An update on tinea capitis in children.

Tinea capitis presents a significant public health care challenge due to its contagious nature, and potential long-term consequences if unrecognized and untreated. This review explores the prevalence, risk factors, diagnostic methods, prevention strategies, impact on quality of life, and treatment options for pediatric tinea capitis. Epidemiological analysis spanning from 1990 to 1993 and 2020 to 2023 reveals prevalence patterns of pediatric tinea capitis influenced by geographic, demographic, and environmental factors. Notably, Trichophyton species is most prevalent in North America; however, Microsporum species remain the primary causative agent globally, with regional variations. Risk factors include close contact and environmental conditions, emphasizing the importance of preventive measures. Accurate diagnosis relies on clinical evaluation, microscopic examination, and fungal culture. Various treatment modalities including systemic antifungals show efficacy, with terbinafine demonstrating superior mycological cure rates particularly for Trichophyton species. Recurrent infections and the potential development of resistance can pose challenges. Therefore, confirming the diagnosis, appropriately educating the patient/caregiver, accurate drug and dose utilization, and compliance are important components of clinical cure. Untreated or poorly treated tinea capitis can lead to chronic infection, social stigma, and psychological distress in affected children. Prevention strategies focus on early detection and healthy lifestyle habits. Collaborative efforts between healthcare providers and public health agencies are important in treating pediatric tinea capitis and improving patient outcomes. Education and awareness initiatives play a vital role in prevention and community-level intervention to minimize spread of infection. Future research should explore diagnostic advances, novel treatments, and resistance mechanisms in order to mitigate the disease burden effectively.

Antifungal resistance in dermatophytes - review of the epidemiology, diagnostic challenges and treatment strategies for managing trichophyton indotineae infections.

INTRODUCTION: There is an increasing number of reports of Trichophyton indotineae infections. This species is usually poorly responsive to terbinafine. AREAS COVERED: A literature search was conducted in May 2024. T. indotineae infections detected outside the Indian subcontinent are generally associated with international travel. Reports of local spread are mounting.As a newly identified dermatophyte species closely related to the T. mentagrophytes complex with limited genetic and phenotypic differences, there is an unmet need to develop molecular diagnosis for T. indotineae. Terbinafine has become less effective as a first-line agent attributed to mutations in the squalene epoxidase gene (Leu393Phe, Phe397Leu). Alternative therapies include itraconazole for a longer time-period or a higher dose (200 mg/day or higher). Generally, fluconazole and griseofulvin are not effective. In some cases, especially when the area of involvement is relatively small, topical non-allylamine antifungals may be an option either as monotherapy or in combination with oral therapy. In instances when the patient relapses after apparent clinical cure then itraconazole may be considered. Good antifungal stewardship should be considered at all times. EXPERT OPINION: When both terbinafine and itraconazole are ineffective, options include off-label triazoles (voriconazole and posaconazole). We present four patients responding to these newer triazoles.

Ringworm (dermatophytosis, tinea) is a fungal infection of the skin, hair and nails that is commonly seen by primary and secondary healthcare providers. An estimated 20-25% of the global population is affected by this condition. In Europe and the United States, tineas are often treated empirically using over-the-counter medications, which can increase the risk of resistance development.While antifungal resistance is not a new problem, this topic has garnered the attention of physicians and researchers in recent years due to an outbreak from South Asia caused by a new pathogen known as Trichophyton indotineae. In this review, we summarize the global prevalence, diagnosis methods, antifungal resistance profile and treatment options for T. indotineae. While most cases outside of South Asia are linked to international travel, there is evidence suggesting local person-to-person transmission and transmission via animal contact. One hurdle to surveilling the spread of this pathogen is the requirement of complex molecular diagnosis, tackling this challenge will require the development of newer assays.Terbinafine, a widely available antifungal drug, is becoming less effective owing to resistance mutations of the squalene epoxidase gene. Itraconazole has shown effectiveness, especially with a higher dose and a longer treatment duration. There is a significant risk of T. indotineae infections becoming chronic with episodes of relapse. When both terbinafine and itraconazole fail, newer agents such as posaconazole and voriconazole can be considered. Combination therapy using oral and topical medications should also be considered.

Comparison of therapeutic agents' short-term effects on facial and scalp actinic keratosis: A network meta-analysis.

