ArticlePDF AvailableLiterature Review

Treatment for cellulite

October 2018
International Journal of Women’s Dermatology 5(1)

DOI:10.1016/j.ijwd.2018.09.002

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CC BY-NC-ND 4.0

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Cellulite is a multifactorial condition that is present in 80% to 90% of postpubertal women and is one of the most intolerable esthetic imperfections. There are several theories on the pathophysiology of cellulite, and a number of different therapeutic regimens have been developed, from topical treatments to mechanical or energy-based devices. In this brief review, we summarize the scientific landscape to determine the clinical evidence with regard to the safety and efficacy of cellulite treatment options. Clinical protocols and the author's experience using a combination of internal and external procedures are also discussed. Studies using laser and light modalities along with radiofrequency have shown improvements in cellulite and a good safety profile, but acoustic wave therapy, subcision, and the 1440-nm Nd:YAG minimally invasive laser have demonstrated the most beneficial results in cellulite reduction. Although there is paucity of scientific evidence for treatments that improve cellulite, future emerging options and their combination may pave the way to eradicate this primarily cosmetic esthetic concern.

Before (left) and after (right) seven treatments in the outer thigh with Venus Legacy (Venus concept, Toronto, Ontario, Canada).

…

Before (left) and after (right) one treatment in the buttocks with 1440 nm Cellulaze (photograph courtesy of Cynosure).

…

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Available via license: CC BY-NC-ND 4.0

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Treatment for cellulite

Neil Sadick, MD ⁎

Department of Dermatology, Weill Cornell Medical College, New York, New York

Sadick Dermatology, New York, New York

abstractarticle info

Article history:

Received 14 June 2018

Received in revised form 10 September 2018

Accepted 11 September 2018

Keywords:

Cellulite

pathophysiology

adipocytes

radiofrequency

lasers

Cellulite is a multifactorial condition that is present in 80% to 90% of postpubertal women and is one of the

most intolerable esthetic imperfections. Thereare several theories on thepathophysiologyof cellulite, and a

number of different therapeutic regimens have been developed, from topical treatments to mechanical or

energy-based devices. In this brief review, we summarize the scientiﬁc landscape to determine the clinical

evidence with regard tothe safety and efﬁcacy of cellulite treatment options.Clinical protocols and the au-

thor’s experience using a combination of internal and external procedures are also discussed. Studies using

laser and light modalities along with radiofrequency have shown improvements in cellulite and a good

safety proﬁle, but acoustic wave therapy, subcision, and the 1440-nm Nd:YAG minimally invasive laser

have demonstrated the most beneﬁcial results in cellulite reduction. Although there is paucity of scientiﬁc

evidence for treatments that improve cellulite, future emerging options and their combination may pave

the way to eradicate this primarily cosmetic esthetic concern.

BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Cellulite is a skin condition that affects up to 80% of postpubertal

women (Luebberding et al., 2015). Cellulite is different from general-

ized obesity because with obesity, adipocytes undergo hypertrophy

and hyperplasia; cellulite is characterized by large, metabolically sta-

ble adipocytes that are limited to lower body areas (e.g., pelvis,

thighs, and abdomen; Quatresooz et al., 2006). Also known as edem-

atous ﬁbrosclerotic panniculopathy, cellulite was ﬁrst described by

Alquin and Pavot in 1920 and originally thought to be “interstitial

edema associated with an increase in fat content.”

The phenotype of this condition is distinct, with the skin topogra-

phy changing to a surface that resembles an orange peel. This is due

to the herniation of subcutaneous fat lobules through the

dermohypodermal junction, where ﬁbrosis of the collagen septa

leads to their shortening and ultimatelytheir retraction,which causes

the depressions that characterize cellulite. Although several factors

are known to contribute to the development of cellulite (sex, genet-

ics, lifestyle; Querleux, 2004; Querleux et al., 2002), the exact patho-

physiology is not understood. The most prevalent models that have

been proposed span from vascular/inﬂammatory to hormonal and/

or structural causes.

Understanding the etiology of cellulite is key to developing targeted

approaches, and a plethora of options is available to dermatologists

to offer to their patients with cellulite. Topical agents, energy-based

devices, subcision,injectable biologic medications, and more recently

dermal ﬁllers have all been used and studied in peer-reviewed publi-

cations for their safety and efﬁcacy to treat cellulite (Table 1).

Topical agents

Topical agents, combined with vigorous massage, were the earli-

est attempts to treat cellulite. As with all topical treatments, the

main challenge of these therapies is for the active ingredients to

reach their target in sufﬁcient concentration to have a therapeutic ef-

fect. Methylxanthines (aminophylline, theophylline, and caffeine)

and retinoids have been the most extensively evaluated ingredients

used in topical formulations for cellulite.

Methylxanthines are hypothesized to improve cellulite by stimu-

lating lipolysis and inhibiting the enzyme phosphodiesterase, which

increases the concentration of cyclic adenosine monophosphate. Ret-

inoids, on the other hand, are thought to reduce cellulite by increas-

ing dermal thickness, increasing angiogenesis, synthesizing new

connective tissue components, and increasing the number of active

ﬁbroblasts. For both agents, there have been several peer-reviewed

publications with promising data, but the studies have been small

with no long-term follow-up. Overall, certain formulations can

International Journal of Women's Dermatology 5 (2019) 68–72

⁎Department of Dermatology, Weill Cornell Medical College, New York, New York.

E-mail address: nssderm@sadickdermatology.com.

https://doi.org/10.1016/j.ijwd.2018.09.002

by-nc-nd/4.0/).

Contents lists available at ScienceDirect

International Journal of Women's Dermatology

improve collagen production and reduce skin laxity, but they are

rarely effective on cellulite, which requires extensive fat, collagen,

and connective tissue remodeling (Bertin et al., 2001; Green et al.,

2015; Lupi et al., 2007; Pierard-Franchimont et al., 2000).

