Prof. Dr. Uwe Paasch Department of Dermatology, Venereology and Allergy, University of Leipzig Ph.-Rosenthal-Strasse 23-25 D-04103 Leipzig, Germany Tel.: +49-341-9718619 Fax: +49-341-9718611 E-mail: email@example.com
Treatment of sun-damaged skin and wrinkles is attracting increasing interest as the possible approaches expand. Recently mono- und bipolar radiofrequency devices have been introduced as new treatment options for skin rejuvenation. Initial studies have demonstrated changes in collagen content of the skin as the molecular basis of skin texture improvement. However, there are many possible risks and side effects. We describe a patient referred to us with severe facial scarring as a result of a bipolar radiofrequency treatment performed by non-medical personnel. Due to the risk of permanent tissue damage, the indications for radiofrequency interventions should be made carefully. Potential contraindications should be considered and written informed consent about all possible side effects and risk factors should be obtained. According to current knowledge, the experience of the physician using radiofrequency devices is most important in determining the outcome of this procedure. Therefore the use of radiofrequency therapy requires extensive training.
With increasing life expectancy of humans with improved general health status, signs of aging on the skin gain importance for individual well-being. Wrinkles are the dominant characteristic of aged skin and the target of new intervention strategies that aim at regaining a younger appearance and are often termed “skin rejuvenation”, “skin resurfacing” or “skin subsurfacing”.
At present numerous methods to treat facial wrinkles or wrinkles at other skin sites are offered (review in ). In addition to variants of classical dermabrasion, it is known that the application of heat can lead to the desired effects. It is problematic to deliver the necessary heat into the deep connective tissue while sparing the epidermis in order to guarantee an as short as possible healing time. The latest development utilizes the generation of heat in the dermis by alternating current. We are standing at the start of this development; at present very different systems in terms of design and use are available.
The first high-frequency strategies aimed at a single application with the highest possible effect. This was often associated with side effects and a few years after introduction it was evident that low-energy, repetitive treatment schemes could reduce the spectrum of side effects and the frequency of complications [2, 3]. Along with increasing knowledge on the possibilities of skin rejuvenation demands on the expertise of the therapist rose, as he is responsible for the correct selection of the appropriate method for the individual patient in order to guarantee safety, cosmetic efficacy and acceptance of the procedure.
Biophysical effects of electric current on dermal collagen
The human dermis consists to a large part of type I collagen. This collagen is formed of three polypeptide chains that are stabilized by a triple helix conformation resulting from cross-linking. Skin aging reduces among others the stability of this cross-linking resulting in wrinkles.
The use of electric high-frequency alternating current in the frequency range of 0.3–10 MHz for connective tissue tightening (radiofrequency tissue tightening) by means of heat is a further development of electrocautery used for a long time in medicine [4, 5]. Alternating currents with wavelengths in the range of radiofrequencies have already been used for various purposes in medicine: tightening of articular capsules, contouring of cartilage and bone, tumor therapy and pain therapy among many others [6–9]. Changes of collagen are primarily mediated by heat that develops by alternating current flowing through biological tissue in accordance to Ohm's law as a result of inherent resistance. Tissue resistance or impedance (impedance = apparent resistance: the resistance occurring in serial or parallel circuits of ohmic resistance and inductive and capacitive reactants in an alternating current circuit) is inversely proportional to the electrical conductivity (σ). The resulting amount of heat depends on the current density and the specific electric conductivity (σ) according to Joule's law: H=j2/σ. Heating of connective tissue by the flow of alternating current in biological tissue is a complex process that also depends on amplitude and frequency and tissue factors such as electrolyte content, water content, temperature and other factors . First heat-labile cross-links of collagen break open and transform the highly organized fiber system via a crystalline structure into a gel state . The process of denaturation has several intermediate steps and differs among species . Complete liquefaction does not occur as heat-stable bonds remain. Thermal denaturation typically occurs above 60–65 °C in dependence on duration of exposition [14, 15]. By reducing heat exposition to the range of milliseconds, temperatures of about 85 °C are necessary . The first observable clinical effect is contraction of collagen that theoretically could smooth visible superficial wrinkles. The amount of newly produced collagen is directly dependent on the intensity of heating of connective tissue [17, 18]. Heat applied for only short periods of time improves the profile of side effects, as especially the epidermis is spared.
