Expert guideline on the use of porcine collagen in aesthetic medicine

EVOLENCE® and EVOLENCE® Breeze™ are injectable fillers derived from porcine collagen. EVOLENCE® and EVOLENCE® Breeze™ had been available on the European market from 2007 to 2009. In 2009 the manufacture and marketing of EVOLENCE® products was discontinued. However the sold product is still widely available and will continue to be used in the next couple of years. These porcine products differ from bovine collagen products in being significantly less allergenic [1] and possessing longer stability after injection. A sugar molecule (ribose) is employed for cross-linking instead of a chemical stabilizer [2]. In contrast to many other injectable filler materials, controlled clinical studies on efficacy and safety of this product exist [3-5]. Further, for the treatment of lips a case series with 51 patients has been published [6]. EVOLENCE® and EVOLENCE® Breeze™ are not hyaluronic acid products. They have a different appearance and also behave differently during and after injection. In order to set standards for use a user meeting with the goal of developing an expert guideline (S1) was held at the beginning of May. The consensus meeting took place in the framework of the German STAR™ (Specialized Training for Accurate Results)-Meeting from May 8–9, 2009 in Hamburg. Participants of the STAR™-Meeting were dermatologists, plastic surgeons as well as representatives of other physician groups. Prerequisite for participation was long experience with the use of fillers (especially EVOLENCE® and EVOLENCE® Breeze™). The consented passages are indicated in italics. When not noted otherwise, strong consensus was obtained. Strong consensus required the agreement of 90 % of participants or more. The correct selection of patients determines the success of therapy. The following indications and contraindications must be observed here. The main indication for fillers is filling of mimic wrinkles and correction of volume loss of subcutaneous fatty tissue due to disease or age (Table 1). A further important indication is structural improvement of the skin in severe elastosis [7]. In the presence of strong mimic combination treatment with botulinum toxin A, in the presence of severe elastosis combination with other ablative methods of aesthetic dermatology such as mid-level or deep peeling or erbium:YAG and/or CO2 laser are recommended. An absolute contraindication is dysmorphophobia. Characteristic for this disorder is the repeated refusal to accept physician's counsel that no bodily disease is present. It appears that mental burdens and conflicts play a key role in the pathogenesis of body dysmorphic disorders. It is not always easy to diagnose patients with dysmorphophobia. Caution is advised when dealing with patients whose complaints are difficult to objectify and who have a long history with frequent change of physicians. Autoimmune disorders are contraindications as are pregnancy and nursing. When EVOLENCE® and EVOLENCE® Breeze™ are mixed with lidocaine prior to injection, allergy to lidocaine or related local anesthetics must also be excluded. A further contraindication is the administration of anticoagulants (e.g. phenprocoumon), as widespread and extensive hematomas at the injection sites cannot be ruled out. A relative contraindication is the administration of acetylsalicylic acid. Here benefit and possible side effects (hematomas) must be balanced in the individual case. An allergy to bovine collagen or intolerance of a hyaluronic acid product is not a contraindication to treatment with EVOLENCE® and EVOLENCE® Breeze™. For the greatest possible safety for the patient and the treating physician there are no arguments in such a special case against intracutaneous skin testing with the product. The patient should be provided with comprehensive written information before treatment. The patient must be informed about the nature, course, goal, consequences, side effects, alternatives and risks of the planned procedure. Even rare consequences and risks must be mentioned in the informative discussion. A discussion of expected costs is also of importance. For large substance defects the calculation should not be too economical and even in the first discussion the necessity of a follow-up injection after 2 to 6 weeks should be mentioned. Before the first treatment comprehensive information on the product and indication is recommended. Information should be in written and oral form. Before each fist treatment (and when deemed sensible later) photographic documentation should occur. Depending on the planned correction a lateral view may also be appropriate. When digital photography is used, it is recommended to use the digital image at the time of the initial discussion, as the digital image of the patient objectifies his view of himself and facilitates the discussion of aesthetic questions. Photographic documentation is recommended before each initial treatment. EVOLENCE® and EVOLENCE® Breeze™ are the only porcine collagen products available on the European market. They contain the same collagen concentration per milliliter (35 mg/ml). Modifications in the production