The Influence of UV Varnishes on the Content of Cysteine and Methionine in Women Nail Plates-Chromatographic Studies.

The main purpose of this work was to determine if the use of hybrid nail polishes causes changes in concentration of the most important sulfur amino acids that build nail plate structures, cysteine and methionine. We found that the average contents of cysteine and methionine in studied samples before the use of hybrid manicure were 1275.3 ± 145.9 nmol mg-1 and 111.7 ± 23.8 nmol mg-1, respectively. After six months of hybrid manicure use, the average amount of these sulfur amino acids in studied samples were 22.1% and 36.5% lower in the case of cysteine and methionine, respectively. The average amounts of cysteine and methionine in nail plate samples after the use of hybrid manicures were 992.4 ± 96.2 nmol mg-1 and 70.9 ± 14.8 nmol mg-1, respectively. We also confirmed that in studied women the application of UV light varnishes reduced the thickness of the nail plate, from 0.50 ± 0.12 mm before to 0.46 ± 0.12 mm after the use of the hybrid manicure.

Surgical Intervention for Paronychia Induced by Targeted Anticancer Therapies.

BACKGROUND: Paronychia is a common toxicity associated with targeted anticancer therapies. Antibiotics and steroids are the standard treatments for severe paronychia, yet they are often inadequate, prolonging the patient's suffering and resulting in changes to effective cancer therapy. OBJECTIVE: This article describes the clinical course of drug-induced paronychia and attempts to identify circumstances under which nail surgery may be beneficial. MATERIALS AND METHODS: This is a retrospective case series from a single institution's electronic medical record for patients on paronychia-inducing anticancer therapies with nail disease visit diagnosis codes. RESULTS: The authors identified 36 nail procedures performed on 12 patients, all of whom were managed with conservative steroid and antibiotic therapy with varying degrees of improvement; however, no further improvement was seen after 90 days. Partial matricectomy, nail avulsion, debridement/clipping, and incision and drainage were performed with resolution rates of 100% (11/11), 38.5% (5/13), 12.5% (1/8), and 0% (0/4), respectively. The average time to surgical intervention was 196 days, and the average time to resolution was 268 days. CONCLUSION: This series highlights the prolonged course of severe drug-induced paronychia and the importance of surgical intervention to reduce pain and impact on cancer treatment. Partial matricectomy should be considered for paronychia unresponsive to conservative therapy by 3 months.

A novel technique to evaluate nail softening effects of different urea formulations.

Urea has been incorporated into several topical ungual formulations to hydrate and soften the nail plate. In this study, we employed various characterization techniques (visual observation, scanning electron microscopy, measurement of thickness, transonychial water loss, nail electrical resistance, and mechanical study) to investigate the effect of urea concentration on the hydration of bovine hoof membranes - an in vitro model of infected human nails. We obtained inconsistent results in the thickness, transonychial water loss, nail electrical resistance, and scanning electron microscopy studies. In the mechanical study using a modified Texture Analyzer method, we reported an inverse and linear correlation between urea concentrations in the formulations and the force required to puncture the treated membrane (R2 = 0.9582, n ≥ 8). As the urea concentration decreased from 4x to 2x, 1x, and 0x % w/w, the puncture force increased significantly from 0.47 ± 0.07 to 0.77 ± 0.07, 0.91 ± 0.09, and 1.33 ± 0.26 N, respectively (p < 0.05). Thus, urea provided a positive softening effect on the membranes and the puncture force could indicate the urea level in topical formulations. In this study, we provided a novel, efficient, and reliable tool to evaluate the hydration level and physical properties of bovine hoof membranes.

Iontophoresis to Overcome the Challenge of Nail Permeation: Considerations and Optimizations for Successful Ungual Drug Delivery.

Iontophoresis is a widely used drug delivery technique that has been used clinically to improve permeation through the skin for drugs and other actives in topical formulations. It is however not commonly used for the treatment of nail diseases despite its potential to improve transungual nail delivery. Instead, treatments for nail diseases are limited to relatively ineffective topical passive permeation techniques, which often result in relapses of nail diseases due to the thickness and hardness of the nail barrier resulting in lower permeation of the actives. Oral systemic antifungal agents that are also used are often associated with various undesirable side effects resulting in low patient compliance. This review article discusses what is currently known about the field of transungual iontophoresis, providing evidence of its efficacy and practicality in delivering drug to the entire surface of the nail for extended treatment periods. It also includes relevant details about the nail structure, the mechanisms of iontophoresis, and the associated in vitro and in vivo studies which have been used to investigate the optimal characteristics for a transungual iontophoretic drug delivery system. Iontophoresis is undoubtedly a promising option to treat nail diseases, and the use of this technique for clinical use will likely improve patient outcomes.Graphical abstract.

A review of recent research on antifungal agents against dermatophyte biofilms.