BACKGROUND: Care for actinic keratosis (AK) can be improved with more knowledge on the relative of effect of indicated therapies. OBJECTIVES: Using network meta-analyses, we quantitatively determined the comparative "short-term" effects of interventions in adults with facial and scalp AK. METHODS: On February 28, 2023, evidence from the peer-reviewed literature was systematically obtained from OVID, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. We analyzed data from studies published in English, of a trial design, and investigating the effect of an actinic keratosis monotherapy. Patient complete clearance, patient partial clearance or lesion-specific clearance across adults were analyzed at 8-12 weeks after therapy. Patient complete clearance pertained to proportion of participants who experienced complete clearance of actinic keratosis lesions; patient partial clearance corresponded to percentage of subjects who achieved at least 75% clearance of actinic keratosis lesions; lesion-specific clearance represented the percentage of all lesions that were cleared. In the main (i.e., base) analyses, nodes were analyzed only at the level of the agent. RESULTS: Data from a total of 84 studies were used-across which 22 active agents were identified. Estimates of interventions' surface under the cumulative ranking curve rankings and (pairwise) relative effects were estimated. Across the three outcomes, fluorouracil 5% was ranked the most effective. CONCLUSIONS: Our work is the first to provide information on covariate-adjusted relative effects of actinic keratosis therapies- including the more recently reported treatments-for the face and scalp; this knowledge may help physicians and patients make more informed decisions.

Potential emergence of terbinafine resistance by squalene epoxidase gene mutations: An 18-month cohort study of onychomycosis patients in the United States.

BACKGROUND: There is a concerning rise in antifungal-resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. OBJECTIVES: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. CONCLUSION: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.

A bibliometric analysis of alternative drug therapy options in the treatment of androgenetic alopecia.

BACKGROUND: Oral finasteride and topical minoxidil formulations are the only FDA-approved drug therapies for androgenetic alopecia (AGA). Research into dutasteride, topical finasteride, and nontopical minoxidil (low-dose oral and sublingual) formulations in the treatment of AGA has spiked within recent years. Early findings show that these alternative drug therapies may have similar to improved efficacy and safety profiles relative to the conventional treatment options. AIMS: Conducting a bibliometric analysis, compare trends in publications on these alternative drug therapies, identify key contributors, evaluate major findings from top-cited articles, and elucidate gaps in evidence. METHODS: A search was conducted on the Web of Science database for publications on the use of alternative drug therapies in the treatment of AGA. A total of 95 publications, published between January 2003-March 2024, and their citation metadata were included in the analysis. RESULTS: Dutasteride showed the greatest (n = 37) and longest (20+ years) history of publications, as well as the highest cumulative citations (n = 914); however, nontopical minoxidil showed a burst in research activity within the last 5 years (n = 33 publications since 2019). A relatively low number of randomized control trials (n = 3) for nontopical minoxidil suggests a need for higher-quality evidence. CONCLUSIONS: Our analysis reveals major trends, contributors, and gaps in evidence for alternative drug therapies for AGA, which can help inform researchers on their future projects in this growing field of study. There is enthusiasm for exploring off-label formulations: nontopical forms of minoxidil (oral and sublingual), topical finasteride, and mesotherapy.

Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management.

INTRODUCTION: The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies. METHODS: A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction. RESULTS AND DISCUSSION: A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing. CONCLUSION: Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.

Global prevalence of onychomycosis in general and special populations: An updated perspective.

BACKGROUND: Onychomycosis is a chronic nail disorder commonly seen by healthcare providers; toenail involvement in particular presents a treatment challenge. OBJECTIVE: To provide an updated estimate on the prevalence of toenail onychomycosis. METHODS: We conducted a literature search using PubMed, Embase and Web of Science. Studies reporting mycology-confirmed diagnoses were included and stratified into (a) populations-based studies, and studies that included (b) clinically un-suspected and (c) clinically suspected patients. RESULTS: A total of 108 studies were included. Based on studies that examined clinically un-suspected patients (i.e., with or without clinical features suggestive of onychomycosis), the pooled prevalence rate of toenail onychomycosis caused by dermatophytes was 4% (95% CI: 3-5) among the general population; special populations with a heightened risk include knee osteoarthritis patients (RR: 14.6 [95% CI: 13.0-16.5]), chronic venous disease patients (RR: 5.6 [95% CI: 3.7-8.1]), renal transplant patients (RR: 4.7 [95% CI: 3.3-6.5]), geriatric patients (RR: 4.7 [95% CI: 4.4-4.9]), HIV-positive patients (RR: 3.7 [95% CI: 2.9-4.7]), lupus erythematosus patients (RR: 3.1 [95% CI: 1.2-6.3]), diabetic patients (RR: 2.8 [95% CI: 2.4-3.3]) and hemodialysis patients (RR: 2.8 [95% CI: 1.9-4.0]). The prevalence of onychomycosis in clinically suspected patients was significantly higher likely due to sampling bias. A high degree of variability was found in a limited number of population-based studies indicating that certain pockets of the population may be more predisposed to onychomycosis. The diagnosis of non-dermatophyte mould onychomycosis requires repeat sampling to rule out contaminants or commensal organisms; a significant difference was found between studies that performed single sampling versus repeat sampling. The advent of PCR diagnosis results in improved detection rates for dermatophytes compared to culture. CONCLUSION: Onychomycosis is an underrecognized healthcare burden. Further population-based studies using standardized PCR methods are warranted.

