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Case 4 a initial appearance of DIR to HA placed in the right tear trough, b inflammation extending to left tear trough (c) resolution of inflammation and majority of the swelling
Source publication
We present the first reported cases of delayed inflammatory reactions (DIR) to hyaluronic acid (HA) dermal fillers after exposure to the COVID-19 spike protein. DIR to HA is reported to occur in the different scenarios including: secondary to poor injection technique, following dental cleaning procedures, following bacterial/viral illness, and afte...
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(1) Background: Injectable hyaluronic acid (HA) dermal fillers are used in several chirurgical practices and in aesthetic medicine. HA filler stability can be enhanced through different cross-linking technologies; one of the most frequently cross-linker used is 1,4-butanediol diglycidyl ether (BDDE), also present in the HA-BDDE dermal filler family...
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Unlabelled:
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This study evaluated the reliability of a standardized grading system for scoring the overall sever...
Citations
... This is supported by the CARE board's observation that many patients with LORs also have a form of active autoimmune disease, diagnosed before or after LOR clinical manifestation [33][34][35][36][37]. Additionally, the human leukocyte antigen (HLA) polymorphisms HLA-B*08 and DRB1*03 have been associated with LORs, indicating a potential immune pathway for reactions in these patients [7]. Changes in the patient's immune status due to flu-like symptoms and vaccinations have also been correlated to the incidence of LORs [5,11,27,[38][39][40][41][42][43]. ...
... Late onset reactions may also be triggered by vaccines [40], including the coronavirus disease 2019 (COVID-19) vaccine [41,65]. The mechanism behind the association between LORs and the COVID-19 vaccine involves a downregulation of the angiotensin converting enzyme 2 (ACE2), which is elevated in the filler implant sites, in homeostatic conditions. ...
... The mechanism behind the association between LORs and the COVID-19 vaccine involves a downregulation of the angiotensin converting enzyme 2 (ACE2), which is elevated in the filler implant sites, in homeostatic conditions. Exposure to the COVID-19 spike protein blocks ACE2, resulting in a localized proinflammatory response and subsequent inflammation, oxidative stress, and fibrosis [40,66]. Similarly, LORs have been reported following administration of influenza and chickenpox vaccines [42,43]. ...
Hyaluronic acid (HA) dermal fillers, generally considered low-risk, can lead to rare late-onset reactions (LORs) manifesting between 3 and 4 months postinjection, occasionally even as early as 24 h postinjection. The Complication Assessment and Risk Evaluation (CARE) board was established to review these reactions. In this publication, the authors aims to explore the etiological hypotheses underlying LORs, associated risk factors, prevention, and management approaches suggested by the CARE board. The CARE board identified three etiological hypotheses contributing to LORs. Firstly, the physicochemical structure of the filler, particularly low molecular weight HA, which may trigger an immune response. Secondly, infection, potentially introduced during injection or by dormant biofilm activation. Lastly, an imbalance in the host immune system, caused by factors like autoimmune diseases or viral infections, may lead to extended foreign body reactions, delayed type IV hypersensitivity, or adjuvant-based reactions. Based on these hypotheses, the board categorized various risk factors as patient-related (e.g., recent dental treatment, current medical status, active autoimmune disease), product-related (e.g., molecular weight), and procedure-related (e.g., aseptic technique and trauma). To reduce the risk of LORs, the CARE board recommends diligent patient selection, including comprehensive medical history assessment and informed consent. Practitioners should maintain an effective aseptic technique, and choose an appropriate product and injection depth for the anatomical location. Post-procedure, patients should receive education on proper filler care. Management of LORs depends on the suspected etiology, and the CARE board has proposed an algorithm to determine the most appropriate treatment. Hyaluronidase is recommended for noninflammatory reactions in the absence of active infection, while watchful waiting and/or steroid treatment may be preferred for inflammatory reactions. Hyaluronidase is not recommended as a first-line treatment for infections, which require drainage, bacterial culture, and antibiotic treatment. However, the board emphasizes the need for individualized evaluation and treatment in all cases.