Dermatophytoses are inflammatory cutaneous mycoses caused by dermatophyte fungi of the genera Trichophyton, Microsporum, and Epidermophyton that affect both immunocompetent and immunocompromised individuals. With therapeutic failure, dermatophytoses can become chronic and recurrent. This is partly due to their ability to develop biofilms, microbial communities involved in a polymeric matrix attached to biotic or abiotic surfaces, contributing to fungal resistance. This review presents evidence accumulated in recent years on antidermatophyte biofilm activity. The following databases were used: Web of Science, Medline/PubMed (via the National Library of Medicine), Embase, and Scopus. Original articles published between 2011 and 2020, emphasizing the antifungal activity of conventional and new drugs against dermatophyte biofilms were eligible. A total of 11 articles met the inclusion criteria and were reviewed - the studies used in vitro and ex vivo (fragments of nails and hair) experimental models. The articles focused on reports of antibiofilm activity for conventional antifungals, natural drugs, and new therapeutic tools. The strains reported on were T. mentagrophytes, T. rubrum, T. tonsurans, M. canis, and M. gypseum. Between the studies, the wide variability of experimental conditions in vitro and ex vivo was observed. The data suggest the need for methodological standardization (at some minimum). This review systematically presents current studies involving agents that present antibiofilm activity against dermatophytes; and an overview of the ideal in vitro and ex vivo experimental conditions to guarantee biofilm formation that may assist future research. LAY ABSTRACT: This review presents the current studies on the antibiofilm activities of drugs against dermatophytes and ideal experimental conditions, which might guarantee in vitro and ex vivo biofilm formation. It can be useful to examine the efficacy of new antimicrobial drugs against dermatophytes.

Human Nails Permeation of an Antifungal Candidate Hydroalcoholic Extract from the Plant Sapindus saponaria L. Rich in Saponins.

We evaluated a hydroalcoholic extract of Sapindus saponaria L. pericarps (ETHOSS), as a candidate to a topical antifungal medicine for onychomycosis. ETHOSS was produced by extracting the crushed fruits in ethanol. The saponin contents were identified and characterized by electrospray ionization mass spectrometry. We measured the in vitro antifungal activity against three dermatophyte fungi, isolated from onychomycosis: Trichophyton rubrum, T. mentagrophytes, and T. interdigitale, using broth microdilution tests. The minimum fungicide concentration of ETHOSS ranged from 195.31 to 781.25 µg/mL. The cytotoxicity of the crude extract was tested on the HeLa cell line, and its ability to permeate into healthy human nails by photoacoustic spectroscopy and Fourier transformation infrared spectrometer (FTIR) spectroscopy by attenuated total reflection. Besides its strong antifungal activity, ETHOSS showed low cytotoxicity in human cells. It was able to permeate and reach the full thickness of the nail in one hour, without the aid of facilitating vehicles, and remained there for at least 24 h. These results suggest that ETHOSS has great potential for treating onychomycosis.

Comparison of a fractional 2940-nm Er:YAG laser and 5% amorolfine lacquer combination therapy versus a 5% amorolfine lacquer monotherapy for the treatment of onychomycosis: a randomized controlled trial.

Onychomycosis is a fungal infection of the nail. The aim of this randomized controlled clinical trial was to compare the efficacy of 2940-nm Er:YAG laser treatment combined with a 5% amorolfine lacquer versus amorolfine monotherapy for treating onychomycosis. In this study, patients with onychomycosis of the great toenail were randomly assigned to a combination therapy group and a monotherapy group. In the combination therapy group, the included toenails were treated with a fractional 2940-nm Er:YAG laser at weeks 1, 2, 3, 4, 8, and 12, combined with a 5% amorolfine lacquer twice a week for 12 weeks, while in the monotherapy group, the included toenails were treated with only a 5% amorolfine lacquer twice a week for 12 weeks. The onychomycosis severity index (OSI) score and the mycological clearance rate (MCR) of the included toenails were assessed at baseline, week 12, and week 24. At weeks 12 and 24, the great toenails with mild and moderate onychomycosis in the combination therapy group showed obvious improvement and a greater decrease in OSI than those in the monotherapy group. At week 24, the toenails with mild and moderate onychomycosis in the combination therapy group also showed a better MCR. For the toenails with severe onychomycosis, little improvement was observed in either group at week 12 or week 24. In conclusion, fractional 2940-nm Er:YAG laser treatment combined with a 5% amorolfine lacquer is more effective than amorolfine monotherapy in short-term improvement of onychomycosis.

Nail Psoriasis Treatment: Insights into Current Progress and Future Trends.

