Jesper Thulesen explains what an injector needs to be aware of in order to minimise the chances of complications from HA filler injections to the face 

Jesper Thulesen, MD, PhD, Dr. Med. Sci., FEBO
is an Oculoplastic Surgeon and Aesthetic Medical Physician at Clinic Aesthetica Kongens Nytorv, Store Kongensgade 36, 3., 1264 Copenhagen K, Denmark, www.clinicaesthetica.dk

email: [email protected]

According to the American Society of Plastic Surgeons (ASPS), hyaluronic acid (HA) containing fillers are ranked as the second most popular treatment on the list of non-surgical modalities for facial aesthetic enhancement1. With the increase in the availability of HA-fillers, number of aesthetic practitioners, and the demand for aesthetic procedures, its popularity continues to rise. 

Treatment with HA-fillers has been associated with mild and transient adverse events such as bruising, swelling, and surface irregularities. More serious adverse events are in general avoidable with proper planning and technique. 

A skilled aesthetic professional with comprehensive knowledge of anatomy and aseptic injection techniques minimises the risk of complications by paying attention to:

  • Patient factors — comprehensive patient history (especially no recent dental work), appropriate selection, management of expectations
  • Product selection — high-quality HA-fillers with strong scientific evidence as well as pure well-tested products (free from animal proteins, biotoxins, and other possible contaminants), using a product suitable for the specific anatomical area of interest
  • Injection technique — aspirate, limit number of needle skin perforations, blunt cannula technique.

However, with the increased use of HA-fillers worldwide, and more practitioners treating high-risk areas in the face, such as the periorbital area, nose, and nasolabial folds, the number of more severe and permanent adverse events is likely to rise. A responsible injector should be aware of the most common complications and know when and how to intervene in order to manage the spectrum of complications. This article provides the practitioner with a general guide and overview of complications related to treatment with HA-fillers and divides these into the following categories:

  • Non-vascular / non-infectious complications: (a) with immediate onset (<48 hours), or (b) delayed onset (2 days–2 weeks)
  • Infectious complications: (a) with immediate onset (<48 hours), or (b) delayed onset (from 2 days to more than 2 weeks)
  • Nodules / granulomas: (a) non-inflammatory, or (b) inflammatory
  • Vascular compromise: (a) peripheral arterial ischemia, (b) peripheral venous ischemia, (c) retinal ischemia, or (d) ischemia in the internal carotid arterial system.

Non-vascular/non-infectious complications with immediate onset (within 48 hours)

Haematoma

Onset of symptoms: within minutes to hours.

Symptoms/pathogenesis: bruises (Figure 1), deep haematoma may appear as a subacute swelling, with no visible discolouration, temporary or permanent haemosiderin deposits are possible.

Figure 1 Displaying haematoma on the upper lip

Differential diagnosis: erythema (several possibilities), ischemia (intravenous occlusion or blue-grey phase in situations with vascular compromise), or post-inflammatory hyperpigmentation.

Prophylaxis: apply immediate compression when visible bleeding is seen, use blunt cannulas, beware of patients using oral anticoagulants.

Treatment: none, heparin- or vitamin K-containing ointment, low-level laser therapy.

Cutaneous blanching

Onset of symptoms: within minutes.

Symptoms/pathogenesis: vascular compromise induced by the filler injection can lead to immediate blanching (also see vascular compromise), overcorrection, filler material applied in more superficial tissue layers than its recommendations2,3

Prophylaxis: select the right HA-filler and avoid too much of a superficial placement. Inject slowly to avoid migration due to the pressure of immersion. Split the treatment over multiple sessions.

Treatment: exclude ischemia, overcorrection can be reversed by injection of hyaluronidase, gentle massage.

Post-interventional oedema

Onset of symptoms: within hours.

Symptoms/pathogenesis: oedema without inflammatory signs (Figure 2) — perhaps a slight degree of erythema. Typically reaches maximum severity 24–48 hours post-treatment.

Figure 2 Post-interventional oedema

Differential diagnosis: overcorrection, type-1 hypersensitivity/histamine release oedema.

Prophylaxis: split the treatment over multiple sessions.

Treatment: cooling, keep head in an elevated position at night, systemic low-dose steroid treatment.

Type 1 hypersensitivity/histamine release oedema

Onset of symptoms: within minutes to hours.

Symptoms/pathogenesis: oedema, pruritus, and/or erythema (Figure 3) — in extreme cases, can lead to the development of anaphylaxis. Develops due to an immediate B-cell-mediated response with IgE-production and the degradation of mast cells followed by the release of histamine and/other inflammatory mediators.

Differential diagnosis: post-interventional oedema, overcorrection, physical urticaria.