... Reported adverse reactions to dermal fillers include pain, erythema, infection and hypersensitivity [57]. Despite hyaluronic acid fillers being structurally similar to endogenous hyaluronic acid and thus having low immunogenicity, a number of cases of delayed inflammatory reactions were reported, some of which were related to the coronavirus disease 2019 (COVID-19) spike protein [57][58][59][60]. Use of supplementation as a strategy to support skin appearance could be an alternative strategy to dermal injections, as supplements are generally well tolerated. ...
With ageing, collagen production slows down, leading to wrinkle appearance and loss of elasticity. Replenishing key structural molecules through oral supplementation is a promising strategy that complements the topical delivery of cosmetic products and creates a holistic skincare regimen. The present study assessed the effectiveness of a food supplement with collagen peptides, vitamins and minerals in improving the quality of the skin and general wellbeing of healthy women.
This was an open-label study of 135 women aged between 45 and 65 years. A 3-month treatment phase followed a 4-week washout phase, with visits scheduled at baseline and after each month of treatment. Subjects received three tablets of Richelet Skin Renewal daily. The primary outcome was change from baseline to month 3 in global wrinkles score by expert grader analysis. Secondary outcomes included changes in skin elasticity and other skin attributes, product assessment via self-perception questionnaires and total antioxidant status.
A total of 116 subjects completed the study. The mean global wrinkles score indicated a statistically significant decrease from 5.9 at baseline to 5.0 at month 3 (p < 0.0001), with 83.6% of subjects showing an improvement; significant changes were reported at all intermediate visits. The increase in skin elasticity was also statistically significant (R2 score 0.74 at month 3; p < 0.0001). All subjects (100%) demonstrated significant improvements in skin texture, skin tone evenness, skin radiance and overall skin quality at the month 3 visit.
The study product achieved statistically significant, noticeable effects on global wrinkles, skin elasticity and a range of skin attributes after 3 months of use in healthy women. These results strengthen the evidence for supplementation of collagen peptides and other micronutrients as an effective component of anti-ageing skincare.
... Regarding acute cholecystitis management, antibiotics [117], percutaneous cholecystostomy [118,119], and laparoscopic or open cholecystectomy [117,120] have been applied. When medical treatment with antibiotics only or cholecystostomy are considered insufficient, urgent cholecystectomy is indicated [101,121,122] (Table 1). ...
Acute acalculous cholecystitis (AAC) represents cholecystitis without gallstones, occurring in approximately 5–10% of all cases of acute cholecystitis in adults. Several risk factors have been recognized, while infectious diseases can be a cause of cholecystitis in otherwise healthy people. Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has spread worldwide, leading to an unprecedented pandemic. The virus enters cells through the binding of the spike protein to angiotensin-converting enzyme 2 (ACE2) receptors expressed in many human tissues, including the epithelial cells of the gastrointestinal (GI) tract, and this explains the symptoms emanating from the digestive system. Acute cholecystitis has been reported in patients with COVID-19. The purpose of this review is to provide a detailed analysis of the current literature on the pathogenesis, diagnosis, management, and outcomes of AAC in patients with COVID-19.
... In the case of inflammatory nodules, infection, biofilms, type IV hypersensitivity reactions, or granulomatous reactions may be the cause, particularly in nodules arising in proximity to infection or vaccination. 4,15,16 These nodules often have delayed onsets and are characterized histologically by inflammatory cell infiltration, which is generally not observed as a normal clinical effect of CaHA-CMC. 17,18 These nodules may present clinically as erythematous, tender, and edematous. ...
