Delayed immune-mediated adverse effects related to hyaluronic acid and acrylic hydrogel dermal fillers: Clinical findings, long-term follow-up and review of the literature

J. Alijotas-Reig, V. Garcia-gimenez

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98 Citations (Scopus)


Introduction: Implantation of dermal filler for cosmetic purposes is becoming increasingly common worldwide. It is thought that hyaluronic acid (HA) alone or combined with acrylic hydrogels (HA-AH) does not have severe nor persistent side-effects. However, recent evidence may show that major, local and/or systemic, immediate or delayed adverse effects may appear in relation with its use. Objective: To evaluate the clinical complaints, laboratory data, treatment and follow-up of patients with delayed adverse effects related to HA and HA-AH implant fillers. Design: Prospective, case-series study of patients filled with HA and HA-AH compounds. Setting: The study has been done in a tertiary, teaching university hospital. Patients: We report on a series of 25 patients, 15 of them in prospective manner, with severe, delayed side-effects related to HA-AH. Inclusion criteria have been drawn up. Patients with immediate side-effects were excluded. Patients were submitted to a clinical follow-up, battery of blood tests and thorax X-ray films. Besides, a review of the literature was made. We undertook a computed-assisted (MEDLINE), National Library of Medicine, Bethesda, MD, USA, search of the literature from 1996 up to December 2005. Main outcome: Clinical evaluation of granulomas, skin manifestations and other local and systemic immune-mediated disorders possibly related to HA and HA-AH fillers or their cumulative interaction with previously administered fillers. Results: Of 25 cases, 16 were filled with HA alone and 9 with a HA-AH compounds. Of 15 cases analysed and with long-term follow-up, 10 were filled with HA alone, and the remaining five were filled with a HA-AH. Time latency average up to beginning of symptoms was 13.7.months. Three of these 15 cases had been filled before with silicone and another one with Artecoll. Tender nodules were seen in 14 patients. Systemic manifestations appeared in three cases. Laboratory abnormalities were noted in all studied cases. After 16-month average follow-up, seven patients seem to be cured, and six have recurrent bouts. Two cases were lost during follow-up. Conclusion: Although in some cases, these clinical complications might have been associated with previous fillers or with other unknown foreign bodies, we feel that, although infrequently, delayed and recurrent chronic inflammatory and granulomatous reactions may complicate HA and HA-AH implant fillers. © 2007 The Authors Journal compilation © 2007 European Academy of Dermatology and Venereology.
Original languageEnglish
Pages (from-to)150-161
JournalJournal of the European Academy of Dermatology and Venereology
Issue number2
Publication statusPublished - 1 Feb 2008


  • Adverse effects
  • Dermalive
  • Ethylmethacrylate
  • Granulomas
  • Hyaluronic acid
  • Restylane treatment


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