Sociedade Brasileira de Dermatolodia Surgical & Cosmetic Dermatology


ISSN-e 1984-8773

Volume 3 Number 2

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Original Article

Evaluation of the duration of injectable hyaluronic acid in nasolabial folds and perioral rhytids

Avaliação da permanência do ácido hialurônico injetável no sulco nasogeniano e rítides labiais

Celia Luiza Petersen Vitello Kalil1, Ana Paula Avancini Caramori1, Mercedes Dalpias Balkey1

Received on: 22/03/2011
Approved on: 25/04/2011

This study was carried out at the Complexo
Hospitalar Santa Casa de Porto Alegre – Porto
Alegre (RS), Brazil.

Conflicts of interests: None
Financial support: None



Introdução: Hyaluronic acid has been increasingly used in aesthetic procedures. Objective: To evaluate the degree of improvement and duration of results in patients who received treatment for wrinkles with hyaluronic acid.
Methods: Prospective, open, non-randomized, non-controlled study of 20 female patients who presented superficial wrinkles in the superior lips contour and a prominent nasolabial fold. The efficacy of hyaluronic acid was assessed using the Wrinkle Severity Rating Scale. The duration of results was assessed through biopsies. Safety was evaluated through clinical observation and reports of adverse events.
Results: A significant clinical improvement was observed after 15 days, which was sustained for 4 months. A minor worsening was observed after that period, although patients still presented favorable aesthetic results up to 12 months after the procedure. A majority of patients (n = 17) had a biopsy in the left retro-auricular region 180 days after the procedure. From this group, the substance was observed in 13 slides (76.4%).
Conclusion: Hyaluronic acid is an effective and safe product. This study has proven that the product remains in the dermis for up to 6 months.



Hyaluronic acid (HA) was first described by Karl Meyer as a substance contained in the vitreous humor of cats'''''''' eyes, in 1934. A natural polysaccharide, it is part of the intercellular matrix of the dermis and can also be found in the conjunctive tissue, bones and interstitial membranes.

It is an extremely biodegradable and biocompatible sub- stance with a chemical structure that is consistent among all ani- mal species. Its invariable chemical structure decreases the risk of immunological reactions, which is an advantage when com- pared to other filling substances. Cutaneous tests are not usual- ly necessary before HA injections.

Dermatologists and plastic surgeons have used HA for cos- metic purposes since 1996, to fill wrinkles and scars, and increase the volume of lips, for example. Since then, different companies in the pharmaceutical industry have developed their own products with HA as the active ingredient.

HA is a powerful water retainer and is effective in adding volume to injected tissues. However its non-modified form has a short half-life, and is eliminated rapidly in the dermis. To be used as a filling agent to improve rhytids and scars or add vol- ume, HA should be stabilized to give it a long half-life. The sta- bilization process varies by manufacturer and brand, which explains the differences in the viscosity of HA and the duration of the effects that are found in the diverse products on the mar- ket. 1 Since HA fillings are not permanent, the procedure must be repeated at variable intervals, according to the need (a few months on average). 2

HA is currently the safest agent used in cosmetic fillers, and rarely presents adverse effects, which the physician must be aware of and inform the patient about before using the product. Most complications are not serious – primarily erythema or a burning sensation at the site of injection –and disappearances when the product is degraded. 3-5

Although the duration of the effect is limited, products containing HA are the most popular among cosmetic fillers. They produce considerably significant results and few undesir- able reactions. Physicians and patients prefer fillers containing HA due to their good tolerance, natural effect and few side effects.


To evaluate the degree of improvement in patients who received HA injections in the nasolabial fold (NLF) and in the superficial rhytids in the upper lip margin (ULM) and the dura- tion of the product in the retroauricular region.


Female patients (n = 20) from the Dermatology Outpatient Clinic of the Complexo Hospitalar Santa Casa de Porto Alegre who presented superficial wrinkles in ULM and prominent NLF were included in this prospective, open, non- randomized and non-controlled study.

Patients who were pregnant, had acute or chronic disorders that could influence the evaluation of results, presented with a personal or family history of keloids or allergy to HA, and those who had previously been treated with any type of filler in the areas to be studied were excluded.

The present study was submitted to and approved by the Research Ethics Committee of the Complexo Hospitalar Santa Casa de Porto Alegre. All patients signed a term of free and informed consent prior to the start of the treatment.

The patients were photographed in frontal and angled per- spectives, in a standardized way, on each visit with a Canon Rebel XT camera. A stereotactic device that allows the stan- dardization of the positioning of the head and focal distance was used.

