Rejuvenation of aging hands with a hyaluronic acid soft tissue filler range: efficacy, safety and patient satisfaction during six months

Received on: 12/05/2017
Approved on: 09/12/2017
Financial support: Este foi um estudo de iniciativa do investigador. Foi recebido Financial support da Galderma (França) para condução do estudo
Conflict of interests: A Dra. Doris Hexsel conduziu estudos clínicos para Ipsen, Allergan, Galderma, and Medicis, e prestou consultorias para Galderma e Merz. A Dra. Taciana Dal'Forno conduziu estudos clínicos e presta consultorias para Galderma. As demais autoras não tem conflito de interesse a declarar

Abstract

Introduction: Hyaluronic acid-based soft tissue fillers are considered one of the treatment options for hands rejuvenation.
Objective: To evaluate the efficacy a range of soft hyaluronic acid (HA) gels in women with loss of adipose tissue and dermal reabsorption as a sign of aging hands.
Methods: Fifteen subjects received treatment with two firmer HA gels combined with the softest gel of the range (group 1). Fifteen subjects received the two firmer HA gels only (group 2). Efficacy and safety assessments were performed at month one, three and six. Patient satisfaction and self-assessment questionnaires were applied.
Results: Most subjects were Caucasian (Fitzpatrick skin type III and IV) with a mean age of 56.6 years. Six months after treatment, all the subjects in Group 1 and 93% in Group 2 had clinical improvement; and 90% of the subjects in both groups presented global aesthetic improvement. Mild pain was reported in both groups. All related adverse events were mild or moderate.
Conclusions: Both treatments were effective and safe, and improvement was seen for up to six months after treatment. Subjects reported high satisfaction with both treatments up to the end of study.

Keywords: hand; rejuvenation; hyaluronic acid; skin aging

INTRODUCTION

In the last decades, signs of aging in hands have become a common area of concern in the aesthetic dermatology field. There are three-dimensional changes in the aging process of the hands, involving bone, subcutaneous structures, such as adipose tissue reabsorption, and the skin, as decreased collagen and hyaluronic acid content.¹

Different treatments have been reported to enhance the appearance of aging hands,^2-6 including intense pulsed light, chemical peels, microdermabrasion, and cryotherapy for pigmentation irregularities;^3,7 sclerotherapy for enlarged and visible veins. One of the most noticeable sign of aging in hands is the loss of subcutaneous fat, which can be replaced with different soft tissue fillers such as poly-l-lactic acid, calcium hydroxyapatite, and hyaluronic acid.^3,7 Hyaluronic acid (HA)-based soft tissue fillers are safe and can be considered one of the treatment options for hand rejuvenation.^8-10

A wide variety of commercially available HA fillers exist with different characteristics and chemical properties.¹¹ The Emervel^® (Galderma S.A., Lausanne Switzerland) range of HA soft tissue fillers has been approved in Europe since 2008 and in Brazil since 2011. Although the safety and efficacy of the these products have been reported for full face rejuvenation,^12,13 no previous clinical trials have assessed their efficacy for hand rejuvenation. All the five products of this range have been developed with the same concentration of HA (20mg/mL), varying the degree of cross-linking, particle size and gel firmness.¹⁴ Except for Emervel^® Touch, all fillers of this range are presented in two different formulations either without or with lidocaine (L).¹⁴Both Emervel^® VolumeL and Emervel^® DeepL are transparent, bioresorbable gels composed of cross-linked HA with 0.3% (w/v) lidocaine hydrochloride. They have medium to large sized particles.¹⁴ Facial indications, such as cheek and tear troughs, have been treated with these two products.^12,15 Among the Emervel^® range of products, there is no specific filler for a given indication in full-face rejuvenation so the choice of filler can be tailored to the individual.¹²

Emervel^® VolumeL and Emervel^® DeepL are firmer gels than Emervel^® Touch and are considered suitable to restore loss of subcutaneous tissue in hands. Emervel^® Touch, on the other hand, is a softer gel.¹⁴ It is ideally suited to treat superficial wrinkles. Due to the lack of data on the use of these fillers in hands, this trial was designed to evaluate the efficacy of the two firmer HA gels (Emervel^® VolumeL and Emervel^® DeepL) with or without concomitant injections of the HA softer gel (Emervel^® Touch) in women with loss of adipose tissue as a sign of aging hands.

