Investigating the Anatomic Location of Soft Tissue Fillers in Noninflammatory Nodule Formation: An Ultrasound-Imaging-Based Analysis.

INTRODUCTION: Noninflammatory nodules may be persistent to dissolve. To evaluate the possible reasons, a case series of ultrasound images and medical data of patients who were prospectively referred with noninflammatory nodules were evaluated. MATERIALS AND METHODS: A total of 27 patients with nodules but without signs of inflammation were included. All cases were assessed with an 18-MHz linear ultrasound device. Exact location of the filler material was noted. Relations with clinical data were analyzed using chi-square tests. RESULTS: Early onset of complaints (<2 weeks) was found in 16 patients and late onset (>2 weeks) in 11. All patients had multiple nodules. In all cases, the filler nodule was found to be located inside the fascia. Extension to the subcutaneous tissue was seen in 8 cases and to the deeper planes in 5. In 14 cases, the filler material was completely located inside layers of the fascia, and migration was observed in 5 cases. DISCUSSION: Accumulation of filler material in the superficial musculoaponeurotic system or fascia may be an important cause for the occurrence of persistent noninflammatory nodules, either by initial faulty injection technique or by later accumulation through the pathway generated with a needle or cannula. Ultrasound-guided injections are helpful to dissolve the nodule.

No association found between late-onset inflammatory adverse events after soft tissue filler injections and the adaptive immune system.

BACKGROUND: To date, it is unknown why some individuals develop late-onset inflammatory adverse events after treatment with fillers. These events may result from various factors, including an immunological response of the adaptive immune system. OBJECTIVE: In a pilot study, we looked for evidence that is there a relation between late-onset inflammatory adverse events and the presence of immune cells surrounding the injected filler. METHODS AND MATERIALS: We included 47 patients, of whom 20 experienced late-onset inflammatory adverse events to different fillers (inflammatory group) and 27 who did not (reference group). A biopsy was taken from the area of the adverse event. Hematoxylin-eosin staining and immunohistochemistry analysis with CD3 (T-cells) and CD68 (macrophages) on paraffin tissue sections was used to assess the biopsies. RESULTS: Immune cells were found in biopsies obtained from 18 of 47 patients: Nine biopsies from the inflammation group and nine from the reference group. All these 18 cases showed CD68-positive immune cells. Virtually no CD3-positive immune cells were found. CONCLUSION: Our results indicate that there is no T-cell activity in biopsies from areas with late-onset adverse events after filler injections. The macrophages found in the biopsies are probably not responsible for the inflammatory response.

The Dutch Hyacorp® filler catastrophe: new EU legislation will prevent this from happening again

Background: In 2014, the hyaluronic acid-based fillers, Hyacorp-1000 and Hyacorp H-S (H-800), were withdrawn from the Dutch market after concerns about their safety Objectives: To determine the most plausible factors for the increased number of adverse events, either patient-related factors or those inherent to the filler itself. We also assessed how new European legislation will affect the approval process for new fillers and improve related safety issues Materials & Methods: A total of 42 patients­37 women (88%) and five men (11%)­were included. Patients were separated into three groups: 13 patients injected with Hyacorp-1000 and Hyacorp H-S (H-800) who had reported inflammatory adverse events; 12 injected with Hyacorp-1000 and Hyacorp H-S (H-800) who had not reported inflammatory adverse events; and 17 injected with other HA fillers who had reported inflammatory adverse events Results: Patients treated with Hyacorp-1000 and Hyacorp-S (H-800) who reported adverse events were significantly older than those in the Hyacorp-1000 and Hyacorp-S (H-800) group without adverse events, and the filler remained in situ for significantly longer than in patients who had adverse events related to another HA filler Conclusion: Hyacorp-1000 and Hyacorp-S (H-800) filler is associated with an increased chance of developing adverse events compared to other HA fillers, probably because it remains in the body for a longer period of time. The upcoming legislative EU update of the Medical Device Regulation (MDR) will prevent unsafe filler from entering the EU market and will enable issues related to safety to be identified much earlier

Inflammatory immune-mediated adverse reactions induced by COVID-19 vaccines in previously injected patients with soft tissue fillers: A case series of 20 patients.

BACKGROUND: Adverse events (AE) after COVID-19 vaccines, particularly, but not solely, with those messenger RNA (mRNA)-based vaccines, have rarely been reported in patients previously treated with dermal fillers (DF). OBJECTIVE: To evaluate the morphology, clinical characteristics, the timing of presentation, and outcomes of inflammatory AE appeared in patients injected with DF, after anti-COVID-19 vaccination. METHODS: Descriptive study of a case series of 20 consecutive patients collected after the occurrence of AE in previously filled areas post COVID-19 vaccination. RESULTS: From January 2021 to July 2021, we analyzed 20 AE reactions triggered by COVID-19 vaccines in the previously mentioned cohort. They were vaccinated with Pfizer/Biontech (11; 55%), Moderna (5; 25%), Astra-Zeneca (3; 15%), and Sputnik (1; 5%). The most common manifestations were oedema/swelling, angioedema, erythema, skin induration, and granuloma. Less common reactions included myalgia and lymphadenopathy. In 13/20 (65%) cases, the AE appeared after the first dose of vaccine. These inflammatory AE appeared more rapidly after the second dose than after the first one. In 13/20 (65%) cases, the symptomatology subsided with anti-inflammatory/antihistaminic drugs, while spontaneously in 3/20 (15%). The manifestations are ongoing.in the remaining four cases (20%). CONCLUSION: Although probably rare, both RNA-based and adenovirus-based anti-COVID-19 vaccines can cause inflammatory bouts in patients previously treated with DF. In these cases, caution should be paid on subsequent vaccine doses, considering a tailored risk/benefit for any case before next vaccination.

