INTRODUCTION
Fillers used in aesthetic medicine can be divided into 2 major groups: absorbable
fillers and permanent fillers1. Some of
the advantages of absorbable fillers include the reversibility of undesired
results, whether by action of an “antidote” or through resorption by the body
itself. With permanent fillers, however, complications become a real problem due
to persistence of the product and perpetuation of unwanted results2.
These complications are inherent to all types of fillers and may be classified as
acute or chronic. Acute complications include vascular embolism, necrosis,
allergic reactions, and infections. Chronic complications include granuloma
formation, deformities, and inflammatory reactions2.
The acute complications deserve attention because they depend directly on
practitioner qualifications and training. For the most part, this type of
complication is more related to treatment technique and not necessarily to the
product used3.
The most commonly used permanent filler is polymethylmethacrylate (PMMA). PMMA is
available as polymeric microspheres ranging in size from 30 to 103 µm. These
spheres are suspended in a vehicle of bovine collagen, carboxymethylcellulose,
or sodium hyaluronate, which are resorbed after a few days2.
In 2006, the U.S. Food and Drug Administrationapproved
ArteFill for use by physicians alone, and limited its
application to perioral volume augmentation, e.g., nasolabial filling, excluding
that of the lips4. In Brazil, the National
Health Surveillance Agency (Agência Nacional de Vigilância Sanitária, ANVISA)
recommends use by trained medical professionals, and does not contraindicate use
for body filling or provide guidelines for aesthetic use5.
As PMMA is inexpensive and easily obtained, numerous cases of complications have
occurred, arising from use by untrained professionals in substandard aesthetic
centers. This case report describes complications due to use of PMMA filler in a
clandestine clinic in the city of São Paulo, and discusses the current status of
PMMA use in Brazil.
CASE REPORT
A 21-year-old female presented with a history of injection of 900 ml of PMMA in
the buttocks 12 days prior. The procedure was performed in a beauty salon by a
nonmedical professional. She had pain and ulcerated wounds with purulent
secretions at the injection site (Figure 1), and had already received ciprofloxacin and clindamycin for 7 days
without improvement, as well as day hospital treatment with ceftriaxone and
prednisone.
Figure 1 - Surgical wound appearance after serial debridement. a: left
lateral, b: posterior, c: right lateral; I: at 14 days;
II: after first debridement; III:
after second debridement, circumferential increase in surgical wound
hyperemia and coalescence of wounds in the sacral region;
IV: after third debridement, circumferential
increase in surgical wound hyperemia; V: after fourth
debridement, appearance of necrosis in the sacral region.
Figure 1 - Surgical wound appearance after serial debridement. a: left
lateral, b: posterior, c: right lateral; I: at 14 days;
II: after first debridement; III:
after second debridement, circumferential increase in surgical wound
hyperemia and coalescence of wounds in the sacral region;
IV: after third debridement, circumferential
increase in surgical wound hyperemia; V: after fourth
debridement, appearance of necrosis in the sacral region.
On admission, the patient was afebrile and hemodynamically stable. Laboratory
tests showed leukocytosis and elevated C-reactive protein, and computed
tomography showed densification and thickening of the skin and subcutaneous
tissue of the gluteal regions, in addition to multiple nodular formations
consistent with exogenous material/granulomas (Figure 2), but no evidence of collections.
Figure 2 - 3D tomographic reconstruction on admission. Blue represents
infiltration of subcutaneous tissue in the bilateral gluteal regions
at PMMA application sites. A: anterior view;
B: posterior view. In retrospective analysis, image
of infiltrated area coincided with that of debridement area.
Figure 2 - 3D tomographic reconstruction on admission. Blue represents
infiltration of subcutaneous tissue in the bilateral gluteal regions
at PMMA application sites. A: anterior view;
B: posterior view. In retrospective analysis, image
of infiltrated area coincided with that of debridement area.
She initially received empirical broad-spectrum antibiotic therapy, but the wound
deteriorated. Serial debridement was performed (Figure 1), and continuous negative pressure therapy was applied at
125 mmHg, with sequential exchanges every 3 to 5 days. Suppuration and necrosis
of the dermis (Figure 3) and subcutaneous
tissue were observed, with nodular formations containing pus and exogenous
material in addition to signs of bilateral gluteus maximus fasciitis. Fragments
of soft tissue were sent for culture, but no microorganism was identified.
