Reprinted by permission of Blackwell from Nurnberger F, Muller G 1978 So-called cellulite: An invented disease. Journal of Dermatologic Surgery and Oncology 4:221.

Figure 8.2 Structured patterns of the fibrous septae network according to sex and presence of cellulite. Our quantitative findings give more evidence about the heterogeneity in the directions of the septae, and highly suggest that modeling the 3D architecture of fibrous septae as a perpendicular pattern in women but tilted at 45 degrees in men would be an oversimplification.

Reprinted by permission of Blackwell from Querleux B, Cornillon C, Jolivet O, Bittoun J 2002 Anatomy and physiology of subcutaneous adipose tissue by in vivo magnetic resonance imaging and spectroscopy: relationships with sex and presence of cellulite. Skin Research and Technology 8:118-124.

Figure 8.3 Visualization of the 3D architecture of fibrous septae in subcutaneous adipose tissue: (A) woman with cellulite, (B) normal woman, and (C) man.

Figure 8.4 Color sonographs of the thigh of an affected woman, an unaffected woman, and an unaffected man. Note the extrusion of adipose tissue into the dermis of the affected individual.

Reprinted by permission of Pierard-Franchiemont C, Pierand GE, Henry F, et al 2000 A randomized, placebo controlled trial of topical retinal in the treatment of cellulite. American Journal of Clinical Dermatology 1:369-374.

It is less well established whether excess adipose tissue contributes to the appearance of cellulite. There are many thin females who have the appearance of cellulite on their bodies, whereas some heavier females may display only a subtle appearance of any cellulite. It is likely that excess adipose tissue may predispose or exacerbate the cellulite, but it is less likely that excess adipose tissue alone is a driving factor. We believe that excess fatty tissue and cellulite should be considered as two distinct entities, and that they should be evaluated and treated as such.

Evaluation of fatty tissue and cellulite

Body mass index (BMI = person’s weight in kilograms divided by the square of their height in meters), remains the classic method for determining obesity. However, this may be an over-simplification, as it does not necessarily take into account the patient’s mixture of muscle and adipose tissue or their overall body type. Furthermore, many patients presenting for non-invasive body sculpting may be in very good shape overall with only a few small problem areas such as the thighs or flanks. Although BMI may be a useful tool for defining obesity in large populations, we do not find it particularly useful in our practice. More commonly, we utilize measurements such as thigh circumference, waist circumference, skinfold thickness, visual assessment, and photographic comparisons pre- and post-procedure in our practice, as these more typically reflect the patient’s ultimate clinical presentation and outcome.

Pearl 2

BMI is a simple tool to assess overall body habitus. However, BMI is often not the best method to assess localized areas of fat excess and is not often used in our clinical assessments. Furthermore, obese patients (BMI > 30) are often not good candidates for non-invasive body contouring and may require diet, bariatric, or other surgical interventions.

Cellulite can similarly be assessed with various measurements and definitions. Typically, direct observation with side lighting is the simplest and most effective assessment. Based upon these observations, a relatively simple scoring system for the appearance of cellulite has been described (Table 8.1).

Table 8.1 Cellulite classification

Grade I	No or minimal skin irregularity upon standing, pinch test, or muscle contraction
Grade II	No or minimal skin irregularity upon standing. Dimpling becomes apparent by pinching or muscle contraction
Grade III	Classic skin dimpling at rest with palpable, small subcutaneous nodularities
Grade IV	More severe puckering and nodularity

More recently, technologies such as ultrasound, MRI, and electrical conductivity have been utilized to assess adipose tissue and cellulite. These technologies are often employed in clinical trials in order to assess the potential efficacy of a novel therapeutic option. However, they are typically not necessary in the evaluation and management of patients’ in general practice.

Therapeutic options

There are many different technologies and techniques for non-invasive body sculpting. Options include: topical creams, injectable agents, physical manipulation, lasers and light sources, and cryolipolysis. The best option for your patient is dependent on their clinical presentation, treatment goal, and most importantly, their preferences. It is important to emphasize that none of these treatments provides more than a modest, local contouring benefit in most instances.

