The Use of Hyaluronidase in Aesthetic Practice: A Comparative Study of Practitioner Usage in Elective and Emergency Situations.

BACKGROUND: Hyaluronic acids (HAs) continue to be the fillers of choice worldwide and their popularity is growing. Adverse events (AEs) are able to be resolved through the use of hyaluronidase (HYAL). However, routine HYAL use has been at issue due to perceived safety issues. OBJECTIVES: There are currently no guidelines on the use of HYAL in aesthetic practice, leading to variability in storage, preparation, skin testing, and beliefs concerning AEs. This manuscript interrogated the use of this agent in daily practice. METHODS: A 39-question survey concerning HYAL practice was completed by 264 healthcare practitioners: 244 from interrogated databases and 20 from the consensus panel. Answers from those in the database were compared to those of the consensus panel. RESULTS: Compared to the database group, the consensus group was more confident in the preparation of HYAL, kept reconstituted HYAL for longer, and was less likely to skin test for HYAL sensitivity and more likely to treat with HYAL in an emergency, even in those with a wasp or bee sting anaphylactic history. Ninety-two percent of all respondents had never observed an acute reaction to HYAL. Just over 1% of respondents had ever observed anaphylaxis. Five percent of practitioners reported longer-term adverse effects, including 3 respondents who reported loss of deep tissues. Consent before injecting HA for the possible requirement of HYAL was always obtained by 74% of practitioners. CONCLUSIONS: Hyaluronidase would appear to be an essential agent for anyone injecting hyaluronic acid filler. However, there is an absence of evidence-based recommendations with respect to the concentration, dosing, and treatment intervals of HYAL, and these should ideally be available.

Making Sense of Late Tissue Nodules Associated With Hyaluronic Acid Injections.

BACKGROUND: The pathogenesis of delayed-onset tissue nodules (DTNs) due to hyaluronic acid (HA) injections is uncertain. OBJECTIVES: To formulate a rational theory for DTN development and their avoidance and treatment. METHODS: A multidisciplinary and multicountry DTN consensus panel was established, with 20 questions posed and consensus sought. Consensus was set at 75% agreement. RESULTS: Consensus was reached in 16 of 20 questions regarding the pathogenesis of DTNs, forming the basis for a classification and treatment guide. CONCLUSIONS: The group believes that filler, pathogens, and inflammation are all involved in DTNs and that DTNs most likely are infection initiated with a variable immune response. Injected filler may incorporate surface bacteria, either a commensal or a true pathogen, if the skin barrier is altered. The initially high molecular weight HA filler is degraded to low molecular weight HA (LMWHA) at the edge of the filler. Commensals positioned within the filler bolus may be well tolerated until the filler is degraded and the commensal becomes visible to the immune system. LMWHA is particularly inflammatory in the presence of any local bacteria. Commensals may still be tolerated unless the immune system is generally heightened by viremia or vaccination. Systemic pathogenic bacteremia may also interact with the filler peripheral LMWHA, activating Toll-like receptors that induce DTN formation. Given this scenario, attention to practitioner and patient hygiene and early systemic infection treatment deserve attention. Classification and treatment systems were devised by considering each of the 3 factors-filler, inflammation, and infection-separately.

Immunostained Frozen Sections Vs Traditional Permanent Paraffin Sections for Lentigo Maligna Treated With Mohs Micrographic Surgery.

BACKGROUND: Mohs micrographic surgery (MMS) has risen in popularity as a management option for treating lentigo maligna (LM) because of its ability to accurately detect subclinical spread while conserving tissue. The primary concern for opponents of MMS in melanoma remains the difficulty associated with interpretation of frozen sections compared with traditional paraffin sections; this has been made easier with the advent of immunostaining. OBJECTIVE: Our study aims to assess the concordance in clearance reporting of LM in immunostained frozen sections compared with permanent paraffin sections and hematoxylin and eosin staining. METHODS: We conducted a retrospective analysis of 38 LM cases treated by MMS between 2017 and 2020 in Melbourne, Australia. Immunostained frozen sections were assessed by a Mohs surgeon, whereas permanent paraffin sections were assessed by an external dermatopathologist. RESULTS: We report 86% agreement in reporting of LM in immunostained frozen sections compared with permanent paraffin sections. In 5/38 cases, permanent paraffin sections were reported as clear for LM, but the Mohs surgeon had detected positive margins, requiring further excision. CONCLUSION: For LM treated with MMS, there is a high agreement of clearance reporting between immunostained stained frozen sections and permanent paraffin sections without immunostaining; however, immunostained frozen sections may be more sensitive.

