Case Report 13 ‘Removal of BioAlcamid presenting as a late onset infective complication in a patient with HIV + facial lipoatrophy’?

 A 43yo Irish HIV + self-referred to Ailesbury Clinic with a gross left  malar swelling for a period of over five days. They were apyrexial but the area involved was swollen  with clinical suspicion of an underlying abscess. The patient had a history of their malar area being injected at the clinic with BioAlcamid ten years before for the condition of (HIV) related facial lipoatrophy, a devastating adverse effect of their previous antiretroviral therapy. It was known to the author that Bio-Alcamid treatment of HIV-related FLA has more recently been associated with a high rate of infectious complications, often presenting many years after treatment. The patients note showed that they had been injected bilaterally with 15-30cc of a polyalkylimide gel (BioAlcamid?, Polymekon, Italy) into the buccal, malar, and temporal areas of the face in 2004 in an attempt to replace subcutaneous fat that had atrophied as a result of severe facial lipodystrophy. At the time the psychological effects of their condition (both abnormal fat loss and abnormal fat accumulation) were severely distressing, creating low self-esteem as they felt they were recognizable as HIV-positive by their physical appearance. Case non gender specific to provide anonymity.

Physical Examination

The physical exam findings included a 5 x4 cm fluculent lesion in the left malar area with no evidence of either skin erythema, oedema or warmth. The proximity of a potential infection to adjacent structures was determined. Patients with infection near the eye and nose are of particular concern due to the adjacent facial structures and the anatomy of the venous drainage. The proximity of the infection to. the “danger zone” (the triangle formed by the bridge of the nose and the corners of the mouth) was established. It is recognised that venous drainage in this area forms a communication with the brain via the superior and inferior ophthalmic veins, which empty into the cavernous sinus, creating the potential for facial infections to spread to the brain and cause serious complications such as vision loss, ophthalmoplegia, meningitis, encephalitis, intracranial abscess, sepsis, seizure, coma, and possibly death (1)

Method

The patient had a recent full hematologic evaluation including full blood count, biochemistry, liver function, lipids, glucose, lactate, viral load and CD4 cell count, which they verbally documented. The abscess was drained through a small 11 blade incision taking care to grasp the abscess from the underlying structures (facial nerve and vasculature). About 3mls of plasma coloured gel (possible pus) was removed for culture and sensitivity and the abscess drained.  

 Result

The culture returned negative but clinical suspicion at the time of drainage assumed any organism was probably methicillin-sensitive Staphylococcus aureus and the patient was commenced on Flucloxacillin 500mgs qid x 5/7. Klacid 500mgs bd would have been considered for the same period if infective evidence was more pronounced. In view of suspicion a second more cephalic abscess that could not be easily reached during drainage, the patient was later reviewed and required further drainage of a second abscess one week later. 

Discussion

The human immunodeficiency virus (HIV)-lipodystrophy syndrome (HLS) was a major problem for many HIV patients undergoing long-term use of highly active antiretroviral therapy (HAART) (2). It was characterised by a loss of subcutaneous fat, especially in the cheeks, tempomanbidular and periorbital areas. The psychological effects of HLS, with the significant alteration in facial shape that accompanies it, has a profound impact upon the psychological well The psychological effects include low self-esteem, depression, anxiety, reduced confidence as well as social withdrawal being of patients with this condition. (3)

Many strategies were used to compensate for facial fat loss. These including a range of dermal fillers including Sculptra? but this was limited in that it is was difficult to inject, it usually took many months to see the eventual effect, requiring up to five sessions to administer and the resultant contouring effect lasted two and a half years. Two studies with a follow up at 24 weeks have suggested the efficacy of treating HIV- Associated Lipoatrophy with intradermal injections of Polylactic Acid in an effort to improve appearance and reduce depression scores (4)(5). In addition, PLA did not actually restore lost fat mass where it is injected, but rather it expanded the thickness of the dermis by neocollagenesis through fibroblast stimulation. This substance was also limited due to the required multiple sessions of injections and the fact that the final effect was difficult for the patient and the proceduralist to foresee. (6)(7).

Restoring facial contour by autologous fat transfer was also deficient, in that it is limited by the availability of patient donor sites and the fact that the transferred fat is further metabolized by the on-going lipodystrophic process. Other techniques have been used in HIV-related FLA, none of which have been found to be ideal. Hyaluronic Acid is limited due to the expense involved and the rapid decline in resultant contour, which has to be replenished on a periodic basis. Some other authors experimented with bovine collagen; but the effects declined after three to six months (8)(9). Autologous fat transfer continued to atrophy, and its benefits lasted for only 6–12 months (10)(11)(12). Bio-Alcamid found favour in HIV lipodystrophic patients as it had advantages over other dermal fillers in respect to its apparent safety record and permanence.