Figure 3 Type 1
hypersensitivity
following treatment of
the tear trough

Prophylaxis: anamnestic data on previous reactions to HA-filler-treatment. In unclear cases, perform a skin test and apply the preventative use of antihistamines before the procedure.

Treatment: antihistamine — if the reaction is severe, systemic prednisolone should be considered. The reaction of anaphylaxis requires an emergency set-up that is mandatory in any clinic with injections.

Neurological affection

Onset of symptoms: within hours.

Symptoms/pathogenesis: dysesthesia, paresthesia or anaesthesia due to iatrogenic nerve damage caused by direct injection into the nerve fibres or compression of the nerve due to injected filler material. This complication is rare but is described for the infraorbital nerve, marginal mandibular nerve, and as a cause for Bell’s palsy4-6.

Differential diagnosis: prolonged effect of lidocaine-containing HA-filler.

Prophylaxis: the practitioner should have a thorough understanding of facial anatomy.

Treatment: injections of hyaluronidase in HA-filler treated areas. Refer to a neurologist if symptoms persist.

Non-vascular/non-infectious complications with delayed onset (within 2 weeks)

Type IV hypersensitivity

Onset of symptoms: within days.

Symptoms/pathogenesis: oedema often with erythema, itching and/or visible cutaneous microvesicles (Figure 4). Develops due to a T-cell mediated response that typically develops weeks after the treatment with the HA-filler and can persist for several months. 

Prophylaxis: anamnestic data on previous reactions – contraindication for HA-filler treatment. 

Differential diagnosis: infection, transition into a foreign body granuloma through chronic immune stimulation may be possible.

Treatment: injections of hyaluronidase in HA-filler treated areas to reduce the load of antigen. Supplementary systemic low-dose steroid treatment is often advised7,8.  

Figure 4 Before (A) and after (B) developing hypersensitivity IV following filler treatment of the lips

Tyndall effect 

Onset of symptoms: within days, weeks, or months.

Symptom/pathogenesis: bluish colouration or brightening effects of the skin where overlying skin is thin, such as the tear trough area, or if filler is injected too superficially9.

Prophylaxis: select the correct filler for each treatment area, avoid superficial placement of filler, inject slowly to avoid migration due to the pressure of immersion.

Differential diagnosis: (malar) oedema.

Treatment: injections of hyaluronidase in HA-filler treated areas.

Infectious complications with immediate onset (within 48 hours)Acute bacterial infection

Onset of symptoms: within minutes, days or months.

Symptoms/pathogenesis: sharp (erysipelas) or non-sharply defined (cellulitis) inflammatory swelling, or with a palpable, fluctuating mass (abscess) (Figure 5), sometimes fever or malaise, sometimes lymphadenopathy. Causative microbes: Streptococcus pyogenes, Staphylococcus10.

Differential diagnosis: type IV immune reaction, oedematous granuloma (early-onset unusual), cystic granuloma (early-onset unusual)

Figure 5 Patient with inflammatory swelling, erysipelas, and abscess formation following
filler treatment of the nasolabial fold

Prophylaxis: aseptic (use 2% chlorhexidine gluconate in 70% isopropyl alcohol for disinfection) environment during treatments, use high-quality products, use small gauge needles, reduce the number of needle skin perforations, avoid massage in order to prevent spreading infection.

Treatment: swab for culture, aspiration of abscesses, blood tests, antibiotics, in severe cases, refer to hospital.

Infectious complications with delayed onset (within or later than 2 weeks)

Bacterial infection

Symptoms/pathogenesis: as described in acute bacterial infection. When delayed onset (and even more than two weeks after filler treatment), atypical bacteria may be involved (mycoplasma, escherichia coli)11.

Differential diagnosis: type IV immune reaction, oedematous granuloma, cystic granuloma.

Prophylaxis: as described in acute bacterial infection.

Treatment: as described in acute bacterial infection.

Herpes simplex reactivation

Figure 6 Herpetic vesicles — in this case secondary to a venous embolus after filler treatment

Symptoms/pathogenesis: herpes-typical vesicles (Figure 6), sometimes lymphadenopathy, herpes simplex type I.

Differential diagnosis: Vascular compromise (necrosis).

Prophylaxis: visible active elements are contraindicative for HA-filler treatment. If the patient has a history of regular herpes: initiate prophylactic treatment with valacyclovir. 

Treatment: anti-viral therapy10.

Nodules/granuloma

Non-inflammatory nodules — onset often immediately

Symptoms/pathogenesis: localised lump/nodule, often indolent, occasionally with transparent discolouration due to visible HA-filler in the skin immediately after HA-filler treatment (Figure 7). Causes can be (a) injection of filler in the wrong anatomical tissue level, (b) injection of a HA-filler not intended to be used in the specific area or tissue level, (c) injection of excess volume of HA-filler, or (d) misjudgment of the anatomical structures.

