Skin and soft tissue infection of Nontuberculous mycobacterium after injection lipolysis

Injection lipolysis is used for body and face contouring due to its minimal invasiveness and cost‐effectiveness, but related complications such as nontuberculous mycobacterium infection significantly affect its clinical application.


| INTRODUC TI ON
With the improvement of living standards and lifestyle changes, obesity, defined as an excessive accumulation of adipose tissue, has become a global epidemic associated with comorbidities. 1 The reduction in adipose tissue is important both medically and esthetically and can be achieved through changes to diet, exercise, and surgery. Commonly, people who visit plastic departments or clinics are more concerned about body remodeling for esthetic purposes, and some of whom may choose to undergo surgery, such as liposuction. 2 Compared with invasive operations, new techniques, including injectable chemical lipolysis, are welcomed by people because they are minimally invasive and can be used for the remodeling of some small and delicate parts such as the jaw and neck. 3 However, there have been some reports concerning skin and soft tissue infections of nontuberculous mycobacterium (NTM) after injection lipolysis, which are difficult to diagnose and treat. 4,5 Such infections may occur after traumatic injury, plastic surgery, acupuncture, or cosmetic procedures, of following wound exposure to the soil, water, contaminated prosthetic, or other medical devices. 6,7 Some researchers believe that the increasing demand for cosmetic and plastic surgery is associated with sporadic cases and outbreaks of skin and soft tissue infections of NTM. This article will discuss the mechanism of injection lipolysis, the possible association between NTM infection and injection lipolysis, and clinical experience in the diagnosis and treatment of the infection. To the best of our knowledge, this is the first study to review the skin and soft tissue infections caused by NTM and injection lipolysis.

| INJEC TION LIP OLYS IS
Injection lipolysis is a type of "mesotherapy," first created by the French doctor Michel Pistor in the 1950s. He found numerous health benefits of subcutaneous injections of procaine, a local anesthetic. 4,8 Shortly thereafter, numerous pilot studies reported that adipose tissue could be reduced by the subcutaneous injection of lipolysis drugs and that local fat reduction could be achieved by injecting drugs into a targeted depot. 9 Lipostabil Endovena (Nattermann & Cie) has been used to treat localized fat deposits since 1998, 10 while ATX-101 (Kybella in the United States and Belkyra in Canada; Kythera Biopharmaceuticals, Inc.) injection is the first FDA-approved medication for the reduction of unwanted submental fat. ATX-101 offers a durable, minimally invasive alternative to liposuction and surgery for addressing submental fullness. 11 However, due to the lack of a complete understanding of the mechanism of these drugs and their off-label use, the efficacy and safety of injection lipolysis cannot be guaranteed, and consequently, they have not yet been approved for use worldwide. These lipolytic drugs have been reported to cause clinical complications such as pain, swelling, ecchymosis, hematoma, and granuloma. 5,12,13 Providers should understand the mechanism, indications, and associated risks of injection lipolysis when injecting fat-dissolving drugs to reduce localized fat.
Mesotherapy can be classified into two categories according to the mechanism of fat reduction: one is to stimulate lipolysis by activating lipase and the other is based on the use of detergents to destroy fat cells. Fat distribution is determined by the relative lipolysis thresholds of adipocytes in different parts of the body. 14 Indeed, more α 2 adrenergic receptors (α 2 -ARs) have been found on adipocytes in the hips and thighs of women because of the effects of estrogen, and these α 2 -ARs are known to inhibit lipolysis. 15,16 Therefore, fat distribution in women is often dominated by the hips and thighs. Due to the elevated lipolysis threshold, it is more difficult to lose fat in the hips and thighs than in the abdomen and breasts, where the lipolytic threshold is relatively low. Under normal circumstances, preferential fat loss in specific body areas, especially the hips and thighs, is not possible because endogenous lipolysis stimulators such as catecholamines lower all body lipolysis thresholds to the same degree.
β-adrenergic stimulants, such as isoproterenol, are based on the principle of activating lipolysis of the body's own fat cells. 15 These stimulants can be injected locally into specific adipose tissues, lowering the lipolytic threshold and accelerating differential fat loss in this area. Previous studies have identified at least three mechanisms that increase lipolysis, including inhibition of phosphodiesterase or adenosine receptors, activation of β-adrenergic receptors (β-ARs), and inhibition of α 2 -ARs. 4 Aminophylline, isoproterenol or forskolin, and yohimbine are thought to mediate effects through three lipolytic signaling pathways. 16 These compounds increase the concentration of cyclic adenosine monophosphate (cAMP) to activate lipolysis by increasing adenylate cyclase activity or inhibiting the degradation of cAMP. Elevated intracellular cAMP levels activate protein kinase A and increase the activity of hormone-sensitive lipase, resulting in the degradation of triglycerides, the release of fatty acids and glycerol from cells, 17,18 and a reduction in adipocyte size. Previous studies have used aminophylline cream and subcutaneous injection of isoproterenol to reduce fat locally, and observed a better fat reduction effect than the control group; however, most of these studies were small sample, single-center studies, and further research is needed. 16,19,20 Additionally, several studies have found that the combined application of aminophylline, isoproterenol, and yohimbine is more effective than the use of each component individually. 16 The most commonly used injectable lipolytic drugs based on the principle of adipocyte destruction are phosphatidylcholine (PC) and sodium deoxycholate (DC), the main components of Lipostabil Endovena. Currently, the only FDA-approved drug for injection lipolysis is ATX-101, the components of which are deoxycholic acid injection, an analog of DC. 11,20 Several studies have shown that PC and DC treatments can destroy accumulated fat tissue. 21 Phosphatidylcholine is a natural phospholipid that is esterified from the glycerol backbone to choline and is approved for intravenous treatment of fat embolism and dyslipidemia outside the United States. 22,23 DC is used as a detergent or surfactant and as a cleaning agent for fat cell membranes. It has been shown that the destruction of adipocytes through the cleansing of DCs, followed by emulsification of the fatty acids released through PCs, is a feasible treatment for localized fat accumulation. 24 Rotunda et al. 24

