Abstract Background Cryolipolysis is a minimally invasive technique used to decrease local adipose tissue by thermal cooling. Paradoxical adipose hypertrophy (PAH) is a rare complication of cryolipolysis with important aesthetic consequences. Objectives The objective of this study was to describe four cases of PAH after a cryolipolysis treatment. Methods Between January 2014 and January 2017, all patients who had undergone a cryolipolysis treatment in a single center were reviewed. The device used was a CoolSculpting device and the same operator performed all the cryolipolysis treatments. We retrospectively included all patients who had a suspicion of PAH. Results In our study, 398 patients underwent a session of cryolipolysis. Four patients presented with a voluminous painless swelling in the treated area, between 2 and 4 months after the cryolipolysis session. One patient was treated with liposuction. Histological analysis of the adipose tissue in this patient revealed a nonspecific panniculitis. The other three patients did not receive any additional treatment, and their symptoms stabilized after several months. Conclusions Although cryolipolysis generally yields good results, it can be complicated with PAH, which tends to occur a few months after the cryolipolysis treatment. Patients should be informed of the possibility of developing this complication and encouraged to attend regular follow up for at least 6 months, so that this condition can be readily detected. Surgical treatment should be offered if there is no spontaneous improvement of the symptoms. Level of Evidence: 5 Cryolipolysis is a minimally invasive technique for decreasing local adipose tissue via thermal cooling.1 The US Food and Drug Administration approved this technique for the flank area in 2010 and for the abdominal area in 2011. The technique, which is widely used in the United States, has recently gained popularity in France.2-4 Cryolipolysis is associated with few complications and provides satisfactory results.5,6 Paradoxical adipose hypertrophy (PAH) is a rare complication of cryolipolysis with important aesthetic consequences. Herein, we report four cases of PAH. METHODS Between January 2014 and January 2017, patients who underwent a treatment of cryolipolysis were included in our retrospective study. All patients gave their written informed consent, and the study was performed in accordance with the Helsinki declaration. The device used was a CoolSculpting machine (Zeltiq Aesthetics, Pleasanton, CA) and the same operator (N.G.) performed all the cryolipolysis treatments. All patients who presented with a voluminous painless swelling mass in the treated area a few months after the session which was suggestive of PAH were included. RESULTS A total of 398 patients underwent cryolipolysis at our center. Of these, four patients developed PAH. The mean age of the overall patient cohort was 46 years (range, 21-82 years), and women accounted for 80% (n = 318) of this cohort. The average body mass index (BMI) was 28 kg/m2 (range, 18-36 kg/m2). The mean number of sessions performed per patient was 2 (range, 1-5). The mean follow up of the patients was 20 months (range, 4-40 months). Between 2 and 4 months after the cryolipolysis session, 4 of the 398 patients presented with a voluminous painless swelling in the treated area, which was suggestive of PAH. The others complications found in our series were: 1 case of abdominal nodular panniculitis which disappeared after 6 months, 3 cases of mild abdominal panniculitis with a spontaneous regression in one month, 5 cases of paresthesia in the treated area (abdominal in 3 cases, flanks in 2 cases) for 3 weeks, and 2 cases of hematoma after an abdominal cryolipolysis with a large hand-piece which did not require surgical treatment. The four cases of PAH have been presented below. Case 1 A 54-year-old woman (BMI, 24 kg/m2) without any history underwent a single session of cryolipolysis for abdominal fat removal in December 2014 (Supplemental Figure 1). A large hand-piece was used over the subumbilical abdominal area for 60 min. After initial improvement in the treated area during the first few weeks, she developed a progressively increasing mass in the treated region 3 months after the cryolipolysis treatment. The mass stabilized after 2 years. She has not yet been treated for PAH but wishes to undergo liposuction. At 3 months after the cryolipolysis session, her BMI was 25 kg/m2 and at 2 years after the session her BMI stabilized at 24 kg/m2. Case 2 A 78-year-old woman with a history of breast implants and breast cancer and treatment with Seroplex (Lundbeck SAS, Paris, France) for depression, underwent one session of cryolipolysis over the subumbilical abdominal area in April 2014 (Figure 1). A large hand-piece was used, and the session lasted 60 min. Her BMI before the session was 26 kg/m2. She had no history of diabetes or hyperlipidemia. She had received hormone therapy for breast cancer for 10 years. She had not undergone liposuction or lipofilling for breast reconstruction. Figure 1. View large Download slide View large Download slide A 78-year-old woman (patient 2) underwent a