Topical creams

A simple trip to any cosmetic aisle or beauty store demonstrates that there are numerous topical creams that purport to melt away fat and cellulite. Generally speaking, the active ingredients in these products are thought to stimulate improved circulation, improve lymphatic drainage, or cause lipolysis to improve the appearance of fat and cellulite. Unfortunately, many of these agents have little or no evidence to support their claims.

Pearl 3

Many topical creams are advertised to improve the appearance of fat and cellulite. These claims, in our view, should be regarded skeptically.

Topical retinol compounds have long been a mainstay in cosmetic regimens owing to their ability to stimulate neocollagenosis. Topical retinoids could theoretically improve the appearance of cellulite by increasing collagen deposition and promoting glycosaminoglycan synthesis, thereby resulting in stronger and denser fibrous septae. In clinical studies, the results have been modest. Kligman et al conducted a double-blind study of 20 patients who applied topical retinol twice daily for 6 months, and demonstrated a clinical improvement. A further study of 15 patients by Pierard-Franchimont et al demonstrated a phenotypic shift of connective tissue cells, but no visible improvement in overt cellulite appearance following 6 months of application of topical retinol. Thus, although topical retinoids may be of benefit in improving the appearance of fat and cellulite, this benefit is likely modest at best.

Methylxanthines, such as aminophylline, have also been reported to be effective in treating cellulite. These agents act as phosphodiesterase inhibitors, which, when applied, result in an increase in cyclic adenosine monophosphate (cAMP) levels. This increase in cAMP could theoretically activate hormone-sensitive lipase and thereby stimulate lipolysis in the treated areas. Although there were some initial promising results, other studies have failed to document substantial clinical improvements in the appearance of fat and cellulite.

Numerous herbal therapies have also been reported to be effective in treating fat and cellulite (Table 8.2). Many of these herbal supplements have not undergone rigorous testing to determine their efficacy, and their clinical utility remains to be fully elucidated.

Table 8.2 Herbal treatments for cellulite

Injectable agents

Many different agents have been injected with the goal of dissolving excess adipose tissue and cellulite. Mesotherapy, or intradermotherapy, is performed by the direct injection of pharmacologic agents into the dermal–subcutaneous junction of the skin. This procedure is purported to work by acting directly on the adipocyte to promote lipolysis or adipolysis, and thereby improve the appearance of fat and cellulite. Closely related, but separate, is a technique known as injectable lipolysis, in which detergents like bile salts (i.e. sodium deoxycholate) are injected into the subcutis to chemically ablate adipose tissue. Although some of these injectibles are currently being developed, none is currently cleared by the FDA and a full discussion of these emerging techniques and agents is beyond the scope of this chapter.

Physical manipulation

Endermologie^® (LPG Systems, Valence, France) is an FDA-cleared device that massages and kneads the skin to improve the appearance of cellulite. The device utilizes two rollers, as well as positive and negative pressure, to manipulate the patient’s skin. The technique is thought to stimulate blood and lymphatic flow, thereby altering the architecture of the fat and improving the appearance of cellulite. In clinical studies, modest clinical improvements have been observed. A study by Gulec, of 33 women who were treated with Endermologie^® for 15 sessions, demonstrated a statistically significant improvement in the appearance of cellulite as assessed by a visual scale; however, few of the patients (5 of the 33) actually demonstrated clinical improvement. A study by Collis et al compared twice weekly treatment with Endermologie^® to a combination treatment of aminophylline cream and Endermologie^®. The authors concluded that Endermologie^® is not an effective treatment of cellulite, although 10 out of 35 patients with Endermologie^®-treated legs reported that their cellulite appearance improved. In summary, Endermologie^® may result in modest improvements in the appearance of fat and cellulite in some patients, though it likely requires continuing treatments to maintain any improvement. Home therapy units, such as Well Box^®, are available to facilitate ongoing convenient treatment, and may be of benefit to patients.

Pearl 4

Physical manipulation, such as Endermologie^®, may result in modest temporary improvement in the appearance of cellulite, but the results are transient and often require ongoing treatments. At-home units may be a convenient and effective option for patients.