Energy-based devices

Energy-based devices that harness power from various sources

such as lasers, light, radiofrequency (RF), and acoustic waves have

been extensively tested for the treatment of localized adiposities

and/or skin laxity.

Radiofrequency

RF devices deliver thermal energy to the dermal/subcutaneous

plane via electrode(s). By elevating the tissue temperature at the tar-

get area, collagen denaturation, remodeling and neocollagenesis is

stimulated, but lipolysis is also triggered. Depending on theelectrode

or generator conﬁguration, RF devices come in various iterations,

starting with the ﬁrst generation (e.g., unipolar, monopolar, and bi-

polar) to the latest generation (e.g., multipolar, multigenerator, and

temperature-controlled) devices. Some RF devices also integrate

other energies in their technological design, such as infrared light,

vacuum suction, and pulsed-electromagnetic ﬁelds (Sadick, 2007;

Sadick and Rothaus, 2016a, 2016b; Sadick and Sorhaindo, 2005;

Sadick et al., 2014).

The latest generation of RF devices have been studied and shown

to be effective in clinical trials to reduce the appearance of cellulite

(Luebberding et al., 2015; Romero et al., 2008; Sadick, 2009; Sadick

and Magro, 2007; Sadick and Mulholland, 2004; Wanitphakdeedecha

et al., 2017). Speciﬁcally, Velasmooth and Velashape systems

(Syneron Medical, Israel) that combine infrared light, bipolar RF,

and mechanical manipulation of the skin with suction and massage

have been shown to reduce cellulite.

In a study by Sadick and Magro (2007) where 16 subjects with

cellulitewere treated twice weekly for 6 weeks with the VelaSmooth

system, there was a 71.87% decrease in thigh circumference and 25%

improvement of cellulite in N50% of subjects at the end of the study.

In another study, where 35 female subjects with cellulite were re-

ceived eight to 16 treatments twice weekly with the VelaSmooth de-

vice, 70% of patients showed a reduction in thigh circumference after

4 weeks of treatment,and 100% of patients showed some level of im-

provement in skin texture and cellulite (Sadick and Mulholland,

2004). Researchers have hypothesized that this is achieved due to in-

creased circulation, stimulation of the adipocyte metabolism, and

mechanical stretching of the ﬁbrous cords.

Other devices that have been approved by the U.S. Food and Drug

Administration (FDA) for the noninvasive treatment of cellulite in-

clude Exilis Elite (BTL Aesthetics, United Kingdom), which is a

monopolar RF device; Venus Legacy (Venus Concept, Ontario, Can-

ada), which is a multipolar RF device with pulsed magnetic ﬁelds;

Endymed Body Shaper (Endymed), a multigenerator RF device, and

ThermiRF (Thermi Aesthetics, Hayward, CA), a novel temperature-

controlled RF device with internal probes (Fig. 1).

Recently, the Venus Legacy devices were used to evaluate their ef-

ﬁcacy to treat abdominal cellulite in 25 healthy adult women who

underwent eight weekly treatments. A reduction in subcutaneous

thickness in the axial and sagittal plane of the abdomen was observed

at 1 week after treatment initiation, and assessments by a blinded in-

vestigator at 1, 4, and 12 weeks after the ﬁnal treatment demon-

strated a signiﬁcant improvement in cellulite appearance. No

adverse effects were reported, and the treatment was well tolerated

(Wanitphakdeedecha et al., 2017).

Laser and light

Laser and light devices, depending on their wavelength, emit en-

ergy to the dermis/subcutaneous plane; by heating the local tissue

they can stimulate collagen remodeling and increase microcircula-

tion, which can improve the appearance of cellulite. The impact of

these devices is not very substantial in terms of adipolysis or even

disruption of the ﬁbrous septa that characterize cellulite, but they

can improve the appearance of the skin and smooth the surface.

The main laser technology that has been proven effective to treat

cellulite is a minimally invasive side-ﬁring ﬁber 1440-nm Nd:YAG

laser (DiBernardo et al., 2013, 2016; Sasaki, 2013). This technology

provides a highly targeted means of delivering laser energy into the

targeted anatomical structures that underlie the cellulite as the ther-

mal-sensing cannula is integrated with the laser delivery system to

provide a safe and even distribution of energy to the treatment site.

Only one treatment is required, and aside from the clinical improve-

ment of cellulite, there is high subject satisfaction and minimal ad-

verse events (Fig. 2).

In a multicenter clinical trial, where 57 patients underwent a

three-step cellulite treatment with a 1440-nm Nd:YAG laser with a

side-ﬁring ﬁber and temperature-sensing cannula, the average im-

provement score was 1.7 for dimples and 1.1 for contour irregulari-

ties at the 6-month follow-up examination. The average satisfaction

score was 5.6 for the physician and 5.3 for the patient on a 6-point

scale. Treatment was well tolerated by patients (DiBernardo et al.,

2016).

Acoustic wave therapy

Acoustic wave therapy (AWT) is another energy-based therapy,

whereby pressure waves are transmitted to the subcutaneous tissue

and promote lipolysis, improve local blood ﬂow, enable lymphatic

drainage, and stimulate the production of new collagen. Two types

of acoustic waves have been used to treat cellulite: focused shock

waves (ESWT) and radial shock waves. The main devices that have

been used for cellulite include Cellactor (Storz, Switzerald) and Z-

wave (Zimmer, Irvine, CA; Angehrn et al., 2007; Knobloch and

Kraemer, 2015; Nassar et al., 2015; Russe-Wilﬂingseder et al.,

2013). On average, AWT requires seven treatment sessions, does

not require topical anesthesia, and results in only minor pain (Fig.

3;Schlaudraff et al., 2014).

AstudybyNassar et al. (2015) evaluated the efﬁcacy of ESWT in

15 individuals, and eight sessions during 4 weeks were carried out.