single session of cryolipolysis over the subumbilical abdominal area. (A, C, E, G, I) Before cryolipolysis (BMI, 26 kg/m2) and (B, D, F, H, J) 5 months after cryolipolysis (BMI, 27 kg/m2). Figure 1. View large Download slide View large Download slide A 78-year-old woman (patient 2) underwent a single session of cryolipolysis over the subumbilical abdominal area. (A, C, E, G, I) Before cryolipolysis (BMI, 26 kg/m2) and (B, D, F, H, J) 5 months after cryolipolysis (BMI, 27 kg/m2). She experienced an initial improvement in the treated region, but 2 months after the cryolipolysis treatment, she presented with a painless swelling in the treated area that progressively increased in size. This abdominal mass stabilized after 5 to 6 months. Owing to a strong suspicion of PAH, liposuction was offered but was refused by the patient. Two massages of the area were carried out without success. The symptoms have remained stable for 2 years, without any spontaneous improvement. Her BMI 2 years after cryolipolysis stabilized at 27 kg/m2. Case 3 A 52-year-old man with a history of hyperlipidemia, sleep apnea syndrome, and chronic bilateral glaucoma underwent a single session of CoolSculpting in February 2016 (Supplemental Figure 2). His BMI before the session was 28.5 kg/m2. The session lasted 1 h, and a large hand-piece (10 × 20 cm) was used over the subumbilical abdominal region. After the procedure, mild edema with some pain and cutaneous erythema occurred. Two months after the cryolipolysis session, the subumbilical abdominal area progressively increased in size and stabilized at 3 months after the procedure. The treated area was painless and presented an edematous and hypertrophic appearance. Clinical examination revealed a large, supple, painless, cutaneous, fatty mass in the subumbilical abdominal area, with nonpitting edema and without any signs of inflammation or fever. Abdominal tomodensitometry revealed a parietal, nonnecrotic, pseudo-mass with a fatty appearance, without any signs of necrotizing fasciitis or liquid effusion (seroma or hematoma). Abdominal magnetic resonance imaging (MRI) confirmed these findings and revealed hypertrophy of the superficial abdominal adipose tissue, above the fascia superficialis (Figure 2). Figure 2. View largeDownload slide Abdominal axial T1-weighted MRI scan taken after gadolinium injection in patient 3. The yellow line corresponds to the fascia superficialis. The red line corresponds to the superficial and deep fat of the abdominal wall. Figure 2. View largeDownload slide Abdominal axial T1-weighted MRI scan taken after gadolinium injection in patient 3. The yellow line corresponds to the fascia superficialis. The red line corresponds to the superficial and deep fat of the abdominal wall. Owing to a strong suspicion of PAH, we decided to carry out liposuction to remove the mass. The surgery was scheduled 1 month after the diagnosis had been established. The patient’s preoperative BMI was 29 kg/m2. Histological analysis of the pathological adipose tissue was carried out after the surgery (Figure 3). This revealed nonspecific lobular panniculitis, septal thickening, interstitial infiltration of foamy macrophages, and foci of adiponecrosis. In addition, adipocytes of variable size were present. No vascular lesion or interstitial fibrosis was observed. The aesthetic results improved 3 months after the liposuction, and the lesion and BMI stabilized at 29 kg/m2. Figure 3. View largeDownload slide Histological analysis of the diseased adipose tissue removed by liposuction in patient 3. Figure 3. View largeDownload slide Histological analysis of the diseased adipose tissue removed by liposuction in patient 3. Case 4 A 43-year-old woman with a history of thyroiditis treated with carbimazole and depression treated with antidepressant therapy, underwent one session of cryolipolysis over the submental area in April 2016 (Figure 4). The small hand-piece was used for 60 min. Her BMI was 23 kg/m2. After a significant improvement of the treated area during the first 2 months, the patient presented with a progressively increasing mass in the treated region at 4 months after treatment. The mass stabilized after 1 year. The patient has not yet been treated for PAH. One year after the cryolipolysis session, her BMI stabilized at 23 kg/m2. Figure 4. View largeDownload slide A 43-year-old woman (patient 1) underwent a single session of cryolipolysis over the submental area. (A, B) Before cryolipolysis, (C, D) 2 months after cryolipolysis, and (E, F) 1 year after cryolipolysis (BMI, 24 kg/m2 at each time point). Figure 4. View largeDownload slide A 43-year-old woman (patient 1) underwent a single session of cryolipolysis over the submental area. (A, B) Before cryolipolysis, (C, D) 2 months after cryolipolysis, and (E, F) 1 year after cryolipolysis (BMI, 24 kg/m2 at each time point). DISCUSSION PAH is a rare complication of cryolipolysis, but is responsible for serious aesthetic sequelae that clash with the initial cosmetic request. PAH is characterized by localized fatty hypertrophy in the treated area. The first case of PAH after CoolSculpting was reported in 20147 as a case of “paradoxical