Subcision is a relatively simple technique to attempt to improve the appearance of cellulite. A special notched catheter needle is placed into the subcutis of the affected area. The catheter is then physically manipulated by pushing and pulling, in order to break up the fibrous stranding and tethers that are thought to be responsible for the appearance of cellulite. By destroying these fascial tethers, the appearance of cellulite is thought to improve. Side effects such as ecchymosis and edema are common. The clinical utility of this method likely varies depending on the skill of the surgeon, and its clinical utility remains to be fully determined.

Liposuction remains the gold standard treatment for physical removal of excess adipose tissue. A full discussion of liposuction techniques is beyond the scope of this discussion. It is important to note, however, that liposuction’s role in the treatment of cellulite is not well established. There are reports of liposuction improving, as well as worsening, the appearance of cellulite. Given the architectural component of cellulite physiology, it is not unexpected that bulk fat removal alone would not improve its appearance.

Pearl 5

Liposuction is the gold standard for large volume fat removal, but is much less reliable for small, localized fat excess. Liposuction is best in patients with >1 inch (25 mm) of pinched skin and fat on exam. Liposuction is also less reliable for the treatment of cellulite.

Case Study 1

A female patient presents to discuss non-invasive fat treatment options. She is 35 years old, weighs 185 pounds (84 kg) and is 5′4″ (1.63 m) tall. She has also developed early onset type II diabetes. She has previously tried to lose weight with diet and exercise, but has been previously unsuccessful. She was recently evaluated by her PCP, who encouraged her to lose weight to improve her diabetes and overall health. She presents to your office, as she would like a procedure to treat her excess adipose tissue.

This patient has a common misconception that non-invasive fat treatment can substitute for large-scale weight loss. This patient’s BMI is 31.8, which defines her as obese. Furthermore, she already has a medical comorbidity, diabetes, associated with her obesity. This patient absolutely needs help losing weight and improving her medical health, particularly since she has tried and failed previous weight loss strategies. She should be referred to a bariatric weight loss program in order to help her achieve her goals of weight loss.

If she is interested in a procedure to help improve her chances of successfully losing weight, this patient may be a good candidate for laparoscopic banding, partial gastrectomy, or gastric bypass. Once the patient has lost weight and is closer to her ideal weight, if she continues to have focal trouble spots of excess fat, she may benefit from a non-invasive body sculpting procedure at that time.

Radiofrequency devices

Radiofrequency (RF) devices pass sinusoidal, alternating current (AC) through tissue to generate heat. The AC causes ionic flow in the treatment tissue, thereby creating heat from molecular friction. In essence, the tissue itself is the source of the heat, rather than the actual device. As a result, RF is thought to cause localized heating of a targeted tissue mass, while limiting the potential for collateral spread of energy, neuromuscular reaction, or electrolysis. Adipose tissue has high tissue resistance and a relatively low heat transfer coefficient; as a result, adipose tissue can be readily heated and the heat will be predominantly confined to the adipocytes. Recently, many RF devices have been advertised to improve the appearance of fat and cellulite.

The VelaSmooth^® and VelaShape^® (Syneron Medical Ltd, Irvine, CA) devices combine physical manipulation (massage and suction), with bipolar RF energy and infrared light (700–2000 nm) to treat excess fat and cellulite. It has been proposed that these devices improve fat and cellulite by heating the subcutaneous tissue and fat, thereby causing increased localized blood flow and lipolysis. In a randomized clinical study by Nootheti et al, comparing the VelaSmooth^® device with another laser device for cellulite (TriActive^®, Cynosure Inc., Westford, MA), patients were treated twice weekly for 6 weeks. Following the treatments, patients were observed to have an improvement in the upper and lower thigh circumference, as well as in the appearance of cellulite (Figs 8.5 and 8.6). Seventy-five percent of patients were observed to have an improvement, when comparing pre- and post-treatment photographs, but the results were modest. There were no statistically significant differences in the efficacies of the two devices. Bruising can occur following treatment with the VelaSmooth^® device, and was more common with this device than the Triactive^® device (Fig. 8.7).

