Fillers in Dermatology

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FILLERS

• Volumetric rejuvenation of the face using fillers have exponentially increased in the last decade • Replacing lost fat pads with filler or fat is one approach to restore the beauty of the aging face

HISTORY • Neuber - autologous fat for tissue augmentation, 1893 • Gersuny - use a bioinjectable material to correct cosmetic defects • Injection of liquid silicone - Japan - given up because of foreign body reactions (siliconoma) • In 1977, Knapp, Luck, and Daniel - collagen implants in the dermal and subcutaneous planes • 1996 – hyaluronic acid launched in Europe • 2003 – hyaluronic acid is FDA approved

INJECTABLE FILLERS Injectable fillers are a group of artificial filler substances used for soft tissue augmentation

CLASSIFICATION Based on site of placement

• Dermal • Subdermal • Supraperiosteal

Based on origin of filler material

• • • •

Heterograft Allograft Autograft Synthetic material

Based on mechanism of action

Based on longevity

• Replacement dermal fillers • Stimulatory dermal fillers

• Temporary • Semi-permanent • Permanent

Based on origin of filler material

• Heterografts (a) Bovine collagen (b) Hyaluronic acid derivative implant (c) Porcine collagen • Allografts : human derived collagen

• Autograft (a) autologous fat (b) autologous collagen • Synthetic material (a) Polytetrafluoroethylene (b) Silicone (c) Calcium Hydroxylapatite (d) Polyacrylamide

Based on longevity Temporary (Biodegradable) 2 Years

• Collagen • Hyaluronic acid

• Calcium hydroxylapatite • Dextran • Poly L lactic acid • Poly vinyl alcohol

• Polymethyl methacrylate • Polyalkylamide • Polydimethyl siloxane

Based on mechanism of action Replacement fillers

Stimulatory fillers

Little cellular response

Induce fibrogenesis and collagen production Strong cellular reaction

• Collagen • Fat • HA

• PLLA • PMMA • CaHA

PROPERTIES OF AN IDEAL DERMAL FILLER Safe and effective Inexpensive Hypoallergenic and requires no pretesting Malleable Biocompatible Easy to distribute, easy to store Easy to inject Exert no or minimal downtime on the patient Have no or minimal risk of complications Adequate lifting, long-lasting, consistent, predictable and easy to remove if necessary • Non-toxic, non-carcinogenic, no teratogenicity • • • • • • • • • •

US FDA APPROVED DERMAL FILLERS Temporary • Collagen • Hyaluronic acid gel • Calcium hydroxy apatite • Poly-L-lactic acid Permanent • Polymethylmethacrylate beads

INDICATIONS OF DERMAL FILLERS

AESTHETIC

MEDICAL

AESTHETIC CONDITIONS

Facial areas • Facial lines (wrinkles, folds) • To correct volume loss deficiencies • Enhancement of facial contours • Nose remodeling • Lip augmentation • To improve hydration and skin texture • Depressed scars • Periocular melanoses and sunken eye Nonfacial areas • Neck rejuvenation • Hand rejuvenation • Breast and buttocks augmentation • Earlobe augmentation

1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15.

Forehead lines/ pillow lines Frown/ glabellar lines Periorbital lines Tear trough Non surgical nose job Cheek enhancement Nasolabial fold Perioral lines Oral commissures Lip enhancement Jaw line contouring Hand rejuvenation Chin augmentation mental crease Neck lines decolletage

MEDICAL CONDITIONS • Angular cheilitis • Scleroderma • HIV lipodystrophy • Corns and calluses: To reduce contact point and risk of ulcer formation

CONTRAINDICATIONS OF FILLERS • Known allergy to fillers • History of anaphylactic shock, fainting, low blood pressure • Unrealistic expectation • • • • • • •

Recent treatment with other fillers within 6 months to 1 year Permanent fillers or implants of any kind Skin cancer Keloid or hypertrophic scars Autoimmune diseases, angina, epilepsy, diabetes On drugs like aspirin/warfarin/steroids Depression and stress.

• Herpes simplex without prophylaxis, any active infection • Pregnancy and breastfeeding

ABSOLUTE

RELATIVE

TEMPORARY

FAT COMPARTMENTS IN AGING FACE • Superficial and deep fat compartments • Ligaments confine fat areas • Grooves and folds on the skin surface reflect volume depletion of fat in the area along with ligament fixation

PROCEDURE Counseling regarding the entire treatment plan

Written informed consent

Pre- and post-treatment clinical photograph

Clean the area with topical antiseptics

Anesthesia • • • •

Ice application Topical eutectic mixture of local anesthetic (EMLA) cream Regional nerve blocks Talkesthesia: Comforting the patient by talking in a soothing and comforting manner

Markings

THE HINDERER LINE

Vertical line from lateral canthus to oral commissure (anterior extend of malar prominence ) An intersecting line marked from tragus to upper alar lobule Fillers can be put in outer and lateral compartment

Ogee curve

S shaped Consisting of a concave arc flowing into a convex arc Cheek mount should be restored by injecting on the highest point

Injection technique Linear threading technique Full length of the needle is inserted into the middle of the wrinkle Substance is injected while pulling the needle slowly backward