Infantile hemangioma affecting the iris.

An infant girl developed a hemangioma affecting her left iris concurrently with diffuse cutaneous infantile hemangiomas from day 2 of life. Intraocular hemangiomas are rarely reported and are usually associated with neonatal hemangiomatosis, the presence of which indicates a high risk for visceral lesions. This striking case highlights the unusual clinical presentation of iris hemangioma and demonstrates the importance of conducting visceral screening when faced with these lesions. Oral propranolol was commenced and resulted in rapid improvement of all lesions without complication.

Guidance on infection control and plume management with Laser and Energy-Based Devices taking into consideration COVID-19.

BACKGROUND: The COVID-19 pandemic has disrupted the practice of medicine. Dermatologic laser and energy-based device (EBD) treatments carry a potential risk for the transmission of SARS-CoV-2 both for the patient and the practitioner. These risks include close practitioner to patient proximity, the treatment of higher viral load areas such as the face, the potential for infective bioparticles being carried by generated plumes and aerosols, and the direct contact between device, practitioner and patient. OBJECTIVES: SARS-CoV-2 is a highly infective respiratory pathogen transmitted by respiratory droplets, respiratory/mucosal secretions, medically generated aerosols and via its transfer from contaminated fomites. This requires a review of the appropriateness of infection control protocols in regard to dermatologic laser and energy-based device treatments. METHODS: A critical evaluation of patient skin preparation including skin asepsis, device disinfection, laser and electrosurgical plume management and PPE in regard to SARS-CoV-2 was performed. RESULTS: The adherence to a high standard of skin preparation and asepsis, device disinfection, laser and electrosurgical plume and aerosol management and appropriate PPE should help mitigate or reduce some of the inherent treatment risks. Head and neck treatments along with aerosol and laser plume generating treatments likely carry greater risk. CONCLUSIONS: COVID-19 needs to be considered in the clinic set-up along with the planning, treatment and post-treatment care of patients utilising EBD procedures. Some of these treatment precautions are COVID-19 specific; however, most represent adherence to good infectious disease and established laser and EBD safety precautions.

A Consensus on Minimizing the Risk of Hyaluronic Acid Embolic Visual Loss and Suggestions for Immediate Bedside Management.

BACKGROUND: Hyaluronic acid fillers have a satisfactory safety profile. However, adverse reactions do occur, and rarely intravascular injection may lead to blindness. Currently there is no internationally recognized consensus on the prevention or management of blindness from hyaluronic acid filler. OBJECTIVES: The authors sought to give guidance on how to minimize the risk and optimize the management of this rare but catastrophic adverse reaction. METHODS: A multinational group of experts in cosmetic injectables from multiple disciplines convened to review current best practice and develop updated consensus recommendations for prevention and bedside intervention if visual loss occurs after cosmetic injection of hyaluronic acid filler. RESULTS: The consensus group provided specific recommendations focusing on the consenting process, prevention, and early management of visual impairment related to intravascular hyaluronic acid filler injection. CONCLUSIONS: Although visual loss due to filler injections is rare, it is important that both patient and physician be aware of this risk. In this paper the authors describe methods and techniques available to reduce the risk and also document suggested initial management should a clinician find themselves in this situation.

Retrospective review of screening for Sturge-Weber syndrome with brain magnetic resonance imaging and electroencephalography in infants with high-risk port-wine stains.

BACKGROUND: There is a lack of consensus regarding how best to screen children with facial port-wine stains for Sturge-Weber syndrome. Many favor brain magnetic resonance imaging, and adjunctive electroencephalography is increasingly used. However, the sensitivity, specificity, and negative and positive predictive value of magnetic resonance imaging and electroencephalography and whether screening improves seizure recognition is unclear. METHODS: A retrospective review of children with high-risk port-wine stains presenting consecutively to the outpatient laser clinic of a tertiary pediatric hospital between December 2015 and November 2016 was undertaken. Primary outcome measures were yield, accuracy, age of and protocols for screening magnetic resonance imaging and electroencephalography, type of and age at presenting seizure, and percentage referred to neurology. RESULTS: Of 126 patients with facial port-wine stains, 25.4% (32/126) were at high risk of Sturge-Weber syndrome (hemifacial, median, and forehead PWS phenotypes); 43.7% of these (14/32) underwent screening magnetic resonance imaging. Sturge-Weber syndrome was detected in 7.1% (1/14). Magnetic resonance imaging had false-negative results in 23.1% (3/13) of those screened. Screening magnetic resonance imaging had sensitivity of 25%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 76.9% for the detection of Sturge-Weber syndrome (hemifacial, median and forehead PWS phenotypes). Only one-third of those with false-negative magnetic resonance imaging were referred to neurology. Mean age of first seizure in those with false-negative screening magnetic resonance imaging was 28 months, vs 14 months in those not screened. Abnormal electroencephalographic signs were detected in the two infants who underwent presymptomatic electroencephalography. CONCLUSIONS: Findings from this small cohort of individuals with port-wine stains that put them at high risk of Sturge-Weber syndrome suggest that children with positive screening magnetic resonance imaging will almost certainly develop Sturge-Weber syndrome but that negative screening magnetic resonance imaging cannot exclude Sturge-Weber syndrome (in up to 23.1% of cases). False-negative magnetic resonance imaging may delay seizure recognition. Seizure education, monitoring, and consideration of adjunctive electroencephalography are important irrespective of magnetic resonance imaging findings.