Nontuberculous mycobacteriums are mycobacteria other than
Mycobacterium leprae and the Mycobacterium tuberculosis complex; they are widely present in the natural environment, water sources, soil, and biofilms, with more than 100 subtypes found to date. 28 Although the majority of NTMs are not pathogenic to humans, almost all of them can behave as opportunistic pathogens. NTM infections can occur in the presence of susceptible conditions, but the exact mechanism of transmission is currently unknown. 29 33 Sañudo et al. 34 reported on 15 patients with NTM infection after injection of lipolysis with mesoderm therapy.
Although the exact composition of the drug injected into these patients could not be determined, the main components were procaine, soybean lecithin, artichoke extract, aminophylline, and silicone. 34 Regnier et al. 35

| Treatment
Treatment of NTM infection is challenging because it may depend on multiple factors, including the causative microorganism, patient's immune status, and extent of disease involvement. and differ in their susceptibility to antimicrobial agents, susceptibility testing should be performed for these agents. 39 According to the drug susceptibility results, early, standardized, long-term, and combined drug use should be used to exert the synergistic effect of drugs to reduce NTM drug resistance. Aminoglycosides (amikacin and tobramycin), fluoroquinolones (moxifloxacin and ciprofloxacin), macrolides (clarithromycin and azithromycin), cefoxitin, and imipenem usually have antibacterial activity and are more commonly used as therapeutic drugs. The drug treatment cycle is usually not less than 2 months, and the total course of treatment is 6-12 months.

| Prevention
Strict disinfection and sterilization management practices are the most important measures to prevent NTM infection. Additionally, it is important to avoid contact with tap water and trace suspected cases of nosocomial infections. Surgeons should also avoid performing plastic and cosmetic treatments, such as injection fatdissolving and fat transplantation, for high-risk groups, such as those who are immunodeficient and taking immunosuppressive agents.

ACK N OWLED G EM ENT
We are particularly indebted to Mr Wenjun Xie, who gave kind encouragement throughout the writing of the article.

CO N FLI C T O F I NTE R E S T
The authors declare no conflict of interest.

DATA AVA I L A B I L I T Y S TAT E M E N T
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

E TH I C A L A PPROVA L
There are no ethical issues involved in this study.