process (cutting, filtration and homogenization) result in differing filler materials with variations in application and flow characteristics, i.e. EVOLENCE® Breeze™ has a somewhat lower viscosity. EVOLENCE® is supplied with a 27-gauge needle, EVOLENCE® Breeze™ with a 30-gauge needle. EVOLENCE® is more suitable for deep folds and volume augmentation, EVOLENCE® Breeze™ more for medium and fine wrinkles. For lip contouring primarily EVOLENCE® Breeze™ should be used. The injection can be performed in an anterograde fashion, i.e. during advancement of the needle or in a retrograde fashion during withdrawal of the needle. The injection of EVOLENCE® and EVOLENCE® Breeze™ can be performed in an anterograde or retrograde fashion. The glabella is a region that should be reserved for treatment with botulinum toxin A. In exceptional cases correction with EVOLENCE® Breeze™ can be considered for a persistent wrinkle or furrow. The injection should be into the deep dermis (i.e. not too deep) and should not exceed 0.2 ml. The goal of cheek augmentation is improved contouring of the cheek by reconstruction of the malar fat pad [8]. In order to avoid changes and irregularities in mimic activity, injection should be deep in the upper or mid subcutis. The injection can be performed from a caudal and/or lateral approach (1.1, 1.2). For cheek bone augmentation the lateral approach should be selected. Cheek augmentation. Injection of EVOLENCE® from caudal (injection by W. Prager). Cheek augmentation. Injection of EVOLENCE® from lateral (injection by W. Prager). For deep augmentation EVOLENCE® should be used. EVOLENCE® Breeze™ can be employed for superficial correction, e.g. widespread superficial defects. Depending on the degree of lipoatrophy and the desired correction 0.5 to 1.5 ml are used for each side. For deep injection the somewhat longer 26-gauge needle (Sterican® 0.45 × 25 mm BL/LB 26 G × 1”, Gr. 18, B. Braun AG, Melsungen, Germany) can be employed. In contrast to EVOLENCE® Breeze™, EVOLENCE® should not be injected too superficially in order to avoid irregular contours. In extensive filing of the face it is important to control from several sides in order to achieve uniform reconstruction. For cheek augmentation EVOLENCE® is recommended. Injection of EVOLENCE® should be into the deep subcutis or supraperiosteum. Cheek augmentation and tear trough augmentation are not identical. Tear trough is the term for an infraorbital lipoatrophy that extends from the medial canthus in a laterocaudal direction. For augmentation in this indication EVOLENCE® and EVOLENCE® Breeze™ can be used (Figure 2). Too superficial injection must definitely be avoided to prevent the material from becoming palpable or visible through the thin skin. Per side about 0.5 ml should be employed. This region should be reserved for experienced therapists. Before/after image of augmentation of the tear trough with 0.5 ml EVOLENCE® Breeze™ per side. EVOLENCE® Breeze™ is recommended for augmentation of the tear trough. Here, too, injection should be into the deep dermis, subcutis or supraperiosteum. Nasolabial folds are one of the main indications for augmentation with injectable fillers. Treatment is usually performed using the tunnel technique. The serial puncture or the fanning technique (lateral injections to fill the nasolabial folds) can be used supplementally to lift especially sunken areas in a targeted manner or to smooth the transition to untreated areas. Mostly the layering technique is used, i.e. the various fillers are layered on top of each other. Filling the nasolabial fold should be done with an orientation in the medial direction. With more lateral injection of the filler gravity can induce ptosis of the cheek giving the impression of “hamster cheeks”. In filling the nasolabial fold it is important to take the small triangle next to the ala nasi into consideration. Particularly in elastotic skin injection can be facilitated by smoothing the nasolabial folds, e.g. with thumb and index finger. Depending on the depth of the folds EVOLENCE® or EVOLENCE® Breeze™ or both products are employed. First the deeper aspects of the folds are filled with EVOLENCE® followed by a superficial layer with EVOLENCE® Breeze™. Depending on the depth of the fold between 0.5 and 1.5 ml of the collagen is injected on each side. For augmentation of nasolabial folds both EVOLENCE® and EVOLENCE® Breeze™ are recommended. It is recommended that injection be targeted slightly medial with respect to the fold. Following the nasolabial folds the upper and lower lips are anatomic regions which are preferably treated with injectable fillers [9, 10]. As both upper and lower lips are painful regions, in the majority of patients local anesthesia is performed. In principle three alternatives exist: Pretreatment with EMLA® cream or a lidocaine-tetracaine gel EMLA® cream is applied to the site to be treated. To intensify the effect the cream is covered with e.g. Tegaderm™ transparent bandage. Depending on location the foil may have to be cut to size. Sufficient time (about 45 to 60 minutes) should be allowed for therapy to be effective. For a similar pretreatment a lidocaine-tetracaine gel can