Established in dermatology up to now are non-ablative systems that apply high-frequency alternating current. In principle electricity always flows through tissue from a point of origin to an end point and in the case of alternating current in alternating directions. Therefore, a point of entry and a point of exit are always necessary. Applicators of electric current are termed electrodes. The frequencies or wavelengths used are in the range of radio waves, which is why the term radiofrequency therapy has been established. Depending on the construction of these electrodes, uni or monopolar (monopolar radiofrequency therapy, MRF, Figure 1) is differentiated from bipolar current application (bipolar radiofrequency therapy, BRF, Figure 2) .
The energy field applied to tissue by the electrode configurations differs with respect to depth of penetration and side effects, while the basic cellular effects are identical. In a monopolar system a specially designed electrode emits while a usually large surface collecting electrode serves as the opposite pole. The advantage of this construction is a higher possible energy density on or in the vicinity of the emitting electrode paired with a greater depth of penetration . Pain is a disadvantage. Bipolar systems usually unite both electrodes in very close proximity in one applicator. Thus, the amount of energy and its distribution in tissue can be controlled better at the cost of possible penetration depth .
Monopolar radiofrequency therapy
Non-ablative medical face-lifting employing monopolar radiofrequency around 6 MHz (ThermaCoolTC, Manufacturer: Thermage Inc., Hayward, California, USA) was developed around 2000 . The system consists of a high-frequency generator, a handpiece with variable delivery devices and a cooling system module.
In 2002 this therapy method was approved by the American Food and Drug Administration (FDA) for the treatment of periorbital wrinkles (www.thermage. com), after being approved for this indication in Canada . In 2003 this method was rated as acceptable in terms of safety despite the occurrence of scars . In June 2004 finally approval for the treatment of the entire facial skin and in 2007 for the eyelids was granted by the FDA. In 2006 it was already approved in Canada for treating the skin on the trunk and limbs (www.fda.gov). With this method electric current is applied to the skin via electrodes. For better coupling and to prevent burns a special coupling gel is used. As a result of the resistance (impedance) of the skin heating and thus a directed volumetric and thus selective denaturation of the skin at a depth of 5–6 mm occurs . The system causes deep heating on the connective tissue to 65–75 °C, while only 35–45 °C are measured in the epidermis [23–25]. The cooling module reduces heat effects on the epidermis by cooling before, during and after the actual MRF therapy in order to prevent superficial burns [20, 26]. So that relatively high flows can pass through the epidermis without damage, an additional special capacitive coupling method was developed. With this a larger dermal volume can be heated per unit of time . The latter depends directly on the geometry of the applicator and allows the therapist to adapt to different anatomical regions by selecting the appropriate delivery device . Especially the punctuate focusing of the electrical field at transition sites can thus be prevented by the correct use of the applicator. The degree of superficial unwanted and desired deep heating is – in the end – determined by the amount of applied energy (duration of current flow), the size of the applicator, the quantity of superficial cooling and the tissue impedance in the treated area. The latter is again dependent on the skin thickness, the thickness of the adipose tissue below, the size and distribution as well as the density of connective tissue septa in the subcutaneous fat and the number, form, density and development of adnexal structures .
In the deep the heat spreads by convection relatively uniformly down to the adipose tissue. In fact, a selective heating of the collagenous septa occurs due to the lower impedance of connective tissue in comparison to fat . The alteration of connective tissue in the sense of tightening is mainly the result of contracture of collagen fibers as in mechanical damage [20, 30, 31]. Contracture is primarily made possible by breaking of oxygen bonds. In electron microscopy thickening of collagen fibers is observed . By application of 58–144 J/cm2 by the 1 cm2 large applicator good clinical effects on the forehead, cheeks, periorbital region, the lower chin and nape of the neck were attained [2, 3, 21, 33–35]. One-half of patients treated in this fashion were supposed to have experienced an over 50 percent improvement of the skin condition after a single application .When up to 5 applications with lower energy (83 J/cm2, 556 pulses) were performed, improvement in 84–92% was reported [32, 36]. In the nasolabial area (130 J/cm2) patients report a subjective improvement rate of 35–40% and submandibular or on the neck 30–35% (110 J/cm2) . Recently applicators sized 0.25, 1.0, 1.5 and 3 cm2 have become available . On the whole, it is expected that in two-thirds of cases an improvement of the cosmetic appearance of the patient will be determined . Subsequently remodeling of collagen is initiated with the identification of increased collagen I mRNA as seen in wound healing. Four months after treatment an increase in the number of collagen fibers was already observed . On a histological level scar formation is seen. The effects of treatment have been reported to last for up to one year [2, 21, 25, 33, 38]. On the whole, for the use of MRF a moderate and realistic improvement of the appearance of skin measured by the number and depth of wrinkles in comparison to more invasive procedures can be expected. The procedure is recommended for patients with early, mild to moderate wrinkles or for a recurrence after a lifting operation . Lifting of the eyebrows by 1–4 mm can be expected after a single MRF application in contrast to 1 cm after minimally invasive surgery [21, 25, 35, 39]. Purely photographic comparisons demonstrate a reduction in the pronouncement of wrinkles by up to 83%.