 

MATERIAL AND METHODS

Study design and Subjects

This single center, phase IV, randomized, investigator-blind, parallel-group study was conducted at the Brazilian Center for Studies in Dermatology, Porto Alegre, Brazil. The study was reviewed and approved by the Ethics Committee of Moinhos de Vento Hospital prior to initiation and conducted in accordance with all ethical principles applicable to clinical research and in compliance with local regulatory requirements. Five visits were performed for each subject: screening; baseline/ procedure, and follow-up visits one, three and six months after the procedure.

The main inclusion criteria were women between 18 and 65 years, having never performed soft tissue augmentation on the dorsum of the hands, having at least grade 2 according the 5-point Validated Hand Grading Scale¹⁶ (Table 1), and presenting similar loss of fatty tissue on the dorsum of the both hands.

Treatment

Eligible subjects were randomly allocated to one of the two groups at 1:1 proportion. Group 1 received treatment with the firmer HA gels, one in each hand, combined with the softer gel. And Group 2 received the firmer HA gels, one in each hand, without the softer gel. Firmer gels were randomly dispensed to either right or left hand for both groups. A touch up could be done 28 days after the procedure if considered necessary by the investigator.

The firmer HA soft tissue fillers were injected in the subcutaneous tissue with a 7 cm 21G cannula. The product was uniformly placed between the tendons using retrograde injections. The softer gel, only for group 1, was injected in the mid dermis with serial punctures, using the 30G needle provided with the product.

Assessments

The severity of fat tissue loss and the aesthetic aspect of subjects’ hands were assessed by a blinded investigator using the Validated Hand Grading Scale (VHGS) (Table 1)¹⁶ and the Global Aesthetic Improvement Scale (GAIS) (Table 2).¹⁷Fat tissue loss was assessed at baseline and follow-up visits and the aesthetic improvement was assessed in follow-up visits (month 1, 3 and 6).

Subjects completed a global satisfaction and self-assessment questionnaire one, three and six months after treatment. Subjects rated skin elasticity, moisturizing, beauty, and volume augmentation on a 10-point scale from 1 (little) to 10 (much), and stated percentage improvement for skin elasticity, moisturizing, beauty and volume augmentation.

The blinded investigator asked the subjects to assess pain sensation using the visual analogue scale (VAS) for pain assessment related to the procedure and the touch up. As in Jensen et al,¹⁸ 0 - 4 mm were considered no pain; 5 - 44 mm mild pain; 45 - 74 mm moderate pain; and 75 - 100 mm severe pain. All adverse events were recorded throughout the study. Standardized photographs were taken at each visit.

 

Statistical Methods

Considering that this was an exploratory study, a convenience sample size of 30 subjects was defined. Data were expressed by mean and standard deviation or percent.

 

RESULTS

All the 30 enrolled women completed the study. Overall, most subjects were Caucasian (phototypes III and IV) with a mean age of 56.6 years. Most subjects presented with severe loss of fatty tissues with a mean ofVHGS of 3.1 for Group 1 and 2.9 for Group 2. The two groups were comparable in terms of demographic and clinical baseline characteristics. Demographic data and clinical baseline characteristics are shown in Table 3.

All the subjects received 2 mL of Emervel^® VolumeL and 2 mL of Emervel^® DeepL, one in each hand. Subjects of Group 1 received also 1 mL of Emervel^® Touch in each hand concomitantly to the treatment with the firmer gels. A touch up with 1 mL of each product was performed in all the subjects.

All the subjects presented at least a 1-grade improvement in VHGS at one and three months after treatment. Six months after treatment, all the subjects in Group 1 still had at least a 1-grade improvement in VHGS and 93% in Group 2 (Figure 1). Six months after treatment, aesthetic appearance was much or very much improved for about 90% of the subjects of both groups, according to the GAIS (Figure 2). Standardized photographs show the visual appearance of the back of the hands of Group 1 and Group 2 before and after treatment (Figures 3 and 4).