Figure 3 - Skin necrosis in a surgical specimen. A: purplish
spots on the surface; B: epidermis folded back to show
dermis and subcutaneous tissue with extensive necrosis.
Figure 3 - Skin necrosis in a surgical specimen. A: purplish
spots on the surface; B: epidermis folded back to show
dermis and subcutaneous tissue with extensive necrosis.
Due to the severity of the inflammatory/infectious process, she remained in the
intensive care unit for 14 days, and developed acute renal failure. She showed
progressive improvement after the 3rd debridement.
Given the size of the wound after sequential debridement and the extensive loss
of nutrients, hemoglobin, and microelements, bilateral homologous skin grafting
was performed over the gluteus maximus (Figure 4), with addition of negative pressure therapy (Figure 5).
Figure 4 - Wound appearance after serial debridement and homologous skin
grafting. a: left lateral, b: posterior,
c: right lateral; VI: after sixth
debridement, showing extension to the sacral region;
VII: 1:1.5 mesh graft over the gluteus maximus
bilaterally.
Figure 4 - Wound appearance after serial debridement and homologous skin
grafting. a: left lateral, b: posterior,
c: right lateral; VI: after sixth
debridement, showing extension to the sacral region;
VII: 1:1.5 mesh graft over the gluteus maximus
bilaterally.
Figure 5 - Negative pressure therapy at homologous graft sites.
A: left gluteal wound with 1:1.5 mesh graft and
right gluteal wound with non-adherent gauze on the graft;
B: negative pressure dressing sponge in place;
C: continuous vacuum at 125 mmHg.
Figure 5 - Negative pressure therapy at homologous graft sites.
A: left gluteal wound with 1:1.5 mesh graft and
right gluteal wound with non-adherent gauze on the graft;
B: negative pressure dressing sponge in place;
C: continuous vacuum at 125 mmHg.
After 3 weeks of treatment with biological dressings (homologous grafts) and
improvement of nutritional parameters, autologous skin grafting was performed
(Figure 6) with 1:1.5 mesh. The graft
showed good integration (Figure 7) without
functional deficits, and the patient was discharged after 68 days of
hospitalization.
Figure 6 - Wound appearance after 3 weeks with homologous grafting and
subsequent immediate autologous grafting. a: left
lateral; b: posterior; c: right lateral;
VIII: after ninth debridement and 3 weeks of
homologous grafting over the gluteus maximus; IXa:
1:1.5 mesh graft over gluteus maximus after debridement of
hypertrophic granulation and epidermal remnants of previous
homologous graft; IXc: appearance of wound bed after
debridement of previous homologous graft.
Figure 6 - Wound appearance after 3 weeks with homologous grafting and
subsequent immediate autologous grafting. a: left
lateral; b: posterior; c: right lateral;
VIII: after ninth debridement and 3 weeks of
homologous grafting over the gluteus maximus; IXa:
1:1.5 mesh graft over gluteus maximus after debridement of
hypertrophic granulation and epidermal remnants of previous
homologous graft; IXc: appearance of wound bed after
debridement of previous homologous graft.
Figure 7 - A: Sixth postoperative day. Appearance of partial,
autologous 1:1.5 skin mesh graft. B: 1-month
postoperatively, showing integration of graft and wound.
Figure 7 - A: Sixth postoperative day. Appearance of partial,
autologous 1:1.5 skin mesh graft. B: 1-month
postoperatively, showing integration of graft and wound.
PMMA in Brazil
The use of PMMA as a filler has been approved under federal law since 2004
for treatment of HIV-associated lipodystrophy6. However, indiscriminate use for aesthetic purposes without
scientific evidence merited a public alert by the Federal Medical Council
(Conselho Federal de Medicina, CFM) in 2006, as non-qualified practitioners
promoted a technique known as “bioplasty”.7
In 2007, ANVISA prohibited the preparation of PMMA products by compounding
pharmacies in order to regulate quality and purity8.
In 2008, complications related to PMMA use in a series of 32 cases led to
classification into 5 types: necrosis, granuloma, chronic inflammatory
reaction, lip complications, and infection. Necrosis is always an acute
complication, whereas inflammatory complications can occur many years after
injection. The rarity of the complications was highlighted, but it was
difficult to estimate the incidence and prevalence in the entire population.