... Infections or vaccinations are known contributors in DONs, a phenomenon that has been captured and articulated post-COVID. 15,19,20 If infection is thought to be involved in nodule pathogenesis, it is generally recommended to deploy broad-spectrum antibiotics based on cultures. 9 In cases in which nodules are recurrent without repeated injection, or persist following standard treatments described here, one may suspect biofilm formation, although it has been shown that the biofilm potential of CaHA-CMC is significantly lower than that of hyaluronic acid fillers. ...
Background
Radiesse, a widely used calcium hydroxylapatite (CaHA) dermal filler, has shown effectiveness in soft tissue augmentation and regeneration. As with all dermal fillers, the potential for nodules may arise. Understanding the pathogenesis of these nodules and exploring effective treatment methodologies are crucial for optimizing patient outcomes.
Objectives
A literature search was carried out to identify published literature documenting reversal of CaHA nodules. After identification, a consensus panel developed a structured approach, denoted by levels, for applying such reversal methods.
Methods
This concise review presents an algorithmic approach to addressing CaHA focal accumulations (non-inflammatory nodules) based on invasiveness, cost, and potential risks based on published literature.
Results
Level 0 involves no intervention, relying on natural degradation for asymptomatic nodules. Level 1 interventions utilize mechanical dispersion techniques, including massage and in situ dispersion, which have demonstrated high success rates, cost-effectiveness, and minimal invasiveness. Level 2 introduces alternative modalities such as pharmacological treatments with 5-fluorouracil and corticosteroids, lasers, and experimental approaches. Level 3 represents last-resort options, including calcium chelating agents, manual removal, and surgical excision.
Conclusions
The article offers a structured approach to manage CaHA focal accumulations.
... Skin/soft tissue reactions are attributed to result from vaccine adjuvants, which led to autoimmune/in ammatory syndromes induced by adjuvants (ASIA) (Shoenfeld and Agmon-Levin 2011). Other postulated mechanisms included interaction between the skin ACE-2 receptors and the vaccine's spike protein (Munavalli et al. 2022). ...
This chapter utilizes an eco-social embeddedness framework to describe the sub-systems that influenced the economic impact of the COVID-19 pandemic on dermatology practice and dermatologists. A proper understanding can only be achieved by reference to the pandemic’s effects on the global economy and the supply and demand for healthcare services. Government infection control policies, the availability of prophylactic and therapeutic agents, and the influence of information and communications technologies were major factors in determining the depth and scope of the economic effects, which then shaped the behavior of dermatologists and their practices. We explore the implications for dermatology practice in the post-COVID-19 world and the role of technology in the next pandemic.
... Embora seja raro, pode ser preocupante para pacientes, pois afeta a qualidade de vida do paciente. Dessa forma, é importante que os especialistas em harmonização orofacial estejam cientes dessa complicação e saibam como tratá-la adequadamente, a fim de minimizar os riscos e garantir os melhores resultados para o paciente (Munavalli et al., 2022). ...
... O ETIP é uma complicação rara que tem sido associada à aplicação de preenchedores dérmicos, notadamente o ácido hialurônico, na prática clínica da harmonização orofacial. Os pacientes que desenvolvem essa condição apresentam sintomas como inchaço, vermelhidão e sensibilidade na área tratada, os quais podem persistir por dias ou semanas após o procedimento (Munavalli et al., 2022). Research, Society andDevelopment, v. 12, n. 11, e139121143888, 2023 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v12i11.43888 ...
Desde o surgimento da COVID-19 em Wuhan, a pandemia se espalhou pelo mundo, causando muitas mortes e afetando milhões de pessoas. Enquanto isso, o ácido hialurônico tem sido utilizado na harmonização orofacial para preencher rugas e sulcos na pele. No entanto, a aplicação de preenchedores dérmicos, como o ácido hialurônico, pode levar a uma complicação rara chamada edema tardio intermitente e persistente (ETIP), que causa inchaço e vermelhidão na área tratada. A relação entre a ETIP, a vacinação da COVID-19 e a harmonização orofacial tem sido estudada por especialistas que sugerem que a ETIP pode ser decorrente e iniciada após a aplicação da vacina. É importante que os profissionais de saúde estejam cientes dessa possível relação e informem seus pacientes sobre os riscos antes de realizar qualquer procedimento estético. Dessa forma, essa revisão narrativa da literatura tem como objetivo ofertar um documento catalogado sobre a relação entre ETIP, COVID-19 e ácido hialurônico como preenchedor dérmico na prática clínica da harmonização orofacial.
