Complication Management of Restylane® / Perlane®

HA fillers have an impressive safety record.  Despite this impressive safety record, adverse events occur when injecting HA fillers.  It is important to be familiar with potential complications and management.

Complication can be divided into early and delayed in time of occurrence, and minor and major in severity.

Early minor complications include bruising, pain, edema and erythema.  These can occur immediately or within hours and resolve within a week.  Most patients will develop at least one of these local injection site reactions, so it is important to discuss this with them.  Pretreatment with anesthetic or ice prior to treatment is recommended to minimize pain in site that contains high sensory innervation, such as the lips.  Avoiding anticoagulants and supplements that are not medically necessary will minimize post injection ecchymosis.  Some use homeopathic ointment called Arnica in reducing ecchymosis.  Helenalin, an extract of Arnica, has shown to have anti-inflammatory effects, although clinical studies are not conclusive.

Other early minor complications of asymmetry, lumpiness, or bluish discoloration are typically due to injection technique.  Incorrect filler placement can cause nodules or papules.  When the filler is implanted too superficially, a bluish hue is visible (Tyndall effect).  Such reactions can be treated with manual massage, aspiration, incision and drainage, or hyaluronidase.

A rare early major complication is an anaphylaxis due to an immediate hypersensitivity reaction.  It is estimated that 1 in 10,000 individuals with HA report a mild to severe hypersensitivity reaction.  In 2005, a patient developed angioedema-type of reaction 1 hour after Restylane injection into the lips.  This patient responded to corticosteroid injection with complete resolution.  It is always recommended that you should have a protocol in your office should any such emergency should arise.

Cellulitis is a complication seen with any injection procedure.  Common bacterial causes are Staphylococcus and Streptococcus.  Lesions should be cultured and treated with antibiotics.  The use of chlorhexidine will minimize the risk of infection.

Trauma from the injection can trigger a recurrent herpetic lesion.  Prophylactic antiviral treatment is recommended when injecting the lips.  Also, injection should be avoided during an active herpes outbreak.

Inflammatory nodules can occur if bacteria is injected with the filler, and the HA encapsulates the bacteria within the skin.  These inflammatory nodules will be red and painful.  Incision and drainage should be performed, with cultures, and antibiotic, such as clarithromycin should be started for at least 2 – 6 weeks.  The use of steroid can worsen the situation.  Patients with diabetes, immunocompromised, chronic sinusitis, or chronic dental problems should be treated with care.

Delayed major complication is the formation of granulomas which can occur 6 months after the injection.  HA fillers are rarely linked to granuloma formation, but it has been reported in 0.1% of the patients who are typically injected with permanent or semi-permanent fillers.  The body mounts a foreign body reaction with fibrosis occurring at the injection site.  This can be treated with steroid injections, surgical excision, or hyaluronidase.

Delayed hypersensitivity reaction can also occur.  In 2009, a case report was described a patient who developed acute facial angioedema with urticarial 3 weeks after Restylane in her nasolabial folds.

The most severe, delayed complication is tissue necrosis, due to direct blockage of a vessel, compression near the vessel, or injury to the vessel.  This has been reported in 0.09% of the patients who received collagen injections.  The patient will experience delayed capillary refill and pain, followed by a mottled pattern of purple discoloration, and ulceration due to necrosis.  This can occur in the glabellar area due to blockage of the supratrochlear or supraorbital artery and the alar or nasal area due to the blockage of nasal arteries.  This can also occur along facial and angular artery.  A thorough understanding of the facial anatomy is recommended to prevent this complication.  Steps such as aspiration, slow anterograde injection, constant needle motion, using small particle size fillers, superficial use, avoiding injection near vessels, and blunt tip cannulas can help reduce the risk of intravascular injection.  This can be treated with massage, heat application, nitroglycerin paste (1/2 inch of 2% nitroglycerin) to vasodilate the area, and hyaluronidase to remove the filler.  When nitroglycerin is used topically, the patient should be warned of the potential side effects, such as headache, bradycardia, and hypotension.


Hyaluronidase is an enzyme that breaks down and hydrolyzes hyaluronic acid.  Multiple reports have been documented on successful elimination of unwanted HA implantation.  Hyaluronidase has been used to correct asymmetry, overcorrection, Tyndall effect and vascular occlusion.  Hyaluronidase will dissolve the filler and reduce edema, which will help minimize occluded vessel pressure.

Hyaluronidase is diluted with saline in 1:1 ratio.  Skin testing is mandatory when using hyaluronidase.  Inject 3 – 5 units intradermally.  A wheal formation within 5 minutes and persisting for 20 -30 minutes with localized itching is a positive skin test.  Total of 10 – 30 units should be injected per 2 X 2 cm area of impending necrosis.

Please check the package insert for any Hyaluronidase product for complete instructions and warnings and contraindications.


During the consultation phase, collection of a thorough medical history, including medications and allergies, is essential.  The injector must be aware of the techniques and understand the depth of the implantation.

A minor complication in your eyes may not be minor in your patient’s eyes.  As one can clearly see, using Hyaluronic Acid based fillers offers additional options in treating any complications.  Early recognition, education, treatment and psychological support will minimize any potential disasters.

A detailed consultation is a must.  Educate your patients.  Under-promise and over-deliver.