be used (formula: lidocaine base 23 %, tetracaine base 3.5 %, tetracaine HCL 3.5 %, Lipo-Thene 133™ base ad 20.0). Application time here is stated as 10–20 minutes. With this preparation some colleagues waive foil occlusion. Addition of lidocaine to EVOLENCE® or EVOLENCE® Breeze™ To further reduce pain a local anesthetic can be added to EVOLENCE® or EVOLENCE® Breeze™. EVOLENCE® or EVOLENCE® Breeze™ and 0.2–0.3 ml 1 % lidocaine are mixed using an adapter (w/w 2 Braun). For this the mixture must be passed between both syringes several times to ensure a uniform mixture. Peripheral nerve blockade In order to adequately anesthesize the upper or lower lip a peripheral nerve blockade can also be performed. For this purpose e.g. Ultracain® DS 1 : 200 000 or another local anesthetic can be used. Ultracain® DS is injected with a cylinder ampule syringe (e.g. Uniject® K) and a 27-gauge needle. Depending on the indication to be treated the infraorbital nerve and/or the mental nerve are anesthesized. It must be kept in mind that the local anesthesia is accompanied by paralysis which alters facial contours. In anesthesia of the infraorbital nerve the nasolabial folds flatten, the upper lip is lengthened and upper lip wrinkles are reduced. Some colleagues therefore mark the lip wrinkles that are to be filled beforehand. The patients should be advised that the anesthesia may lead to transient asymmetry. Treatment of the lip can be subdivided into three indications: Lip wrinkles Lip volume Positioning of the angle of the mouth These sub-indications are not to be viewed solitarily, but merge with another, e.g. in the course of treatment of lip wrinkles volume improves. By improving volume, conversely lip wrinkles improve. For this indication EVOLENCE® Breeze™ should be used [6]. EVOLENCE® Breeze™ should be injected deep subcutaneously and not too superficially in the dermis, as it otherwise might appear yellowish through the mucous membranes or severely elastotic skin. Treatment with EVOLENCE® is not recommended for this indication. Care is called for in highly elastotic lips. Here volume augmentation should be performed carefully to avoid so-called “duck beak” or “trout pout” lip deformities (i.e. a massively enlarged, unnatural lip). In severely elastotic lips combination with ablative methods is recommended. For the treatment of the lip (contouring and volume augmentation) EVOLENCE® Breeze™ is recommended. Treatment with EVOLENCE® is not recommended. Lip wrinkles can be found on the upper and lower lips. In treatment of upper lip wrinkles first the edge of the vermilion border of the lip should be injected in the tunnel technique while attention is paid to the Cupid's bow. In a further step the philtrum can be contoured. Finally, radial wrinkles can be lifted. This can be performed in tunnel technique from the edge of the vermilion border of the lip or in the serial puncture technique with the individual punctures under the wrinkles being performed from laterally here. The patient should (only possible if anesthesia was achieved with a topical preparation) occasionally purse the lips so that possible irregularities can be detected and corrected immediately. The goal is to attain or restore the most natural contouring of the upper lip as possible. Treatment of the lower lip is analogous. For contouring of the edge of the vermilion border EVOLENCE® Breeze™ should be used. The injection should be made deeper than with a hyaluronic acid product. Initially, about 0.5 ml should be used. For contouring of the lips EVOLENCE® Breeze™ is recommended. It is recommended to inject EVOLENCE® Breeze™ subcutaneously and not into the dermis and thus somewhat deeper than comparable hyaluronic acid products. The goal is to increase the volume of the lip. Here the injection is performed parallel in tunnel technique either directly in the middle of the vermilion border or more to the interior side of the lip termed the wet-dry border. Alternatively, on the upper lip the injection can be performed from the vermilion border vertically upwards (Figure 3.1). Treatment of the lower lip should be performed parallel to the edge of the vermilion border (Figure 3.2). The amount per injection is about 0.1 ml EVOLENCE® Breeze™. The total amount for augmentation of the upper and lower lips is about 1–1.5 ml. In normal anatomic situations 2/3 of the total amount should be injected in the upper lip and 1/3 in the lower lip (Figure 4). Augmentation of the upper lip. Injection of EVOLENCE® Breeze™ from caudal (injection by S. Hilton). Contouring of the lower lip. Injection of EVOLENCE® Breeze™ from lateral (injection by S. Hilton). Before/after image of contouring and volume augmentation of the lips with 0.6 ml (upper lip) and 0.4 ml (lower lip) EVOLENCE® Breeze™. In lip augmentation one should not forget emphasizing the medial portion of the lip (the tuberculum). Between 0.1 and 0.2 ml EVOLENCE® Breeze™ should be injected here. Just as in reduction of upper lip wrinkles here, too, subcutaneous injection should be performed in order to avoid the material becoming visible through the mucous membrane as a yellowish deposit! For volume augmentation of the lips a subcutaneous