Journal of Plastic, Reconstructive & Aesthetic Surgery (2011) 64, 401e405

CASE REPORT

Early and late complications of polyalkylimide gel(Bio-Alcamid)�

Lisa Nelson *, Kenneth J. Stewart

Edinburgh Plastic Surgery Unit, St Johns Hospital, Livingston, Howden Road, West Lothian EH56 6PP, Scotland, UK

Received 23 February 2010; accepted 23 April 2010

KEYWORDSPolyalkylimide gel;Complications;HIV lipodystrophy

* Corresponding author. Canniesburgow Royal Infirmary, 84 Castle Streetþ44 141 211 4000.

E-mail address: drlisanelson@hotm

1748-6815/$-seefrontmatterª2010Bridoi:10.1016/j.bjps.2010.04.039

Summary This case report summarises early and late of complications that have developedinpatients treated with Bio-Alcamid for HIV-associated facial lipoatrophy and describes themanagement strategy employed to treat the most serious of these cases.ª 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published byElsevier Ltd. All rights reserved.

Bio-Alcamid� (Polymekon, Milan, Italy) is a non-biodegrad-able hydrogel polymer that has gained widespread use incosmetic and reconstructive practise since obtaining the CE(Conformite European) certificate in 2001. The product is analkylic resin containing 96% pyrogen-free water and 4%alkylimide-amide groups, and is considered tobeapermanentfiller due to the stability of its chemical properties andresistance to hydrolysis.1 Once injected, Bio-Alcamid�becomes enclosed within a thin (0.02 mm) collagen capsule.2

The process commences within a few days of injection and iscompleted by 6 weeks. Bio-Alcamid� is thus considered tobe an endoprosthesis due to the encapsulation process whichisolates the injected material from surrounding host tissues.This is reported to contribute to the safety of the productand prevent migration of injected material.3

Several authors have reported success of Bio-Alcamid� forthe treatment of patients with HIV-associated lipoatrophy

n Plastic Surgery Unit, Glas-, Glasgow G4 0SF, UK. Tel.:

ail.com (L. Nelson).

tishAssociationofPlastic,Reconstruc

with minimal side-effects.2,4-6 However, reports of long-termcomplications following injection theproduct arebeginning toemerge.7-9 We report a summary of complications that havedeveloped in seven HIV patients treated with Bio-Alcamid�for HIV-associated facial lipoatrophy and describe themanagement strategy employed to treat some of these cases.

Complications with Bio-Alcamid�

Eighteen patients with HIV-associated facial lipoatrophyunderwent treatment using Bio-Alcamid� within a clinicaltrial in the Edinburgh Unit between September 2005 andSeptember 2007. A summary of complications is provided intable one. The onset of complications following injection ofBio-Alcamid� ranged from 2 months to 3 years and sixpatients developed more than one type of complication.Nine patients required minor revision procedures to correctareas of asymmetry or irregularity. All primary proceduresand revisions were performed in the operating theatreunder general or local anaesthesia using aseptic techniqueand prophylactic co-amoxiclav. Infection occurred in fourpatients necessitating surgical removal in one patient. A

tiveandAestheticSurgeons.PublishedbyElsevierLtd.All rightsreserved.

402 L. Nelson, K.J. Stewart

minor revision procedure preceded infection in 2 of thesepatients but no precipitating event occurred in the other 2patients. Inferior migration of the product from the malarregion to the jowls occurred in three patients and excessivecapsule formation was observed in two patients. Allpatients had stable HIV haematological parametersthroughout treatment and follow-up (Table 1).

Case reports

Case 1

A 45-year-old man underwent injection of 37 cc Bio-Alcamid� to each cheek and temple. Fourteen monthslater, he developed of chronic swelling of the left temple.Viscous fluid was present surrounding the capsule suggest-ing low-grade infection, although pus was subsequentlyaspirated from this region and both cheeks. Two monthslater, the patient presented with an acute abscess of theright cheek requiring incision and drainage. Microbiologicalassessment isolated clostridium perfringens and thepatient was commenced on a prolonged course of oralmetronidazole. At follow-up assessment, pus dischargingfrom a sinus tract at the right cheek was discovered(Figure 1). Therefore, all remaining Bio-Alcamid� wasremoved from the right cheek and temple via stab incisions,curettage and irrigation. The patient refused removal ofthe product from the left side of his face and long-termoral metronidazole therapy was continued. Four monthslater, the areas of inflammation remained quiescent butresulted in undesirable facial scarring (Figure 2). In addi-tion, the patient also developed problematic metronida-zole-induced paraesthesia.

Table 1 Summary of complications associated with the use of

Case Sex Age Complication Onset Treatment

1. M 51 Infection 2 months Oralaugmentin

2. M 47 Infection 6 months Oralaugmentin

3. M 52 Asymmetry 1month 2 attempts atremoval vianeedle puncture.

4. M 45 Asymmetry 1 month Revision by furtherinjection ofBio-Alcamid�.

5. M 41 Asymmetry 1 month Revision by aspiration& further injection ofBio-Alcamid�.

6. M 39 Asymmetry 1 month Revision by aspiration &further injection ofBio-Alcamid�

7. M 59 Inferiormigration

3 years Removal of Bio-Alcamid�.