Bipolar radiofrequency therapy
A newer system (Aluma-System, Lumenis Inc., Santa Clara, California, USA) utilizes Functional Aspiration Controlled Electrothermal Stimulation (FACES; controlled electrostimulation through functional aspiration), where the skin is suctioned into the handpiece containing the electrodes by negative pressure (8–28 mmHg; in levels 1–5).
Here the skin is highly folded so that it can be fixated with direct contact between both electrodes. The aperture size of the prototype was 3 × 18 or 6 × 25 mm. The radiofrequency used was 468 kHz. It is possible to apply 2–10 Watt (set as energy level 1–5).
Single impulses with a duration of 1–6 seconds with resulting energies of 2–60 J are applied as a standard. For coupling a contact fluid is used so that the radiofrequency energy is actually converted into heat in the dermis and that the epidermis remains free of thermal damage. The combination of directly applied heat and the mechanical stress on fibrob-lasts may have positive effects on collagen neosynthesis .
Advantageous is the exactly limited skin volume to be treated with resulting lower energy demands and thus hypothetically an improved safety profile with consecutively less side effects and complications along with less potential for pain. The risk profile in principle does not differ from other uses of radiofrequency on the skin. The evaluation of the prototype was performed on test persons with the consideration of exclusion criteria: recent (6 months) oral retinoid therapy, botulinum toxin therapy, tissue augmentation, photorejuvenation, chemical peeling, mi-crodermabrasion, skin resurfacing or liftings. Also pregnant women, patients with pacemakers, with immunosuppression, keloids, collagen-vascular diseases or vascular diseases were excluded .
The treatment parameters selected were titrated according to the subjective sensations of the patients such as tingling of the skin, sensation of heat, erythema and pain . After 8 treatments at intervals of 1–2 weeks with 2–8 Watt under application of maximum negative pressure for a pulse duration of 2 seconds an improvement of elastosis was measured according to the Fitzpatrick-Goldman classification in 46 patients . An average improvement from moderate (grade II) to mild (grade I) elastosis within 6 months after treatment was observed. No improvement was observed by 15% of patients. Less than 7% of those treated were dissatisfied, more than one-half were satisfied or very satisfied with the results of therapy. The pain of the procedure was rated as mild (89%); only two percent classified pain as severe. Of the 46 patients included 16 (34.7%) experienced side effects (frequency 7.2%) usually during the first two treatments (60%). This was attributed to lack of experience with the treatment. Reported were erythema (2.4%), burns/blisters (4.5%), edema (0.9%), purpura (0.9%), crusts (0.3%) and transient hyperpigmentation (0.3%). All side effects healed without leaving permanent damage .
Combination of radiofrequency and light therapy
The systems Polaris (900 nm diode laser combined with a radio wave system) WR (wrinkle reduction), Polaris DS (hair removal), Polaris LV (vascular lesions and leg vein removal) and Aurora (IPL combined with a rediowave system) SR (skin rejuvenation), DS (hair removal) are combination devices (from Syneron Medical Ltd., Yokneam, Israel). The system Polaris WR uses bipolar radiofrequency application together with a 900 nm diode laser, while the Aurora system combines the same radiofrequency application with a flash lamp (intense pulsed light, IPL) [43, 44]. At present this company sells combinations of radiofrequency applicators and optical systems under the name eMAX™. With the ReFirme™-ST applicator (combination of infrared light and bipolar radio waves) the spectrum of combination devices was expanded (www.syneron.com). The combination of optical and radio wave therapy is supposed to have synergistic effects (ELOS: electro-optical synergy). Under the assumption that radio waves selectively spread in pre-heated areas, a reduction of the optical energy to achieve a desired effect is theoretically possible. This is possibly associated with an improved safety profile for the patient . The bipolar electrodes are applied flush to the skin in this system. With the Polaris system in more than one-half of treated patients an improvement of skin appearance by more than 50% was reported .