Figure 8.5 A 47-year-old woman (A) before, and (B) after six treatments with the VelaShape^® device.

Photos courtesy of Neil S. Sadick, MD. Reprinted with permission from Sadick NS 2010 VelaSmooth and VelaShape. In Goldman MP, Hexsel D (eds) Cellulite: pathophysiology and treatment, 2nd edn. Informa Healthcare, New York, NY, p 108-114.

Figure 8.6 A 37-year-old woman (A) before, and (B) after seven treatments with the VelaShape^® device.

Photographs courtesy of Neil S. Sadick, MD. Reprinted with permission from Sadick NS 2010 VelaSmooth and VelaShape. In Goldman MP, Hexsel D (eds) Cellulite: Pathophysiology and Treatment, 2nd edn. Informa Healthcare, New York, NY, p 108-114.

Figure 8.7 Purpura after treatment with (A) Triactive^® and (B) Velasmooth^®.

Reproduced with permission from: Nootheti PK, Magpantay A, Yosowitz G, Calderon S, Goldman MP 2006 A single center, randomized, comparative, prospective clinical study to determine the efficacy of the Velasmooth system versus the Triactive system for the treatment of cellulite. Lasers in Surgery and Medicine 38:908-912.

Pearl 6

Bruising is a common side effect of laser and light source treatments for fat. Most commonly, the bruising is related to the vacuum pressure and physical manipulation of the device, rather than the actual laser.

Unipolar, volumetric RF devices with more diffuse, deep heating have also been advocated for the treatment of fat and cellulite. Goldberg et al treated 30 patients with a unipolar RF device (Accent^®, Alma Lasers US, Buffalo Grove, IL) every other week for a total of six treatment sessions. A decrease in mean leg circumference of 2.45 cm was observed, although the study was limited due to a lack of comparative controls. In general, circumference is not a good end point to assess cellulite improvement. Histological specimens did demonstrate dermal fibrosis that could explain the clinical improvement, although the results were limited. Further clinical studies are necessary to establish the potential role for these RF devices.

Ultrasound devices

Patients are typically accustomed to the diagnostic utility of ultrasound imaging devices. More recently, focused ultrasound devices have been developed to treat the subcutis and adipocytes. These devices have shown promising initial results, and long-term clinical studies are ongoing. Recently, the Liposonix^® device (Solta Medical Inc., Hayward, CA) was FDA cleared for non-invasive waist circumference reduction. Additional ultrasound devices are currently being evaluated for possible FDA clearance.

A study by Jewell et al of the Liposonix^® device (Solta Medical Inc., Hayward, CA) documented significant improvement following a single treatment session. One hundred and eighty patients were randomized to either a sham treatment or one of two doses of high intensity focused ultrasound. Twelve weeks after the ultrasound treatment, the patients treated with the higher dose had achieved a statistically significant improvement in waist circumference compared with the sham group (−2.44 cm versus −1.43 cm). Patients were observed to have ‘improved’ or ‘much improved’ outcomes as assessed by physicians, and patients were satisfied with their treatments. The procedure is often painful, and bruising and edema develop after treatments. However, no significant laboratory abnormalities were observed following treatment, including: lipid profiles, markers of inflammation, coagulation, liver or renal function, hematologic assessments, or blood chemistry.

The Ultrashape Contour I^® (Ultrashape Ltd, Tel Aviv, Israel) is being used in Europe and the United Kingdom for the treatment of excess adipose tissue. At the time of writing, the Ultrashape I^® Contour device was not FDA cleared. A prospective, non-randomized, controlled trial of 164 patients was conducted by Teitelbaum et al to determine the efficacy of the device; 137 patients underwent one ultrasound treatment to the abdomen, thighs, or flanks; 12 weeks later, mean circumference reductions of 2.3 cm (abdomen), 1.8 cm (thighs), and 1.6 cm (flanks) were observed. The majority (77%) of the improvement in circumference was noted to occur within the first 14 days following the treatment.

