Paradoxical Adipose Hyperplasia after Cryolipolysis CoolSculpting

Aesthetic cryolipolysis was first approved for use by the U.S. Food and Drug Administration (FDA) in 2010, acquired in 2017 by Allergan Aesthetics and marketed under the name CoolSculpting (Allergan Aesthetics, an AbbVie Company, Irvine, CA). Simplistically, the technology isolates deposits of targeted adipose tissue by a moderate vacuum and removes a controlled amounts of heat from the tissue over a 30 to 60 minutes procedure, followed by massage of the treated area. This cooling preferentially affects adipocytes due to the higher freezing temperature of the lipids they contain. Within 3 days, adipocyte apoptosis is evident, followed by an inflammatory infiltrate for 14 to 60 days after treatment featuring phagocytosis of the devitalized adipocytes by macrophages. Collagen in the fibrous septae of the adipose tissue is relatively increased (likely due to the decreased proportion of fat as well as the post-treatment inflammatory response) and skin contour changes can be seen after 6 weeks.[1]

Initially approved for the treatment of abdominal and flank fat deposits, CoolSculpting was approved by FDA in 2018 for the treatment of fat deposits and to affect the appearance of tissue in the submental and submandibular areas in patients with body mass index less than or equal to 46.2. The technology was touted as safe and effective that generally requires two or more treatments per each area. CoolSculpting is contraindicated in patients with cryoglobulinemia, paroxysmal cold hemoglobinuria, and cold agglutinin disease. Occurrence and incidence of complications disclosed by the manufacturer include paradoxical adipose hyperplasia (PAH, 0.033%, which may present 2 to 5 months after treatment), severe pain (0.017%, associated with the treatment), late-onset pain (0.017%, developing several days after treatment and resolving within several weeks), hyperpigmentation (0.009%), frostbite (0.006%), treatment area demarcation (0.005%, highlighted by excessive fat removal), vasovagal symptoms (0.003%, during or immediately after treatment), subcutaneous induration (0.003%), cold panniculitis (0.002%), and development of a new or worsening of a preexisting hernia (0.001%).[2]

PAH after cryolipolysis, defined as “a visibly enlarged tissue volume within the treated area which may develop 2 to 5 months after treatment” and an inherent risk of cryolipolysis for localized fat reduction,[3] was first reported in medical literature in 2014 by Jalian et al.[4] These authors performed a histological analysis of the tissue after removal by abdominoplasty and noted thickened fibrous septae, increased vascularity and adipocyte hyperplasia, and also noted patients who developed PAH were disproportionately male. Patients presented with firm areas of greater volume than the fat they were trying to treat, and many complained of a “brick”-like appearance of the area. A variety of etiologies of PAH have been proposed, including hypertrophy of pre-existing/surviving adipocytes, recruitment of preadipocytes/stem cells or as a response to fat septal thickening-induced hypoxia.[4]

Nikolis and Enright reported on 9 of 2,114 (0.42%) patients who developed PAH in 13 of 8658 (0.15%) treatment cycles after treatment at one of eight Canadian centers in the period 2015 through 2019. Most (61.5%) of these areas developed PAH after a single treatment, were more likely (55%) to be male (similar to the report by Jalian et al) and developed PAH in all areas treated. Six patients underwent liposuction with resolution, while one was retreated with repeat cryolipolysis without any change.[5] Other authors have reported higher incidences in smaller, single practice experiences, and the true incidence of PAH may be underreported. In a consensus panel report of international experts published in 2022, 8 of 11 panelists had experience with cryolipolysis-related PAH.[6] This panel recommended liposuction as first-line treatment for PAH.

Recently, there have been an increasing number of reports of PAH in the lay press, including some high-profile cases. A review of the FDA Manufacturer and User Device Experience[3] database returned 300 entries for “CoolSculpt” in the first 3 months of 2023. Of these, 97% are (mostly patient reported) cases of PAH. A review of these cases shows an interesting distribution of the areas affected by PAH, possibly reflecting the frequency that this treatment is performed in these areas ([Fig. 1]).

Fig. 1 Complications listed in U.S. Food and Drug Administration Manufacturer and User Device Experience database reports for term “CoolSculpt” from January 1 to March 31, 2023. PAH, paradoxical adipose hyperplasia.

While submental PAH thus far represents only a minority (13%) of reported cases, it is important to remember that submental and submandibular treatment was FDA cleared several years after the initial device clearance, and submental PAH may increase in frequency with increasing submental and submandibular treatment. PAH is an uncommon but reported complication after cryolipolysis, can be disfiguring, has never been reported to resolve spontaneously, and is generally amenable to treatment with suction (recommended as first-line treatment) or direct lipectomy with good results. PAH is important entity with which facial plastic surgeons should be familiar.

Publikationsverlauf

Artikel online veröffentlicht:
14. August 2023

• References

• 1 Zelickson B, Egbert BM, Preciado J. et al. Cryolipolysis for noninvasive fat cell destruction: initial results from a pig model. Dermatol Surg 2009; 35 (10) 1462-1470
• 2 Accessed May 16, 2023 at: https://www.coolsculpting.com/pdfs/CSC125713-v3-CoolSculpting-Important-Safety-Information.pdf
• 3 Accessed May 16, 2023 at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm
• 4 Jalian HR, Avram MM, Garibyan L, Mihm MC, Anderson RR. Paradoxical adipose hyperplasia after cryolipolysis. JAMA Dermatol 2014; 150 (03) 317-319
• 5 Nikolis A, Enright KM. A multicenter evaluation of paradoxical adipose hyperplasia following cryolipolysis for fat reduction and body contouring: a review of 8658 cycles in 2114 patients. Aesthet Surg J 2021; 41 (08) 932-941
• 6 Altmann J, Burns AJ, Kilmer SL. et al. Global expert opinion on cryolipolysis treatment recommendations and considerations: a modified Delphi study. Aesthet Surg J Open Forum 2022; 4: ojac008