A systematic review of the uses of metformin in dermatology.

Metformin is an established staple drug in the management of Type 2 diabetes mellitus. In this systematic review, we sought to establish the clinical utility of metformin in a range of dermatological conditions. The pathophysiology of acne vulgaris and polycystic ovarian syndrome (PCOS) is well suited to the pharmacological profile of metformin, and we found evidence for its efficacy in managing these conditions. We found some evidence for the use of metformin particularly in acne and PCOS; however, the evidence base is of mixed quality. There is scope for clinicians to consider metformin as an adjunct therapy in acne and PCOS. There is generally insufficient evidence to recommend metformin in other dermatological conditions.

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.

A core outcome domain set for clinical research on capillary malformations (the COSCAM project): an e-Delphi process and consensus meeting.

BACKGROUND: There is limited evidence on the best available treatment options for capillary malformations (CMs), mainly due to the absence of uniform outcome measures in trials on therapies. A core outcome set (COS) enables standard reporting of trial outcomes, which facilitates comparison of treatment results. OBJECTIVES: To develop a core outcome domain set (CDS), as part of a core outcome set (COS), for clinical research on CMs. METHODS: Sixty-seven potentially relevant outcome subdomains were recognized based on the literature, focus group sessions, and input from the COSCAM working group. These outcome subdomains were presented in an online Delphi study to CM experts (medical specialists and authors of relevant literature) and (parents of) patients with CM (international patient associations). During three e-Delphi study rounds, the participants repeatedly scored the importance of these outcome subdomains on a seven-point Likert scale. Participants could also propose other relevant outcome subdomains. Consensus was defined as ≥ 80% agreement as to the importance of an outcome subdomain among both stakeholder groups. The CDS was finalized during an online consensus meeting. RESULTS: In total 269 participants from 45 countries participated in the first e-Delphi study round. Of these, 106 were CM experts from 32 countries, made up predominantly of dermatologists (59%) and plastic surgeons (18%). Moreover, 163 (parents of) patients with CM from 28 countries participated, of whom 58% had Sturge-Weber syndrome. During the two subsequent e-Delphi study rounds, 189 and 148 participants participated, respectively. After the entire consensus process, consensus was reached on 11 outcome subdomains: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence. CONCLUSIONS: We recommend the CDS to be used as a minimum reporting standard in all future trials of CM therapy. Our next step will be to select suitable outcome measurement instruments to score the core outcome subdomains. What is already known about this topic? Besides physical and functional sequelae, capillary malformations (CMs) often cause emotional and social burden. The lack of uniform outcome measures obstructs proper evaluation and comparison of treatment strategies. As a result, there is limited evidence on the best available treatment options. The development of a core outcome set (COS) may improve standardized reporting of trial outcomes. What does this study add? A core outcome domain set (CDS), as part of a COS, was developed for clinical research on CMs. International consensus was reached on the recommended core outcome subdomains to be measured in CM trials: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence. This CDS enables the next step in the development of a COS, namely to reach consensus on the core outcome measurement instruments to score the core outcome subdomains. What are the clinical implications of this work? The obtained CDS will facilitate standardized reporting of treatment outcomes, thereby enabling proper comparison of treatment results. This comparison is likely to provide more reliable information for patients about the best available treatment options.

Energy-based devices for the treatment of Acne Scars: 2022 International consensus recommendations.

BACKGROUND AND OBJECTIVES: Acne scars are one of the most distressing and long-term consequences of acne vulgaris, with damaging effect on a person's physical, mental, and social well-being. Numerous treatment options are available including surgical and nonsurgical techniques, depending on the clinical presentation. Although considerable advances in the development of new treatment technologies and applications have been made in the last decade, international treatment guidelines and reimbursement schemes have not yet caught up with current knowledge and practice in many centers. The authors intend to highlight the potential utility of energy-based devices (EBDs) for acne scarring, offer recommendations for safe and efficacious treatment, and provide consensus-based EBD treatment options based on varying presentations demonstrated in a series of real-life clinical photographs. STUDY DESIGN/MATERIALS AND METHODS: An international panel of 24 dermatologists and plastic surgeons from 12 different countries and a variety of practice backgrounds was self-assembled to develop updated consensus recommendations for the treatment of acne scars. A two-step modified Delphi method took place between March 2020 and February 2021 consisting of two rounds of emailed questionnaires. The panel members approved the final manuscript via email correspondence. RESULTS: The manuscript includes a comprehensive discussion and panel recommendations regarding the following topics: 1. the role of EBD in mitigating and treating acne scars in a patient with active acne, 2. the use of various EBDs for the treatment of different acne scar types with special focus on commonly used laser platform such as vascular lasers, ablative fractional lasers (AFLs) and non-AFLs (NAFLs), 3. treatment combinations, and 4. acne scar treatments in skin of color. The last part comprised of 10 photos of real-life clinical cases with the panel recommendation treatment plan to achieve best aesthetic outcome. CONCLUSION: Panel members were unanimous in their view that EBDs have a role in the management of acne scars, with AFLs, NAFLs, vascular lasers, and RF devices preferentially selected by most of the panel experts. EBDs are considered a first-line treatment for a variety of acne scar types and patients without access to these treatments may not be receiving the best available care for optimal cosmetic results. Future high-quality research and updated international treatment guidelines and reimbursement schemes should reflect this status.