Side effects, risks, complications and contraindications of radiofrequency therapy
According to manufacturer information with over 300,000 patients treated world-wide with an MRF system side effects have been reported in less than 0.2% of cases (http://www.thermage.de/body_sicherheit.php?s=3&u=41, on Aug. 6, 2007). Exact statements on devices with BRF are not known. The immediate and delayed side effect profile is by all means diverse and at least in controlled studies common, i. e. in 41.9%. Reported as immediate and usually transient events were abrasions (2.3%), edema (13.9%), erythema (36.0%), hyperpigmentation (4–26%) blistering (2.3%), blanching (1.2%), purpura (1.2%), scars (3.8%) and ulcerations (2.3%) [3, 5]. In 3% of cases persistent edema that had to be treated with systemic corticoids was observed [29, 36]. Urticarial reactions , the formation of subcutaneous nodules  or hematoma  were also reported. Numbness of treated skin areas, especially along the course of nerves, always fully reversible, is also reported [2, 29, 36].
The main side effect profile in MRF centers on unpleasant sensations during treatment. These can usually be attributed to inadequate anesthesia or excessive energy application [25, 45]. In a treatment of the entire face up to 600 applications are necessary, making sufficient analgesia obligatory. In initial studies lidocaine cream in varying concentrations was used [2, 3, 34, 35, 45], but topical anesthetics and tumescence methods are not recommended by the manufacturer due to effects on tissue impedance. Therefore oral analgetics (oxycodone, hydrocodone, Toradol®) or anxiolytics – with short-term effects –(diazepam, lorazepam or alprazolam) are recommendable [2, 29, 45]. In other studies locoregional anesthesia was employed as an option [35, 36].
Risks and complications
Risks of treatment primarily consist in the formation of scars . The system BTC2000, for example, measures applied pressure of the applicator, skin temperature and current flow/ impedance in order to prevent coupling problems. When internally set limits are exceeded, the system automatically interrupts the treatment . The incidence of complications per MRF application is reported to be extraordinarily low [2, 21, 25, 33, 35, 38, 39].
In relation to the individual treated patient the observed events are in the percent range, as many individual applications are performed in each treatment session (220–720) . Inflammation of the platysma occurs especially after the application of high energies (> 115 kJ/cm2). Despite the built-in cooling system, burns of the skin are possible (about 2%, <5 mm), that according to the authors are due to uneven contact of the electrodes of the system (ThermaCool™, Thermage Inc., Hayward, USA) with the skin with resulting “arcing” of MRF energy . After use of antibiotics these areas healed without scarring.
In another study burns were observed in 17.4% of cases . In total 4.7% of patients underwent scar formation; two patients had temporary skin atrophy . All together in about 8.4% of cases negatively rated changes (scars, alterations of texture and elasticity) lasting for 6 months must be anticipated . The complication rate depends especially on the experience of the therapist . Further, the risk of thermal side effects and associated complications rises with the amount of energy applied. Measures recommended to minimize such unwanted effects are: (1) reduction of applied energy in areas close to underlying bone (cheek bone, chin, temples, forehead), (2) complete degreasing of the skin immediately before the procedure, (3) application of a sufficient quantity of coupling gel to prevent epidermal overheating, (4) uniform placing of the applicator with constant pressure to avoid uneven energy application [21, 36]. It is important to remove any metallic jewelry before the treatment, as otherwise burns and scars can very easily be induced by changes in cutaneous impedance. Changes of impedance can occur relatively easily if the electrodes are not applied in a flat fashion. Focally the transition resistance is altered and thus heat induction. As a result burns (up to 17.4%) and scars (3.48–4.65%) can develop [21, 29]. According to manufacturer information overheating of tissue can be expected in about 0.15% (150,000 applications; statements from 2005 ). Second-degree burns have been observed in 0.4% of treatments . By rule the patient must be informed about all frequent complications before therapy and this must be documented in writing.