The authors concluded that ESWT was efﬁcient in the improvement

of body contour (i.e., reduction of circumference and fat layer) as

well as in the appearance of cellulite 3 months after treatment. Hexsel

et al. (2017) also recently evaluated the efﬁciency of ESWT in the

treatment of cellulite in 30 women who received 12 sessions over 6

weeks. The treatment reduced cellulite severity from baseline up to

12 weeks after the last treatment session (subjects with severe cellu-

lite: 60%-38%), and the average thickness of the subcutaneous fat tis-

sue decreased (28.3 ± 6.5 mm to 26.7 ± 6.1 mm; pb.001). The

Table 1

Treatment type Brand

Topical agents Bliss, Clarins, Shisheido, Glytone

Radiofrequency devices Venus Legacy (Venus Concept), Endymed

PRO (Endymed), Velashape (Cynosure)

Laser/light devices Cellulaze (Cynosure)

Acoustic wave therapy Z-wave (Zimmer), Cellactor (Storz)

Subcision Cellﬁna (Merz)

Injectable biologic treatments EN3835 (Endo)

Fillers Calcium hydroxyapatite (Radiesse),

poly-l-lactic acid (Sculptra)

69N. Sadick / International Journal of Women's Dermatology 5 (2019) 68–72

treatment also improved patients’quality of life, and no serious ad-

verse events were reported (Hexsel et al., 2017).

Subcision

Manual subcision has also been evaluated for the treatment ofcel-

lulite. During this procedure, the areas are numbed with a topical an-

esthetic agent (vasoconstrictor with lidocaine), a needle (18 G) is

inserted under the skin, and a fanning technique is used to release

the ﬁbrous cords of cellulite. Although efﬁcacious, the main draw-

backs of this treatment are the side effects, including edema, discom-

fort, pain, and bruising (Hexcel and Mazzuco, 2000).

Recently, a novel tissue stabilized-guided subsicion (TS-GS) sys-

tem (Cellﬁna System;Merz North America, Inc., Raleigh, NC) was de-

veloped and FDA approved for the improvement of cellulite in the

buttocks and thigh areas of adult women. The beneﬁts of Cellﬁna

over traditional manual subscision with a needle are its precise con-

trol of treatment depth and area of tissue (ﬁbrous septae) and a

unique vacuum-assisted design.Cellﬁna has been shown in multicen-

ter clinical studies to improve cellulite with results lasting N3 years

(Kaminer et al., 2017).

In the latest clinical study, 45 subjects were followed for an ex-

tended period of up to 3 years after receiving a single treatment

using the TS-GS system. The results of this trial supported an FDA

clearance of the device for the long-term reduction in the appearance

of cellulite following TS-GS (Kaminer et al., 2017).

Injectable treatments for cellulite

Among minimally invasive procedures for cellulite, active biologic

agents and dermal ﬁllers have been used to treatcellulite, with prom-

ising results.

Collagenase Clostridium histolyticum

Collagenase enzymes isolated and puriﬁed from the fermentation

of Clostridium histolyticum are used in clinical trials for the treatment

of cellulite. Collagenase I (AUX-I, Clostridial class I collagenase) and

Collagenase II (AUX-II; Clostridial class II collagenase) are not immu-

nologically cross-reactive and have different speciﬁcities; mixed in a

1:1 ratio, theybecome synergisticand provide a very broad hydrolyz-

ing reactivity toward collagen (Yang and Bennett, 2015). Thus, they

can hydrolyze the triple-helical region of collagen and have the

Fig. 1. Before (left) and after (right) seven treatments in the outer thigh with Venus Legacy (Venus concept, Toronto, Ontario, Canada).

Fig. 2. Before (left) and after (right) one treatment in the buttocks with 1440 nm Cellulaze (photograph courtesy of Cynosure).

70 N. Sadick / International Journal of Women's Dermatology 5 (2019) 68–72

potential to be effective in lysing subdermal collagen, such as those

observed in the dermal septa (underlying cause of cellulite).

In phase 2b trials, a collagenase mixture, EN3835 (Endo pharma-

ceuticals, Malvern, PA), has been shown to be well tolerated by all

dose groups, and most adverse events were mild to moderate and

primarily limited to the local injection area. A phase 3 multicenter,

randomized, double-blind, placebo-controlled study is currently un-

derway to evaluate the safety and efﬁcacy of this agent in reducing

the appearance of cellulite (Callaghan et al., 2017).

Dermal ﬁllers

Another up-to-date option to treat cellulite is the new generation

dermal ﬁllers injections, such as calcium hydroxyapatite (CaHa) and

poly-l-lactic acid microspheres (Fig. 4). These ﬁllers have been used

extensively to treatscars and can also be applied to smoothen thecel-

lulite-induced skin irregularities. A recent study evaluated the effects

of microfocused ultrasound with visualization (Ultherapy) in combi-

nation with diluted calcium hydroxylapatite (CaHA; Radiesse) on cel-

lulite appearance in 20 women. The results showed statistically

signiﬁcant improvements compared with baseline for each item on

the cellulite severity scale (pb.001) with a 4.5-point improvement

in mean overall score (pb.001) after a single microfocused ultra-

sound with visualization/CaHA treatment. Both procedures were

well tolerated, and subject satisfaction was high (Casabona and

Pereira, 2017).

Conclusions

Despite multiple therapeutic approaches that attempt to treatcel-

lulite, no procedures have been proven successful long term. Topical

agents, injectable treatments, and energy-based devices can

ameliorate the appearance of cellulite, sometimes to a satisfactory

degree, but never eradicate cellulite because this involves extensive

tissue remodeling.

In the author’s opinion, a combination approach where internal

and external approaches are used strategically and in a staged man-

ner to yield synergistic results has the best clinical outcome. For ex-

ample, injections with CaHa followed by ﬁve weekly treatments

with an RF device can result in improvements of severe cellulite

around 3 months after the ﬁnal treatment. Other examples of com-

bining strategies can be six sessions ofweekly acoustic wave therapy,

followed by a one-side ﬁring of an 1440 nm laser.

