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1. Patients with adverse reactions to subcutaneous
injection of Aquamid (polyacrylamide hydrogel)
Lise Christensen, MD, dr.med.
Senior pathologist
Rigshospitalet, Copenhagen, Denmark

2. Polyacryl amide hydrogel (PAAG)
A gel consisting of a backbone of approximately 2.5 % cross-
linked polyacrylamide and 97.5 % water
soft contact lenses, opthalmic surgery, packaging agent
in food, clarification agent for sugar juices , in water
purification
Has been used in plastic and aesthetic surgery in the former
Soviet Union for more than 15 years and in Europe for 7 years
Excellent plasticity, widely atoxic and non-immunogenic

3. Normal host response to foreign material
1. 24 hours: neutrophils and small round cells predominate
2. 48 hours: monocytes predominate – no neutrophils from now on
3. 7 days: early formation of foreign-body giant cells occur
4. 2 weeks: the cellular response remains mild
5. 4 weeks: monocytes diff. into epitheloid cells, fibroblasts appear
6. 6 weeks: foreign-body giant cells common, increase of coll. deposition
7. 8 weeks: chronic inflammatory cells and a heavy collagen deposition
8. 6 months: stable giant cell and low-grade cellular response along with
a reduced amount of more dense collagen and the conversion
of fibroblasts into fibrocytes

4. Heavy for eign body
r esponse in cheek
tissue after 2 months
No gr anulocytes
No clinical symptoms

5. PA A G (A quamid) in
fr ont tissue (glabella)
after 7½ months.

6. After 2 years.
Hardly any cellular reaction

7. HUMAN TISSUE AFTER 2 YEARS

8. Adverse reactions

9. It is common to see some swelling about 10
days after Aquamid injection. This swelling is
probably due to a tissue response to the gel in
order to reach a steady-state.
This swelling disappears spontaneously after
12-13 days
Classical signs of infection are not present
(warmth, pulsation, pain and redness)

10. Generalised adverse reactions
1. Allergic/hypersensitivity reactions (rash, Quinckes oedema,
anaphylactic chok)
2. Autoimmune reactions (collagenoses- LED, rheum arthr. lung
fibrosis, PBC, Mb Graves, atherosclerosis etc)
Local or regional adverse reactions
1. Short-term reactions: pain, oedema, pruritus, ecchymosis, pigmentation
changes, excessive elevation and embolism, if gel is accident.injected into
the vascular system
appear within 2 days of the injection and disappear spontaneously within 1-2
weeks. Pruritus subside within weeks or months
2. Long-term reactions: inflammatory nodule (clinically a granuloma)
appear after weeks, months or years and present as a tender nodule and/or
Swelling and redness at the point of injection. Later this may lead to
fistulation, ulceration, discharge of pus and/or filler material and tissue
destruction.

11. Inflammatory nodule
Characterised by polymorphnuclear
granulocytes and microorganisms (bacteria)
– which may be difficult to detect –
As well as the foreign-body reaction which
is seen in all tissues injected with a foreign
material.

12. Adverse reaction, 6 weeks
Granulomatous inflamm.

13. Injection technique
Sterility precautions should be as in open surgery:
1. Gloves, mask, hut
2. Skin disinfection of injection site
3. Retraction of injection needle as prescribed
4. Tell patient to refrain from activities increasing
risk of contamination with micro-organisms
for 8 hours after the injection

14. Incidence of Microorganisms in Human tissue
Cultures taken from breast tissue far away from the papilla
and not previously operated upon have shown a 53% positivity
for coagulase-negative staphylococci. Propionibacterium acne was
the most frequently found anaerobic bacterium (Thornton, 88).
Cultures from 389 periprosthetic breast tissues with no clinical
signs of infection have shown 23.5 % microorganisms including
aerobic and anaerobic bacteria as well as fungi and other organisms
(Netscher, 95),

15. We all harbour bacteria within out tissues. Our
immune system take care of them.
Patients with long-term antibiotic treatment for
different diseases (colitis ulcerosa, Mb. Crohn, DM)
may grow antibiotic-resistant bacterial strains
Patients on long-term steroid or NSAID treatment
(collagenoses) have a reduced immune system.