In addition, concern was raised about serious complications, which, in
addition to being permanent, are often untreatable2.
In 2009, another series of 18 cases with various complications related to
PMMA use highlighted the indiscriminate use of this substance owing to its
low cost and the lack of regulation of its sale to nonspecialist physicians
and nonphysicians9. In 2012, a
histopathological study of 63 cases of complications attributed to PMMA
identified 5 cases with acute complications, all of which developed necrosis
after injection10.
In 2010, the Regional Medical Council of Paraná (Conselho Regional de
Medicina do Paraná, CRM-PR) issued an opinion that the unrestricted use of
PMMA in gluteal augmentation, or use in large quantities, was unsafe and
unpredictable, and could lead to chronic reactions and unmanageable
complications11. In 2012, ANVISA
issued a safety alert highlighting the possible chronic complications of
PMMA, as well as the need for professional training in its use12,13.
In 2013, the CFM issued a new opinion reinforcing the 2010 opinion of the
CRM-PR and reaffirming the limited indications for PMMA injection, noting
that use in large quantities could lead to unpredictable results14. In this opinion, both the Brazilian
Society of Plastic Surgery (Sociedade Brasileira de Cirurgia Plástica, SBCP)
and the Technical Chamber of Plastic Surgery of the CFM recommended that
PMMA only be used by physicians, as well as in small doses and with
restrictions.
The 2016 census by the SBCP-SP (regional São Paulo branch) reported that a
total of 4,432 procedures were performed to treat complications of PMMA
injection, equivalent to 0.7% of the total number of reparative procedures
in that year15. In the same year,
more than 17,000 complications associated with use of PMMA were recorded in
Brazil. Meanwhile, the use of nonsurgical procedures (primarily for filling)
increased by 390% in a 2-year period16.
DISCUSSION
Based on the data for the last decade, concerns about these procedures are
inevitable. Despite the significant and immediate results in aesthetic filling,
the unregulated popularization of PMMA use, in addition to its use in large
volumes with inadequate technique, have shown that PMMA can be harmful when
misused for this purpose.
In Brazil, the regulation and supervision of aesthetic medical centers by
responsible agencies remain inadequate. In addition, despite the efforts of
medical societies, misinformation is widely disseminated, made worse by
increasing exposure on social media. This misinformation exposes patients to
unsafe procedures.
With reports of significant adverse outcomes in the Brazilian media in recent
years, including mutilating and fatal cases, medical societies have spoken out
against the use of PMMA for aesthetic purposes. In 2018, both the SBCP and the
Brazilian Society of Dermatology (Sociedade Brasileira de Dermatologia, SBD)
issued a warning on the use of PMMA, with a contraindication for use in large
amounts, reinforcing the unpredictability of results and requesting the
recategorization and restriction of its use by ANVISA17.
Reports of adverse outcomes related to PMMA are rare in the medical literature,
with complication rates ranging from 0.01% to 3%2,18. Although
small, these numbers deserve attention, since underreporting of complications is
known to occur, both because they may be delayed and also due to omission of
reporting in the medical record3.
Furthermore, it may be unclear whether complications are caused by PMMA itself
or poor technique. Complications caused by permanent fillers deserve special
attention, because they create chronic problems and are difficult to treat.
Despite the availability of protocols, there is no consensus on standardization
of treatment19.
Complications, such as necrosis, are even rarer (0.003%)18. Technical failure is attributed to the application of
needles in flat surfaces and not necessarily to PMMA. In one author’s account of
personal experience with more than 5,000 cases published in 201220, a complication rate of 0.01% was
reported, with no necrosis observed. This was ascribed to adherence to 3
principles: deep plane application, use of a microcannula, and use of pure and
certified PMMA.
In the case described herein, both the quality of the product and the technique
used were questionable. The combination led to severe complications.
Acute local inflammation within the first hours after treatment was an important
warning sign that required close monitoring. With progression to necrosis,
aggressive surgical debridement combined with negative pressure therapy were
imperative for treatment of inflammation and preparation of the wound bed21. Debridement surgery is challenging,
because healthy tissue is invaded by necrotic tissue, creating a false
impression of satisfactory treatment. Coverage of the wound after proper
cleaning is also challenging, however, and sequelae and deformities may not be
be fully corrected by plastic surgery.
