Oral Methotrexate Treatment of Delayed-Onset Inflammatory Reactions to Dermal Fillers.

Background: In aesthetic practice, delayed-onset (late) inflammatory reactions (DIRs) to dermal fillers are encountered. The treatment of DIRs can be challenging, with a response to established therapies, including oral antibiotics, intralesional and oral steroids, and hyaluronidase injection, occasionally reported as unsatisfactory. Objectives: Evaluate the efficacy of low-dose oral methotrexate (MTX) therapy in treating recalcitrant DIRs. Methods: We retrospectively reviewed cases of recalcitrant DIRs treated with oral MTX. Data collected included individuals' gender and age, medical history, filler type, facial area(s) injected, previous treatments attempted to dissolve the DIR, MTX treatment dosage and duration, and outcome. Adverse events were monitored throughout the treatment. Results: Thirteen females with a mean age of 52.6 years (range, 31-67 years) who developed recalcitrant DIRs to dermal filler injection are included. Eight reactions were triggered by the injection of hyaluronic acid (HA) fillers, 4 by liquid injectable silicone (LIS), and 1 by polymethylmethacrylate (PMMA). The average starting dosage of MTX was 12.1 mg/week (range, 7.5-12.5 mg/week). Patients were treated for 2 to 3 months in most cases. The average follow-up post-MTX therapy was 11.8 months (range, 2-36 months). A complete response to MTX treatment was observed in 10 patients (6 HA and 4 LIS cases), partial response in 1 (HA case), and an unsatisfactory response in 2 (HA and PMMA cases). Treatment was well tolerated. Conclusions: A short course of low-dose oral MTX is a possible treatment for DIRs that have not responded to established therapies. The promising results of this report require validation by powered studies.

Phenol-Croton Oil Chemical Peeling Induces Durable Improvement of Constitutional Periorbital Dark Circles.

BACKGROUND: Constitutional periorbital dark circles (PDC) are common in skin of color and represent a therapeutic challenge. OBJECTIVE: To summarize the experience of the International Peeling Society on the safety and effectiveness of deep chemical peeling in the treatment of constitutional PDC. MATERIALS AND METHODS: Multi-institutional, retrospective case series (1990-2020) of constitutional PDC treated by deep chemical peeling. Descriptive analysis by age, sex, Fitzpatrick phototype, phenol-croton formula, degree and durability of improvement, and complications. RESULTS: Fifty-five phenol-croton oil peels were performed in 52 patients: 3 patients received a second peel for periorbital rhytids 72 to 84 months after the first peel. 92% (48/52) of patients were women; the median age was 46 years (range, 23-68 years). 89% (46/52) of patients were Fitzpatrick III-IV. Most common formula included phenol 60% to 65% and croton oil 0.6% to 0.7%. 89% (49/55) of peels demonstrated >50% clinical improvement. The median duration of improvement was 24 months (range, 1.5-168 months), and 69% (36/52) of patients demonstrated ongoing improvement at the last follow-up. 4% (2/55) of peels exhibited complications of persistent erythema that resolved without scarring. CONCLUSION: Based on its safety and effectiveness, deep chemical peels are a treatment of choice for constitutional PDC.

"COVID-19/SARS-CoV-2 virus spike protein-related delayed inflammatory reaction to hyaluronic acid dermal fillers: a challenging clinical conundrum in diagnosis and treatment".

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 after vaccination. In this report of 4 cases with distinct clinical histories and presentations: one case occured following a community acquired COVID-19 infection, one case occured in a study subject in the mRNA-1273 clinical phase III trial, one case occurred following the first dose of publically available mRNA-1273 vaccine (Moderna, Cambridge MA), and the last case occurred after the second dose of BNT162b2 vaccine (Pfizer, New York, NY). Injectable HA dermal fillers are prevalent in aesthetic medicine for facial rejuvenation. Structural modifications in the crosslinking of HA fillers have enhanced the products' resistance to enzymatic breakdown and thus increased injected product longevity, however, have also led to a rise in DIR. Previous, DIR to HA dermal fillers can present clinically as edema with symptomatic and inflammatory erythematous papules and nodules. The mechanism of action for the delayed reaction to HA fillers is unknown and is likely to be multifactorial in nature. A potential mechanism of DIR to HA fillers in COVID-19 related cases is binding and blockade of angiotensin 2 converting enzyme receptors (ACE2), which are targeted by the SARS-CoV-2 virus spike protein to gain entry into the cell. Spike protein interaction with dermal ACE2 receptors favors a pro-inflammatory, loco-regional TH1 cascade, promoting a CD8+T cell mediated reaction to incipient granulomas, which previously formed around residual HA particles. Management to suppress the inflammatory response in the native COVID-19 case required high-dose corticosteroids (CS) to suppress inflammatory pathways, with concurrent ACE2 upregulation, along with high-dose intralesional hyaluronidase to dissolve the inciting HA filler. With regards to the two vaccine related cases; in the mRNA-1273 case, a low dose angiotensin converting enzyme inhibitor (ACE-I) was utilized for treatment, to reduce pro-inflammatory Angiotensin II. Whereas, in the BNT162b2 case the filler reaction was suppressed with oral corticosteroids. Regarding final disposition of the cases; the vaccine-related cases returned to baseline appearance within 3 days, whereas the native COVID-19 case continued to have migratory, evanescent, periorbital edema for weeks which ultimately subsided.