Prophylaxis: appropriate product selection for intended treatment, ensure comprehensive knowledge of anatomy for injection in the right tissue level, inject slowly, redistribute injected filler material via massage.

Treatment: redistribute by massage, hyaluronidase injection; for a superficial, well-defined lump, incision and extrusion may be considered8.

Inflammatory nodules — onset weeks to months, sometimes years

Figure 7 Mucosal lump of filler product

Symptoms/pathogenesis: inflammatory (hyperemic) tender lumps/nodules. Biofilm seems pivotal by inducing an immune response, thus leading to a chronic granulomatous reaction. Other immunological phenomena may play a role, such as excessive foreign body reaction, and type IV reaction. Occasionally, another infection, such as influenza infection or gastroenteritis, may precede and trigger delayed inflammatory response (DIR). Multiple needle passes, product factors, and patient factors also play a role (Figure 8)12.

Differential diagnosis: fluctuating nodule, abscess, or  sarcoidosis.

Prophylaxis: asepsis, limit number of needle skin perforations, the risk may be slightly increased when using biphasic hyaluronic acid fillers. 

Treatment: antibiotics (macrolide, fluoroquinolone), hyaluronidase, intralesional steroid injection; if abscesses are present, aspiration for bacteriology.

Vascular compromise

Peripheral arterial ischemia

Symptoms/pathogenesis: blanching skin phase —  immediate onset, duration <1 min, sometimes painful. Livedo reticularis phase (marbling) — after a few minutes (seldom within a few hours), due to lack of oxygen resulting in venous dilation, virtually pathognomonic (Figure 9). Blue-grey skin phase — tens of minutes to hours, due to sustained lack of oxygen. Blister phase — after 1–2 days, as the first sign of skin necrosis. Demarcation and ulceration phase — after days to weeks, healing by secondary intention.

Figure 8 Delayed inflammatory response several months after filler treatment

Differential diagnosis: vasoconstriction due to epinephrine containing local anaesthesia (blanching phase), haematoma (blue-grey phase), herpes simplex/herpes zoster lesions (blister phase).

Prophylaxis: aspiration (needle), use blunt cannulas (minimum 25G) in high-risk areas, delivery of material at different points and in small volumes per pass, slow injection with minimal pressure.

Risk factors: previous surgery, scars (including acne scars), small-gauge needles/cannulas.

Treatment: high-dose hyaluronidase within a few minutes to hours, repeat every hour until sufficient capillary response, warm compresses, aspirin13,14.

Peripheral venous occlusion

Figure 9 Arterial compromise approximately twelve hours after filler treatment of the tear trough

Symptoms/pathogenesis: usually delayed onset compared to the symptoms with arterial ischaemia but might appear immediately as a haematoma (Figure 10). Diffuse pain, oedema, and bluish discolouration15-17.

Differential diagnosis: haematoma, arterial vascular compromise.

Prophylaxis: aspiration (needle), use blunt cannulas (25G) in high-risk areas, delivery of material at different points and in small volumes per pass, slow injection with minimal pressure.

Risk factors: previous surgery, scars (including acne scars), small-gauge needles/cannulas.

Treatment: high-dose hyaluronidase, warm compresses, and aspirin.

Retinal ischemia

Symptoms/pathogenesis: sudden blurry vision, complete or partial visual loss often combined with ocular pain. Blepharoptosis and ophthalmoplegia with diplopia. The filler material enters the lumen of an artery and progresses in a retrograde manner against the bloodstream because of the pressure exerted by the injector on the syringe plunger. When the pressure is released, the filler material flows downstream due to the arterial pressure and becomes wedged in the ophthalmic artery circulation.

Figure 10 Venous embolus — presented acutely as a haematoma

Differential diagnosis (unlikely, but theoretical possible): thromboembolic central retinal arteria occlusion (CRAO), or internuclear ophthalmoplegia (INO).

Prophylaxis: aspiration (needle), use blunt cannulas (25G) in high-risk areas, delivery of material at different points and in small volumes per pass, slow injection with minimal pressure.

Risk factors: previous surgery, scars (including acne scars), small-gauge needles/cannulas.

Treatment (casuistic experiences): if experienced with the technique, retrobulbar injections with high-dose, concentrated hyaluronidase solutions, injections with hyaluronidase in the HA-filler treated areas, aspirin, tension-lowering eye drops, and aspirin can all be used.  The patient should breathe into a paper bag, and referral to a tertiary care facility for specialist evaluation and intervention should be made (accompanied by a staff member from the aesthetic injection clinic who also brings vials with hyaluronidase)18.