Pattern hair loss and health care professionals: How well are we connecting with our audience?

BACKGROUND: Pattern hair loss, the most common form of hair loss, affects millions in the United States. Americans are increasingly seeking health information from social media. It would appear that healthcare professionals contribute relatively minimally to pattern hair loss content, thereby posing serious concerns for credibility and quality of information available to the general public. OBJECTIVES: This study evaluates popular pattern hair loss-related content on Instagram, TikTok, and YouTube, aiming to understand effective engagement strategies for healthcare professionals on social media. METHODS: The top 60 short-form videos were extracted from Instagram, TikTok, and YouTube, using the search term "pattern hair loss" and inclusion of USA-based accounts only. Videos were categorized by creator type (healthcare vs. non-healthcare professional), content type (informational, interactional, and transactional), and analyzed for user engagement and quality, using engagement ratios and DISCERN scores, respectively. CONCLUSIONS: Healthcare professionals, especially dermatologists, play a crucial role in delivering credible information on social media, supported by higher DISCERN scores. Multi-platform presence, frequent activity, and strategic content creation contributes to increased reach and engagement. Duration of short-form videos does not impact engagement. The "Duet" or "Remix" options on TikTok, Instagram, and YouTube serve as a valuable tool for healthcare professionals to counter misinformation. Our study underscores the importance of optimizing educational impact provided by health care professionals at a time when the public increasingly relies on social media for medical information.

An update on antifungal resistance in dermatophytosis.

INTRODUCTION: The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention. AREAS COVERED: This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was T. mentagrophytes. However, T. indotineae emerged as the most prevalent isolate with mutations in the SQLE gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole.Overall, the most prevalent SQLE mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent). EXPERT OPINION: Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of SQLE mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered.

Infants who develop autism show smaller inventories of deictic and symbolic gestures at 12 months of age.

Gestures are an important social communication skill that infants and toddlers use to convey their thoughts, ideas, and intentions. Research suggests that early gesture use has important downstream impacts on developmental processes, such as language learning. However, autistic children are more likely to have challenges in their gestural development. The current study expands upon previous literature on the differences in gesture use between young autistic and non-autistic toddlers by collecting data using a parent-report questionnaire called the MCDI-Words and Gestures at three time points, 12, 18, and 24 months of age. Results (N = 467) showed that high-likelihood infants who later met diagnostic criteria for ASD (n = 73 HL-ASD) have attenuated gesture growth from 12 to 24 months for both deictic gestures and symbolic gestures when compared to high-likelihood infants who later did not meet criteria for ASD (n = 249 HL-Neg) and low-likelihood infants who did not meet criteria for ASD (n = 145 LL-Neg). Other social communicative skills, like play behaviors and imitation, were also found to be impacted in young autistic children when compared to their non-autistic peers. Understanding early differences in social communication growth before a formal autism diagnosis can provide important insights for early intervention.

Effectiveness and safety of oral terbinafine for dermatophyte distal subungual onychomycosis.