Ultrasound technologies represent a new and evolving area within the field of non-invasive fat treatment. Initially, many of the ultrasound technologies were incorporated into liposuction treatments, known as ultrasound-assisted liposuction (UAL). However, more recently, high-intensity focused ultrasound is being developed as a stand-alone non-invasive treatment for improving the appearance of fat and cellulite. These devices require further clinical study in order to determine their long-term efficacy and safety profile. Nevertheless, they represent an exciting and promising opportunity within this field.

Lasers and light sources

Many different light sources and lasers have been advocated as therapeutic options for fat and cellulite. Many are incorporated into liposuction procedures, known as laser-assisted liposuction (LAL); these devices, however, still require invasive liposuction. Other devices have been marketed as being effective, non-invasive therapies for fat and cellulite, though definitive objective evidence of their efficacy may be lacking. Several devices that are advertised to improve fat and cellulite do not actually affect the adipocytes themselves, but rather target the dermis in an attempt to stimulate collagen formation / remodeling. Devices with wavelengths in the near-infrared region, as well as intense pulsed light (IPL) sources, fall into this category.

The TriActive^® device (Cynosure Inc., Bedford, MA) combines deep tissue massage and suction (similar to Endermologie^®), with contact cooling and a low-intensity diode laser (808 nm). The device purports to increase lymphatic drainage, improve blood flow, and simultaneously tighten skin in the treated areas, which is thought to improve the appearance of cellulite. Patients typically are treated with the device twice weekly, with a progressive improvement following the treatments. In clinical studies, patients were noted to achieve improvement in the appearance of cellulite, as well as objective improvement in hip and thigh circumferences. Subjective improvement included reduction in the appearance of skin dimpling, improvement in the overall contour of the limb, and improvement in overall skin texture (Fig. 8.8). The treatments were well tolerated, although many patients (~20%) developed mild bruising.

Figure 8.8 Cellulite treatment with Triactive^®: subject (A) before, and (B) following 10 treatments.

Reproduced with permission from: Boyce S, Pabby A, Chuchaltkaren P, Brazzini B, Goldman MP 2005 Clinical evaluation of a device for the treatment of cellulite: Triactive. American Journal of Cosmetic Surgery 22:233-237.

The SmoothShapes^® device (Eleme Medical, Merrimack, NH) combines two different wavelengths with a massage system similar to Endermologie^®. The 915 nm diode wavelength is reported to cause liquefaction of the fat, while the 650 nm wavelength is thought to improve fat membrane permeability, thereby allowing the adipocytes to be mobilized to the interstitium. Multiple passes with the device are typically performed during a treatment session, with 2–3 sessions being performed each week for best results. In clinical studies by Lach & Kulick, the SmoothShapes^® device resulted in reduction of the thickness of the subcutaneous fat pad, as assessed by MRI. The device was well tolerated with no significant associated adverse events.

The VelaSmooth^® and VelaShape^® (Syneron Medical Ltd, Irvine, CA) devices, as discussed previously, combine physical manipulation with radiofrequency energy, as well as infrared energy, to facilitate a multimodality approach to fat and cellulite treatment. The efficacy of these devices was previously discussed in the above section on radiofrequency. In the future, more devices may approach fat and cellulite treatment through this multimodality approach in an effort to achieve greater efficacy.

Fat-specific lasers are also being studied, which would selectively target adipocytes themselves rather than modulating the fascia or dermis. Wavelengths such as 1210 nm and 1720 nm are intriguing, given the relative absorption peaks of lipids in these regions. At the present time, however, no commercial laser device that selectively targets fat via selective photothermolysis has been FDA approved.

Cryolipolysis

CoolSculpting^® (Zeltiq Aesthetics, Pleasanton, CA) is a relatively novel FDA-cleared device for non-invasive fat reduction; it utilizes cryolipolysis technology to selectively cool fat, extracting energy, and ultimately causing apoptosis. The treatment consists of applying a treatment applicator to the patient’s desired treatment area, typically the flank ‘love handle’, the back ‘back fat pads’ or the abdomen ‘muffin top’. A moderate vacuum is then created by the device, drawing the tissue between the treatment plates and clamping down on local cutaneous blood flow to increase the efficiency of cooling. The treatment cycle lasts up to 60 minutes per cycle, at the conclusion of which the skin appears cool, firm, and erythematous. The tissue is typically molded into the shape of the treatment applicator. At the conclusion of the treatment, the physician massages the area gently to break up any crystallized adipocytes. Over the next several weeks to months, the adipocytes are mobilized and eliminated by the body.