Patient Satisfaction with AbobotulinumtoxinA for Aesthetic Use in the Upper Face: A Systematic Literature Review and Post-hoc Analysis of the APPEAL Study.

BACKGROUND: AbobotulinumtoxinA (AboBoNT-A; Dysport®; Ipsen, Boulogne-Billancourt, France/Azzalure®; Galderma, Lausanne, Switzerland) is a botulinum neurotoxin type A approved for aesthetic use in the treatment of glabellar lines in adult patients under 65 years in Europe, the United States, and other countries. OBJECTIVE: We sought to analyze current literature on patient satisfaction with aboBoNT-A for upper facial aesthetic indications. METHODS: A systematic review of literature databases (PubMed/MEDLINE, Embase, the Cochrane Library, and Google Scholar) was performed to identify English-language publications reporting on patients with aesthetic indications (including glabellar lines and wrinkles) receiving aboBoNT-A, that assessed patient and/or physician satisfaction with treatment, with no restrictions on comparator studies. Structured data extraction was used to enable inter-study analysis. A post-hoc analysis was also performed to assess patient satisfaction by sex and age, using results from the noninterventional APPEAL study of patients' satisfaction with aboBoNT-A for treating glabellar lines. RESULTS: Overall, 22 original research papers were identified. Patient satisfaction rates for aboBoNT-A treatment were significantly higher versus placebo from two weeks to between three and five months postinjection. At two to three weeks postinjection, patient satisfaction rates were 52% and 99% across studies. In studies with later time points, patient satisfaction rates were 85 to 87 percent at 5 months and between 25 and 100 percent at 6 months post-injection. Physician satisfaction was also high (97%-100%, across three treatments). No notable differences in patient satisfaction by sex or age were observed in the APPEAL study. CONCLUSION: High rates of patient satisfaction have been achieved with aboBoNT-A treatment for upper facial aesthetic indications. Despite the current recommended interval of ≥12 weeks, satisfaction with the aesthetic results of aboBoNT-A therapy is still evident up to 6 months post-injection in some patients.

Skin Quality - A Holistic 360° View: Consensus Results.

INTRODUCTION: Skin quality is an important component of human attractiveness. To date, there are no standardized criteria for good skin quality. To establish a consensus for good skin quality parameters and measurement and treatment options, a virtual skin quality advisory board consisting of a global panel of highly experienced aesthetic dermatologists/aesthetic physicians was convened. METHODS: A total of 10 dermatologists/aesthetic physicians served on the advisory board. A modified version of the Delphi method was used to arrive at consensus. Members accessed an online platform to review statements on skin quality criteria from their peers, including treatment and measurement options, and voted to indicate whether they agreed or disagreed. Statements that did not have agreement were modified and the members voted again. Consensus was defined as: strong consensus = greater than 95% agreement; consensus = 75% to 95% agreement; majority consent = 50% to 75% agreement; no consensus = less than 50% agreement. RESULTS: There was strong consensus that good skin quality is defined as healthy, youthful in appearance (appearing younger than a person's chronological age), undamaged skin and that skin quality can be described across all ethnicities by four emergent perceptual categories (EPCs): skin tone evenness, skin surface evenness, skin firmness, and skin glow. The EPCs can be affected by multiple tissue layers (ie, skin surface quality can stem from and be impacted by deep structures or tissues). This means that topical approaches may not be sufficient. Instead, improving skin quality EPCs can require a multilayer treatment strategy. CONCLUSION: This global advisory board established strong consensus that skin quality can be described by four EPCs, which can help clinicians determine the appropriate treatment option(s) and the tissue or skin layer(s) to address. Skin quality is important to human health and wellbeing and patients' perception for the need for aesthetic treatment.