Increased risk of late-onset, immune-mediated, adverse reactions related to dermal fillers in patients bearing HLA-B*08 and DRB1*03 haplotypes.

Even though manufacturers claim that the dermal fillers are nontoxic and nonimmunogenic, adverse events may occur. Clinically and histologically, most of the late onset adverse events present as an inflammatory response. To assess whether HLA polymorphisms are associated with late-onset inflammatory adverse events related to dermal fillers. A total of 211 patients were included, of whom 129 experienced late-onset inflammatory adverse events to different fillers (Inflammation group) and 82 who did not (Reference group). Patients completed a standardized questionnaire and provided a blood sample or oral swap for HLA testing. The study population consisted of 188 (89%) women and 23 (11%) men. The two study groups were similar in the distributions of filler type, location of injecting, allergy, autoimmune disease, gender, age, ethnicity, and smoking status. Of the 211 patients in the sample, 25 had the combination of HLA subtype-B*08 and HLA subtype-DRB1*03. This was 16.3% of the inflammatory group and 4.9% of the reference group. This combination of HLA subtypes was associated with an almost 4-fold increase in the odds of developing immune mediated adverse events (odds ratio = 3.79, 95% CI 1.25-11.48). Genetic polymorphisms such as HLA combinations may identify patients at risk of developing late onset immune mediated adverse events to dermal fillers.

Unilateral facial edema after filler injection of the lower eyelid.

The use of hyaluronic acid (HA) gel fillers for rejuvenation of the face has been increasing in popularity over the years. This nonsurgical, temporary technique is commonly used in the periocular region to restore volume. The aim of this study was creating awareness in the potential causes of edema after hyaluronic acid gel filler injections under the eyes. A 32-year-old woman presented for a cosmetic consultation to address unilateral swelling of the left check. She states she had an HA filler injected in the tear trough on both sides. Extensive evaluation and ultrasound were performed by physicians of different specialties. Intra-oral and radiological examination revealed a tooth-related cause known as apical periodontitis. Removal of this tooth resulted in complete resolution of the patient's presenting symptoms. Familiarity with all the potential causes of adverse events after injections with hyaluronic acid gel fillers accelerates the treatment and healing of the patient with complications. Reporting this case should raise awareness about possible teeth-related complications.

Pneumosinus dilatans following dermal filler injections.

When an adverse event occurs after a dermal filler treatment, simple ultrasound can be of help for diagnosis. But sometimes a more sophisticated imaging technique as MRI is needed to find the true reason for a complication. As in the case of pneumosinus dilatans after injection of a dermal filler, we present. The relation of this rare disorder and filler injection is discussed.

Ultrasound to improve the safety of hyaluronic acid filler treatments.

BACKGROUND: Hyaluronic acid fillers are known for a reliable safety profile, but complications do occur, even serious vascular adverse events. OBJECTIVE: To improve the safety of hyaluronic acid filler treatments. METHODS: Ultrasound is used to image hyaluronic acid fillers. RESULTS: Before a filler treatment is performed with ultrasound, previous filler treatments can be brought in to sight and vascular mapping can be performed. In case of adverse events, the filler and the surrounding tissues are visible. Dislocation, abscesses, and vascular adverse events can be seen. Under ultrasound guidance, hyaluronidase can be injected directly into the filler deposit. CONCLUSION: Ultrasound examination can be an important tool to improve the safety of hyaluronic acid filler treatments.

Intralesional Laser Treatment for Dermal Filler Complications.

BACKGROUND: For complications caused by filler treatments, in general, two treatment regimens are advised: systemic drugs and surgical removal of the material. Another possible treatment option would be removal of the material by intralesional laser treatment. METHODS: Two hundred forty-two patients with complications caused by fillers were treated with intralesional laser treatment. RESULTS: In the majority of patients, an improvement was achieved (92 percent), in 9 percent the complication was resolved, and in 3 percent it was not improved (unknown in the rest). CONCLUSION: Considering the large number of patients treated until now and the efficacy and good safety profile of this treatment, the authors plead that intralesional laser treatment may be considered as a treatment option before surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

A dietary fiber mixture versus lactulose in the treatment of childhood constipation: a double-blind randomized controlled trial.

BACKGROUND: Constipation is a common problem in children. As first-line treatment, increased dietary fiber is often advocated. To our knowledge, however, no large studies evaluating the effect of dietary fibers in childhood constipation have been published. PATIENTS AND METHODS: A randomized, double-blind, prospective controlled study was performed. Patients received either a fiber mixture or lactulose in a yogurt drink. After a baseline period of 1 week, patients were treated for 8 weeks followed by 4 weeks of weaning. Polyethylene glycol 3350 was added if no clinical improvement was observed after 3 weeks. Using a standardized bowel diary, parents recorded defecation frequency during the treatment period. In addition, incontinence frequency, stool consistency, presence of abdominal pain and flatulence, necessity for step-up medication, and dry weight of feces were recorded, as were adverse effects. RESULTS: A total of 147 children were eligible; 12 children wished not to participate. Of the remaining children, 65 were randomized to treatment with fiber mixture and 70 to treatment with lactulose. In all, 97 children completed the study. No difference was found between the groups after the treatment period concerning defecation frequency (P = 0.481) and fecal incontinence frequency (P = 0.084). However, consistency of stools was softer in the lactulose group (P = 0.01). Abdominal pain and flatulence scores were comparable (P = 0.395 and P = 0.739, respectively). The necessity of step-up medication during the treatment period was comparable (P = 0.996), as were taste scores (P = 0.657). No serious adverse effects were registered. CONCLUSIONS: A fluid fiber mixture and lactulose give comparable results in the treatment of childhood constipation.