adipose hyperplasia.” To date, the manufacturer has reported 33 such cases worldwide. The incidence of PAH is estimated to be between 0.021% according to the manufacturer and 0.78% according to the most recent publications,8 but it is probably underestimated. In our series, we found an incidence rate of 1%. A recent publication has found 16 cases published in the literature.9 Today, many of the more than 2 million patients treated with cryolipolysis worldwide are affected by PAH. The following risk factors for PAH have been identified: male sex, large hand-piece, abdominal region, Hispanic origin, history of cryolipolysis, and genetic factors.8 PAH has been reported to show a male predominance,10 and according to the manufacturer, 55% of cases have occurred in men. Out of the seven cases described in the literature, five concerned men (71%). In a prospective study of 21 patients with pseudo-gynecomastia treated using cryolipolysis, only one case of PAH occurred.11 Initially, a large hand-piece was incriminated as a causative factor of PAH. One hypothesis stated that when a more extensive surface area was treated, apoptosis was likely to occur, and adipose cells could become pathological. However, this risk factor has been questioned because PAH has been found to occur with hand-pieces of different sizes. A genetic cause was raised by an article reporting the occurrence of PAH in twins who underwent cryolipolysis in two different centers.8 The physiopathology of PAH has not yet been clearly established, but some studies have suggested that the process of apoptosis triggered by the cooling and hypoxia of the adipose tissue is responsible for the secondary paradoxical hypertrophy of the residual fat.12,13 However, cryolipolysis-induced apoptosis does not explain the development of panniculitis in PAH. Another hypothesis is that the massage carried out at the end of the cryolipolysis session, with the aim of increasing lipolysis, causes trauma to the adipocyte membranes, resulting in inflammatory adipocytolysis. Cookson described this phenomenon as pyroptosis, and reported that it resembles apoptosis but is inflammatory and is found in different pathological situations such as infection.14-17 The process of inflammatory adipocytolysis is caspase-3 dependent and entails the formation of holes in the adipocyte membranes, leading to an inflammatory process of repair; however, some holes are irreparable, and thus the adipocytes become necrotic.18-20 Jalian et al reported that histological analysis of the adipose tissue in PAH patients reveals increased vascularization in the affected adipocytes.7 However, Seaman et al21 found contradictory results to those of Jalian et al,7 and reported a decrease in the vascularization of diseased adipocytes. Furthermore, a decrease in live interstitial cells was found in the affected tissue, as compared to the healthy tissue treated by cryolipolysis.21 These cells, which consist of macrophages, endothelial cells, adipocyte stem cells, and blood cells, are involved in the remodeling of adipose tissue. However, in the study by Jalian et al,7 the histological analysis was carried out at 3 months after the cryolipolysis session vs 7 months after the session in the study by Seaman et al.21 In contrast, our histological analysis was carried out 5 months after the cryolipolysis session in case 3. We did not find hypervascularization nor any decrease in live interstitial cells. Foci of adiponecrosis and macrophage infiltration were found and indicate that apoptosis occurred as a result of cryolipolysis, which demonstrates its efficacy. The presence of adipocytes of varying sizes was probably related to two distinct pathophysiologies. Adipocyte hypertrophy could be linked to septal thickening, leading to hypoxia and therefore local hypervascularization.22 Adipocyte hyperplasia could be secondary to the recruitment of preadipocytes and stem cells by growth factors. The imaging examinations in our study did not reveal any inflammatory process for this pathology. The MRI carried out for patient 3 was suggestive of superficial subcutaneous fat hypertrophy (Supplemental Figure 2). One hypothesis states that since the superficial region is closer to the hand-piece, it is exposed to greater amounts of hypothermic shock than the deep subcutaneous fat under the superficialis fascia. PAH generally occurs long after cryolipolysis, often 2 to 3 months later, after an initial transient improvement; this was confirmed in our case series. Therefore, it is important to regularly follow-up patients after cryolipolysis, ideally for 6 months, and to inform patients of the possibility of this complication so that it may be readily diagnosed during follow up. In all of the cases described here, there was no favorable spontaneous evolution of this pathology. Some authors have described an aggravation of symptoms after having attempted to treat this complication with another session of cryolipolysis.23 Liposuction or tummy tuck if there is a large amount of excess skin have been suggested as treatments. Surgical treatment is essential to improve PAH and should be proposed to patients once the condition