INTRODUCTION: Terbinafine has been a cornerstone in dermatophyte infection treatment. Despite its global efficacy, the emergence of terbinafine resistance raises concerns, requiring ongoing vigilance. AREAS COVERED: This paper focuses on evaluating the efficacy and safety of terbinafine in treating dermatophyte toenail infections. Continuous and pulse therapies, with a 24-week continuous regimen and a higher dosage of 500 mg/day have demonstrated superior efficacy to the FDA approved regimen of 250 mg/day x 12 weeks. Pulse therapies, though showing comparable effectiveness, present debates with regards to their efficacy as conflicting findings have been reported. Safety concerns encompass hepatotoxicity, gastrointestinal, cutaneous, neurologic, hematologic and immune adverse-effects, and possible drug interactions, suggesting the need for ongoing monitoring. EXPERT OPINION: Terbinafine efficacy depends on dosage, duration, and resistance patterns. Continuous therapy for 24 weeks and a dosage of 500 mg/day may enhance outcomes, but safety considerations and resistance necessitate individualized approaches. Alternatives, including topical agents and alternative antifungals, are to be considered for resistant cases. Understanding the interplay between treatment parameters, adverse effects, and resistance mechanisms is critical for optimizing therapeutic efficacy while mitigating resistance risks. Patient education and adherence are vital for early detection and management of adverse effects and resistance, contributing to tailored and effective treatments.

Concepts, Terminology, and Innovations in Follicular Unit Excision Hair Restoration Surgery.

Follicular unit excision (FUE) has emerged as the preferred method for hair transplants. Standardized terms and definitions established by members of the International Society of Hair Restoration Surgery and prominent hair restoration surgeons have become the standard, enabling effective knowledge sharing. This chapter provides an overview of the terminology relating to the field.The historical evolution of FUE and its pivotal role in modern hair transplantation is summarized. Anatomical terminology and graft-related definitions follow, providing insights into the scalp's complex structures and graft characteristics. The subsequent sections detail the terminology associated with graft excision and extraction, shedding light on the precise techniques and procedures employed. An exploration of various FUE techniques and the evolving landscape of FUE devices underscores the continual refinement of hair restoration practices. The chapter proceeds to discuss the "safe'" scalp donor zones, donor assessment terminology, and elements in identifying the optimal donor area for a successful FUE procedure. Additionally, punch dynamics and technique characteristics are examined, emphasizing their pivotal role in achieving superior FUE outcomes. The chapter concludes by discussing the classification of punches and graft evaluation terms, offering insights into the tools, and criteria used to assess graft quality and viability.

LITFULOTM (Ritlecitinib) Capsules: A Janus Kinase 3 Inhibitor for the Treatment of Severe Alopecia Areata.

LITFULOTM (ritlecitinib) capsules were recently approved for the treatment of severe alopecia areata in adolescents and adults, aged ≥12 years. Ritlecitinib is the active ingredient and a dual inhibitor of Janus kinase 3 and the tyrosine kinase expressed in hepatocellular carcinoma kinase family. It prevents immune attack on the hair follicles that leads to hair loss. In a phase 2b-3 dose-dependant study, five doses of oral ritlecitinib and placebo administered once daily (QD) were investigated. Ritlecitinib demonstrated efficacy in achieving the primary outcome, Severity of Alopecia Tool (SALT) score of ≤20, at week 24 (31% [38/124] 200-mg ritlecitinib QD for 4 weeks, then 50 mg QD for 20 weeks; 22% [27/121] 200-mg ritlecitinib QD for 4 weeks, then 30 mg QD for 20 weeks; 23% [29/124] 50-mg ritlecitinib QD; 14% [17/119] 30-mg ritlecitinib QD; 2% [1/59] 10-mg ritlecitinib QD; and 2% [2/130] placebo). Mild to moderate common adverse effects were observed, which included headache, nasopharyngitis, and upper respiratory tract infection. The recommended regimen of ritlecitinib capsules is 50 mg QD with without food and swallowed whole.

Navigating fungal infections and antifungal stewardship: drug resistance, susceptibility testing, therapeutic drug monitoring and future directions.

Antifungal stewardship refers to the rational use of antifungal agents. Historically, in some instances, the misuse or overuse of antifungal agents has predisposed patients to an elevated risk of systemic side-effects and treatment resistance, as well as increased healthcare costs. Superficial mycoses, such as onychomycosis, are sometimes treated without any diagnostic testing and is associated with a high likelihood of self-diagnosis and self-treatment, potentially leading to the emergence of resistance against commonly used antifungals like terbinafine. Practitioners need to ensure that a proper clinical diagnosis is backed up by appropriate testing. This may include the traditional light microscopy and culture; additionally, molecular techniques (such as polymerase chain reaction, terbinafine gene mutational analysis) and antifungal susceptibility testing are considerations as appropriate. The choice of antifungal agent should be guided by what is the standard of care in the location where the clinician practices as well as more broadly state and national prescription patterns. Recently, reports of treatment resistance concerning both superficial and deep fungal infections have added another layer of difficulty to clinical practice. This review aims to explore the phenomenon of antifungal drug resistance, and highlights the importance of adopting antifungal stewardship programs. We provide an overview of treatment resistance and mechanisms of resistance reported thus far in dermatophytes. Challenges of performing antifungal susceptibility testing and therapeutic drug monitoring are discussed, as well as principles, recommendations and future directions of antifungal stewardship programs.