Our experience using 1064 nm Nd:YAG in palmoplantar warts.

Common warts (verruca vulgaris) are the most commonly seen benign cutaneous tumors occurring in both males and females of various ages. However, warts on the hands and feet (plantar warts and palmar warts) often respond poorly to traditional treatments such as topical salicylic acid, cryotherapy, surgical excision, electrocautery, and bleomycin injection. Recently, the long-pulsed 1064 nm Nd:YAG laser (LPNYL) has attracted attention in the treatment of palmoplantar warts. This study aims to evaluate the effectiveness of the LPNYL in the treatment of palmoplantar warts. We conducted a comparative cross-sectional descriptive study in 88 patients (49 males and 39 females) with palmoplantar warts. During the period from 2018 to 2020, the patients underwent up to three treatment sessions at intervals of 2-4 weeks between sessions. The LPNYL parameters comprised a spot size of 5 mm, 30 ms pulse width, 1 Hz repetition rate, and a fluence range of 140-180 J/cm2. The patient mean age was 29.0 ± 14.5 years (range, 4-66 years). Good results were seen in 72.9% (64/88) of patients. The remaining 27.1% (24/88) felt their treatment was unsuccessful. As for adverse events, 5 (5.6%) patients reported hemorrhagic blistering after treatment. At the 3- and 6-month follow-up assessments, no recurrence was seen (Figures 2-4). Our study showed that the LPNYL treatment was safe and effective in the majority of palmoplantar warts. The duration of treatment was shorter than most traditional methods; however, the limitations of this method are that the treatment required several sessions, the procedure was painful, and adverse events occurred in just over 5% of the patients.

Intralesional methotrexate in dermatology: Diverse indications and practical considerations.

Intralesional methotrexate (IL-MTX) is a long-established treatment, which is arguably underutilized by dermatologists. We describe the underlying evidence base and practical considerations for its broad range of cutaneous indications, including in cutaneous oncology (keratoacanthomas, squamous cell carcinomas, lymphomas), inflammatory dermatology (nail psoriasis, plaque psoriasis, pyoderma gangrenosum, cutaneous Crohn's disease, amyloidosis), cutaneous infections (viral warts) and for treatment of filler complications. In certain circumstances, IL-MTX can be more efficacious and less invasive than other treatments, with fewer adverse effects. Dermatologists should consider using IL-MTX for a range of recalcitrant cutaneous conditions, particularly for those patients not amenable to surgery or systemic therapy.

5-Fluorouracil in Dermatology: The Diverse Uses Beyond Malignant and Premalignant Skin Disease.

BACKGROUND: 5-fluorouracil (5-FU) is widely used for treatment of malignant and premalignant skin cancers; however, its use in other common cutaneous conditions has been less widely reported. OBJECTIVE: We investigated the off-label uses of 5-FU beyond malignant and premalignant skin disease. METHODS: We conducted a literature review searching multiple databases to evaluate the evidence for the off-label uses of 5-FU. The level of evidence was evaluated and selected accordingly listing the studies with the highest level of evidence first using the Oxford Centre of Evidence-Based Medicine 2011 guidance. RESULTS: We found underlying evidence to support the use of 5-FU for a wide range of noncancerous cutaneous indications including scarring (keloid, hypertrophic), pigmentary disorders (vitiligo, idiopathic guttate hypomelanosis), cutaneous infections (viral warts, molluscum contagiosum), inflammatory dermatoses (Darier's disease, Hailey-Hailey disease and sarcoidosis), and cosmetic indications (photoaging, treatment of filler nodules and granulomas). CONCLUSION: In selected patients, 5-FU can be as effective as more established treatments, with fewer side-effects.