The use of diagnostic tomography in the present case was a predictor of the
extent of necrosis, since it revealed densification of affected tissue, even in
areas that still appeared clinically healthy. The findings coincided with the
debrided areas. There are no comparable studies in the literature.
CONCLUSION
Despite low published complication rates in Brazil, an excessive number of repair
procedures are needed to correct complications from use of PMMA. The severity of
the reported case highlights the need to combat bad practice by untrained
practitioners, as well as the need for greater regulation of the
commercialization of PMMA. Complications can lead to death and permanent
deformity, and treatment is challenging.
COLLABORATIONS
KTK
|
Analysis and/or data interpretation, conception and design study,
data curation, final manuscript approval, investigation,
methodology, project administration, realization of operations
and/or trials, writing - original draft preparation, writing -
review & editing.
|
MM
|
Realization of operations and/or trials.
|
DAM
|
Realization of operations and/or trials, supervision, writing -
review & editing.
|
AAMJ
|
Supervision.
|
RG
|
Supervision, visualization.
|
REFERENCES
1. Carruthers J, Carruthers A, Humphrey S. Introduction to Fillers.
Plast Reconstr Surg. 2015;136(5 Suppl):120S-31S.
2. Salles AG, Lotierzo PH, Gemperli R, Besteiro JM, Ishida LC, Gimenez
RP, et al. Complications after polymethylmethacrylate injections: report of 32
cases. Plast Reconstr Surg. 2008;121(5):1811-20. PMID: 18454007 DOI: https://doi.org/10.1097/PRS.0b013e31816b1385
3. Rzany B, DeLorenzi C. Understanding, Avoiding, and Managing Severe
Filler Complications. Plast Reconstr Surg. 2015;136(5
Suppl):196S-203S.
4. U. S. Food and Drug Administration - FDA. ArteFill® -
P020012. Silver Spring: FDA; 2006 [acesso 2018 Set 5]. Disponível em: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P020012
5. Brasil. Ministério da Saúde. Agência de Vigilância Sanitária
(Anvisa). Anvisa esclarece sobre indicações do PMMA. Brasília: Anvisa; 2018
[acesso 2018 Set 5]. Disponível em: http://portal.anvisa.gov.br/rss/-/asset_publisher/Zk4q6UQCj9Pn/content/anvisa-esclarece-sobre-indicacoes-do-pmma/219201?inheritRedirect=false
6. Brasil. Ministério da Saúde. Secretaria de Atenção à Saúde. Portaria
Conjunta SAS SVS Nº 01, de 20 janeiro de 2009. Brasília: Ministério da Saúde;
2009 [acesso 2018 Set 5]. Disponível em: http://portal.anvisa.gov.br/documents/33868/2492231/doc_alerta_954.pdf
7. Jornal da Associação Médica. Especialidade: CFM faz alerta sobre
bioplastia [acesso 2018 Set 5] 2006. Disponível em: http://portal.anvisa.gov.br/documents/33868/2492231/doc_alerta_953.pdf
8. Brasil. Ministério da Saúde. Agência de Vigilância Sanitária
(Anvisa). Resolução - RE Nº 2.732, de 5 de setembro de 2007. Brasília: Diário
Oficial da União; 2007 [acesso 2018 Set 5]. Disponível em: http://portal.anvisa.gov.br/documents/33868/2492231/doc_alerta_955.pdf
9. Vargas AF, Amorim NG, Pitanguy I. Complicações tardias dos
preenchimentos permanentes. Rev Bras Cir Plást.
2009;24(1):71-81.
