Surgical correction of HIV-associated facial lipoatrophy

Introduction Lipodystrophy was first described in HIV-1-infected patients in 1998 [1–5]. The main clinical feature is subcutaneous fat loss or lipoatrophy of the face, limbs, and buttocks [6,7]. Patients can also experience fat accumulation within the abdomen, neck or breasts [8,9]. The pathogenesis of lipoatrophy appears to be multifactorial. Contributing factors are CD4+ lymphocyte cell count, HIV clinical stage, race, sex, exercise level, age at start of antiretroviral therapy [8], and the rapidity of its onset may depend on the individual total fat mass. The driving force behind lipoatrophy is undoubtedly the cumulative exposure to thymidine analogue drugs. These drugs, in particular stavudine and to a lesser extent zidovudine, block mitochondrial DNA polymerase function producing apoptosis of fat cells [9,10]. Earlier detection and treatment of HIV infection [11], as well as the use of antiretroviral drugs with less deleterious effects on body fat, make it reasonable to hypothesize a decrease in prevalence of lipodystrophy in the coming years. Facial lipoatrophy is characterized by loss of the buccal and/or temporal fat pads, leading to facial skeletonization with concave cheeks, prominent naso-labial folds, periorbital hollowing, and visible facial musculature [10–12]. A volume deficit of this type will alter the youthful, healthy, convex curves of the face into aged, pathologic, concave contours [13–16]. Facial fat depletion may occur within the first year of treatment [15] and the risk increases along with cumulative exposure to highly active antiretroviral therapy (HAART) [16]. Patients with HIV-associated lipoatrophy have a fairly rapid and localized loss of facial soft tissue, unlike the slower loss of facial fullness associated with aging [17]. Facial lipoatrophy is a stigmatizing feature of HIV-related lipodystrophy. Facial appearance is usually perceived as a manifestation of health and cannot be hidden behind clothes. Studies have demonstrated the negative psychosocial impact and impairment of quality of life (QoL) from lipodystrophy due to erosion of self-image and self-esteem, demoralization and depression, problems in social and sexual relations [18,19]. In addition, lipodystrophy often may result in HIV disclosure [20]. Several studies have demonstrated the potential for reversibility of lipoatrophy by switching from stavudine or zidovudine to thymidine analogue-sparing regimens, although improvement in subcutaneous fat is slow and incomplete [21–23]. Initial promising data on the beneficial effects of certain drugs such as rosiglitazone, pioglitazone, pravastatin or uridine on lipoatrophy has been either inconclusive or unconfirmed [24–27]. For this reason, as in other acquired or congenital lipoatrophies, plastic surgery seems to be up to now the mainstay of treatment, offering either lipofilling, or biodegradable, or nonbiodegradable filler injections. Search strategies and selected criteria Data to review were identified by protocolized searches through MEDLINE, references from relevant articles, and abstract books of the first nine International Workshops on Adverse Drug Reactions and Lipodystrophy. Search terms were ‘Lipodystrophy’, ‘HIV’, and ‘Plastic surgery’. Studies reported in the English language only were included. We aimed at providing an updated comprehensive knowledge of the surgical approaches for reconstruction of HIV-related facial lipoatrophy. We specifically looked for criteria to qualify for surgery, to choose among surgical interventions, to identify clinical outcomes and to manage side effects. Indications for surgical treatment of HIV-related face lipoatrophy Severity of facial lipoatrophy The severity of facial lipoatrophy is probably the most important issue to qualify for surgical treatment. However, assessment of HIV facial lipoatrophy is not easy. Objective methods have occasionally been used, but the measurement of facial fat is challenging [28,29]. Up to now there is neither a standardized available tool to measure facial pad thickness, nor clear facial reference points that could be of use in the clinical setting. In an attempt to standardize lipoatrophy severity, a photo comparison grading scale has been proposed and utilized. James et al.[30] suggested to consider a four-stage severity scale. Degree 1 is defined as a minimal fat wasting of the cheeks only, and slight enhancement of the naso-labial folds. Degree 2 refers to moderate fat wasting of the cheeks, obvious enhancement of the naso-labial folds and appearance of ‘naso-labial bands’. Degree 3 is characterized by moderate fat wasting of cheeks and temporal regions with prominent naso-labial folds (naso-labial bands), and in degree 4 there is severe fat wasting and hollowing of cheeks, temporal, and periocular regions, resulting in visible facial bony prominences [31]. Fontdevila et al.[32], more recently, suggested to consider a three-degree severity scale only (mild, moderate, severe) and was able to validate a new photo comparison grading scale with objective volume measurement obtained by CT scan. Fig. 1 represents these pictures currently used both at Modena Metabolic Clinic (Italy) and at Barcelona Hospital Clinic (Spain) as comparison references. The main difference between these classification system concerns degree 1 alias ‘mild facial lipoatrophy’. Patients with malar flattening, but no noticeable nasolabial folds are included in this category. Plastic surgery is usually offered to patients presenting with moderate to severe facial lipoatrophy.Fig. 1: Classification of facial lipoatrophy in clinical stages and picture comparison.Psychological repercussion of facial lipoatrophy Psychological repercussion is another characteristic that may qualify for surgical treatment. Psychometric inclusion criteria take into account psychological consequences of lipodystrophy by examining body image perception by means of the ‘Assessment of Body Change and Distress Questionnaire’ especially conceived to analyse perceptions, attitudes, feelings, emotions, actions and satisfactions concerning body