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.

Pulsed dye laser followed by intradermal botulinum toxin type-A in the treatment of rosacea-associated erythema and flushing.

Rosacea is a common inflammatory skin disease characterized by erythema, episodes of flushing, and inflammatory lesions. It typically affects the face and is more prevalent among fair skin individuals affecting women more than men. Various treatments are available for rosacea with light-based therapies commonly used in the management of erythema. The use of intradermal botulinum toxin type-A has been reported to be beneficial in the treatment of rosacea-associated erythema and flushing with good results and a low side-effect profile. In this article, we present our experience on the successful combination of both pulsed dye laser and intradermal botulinum toxin type-A in erythema and flushing in 20 rosacea patients. In addition to subjective improvement, we measured the degree of erythema using a 3D Antera camera in order to quantify our results. We demonstrated high efficacy and satisfaction rate with this combined approach and a low side-effect profile. To our knowledge, the combination of laser and intradermal botulinum toxin in the management of rosacea has not been previously reported.

The top 10 cosmeceuticals for facial hyperpigmentation.

Disorders of facial hyperpigmentation including melasma, postinflammatory hyperpigmentation and solar lentigines are common cutaneous conditions which can have a huge impact on patients' quality of life and often prove difficult to treat. The nascent market of cosmeceutical options provides a potentially safer and efficacious alternative for treating these challenging conditions. These can be used alone or in combination with other established treatments. Many cosmeceutical products are thought to work through inhibition of tyrosinase, a key enzyme of melanogenesis. We discuss the mode of action and provide an up-to-date review of the underlying evidence base for the top 10 cosmeceutical products for hyperpigmentation and melasma. Possible safer and more efficacious cosmeceutical therapies we discuss include thiamidol, kojic acid, vitamin C, arbutin, retinol, nicotinamide, ferulic acid, resorcinol, licorice root extract, and soy.

Histological characterization of age-related skin changes following the use of picosecond laser: Low vs high energy.

Fractional lasers have become widespread in dermatology owing to their efficacy and safety. Comparative analysis of histological features after laser rejuvenation using a 1064-nm fractionated handpiece picosecond laser with different energy fluence levels (1.1 or 2.1 J/cm2 ). An open-label, study of 28 women aged 36 to 60 years with signs of age-related photodamage and skin changes of the face and neck was conducted using a fractional picosecond 1064 nm laser in low vs high fluence. The clinical assessment at 3 weeks showed more pronounced effect on facial skin rejuvenation with the higher fluence of 2.1 J/cm2 compared to 1.1 J/cm2 . The effect and safety of laser rejuvenation using a picosecond laser has been shown with more pronounced histological effects at higher fluences.

Laser Treatment of Traumatic Scars and Contractures: 2020 International Consensus Recommendations.

BACKGROUND AND OBJECTIVES: There is currently intense multidisciplinary interest and a maturing body of literature regarding laser treatments for traumatic scars, but international treatment guidelines and reimbursement schemes have not yet caught up with current knowledge and practice in many centers. The authors intend to highlight the tremendous potential of laser techniques, offer recommendations for safe and efficacious treatment, and promote wider patient access guided by future high-quality research. STUDY DESIGN/MATERIALS AND METHODS: An international panel of 26 dermatologists and plastic and reconstructive surgeons from 13 different countries and a variety of practice backgrounds was self-assembled to develop updated consensus recommendations for the laser treatment of traumatic scars. A three-step modified Delphi method took place between March 2018 and March 2019 consisting of two rounds of emailed questionnaires and supplementary face-to-face meetings. The panel members approved the final manuscript via email correspondence, and the threshold for consensus was at least 80% concurrence among the panel members. RESULTS: The manuscript includes extensive detailed discussion regarding a variety of laser platforms commonly used for traumatic scar management such as vascular lasers and ablative and non-ablative fractional lasers, special considerations such as coding and laser treatments in skin of color, and 25 summary consensus recommendations. CONCLUSIONS: Lasers are a first-line therapy in the management of traumatic scars and contractures, and patients without access to these treatments may not be receiving the best available care after injury. Updated international treatment guidelines and reimbursement schemes, additional high-quality research, and patient access should reflect this status. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Hyaluronidase in Dermatology: Uses Beyond Hyaluronic Acid Fillers.

