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Qt5085f0pn.Pdf UC San Diego UC San Diego Previously Published Works Title Foreign Body Granulomas after All Injectable Dermal Fillers: Part 2. Treatment Options Permalink https://escholarship.org/uc/item/5085f0pn Author Lemperle, Gottfried Publication Date 2015-04-05 Peer reviewed eScholarship.org Powered by the California Digital Library University of California SPECIAL TOPIC Foreign Body Granulomas after All Injectable Dermal Fillers: Part 2. Treatment Options Foot Gottfried Lemperle, M.D., Summary: Foreign body granulomas occur at certain rates with all injectable Ph.D. dermal fillers. They have to be distinguished from early implant nodules, which Nelly Gauthier-Hazan, M.D. usually appear 2 to 4 weeks after injection. In general, foreign body granulomas San Diego, Calif.; and Paris, France appear after a latent period of several months at all injected sites at the same time. If diagnosed early and treated correctly, they can be diminished within a few weeks. The treatment of choice of this hyperactive granulation tissue is the intralesional injection of corticosteroid crystals (triamcinolone, betamethasone, or prednisolone), which may be repeated in 4-week cycles until the right dose is found. To lower the risk of skin atrophy, corticosteroids can be combined with antimitotic drugs such as 5-fluorouracil and pulsed lasers. Because foreign body granulomas grow fingerlike into the surrounding tissue, surgical excision should be the last option. Surgery or drainage is indicated to treat normal lumps and cystic foreign body granulomas with little tissue ingrowth. In most patients, a foreign body granuloma is a single event during a lifetime, often triggered by a systemic bacterial infection. (Plast. Reconstr. Surg. 123: 1, 2009.) n increasing number of various injectable even microspheres.11 Unfortunately, polymethyl- dermal filler substances are being used for methacrylate products with a high percentage of Athe treatment of wrinkles, acne scars, and impurities are widely injected in Brazil.12,13 Today, facial lipodystrophy. They have been developed ArteFill is a third-generation polymethyl-methac- because injection of earlier substances, such as rylate–based filler that has substantial improve- paraffin and silicone oil, was followed by a high ments, including microspheres, which have en- incidence of late granuloma formation.1 In addi- hanced uniformity and consistency, compared tion, the effects of collagen and hyaluronic acids, with the second-generation polymethyl-methacry- considered the accepted standard, do not last late–based product, Artecoll. longer than 6 months before they are resorbed. At the end of the 1990s, Dermalive, a suspen- Paraffin oil used some 100 years ago led to sion of slowly resorbable acrylic (hydroxyethyl- paraffinomas,2 and injection of low-viscosity sili- methacrylate) particles from ground intraocular cone oil of 350 centistoke caused late siliconomas lenses,14 and New-Fill/Sculptra, faster resorbed in selected patients3–5 in the 1970s. In the early microspheres from polylactic acid, entered the 1980s, bovine collagen (Zyderm and its cross- European market.15 A few years later, the first re- linked form Zyplast)6 appeared to be safe but ports of late granuloma formation appeared.16 Re- caused granulomas in selected patients as well.7 stylane, a hyaluronic acid derived from Streptococ- In the early 1990s, the first particulate in- cus equi,17 was introduced in 1998, and some jectables, Bioplastique8 and Arteplast,9 were intro- patients reacted with the formation of late duced in Europe. These substances, however, granulomas.18,19 caused foreign body granulomas at unacceptably Radiesse (formerly Radiance), consisting of high rates–-the first because of the irregular shape microspheres composed of calcium-hydroxylapa- of its silicone particles,10 the latter due to a high amount of small phagocytosable polymethyl- methacrylate particles among the smooth and Disclosure: Gottfried Lemperle, M.D., Ph.D., is not affiliated with nor an agent nor a representative From the Division of Plastic Surgery, University of Califor- of Artes Medical, Inc., which is the manufacturer of nia, San Diego, and private practice. ArteFill. Dr. Lemperle is a shareholder of Artes Med- Received for publication August 24, 2007; accepted Decem- ical, Inc. Nelly Gauthier-Hazan, M.D., has no fi- ber 5, 2007. nancial interest in any of the products mentioned in Copyright ©2009 by the American Society of Plastic Surgeons this article. DOI: 10.1097/PRS.0b013e3181858f4f www.PRSJournal.com 1 Color Figure(s): F1-4 Art: PRS200503 Input-nlm/4 21:54 09/28/4 1؍rich3/zpr-prs/zpr-prs/zpr00609/zpr2432-09z xppws S Color Figure(s): F1-4 Art: PRS200503 Input-nlm/4 21:54 09/28/4 1؍rich3/zpr-prs/zpr-prs/zpr00609/zpr2432-09z xppws S Plastic and Reconstructive Surgery • June 2009 tite and suspended in methyl-cellulose,20 is a filler period has been observed.31,32 If the reaction is substance introduced in the United States in 2002 limited to firm nodules, corticosteroid injections for off-label use in wrinkles and lip