 

 

 

 

At the end of the study (month 6), the high level of efficacy was confirmed by overall satisfaction; 86.6% of Group 1 were satisfied with the treatment, and 100% in Group 2 (Figure 5). Six months after treatment, subjects of both groups graded their skin elasticity as 7, on the 10-point scale. Skin moisturizing, beauty, and volume, were graded 6.4, 7.2 and 7.1, respectively, by the subjects of Group 1. And graded 6.9, 7.2 and 7.1 by the subjects of Group 2.

 

 

After each injection, mild pain was reported in both groups. The mean score of pain using the VAS never exceeded 40 mm in any group. Overall, no particular safety concerns were observed and no serious adverse events or device complaints were reported during the study. Eight subjects presented procedure-related hematomas, 6 from Group 1 and 2 from Group 2. Ten subjects presented adverse events related to the product, 8 from Group 1 and 2 from Group 2. The most frequent adverse events were nodulation, which occurred in 6 subjects (20% of the patients), all from Group 1, and edema which occurred in 5 subjects (17%), 3 from Group 1 and 2 from Group 2. The duration of the nodulations observed lasted from 2 weeks to less than 6 months. All resolved spontaneously. Edema lasted from 2 to 10 weeks, and resolved spontaneously in 3 patients, whereas two patients required treatment with oral corticoids. Pruritus and hyperemia occurred in two subjects (7%) of Group 1, and only one patient (Group 2) reported pain up to 3 days after the procedure.

DISCUSSION

This study assessed the efficacy and safety of two firmer hyaluronic acid gels combined with or without a softer gel of a specific range of soft tissue fillers, for hand rejuvenation. Both treatments were effective and results were seen for up to six months after treatment.

All the subjects in both groups showed clinical improvement one and three months after treatment, and the great majority showed improvement up to six months. Aesthetic evaluations also suggest high efficacy of the product, since about 90% of the subjects showed much or very much improvement in the appearance of their hands at the end of the study as assessed by a blinded evaluator.

Subject reported outcomes also indicate treatment efficacy for both groups. More than 85% percent of subjects were still satisfied six months after treatment. Results show a slightly higher satisfaction in Group 2.

Previous studies^8-10 evaluated the safety and efficacy of soft tissue augmentation in hands with different types of HA fillers. A HA filler was shown to be more efficacious than collagen for reducing signs of intrinsic aging in hands.⁹ Similarly to our study, Brandt and colleagues also showed a six-month clinical effect of a HA filler.⁸ However, their results regard the use of a small particle HA gel alone.

Soft gels have been used for face and hand rejuvenation and, to improve skin quality.^19,20 These products are applied in the mid-dermis using a multi puncture technique. Two studies have demonstrated global aesthetic improvement of aging hands for up to one year after three monthly injections of a stabilized hyaluronic acid gel (Restylane Vital^®, Galderma S.A., Lausanne, Switzerland).^19,20 Both studies assessed the effects of this product used alone. In the present study, we observed that the HA softer gel combined with the firmer HA fillers resulted in no additional improvement in hand appearance.

Subjects reported high satisfaction with both treatments in the present study up to six months after treatment. Long-term subject satisfaction is commonly observed with the use of HA-based fillers for facial or hand rejuvenation.^{8,12,13,19-21} Since hyaluronic acid fillers are expected to last up to 12 months,^22-24 probably the patients could be satisfied with the results after the 6-month follow up period.

All the subjects received lidocaine-containing gels. Mild pain was observed for both groups at the moment of the injections in the treatment and also touch-up procedures, as expected with lidocaine HA fillers,^25-28 since the anesthetic effects take a few minutes to occur. Products showed a good safety profile. Only transient procedure-related adverse events at the injection site were seen, such as hematoma, nodules, edema, pruritus and erythema. These adverse events may be expected after treatment with HA-based soft tissue fillers^{12,13,19,20,29}, and all disappeared during the study. As expected, there were more AEs related to the injection procedures in Group 1, since more injections were done in this group.