... Reports of delayed inflammatory reactions to hyaluronic acid fillers have increased in after COVID-19 vaccination [47] and infections [48,49]. It has been suggested that the COVID-19 spike protein acts as a trigger for the formation of a delayed inflammatory reaction [50]. Spike protein interactions with angiotensin-converting enzyme receptors cause a pro-inflammatory Th1 response and promote CD8+ T cell-mediated reactions [50]. ...
... It has been suggested that the COVID-19 spike protein acts as a trigger for the formation of a delayed inflammatory reaction [50]. Spike protein interactions with angiotensin-converting enzyme receptors cause a pro-inflammatory Th1 response and promote CD8+ T cell-mediated reactions [50]. Anti-inflammatory drugs or steroids have been used for delayed inflammatory reaction [13,49,51]. ...
The etiology and pathophysiology of delayed inflammatory reactions caused by hyaluronic acid fillers have not yet been elucidated. Previous studies have suggested that the etiology can be attributed to the hyaluronic acid filler itself, patient immunological status, infection, and injection technique. Hyaluronic acid fillers are composed of high-molecular-weight hyaluronic acids that are chemically crosslinked using substances such as 1,4-butanediol diglycidyl ether (BDDE). The mechanism by which BDDE crosslinks the two hyaluronic acid disaccharides is still unclear and it may exist as a fully reacted crosslinker, pendant crosslinker, deactivated crosslinker, and residual crosslinker. The hyaluronic acid filler also contains impurities such as silicone oil and aluminum during the manufacturing process. Impurities can induce a foreign body reaction when the hyaluronic acid filler is injected into the body. Aseptic hyaluronic acid filler injections should be performed while considering the possibility of biofilm formation or delayed inflammatory reaction. Delayed inflammatory reactions tend to occur when patients experience flu-like illnesses; thus, the patient’s immunological status plays an important role in delayed inflammatory reactions. Large-bolus hyaluronic acid filler injections can induce foreign body reactions and carry a relatively high risk of granuloma formation.
... In the early beginning of investigations on SARS-CoV-2 vaccination, the Food and Drug Administration (FDA) reported on three patients with soft tissue fillers who experienced adverse events after vaccination with Moderna [26]. Hereafter, more and more case reports were published regarding adverse events related to SARS-CoV-2 infection and vaccination [27][28][29][30][31][32]. We therefore previously performed a systematic review on LIRs after SARS-CoV-2 infection and vaccination [33]. ...
Soft tissue fillers are widely used and are commonly considered to be safe. Nonetheless, adverse events such as late inflammatory reactions (LIRs) are reported for every type of filler. As of the start of the COVID-19 pandemic, LIRs have been reported after SARS-CoV infection or vaccination. In the past, we reviewed these adverse events; however, since then, we faced a wave with the Omicron, and the vaccination programs continued with booster vaccines. We therefore aimed to perform an up-to-date review of the literature on LIRs after COVID-19 infection and vaccination with additional learned lessons from this pandemic.
We performed a systematic review on soft tissue filler-related LIRs after SARS-CoV-2 infection or vaccination in line with the PRISMA guidelines. Eligible studies were searched in the database PubMed from 1 August 2021 until 1 June 2023. Data on patient characteristics, filler characteristics, clinical findings, and treatment options were retrieved.