Relative Effects of Minoxidil 5%, Platelet-Rich Plasma, and Microneedling in Pattern Hair Loss: A Systematic Review and Network Meta-Analysis.

Background: Combination treatments may improve the utility of approved agents for the treatment of pattern hair loss (PHL); however, head-to-head comparisons are lacking. Objective: The aim of the study was to compare the efficacy of 5% minoxidil, platelet-rich plasma (PRP), and microneedling across adults with PHL insofar as change in total hair density at 24 weeks. Methods: We conducted a literature search in July 2022. Through our Bayesian network meta-analysis, we estimated treatments' surface under the cumulative ranking distribution (SUCRA) values and relative effects - in terms of mean difference (MD). Results: Data from 27 trials, totaling 1,110 patients, were extracted. Interventions were ranked based on the probability of inducing hair density improvements: 5% minoxidil plus microneedling (SUCRA = 95.8%), 5% minoxidil plus PRP (SUCRA = 64.7%), 5% minoxidil (SUCRA = 53.9%), PRP (SUCRA = 34.9%), microneedling (SUCRA = 27.8%), and PRP with microneedling (SUCRA = 22.9%). The efficacy of 5% minoxidil plus microneedling in improving total hair density was significantly greater (p < 0.05) than 5% minoxidil monotherapy (MD = 13 hairs/cm2), PRP monotherapy (MD = 16 hairs/cm2), and microneedling monotherapy (MD = 17 hairs/cm2). Conclusion: Five percent minoxidil plus microneedling is an effective treatment option for improving hair density at 6 months in adult PHL patients.

ZORYVETM (Roflumilast) Cream: A Topical Phosphodiesterase-4 Inhibitor for the Treatment of Psoriasis.

ZORYVETM (roflumilast) cream is a topical phosphodiesterase-4 (PDE-4) inhibitor that has been recently approved for the treatment of plaque psoriasis. It is also indicated for use in intertriginous areas. Roflumilast, the active ingredient, inhibits PDE-4, leading to the suppression of pro-inflammatory immune responses in psoriatic lesions. Two phase 3 clinical trials have demonstrated the efficacy of once daily application of roflumilast to treat plaque psoriasis in patients aged 12 years and older. At week 8, an investigator's global assessment score of 0 or 1 with a grade 2 improvement from baseline, the primary efficacy end point, was observed in 39.1% (225/576) of patients applying roflumilast, compared to 6.6% (20/305) of patients applying vehicle. Common adverse events reported were diarrhea, headache, insomnia, nausea, pain at application site, upper respiratory tract infection, and urinary tract infection.

Utility of devices for onychomycosis: a review.

Onychomycosis is difficult to treat due to long treatment durations, poor efficacy rates of treatments, high relapse rates, and safety issues when using systemic antifungal agents. Device-based treatments are targeted to specific regions of the nail, have favorable safely profiles, and do not interfere with systemic agents. They may be an effective alternative therapy for onychomycosis especially with increasing reports of squalene epoxidase gene mutations and potential resistance to terbinafine therapy. In this review, we discuss four devices used as antifungal treatments and three devices used as penetration enhancers for topical agents. Lasers, photodynamic therapy, microwaves, and non-thermal plasma have the capacity to inactivate fungal pathogens demonstrated through in vivo studies. Efficacy rates for these devices, however, remain relatively low pointing toward the need to further optimize device or usage parameters. Ultrasound, nail drilling, and iontophoresis aid in improving the permeability of topical agents through the nail and have been investigated as adjunctive therapies. Due to the paucity in clinical data, their efficacy in treating onychomycosis has not yet been established. While the results of clinical studies point toward the potential utility of devices for onychomycosis, further large-scale randomized clinical trials following regulatory guidelines are required to confirm current results.