Nail psoriasis is a chronic condition which causes pain and functional impairment; thus, it restricts the activities of daily living and worsens the quality of life. Different chemotherapeutic options are available for treating nail psoriasis such as systemic, intralesional, and topical therapies. However, current chemotherapy suffers from several limitations and to overcome them, new advancements are being made worldwide. Various reports have been published on current progress in the treatment of nail psoriasis such as clinical efficacy studies of novel antipsoriatic agents and novel formulation strategies for current chemotherapy. There are several novel nail formulations for the treatment of nail disorders, particularly onychomycosis, such as vesicular colloidal structure (liposomes, niosomes, transfersomes, ethosomes, etc.) and nonvesicular colloidal structures (nano-emulgel, nanocapsules, thermosensitive gel, etc.) These formulations can also prove beneficial for the treatment of nail psoriasis, and will be heavily explored in the near future. This review provides a brief introduction to the disease, its pathogenesis, and its treatment modalities. The review also throws light onto progress and future perspectives in nail psoriasis treatment.

Potential of Naftifine Application for Transungual Delivery.

Naftifine is used to treat fungal skin infections as it inhibits dermatophytes, which are the cause of onychomycosis. However, naftifine's ability to permeate the human nail barrier has not been investigated, thus, the antimycotic potential is not clearly established. This work aims to evaluate the effect of penetration enhancing factors on the accumulation of naftifine hydrochloride through human nail clippings. Naftifine polymeric nail lacquers with Eudragit RL100 were developed as a suitable delivery system. Low penetration of naftifine into nail has been determined as less than 10% of applied drug dose accumulated in the nail layers. Incorporation of thioglycolic acid into formulations resulted in increased accumulation of antifungal agent in the nail layers by 100% compared with a control group. Salicylic acid did not effect naftifine accumulation in the human nail. The permeation of naftifine through the nail increased by threefold when the thioglycolic acid-containing formulation was applied and the nail was pretreated with a fractional CO2 laser. Structural changes of the nail barrier, induced by fractional CO2 laser, were visualized by microscopy. The results suggest, that naftifine nail penetration could be significantly increased when physical and chemical enhancing factors are applied.

Clinical significance of Candida isolation from dystrophic fingernails.

BACKGROUND: Candida onychomycosis mostly involves fingernails. Yet, in contrast to dermatophytes, Candida isolation from dystrophic fingernails does not prove casualty, as sample contamination and non-pathogenic Candida growth occur. Characterising treatment outcome of Candida-positive dystrophic nails is crucial to avoid unnecessary treatment. OBJECTIVE: To investigate predicators associated with treatment outcome among Candida-positive dystrophic fingernails. PATIENTS AND METHODS: A retrospective cohort study was carried out among 108 adults with Candida-positive dystrophic fingernails not cured with adequate systemic anti-fungal course. Diagnosis was based on a single mycological culture. Patients with treatment failure (n = 85; 78.7% of the cases) were compared to patients with partial response (mild to almost cure; n = 23; 21.3% of the cases) at 9 to 12 months following treatment initiation. RESULTS: Treatment failure was significantly associated with primary onycholysis (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.1-7.4) and prolonged dystrophy (12.8 vs. 3.7 years in average), compared to partial treatment response. Non-responders had lower odds to present with distal lateral subungual onychomycosis, compared to partial responders (OR 0.3; 95% CI 0.1-0.7). Demographic and mycological characteristics, as well as number of nails affected, co-presence of paronychia, and treatment regime were not found to be associated with treatment response. CONCLUSION: Candida-positive primary onycholysis was shown to be non-responsive to systemic anti-fungal treatment, suggesting that anti-fungal treatment is not indicated. For other clinical scenarios, high proportions of treatment non-response suggest that determining causality of Candida should not be based on a single positive mycological culture.

Effect of Nail Thickness on Visible Radiation Transmittance: Implications for New Photodynamic Therapy Technologies in Onychomycosis.

Photodynamic therapy is taking importance as a nonintrusive treatment for nail onychomycosis. Knowledge of true transmittance values across nails could lead to qualitative and quantitative improvements in light-based treatments. We have characterized the spectral transmittance of healthy and fungally infected human fingernails and toenails according to nail thickness, and we propose a surface transmittance model for the small-scale optimization of light-based treatments. Transmittance of fingernails and toenails was analyzed by means of spectroradiometric measurements under solar-simulated visible light radiation (400 nm to 750 nm). The nail thickness was measured by means of microscope measurement. Transmittance was highest at longer wavelengths and decreased gradually as the wavelengths became shorter but with a significant nail transmittance of around 20% in the blue region of the spectrum. In the case of nails affected by onychomycosis, transmittance fell to under 10% because of the thickness of the nails, with no changes in spectral characteristics of transmitted light. Nail thickness is the main variable controlling exponentially light transmission in the visible spectrum and not only red radiation is effective for nail onychomycosis PDT. Blue light, the spectral band more effective for PPIX absorption is also effectively transmitted.