Case Study 2

A 53-year-old female, who is 5′6″ (1.68 m) tall and weighs 145 pounds (66 kg), presents for treatment of small pockets of excess fat around her abdomen. She would like to discuss non-invasive treatment options, as she is concerned about the risks of invasive surgery.

This patient’s BMI is 23.4, which is within the normal range. She does have localized pockets of excess adipose tissue below the umbilicus, without substantial skin redundancy. This patient could be a good candidate for localized, tumescent liposuction, if she desired. However, she states she does not want an invasive procedure. After discussing options, she elects to have the area treated with CoolSculpting^®. The proposed treatment area is marked (a separate, but representative patient is shown in Fig. 8.9A). Due to the size, two applications in the same treatment session will be necessary to treat the complete area, each marked with an X (Fig. 8.9B). A pinch test is performed to insure that the area can be effectively elevated in the device (Fig. 8.9C). The patient undergoes treatment with no adverse effects.

Figure 8.9 A female patient presents for treatment of a localized accumulation of excess adipose tissue below the umbilicus. (A) The treatment area is outlined by the treating physician. (B) The treating physician then compares the size of the treatment applicator with the planned treatment area. In this case, given the size of the planned treatment area, two treatment applications will be necessary to treat the entire area. The center of each treatment area is marked with an X. (C) A pinch test is performed on the area prior to the treatment to insure that the area can be effectively elevated in the device. (D) A baseline photograph of the treatment area is taken prior to the patient’s cryolipolysis treatment. (E) The patient is shown 16 weeks after a single cryolipolysis treatment to the abdomen. Note the significant improvement in the appearance of the thickness of the fat pad.

Photos (A–C) courtesy of Zeltiq Inc., Pleasanton, CA. Photos (D) and (E) courtesy of Dr Flor Mayoral, Coral Gables, FL and Zeltiq Inc., Pleasanton, CA, USA.

It is important to remind the patient that the full effect of the treatment will not be visible for 2–3 months. In the post-procedure photo, taken 16 weeks after the patient’s single cryolipolysis treatment session, a noticeable reduction in the volume and appearance of the abdominal fat ‘muffin top’ is clearly observable (Fig. 8.9D, E).

In a recent clinical study, a significant reduction in the thickness of the fat in the treatment area was observed following a single CoolSculpting^® treatment (mean fat pad thickness reduction of 22.4%, as measured on high-resolution ultrasound). Of the 32 patients in the study, all had achieved a significant visible contour improvement following a single treatment. The best results were in patients with localized, discrete fat bulges. Another study demonstrated that 79% of patients reported clinical improvement in the appearance of their abdominal fat 2–4 months following a single CoolSculpting^® treatment. In these studies, the treatment was well tolerated. Patients may bruise following the procedure, likely due to the vacuum effect of the device. Many patients develop transient altered sensation, numbness or even sharp pain in the treatment area, lasting up to 2 weeks. In rare instances, the pain is sufficient to warrant treatment with pain medications. No significant changes in lipid profiles or liver function tests following cryolipolysis have been demonstrated in either the initial animal studies or human clinical studies. There is a cost for each treatment cycle for the treating physician (i.e. disposable). Finally, no cases of scarring or ulceration of the skin have been reported to date.

Pearl 7

Following a CoolSculpting^® treatment, gentle massage of the treated area should be performed to break up crystallized adipocytes and improve the efficacy of the treatment.

Cryolipolysis represents a novel, non-invasive treatment option for fat. Patients can undergo a safe, effective, and simple procedure, which will gradually reduce the appearance of unwanted fat over the following 2–4 months. It should be noted that the device works best for localized, discrete fat bulges and is not intended for the treatment of obesity or as a substitute for large-volume liposuction.