JL, Edkins R, Cairns BA, Hultman CS. Incidence and management of adverse events after the use of laser therapies for the treatment of hypertrophic burn scars. Ann Plast Surg 2013;70:500-5.  Back to cited text no. 21
    22.Choi JE, Oh GN, Kim JY, Seo SH, Ahn HH, Kye YC. Ablative fractional laser treatment for hypertrophic scars: Comparison between Er: YAG and CO2 fractional lasers. J Dermatolog Treat 2014;25:299-303.  Back to cited text no. 22
    23.Al Janahi S, Lee M, Lam C, Chung HJ. Laser-assisted drug delivery in the treatment of keloids: A case of extensive refractory keloids successfully treated with fractional carbon dioxide laser followed by topical application and intralesional injection of steroid suspension. JAAD Case Rep 2019;5:840-3.  Back to cited text no. 23
    24.Salah M, Samy N, Fawzy MM, Farrag AR, Shehata H, Hany A. The effect of the fractional carbon dioxide laser on improving minoxidil delivery for the treatment of androgenetic alopecia. J Lasers Med Sci 2020;11:29-36.  Back to cited text no. 24
    25.Sun L, Wang C, Cao Y, Lv X, Tian L, Liu D, et al. Fractional 2940-nm Er: YAG laser-assisted drug delivery of timolol maleate for the treatment of deep infantile hemangioma. J Dermatolog Treat 2021;32:1053-9.  Back to cited text no. 25
    26.Coates M, Patel J, Powers C, Burton C. Laser-assisted delivery of topical cidofovir in the treatment of plantar warts. J Drugs Dermatol 2019;18:663-5.  Back to cited text no. 26
    27.Badawi AM, Osman MA. Fractional erbium-doped yttrium aluminum garnet laser-assisted drug delivery of hydroquinone in the treatment of melasma. Clin Cosmet Investig Dermatol 2018;11:13-20.  Back to cited text no. 27
    28.Verma N, Yumeen S, Raggio BS. Ablative laser resurfacing. In: StatPearls. Treasure Island (FL): StatPearls Publishing LLC; Copyright © 2021.  Back to cited text no. 28
    29.Shah S, Alster TS. Laser treatment of dark skin: An updated review. Am J Clin Dermatol 2010;11:389-97.  Back to cited text no. 29
    30.Preissig J, Hamilton K, Markus R. Current laser resurfacing technologies: A review that delves beneath the surface. Semin Plast Surg 2012;26:109-16.  Back to cited text no. 30
    31.Brightman LA, Brauer JA, Anolik R, Weiss E, Karen J, Chapas A, et al. Ablative and fractional ablative lasers. Dermatol Clin 2009;27:479-89, vi-vii.  Back to cited text no. 31
    32.Khatri KA, Ross V, Grevelink JM, Magro CM, Anderson RR. Comparison of erbium: YAG and carbon dioxide lasers in resurfacing of facial rhytides. Arch Dermatol 1999;135:391-7.  Back to cited text no. 32
    
  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
  [Table 1]
  Top

留言 (0)

沒有登入
gif