injection of EVOLENCE® Breeze™ is recommended. On the upper lip injection can be performed in a parallel or vertical fashion. On the lower lip the parallel injection technique should be preferred. When both lip wrinkle reduction and volume augmentation are desired, this can be done in one treatment step. The injected volume in lip contouring in and of itself leads to an improvement of lip wrinkles as well as lip volume. The total amount for the first treatment should not exceed 1–1.5 ml for upper and lower lip. Sinking of the angle of the mouth can cause an unwanted sad facial expression. EVOLENCE® Breeze™ is very well-suited here to support the tissue and thus lift the angle of the mouth. For this first the caudal portion of the angle of the mouth is lifted with about 0.2 ml per side. A further 0.2 ml is injected in a fan-like fashion in the angle of the mouth (i.e. with inclusion of the upper lip). To achieve an optimal lift effect the injection should be performed into the deep dermis. Here, too, injection close to the mucous membranes should be avoided. To lift the corner of the mouth EVOLENCE® Breeze™ is recommended. To achieve an optimal lift effect the injection should be performed into the deep dermis. Marionette lines can constitute a downward continuation of the nasolabial folds. They can also present independently extending from the corner of the mouth to the chin. It is important to always treat them when the nasolabial folds are being treated. Otherwise a difference is created between the perfectly corrected nasolabial fold and the marionette lines. The treatment corresponds to the treatment of the nasolabial folds. For this indication EVOLENCE® and EVOLENCE® Breeze™ can be used (Figure 5). Usually 0.5 ml per side is sufficient. Before/after image of augmentation of the marionette lines with EVOLENCE®. For the treatment of marionette lines both EVOLENCE® and EVOLENCE® Breeze™ can be recommended. When treating nasolabial folds in the presence of distinct marionette lines co-treatment of the marionette lines should always be considered to achieve a harmonic overall appearance. To minimize irregularities after the injection of EVOLENCE® and EVOLENCE® Breeze™ manual molding of the material is recommended. This should be performed in close temporal relationship to the injection. After injection manual molding of the material is recommended to optimize results. EVOLENCE® and EVOLENCE® Breeze™ are characterized by the durability of the material. In some patients the material remains palpable over several weeks. This is tolerated well by most patients. It is important here to inform the patient of this in advance (consent form). When EVOLENCE® and EVOLENCE® Breeze™ are injected too superficially the product, especially in highly elastotic skin, can become visible as a whitish or yellowish deposit [11]. In this case an incision can be made at the affected site immediately after the injection to extrude the material. Alternatively, a puncture with a large-bore needle (e. g. 18-gauge) can be performed. This should take place soon after the injection. After about two days removal of the material by incision is difficult. If after too superficial injection of EVOLENCE® and/or EVOLENCE® Breeze™ visible deposits in the mucous membrane or skin are seen, an early small incision or puncture is recommended in order to manually stroke out material. In individual cases after a long-past injection surgical removal can be considered. Alternatively, an attempt can be made to reduce tissue by targeted glucocorticosteroid injection (e. g. Volon A® 10). Here small doses (0.05 ml per injection site) should be used to avoid fatty tissue atrophy. To reduce small superficial papules a therapy attempt with a fractional laser may be made. Good clinical data on these interventions do not exist. The meeting and the preparation of the report were sponsored by Colbar LifeScience, Johnson & Johnson GmbH (Johnson & Johnson, Platz 2, Neuss, Germany). Some authors held lectures for Johnson & Johnson GmbH. Participants of the conference were Berthold Rzany1, Said Hilton2, Welf Prager3, Vanessa Hartmann1, Gertrud Brandl4, Tanja C. Fischer5, Oliver Gekeler6, Simone Glöckner7, Gebhard Gramlich8, Melanie Hartmann9, Kathrin Lederman10, Jana Luckner-Neugebauer11, Tatjana Pavicic12, Sabine Stangl13, Torsten Walker14, Sabine Zenker15, Marianne Wolters16 1 dEBM, Department of Dermatology, Charité University Medicine Berlin, Berlin 2 Medical Skin Center, Düsseldorf 3 Dermatologikum, Hamburg 4 Dermato-Aesthetik, Munich 5 Skin and Laser Center, Potsdam 6 Medex Antiaging Center, Reutlingen 7 Office for Aesthetic Medicine, Munich 8 Private Clinic Hagenmühle GbR, Seckach-Großeicholzheim 9 Dermocosmetic Center, Hamburg 10 aesthetic plastic face surgery, Düsseldorf 11 Ambulanz Laurea, Leonberg 12 Department of Dermatology, LMU, München 13 Department of Dermatology, UKE, Hamburg 14 Office for Dermatology, Ludwigshafen 15 Office for Dermatology, Munich 16 Office for Medical Wrinkle Treatment, Frankfurt (all Germany) Completed: 15.07.2009 Revision planned: 15.07.2011 ICD 10: L57.4: Elastosis senilis and E 88.1 Lipodystrophy Level: S1 with structured consensus