This is an exploratory study, thus there was no calculation to define the sample size. Nevertheless, results can show aesthetic improvement of aging hands for both groups compared to baseline.

 

CONCLUSIONS

The present results demonstrate that the HA fillers used in this study are safe and efficient for rejuvenation of aging hands. Patients of both groups, either receiving additionally the softer gel or not, had improvement in the visual aspect of the aging hands. Emervel^® fillers provide physicians with another possible option for this increasingly popular cosmetic treatment, but more studies could be developed to evaluate the efficacy and safety profile of these products.

 

DECLARATION OF PARTICIPATION:

Doris Hexsel

Data collection, manuscript writing and final review

Taciana Dal’Forno Dini

Manuscript writing and final review

Juliana Schilling de Souza

Data collection and manuscript writing

Carolina Siega

Data collection and analysis, manuscript writing and final review

 

REFERENCES

1. Jakubietz RG, Kloss DF, Gruenert JG, Jakubietz MG. The ageing hand. A study to evaluate the chronological ageing process of the hand. J Plast Reconstr Aesthet Surg. 2008;61(6):681-6

2. Shamban AT. Combination hand rejuvenation procedures. Aesthet Surg J. 2009; 29(5):409-13

3. Fabi SG, Goldman MP. Hand rejuvenation: a review and our experience. Dermatol Surg. 2012;38(7 Pt 2):1112-27

4. Goldman A, Prati C, Rossato F. Hand rejuvenation using intense pulsed light. J Cutan Med Surg. 2008;12(3):107-13

5. Hexsel DM, Mazzuco R, Bohn J, Borges J, Gobbato DO. Clinical comparative study between cryotherapy and local dermabrasion for the treatment of solar lentigo on the back of the hands. Dermatol Surg. 2000;26(5):457-62

6. Hexsel D, Hexsel C, Porto MD, Siega C. Triple combination as adjuvant to cryotherapy in the treatment of solar lentigines: investigator-blinded, randomized clinical trial. J Eur Acad Dermatol Venereol. 2015;29(1):128-33

7. Butterwick K, Sadick N. Hand Rejuvenation Using a Combination Approach. Dermatol Surg. 2016;42(Suppl 2):S108-18.

8. Brandt FS, Cazzaniga A, Strangman N, Coleman J, Axford-Gatley R. Long-term effectiveness and safety of small gel particle hyaluronic acid for hand rejuvenation. Dermatol Surg. 2012;38(7 Pt 2):1128-35

9. Man J, Rao J, Goldman M. A double-blind, comparative study of nonanimal- stabilized hyaluronic acid versus human collagen for tissue augmentation of the dorsal hands. Dermatol Surg. 2008;34(8):1026-31

10. Dallara JM. A prospective, noninterventional study of the treatment of the aging hand with Juvéderm Ultra^® 3 and Juvéderm^® Hydrate. Aesthetic Plast Surg. 2012;36(4):949-54

11. Kablik J, Monheit GD, Yu L, Chang G, Gershkovich J. Comparative physical properties of hyaluronic acid dermal fillers. Dermatol Surg. 2009;35 (Suppl 1):302-12

12. Rzany B, Cartier H, Kestemont P, Trevidic P, Sattler G, Kerrouche N, et al. Full-face rejuvenation using a range of hyaluronic acid fillers: efficacy, safety, and patient satisfaction over 6 months. Dermatol Surg. 2012;38(7 Pt 2):1153-61

13. Rzany B, Bayerl C, Bodokh I, Boineau D, Dirschka T, Queille-Roussel C, et al. Efficacy and safety of a new hyaluronic acid dermal filler in the treatment of moderate nasolabial folds: 6-month interim results of a randomized, evaluator-blinded, intra-individual comparison study. J Cosmet Laser Ther. 2011;13(3):107-12

14. Segura S, Anthonioz L, Fuchez F, Herbage B. A complete range of hyaluronic acid filler with distinctive physical properties specifically designed for optimal tissue adaptations. J Drugs Dermatol. 2012;11(1 Suppl):s5-8