Characterizing the adverse dermatologic effects of hydroxychloroquine: A systematic review.

BACKGROUND: Hydroxychloroquine is associated with myriad adverse dermatologic effects, most of which are poorly characterized by the literature, with unknown frequencies and risk factors. OBJECTIVE: To conduct a systematic review of the adverse dermatologic effects and predisposing factors of hydroxychloroquine toxicity. RESULTS: The review included 94 articles comprising 689 dermatologic adverse effects. A total of 21 unique dermatologic reactions were reported, most commonly drug eruption or rash (358 cases), cutaneous hyperpigmentation (116), pruritus (62), acute generalized exanthematous pustulosis (27), Stevens-Johnson syndrome or toxic epidermal necrolysis (26), hair loss (12), and stomatitis (11). Almost all underlying conditions were rheumatologic or autoimmune in nature, composed primarily of lupus erythematous (72% of all cases) and rheumatoid arthritis (14%). The range of reported mean cumulative dosages was wide, with some adverse reactions found after as little as 3 g or as much as 2500 g. LIMITATIONS: Dermatologic adverse events and primary diagnoses related to the use of hydroxychloroquine may be under-reported as only case reports and clinical trials that reported at least 1 dermatologic adverse effect were included. CONCLUSION: Although hydroxychloroquine is generally well tolerated, dermatologic adverse effects involving the skin, hair, or nails are a frequent and significant complication. Most of these reactions occurred after treatment of autoimmune conditions, often manifesting on the skin after a wide range of cumulative dosages.

NP213 (Novexatin®): A unique therapy candidate for onychomycosis with a differentiated safety and efficacy profile.

NP213 (Novexatin®) is a novel antifungal peptide specifically designed for the topical treatment of onychomycosis. NP213 was designed using host defense peptides (HDP), essential components of the innate immune response to infection, as a template. NP213 is a water-soluble cyclic fungicidal peptide that effectively penetrates human nail. NP213 demonstrated a promising preclinical and clinical safety profile, with no evidence of systemic exposure following topical application to the skin and nails. NP213 was efficacious in two phase IIa human trials with 43.3% of patients having no fungi detectable by culture of fragments from NP213-treated nails after 180 days in the first study and likewise 56.5% of patients were culture negative for dermatophytes after 360 days in the second phase IIa study. In both trials, NP213 was applied daily for only 28 days in marked contrast to other topical onychomycosis treatments that require application for up to 52 weeks. Patient reported outcomes from the phase IIa studies were positive with participants recording an improved appearance of their nails after only 14 days of application. All fungi identified in these studies were Trichophyton spp. NP213 (Novexatin®) is a promising, highly differentiated peptide-based candidate for the topical treatment of onychomycosis, addressing the infectious cause and cosmetic issues of this very common condition.

Treatment and management strategies of onychomycosis.

Onychomycosis is one of the most prevalent and severe nail fungal infections, which is affecting a wide population across the globe. It leads to variations like nail thickening, disintegration and hardening. Oral and topical drug delivery systems are the most desirable in treating onychomycosis, but the efficacy of the results is low, resulting in a relapse rate of 25-30%. Due to systemic toxicity and various other disadvantages associated with oral therapy like gastrointestinal, hepatotoxicity, topical therapy is commonly used. Topical therapy improves patient compliance and reduces the cost of treatment. However, due to poor penetration of topical therapy across the nail plate, research is focused on different chemical, mechanical and physical methods to improve drug delivery. Penetration enhancers like Thioglycolic acid, Hydroxypropyl-ß-cyclodextrin (HP-ß-CD), Sodium lauryl sulfate (SLS), carbocysteine, N-acetylcysteine etc. have shown results enhancing the drug penetration across the nail plate. Results with physical techniques such as iontophoresis, laser and Photodynamic therapy are quite promising, but the long-term suitability of these devices is in need to be determined. In this article, a brief analysis of the treatment procedures, factors affecting drug permeation across nail plate, chemical, mechanical and physical devices used to increase the drug delivery through nails for the onychomycosis management has been achieved.

Isolated nail lichen planus: An expert consensus on treatment of the classical form.

Lichen planus is a benign inflammatory disorder of unknown etiology that may affect the skin, mucosae, scalp, and nails. When the nails are affected, it may lead to permanent destruction with severe functional and psychosocial consequences. Therefore, prompt diagnosis and early treatment are essential, even in mild cases. There are currently no guidelines for the management of nail lichen planus and the published literature on treatment is limited. The aim of this review is to provide practical management recommendations for the classical form of nail lichen planus, especially when restricted to the nails. Topical treatment has poor short-term efficacy and may cause long-term side effects. Instead, intralesional and intramuscular triamcinolone acetonide should be considered first-line therapies. Oral retinoids are second-line choices, and immunosuppressive agents may also be considered.