16. 1. Aquamid should be treated like any other implant
(heart valves, artificial blood vessels, breast silicone
prostheses and hip replacement prostheses).
The local immune defence is reduced
2. In case of sepsis
(e.g. tooth extraction, pneumonia, abdominal surgery)
antibiotic treatment should be given

17. A negative tissue culture is no proof
that microorganisms are not present
A negative GRAM or PAS stain on
microscopy of a cell smear or tissue section is no
proof that microorganisms are not present
Antibiotic therapy prior to a culture swap
or biopsy may immobilize or reduce the number
of microorganisms hindering their detection

18. Report on 56 cases of adverse events out of 40.000
patients injected with Aquamid (1.4 ‰)
Information from treating physicists and patients on filled-in
pre-printed forms distributed by and sent to the manufacturer
Number of patients: 56
Patient age (75%): 23-60 years - mean 44, median 45

19. Study period: May 21. 2001 to September 15. 2003
Contributing countries:
Australia (9 pt.s), Austria (4 pt.s), Belgium (1 pt.),
Brazil (5 pt.s), Equador (1 pt.), France (7 pt.s),
Germany (7 pt.s), Holland (3 pt.s), Israel (1 pt), Italy
(7 pt.s), New Zealand (1 pt), Spain (6 pt.s), Sweden (1
pt), Switzerland (2 pt.s), USA (1 pt.)

20. Injection sites:
Lip 32
Naso-labial folds 24
Glabella 5
Cheekbone 4
Cheek 2
Chin 2
Forearm, allergy test 2
Nosetip 1

21. Type of physician:
Plastic surgeon 23
Dermatologist 12
Aesthetic/cosmetic doctor 20
Unknown 1
Symptoms: Swelling, redness, pain, fistulation, pus
discharge
Symptom delay (Time from last injection to first symptom
of adverse reaction: median 12 days.

22. Established causes of adverse reactions
(found in 18 (32%) of patients)
Bacteria Herpes labialis
1. Positive culture 5 cases
Streptococci viridans: 3
cases Too superficially injected
Atypical mycobacteriae: 1 case 2 cases
2. DNA cloning
Shigella 1 case Palsy 1 case
Streptococci viridans 1 case
3. Microscopy (gram stain)
Gram positive cocci 2 cases Breast cancer subsequently
Gram positive rods 1 case . 1 case
Total: 9 cases

23. Known contraindications:
Several previous injections at the same site: 9 patients
Mb. Crohn and Colitis Ulcerosa: 2 patients
Pemphigus: 1 patient
Insulin dependent Diabetes Mellitus: 1 patient
Dentistry at the injection site: 1 patient
Face-lift just prior to injection: 1 patient
Oral sex right after injection: 1 patient
Make-up during injection: 1 patient

24. First line Treatment:
None: 6 patients
Antibiotic alone: 10 patients
Antibiotic+steroid: 13 patients
Antibiotic+steroid+NSAID: 7 patients
Steroid: 6 patients
NSAID: 6 patients
Anti-histamine: 4 patients
Drainage only: 4 patients
Total 56 patients

25. Second line treatment: 32 patients
Antibiotic: 29 patients
Steroid: 3 patients
Third line treatment 8 patients
Antibiotic: 8 patients
___________________________________________________
Primary treatment .
Steroid + weak antibiotic: 2 patients
Steroid alone: 2 patients
Steroid + NSAID and/or antihistamine 3 patients
Antihistamine 1 patient
They all received antibiotics the third time with improvement or complete
recovery.

26. Fastest recovery was obtained for those patients treated
with antibiotics from the start - in spite of negative findings
on culture and/or microscopy.
A prolonged course resulted if primary (antibiotic)
treatment was delayed/weak or if it included steroids or
NSAIDs.
Anti-histamines or anti-viral drugs did not hinder recovery.

27. Cause of adverse
reactions
Bacteria, sometimes preceded by herpes
Treatment of adverse reactions
Antibiotics in high dosage i.m. or i.v.– steroids
or NSAIDs are stongly contraindicated

28. Treatment of adverse inflammatory
reactions:
Immediate administration of a broad-spectered
antibiotic in high dosage, e.g.:
1. Fluoroquinolon (Ciproxin) 500 mg x 2 for up to 7
days
2. Vancomycin/Teicomycin, i.m. 1 g x 2 , or
Lincomycin 300 mg x 2 for 2 days followed by ½
dosis for the next 10-20 days.
*Tell patient to go to injecting doctor for treatment and
show patience