The patients received an intradermal application of 0.1 ml of Perfectha Derm® (Comedix Com Produtos Médicos e Farmacêuticos, Brazil) in the right and left retroauricular regions. In order to evaluate allergic reactions and to proceed the subsequent histological examination, the product injected behind the ears belonged to the same batch as the material involved in the study. The histological examination aimed to detect granulomas and verify the product''''''''s duration. Later on, the patients were given injections of Perfectha Derm® in the superficial rhytids of the ULM or in the NLF. The treatment''''''''s objective was to completely correct the rhytids, while avoiding overcorrection.

The sites to be treated were swabbed with chlorhexidine before each application. The patients who had HA treatment in the NLF received topical 4% lidocaine cream (Dermomax® Laboratório Ache, São Paulo, Brazil) before the procedure. The patients who received HA in the ULM had a regional block of the infraorbital nerves with 2% lidocaine, without vasoconstric- tor. The HA was injected in the NLF and the ULM with 27G and 30G needles, respectively. The treated sites were massaged immediately after the injection. The HA was injected in the medium-deep dermis using the retroinjection technique, with the needle''''''''s bevel preferentially turned upward, according to the manufacturer''''''''s recommendation.

The HA''''''''s efficacy was assessed independently by two inves- tigators at 15, 30, 60, 90, 120, 180 and 360 days after treatment, following a clinical evaluation and analysis of pictures. The sever- ity of the wrinkles was scored according to the previously validat- ed Wrinkle Severity Rating Scale (WSRS) 6, 7 (Table 1 and 2) .

The biopsy of the right and left retroauricular regions was also carried out at 30 and 180 days after the procedure, respec- tively. Before the biopsies, those areas were anesthetized with 2% lidocaine without vasoconstrictor and a 2mm punch. The mate- rial that was obtained underwent histological evaluation. Adverse effects and severity level were appropriately reported.


Female patients (n = 20) aged 35-49 (average age 43) were included in the study. Eleven (55%) had treatment of the NLF, and nine (45%) received treatment of the ULM. Five patients (four from the NLF group and one from the ULM group did not complete the protocol, and were therefore excluded. The volume of HA injected in each NLF varied from 1.6 to 2.3 ml (average 2 ml). In the ULM, it ranged from 1.1 to 1.7 ml (aver- age 1.5 ml).

A significant degree of clinical improvement was observed after 15 days, which remained stable for approximately four months. Although a minor worsening was observed after that period, the patients presented favorable aesthetic results that last- ed up to 12 months (Graph 1).


Eighteen patients had a biopsy in the right retroauricular region on the 30th day after the procedure. The analysis of the material, carried out by an experienced pathologist, demonstrat- ed deposits of HA on 13 slides (72.2%).

The rest of the patients (n = 17) had a biopsy in the left retroauricular region 180 days after the procedure. In that group, deposited material was observed on 13 slides (76.4%) (Figure 1). The formation of foreign body granulomas was not observed in any case.

Adverse effects associated with HA and the procedure itself included ecchymoses, edema, erythema and local pain. These findings were of mild to moderate intensity, with a duration of a few days. Only one patient who received filling of the NLF presented the formation of a nodule around 30 days after the application of the product; the nodule disappeared after 15 days of massage with medium potency corticoid.


The results of this study confirm the efficacy of HA in the correction of NLF and ULM, proving it is a well tolerated treat- ment. The positive clinical improvement persisted for more than six months in most of the cases. Such results are in line with those obtained by Beer 8 and Carruthers and others 9 in previous studies. An interesting fact was the observation of intact materi- al in the biopsies carried out in the left retroauricular region, proving that the product can remain in the dermis for up to six months.

The absence of deposited material in some slides can be explained by the fact that the material was obtained using superficial biopsies. The material was most likely present but was not captured due to insufficient depth in the collection pro- cedure.

The durability of the product in the skin depends on the rate of degradation of the substance, the structure of the parti- cle of the HA used and its concentration. Maintaining the treat- ment effect also depends on the texture of the skin, the type and severity of the problem to be corrected, the patient''''''''s age and the technique employed. The site to be treated is also an important factor, for areas that move more frequently tend to present less durable results.

The data reinforce that the use of HA produces good results in the correction of the nasolabial fold and labial rhytids.


As demonstrated in other studies, HA is a safe and effective product to be used in the treatment of NLF and ULM. It was proven, through cutaneous biopsies, that the product remains in the dermis for a period of up to six months.


We would like to thank our dear friend, the late Dr. Jorge Zanol, for his help in analyzing the material in the pathological study.


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