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.

Systemic autoimmune or granulomatous disorders related to biomaterials of human use have rarely been described. The aim of this study was to report cases of autoimmune/inflammatory syndrome induced by adjuvants (ASIA) related to biomaterial injections and prostheses, mainly silicone, hyaluronic acid, acrylamides and methacrylate compounds in a Spanish patient cohort. This study is a retrospective analysis of clinical, laboratory, histopathological and follow-up data of 45 cases of patients suffering from late-onset, non-infectious inflammatory/autoimmune disorders related to bioimplants. Late onset was defined as 3 months or more post injection. Data were obtained through a further non-systematic but comprehensive review of the literature. Forty-five cases of late-onset adverse reactions related to biomaterial injections or prostheses were reviewed. All cases had systemic complaints that could be categorised as ASIA. In all but four patients, inflammatory features at the implantation site preceded distant or systemic manifestations. Abnormal blood tests were common. Localised inflammatory nodules and panniculitis in 40/45 (88.88%) evolved into a variety of disorders, viz., primary biliary cirrhosis, Sjögren's syndrome, sarcoidosis, human adjuvant disease, vasculitis, inflammatory bowel syndrome and inflammatory polyradiculopathy. Five (11.11%) cases presented primarily with systemic autoimmune disorders. Biomaterials and prostheses can provoke late-onset systemic autoimmune disorders fulfilling ASIA criteria, or present primarily local/regional inflammatory reactions that may eventually evolve into systemic autoimmune and/or granulomatous disorders which fall under ASIA.

No abstract

Although it happens infrequently, local and regional delayed and recurrent granulomatous reactions may complicate PA gel injections.

Infrequently, biomaterials other than silicone can provoke local inflammatory adverse reactions that may evolve into systemic autoimmune and/or granulomatous disorders. Whether or not these biomaterials act as an adjuvant, they could be included in the ASIA category.

Background: It has been thought that poly-L-lactic acid (PLLA) injections do not have inflammatory side effects. Recent evidence shows that local/regional/systemic delayed adverse effects may appear with its use. Objective: To evaluate the clinical complaints, treatment response and long-term follow-up of non-HIV patients with delayed immune-mediated adverse effects related to PLLA injections. Methods: Prospective, case series study of 10 patients with delayed adverse effects related to PLLA injections. The inclusion criterion was defined as the onset at least 6 months after PLLA use, with 1 or more of the following clinical signs: oedema, skin induration, swelling/tender nodules with or without discharge of pus or filler material. Several systemic manifestations were also included. Patients with immediate side effects were excluded. Patients underwent clinical management and long-term follow-up. Results: The average latency period to the onset of symptoms was 19.2 months (range: 6–60). Tender, inflammatory nodules and facial oedema were commonly seen. One case presented a systemic granulomatous disorder as a complication. After 50.2 months of average follow-up (range: 38–78), 5 patients are in remission, 4 have recurrent bouts and the last case has been lost to follow-up. Conclusion:Although infrequently, local and/or regional and/or systemic delayed and recurrent granulomatous reactions may complicate PLLA gel injections.

Background: As microbial agents have been associated with late adverse effects related to fillers antibiotic treatment has been envisaged. Objective: To determine whether biomaterials favor bacterial growth and/or attract bacteria. Methods: Hyaluronic acid, semi-permanent fillers, such as calcium hydroxylapatite, and permanent fillers, such as polyalkylimide/polyacrylamide, were used. Experiments were performed with Escherichia coli, strain HVH-U47. Bacteria were transferred to Sven-Gard agar to test mobility. Striae of this bacterial strain with a MacFarland 1 turbulence pattern were seeded from a spot of inoculated biomaterial using Müller-Hinton medium. The chemoattractive properties of the biomaterials were analyzed 10 days after inoculation. Bacterial growth over the biomaterial and in-depth growth were assessed as well. Results: Semi-permanent fillers did not stimulate bacterial growth but they allowed bacterial colonization over the filler. Permanent acrylic compounds neither presented chemoattractant properties nor showed bacterial growth over the biomaterial. Similar results were obtained when performing in-depth cultures. Conclusions: Permanent and semi-permanent fillers did not facilitate bacterial growth when flagellated E. coli HVH-U47 was used. Our results do not argue in favor of antibiotics as the mainstay of therapy in late granulomas related to permanent fillers. In the case of resorbable/semi-permanent fillers, more studies are needed before recommending antibiotic therapy.

Tacrolimus is an effective and well-tolerated drug in cases of severe and refractory late-onset inflammatory reactions, including large panniculitis, that complicate silicone gel injections.