augmentation; into the cellular tissue surrounding the silicone it received U.S. Food and Drug Administration implant should be the first treatment choice. Com- approval for the treatment of nasolabial folds and plete remission of silicone foreign body granulo- human immunodeficiency virus–associated lipo- mas in two patients has been obtained with a sys- dystrophy in 2006. So far, Radiesse appears to temic antibiotic (minocycline 100 mg) given twice cause the lowest rate of foreign body granulomas a day, orally.33 among all filler substances.1 “Liposuction” or puncturing and squeezing of Finally, polyacrylamide gel was the Russian larger silicone fluid implants can be tried, but answer21,22 to the American silicone gel for soft- surgical excisions should be avoided, as removal tissue augmentation in the 1980s and 1990s. To- will seldom be complete due to the silicone’s fin- day, different formulations of polyacrylamide are gerlike insinuation into the tissue. Total excision produced by at least five manufacturers since In- and flap coverage4 should be reserved as a last terfall Ltd., in Kiev, Ukraine, lost its European option in patients with extreme infiltration and patent protection of Formacryl22 and Interfall in inflammation of the skin on the nose or breast. 1995. Aquamid23 and Bio-Alcamid24,25 are the AQ: 1 products most widely used in Europe today, be- Bovine Collagen 2 sides Interfall and Amazing Gel in China. Moscona et al.7 described a woman who de- Recently, resorbable microspheres from 27 veloped severe sclerosing foreign body granulo- dextran suspended in hyaluronic acid were in- mas at all injection sites 2.5 years after implanta- troduced in Europe as dermal fillers under the tion of Zyderm I collagen into her nasolabial folds, trade names Reviderm intra and Matridex. They glabellar frown lines, and a few areas around the are used as urinary bulking agents to treat incon- lips. High doses of oral prednisolone, up to 60 tinence. Matridex is currently in clinical trials in mg/day, resulted in a marked diminution of the the United States. Both stimulate heavy granula- 27,28 swelling, but the foreign body granulomas rapidly tion tissue but have not been used long enough recurred when the treatment was stopped. Further to provide sufficient insight into potential late treatment with intralesional triamcinolone injec- complications. Dextran granuloma, however, has tions resulted in almost complete regression for a been described in rats26 and has caused urinary 29,30 period of 4 to 6 weeks, after which the foreign obstruction in humans. body granulomas recurred. In the latter case, no FOREIGN BODY GRANULOMAS AFTER doses were reported, but we assume that they did DIFFERENT FILLERS not exceed 40 mg per session. Slight improvement was noted over the following years with low daily There are three different clinical and histo- AQ: 3 1 doses of 5 and 10 mg of Dexacort. AQ: 2 logical types of foreign body granulomas. Biolog- ical substances, such as collagen and hyaluronic acids, may cause cystic granulomas, which may even- Hyaluronic Acids tually result in a sterile abscess. They occur be- Late foreign body granulomas developed 2 to tween 2 and 12 months after injection and last 11 months after injection of hyaluronic acids and 34,35 without treatment for 2 to 12 months before spon- lasted 2 to 10 months without treatment. Some 17,33 taneous absorption. Permanent injectable fluids, were treated with intralesional triamcinolone, such as silicone and polyacrylamide, may cause but most resolved without treatment within 1 year. edematous granulomas, with swelling and surround- We are aware of four sclerosing but rather soft ing inflammation. Particulate injectables, such as Restylane granulomas with late onsets of up to 3.5 Artecoll, Dermalive, and Sculptra, may cause scle- years after injection. Systemic or local antibiotics rosing granulomas, which occur between 6 and 24 are ineffective, but puncturing and squeezing out 17,36 months after injection and will remain for several the whitish gel will speed up their resolution. 37 years if not treated. Of course, there is a contin- Surgical excision of this cellular reaction should uum among the three types, and certain granu- certainly be the last solution. lomas sometimes are a blend of two types. Polymethyl-Methacrylate Microspheres Silicone Because of the extensive fibrous network as- The spontaneous disappearance of silicone sociated with polymethyl-methacrylate–related foreign body granulomas after a 3-year follow-up granulomas, intralesional corticosteroid injec- 2 Color Figure(s): F1-4 Art: PRS200503 Input-nlm/4 21:54 09/28/4 1؍rich3/zpr-prs/zpr-prs/zpr00609/zpr2432-09z xppws S Volume 123, Number 6 • Treatment of Dermal Filler Granulomas tions are considered the best treatment.11 We saw Polylactic Acid Microspheres an Arteplast granuloma develop as late as 10 years Powder of polylactic acid beads suspended in after injection; it responded well to high doses of cellulose (New-Fill/Sculptra) was first used suc- F1 local steroids and pulsed light therapy (Fig.
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