Screening for Sturge-Weber syndrome: A state-of-the-art review.

Infants with a high-risk distribution of port-wine stains are commonly screened for Sturge-Weber syndrome using brain magnetic resonance imaging. There is no consensus about which port-wine stain phenotypes to screen, optimal timing, screening sensitivity, or whether presymptomatic diagnosis improves neurodevelopmental outcomes. This state-of-the-art review examines the evidence in favor of screening for Sturge-Weber syndrome, based on its effect on neurodevelopmental outcomes, against the risks and limitations of screening magnetic resonance imaging and electroencephalography. A literature search of PubMed/MEDLINE was conducted between January 2005 and May 2017 using key search terms. Relevant articles published in English were reviewed; 34 articles meeting the search criteria were analyzed according to the following outcome measures: neurodevelopmental outcome benefit of screening, diagnostic yield, financial costs, procedural risks, and limitations of screening magnetic resonance imaging and electroencephalography. There is no evidence that a presymptomatic Sturge-Weber syndrome diagnosis with magnetic resonance imaging results in better neurodevelopmental outcomes. The utility of electroencephalographic screening is also unestablished. In Sturge-Weber syndrome, neurodevelopmental outcomes depend on prompt recognition of neurologic red flags and early seizure control. Small numbers and a lack of prospective randomized controlled trials limit these findings. For infants with port-wine stain involving skin derived from the frontonasal placode (forehead and hemifacial phenotypes), we recommend early referral to a pediatric neurologist for parental education, counselling, and monitoring for neurologic red flags and seizures and consideration of electroencephalography regardless of whether magnetic resonance imaging is performed or its findings.

Infantile Hemangioma with Minimal or Arrested Growth: Further Observations on Clinical and Histopathologic Findings of this Unique but Underrecognized Entity.

BACKGROUND: Infantile hemangioma (IH) with minimal or arrested growth (IH-MAG) is becoming increasingly recognized in the literature. It is important to be aware of their existence, because the correct diagnosis is essential for prognostication and treatment and, in the case of facial segmental lesions, the direction of further investigations if PHACE (posterior fossa abnormalities and other structural brain abnormalities; hemangioma(s) of the cervical facial region; arterial cerebrovascular anomalies; cardiac defects, aortic coarctation, and other aortic abnormalities; eye anomalies) syndrome or Sturge-Weber syndrome is suspected. Although the clinical and histologic characteristics of IH-MAG resemble capillary malformations, positive GLUT-1 status is a delineating feature. METHODS: We reviewed nine cases of infants who presented after 2000 with birthmarks showing unique clinical features suggestive of a special variant of IHs. All patients had serial photographs taken demonstrating resolution of the birthmark over time. Five of these cases had skin biopsy performed, all of which confirmed GLUT-1 positivity. RESULTS: This photographic series of IH-MAG demonstrates their unique clinical, histologic, and immunochemistry features. They were nearly fully formed at birth, and their common clinical features included telangiectasia, venules, and matte erythema with light and dark areas. Spontaneous resolution over time without cosmetic disfigurement was the observed natural history in the majority of cases. CONCLUSION: IH-MAG is a unique clinical subset of hemangioma for which close observation is the preferred treatment. When in doubt, a biopsy for histology and GLUT-1 status may be needed to confirm the diagnosis before embarking on unnecessary laser treatment or medical interventions.

Pulsed dye laser treatment of capillary malformations in infants at 2-weekly versus 3-monthly intervals, reducing the need for general anaesthesia.