10. de Melo Carpaneda E, Carpaneda CA. Adverse results with PMMA
fillers. Aesthetic Plast Surg. 2012;36(4):955-63. DOI: 10.1007/s00266-012-9871-8
DOI: https://doi.org/10.1007/s00266-012-9871-8
11. Conselho Regional de Medicina do Paraná. PARECER Nº 2238/2010
CRM-PR. Processo Consulta Nº 107/2010. Assunto: Procedimento de Bioplastia de
Glúteo. EMENTA: Bioplastia - Uso da Substância Polimetilmetacrilato (PMMA)
[acesso 2018 Set 5]. Disponível em: https://sistemas.cfm.org.br/normas/visualizar/pareceres/PR/2010/2238
12. Brasil. Ministério da Saúde. Agência de Vigilância Sanitária
(Anvisa). Alerta de Segurança para a utilização do Produto POLIMETILMETACRILATO
PMMA. Brasília: Anvisa; 2012 [acesso 2018 Set 5]. Disponível em: http://portal.anvisa.gov.br/resultado-de-busca?p_p_id=101&p_p_lifecycle=0&p_p_state=maximized&p_p_mode=view&p_p_col_id=column-1&p_p_col_count=1&_101_struts_action=%2Fasset_publisher%2Fview_content&_101_assetEntryId=2633703&_101_type=content&_101_groupId=33868&_101_urlTitle=2633700&inheritRedirect=true
13. Requena L, Requena C, Christensen L, Zimmermann US, Kutzner H,
Cerroni L. Adverse reactions to injectable soft tissue fillers. J Am Acad
Dermatol. 2011;64(1):1-34. DOI: https://doi.org/10.1016/j.jaad.2010.02.064
14. Brasil. Conselho Federal de Medicina (CFM). Processo-Consulta CFM Nº
70/12 - Parecer CFM Nº 5/13. Uso indiscriminado do polimetilmetacrilato (PMMA).
EMENTA: Recomenda-se que o PMMA, quando utilizado, seja feito por médicos, em
pequenas doses, pois o uso em grandes doses pode produzir resultados
indesejáveis. Brasília: CFM; 2013 [acesso 2018 Set 5]. Disponível em: http://www.portalmedico.org.br/pareceres/cfm/2013/5_2013.pdf
15. Sociedade Brasileira de Cirurgia Plástica (SBCP). Censo 2016.
Situação da Cirurgia Plástica no Brasil. Análise Comparativa das Pesquisa 2014 e
2016. São Paulo: SBCP; 2017 [acesso 2018 Set 5]. Disponível em: http://www2.cirurgiaplastica.org.br/wp-content/uploads/2017/12/CENSO-2017.pdf
16. Aplicação de PMMA resulta em mais de 17 mil complicações em 2016.
Plast Pau. 2016;60:24 [acesso 2018 Set 5]. Disponível em: http://sbcp-sp.org.br/downloads/revista-plastica-paulista-2016-ed-60.pdf
17. Conselho Regional de Medicina do Estado de São Paulo (Cremesp),
Sociedade Brasileira de Cirurgia Plástica (SBCP), Sociedade Brasileira de
Dermatologia (SBD). Nota de Agravo: CREMESP, SBCP e SBD pedem retratação à
Anvisa sobre indicações do PMMA. São Paulo: Cremesp, SBCP, SBD [acesso 2018 Set
5]. Disponível em: http://www.sbd.org.br/noticias/nota-de-agravo-cremesp-sbcp-e-sbd-pedem-retratacao-a-anvisa-sobre-indicacoes-do-pmma/
18. Blanco Souza TA, Colomé LM, Bender EA, Lemperle G. Brazilian
Consensus Recommendation on the Use of Polymethylmethacrylate Filler in Facial
and Corporal Aesthetics. Aesthetic Plast Surg. 2018;42(5):1244-51. DOI:
https://doi.org/10.1007/s00266-018-1167-1
19. Cassuto D, Pignatti M, Pacchioni L, Boscaini G, Spaggiari A, De
Santis G. Management of Complications Caused by Permanent Fillers in the Face: A
Treatment Algorithm. Plast Reconstr Surg. 2016;138(2):215e-27e. PMID:
27465182
20. Nácul AM, Valente DS. Complications after polymethylmethacrylate
injections. Plast Reconstr Surg. 2009;124(1):342-3. PMID: 19568132 DOI:
https://doi.org/10.1097/PRS.0b013e3181a83ac2
21. Milcheski DA, Ferreira MC, Nakamoto HA, Pereira DD, Batista BN, Tuma
P Jr. Subatmospheric pressure therapy in the treatment of traumatic soft tissue
injuries. Rev Col Bras Cir. 2013;40(5):392-6. DOI: https://doi.org/10.1590/S0100-69912013000500008
1. Hospital das Clínicas, Faculdade de Medicina,
Universidade de São Paulo, São Paulo, SP, Brazil.
Corresponding author: Kleber Tetsuo
Kurimori Rua Estela, nº 287, Apto 13 - Vila Mariana, São Paulo, SP,
Brazil Zip Code 04011-001 E-mail:
kleber.kurimori@gmail.com
Article received: October 18, 2018.
Article accepted: February 10, 2019.
Conflicts of interest: none.