15. Farhi D, Trevidic P, Kestemont P, Boineau D, Cartier H, Bodokh I, et al. The Emervel French survey: a prospective real-practice descriptive study of 1,822 patients treated for facial rejuvenation with a new hyaluronic acid filler. J Drugs Dermatol. 2013;12(5):e88-93

16. Carruthers C, Carruthers J, Hardas B, Kaur M, Goertelmeyer R, Jones D, et al. A validated hand grading scale. Dermatol Surg. 2008;34(Suppl 2):179-83

17. Narins RS, Brandt F, Leyden J, Lorenc ZP, Rubin M, Smith S. A randomized, double-blind multicenter comparison of the efficacy and tolerability of Perlane vs. Zyplast for the correction de nasolabial folds. Dermatol Surg. 2003;29(6):588-95

18. Jensen MP, Chen C, Brugger AM. Interpretation of visual analog scale ratings and change scores: a reanalysis of two clinical trials of postoperative pain. J Pain 2003;4(7):407-14

19. Gubanova EI, Starovatova PA, Rodina MY. 12-month effects of stabilized hyaluronic acid gel compared with saline for rejuvenation of aging hands. J Drugs Dermatol. 2015;14(3):288-98

20. Streker M, Reuther T, Krueger N, Kerscher M. Stabilized hyaluronic acid- based gel of non-animal origin for skin rejuvenation: face, hand, and décolletage. J Drugs Dermatol. 2013;12(9):990-4

21. Bae JM, Lee DW. Three-dimensional remodeling of young Asian women's faces using 20-mg/ml smooth, highly cohesive, viscous hyaluronic acid fillers: a retrospective study of 320 patients. Dermatol Surg. 2013;39(9):1370-5

22. Weiss RA, Moradi A, Bank D, Few J, Joseph J, Dover J, et al. Effectiveness and Safety of Large Gel Particle Hyaluronic Acid With Lidocaine for Correction of Midface Volume Deficit or Contour Deficiency. Dermatol Surg. 2016;42(6):699-709.

23. Glaser DA, Kenkel JM, Paradkar-Mitragotri D, Murphy DK, Romagnano L, Drinkwater A. Duration of effect by injection volume and facial subregion for a volumizing hyaluronic acid filler in treating midface volume deficit. Dermatol Surg. 2015;41(8):942-9.

24. Prasetyo AD, Prager W, Rubin MG, Moretti EA, Nikolis A. Hyaluronic acid fillers with cohesive polydensified matrix for soft-tissue augmentation and rejuvenation: a literature review. Clin Cosmet Investig Dermatol. 2016;9:257-80.

25. Brandt F, Bank D, Cross SL, Weiss R. A lidocaine-containing formulation of large-gel particle hyaluronic acid alleviates pain. Dermatol Surg. 2010;36 (Suppl 3):1876-85

26. Prager W, Micheels P. A prospective, comparative survey to investigate practitioners' satisfaction with a cohesive, polydensified-matrix(^®), hyaluronic acid-based filler gel with and without lidocaine for the treatment of facial wrinkles. J Cosmet Dermatol. 2015;14(2):124-9

27. Monheit GD, Campbell RM, Neugent H, Nelson CP, Prather CL, Bachtell N, et al. Reduced pain with use of proprietary hyaluronic acid with lidocaine for correction of nasolabial folds: a patient-blinded, prospective, randomized controlled trial. Dermatol Surg. 2010;36(1):94-101

28. Weinkle SH, Bank DE, Boyd CM, Gold MH, Thomas JA, Murphy DK. A multi- center, double-blind, randomized controlled study of the safety and effectiveness of Juvéderm injectable gel with and without lidocaine. J Cosmet Dermatol. 2009;8(3):205-10

29. Huang X, Liang Y, Li Q. Safety and efficacy of hyaluronic acid for the correction of nasolabial folds: a meta-analysis. Eur J Dermatol. 2013;23(5):592-9

 

This study was performed at the Centro Brasileiro de Estudos em Dermatologia - Porto Alegre (RS), Brasil.