Capillary malformations (CM) cause significant psychosocial complications. Pulsed dye laser (PDL) treatment at 6-12-weekly intervals under general anaesthesia (GA) commencing in infants at 6 months of age remains the standard of care in order to achieve maximal improvement prior to school age. The safety of repeated GA in children is controversial. Shortening the time between treatments increases the number that can be delivered prior to 6 months of age, thus reducing the number of subsequent treatments needed under GA. We investigated the safety and effectiveness of more frequent PDL treatment of CM in infancy via a pilot, prospective patient-controlled study of 10 patients. Using 595 nm (Vbeam) PDL, the entire CM was treated initially, then half the CM randomly allocated to 2-weekly and half to 3-monthly intervals for two further treatments. Photographs of the CM taken 3 months after treatment completion were evaluated by an independent, blinded dermatologist. Nine infants completed the study. Three infants (33%) had more improvement on the 2-weekly treated side and four (44%) had more improvement on the 3-monthly treated side. Two patients (22%) showed no difference between sides. Treatments were well tolerated without complications. We conclude that 2-weekly PDL treatments of CM in infants aged under 6 months is effective and well tolerated without adverse effects. Our preliminary data suggest a possible superior efficacy with 3-monthly treatment intervals; however, larger studies are warranted for stronger evidence. More frequent non-GA treatment of CM in infants should be further investigated to decrease the risk of repeated GA exposure in young children.

Consensus statement for the treatment of infantile haemangiomas with propranolol.

Although most infantile haemangiomas do not require treatment due to a natural history of spontaneous involution, some require early intervention. The Australasian Vascular Anomalies Network and the Australasian Paediatric Dermatology Network have developed a consensus statement for the treatment of infantile haemangiomas with oral propranolol. Infants with haemangiomas that are life threatening, at risk of ulceration, or at risk of causing a significant functional impairment, psychological impact or physical deformity should be treated early with oral propranolol. Oral propranolol is safe and effective and in most healthy infants oral propranolol can be started in an outpatient setting.

Lasers and laser-like devices: part two.

Part two of this review series evaluates the use of lasers and laser-like devices in dermatology based on published evidence and the collective experience of the senior authors. Dermatologists can laser-treat a wide range of dermatoses, including vascular, pigmentary, textural, benign proliferative and premalignant conditions. Some of these conditions include vascular malformation, haemangioma, facial telangiectases, café-au-lait macules, naevi of Ota, lentigines, acne scarring, rhytides, rhinophyma and miscellaneous skin lesions. Photodynamic therapy with lasers and intense pulsed light is addressed, with particular reference to actinic keratosis and actinic cheilitis. A treatment algorithm for acne scarring based on scar morphology and severity is comprehensively outlined. Following from part one, the various devices are matched to the corresponding dermatological conditions with representative pictorial case vignettes illustrating likely clinical outcomes as well as limitations and potential complications of the various laser and light therapies.

Use of propranolol for treatment of infantile haemangiomas in an outpatient setting.

INTRODUCTION: Propranolol has recently emerged as an effective drug treatment for infantile haemangiomas. The side effect profile of the drug and the safety of administering propranolol in outpatient settings in this age group remain uncertain. We report our experience with 200 infants and children prescribed propranolol to treat infantile haemangiomas, including 37 patients considered to have a poor response to treatment. METHOD: Patients were prescribed propranolol (1 mg/kg/dose bd) as outpatients at the Vascular Anomalies Service at the Royal Children's Hospital, Melbourne. RESULTS: The median age at commencement was 4 months (range 5 days-7 years). Twenty patients were older than 12 months at commencement. The median duration of treatment was 8 months. About 80% of treated haemangiomas were on the face. Approximately 50% of patients were considered to have an excellent response, 30% to have a good response and 20% to have a poor response. All segmental facial haemangiomas responded well. In contrast, 25% of focal facial haemangiomas responded poorly. Sleep disturbance was the most common side effect. Gross motor abnormalities including delayed walking were observed in 13 patients. CONCLUSION: Propranolol appears to be an effective treatment for infantile haemangiomas, particularly large segmental facial lesions. A poor response was seen in 20% of patients. Treatment has been provided in an outpatient setting without major complications and with excellent parental compliance. The side effect profile appears to be favourable, but further follow-up is required to identify unexpected long-term side effects.

Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study.