Systematic review of mesotherapy: a novel avenue for the treatment of hair loss.

Mesotherapy is a technique by which lower doses of therapeutic agents and bioactive substances are administered by intradermal injections to the skin. Through intradermal injections, mesotherapy can increase the residence time of therapeutic agents in the affected area, thus allowing for the use of lower doses and longer intervals between sessions which may in turn improve the treatment outcome and patient compliance. This systematic review aims to summarize the current literature that evaluates the efficacy of this technique for the treatment of hair loss and provides an overview of the results observed. Of the 416 records identified, 27 articles met the inclusion criteria. To date, mesotherapy using 6 classes of agents and their combinations have been studied; this includes dutasteride, minoxidil, growth factors or autologous suspension, botulinum toxin A, stem cells, and mesh solutions/multivitamins. While several studies report statistically significant improvements in hair growth after treatment, there is currently a lack of standardized regimens. The emergence of adverse effects after mesotherapy has been reported. Further large-scale and controlled clinical trials are warranted to evaluate the utility of mesotherapy for hair loss disorders.

Antifungal Resistance, Susceptibility Testing and Treatment of Recalcitrant Dermatophytosis Caused by Trichophyton indotineae: A North American Perspective on Management.

There is an ongoing epidemic of chronic, relapsing dermatophytoses caused by Trichophyton indotineae that are unresponsive to one or multiple antifungal agents. Although this new species may have originated from the Indian subcontinent, there has been a notable increase of its reporting in other countries. Based on current literature, antifungal susceptibility testing (AFST) showed a large variation of terbinafine minimum inhibitory concentrations (MICs) (0.04 to ≥ 32 µg/ml). Elevated terbinafine MICs can be attributed to mutations in the squalene epoxidase gene (single mutations: Leu393Phe, Leu393Ser, Phe397Leu, and double mutations: Leu393Phe/Ala448Thr, Phe397Leu/Ala448Thr). Itraconazole MICs had a lower range when compared with that of terbinafine (0.008-16 µg/ml, with most MICs falling between 0.008 µg/ml and < 1 µg/ml). The interpretation of AFST results remains challenging due to protocol variations and a lack of established breakpoints. Adoption of molecular methods for resistance detection, coupled with AFST, may provide a better evaluation of the in vitro resistance status of T. indotineae. There is limited information on treatment options for patients with confirmed T. indotineae infections by molecular diagnosis; preliminary evidence generated from case reports and case series points to itraconazole as an effective treatment modality, while terbinafine and griseofulvin are generally not effective. For physicians working outside of endemic regions, there is currently an unmet need for standardized clinical trials to establish treatment guidelines; in particular, combination therapy of oral and topical agents (e.g., itraconazole and ciclopirox), as well as with other azoles (i.e., fluconazole, voriconazole, ketoconazole), warrants further investigation as multidrug resistance is a possibility for T. indotineae.

Detection of Squalene Epoxidase Mutations in United States Patients with Onychomycosis: Implications for Management.

Resistance to oral terbinafine, the most commonly used antifungal to treat dermatophytosis and onychomycosis worldwide, is being increasingly reported. In this study, we aimed to investigate the species distribution and prevalence of squalene epoxidase mutations among toenail dermatophyte isolates. Samples from 15,683 patients suspected of onychomycosis visiting the offices of dermatologists and podiatrists in the United States were analyzed. Clinical information was reviewed, and dermatophyte species with or without squalene epoxidase mutations were detected using multiplex real-time PCRs. The frequency of dermatophytes was 37.6%; of isolates belonging to the Trichophyton genus, 88.3% were the T. rubrum complex, and 11.2% were the T. mentagrophytes complex. Individuals aged >70 years exhibited higher infection rates for the T. mentagrophytes complex. The overall mutation rate among Trichophyton spp. was 3.7%, with a higher mutation rate detected in the T. mentagrophytes complex (4.3 vs. 3.6%). Commonly detected mutations were T1189C/Phe397Leu (34.5%), T1306C/Phe415Ser (16.0%), and C1191A/Phe397Leu (11.0%). Squalene epoxidase gene mutations associated with decreased terbinafine susceptibility have been identified in United States patients with toenail onychomycosis. Physicians should be aware of the risk factors for resistance development and engage in antifungal stewardship practices such as directed diagnosis and treatment of dermatophytosis and onychomycosis.