Case 2

A 52-year-old man underwent injection of 39 cc Bio-Alcamid� to the cheek and temple region bilaterally. Tworevision procedures to correct minor asymmetry were per-formed via needle puncture of the capsule. Six monthslater, the patient developed extrusion of Bio-Alcamid tothe buccal mucosa of the right cheek (Figure 3). Manualexpression of Bio-Alcamid� via the fistula tract combinedwith antibiotic prophylaxis was attempted on two occa-sions. However, the patient subsequently required removalof all remaining product via stab incisions and curettage.

Case 4

A 56-year-old man who underwent injection of 30 cc Bio-Alcamid� to both cheeks presented 3 years later withsignificant inferior migration to the jowls bilaterally(Figure 4). Further surgery to remove the product via stabincisions is planned.

Discussion

For patients with severe facial lipoatrophy, Bio-Alcamid�has been advocated as an effective treatment option.When compared to other fillers, polyalkylimide gel can beused in large quantities and a permanent correction can beachieved in one or two sessions. Several authors havereported high patient and surgeon satisfaction with minimalside effects2, 4e6 and improved quality of life.10,11 An early,multicentre study of 2000 patients reported excellentcosmetic results with only 12 complications of S. aureus

Bio-Alcamid� in the Edinburgh Unit

Co-complication(s) Onset Treatment

Capsule formation/Inferior migration

12 months Expression ofBio-Alcamid� viastab incision.

Inferior migration 16 months Removal Bio-Alcamid�& Coleman fattransfer.

Intra-oral extrusion 12 months Surgical removal bystab incisions/curettage.

Chronic inflammation/acuteabscesses at 3 sites.

2 years Surgical removal bystab incsions,curettage & irrigation.I.V. antibiotics &long-term oralantibiotics.

Infection 1 weekpost-revision

I.V. flucloxicillin &benzlypenecillin

Excess capsuleformation

3 months None

Figure 3 Extrusion of Bio-Alcamid�.Figure 1 Sinus of the right cheek.

Early and late complications of polyalkylimide gel 403

infection. This study also reported no observed cases ofmigration, dislocation, granulomas, allergic response orintolerance of the implant.12

More recently, reports have emerged from plasticsurgery units which have become referral centres forcomplications relating Bio-Alcamid�. Schelke et al con-ducted a retrospective review of 3196 patients treatedwith polyalkylimide in the Netherlands and have reporteda patient complication rate of 4.8%.13 The most commoncomplication was inflammation (2%), followed by accumu-lation of the product (1%), hardening of the capsule (1%)and migration (0.7%). The greatest concern with the useof Bio-Alcamid�, particularly in HIV positive individuals,is the potential for infection. Indeed, Schelke et al havealso reported a higher incidence of inflammation in thispatient group (3.3%). Although a number of safety studieshave shown Bio-Alcamid� to be non-toxic, non-allergenic,

Figure 2 Post-operative result following removal of Bio-Alcamid�.

non-reactive, biocompatible and non-biodegradable,1,3,14

it still carries the risk associated with implants to providea favourable environment to harbour bacteria. Severalauthors have emphasised the late appearance ofabscesses months to years after injection of the material.In some cases, the onset of infection was triggered byadditional revision procedures at or near the site ofprevious injections.8 However, complications may alsoarise spontaneously without any history of trauma or localinfection. In most published cases, microbacterialcultures have demonstrated streptococcal or staphylo-coccal bacteria. Interestingly, Clostridium perfringens,an anaerobic bacteria commonly associated with foodborne illness, was isolated in one of our patients. Manage-ment of infection by antibiotic therapy or attempted aspi-ration is often unsuccessful. Surgical incision and drainageis usually required to remove all infected material result-ing in undesirable facial scarring. A technique of drainage

Figure 4 Inferior migration of Bio-Alcamid�.

404 L. Nelson, K.J. Stewart

utilising an irrigation system has been described by oneinstitution to minimise skin incisions.9 The potential forinfection-related complications is a disastrous and unac-ceptable result for patients seeking cosmetic enhance-ment. Because spontaneous inflammatory reactions arepossible years after injection, it has been suggested thatBio-Alcamid� may lead to chronic interference withsurrounding tissues and enhanced susceptibility to infec-tions. Thus, immunocompromised patients with HIV infec-tion may represent an even more vulnerable patient group.Although, warnings against the use of Bio-Alcamid� forcosmetic indications have been published,8 Bio-Alcamid�is still considered to have a role in the management ofsevere reconstructive deficits such as HIV lipodystrophy.However, we would caution against the use of this producteven more so in this patient group.

Bio-Alcamid� is also prone to other risks associated withprostheses such as migration and capsule contraction.Capsule formation around the implant is suggested toprevent migration by providing anchorage with surroundingtissues.3 However, gravitational migration was evident in 3of our patients and is perhaps associated with injection oflarge volumes of the material into mobile areas. It hasbeen suggested that filler migration may occur after mani-pulation of the product with disruption of the surroundingcapsule.15 However, we have also observed marked migra-tion of Bio-Alcamid� in patients who have not undergonerevision procedures. Areas of excessive capsule formationcan also be unpredictable and difficult to treat.