Hyaluronidase is mostly widely recognized for its off-label use in correction of complications of hyaluronic acid fillers. However, its utility in other aspects of dermatology is less widely acknowledged. We describe the varied uses of hyaluronidase in dermatology and the underlying evidence base for its dermatological indications. This includes its uses in enhancing drug delivery (for local anesthesia, keloid and hypertrophic scars, and for Kaposi’s sarcoma), in the treatment of disorders associated with mucin deposition (myxedema, scleroderma, scleredema, and cutis verticis gyrata) and its potential uses in surgery (as a pre-operative adjuvant in dermatofibrosarcoma protuberans, for periorbital edema, and for hematomas). In select circumstances, hyaluronidase might be more efficacious than more established treatments with fewer adverse effects. We propose hyaluronidase as the latest addition to our global dermatological armamentarium and implore dermatologists to consider its use to enhance their practice. J Drugs Dermatol. 2020;19(10):993-998. doi:10.36849/JDD.2020.5416.

Rosacea and the gastrointestinal system.

Rosacea is a common skin condition characterised by erythema, papules and pustules. Increasing evidence suggests that the gut-skin axis is implicated in the pathogenesis of rosacea. Sufficient evidence exists to support the notion that the gut microbiome plays a role in the inflammatory cutaneous response and there appear to be associations with small intestinal bacterial overgrowth and Helicobacter pylori infection. A dysbiotic microbiome and an innate immune system dysregulation contribute to the pathophysiology of rosacea, and further exploration of their roles is warranted. Greater understanding of this condition and the effect of the gut-skin axis could allow for more efficacious and timely treatment. This article reviews our current findings and understanding in the skin and gut relationship in rosacea.

Treatment of striae distensae: An evidence-based approach.

Striae distensae (SD), otherwise known as "stretchmarks," are a common presenting complaint, particularly in young healthy women. SD are hypothesized to form in a patient when the cross-linked collagen is "overstretched" and rupture of this collagen matrix causes the striae. Thus, many treatments work by increasing collagen synthesis. This review critically appraises the evidence to date for the treatment of SD, including both energy-based devices and topical treatments.

Carbon dioxide laser ablation for trichoepitheliomas: The largest reported series.

Trichoepitheliomas are benign cutaneous tumours often occurring on the face and can lead to considerable psychological distress to its sufferers. Treatment is often difficult, and surgery is limited by the obvious scars and multiple numbers of lesions. Carbon dioxide laser ablation can be used safely with good cosmetic outcome and low recurrence rate, and in this article, we describe our experience in the treatment of these tumours with the carbon dioxide laser. This is the largest reported series in the literature.

Pulsed Dye Laser Therapy in the Treatment of Warts: A Review of the Literature.

BACKGROUND: Warts or verrucae vulgaris are common cutaneous infections with currently no definitive curative treatments available. OBJECTIVE: To determine the efficacy of pulsed dye laser (PDL) in the treatment of warts. MATERIALS AND METHODS: A literature search was performed using the PubMed and MEDLINE databases. A search using {(Wart[s], verruca or condylomata)} AND [(Pulsed dye laser)] was used. Forty-four articles were identified as relevant to this review. RESULTS: Simple warts were very responsive to PDL, being treated successfully in over 95% of patients. Facial and anogenital warts also demonstrated excellent outcomes. Recalcitrant warts, displayed significant variability in their response, ranging between 50% and 100% across all articles. The response rates seen in peripheral warts (involving the hands and feet) were also very variable, ranging between 48% and 95%. Recurrence rates at 4 months of follow-up were documented as 0% to 15%. Complications have been described as very few and rare, the main ones being topical discomfort and erythema. CONCLUSION: Pulsed dye laser is a safe and effective modality in the treatment of warts that can be applied to most body parts. Cost and availability remain a limitation to the use of PDL; however, this modality can be used when other more traditional and accessible treatments have failed.

Molluscum Contagiosum: Review and Update on Management.

Molluscum contagiosum (MC) is an infectious dermatosis that commonly presents in children and immunocompromised individuals. Although lesions usually resolve spontaneously after several months, they can be symptomatic and cause psychosocial distress. We review the evidence underlying treatment methods available for MC lesions, including potassium hydroxide, salicylic acid, hydrogen peroxide, retinoids, cantharidin, cryotherapy, curettage, and pulsed dye laser to aid practicing dermatologists in therapy selection.