It also appeared to be an ideal choice as it enabled a larger injection volume and significantly lower number of treatments. The injected material comprised of a network of alkyl-imide groups (approximately 4%) and non-pyrogenic water (approximately 96%). It was marketed as not migrating post-injection as it became coated by a ‘thin collagen capsule’, which transformed it into an endogenous prosthesis The compound has gained popularity in Europe in the treatment of road collision or cancer patients requiring facial reconstruction and more recently with respect to HIV-related facial lipodystrophy (13). One of the advantages of this endoprosthetic material was the ability of large quantities (200mls) being injected at one session. The polymer is an acryl-derivative and its polymeric structure does not contain free monomers, which meant that it appeared to be devoid of the risk of undesirable effects such as toxicity, lumps and pigment changes that are associated with similar materials.

Initially, there was a favorable experience with Bio-Alcamid that was reported by many physicians (14) (15). No problems were encountered in a 3 year follow up of another study concerning its use in the treatment of patients with HIV facial lipodystrophy (16) also radio-transparent and hypoechoic, thus allowing differential diagnosis when there are other structures present in the implant area. These publications tended to suggest that it was an effective long term alternative to adipose tissue auto transplantation for HIV-infected patients. Although it has been used extensively in Europe and America, long-term safety data and extended follow-up of patients who had used the compound eventually noted several complications that eventually led its discontinued use (17)(18)  

        In a retrospective evaluation conducted by the Dutch Society of Cosmetic Medicine in 20009, 40 physicians were surveyed regarding their experiences with BioAlcamid and many problems were highlighted (19). Adverse effects associated with Bio-Alcamid have been presented in a small number of reports (including both HIV and non-HIV patients), which have included migration, hardening, inflammatory reactions, granuloma formation, and infections (20). A later study funded by the Canadian Government published reports of late onset abscesses often appearing up to ten years after the initial treatment and it recommended that the product be discontinued (21) (22).

CONCLUSION: Human immunodeficiency virus (HIV)–related facial lipoatrophy was a devastating adverse effect of antiretroviral therapy. Because of the lack of viable treatment options for the condition, BioAlcamid initially lead to a high satisfaction to treat the condition due to the need for use of a larger volume to treat a more severe degree of facial lipoatrophy and the significant degree of clinical improvement in HLS patients in social functioning, and anxiety and depression scores. Although it had been used extensively in Europe and America, long-term safety data described late-appearing infections and other complications as the implant became vulnerable to contamination by skin or oral flora, especially secondary to dental injection.

References

(1) K. Jackson and S. R. Baker, “Periorbital cellulitis,” Head and Neck Surgery, vol. 9, no. 4, pp. 227–234, 1987.

(2) Oette M, Juretzko P, Kroidl A, Sagir A, et al . Lipodystrophy syndrome and self-

assessment of well-being and physical appearance in HIV-positive patients. AIDS Patient Care STDS. 2002;16:413-417.

(3) Friezel.G . Psychological assessment of patients referred to a multidisciplinary lipodystrophy/metabolic clinic. 7th Annual Conference of the British HIV Association. April 2001. Abstract P15.

(4) Mest DR, Humble G. Safety and efficacy of intradermal poly-L-lactic acid (Sculptra) injections in patients with HIV-associated facial lipoatrophy.Antivir Ther 2004; 9:L36.

(5) Valantin MA, Aubron-Olivier C, Ghosn J, et al. Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA. AIDS 2003;17:2471?77.

(6) ) Gogolewski S, Jovanovic M, Perren SM, Dillon JG, et al. Tissue response and vivo degradation of selected polyhydroxyacids (PLA, PHB, PHB/VA). J Biomed Material Res 1993;27: 1135-1148

(7) Moyle G, Lysakovo L, Brown S, Sibtain N, et al. A randomised, open-label study of immediate vs. delayed polylactic acid injections for the cosmetic management of facial lipoatrophy in persons with HIV injection., HIV Medicine, 2004; 5: 82–87.

(8) Gooderham M, Solish N. Use of hyaluronic acid for soft tissue augmentation of HIV-associated facial lipodystrophy. Dermatol Surg 2005; 31:104–8.