More large-scale studies, particularly with respect to combination

approaches, need to be conducted to evaluate the long-term results

of therapies for cellulite in terms of safety, efﬁcacy, and patient

satisfaction.

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Comparing Collagenase and Tissue Subcision for Cellulite Treatment of the Buttock and Thigh Regions: A Systematic Review and Meta-analysis

Article

Full-text available

Jun 2024

Background In this systematic review, we assessed the therapeutic efficacy and safety of Clostridium histolyticum collagenase (CCH) and tissue subcision (TS) for treating cellulite, which ranges from subtle to pronounced lesions. Methods A systematic review was performed following PRISMA guidelines for CCH and TS treatment to the thigh and gluteal regions. A proportion meta-analysis was then conducted using Stata statistical software. Results A total of 14 studies were incorporated into the final analysis. Nine focused on TS and five on CCH injection, collectively reporting outcomes for 1254 patients. Of these, 465 received CCH injection and 789 underwent subcision. For bruising, rates were 89% [95% confidence interval (CI), 71%–96%] with CCH injection and 99% (95% CI, 85%–99%) for subcision; pain requiring analgesic was reported at 74% (95% CI, 55%–87%) for CCH and 60% (95% CI, 43%–76%) for subcision; both showed induration at 7% (95% CI, 5%–11% for CCH, 95% CI, 2%–25% for subcision), whereas skin discoloration was higher post-CCH injection at 16% (95% CI, 10%–26%) compared with 7% (95% CI, 5%–10%) postsubcision. Conclusions Both CCH and TS seem effective treatments for cellulite. However, upon evaluating the adverse outcomes between the two modalities, subcision demonstrated a higher incidence of bruising, albeit similar rates of induration compared with CCH injection. Conversely, the CCH injection group manifested a higher propensity for pain requiring analgesia and notably exhibited increased instances of skin discoloration compared with their subcision patient group. Further standardized research is crucial for more informed cellulite treatment decisions and for comparing efficacy, safety, and cost-effectiveness between TS and CCH.

Combined approach of nanoemulgel and microneedle pre-treatment as a topical anticellulite therapy

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Nov 2024

Background and purpose: Cellulite is caused by changes in the metabolism of the fatty tissue beneath the skin. Methylxanthines and retinoids are commonly added to the different anticellulite products. However, their topical permeation into the dermis is limited. Thus, the objective of this research is to formulate a nanoemulgel (NEG) containing a triple therapy of caffeine, aminophylline, and tretinoin as a topical anticellulite product to improve their skin permeation. Furthermore, the influence of microneedles (MNs) as skin pre-treatment on the permeation of the NEG was investigated. Experimental approach: Various nanoemulsion (NE) formulations were prepared using high-energy ultrasonication with different compositions and sonication amplitudes. Several characterisation tests were employed to select the optimum NE formulation. Then, the optimised NE formulation was incorporated with hyaluronic acid to prepare the NEG, which was, in turn, subjected to various evaluations. An ex vivo permeation study using human skin was performed for the NEG compared to a control preparation of plain gel. Additionally, a microneedling pen was applied as a skin pre-treatment at varying lengths prior to NEG application to examine its impact on the NEG’s permeation. Key results: The selected NEG has a homogenous and consistent texture with no coarse particles, a droplet size of 175.8 nm and polydispersity index (PDI) of 0.19, an optimum pH value of 5.28, high drug content of caffeine, aminophylline, and tretinoin (99.35, 98.48 and 98.05 %, respectively), high drug release values of approximately 100 % within 6 hours, appro-priate viscosity, minimum skin irritation, and adequate short-term stability. The ex vivo permeation study showed that caffeine, aminophylline, and tretinoin permeated more and deposited in the skin with higher percentages from the NEG than plain gel. This skin deposition within the dermis was increased by applying the microneedling pen at varying lengths of 0.5, 1, and 2 mm as a skin pre-treatment. Conclusion: This combined approach of NEG formulation containing a triple therapy of caffeine, aminophylline, and tretinoin, along with MNs application, has the potential to serve as a topical anticellulite product, reducing cellulite formation and improving skin appearance.

High-Frequency Ultrasound in the Assessment of Cellulite—Correlation between Ultrasound-Derived Measurements, Clinical Assessment, and Nürnberger–Müller Scale Scores

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Full-text available

Aug 2024

Background: Cellulite is a cosmetic defect of multifactorial etiology that affects over 90% of women worldwide. Cellulite-induced skin changes are undesirable and negatively affect self-esteem. Despite a plethora of cellulite-reducing treatments, we still lack objective tools to enable accurate diagnosis and treatment efficacy assessment. The aim of this study was to determine whether high-frequency ultrasound can be helpful in assessing cellulite and whether there is an association between ultrasound-derived measurements, parameters ascertained clinically, and cellulite assessment scale scores. Methods: The study group consisted of 114 women with cellulite in their posterior thighs, assessed using the Nürnberger–Müller scale. Two types of ultrasound devices were used in this study: a conventional scanner with a linear transducer and a skin-dedicated scanner equipped with a mechanical transducer. We used high-frequency ultrasonography to determine epidermal thickness, dermal thickness, the surface area of fat protrusions at the dermal subcutaneous junction, and the thickness and stiffness of the subcutaneous tissue (ultrasound elastography). Results: There was a correlation between cellulite severity and subcutaneous tissue thickness (r = 0.63), the surface area of fat protrusions at the dermal subcutaneous junction (r = 0.64), and the elastographic strain ratio (r = 0.51). An association was also demonstrated between thigh circumference and subcutaneous tissue thickness (r = 0.48). There was a significant difference in the assessed parameters between the subgroups identified by cellulite severity scores. Conclusions: Ultrasound-determined surface area of fat protrusions at the dermal subcutaneous junction as well as the thickness and stiffness of the subcutaneous tissue seem useful in cellulite assessment. Thus, ultrasonography has the potential to become a common tool in aesthetic medicine and cosmetology.