Absolute contraindications of MRF therapy are implanted pacemakers or defibrillators as well as facial implants.
Relative contraindications are based on a possible increased risk of complications or reduced probability of a desired therapeutic result. Such circumstances always require a very careful risk-benefit balance.
Prevention of complications
Without claim of completeness, the factors listed in the following have to date been named by manufacturers, in the literature and in the selection of patients for clinical studies as relative contraindications and should definitely be considered (Table 1). According to current data, the experience of the therapist decisively determines the success of therapeutic interventions with radio waves. Therefore the use of such systems demands comprehensive physician training.
Table 1. Contraindications for radiofrequency therapy according to manufacturer instructions, the literature or to the selection of patients for clinical studies, without claim of completeness .
Dermabrasion, chemical peeling or laser skin resurfacing within the last year
Microdermabrasion within the last 3 months
Fat augmentation within the last 18 months
Therapy with collagen fillers, botulinum toxin or oral retinoids within the last 6 months
Therapy with topical retinoids even in skin care products within the last 2 weeks
Therapy with topical steroids within the last 2 months
Radiofrequency therapy within the last year
Therapy with oral steroids within the last 12 months
A history of recurrent herpes simplex should serve as an indication for preventive antiviral therapy.
Indications of increased photosensitivity, collagen-vascular disease, diabetes, cardiac insufficiency, a history of skin cancer
Active local or systemic infections
Pregnancy and nursing
Atrophic states of the skin: e. g. chronic radiation dermatitis
The induced heat might extend much deeper and injure important anatomical structures .
Little potential for new formation of collagen is to be expected.
A 40-year-old woman who had undergone bone marrow grafting 10 years previously and currently not taking any (not even immunosuppressive) medication underwent a two-time “freshen-up treatment” by a cosmetician with bipolar radiofrequency therapy (Aluma System, Lumenis Inc., Santa Clara, California, USA). The first therapy was done using energy level 2, the second followed after 3 weeks using energy level 3. While no side effects occurred after the first session, the patient noticed significant pain during the second treatment as well as a massive facial edema immediately following it. She therefore consulted her family physician, who administered corticoids i.v. and commenced to treat the already developing blisters with polylysine and panthenol ointment topically.
At the time of first presentation in our clinic two days after the second radiofrequency therapy the patient had crusts, in part purulent, in part with a fibrinous coating (Figure 3). Due to the superinfection systemic therapy with cefuroxime 250 mg t.i.d. was conducted for 7 days; topical therapy was adapted to the skin condition (dabbing with Octenisept®, later Fucidine® cream and Advantan® cream, after the crusts fell off Cicaplast® wound care cream and after disappearance of inflammation scar therapy with Dermatix® gel). Despite simultaneously begun psychological care the patient was unable to work for a total of one month due to the injuries. Eight weeks after therapy complete healing with scarring with clearly visible impressions of the electrodes was observed (Figure 4). The patient was educated in camouflage techniques.
Even though the exact cause of this event is unknown, the scarring with clearly visible impressions of the electrodes in the form of atrophic scars with hyper- and hypopigmentation suggests a possible impedance problem. This could have been caused by coupling problems due to lack of or insufficient application of gel. Other possible errors naturally cannot be excluded, e. g. a failure of the device.
With the approval of mono- and bipolar radiofrequency therapy, new possibilities to treat visible signs of skin aging are available for the dermatologist, also. First studies show a reduction in quality and quantity of wrinkles in the face and even lifting effects on the eyebrows on the basis of demonstrable molecular alterations of collagen . Nonetheless, radiofrequency treatment is associated with a relatively high rate of potential side effects. The causes of this are manifold and can include defective devices, false patient selection, errors in performing therapy, postoperative mismanagement or in an unlucky chain of such or other circumstances . Most importantly, in numerous publications the experience of the therapist is considered a significant parameter for success [7, 41]. Therefore, the use of such systems demands comprehensive physician qualification and training. As facial skin is primarily addressed and as a high level of damage is experienced in this sensitive area and the danger of permanent complications exists, the indication for therapy should be well-considered. Potential contraindications should be regarded. The patient must be informed abut all possible known risks by the physician and written consent obtained.