(9) Guaraldi G, Fontdevila J, Christensen LH, et alSurgical correction of HIV-associated facial lipoatrophy. AIDS 2011;25:1-12

 (10) Pinski KS, Roenigk HH Jr. Autologous fat transplantation: long-. term follow-up. J Dermatol Surg Oncol 1992;18:179–84.

(11) Kaminer SM, Omura NE. Autologous fat transplantation. Arch Dermatol 2001

(12) Guaraldi G, Orlando G, De Fazio D. Prospective, partially randomized, 24-week study to compare the efficacy and durability of different surgical techniques and interventions for the treatment of HIV-related facial lipoatrophy. 6th Lipodystrophy Workshop (6th IWADRLH), Washington. Abstract 12. Antiviral Therapy 2004; 9:L9.

 (13) Pacini*, Ruggiero #, Morucci # , Cammarota**, Protopapa°, and Gulisano° 'Bio-AlcamidTM: A Novelty For Reconstructive and Cosmetic Surgery' The Italian Journal of Anatomy and Embryology Vol. 107, n. 3: 209-14, July-Sep 2002

(14) Nelson L, Stewart KJ. Experience in the treatment of HIV-associated lipodystrophy. JPRAS 2008; 61:366–71.

(15) Treacy PJ, Goldberg DJ. Use of a biopolymer polyalkylimide filler for facial lipodystrophy in HIV-positive patients undergoing treatment with antiretroviral drugs. Dermatol Surg 2006; 32:804–8.

 (16) Protopapa, Sito, Caporale, and Cammarota, 'Bio-AlcamidTM in Drug-Induced Lipodystrophy' Journal of Cosmetic and Laser Therapy 2003; 5: 226-230 Drs.

 (17)  Nelson L, Stewart KJ. Early and late complications of polyalkylimide gel (Bio-Alcamid). J Plas Reconstr Aesth Surg 2011; 64:401–5.

  (18) Jones DH, Carruthers A, Fitzgerald R, Sarantopoulos P, Binder S. Late appearing abscesses after injections of nonabsorbable hydrogel polymer for HIV-associated facial lipoatrophy. Dermatol Surg 2007; 33(suppl 1):193–8.

(19) ) Schelke LW, van den Elzen HJ, Canninga M, Neumann MH. Complications after treatment with polyalkylimide. Dermatol Surg 2009; 35:1625–8.

 (20) Amin SP, Marmur ES and Goldberg DJ. Complications from Injectable Polyacrylamide Gel, a New  Non-biodegradable Soft Tissue Filler. Dermatol Surg. 30: 1507-1509. 2004

 (21)  Goldan O, Georgiou I, Grabov-Nardini G, et al. Early and late complications after a nonabsorbable hydrogel polymer injection: a series of 14 patients and novel management. Dermatol Surg 2007; 33(suppl 1):199–206.

 (22) Clin Infect Dis. 2012 Dec;55(11):1568-74. doi: 10.1093/cid/cis745. Epub 2012 Aug 31. Infectious complications of Bio-Alcamid filler used for HIV-related facial lipoatrophy. Nadarajah JT1, Collins M, Raboud J, Su D, Rao K, Loutfy MR, Walmsley S.

Dr. Patrick Treacy is Chairman of the Irish Association of Cosmetic Doctors and Irish Regional Representative of the British Association of Cosmetic Doctors. Honorary Board Member of the World Medical Trichologist Association. Fellow of the Royal Society of Medicine and the Royal Society of Arts. (London). Honorary Ambassador to the Michael Jackson Legacy Foundation and the Haiti Leadership Foundation, which opened orphanages in both Haiti and Liberia the past year. He holds Honours Degrees in Molecular Biology and Medicine. He is the recipient of the Norman Rae Gold medal from the Royal College of Surgeons in Dublin. He has also received many national and international academic awards including the prestigious AMEC Award in Paris and runner up Aesthetic Doctor of the Year UK & Ireland 2016.  

He has authored or co-authored more than 200 articles in medical and scientific journals and published many peer-reviewed papers within these disciplines, including a sentinel study on the rising incidence of cutaneous malignant melanoma for the Mayo Clinic, Rochester in 1990. He pioneered facial implant techniques for HIV related facial lipodystrophy and early radiosurgery venous thermocoagulation. He is an advanced aesthetic trainer and has trained over 800 doctors and nurses from around the world. 

He is a renowned international guest speaker and features regularly on national television and radio programmes. He has featured on the Today Show, Ireland AM, CNN, Dr. Drew, RTE, TV3, Sky News, BBC and Newsweek.