[PUSTULAR PSORIASIS DURING PREGNANCY: WHEN IS THE RIGHT TIME TO DELIVER?]

INTRODUCTION: General pustular pruritus psoriasis (GPPP), also known by the name impetigo herpetiformis, is a rare type of pustular dermatosis which typically occurs in pregnant women during the 3rd trimester and usually regresses after birth. The disease is characterized by acute abruption of erythematous plaque with a disseminated spread of sterile pustule, and may progress to sepsis and even death. Notably, it also carries obstetric complications and is associated with an increase in neonatal morbidity and stillbirth. We present a case report of a patient, and discuss the importance of proper management in this rare condition.

Botulinum toxin complications in registered and off-label aesthetic indications.

Botulinum toxin A (BTXA) is one of the most popular nonsurgical cosmetic procedures worldwide. Overall, this procedure is associated with favorable complications profile. Nevertheless, any medical intervention carries inherent risks. This synopsis systematically reviews adverse effects of aesthetic BTXA for both approved and off-label indications. Based on published data, the approach for prevention and management is discussed.

Delayed Inflammatory Reactions to Hyaluronic Acid Fillers: A Literature Review and Proposed Treatment Algorithm.

BACKGROUND AND OBJECTIVES: There is a wide diversity of opinions regarding the management of delayed inflammatory reactions (DIRs) secondary to hyaluronic acid (HA)-based fillers. The plethora of approaches has led the authors to conduct a review regarding management and treatment of DIRs as well as establish therapeutic guidelines for this purpose. MATERIALS AND METHODS: A review of the literature was performed through databases such as PubMed using keywords including HA-fillers and complications, delayed HA filler sequelae and therapy, soft tissue and dermal filler reactions and management. Additionally, a survey comprised of questions regarding the management and treatment of DIRs was sent to 18 physicians highly experienced with soft-tissue filler injections in 10 countries. Their answers and recommendations were analyzed and debated amongst these panelists. RESULTS: Sixteen panelists favored antibiotic therapy as first-line treatment for DIRs, specifically dual antibiotic therapy consisting of a fluoroquinolone along with a tetracycline or macrolide for a period of 3-6 weeks. The majority refrained from the use of intralesional (IL) or systemic steroids except in the case of disfiguring or recalcitrant reactions. IL hyaluronidase was recommended by 13 panelists; however, some preferred a watchful waiting approach for a period of 48 hours to 2 weeks prior to IL hyaluronidase, and in cases where antibiotics did not lead to improvement. CONCLUSION: A consensus was reached and summarized to propose a clear, easy-to-follow, stepwise algorithm for the treatment of DIRs.

Management Patterns of Delayed Inflammatory Reactions to Hyaluronic Acid Dermal Fillers: An Online Survey in Israel.

BACKGROUND: Over the past few decades, soft tissue augmentation is ever-increasing, specifically hyaluronic acid (HA)-based filler injections. As the number of these procedures have risen, so have the adverse reactions. Delayed-type inflammatory reactions (DIRs) secondary to tissue fillers are typically classified according to the time of appearance post-procedure and have various presentations including nodules, abscesses, edema, and discoloration. Currently, the treatment of these complications varies among physicians. OBJECTIVE: The aim of this study was to assess the knowledge and experience of practitioners in Israel who inject HA-based tissue fillers with respect to the management of late-onset procedural complications. MATERIALS AND METHODS: A survey regarding management and treatment of late-onset inflammatory reactions was sent to 1120 physicians and dentists in Israel who practice tissue filler injections. RESULTS: Three hundred thirty-four out of the 1120 practitioners replied to the questionnaire. The majority of respondents were dentists (group A) comprising 31% of all respondents. Group B accounted for 31% of injectors and consisted of dermatologists (19%) and plastic surgeons (12%), and group C (38%) accounted for all other practitioners; 48.2% of all injectors indicated that they have not previously encountered a DIR, whereas 11.4% responded that they have encountered more than 5 DIRs. In order to assess treatment management, we presented the injectors with a simulatory case of a woman with a late-onset complication. Most injectors referred the patient to the emergency department. When asked to establish a treatment plan, the majority of practitioners prescribed short-term oral steroids, ie, prednisone (35.3%). A limited number of patients were treated with intra-lesional hyaluronidase (31.4%) injection as only 34% of injectors kept hyaluronidase at their clinic. CONCLUSION: The varied approach regarding the management of delayed type reactions to HA-based filler injections, reflected in our study, illustrates the existing ambivalence in the current literature regarding the management and therapy of late-onset complications.