has stabilized. The main limitation of our study is the retrospective review of patients. These results have to be confirmed with a prospective study. We believe our study contributes to the knowledge base because it confirms that PAH is a rare but real complication of a cryolipolysis treatment. It never heals spontaneously, and a surgical treatment has to be proposed to patients. PAH has never been described over the submental area before. It shows that a small hand-piece can also be responsible of an anarchic adipose apoptotic reaction. CONCLUSION Although generally successful, cryolipolysis can be complicated with PAH, whose incidence is probably underestimated. It is important to identify patients with risk factors for PAH (male sex, cyrolipolysis in the subumbilical abdominal area, use of a large hand-piece) and to inform patients of the possibility of this complication before starting cryolipolysis treatment. After the treatment, regular follow up should be conducted for the early detection of PAH, which generally occurs between 2 and 4 months after the cryolipolysis session. If PAH is suspected, the patient should be reassured and informed of the benign nature of this condition. Considering the lack of spontaneous improvement, patients with PAH should be offered surgical treatment once the disease has stabilized after several months of evolution. Supplementary Material This article contains supplementary material located online at www.aestheticsurgeryjournal.com. Disclosures The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article. Funding The authors received no financial support for the research, authorship, and publication of this article. REFERENCES 1. Jalian HR, Avram MM. Cryolipolysis: a historical perspective and current clinical practice. Semin Cutan Med Surg . 2013; 32( 1): 31- 34. Google Scholar PubMed 2. Swanson E. Cryolipolysis: The importance of scientific evaluation of a new technique. Aesthet Surg J . 2015; 35: NP116- NP119. Google Scholar CrossRef Search ADS PubMed 3. Friedmann DP, Mishra V. Cryolipolysis and laser lipolysis: misnomers in cosmetic dermatology. Dermatol Surg . 2015; 41( 11): 1327- 1328. Google Scholar CrossRef Search ADS PubMed 4. Ortiz AE, Avram MM. Noninvasive body contouring: cryolipolysis and ultrasound. Semin Cutan Med Surg . 2015; 34( 3): 129- 133. Google Scholar CrossRef Search ADS PubMed 5. Derrick CD, Shridharani SM, Broyles JM. The safety and efficacy of cryolipolysis: a systematic review of available literature. Aesthet Surg J . 2015; 35( 7): 830- 836. Google Scholar CrossRef Search ADS PubMed 6. Ingargiola MJ, Motakef S, Chung MT, Vasconez HC, Sasaki GH. Cryolipolysis for fat reduction and body contouring: safety and efficacy of current treatment paradigms. Plast Reconstr Surg . 2015; 135( 6): 1581- 1590. Google Scholar CrossRef Search ADS PubMed 7. Jalian HR, Avram MM, Garibyan L, Mihm MC, Anderson RR. Paradoxical adipose hyperplasia after cryolipolysis. JAMA Dermatol . 2014; 150( 3): 317- 319. Google Scholar CrossRef Search ADS PubMed 8. Kelly E, Rodriguez-Feliz J, Kelly ME. Paradoxical adipose hyperplasia after cryolipolysis: a report on incidence and common factors identified in 510 patients. Plast Reconstr Surg . 2016; 137( 3): 639e- 640e. Google Scholar CrossRef Search ADS PubMed 9. Ho D, Jagdeo J. A systematic review of paradoxical adipose hyperplasia (PAH) post-cryolipolysis. J Drugs Dermatol . 2017; 16( 1): 62- 67. Google Scholar PubMed 10. Keaney TC, Naga LI. Men at risk for paradoxical adipose hyperplasia after cryolipolysis. J Cosmet Dermatol . 2016; 15( 4): 575- 577. Google Scholar CrossRef Search ADS PubMed 11. Munavalli GS, Panchaprateep R. Cryolipolysis for targeted fat reduction and improved appearance of the enlarged male breast. Dermatol Surg . 2015; 41( 9): 1043- 1051. Google Scholar PubMed 12. Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ. The biology of white adipocyte proliferation. Obes Rev . 2001; 2( 4): 239- 254. Google Scholar CrossRef Search ADS PubMed 13. Hausman GJ, Richardson RL. Adipose tissue angiogenesis. 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Fink SL, Cookson BT. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect Immun . 2005; 73( 4): 1907- 1916. Google Scholar CrossRef Search ADS PubMed 19. Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol . 2009; 7( 2): 99- 109. Google Scholar CrossRef Search ADS PubMed 20. Bergsbaken T, Fink SL, den Hartigh AB, Loomis WP, Cookson BT. Coordinated host responses during pyroptosis: caspase-1-dependent lysosome exocytosis and inflammatory cytokine maturation. J Immunol . 2011; 187( 5): 2748- 2754. Google Scholar CrossRef Search ADS PubMed 21. Seaman SA, Tannan SC, Cao Y, Peirce SM, Gampper TJ. Paradoxical adipose hyperplasia and cellular effects after cryolipolysis: a case report. Aesthet Surg J . 2016; 36( 1): NP6- N13. Google Scholar CrossRef Search ADS PubMed 22. Stefani WA. Adipose hypertrophy following cryolipolysis. Aesthet Surg J . 2015; 35( 7): NP218- NP220. 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Aesthetic Surgery Journal – Oxford University Press
Published: Apr 1, 2018
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