Ischemia in the internal carotid arterial system

Symptoms/pathogenesis: symptoms pathognomonic to cerebral transient ischemic attack; ‘mini-stroke’. The filler material enters the lumen of an artery as described for retinal ischemia, but due to a longer retrograde migration in the arterial system, the filler material becomes wedged in the cerebral arterial system19,20.

Differential diagnosis (unlikely, but theoretically possible): cerebral transient ischemic attack.

Prophylaxis: the same as for retinal ischemia.

Risk factors: the same as for retinal ischemia.

Treatment: Aspirin, referral to a tertiary care facility for specialist evaluation and intervention (accompanied by a staff member from the aesthetic injection clinic who also should bring vials with hyaluronidase).

Conclusion

Even though a responsible injector will take all precautions to prevent complications when injecting HA-fillers, they will still happen. However, with a comprehensive knowledge of the facial anatomy, the HA-filler products used, and preparations and precautions that should be taken pre-, per- and post-procedure, the risk can be significantly reduced. If a complication then occurs, it is of major importance that the injector identifies the aetiology or the most likely aetiology of the condition and immediately follow appropriate complication algorithms that reduce the consequences for the patient but also allows the injector to proceed with confidence.

  Declaration of interest None

  Figures 1-10 © Jesper Thulesen

References

  1. American Society of Plastic Surgeons. National Plastic Surgery Statistics 2018. https://www.plasticsurgery.org/documents/News/Statistics/2018/plastic-surgery-statistics-report-2018.pdf
  2. Winslow CP. The management of dermal filler complications. Facial Plast Surg 2009;25:124-128
  3. Lowe NJ, Maxwell CA, Patnaik R. Adverse reactions to dermal fillers, review. Dermatol Surg 2005;31:1616-1625
  4. Fitzgerald R, Bertucci V, Sykes JM, Duplechain JK. Adverse reactions to injectable fillers. Facial Plast Surg 2016;32:532-555
  5. Signorini M, Liew S, Sundaram H et al. Global aesthetics consensus: avoidance and management of complications from hyaluronic acid fillers-evidence- and opinion-based review and consensus recommendations. Plast Reconstr Surg 2016;137:961e–971e
  6. Glass GE, Tzafetta K. Optimising treatment of Bell’s Palsy in primary care: the need for early appropriate referral. Br J Gen Pract 2014;64:e807–e809of fillers
  7. De Boule, K. Management of complication after implantation of fillers. J Cosmet Dermatolog 2004;3:2-15
  8. Funt D, Pavicic T. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. Clin Cosmet Invest Dermatol 2013;12:295-316 
  9. Weinberg MJ. Complication of hyaluronic acid fillers. Facial Plast Surg 2009;25:324–8
  10. Cox SE, Adigun CG. Complications of injectable fillers and neurotoxins. Dermatol Ther 2011;24:524–36
  11. Urdiales-Gálvez F, Delgado NE, Figueiredo V et al. Treatment of soft tissue filler complications: expert consensus recommendations. Aesthetic Plast Surg 2018;42:498-510
  12. DeLorenzi, C. Complications of injectable fillers, part I. Aesthet Surg J 2013;33:561–575
  13. Loh KTD, Phoon YS, Phua V, Kapoor KM. Successfully managing impending skin necrosis following hyaluronic acid filler injection, using high-dose pulsed hyaluronidase. Plast Reconstr Surg Glob Open 2018;9:6
  14. Delorenzi C. New high dose pulsed hyaluronidase protocol for hyaluronic acid filler vascular adverse events. Aesthet Surg J 2017;37:814-825
  15. Sclafani AP, Fagien S. Treatment of injectable soft tissue filler complications. Dermatol Surg 2009;35:1672–1680
  16. DeLorenzi C. Complications of injectable fillers, part 2: vascular complications. Aesthet Surg J 2014;34:584–600
  17. Kassir R, Kolluru A, Kassir M. Extensive necrosis after injection of hyaluronic acid filler: case report and review of the literature. J Cosmet Dermatol 2011;10:224–231
  18. Thulesen J. Iatrogenic vision loss following aesthetic treatment with hyaluronic acid-containing filler: Every injector should be prepared. Dermatologic Therapy. 2020;e13913. https://doi.org/10.1111/dth.13913
  19. Carle MV, Roe RH, Novack RL. Occlusion caused by cosmetic facial filler injection – reply. JAMA Ophthalmol 2015;133:225
  20. Kim SN, Byun DS, Park JH et al. Panophthalmoplegia and vision loss after cosmetic nasal dorsum injection. J Clin Neurosci 2014;21:678–680