appearance and functioning [33,34]. This is an extremely useful tool, as some patients with a mild to moderate face lipoatrophy may experience a deep detriment of body image perception, whereas others with a more severe form could have the psychological resources to better cope with this condition. Treatment efficacy has predominantly been assessed subjectively by clinicians and patients, either by nonstandardized photography, or radiological tools, mainly ultrasound and CT scan [35–38]. It should be stressed that the buccal fat pad has a minor role in the facial appearance and does not have a concrete area in superficial anatomy. For this reason, ultrasound evaluation of the cheek is a controversial end point in plastic facial reconstruction surgery. Surgical treatment of HIV-related face lipoatrophy Surgical interventions can be summarized as follows: autologous fat transplantation (AFT) [39–41], and injections of biodegradable [hyaluronic acid, poly-L-lactic acid (PLA), hydroxyapatites] [42–45] or nonbiodegradable [silicon, polymethylmethacrylate (PMMA), polyacrylamide hydrogel, polyalkylimide) gel fillers [46]. The classification refers exclusively to the biological proprieties of these materials. They do not necessary correlate with the durability of the aesthetic results. For example PLA and hydroxyapatites consist of particles that are slowly degraded, but the bulk of the tissue fibrosis, they provoke, is permanent. It is possible to use in time sequence in the same anatomical site different re-absorbable materials considering their biodegradability, whereas it is absolutely advised not to mix in the same site absorbable and nonabsorbable fillers. Autologous fat transplantation Autologous fat transplantation allows the harvesting of a small intact lump (parcel) of fatty tissue that can be processed to remove nonviable components and simultaneously avoid mechanical trauma or exposure. Utilizing strict sterile procedures the fat is injected through a cannula to ensure intimate tissue incorporation and thus limit migration. There are different phases of AFT as initially reported by Coleman [39–41]. Harvesting: A clinical or ultrasound evaluation is made to define the presence of subcutaneous fat in the abdomen, pubis, male breast, thoracic-dorsal and dorso-cervical region. Local or general anaesthesia or deep sedation is provided after discussing with the patient and considering his clinical conditions. Ringer's lactate with 1: 1 000 000 of epinephrine and 50 ml of 2% lidocaine every 1 l of Ringer's lactate, if local anaesthesia is used, is infiltrated bluntly through a stab incision prior to harvesting. The harvesting device is a 10-ml disposable Luer-lock syringe attached to a two-holed blunt cannula. The entry portal of the cannula is just large enough to allow passage of fatty tissue parcels of a size that will pass through the lumen of the tip of the Luer-lock syringe. To limit the vacuum to a minimum negative pressure, suction is hand-applied by slowly withdrawing the plunger of the 10-ml syringe in a gradual manner. The harvesting relies on the curetting action as well as the suctioning. Transfer and purification: The harvesting cannula is disconnected from the Luerlock and replaced by a cap. The plunger of the syringe is then removed, and the capped 10-ml syringe is placed into a sterilization sleeve in a sterilized central rotor of a centrifuge, which spins it at about 3000 r.p.m. for 3 or 4 min. The aspirated subcutaneous material separates into three basic layers: a top layer composed primarily of oil from ruptured fat cells; a bottom layer, composed almost entirely of blood, lidocaine and Ringer's lactate; and a middle layer of primarily usable fat tissue. The top oily layer is decanted, the dense lower layer is drained, and the remaining fat parcels are transferred in to a 1-ml Luer-lock syringe. Placement: The fat placement is performed using an 18-gauge cannula with an ejection aperture close to the closed distal end. The ejection portal is just large enough to allow passage of the fat parcels. The intact parcels are forced out of the ejection aperture by depressing the plunger on the infiltrating syringe. The size, shape and internal finish of the cannula are designed to reduce clogging and trauma to the parcels of fatty tissue. The distal end is blunt in order to reduce the risk of haematoma, nerve damage, and perforation of nontargeted tissue. The cannula initially creates tunnels inside the recipient tissue, and as it is withdrawn, the plunger of the syringe is depressed in a controlled manner so that a minuscule amount of the refined tissue (usually less than1/8 of a millilitre) is placed evenly over the length of the tunnel. Only a minimal positive pressure is ever placed on the plunger of the infiltration syringe. For 8–12 h postoperatively, cold compresses or ice packs are applied continuously on the infiltrated sites. The patient can be discharged after 2 h if local anaesthesia with sedation has been used and after 8–24 h following general anaesthesia. Apart from the operative risks the only identified complication described has been the facial fat hypertrophy at the same time of recurrence of fat hypertrophy in the harvest site [47]. Biodegradable synthetic gel fillers Biodegradable synthetically produced gel fillers used in HIV-related facial lipoatrophy include cross-linked hyaluronic acid, PLA and hydroxyapatite gel [42–45]. Hyaluronic acid gel Native hyaluronic acid is a normal polysaccharide component of mammalian soft tissues. The type of hyaluronic acid, which in gel form is injected into human tissues, has been molecularly modified – mainly by increasing cross-linkage to delay degradation – and this product, a homogenous polymer hydrogel, is FDA-approved for the treatment of wrinkles. 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The of the to be used on the face lipoatrophy severity, on the of subcutaneous fat and on the different of these procedures in the risk of to face surgery so that the of the the plastic in these is highly controlled be to define the and of the different surgical to HIV-related face lipoatrophy.