Iatrogenic lipoatrophy of the face or body can occur after the administration of many different medications, particularly antiretroviral therapy (ART) prescribed in human immunodeficiency virus (HIV) and intramuscular corticosteroids inadvertently injected into the subcutaneous fat. Both can lead to permanent disfigurement and achieving a durable correction can be challenging. To date, only a few observational studies have documented the efficacy of hyaluronic acid (HA) fillers in the correction of HIV- and/or corticosteroid-related lipoatrophy for up to 12 months after treatment. This report is the first to describe long-term improvement using volumizing, 20 mg/mL HA filler (Juvéderm Voluma [HA-V]; Allergan, Inc., Irvine, CA) lasting for at least 3 years.
A 61-year-old man presented in December 2013 for treatment of HIV-associated facial lipoatrophy. He had been on multiple antiretroviral medications since his diagnosis in 1997, including proteases inhibitors and nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine. At the time of consultation, the patient was taking a combination of efavirenz, emtricitabine, and tenofovir disoproxil (Atripla) with undetectable viral load for nearly a decade. He had never sought treatment for his atrophic changes, and after thorough discussion of the therapeutic options, including augmentation with poly-L-lactic acid (PLLA), calcium hydroxylapatite (CaHA), medical-grade liquid injectable silicone (LIS), polymethylmethacrylate (PMMA), and HA-V, he decided to proceed with the latter.
Ten milliliters of HA-V, each admixed with an additional 0.1 mL of 2% lidocaine with epinephrine 1:100,000, were injected as periosteal depots in the temples and by linear threading into the deep subcutaneous plane at the midface. Two weeks later, the patient returned for follow-up and received another 5 mL of HA-V to the midface, temple, and submalar regions. Optimal correction was noted during evaluation at 2 weeks, 6 months, 1, 2, and 3 years without touch-up (Figure 1).
Similarly, a 48-year-old healthy woman complained of a depression at the right superior buttock developing shortly after an intramuscular corticosteroid injection of unknown brand and quantity performed 5 months before by a primary care physician for an upper respiratory infection. After 1 year of observation, the deficit remained unchanged. Eight milliliters of HA-V admixed with 0.1 mL of 2% lidocaine with epinephrine 1:100,000 were injected to achieve more than 50% improvement. The patient received another 8 mL of HA-V subdermally through the tower technique and linear retrograde tunneling 1 month later. She maintained optimal correction at 1 month, 1, 2, and 3 years without touch-up (Figure 2).
Iatrogenic lipoatrophy of the face and body is a common adverse effect of medical therapies such as antiretroviral drugs and intramuscular corticosteroid injections. Augmentation with large volumes of HA-V can produce long-lasting optimal correction of such deficits; in fact, to the best of our knowledge, the results presented here are the longest duration reported—exceeding anticipated tissue reabsorption time for this hyaluronic acid product.
First described in 1998 as a component of the generalized lipodystrophy seen in patients taking ARTs, the prevalence of HIV-associated lipoatrophy ranges from 40% to 80% of those receiving first generation medications—particularly protease inhibitors and NRTIs—and continues to be a therapeutic challenge even in the era of new HIV drugs or among patients who have never been on therapy.1 Injectable augmentation is the mainstay of management, including treatment with permanent fillers (i.e., LIS or PMMA), PLLA, CaHA, autologous fat transfer, and HA. However, each has its shortcomings. Permanent products, although durable and economical, have a higher risk of granulomas and deformity. For instance, delayed inflammatory reactions occur among 3% of patients after PMMA injection compared with 0.5% to 1% with HA-V.2 In our experience, the rate of PMMA-associated fibrosis is even higher when used for larger quantity volumization; fat transfer is highly technique dependent and requires invasive harvesting of donor adipocytes, but in expert hands, it may provide long-lasting, cost-effective results. Calcium hydroxylapatite and PLLA are FDA approved to treat HIV lipoatrophy, but the effects are temporary, lasting 12 to 24 months in studies.1 And for PLLA, desired correction typically seems only after months of repeat treatment. One observational study using HA-V for HIV-associated lipoatrophy found improvement in overall appearance and patient-reported quality of life at 1 year.1 The case presented here further suggests that HA-V may provide several years of durable correction.
Atrophic soft tissue changes are also a well-documented complication of corticosteroid injection caused by accidental infusion into the subcutaneous fat rather than muscle. Some defects resolve spontaneously, whereas others persist. Successful correction of longstanding atrophy has occurred with serial saline injections into small depressions3 and fat transfer or PLLA into larger areas.4 Again, these techniques have limitations: lack of data for larger lesions, need for a donor site, unpredictable or short-lived results, and delayed time until improvement. A case report described good effect with nonanimal-stabilized HA (Restylane Perlane and Vital Light; Q-Med AB, Uppsala, Sweden).5 Our experience suggests that HA-V may provide safe, immediately appreciable, and even more persistent correction.
Hyaluronic acid–V is currently the only HA filler FDA-approved to correct midfacial volume loss for up to 2 years. This extended duration of efficacy occurs because of its unique combination of low and high molecular weight, short and long chain molecules, which cross link more efficiently. Long-term effects are also volume dependent. Both of our patients required large quantities (15–16 mL) to achieve, and then maintain optimal off-label results for longer than 2 years and longer than previously reported in the literature. Given the burden of disease, further investigation is necessary to establish the duration of and mechanisms by which HA-V counteracts iatrogenic lipoatrophy.
1. Jones DH. Treatment of HIV associated facial lipoatrophy: 2012 update. Dermatol Surg 2012;38:1206–7.
2. Kadouch JA, Kadouch DJ, Fortuin S, van Rozelaar L, et al. Delayed-onset complications of facial soft tissue augmentation with permanent fillers in 85 patients. Dermatol Surg 2013;39:1474–85.
3. Shumaker PR, Rao J, Goldman MP. Treatment of local, persistent cutaneous atrophy following corticosteroid injection with normal saline infiltration. Dermatol Surg 2005;31:1340–3.
4. Brodell DW, Marchese Johnson S. Use of intralesional poly-L-lactic acid in the treatment of corticosteroid-induced lipoatrophy. Dermatol Surg 2014;40:597–9.
5. Di Gregorio C, D'Arpa S. Therapeutic use of hyaluronic acid fillers in the treatment of corticosteroid-induced skin and subcutaneous atrophy. Dermatol Surg 2016;42:1307–10.