Serial puncture technique

Multiple injections are placed serially along the length of the wrinkle/fold. They are made close together Merge into a smooth continuous line that lifts the wrinkle

Fan technique

Needle inserted at the periphery of the area to be treated similar to the linear threading technique. After injecting along one line, the direction of the needle is changed and injected as before along a new line

Cross-hatching technique The needle inserted - periphery of the area intended to be augmented, and the filler is injected similar to the linear threading technique. Withdrawn - reinserted 5–10 mm adjacent to the first puncture site, and injected in the same way. Repeated at right angles to the original lines

Depot technique

Defect is to be repaired at a single point The needle is inserted perpendicular to the skin and a small bolus of product is deposited

Cone/Tower Technique Needle inserted perpendicular to the skin till it reaches bone. Small bolus of product is deposited. As the needle is withdrawn, product is continually injected - cone or pyramid shape is formed. Reinserted along another edge of the pyramid Small quantity of product can lift up or support the overlying tissue like the pillars of a tent

Fern technique

Needle inserted perpendicularly into the fold and after advancing it the implant is injected on either side in retrograde manner. Multiple such injections are placed along the length of the fold

Dual Plane Technique/Sandwich Technique

Two planes, a deep plane and a superficial plane. Any technique described can be used, and even two different types of HA can be combined

Pillar and bridge technique

The pillars are depots or cones of product which are deposited close to one another over a bony support, and then the bridge of a linear thread of filler is deposited superficially over it To minimize the use of product

Botulinum toxin: Better results as it can correct both dynamic and static components of wrinkles in a particular region. Injecting botulinum one to two weeks prior to soft tissue augmentation in areas to be treated results in a synergistic effect. Lesser quantity of product required for correction Increase the longevity of the filler in treated areas

NEEDLES VERSUS CANNULA • Most dreaded complication of any filler technique is an intravascular deposition of filler product • Skin necrosis or even lead to blindness • Blunt-Tipped Microcannula

Blunt-Tipped Microcannula

• Puncture an entry point into the skin using a hypodermic disposable needle • Gauge of the needle should be slightly bigger than the gauge of the cannula chosen • Entry direction of the needle track is 60 to 90° • Remove the sharp needle, and introduce the microcannula

Post treatment care

Avoid strenuous physical activity, massaging or manipulating the injected area, Avoid exposing the part to extreme heat or cold, makeup for the first 24 hours. A touchup treatment may be recommended after 2–4 weeks, if needed

COMPLICATIONS Adverse reactions are more common with permanent fillers Early injection related events such as erythema, swelling, pain, itching, or tenderness - transient and can be treated symptomatically

Erythema Usually transient, but may occasionally persist longer. • Topical corticosteroids • 0.1% tacrolimus • Oral propranolol (20 mg OD), or ibuprofen (200 mg bid) • Avoidance of erythema inducing agents (e.g., alcohol, sun exposure) and exercise

Hematomas and ecchymoses Can follow vigorous massage or can occur in patients on anticoagulants. • Discontinuation of the drugs or alcohol (a vasodilator which increases the chance of bruising) 1 week prior to procedure

Infections Improper or unsterile techniques • Early infections - minimal medical intervention Short course of appropriate antibiotics/ antivirals (herpes reactivation) • late infections - more than 2 weeks post procedure - atypical infection with mycobacteria

Hypersensitivity reactions Localized or generalized Course of systemic steroids and antihistamines should be administered for the latter

Overcorrection Superficial bleeding, lumpiness, or bumpiness Massaging of the injected areas allows uniform dispersion into the surrounding tissue. Too superficial placement of hyaluronic acid can manifest as a blue bump under the skin due to Tyndall effect Hyaluronidase

Necrosis Glabellar area following arterial embolization with hyaluronic acid and bovine collagen Blindness due to vascular occlusion

Retinal artery occlusion as a result of calcium hydroxylapatite in the central retinal artery.

Facial artery anatomy illustrating the most common sites of vascular occlusion.

Granulomas Depending on the physiological properties of the compound, the volume injected, and the local infection or trauma. Intralesional corticosteroids, 5-fluorouracil, topical imiquimod, or a course of allopurinol 600 mg/day for 24 weeks. In resistant cases, only surgical excision is effective

Migration of the fillers locations distant from the treatment site is common with permanent fillers Managed by microliposuction or radical surgical removal

• Do not inject into blood vessels - tissue necrosis.

WARNINGS AND PRECAUTIONS

• Before injecting, always make it a practice of aspirating the needle. But negative aspiration does not mean that the vessel has been spared always. • Blanching in the injected or surrounding area - alarming sign suggesting vascular compromise. Inject hyaluronidase immediately on visible blanching and pallor.

• Avoid the procedure - evidence of active infection or inflammation in treatment area.

WARNINGS AND PRECAUTIONS

• In patients with a history of previous herpetic eruption - start prophylactic oral acyclovir • Follow-up should be done after 48 hours to ensure safety, also to see any early signs of vascular compromise if occurred.

