## 4 Discussion
Notably, of those 9 patients, 8 received Allergan fillers (Vycross or Hylacross technology), and the last one, described in the present paper, also had a history of tardive swelling following Allergan filler injections. Hylacross and Vycross are two different HA technologies developed by Allergan (Irvine, CA, USA); the former is characterized by a higher cross-linking rate of BDDE, ranging from 9% to 11%, to achieve a more viscous and long-lasting filler, while the latter is characterized by a mixture of low- and high-molecular-weight HA to achieve a smoother and long-lasting filler. BDDE could be a potential source for the late-onset of inflammatory reactions: the degradation of cross-linked HA filler may expose traces of BDDE, and the gradual exposure or release of these molecules could trigger the immune system [40; 41]. This could explain the late-onset AE related to the use of Hylacross technology. On the other hand, some concerns related to tardive AE, such as swelling following Vycross technology, have already arisen in the medical literature [28; 39; 42]. [PERSON] et al. (2019) described their experience with Juvederm Vycross fillers and concluded that the introduction of this new class of filler introduced a new variable that may change the immune tolerance of these substances, resulting in a higher incidence of delayed adverse events than previously expected [42]. In 2017, [PERSON] et al. evaluated the effectiveness and safety of Juvederm Volbella (Allergan, Irvine, CA, USA), belonging to the \"Vycross family\", for the correction of infraorbital skin depression (tear trough) in 80 patients. Following the investigators' assessment, some AE were not detectable until six months after the injections. Late-onset, mild-to-moderate edema was detected in 11% of cases at 6 months, 5% at 9 months, and 4% at 12 months [43]. A few more pieces of research investigated the link between Juvederm Volbella (Allergan, Irvine, CA,USA) and delayed complications, revealing an incidence rate ranging from 0.3% to 4.25%. The exact mechanism implicated in delayed AE such as tardive swelling is not completely clear, although it has been postulated that an immunological trigger can be detected [44; 45; 46; 47]. [PERSON] et al. described a case series based on fourteen patients with a history of soft tissue filler injections having experienced tardive AE after the beginning of a flu-like illness [48]. Vycross technology, introduced by Allergan, moved from the 100% high-molecular-weight (HMW) HA filler to a 10% HMW and a 90% low-molecular-weight (LMW) HA filler [47; 49]. HMW HA is known to have an anti-inflammatory effect; on the other hand, it has shown that LMW HA, less than 20 kDa, has a pro-inflammatory effect [50; 51]. [PERSON] et al. suggested that systemic inflammatory responses, such as flu-like illnesses or vaccines, accelerate LMW HA degradation from acute free radical production influencing CD44-HA, signaling and resulting in delayed adverse events [44]. In February 2021, the Cosmetic Surgery Forum (CSF) discussed the risk of delayed facial swelling in filler patients following COVID-19 vaccination [52]. [PERSON], a New York City dermatologist and CSF panelist, stated that, regarding the type of filler that most likely caused tardive reaction following the administration of a COVID-19 vaccine, data were trending more toward Vycross fillers [52].