Exploring the Link Between Metabolic Syndrome and Cellulite

Article

Full-text available

Jun 2024

Metabolic syndrome (MetS) encompasses a cluster of metabolic abnormalities, including insulin resistance, hypertension, abdominal obesity, and dyslipidemia, increasing cardiovascular disease and type 2 diabetes risks. Cellulite, a cosmetic condition marked by dimpled skin, predominantly affects women and shares risk factors with MetS, such as obesity and hormonal imbalances. This review examines the potential link between MetS and cellulite, focusing on shared pathophysiological pathways and implications for clinical practice and future research. Common factors such as inflammation, hormonal changes, and adipose tissue dysfunction are explored. The review highlights the importance of longitudinal studies to track cellulite progression in MetS patients, biomarker identification for early detection, intervention trials to assess therapeutic efficacy, mechanistic studies to elucidate underlying pathways and the impact of comorbidities on cellulite development. Understanding these relationships can enhance prevention, diagnosis, and treatment strategies for both MetS and cellulite, addressing significant public health and cosmetic concerns.

Does electrophysical agents work for cellulite treatment? a systematic review of clinical trials

Article

Full-text available

May 2024
LASER MED SCI

Cellulite, a perceived alteration in skin topography, is predominantly found in adipose tissue-rich body regions such as the hips, buttocks, thighs, and abdomen. Contrary to common belief, the etiology and pathophysiology of cellulite are not well-established or universally agreed upon. This lack of understanding about the actual etiology of cellulite directly influences the selection of suitable treatments that can address both the aesthetic and inflammatory aspects of the condition. Various treatment methods, including electrophysical agents like electric currents, radiofrequency, ultrasound, and photobiomodulation, have been tested. However, the questionable methodological quality of many studies complicates the determination of effective treatments for cellulite. In this study, we conducted a systematic review of clinical studies that utilized electrophysical agents in cellulite treatment. Methods: We employed the PICO (population, intervention, control, and outcome) process to develop our search strategy and establish inclusion/exclusion criteria. We searched five databases: Medline, Central, Scopus, Lilacs, and PEDro, for studies conducted between 2001 and July 2021 that involved cellulite treatment with electrophysical agents. To ensure systematicity and guide study selection, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Results: Our initial search yielded 556 articles: 379 from Medline, 159 from Central, and 18 from Lilacs. After applying our inclusion criteria, only 32 studies remained. Of these, only two (6.2%) were evaluated as having strong and good methodology via the QualSyst tool. Conclusions: Our findings indicate that the quality of evidence from clinical studies on the use of electrophysical agents for cellulite treatment remains subpar. Further studies with robust experimental designs and more precise assessment techniques are necessary. While our study does not refute the effectiveness of the techniques used for cellulite treatment, it underscores the need for additional well-designed trials.

Ultrasonographic Picture Of The Skin And Subcutaneous Tissue In The Treatment Of Cellulite Using The Compressive Microvibration®

Article

Full-text available

Mar 2024

In recent years, the demand for non-invasive methodologies in aesthetic medicine for treating localized adiposity, cellulite, and sagging skin has increased significantly, particularly the demand for massage techniques with mechanical vibrations. The aim of the present study is to evaluate the effectiveness of Compressive Microvibration® in reducing the expression of cellulite and improving skin conditions in women of different ages under ultrasound control during 60 days of observation. A prospective, single-center, nonrandomized study enrolled 27 women with mild to moderate gynoid lipodystrophy, aged 40 to 69 years, who have been subject to twelve sessions of Compressive Microvibration® (Endospheres®). A specialized high-resolution digital ultrasound system, the DUB SkinScanner (tpm GmbH, Germany), has been used to visualize the skin. Also, the sample anthropometric parameters have been measured, the body mass index has been calculated, and photographs have been taken. In the patients included in the study, in all age groups, after complete treatment of Endospheres®, a decrease in BM has been noted, with a reduction of the bitrochanteric and hip circumference. An improvement in the morphological topography of the skin in terms of regularization of skin irregularities, leveling of reliefs, reduction of depressions, and increase in skin elasticity and density has also been recorded. After a cycle of therapy on the anterior surface of the abdomen and the thigh anterior and posterior surfaces, the scannograms revealed a decrease in the thickness of the epidermis at various levels, the resolution of the phenomenon of hyperkeratosis, a compaction of the dermis, and an increase in its homogeneity and echogenicity. The effect obtained was still present during a control examination two months after the conclusion of the treatment. The analysis of the dynamics of ultrasound criteria demonstrated the effectiveness of the Compressive Microvibration® in women with mild to moderate gynoid lipodystrophy to improve their skin conditions and maintain the obtained effect for 2 months of observation without unwanted side complications.

Comparative Analysis of Cellulite Treatment Modalities: A Systematic Review

Article

Nov 2024
AESTHET PLAST SURG

Cellulite is a highly prevalent and aesthetically distressing skin condition. Whilst there are a variety of treatment modalities, none are definitively established. This systematic review aims to assess invasive and noninvasive treatment modalities for cellulite management. The review protocol was published and registered a priori (PROSPERO CRD42022359334). A comprehensive electronic search for relevant randomised controlled trials, (RCTs) was performed in CENTRAL, MEDLINE, Embase and Web of Science databases. Study quality and risk of bias were assessed using Cochrane’s risk of bias tool, respectively. Overall, 753 studies were initially identified, of which 24 randomised controlled trials (RCTs) satisfied the eligibility criteria with a total of 2084 patients with a mean follow-up of 3.33 ± 13.4 weeks. Evaluated interventions included mechanical stimulation, topical therapy, shock wave therapy (SWT), laser and light-based devices, radiofrequency therapy, subcutaneous injectables, and ultrasound. SWT emerged as a standout intervention, demonstrating a consistent cellulite reduction score of 2.07 ± 0.39 across four studies. Radiofrequency therapy exhibited a statistically significant reduction of thigh circumference (− 2.09 cm, p < 0.001) and subcutaneous tissue thickness (− 2.23 cm, p < 0.001). Subcutaneous injectables, specifically collagenase Clostridium histolyticum-aaes, demonstrated a statistically significant improvement in the clinician-reported photonumeric cellulite severity scale (17.0%) and patient-reported photonumeric cellulite severity scale (25.7%) (p < 0.001). The overall quality of the studies using the grading of recommendations, assessment, development and evaluation approach was moderate. This is the first methodologically robust systematic review evaluating interventions for cellulite. SWT, radiofrequency therapy, and subcutaneous injectables have shown promising findings in cellulite treatment. The journal asks authors to assign a level of evidence to each article. For a complete description of Evidence-Based Medicine ratings, see the Table of Contents or the online Instructions for Authors at www.springer.com/00266.

