Late inflammatory reactions in patients with soft tissue fillers after SARS-CoV-2 infection and vaccination: A systematic review of the literature.

INTRODUCTION: Soft tissue fillers are used for cosmetic and reconstructive purposes, and soft tissue filler procedures are among the most common nonsurgical procedures in the USA. Although soft tissue filler procedures are relatively quick and safe, adverse events such as late inflammatory reactions have been reported with every filler product. Infections and vaccinations have been proposed as potential triggers for late inflammatory reactions (LIRs), and it is therefore not surprising that these adverse events have been reported after SARS-CoV-2 infection and vaccination. Therefore, this review aims to give a detailed overview of these cases. MATERIALS AND METHODS: A literature search was undertaken on LIRs in patients with a history of soft tissue filler use after SARS-CoV-2 infection or vaccination. This systematic review was reported according to the PRISMA guidelines. We searched the electronic database PubMed from January 2020 to August 2021. Data on patient characteristics, filler characteristics, clinical findings, and treatment options were included. RESULTS: This review included 7 articles with a total of 19 patients with LIRs after SARS-CoV-2 infection or vaccination. Three patients with postinfection LIRs and 16 patients with postvaccination LIRs were reported. These LIRS mainly occurred in females who had HA injections for cosmetic purposes. Three patients with postinfection LIRs had symptoms of facial swelling and/or lip angioedema in a matter of weeks. Sixteen patients reported reactions after SARS-CoV-2 vaccination (13 following Moderna vaccination and 3 after Pfizer vaccination, after both the first and second doses) from 13 hours up to three weeks. These patients presented with similar clinical symptoms as patients with postinfection LIRs. All patients were treated in a conservative manner. DISCUSSION: This review shows a relationship between LIRs and SARS-CoV-2 infection and vaccination. In the case of vaccination, these adverse events have been reported only after Moderna and Pfizer vaccinations. The reported adverse events are generally minor and self-limiting, and we encourage patients with soft tissue fillers to participate in vaccination programs.

Granulomatous foreign-body reactions to permanent fillers: detection of CD123+ plasmacytoid dendritic cells.

BACKGROUND: Soft-tissue augmentation with permanent fillers can lead to severe granulomatous foreign-body reactions (GFBRs), but the immune pathomechanism of this complication is still unknown. We performed conventional histologic examination and immunostaining for plasmacytoid dendritic cells (pDCs) in skin sections from patients with GFBR to 4 permanent filler agents, which have been widely used in recent decades. METHODS: Twenty-one skin biopsies were studied from 19 patients with GFBR to polyalkylimide 4% gel (PAIG, n = 10), polyacrylamide 2.5% gel (PAAG, n = 2), hydroxyethyl methacrylate/ethyl methacrylate in hyaluronic acid (HEMA/EMA, n = 4), or liquid injectable silicone (n = 5). GFBRs were analyzed in hematoxylin and eosin stained sections and pDCs detected using CD123 antibodies. Anti-CD11c immunostaining was performed for comparison. RESULTS: Grading of the inflammatory infiltrates observed histologically did not correlate with the clinical features of inflammation. Immunostaining for CD123 did not detect pDCs in 8 of 10 polyalkylimide gel, 1 of 2 polyacrylamide gel, and the 5 liquid injectable silicone biopsies. In contrast, all 4 HEMA/EMA biopsies contained collections of pDCs in lymphocytic infiltrates close to filler particles and adjacent sarcoidal granulomas. CONCLUSIONS: Our data suggest that pDCs contribute to the sarcoidal granulomas associated with injected HEMA/EMA. Recruited pDCs may exert their pro-inflammatory effects by the release of interferon-α at the site of these filler deposits.

Complications After Facial Injections With Permanent Fillers: Important Limitations and Considerations of MRI Evaluation.