HYALURONIC ACID • Hyaluronic acid is presently, the most widely used dermal filler across the globe • Most widely chosen by injectors India – safety reversibility versatility • Polysaccharide and a normal extracellular component of most mammalian tissues including the dermis. • Glucoronic acid and N acetyl –d- glucosamine

• Injectable U.S. Food and Drug Administration (FDA)-approved forms: Non– animal-derived stabilized hyaluronic acid products made through a bacterial fermentation process Avian-derived version isolated from cocks’ combs. • Brands differ - concentration of hyaluronic acid per milliliter of product, type of crosslinking or stabilizing agents, viscosity, and particle size

• Native form - short life span • Crosslinking increases its longevity • Proportion and degree of crosslinking increases 🡪 gel becomes more and more like a solid more resistant to degradation by enzymes and free radicals tends to persist longer in tissue • Excellent tolerability profile • Significant discomfort on injection so most hyaluronic acids on the market are combined with lidocaine

POLY-L-LACTIC ACID • Approved by the FDA in 2004 for correction of HIV-related facial atrophy and is also approved for the cosmetic correction of shallow-to deep contour deficiencies • No-downtime, long-lasting filler • Not a direct filling agent but rather a biostimulatory agent • Gradual, subtle change • Papule/nodule formation is the main adverse reaction of PLLA

CALCIUM HYDROXYLAPATITE • Whitish material made from synthetically formed calcium phosphate pearls • Mixed with lidocaine to reduce injection pain • Drug-induced lipoatrophy in HIV patients • Form a scaffold to support the growth of autologous collagen temporary filler + biostimulatory agent • CaHA is visible on X-rays

ALGINATES • Derived from brown algae • Erythema, swelling and even haematomas seemed to be less prevalent compared with HA • Adverse events such as nodule formation • Specifically in areas such as the infraorbital hollow • No corrective antidote was available - filler was removed from the market

BOVINE COLLAGEN • Very early injectable filler • 95% type I, 5% type III • The risk of collagen hypersensitivity reactions - intradermal pretesting was mandatory • Intradermal injection of Zyderm 1 collagen into the volar aspect of the forearm, which was evaluated after 28 days

PORCINE COLLAGEN • Introduced into the European market in 2004 and withdrawn in 2009 • The risk of hypersensitivity reactions for porcine collagen was not of clinical relevance • No skin testing was required

HUMAN COLLAGEN • Derived from natural human collagen grown under controlled laboratory conditions • Not require pretesting

SILICONES • Not widely used • Clear, oily, colourless liquid composed of long chains of polymerized dimethylsiloxane • 0.01 mL microdroplets at 1 mm intervals • Disastrous local and systemic effects

POLYACRYLAMIDES • 97.5% water and 2.5% cross-linked polyacrylamide • Nodules, pain, secondary deformity, discomfort and long-lasting swelling

POLYALKYLAMIDE • Alkylimide group networks (4%) and water (96%) • Migration, hardening, irregularity • Currently the product is not available in Europe

POLYMETHYLMETHACRYLATE • Non-biodegradable, biocompatible, man-made polymer • Used in other medical devices, such as bone cement and intraocular lenses • PMMA beads are tiny, round, smooth particles that are not absorbed by the body • When used as a soft tissue filler, suspended in a solution of 3.5% bovine collagen as a carrier and 0.3% lidocaine for anaesthetic effect • Collagen resorbs over a period of 2–3 months, the PMMA spheres become encapsulated by fibrotic material - remain permanently in the tissue

NOVEL THERAPEUTIC AGENTS AS FILLERS • Stem cells : Adipose tissue – good source of stem cells Soft tissue regeneration or repair • Autologous vein transplantation : Unwanted vein of the patient Soaking in hypertonic saline to destroy endothelial cells Implant remaining to dermal defect

REFERENCES • ACSI textbook of cutaneous and aesthetic surgery 2nd edition • ACSI procedural dermatosurgery • Textbook of dermatosurgery and cosmetology principles and practice 3rd edition Satish S Savant • Rook textbook of dermatology 9th edition • IADVL textbook of dermatology 5th edition • Funt D, Pavicic T. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches. Clin Cosmet Investig Dermatol. 2013;6:295-316 https://doi.org/10.2147/CCID.S50546 • Vedamurthy M, Vedamurthy A. Dermal fillers: tips to achieve successful outcomes. J Cutan Aesthet Surg. 2008 Jul;1(2):64-7. doi: 10.4103/0974-2077.44161. PMID: 20300346; PMCID: PMC2840909. • Galadari H, Weinkle SH. Injection techniques for midface volumization using soft tissue hyaluronic acid fillers designed for dynamic facial movement. J Cosmet Dermatol. 2022 Mar;21(3):924-932. doi: 10.1111/jocd.14700. Epub 2021 Dec 28. PMID: 34964234; PMCID: PMC9303613. • Akinbiyi T, Othman S, Familusi O, Calvert C, Card EB, Percec I. Better Results in Facial Rejuvenation with Fillers. Plast Reconstr Surg Glob Open. 2020 Oct 15;8(10):e2763. doi: 10.1097/GOX.0000000000002763. PMID: 33173655; PMCID: PMC7647625.

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