Common Skin Manifestations Related to Obesity

Chapter

Nov 2024

Obesity, with a body mass index (BMI) over 30 kg/m2, is a growing health concern worldwide, manifesting from early childhood to midlife and stemming from diverse causes including genetics, endocrine disorders, and psychosocial factors. This complex condition not only leads to metabolic issues like insulin resistance and type 2 diabetes mellitus but also precipitates a range of dermatological changes. These skin manifestations include cellulite, acanthosis nigricans, and skin tags linked to insulin resistance, hyperandrogenism, striae from skin overextension, and complications arising from peripheral vascular disease, such as stasis pigmentation and lymphedema. Additionally, the relationship between obesity and skin issues extends to changes in skin barrier function, sebaceous and sweat gland activity, and an increase in the thickness of the stratum corneum, the outermost layer of the epidermis, leading to conditions such as keratosis pilaris and plantar hyperkeratosis. These comprehensive findings underscore the intricate connection between obesity and skin health, highlighting the need for holistic approaches in treatment and management.

New Insight for Enhanced Topical Targeting of Caffeine for Effective Cellulite Treatment: In Vitro Characterization, Permeation Studies, and Histological Evaluation in Rats

Article

Full-text available

Oct 2024
AAPS PHARMSCITECH

Cellulite (CLT) is one of the commonly known lipodystrophy syndromes affecting post-adolescent women worldwide. It is topographically characterized by an orange-peel, dimpled skin appearance hence, it is an unacceptable cosmetic problem. CLT can be modulated by surgical procedures such as; liposuction and mesotherapy. But, these options are invasive, expensive and risky. For these reasons, topical CLT treatments are more preferred. Caffeine (CA), is a natural alkaloid that is well-known for its prominent anti-cellulite effects. However, its hydrophilicity hinders its cutaneous permeation. Therefore, in the present study CA was loaded into solid lipid nanoparticles (SLNs) by high shear homogenization/ultrasonication. CA-SLNs were prepared using Compritol® 888 ATO and stearic acid as solid lipids, and span 60 and brij™35, as lipid dispersion stabilizing agents. Formulation variables were adjusted to obtain entrapment efficiency (EE > 75%), particle size (PS < 350 nm), zeta potential (ZP < −25 mV) and polydispersity index (PDI < 0.5). CA-SLN-4 was selected and showed maximized EE (92.03 ± 0.16%), minimized PS (232.7 ± 1.90 nm), and optimum ZP (−25.15 ± 0.65 mV) and PDI values (0.24 ± 0.02). CA-SLN-4 showed superior CA release (99.44 ± 0.36%) compared to the rest CA-SLNs at 1 h. TEM analysis showed spherical, nanosized CA-SLN-4 vesicles. Con-LSM analysis showed successful CA-SLN-4 permeation transepidermally and via shunt diffusion. CA-SLN-4 incorporated into Noveon AA−1® hydrogel (CA-SLN-Ngel) showed accepted physical/rheological properties, and in vitro release profile. Histological studies showed that CA-SLN-Ngel significantly reduced mean subcutaneous fat tissue (SFT) thickness with 4.66 fold ( p = 0.035) and 4.16 fold ( p = 0.0001) compared to CA-gel, at 7th and 21st days, respectively. Also, significant mean SFT thickness reduction was observed compared to untreated group with 4.83 fold ( p = 0.0005) and 3.83 fold ( p = 0.0043), at 7th and 21st days, respectively. This study opened new avenue for CA skin delivery via advocating the importance of skin appendages. Hence, CA-SLN-Ngel could be a promising nanocosmeceutical gel for effective CLT treatment. Graphical Abstract

Simulation-guided development of advanced PID control algorithm for skin cooling in radiofrequency lipolysis

Article

Feb 2024
BIO-MED MATER ENG

Background: The clinical outcomes of bipolar radiofrequency (RF) lipolysis, a prevalent non-invasive fat reduction procedure, hinge on the delicate balance between effective lipolysis and patient safety, with skin overheating and subsequent tissue damage as primary concerns. Objective: This study aimed to investigate a novel bipolar radiofrequency lipolysis technique, safeguarding the skin through an innovative PID temperature control algorithm. Methods: Utilizing COMSOL Multiphysics simulation software, a two-dimensional fat and skin tissue model was established, simulating various PID temperature control schemes. The crux of the simulation involved a comparative analysis of different PID temperatures at 45 °C, 50 °C, and 55 °C and constant power strategies, assessing their implications on skin temperature. Concurrently, a custom bipolar radiofrequency lipolysis device was developed, with ex vivo experiments conducted using porcine tissue for empirical validation. Results: The findings indicated that with PID settings of Kp = 7, Ki = 2, and Kd = 0, and skin temperature control at 45 °C or 50 °C, the innovative PID-based epidermal temperature control strategy successfully maintained the epidermal temperature within a safe range. This maintenance was achieved without compromising the effectiveness of RF lipolysis, significantly reducing the risk of thermal damage to the skin layers. Conclusion: Our research confirms the substantial practical utility of this advanced PID-based bipolar RF lipolysis technique in clinical aesthetic procedures, enhancing patient safety during adipose tissue ablation therapies.