Therapeutic options for superficial infantile hemangiomas (IH) are limited. Recently, timolol maleate gel, a topical nonselective beta-blocker, has been reported as a potentially effective treatment for superficial IH. This study is an extension of a previously published pilot study designed to further investigate the efficacy and safety and to identify predictors of good response of topical 0.5% or 0.1% timolol maleate gel-forming solution. This was a retrospective cohort study including patients enrolled from five centers. Patients were included if they were treated with timolol maleate 0.1% or 0.5% gel-forming solution and had photographic documentation of the IH and at least one follow-up visit. Patients with concomitant active treatment using other IH treatments were excluded. The primary endpoint was change in the appearance of IH as evaluated using a visual analog scale (VAS). Data from 73 subjects were available for final analysis. Timolol maleate gel-forming solution 0.5% was used in 85% (62/73) of patients, the remainder being treated with 0.1%. The median age at treatment initiation was 4.27 months (interquartile range [IQR] 2.63-7.21 mos), and patients were treated for a mean of 3.4 ± 2.7 months. All patients except one improved, with a mean improvement of 45 ± 29.5%. Predictors of better response were superficial type of hemangioma (p = 0.01), 0.5% timolol concentration (p = 0.01), and duration of use longer than 3 months (p = 0.04). Sleeping disturbance was noted in one patient. This study further demonstrates the efficacy and tolerability of topical timolol maleate and gradual improvement with longer treatment in patients with superficial IH.

Improvement of Burn Scars Treated With Fractional Ablative CO2 Lasers-A Systematic Review and Meta-analysis Using the Vancouver Scar Scale.

Fractional ablative CO2 laser is being used increasingly to treat burn scars; however, objective measures of outcome success vary widely. This systematic review and meta-analysis extracts and pools available data to assess the outcomes of patients with burn scars treated with fractional ablative CO2 laser. A search of MEDLINE, EMBASE, and the gray literature was performed. The review included studies that reported patients with a confirmed diagnosis of scarring as a result of a burn injury, who were treated with fractional ablative CO2 laser and whose progress was recorded using the Vancouver Scar Scale (VSS). Eight studies were included in the systematic review and meta-analysis. Treatment regimens varied amongst studies, as did patient outcomes. Pooled data revealed an average VSS improvement of 29% across 282 patients following fractional CO2 ablative laser treatment. Although the heterogeneity of treatment regimens across studies limits this systematic review's ability to provide specific treatment recommendations, the overall trend towards improvement of burns scars treated with fractional CO2 laser based on the VSS encourages further exploration of this modality as a therapeutic tool.

Skin fluorescence controlled photodynamic photorejuvenation (wrinkle reduction).

BACKGROUND: Identical skin fluorescence can be obtained after one hour spraying with 0.5% liposome-encapsulated 5-ALA and after 0.5 hour application of 20% 5-ALA in a cream base. In this study the clinical outcome and side effects using the 0.5% 5-ALA in Caucasian skin are investigated and compared to earlier reported non-ablative treatments for wrinkles and improvements of skin texture using 20% ALA photodynamic photorejuvenation. METHODS AND MATERIALS: 37 healthy Caucasian female patients participated in a randomized, prospective split face study. Two different intense pulsed light (IPL) treatment modalities were investigated; both employed a pre-treatment of approximately one hour of spraying with 0.5% liposome encapsulated 5-ALA. One modality combined type I photorejuvenation with wrinkle reduction (C-PDT) using a waveband from 530 to 750 nm and short pulse durations (7 J/cm(2), 2 x 2.5 ms, delay 10 ms). The other modality (PDT alone) emitted a band of wavelengths from 400 to 720 nm, three passes were performed (3.5 J/cm(2), 30 ms pulse duration). RESULTS: After a series of three C-PDT or PDT-alone treatments, the patients obtained statistically significant (P< 5 x 10-5) reductions in periorbital and perioral wrinkles. Using the Fitzpatrick wrinkle scale, periorbital wrinkles were reduced by 1.2 grades (SD: 1.1) and 1.1 (SD: 1.1), respectively and perioral wrinkles were reduced by 0.8 grades (SD: 1.0) and 0.7 (SD: 0.9) respectively. The difference in treatment efficacy between. C-PDT and PDT alone treated sides was not statistically significant (P = 0.224). CONCLUSION: The present study shows that statistically significant improvements in wrinkle reduction and skin texture, equivalent to previously reported results obtained with 20% ALA, can be obtained with 0.5% liposome encapsulated 5-ALA. Only minor and infrequent side effects were registered at the 0.5% 5-ALA treated areas. Skin fluorescence monitoring during pre-treatrnent with 5-ALA may improve clinical efficacy, reduce time consumption and increase safety of the treatment.