The Bidirectional Movement of the Frontalis Muscle: Introducing the Line of Convergence and Its Potential Clinical Relevance.

BACKGROUND: Cosmetic treatment of the forehead using neuromodulators is challenging. To avoid adverse events, the underlying anatomy has to be understood and thoughtfully targeted. Clinical observations indicate that eyebrow ptosis can be avoided if neuromodulators are injected in the upper forehead, despite the frontalis muscle being the primary elevator. METHODS: Twenty-seven healthy volunteers (11 men and 16 women) with a mean age of 37.5 ± 13.7 years (range, 22 to 73 years) and of diverse ethnicity (14 Caucasians, four African Americans, three Asians, and six of Middle Eastern descent) were enrolled. Skin displacement vector analyses were conducted on maximal frontalis muscle contraction to calculate magnitude and direction of forehead skin movement. RESULTS: In 100 percent of investigated volunteers, a bidirectional movement of the forehead skin was observed: the skin of the lower forehead moved cranially, whereas the skin of the upper forehead moved caudally. Both movements converged at a horizontal forehead line termed the line of convergence, or C-line. The position of the C-line relative to the total height of the forehead was 60.9 ± 10.2 percent in men and 60.6 ± 9.6 percent in women (p = 0.941). Independent of sex, the C-line was located at the second horizontal forehead line when counting from superior to inferior (men, n = 2; women, n = 2). No difference across ethnicities was detected. CONCLUSIONS: The identification of the C-line may potentially guide practitioners toward more predictable outcomes for forehead neuromodulator injections. Injections above the C-line could mitigate the risk of neuromodulator-induced brow ptosis.

Onset and Duration of AbobotulinumtoxinA for Aesthetic Use in the Upper face: A Systematic Literature Review.

OBJECTIVE: We sought to analyze the current literature regarding time to onset and duration of effect of abobotulinumtoxinA (aboBoNT-A, Dysport®/Azzalure®) for upper facial aesthetic indications. METHODS: We conducted a systematic review of literature databases (PubMed/MEDLINE, Embase, Cochrane Library, and Google Scholar) to identify English-language publications relevant to: population (patients with aesthetic indications [including glabellar lines and wrinkles]); interventions (aboBoNT-A); comparators (no restrictions); outcomes (efficacy, including onset of action and duration of effect); and settings (clinical). A manual search of review paper bibliographies was performed. Structured data extraction was used to enable interstudy analysis. RESULTS: Overall, 42 original research papers relevant to aboBoNT-A onset and/or duration were identified. All 24 studies assessing efficacy within one week post-injection demonstrated some response at the first time point assessed, and all 37 studies assessing duration showed some response after 12 weeks. Although methodologies for assessing onset and duration differed, when outcomes were refined by reported mean/median, at least 50 percent of patients responding to treatment, or significance versus placebo or baseline at a given time point, onset was most often reported within 2 to 3 days (7 studies), and as early as 24 hours (2 studies). Duration was most often reported as four months (18 studies), although four studies provided evidence that aboBoNT-A efficacy was maintained at five months and three studies at or after six months post-injection. CONCLUSION: This review indicates that aboBoNT-A has a median onset of efficacy of 2 to 3 days and a longer duration of action (3-6 months across studies) than the current labelled minimum treatment interval (12 weeks).

Depth Map for Face and Neck Deep Chemical Peel Resurfacing.

BACKGROUND: Chemical peels are applied to the face and neck to improve rhytides and the photoaged appearance of the skin. Peels can be applied to different skin depths depending on the types of chemicals, the volume of solution, and the amount of pressure or friction applied. If a peel is applied too superficially, rhytides will not be removed. If a peel is applied too deeply, scarring or hypopigmentation could occur. OBJECTIVE: To create face and neck depth maps for chemical peeling, which can guide safety when removing rhytides and improving the skin's appearance. MATERIALS AND METHODS: A multicenter retrospective review of records was conducted of patients who underwent phenol-croton oil peeling, from January 1, 2018, to December 31, 2018. Information was collected on facial and neck cosmetic units peeled, peel formula and strength used, outcomes, and complications. RESULTS: A total of 410 patients received deep peels. Two depth maps were created that corresponded to the most common patterns of deep chemical peel applications. CONCLUSION: Different areas of the face and neck are treated with different chemical peel application depths to safely improve rhytides and appearance. Depth maps are created to balance safety and efficacy.