Microfocused Ultrasound with Visualization and Calcium Hydroxylapatite for Improving Skin Laxity and Cellulite Appearance

Article

Full-text available

Jul 2017

Background:. Age-associated skin laxity contributes to worsening of cellulite appearance. This study evaluated the effects of microfocused ultrasound with visualization (MFU-V; Ultherapy) in combination with diluted calcium hydroxylapatite (CaHA; Radiesse) on cellulite appearance and on neocollagenesis. Methods:. Twenty women (18–55 years old) with skin laxity and moderate-to-severe cellulite on the buttocks and thighs were retrospectively enrolled. MFU-V was applied using 4 and 7 MHz transducers (25 lines/transducer/site) and immediately followed by subdermal CaHA injection (1 ml/buttock or thigh). Photographs at baseline and 90 days were assessed by 2 independent, blinded evaluators using a 5-item cellulite severity scale. One subject scheduled for thighplasty received treatment with 6 different CaHA dilutions (0.3 ml/5 cm2) followed by MFU-V. Tissue specimens from each dilution site were examined under polarized light microscopy to assess neocollagenesis. Results:. Both evaluators reported statistically significant improvements compared with baseline for each item on the cellulite severity scale (P < 0.001) with a 4.5-point improvement in mean overall score (P < 0.001) after a single MFU-V/CaHA treatment. At 90 days, histologic analysis showed peak neocollagenesis in samples treated with the 1:1 dilution, whether with CaHA alone or in combination with MFU-V. The highest conversion of collagen type III into collagen type I at month 3 occurred in samples injected with 1:1 and 1:0.6 CaHA dilutions without subsequent MFU-V treatment. Both procedures were well tolerated, and subject satisfaction was high. Conclusions:. Combination treatment with MFU-V and diluted CaHA is effective for improving skin laxity and the appearance of cellulite on the buttocks and upper thighs.

Cellulite: A review of pathogenesis-directed therapy

Article

Dec 2017
SEMIN CUTAN MED SURG

Cellulite is a condition that affects the majority of postpubertal women and can negatively impact quality of life. This review discusses several proposed pathophysiologies of cellulite, and examines treatment options that have been utilized, focusing on the etiologic factor targeted by the therapies. This approach aims to help clarify the pathogenesis of cellulite and provide a road map for developing effective treatment paradigms for patients.

A Multicenter Pivotal Study to Evaluate Tissue Stabilized-Guided Subcision Using the Cellfina Device for the Treatment of Cellulite With 3-Year Follow-Up

Article

Jun 2017
DERMATOL SURG

Background: Cellulite is a common female cosmetic concern for which no single treatment option had been proven effective over the long term. A novel tissue stabilized-guided subsicion system (TS-GS system) has demonstrated significant reduction in the appearance of cellulite after treatment. Objective: The objective of this extended follow-up period was to assess the effectiveness of TS-GS out to 3 years after initial treatment. Patients and methods: After completing an open-label, multicenter, pivotal study, 45 subjects were followed for an extended period of up to 3 years after receiving a single treatment using the TS-GS system. Treatment areas were photographed prior to the procedure and at multiple time points post-treatment throughout the 3 years. In this open-label study, subjects served as their own controls. Effectiveness was assessed based on blinded independent physician panel assessments of improvement from baseline using a cellulite severity scale. Subject aesthetic improvement and patient-reported satisfaction were also collected. Results: The results of this trial supported Food and Drug Administration clearance of the device for the long-term reduction in the appearance of cellulite following TS-GS. Conclusion: These data further demonstrate the safety and efficacy of this treatment with no reduction in treatment benefits out to 3 years.

Efficacy of Multi-Polar Radiofrequency (RF) with Pulsed Magnetic Field Therapy for the Treatment of Abdominal Cellulite

Article

Jan 2017
J Cosmet Laser Ther

Introduction: Cellulite is a metabolic condition, predominately seen in females, that affects the subcutaneous tissue of the posterolateral thighs, buttocks, pelvic region, and abdomen. This condition has a distinct histologic pathology compared to obesity, that is characterized by skin dimpling and lumpiness resembling an orange peel. Despite the wide range of treatment options for cellulite, there is paucity of empirical data supporting their efficacy. The objective of this study was to evaluate the efficacy of a new generation multipolar radiofrequency device for the treatment of cellulite. Methods: A multipolar radiofrequency device with pulsed magnetic fields was used to treat abdominal cellulite. Twenty-five healthy adult females with stage II or stage III abdominal cellulite underwent 8 weekly treatments. Assessments were performed at baseline and at weeks 1, 4, and 12 following the final treatment. Results: Reduction in subcutaneous thickness in the axial and sagittal plane of the abdomen was observed at 1 week following the treatment initiation. Results from self-reported questionnaires revealed a significantly high patient satisfaction (60%). Assessments by blinded investigator at one, four, and twelve weeks after the final treatment demonstrated significant improvement of cellulite appearance. No adverse effects were reported and the treatment was well tolerated. Conclusion: This study demonstrates the safety, efficacy, and subject satisfaction of multipolar RF with pulsed magnetic fields in the treatment of abdominal cellulite.

Minimally Invasive Radiofrequency Devices

Article

May 2016

This article reviews minimally invasive radiofrequency options for skin tightening, focusing on describing their mechanism of action and clinical profile in terms of safety and efficacy and presenting peer-reviewed articles associated with the specific technologies. Treatments offered by minimally invasive radiofrequency devices (fractional, microneedling, temperature-controlled) are increasing in popularity due to the dramatic effects they can have without requiring skin excision, downtime, or even extreme financial burden from the patient's perspective. Clinical applications thus far have yielded impressive results in treating signs of the aging face and neck, either as stand-alone or as postoperative maintenance treatments.