BACKGROUND: Soft-tissue fillers have become more prevalent for facial augmentation in the last 2 decades, even though complications of permanent fillers can be challenging to treat. An investigative imaging tool could aid in assessing the nature and extent of these complications when clinical findings are ambiguous. OBJECTIVES: The authors analyzed the value of magnetic resonance imaging (MRI) in the assessment of delayed-onset complications after injection of patients with permanent fillers. METHODS: Thirty-two patients with complications related to facial fillers were evaluated in this prospective cohort study. Their medical history was documented, and MRI was conducted before treatment of the complications. Radiologists were informed of the injection sites but were blinded to the results of other clinical evaluations. Levels of agreement between clinical and radiologic findings were calculated with the Jaccard similarity coefficient. RESULTS: A total of 107 site-specific clinicoradiologic evaluations were analyzed. The level of agreement was assessed as strong for deposits without complications and noninflammatory nodules (combined 85%), moderate for abscesses (60%), fair for low-grade inflammations (32%), and slight for migrations (9%). Results from the MRI examinations aided in subsequent treatment decisions in 11% of cases. CONCLUSIONS: Study results show that MRI may be useful for diagnosing complications associated with fillers that have migratory potential, for depiction of the extent of deposits before treatment, and for follow-up of low-grade inflammation and abscesses after surgery. LEVEL OF EVIDENCE: 3.

Semipermanent filler treatment of HIV-positive patients with facial lipoatrophy: long-term follow-up evaluating MR imaging and quality of life.

BACKGROUND: Injectable fillers such as poly-L-lactic acid (PLLA) and calcium hydroxylapatite (CaHA) have shown promising results in the treatment of combination antiretroviral therapy (cART)-induced facial lipoatrophy (FLA). However, the effects of these substances on magnetic resonance imaging (MRI) have not yet been described. OBJECTIVE: The authors analyze the association between the effects of treatment with semipermanent fillers on MRI and changes in quality of life (QOL). METHODS: Eighty-two human immunodeficiency virus (HIV)-positive patients with cART-induced FLA (grades 2-4) were enrolled in this prospective study. A mean volume of 58.2 mL (range, 12-105 mL) of PLLA (n = 41 patients) and 9.1 mL (range, 3-23 mL) of CaHA (n = 41) was injected in multiple sessions. The MRI examinations were performed prior to treatment and again 12 months after. The self-reported severity of FLA as well as QOL was measured using questionnaires based on Short Form 36, Medical Outcomes Study HIV Health Survey, and Center for Epidemiologic Studies Depression Scale formats. RESULTS: Significant increases in total subcutaneous thickness (TST) of the injected regions could be identified on MRI in nearly all patients 1 year posttreatment. Patients reported that mental health and social and role functioning improved; depressive symptoms decreased after treatment. In addition, the increase in TST was positively associated with improvement of QOL. CONCLUSIONS: This study confirms that treatment with both PLLA and CaHA not only increases TST but also is associated with improved QOL for HIV-infected patients. Furthermore, the study also demonstrates that MRI can show filler-induced neocollagenesis and quantify FLA treatment effects.

Delayed-onset complications of facial soft tissue augmentation with permanent fillers in 85 patients.

OBJECTIVE: To evaluate factors influencing the onset and type of adverse events in patients injected with permanent fillers in the face and to propose a therapeutic strategy for these complications. METHODS: A prospectively attained series of 85 patients with delayed-onset complications after facial injection with permanent fillers underwent clinical follow-up and treatment of the complications. RESULTS: Lag times until onset and type of delayed-onset complication varied according to filler material. In 28% (n = 24) of the cases, patients reported the onset of complications after dental procedures, additional injections with fillers, or other invasive treatments in the facial area. Forty-eight (57%) patients required invasive treatment. Abscess formation was significantly more frequent in patients with human immunodeficiency virus infection and facial lipoatrophy (p = .001). CONCLUSION: The intrinsic characteristics of the injected filler and the immune status of the patient play important roles in the diversity of time of onset and type of delayed-onset adverse events observed. It seems that invasive facial or oral procedures in the vicinity of filler depots can provoke such complications. We propose a strategy for treating these complications and advise great caution when using permanent filling agents.