A total of 14 papers with in total 52 patients were reported, of which 16 had adverse events after a SARS-CoV-2 infection and 36 after SARS-CoV-2 vaccination. In most cases, it concerned females who had their (mostly temporary) fillers for cosmetic purposes. Symptoms were reported in a matter of hours up to weeks after SARS-CoV-2 vaccination (22 Pfizer, 7 Moderna, 3 AstraZeneca, 3 Sputnik V, and one after Siophram), mostly after the first or second dose but sporadically after a third dose. Most patients were treated in a conservative manner.
LIRs continue to be reported after SARS-CoV-2 infection and vaccination and are currently also reported for non-mRNA vaccines, for non-temporary fillers, and also after a third dose of the vaccine. Although there are more and more papers on this matter, they remain minor and self-limiting. We therefore still advise patients with soft tissue fillers to remain participated in vaccination programs when needed.
Level of evidence: Not gradable.
... There have been numerous reports of cutaneous reactions in skin areas previously treated with cosmetic materials. Such SARSrelated reactions in injection sites have included induration, edema, tenderness, erythema, discoloration, and nodule formation (Rowland-Warmann, 2021; Shome et al., 2021;Munavalli et al., 2022). When considering allergic reactions to Botox in cosmetic settings, a total of six cases have been reported to date (Rosenfield et al., 2014;Careta et al., 2015;Moon et al., 2017;Sudre et al., 2021). ...
Background
The COVID-19 pandemic has brought about significant changes in the medical field, yet the use of botulinum toxin type A has remained uninterrupted. Plastic surgeons must carefully consider the timing of administering botulinum toxin type A to patients who have recovered from COVID-19.
Methods
A questionnaire survey was conducted among patients who had contracted and recovered from SARS-CoV-2 within a month. The survey aimed to investigate various indicators in patients who had received botulinum toxin A injections at the same site before and after their infection, including pain scores and allergic reactions and the occurrence of complications.
Results
The pain scores of patients who contracted SARS-CoV-2 infection between 14-21 days post-infection exhibited significant variation from previous injections. However, patients who contracted the infection between 22-28 days post-infection did not exhibit significant variation from previous injections. Furthermore, the incidence of allergic reactions and complications following botulinum toxin injection within one month after contracting the infection did not significantly differ from that observed prior to infection.
Conclusion
Administering botulinum toxin type A three weeks after COVID-19 recovery is a justifiable and comparatively secure approach.
... These reactions can occur anytime from 24 h after injection to several months [16,51,53] . The nodules can eventually progress to a specific granulomatous reaction [52,54] . ...
... While hyaluronic acid is not typically immunogenic, other components that stabilize these molecules may predispose the filler product to become immunogenic [57] . It has also been theorized that glycosaminoglycans can act as superantigens and activate immune reactive cells [54] . After changes in the manufacturing process reduced the protein load in HA by six-fold, the incidence of inflammatory reactions decreased from 0.15 to 0.06 percent [58][59][60] . ...
... These delayed hypersensitivity nodules often lead to granulomas [54] . A granuloma is considered a form of chronic inflammation that occurs in response to a foreign material that has not been able to be phagocytosed by macrophages [62] . ...
Dermal fillers have been commonly used for the filling of facial rhytids. As the use of dermal fillers has grown, so has the incidence of non-ischemic complications. These complications range from edema, bruising, and erythema to more complex conditions such as delayed hypersensitivity nodules and biofilms. This article sought to review the causes of various non-ischemic complications, discuss their risk factors, and review management techniques. Certain predisposing factors to delayed hypersensitivity nodules, such as Vycross technology, a history of viral illness, or coronavirus disease 19 (COVID-19) infections, are discussed in detail in this review. Prevention techniques such as patient counseling, elucidating certain patient history (viral illness, dental procedures), the use of aseptic technique, and procedural factors are also discussed. Understanding appropriate management for these complications can also help in treatment. Imaging, such as ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI), has taken on a larger role in the management of non-ischemic complications.