Aesthetic Applications of Radiofrequency Devices

Article

May 2016

Radiofrequency (RF)-based devices are used to improve face and neck laxity, a major feature of aging that until recently could only be addressed with surgery. Although these treatments are not meant to replace surgical procedures, patient satisfaction studies have been consistently high. For physicians offering these skin rejuvenation procedures, it is essential to have intimate knowledge of how the devices work, select appropriate candidates, set realistic expectations, and combine treatments to optimize outcomes. This article discusses the various noninvasive RF technologies currently in use and reviews pertinent clinical studies evaluating their efficacy and safety.

A Multicenter Study for Cellulite Treatment Using a 1440-nm Nd:YAG Wavelength Laser with Side-Firing Fiber

Article

Mar 2016

Background: Treatment of cellulite using a 1440-nm YAG wavelength laser with side-firing fiber has proven safe and effective, lasting at least 6 months. Objectives: The authors evaluate the safety and efficacy of a single, subdermal procedure to treat the underlying structure of cellulite for at least 1 year. Methods: Fifty-seven patients underwent a 3-step cellulite treatment with a 1440-nm Nd:YAG laser with a side-firing fiber and temperature-sensing cannula. Efficacy was measured by the blinded evaluators to distinguish baseline photos from those taken at 12 months posttreatment, with results on a 5-point, 2-category ordinal photonumeric scale when comparing baseline photos to 12 months posttreatment. Subject and physician satisfaction was assessed based on completion of a satisfaction survey. Adverse events (AE) were recorded throughout the study. Twelve month data were analyzed and compared to 6 month data. Results: Evaluators chose baseline photographs 97% on average from 6 (-1, +2) months and 91% from the 12 (-3, +2) months posttreatment photographs. At 6 (-1, +2) months, the average improvement score was 1.7 for dimples and 1.1 for contour irregularities. At 12 (-3, +2) months, the average improvement score was 1.4 for dimples and 1.0 for contour irregularities. The average satisfaction score for the physician was 5.6 and the patient was 5.3 on a 6-point scale. Conclusions: A single, 3-step, minimally invasive laser treatment using a 1440-nm Nd:YAG laser, side-firing fiber, and temperature-sensing cannula to treat the underlying structure of cellulite proved to be safe and maintained effectiveness at least 1 year post treatment. LEVEL OF EVIDENCE 2: Therapeutic.

Therapeutic approaches to cellulite

Article

Sep 2015
SEMIN CUTAN MED SURG

Cellulite is a condition that affects the vast majority of women. Although it is of no danger to one's overall health, cellulite can be psychosocially debilitating. Consequently, much research has been devoted to understanding cellulite and its etiopathogenesis. With additional insights into the underlying causes of its clinical presentation, therapeutic modalities have been developed that offer hope to cellulite sufferers. This review examines evidence for topical treatments, noninvasive energy-based devices, and recently developed minimally invasive interventions that may finally provide a solution.

Extracorporeal shock wave therapy (ESWT) for the treatment of cellulite - A current metaanalysis

Article

Jul 2015
Int J Surg

The aim of this metaanalysis was to investigate the effectiveness of extracorporeal shock wave therapy (ESWT) in cellulite. Electronic databases (such as Ovid MEDLINE, Scopus and Ovid) as well as reference lists of the available studies were evaluated in June 2015 by two expert examiners. Assessment of each study's methodological quality was performed with the help of the published quality index tool by Downs and Black. This metanalysis included a total of eleven clinical trials on the effects of ESWT on cellulite with a total of 297 included females. Among the eleven clinical trials five randomized controlled trials on ESWT in cellulite with a total number of 123 females have been published so far. Both, focused as well as radial ESWT devices have been found effective in treating cellulite so far. Typically, one or two sessions per week and six to eight sessions overall were studied in the published clinical trials. Overall, outcome parameters mainly focused on digital standardized photographs, circumference measurements and specific ultrasound examinations. Reporting quality showed substantial heterogenity from 22 to 82 points with a mean of 57 points. This metanalysis identified eleven published clinical studies on ESWT in cellulite with five randomized-controlled trials among them. There is growing evidence that both, radial as well as focused ESWT and the combination of both are able to improve the degree of cellulite. Typically, six to eight treatments once or twice a week have been studied. Long-term follow-up data beyond one year are lacking as well as details on potential combination therapies in cellulite such as with low level laser therapy (LLLT), cryolipolysis and others. Copyright © 2015. Published by Elsevier Ltd.

The History of Collagenase Clostridium Histolyticum

Article

Jun 2015

Introduction After its U.S. FDA approval in 2013, Collagenase Clostridium histolyticum (CCh) has seen increasing use as a nonoperative treatment for Peyronie's disease (PD). We review the history of CCh and trials that led to its adoption. Aim To provide a historical and contemporary context for the evolution of Collagenase Clostridium histolyticum as a treatment modality for Peyronie's disease. Methods A comprehensive search of peer-reviewed literature was performed pertaining to CCh and its biochemical and clinical significance. Main Outcome Measure The main outcome studied was the efficacy and safety profile of CCh in PD. CCh use in other diseases processes and its associated outcomes are also described. Results CCh injection yields objective improvement in penile curvature across multiple trials in PD patients. Recently, level 1 strength of evidence has emerged supporting its widespread use. As such, CCh stands as the only FDA-approved injectable therapy for PD. Adverse events were namely limited to local reactions. Serious systemic complications and need for intervention were rare. Conclusions CCh is a safe and effective treatment for PD patients with deformities and plaque configuration amenable to injectable therapy. Multiple trials have demonstrated improvements in objective and subjective metrics such as penile curvature and bother scores. However, multiyear follow-up is needed to assess durability and its sustained clinical significance. Currently, refinement in dosing and technique has established a niche for CCh in PD patients who are affected by their symptoms but are not yet committed to surgical intervention. Yang KK and Bennett N. The history of collagenase clostridium histolyticum.