The economic burden of complications relating to Bio-Alcamid� must also be considered. The requirement for inpatient admission, intravenous antibiotic therapy, surgicaldrainage and further corrective procedures may incursignificant costs to health trusts. Although private cosmeticpractitioners carry out many of these procedures, patientswith complications often present via acute hospital settingsseeking treatment. In addition, some cosmetic practi-tioners lack the facilities or skill to address complicationsrequiring surgical removal.

As these serious long-term complications of Bio-Alcamid� emerge, several practitioners who previouslyadvocated its use now strongly caution against it. Lettersof concern regarding the use of Bio-Alcamid� have beensubmitted to the National Institute of Clinical Excellence(NICE) in the UK although no recommendations have beenpublished. The Dutch Society of Cosmetic Medicineconsiders the overall complication rate of polyalkylimidetoo high risk for cosmetic treatment and now advisesagainst its use.13 Our early published results using Bio-Alcamid� to treat HIV-associated lipoatrophy were alsofavourable.16 However, extended follow-up of thesepatients within a clinical trial has led us to discontinueBio-Alcamid� injections. We hope our series of complica-tions will add to the growing body of evidence that Bio-Alcamid� may have significant long-term problems andthat its use should be restricted or discontinued entirely.

Conflict of interest statement

None of the authors have any conflict of interest in theresearch or products reported in this article.

Product

The case report describes complications with the use ofBio-Alcamid� (Polymekon, Milan, Italy).

This research was funded by the following charities:

1. The Henry Smith Charity, 6th Floor, 65 LeadenhallStreet, London EC3A 2AD

2. The Sick Kids Foundation, Edinburgh3. The William Rooney Plastic and Reconstructive Surgery

Fund, Edinburgh4. NHS Lothian Endownments Fund, Edinburgh

This research has received full ethical approval from theMulti-Centre Research Ethics Committee for Scotland

References

1. Ramires PA, Miccoli MA, Panzarini L, et al. In vitro and in vivobiocompatibility of a polyalkylimide hydrogel for soft tissueaugmentation. J of BiomedMaterials Research. 2005;72:230e8.

2. Protopapa C, Sito G, Caporale, et al. Bio-alcamid in drug-induced lipodystrophy. J Cosmetic & Laser Ther 2003;5:226e30.

3. Formigli L, Zecchi S, Protopapa C, et al. Bio-Alcamid: an elec-tron microscopic study after skin implantation. Plas ReconSurg. 2004;113:1104e6.

4. Honig JF. Cheek augmentation with Bio-alcamid in facial lipoa-trophy in HIV seropositive patients. J of Craniofacial Surg 2008;19:1085e8.

5. Lahiri A, Waters R. Experience with Bio-alcamid, a new softtissue endoprosthesis. JPRAS 2007;60:663e7.

6. Ramon Y, Lucian F, Ullman Y. Preliminary experiences with Bio-alcamid in HIV facial lipoatrophy. Dermatology 2007;214:151e4.

7. Jones DH, Carruthers A, Fitzgerald R, et al. Late-appearingabscesses after injections of nonabsorbable hydrogel polymerfor HIV-associated facial lipoatrophy. Dermatol Surg 2007;33:193e8.

8. Karim RB, Hage JJ, van Rozelaar L, et al. Complications of pol-yalkylimide 4% injections (Bio-alcamid): a report of 18 cases.JPRAS 2006;59:1409e14.

9. Goldan O, Georgiou I, Grabov-Nardini G, et al. Early and latecomplications after a nonabsorbable hydrogel polymer injec-tion: a series of 14 patients and novel management. DermatolSurg 2007;33:199e206.

10. Loufty MR, Raboud JM, Antoniou T, et al. Immediate versusdelayed polyalkylimide gel injections to correct facial lipoatro-phy in HIV-positive patients. AIDS 2007;21:1147e55.

11. Karim RB, de Lint CA, van Galen SR, et al. Long-term effect ofpolyalkylimide gel injections on severity of lipoatrophy andquality of life. Aesthetic Plastic Surgery. 2008;32:873e8.

12. Pacini S, Ruggiero M, Morucci G, et al. Bio-alcamid: a noveltyfor reconstructive and cosmetic surgery. Ital J Anat Embryol.2002;107:209e14.

13. Schelke LW, Van Del Elzen HJ, Canninga M, et al. Complicationsafter treatment with polyalkylimide. Dermatol Surg 2009;35:1625e8.

14. Pacini S, Ruggiero M, Cammarota N, et al. Bio-alcamid, a novelprosthetic polymer, does not interfere with morphological andfunctional characteristics of human skin fibroblasts. Plas ReconSurg. 2003;111:489e91.

15. Adam RH, Malhotra R. Long-term complications orbitofacial ofPolyalykylimide 4% (Bio-alcamid). Ophth Plast & Recon Surg2009;25:394e7.

16. Nelson L, Stewart KJ. Experience in the treatment of HIV-asso-ciated lipodystrophy. JPRAS 2008;61:366e71.