ArticleLiterature Review

Over-the-counter and Natural Remedies for Onychomycosis: Do They Really Work?

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Abstract

Onychomycosis is a fungal infection of the nail unit that may lead to dystrophy and disfigurement over time. It accounts for up to 50% of all nail conditions , with toenails affected more commonly than fingernails. Onychomycosis may affect quality of life and increase the prevalence and severity of foot ulcers in patients with diabetes. Available oral agents approved by the US Food and Drug Administration (FDA) for the treatment of ony-chomycosis include terbinafine and itraconazole, which have demonstrated good efficacy but are associated with the risk of systemic side effects and drug-drug interactions. Topical medications that are FDA approved for onychomycosis include ciclopirox, efinaconazole, and tavaborole. These therapies generally have incomplete efficacy compared to systemic agents as well as long treatment courses and possible local side effects such as erythema and/or blisters. Given the need for safe, effective, and cost-effective options for onychomy-cosis therapy, there has been a renewed interest in natural and over-the-counter (OTC) alternatives. This review will synthesize the laboratory data, known antifungal mechanisms, and clinical studies assessing the efficacy of OTC and natural products for onychomycosis treatment. Cutis. 2016;98:E16-E25.

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... Recent attention has been given to natural remedies and OTC treatments for onychomycosis. 166 Tea tree oil (TTO) is a volatile oil that is used in Australia, Europe, and North America for treatment of tinea pedis. 167 In C. albicans, TTO has been shown to decrease glucose-induced acidification of media surrounding fungi and alter respiration and permeability of plasma membranes. ...
... The active ingredients are eucalyptus oil 1.2%, camphor 4.8%, and menthol 2.6%, and the inactive ingredients are nutmeg oil, cedarleaf oil, thymol, petrolatum, and turpentine oil. 166 In a pilot study of 18 adult patients with toenail onychomycosis who applied topical cough suppressants (Vicks VapoRub; The Proctor & Gamble Company, Cincinnati, OH) once daily, 173 Natural coniferous resin, derived from the Norway spruce tree (Picea abies) and mixed with boiled butter or animal fat, has been used for centuries to treat wounds and infections. 166 In a prospective, randomized, controlled, investigatorblinded study, 175 73 patients with toenail onychomycosis received either natural coniferous resin 30% once daily for 9 months, amorolfine lacquer 5% once weekly for 9 months, or 250 mg oral terbinafine once daily for 3 months. ...
... 166 In a pilot study of 18 adult patients with toenail onychomycosis who applied topical cough suppressants (Vicks VapoRub; The Proctor & Gamble Company, Cincinnati, OH) once daily, 173 Natural coniferous resin, derived from the Norway spruce tree (Picea abies) and mixed with boiled butter or animal fat, has been used for centuries to treat wounds and infections. 166 In a prospective, randomized, controlled, investigatorblinded study, 175 73 patients with toenail onychomycosis received either natural coniferous resin 30% once daily for 9 months, amorolfine lacquer 5% once weekly for 9 months, or 250 mg oral terbinafine once daily for 3 months. At 10 months, mycologic cure rates were 13% (95% CI, 0-28%), 8% (95% CI, 0-19%) and 56% (95% CI, , respectively (p ≤ 0.002). ...
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Julianne M Falotico,1 Shari R Lipner2 1Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA; 2Weill Cornell Medicine, Department of Dermatology, New York, NY, USACorrespondence: Shari R Lipner, Weill Cornell Medicine, Department of Dermatology, 1305 York Avenue, NY, NY, 10021, USA, Tel +1 646-962-3376, Fax +1 646-962-0033, Email shl9032@med.cornell.eduAbstract: Onychomycosis is the most common nail disease encountered in clinical practice and can cause pain, difficulty with ambulation, and psycho-social problems. A thorough history and physical examination, including dermoscopy, should be performed for each patient presenting with nail findings suggestive of onychomycosis. Several approaches are available for definitive diagnostic testing, including potassium hydroxide and microscopy, fungal culture, histopathology, polymerase chain reaction, or a combination of techniques. Confirmatory testing should be performed for each patient prior to initiating any antifungal therapies. There are several different therapeutic options available, including oral and topical medications as well as device-based treatments. Oral antifungals are generally recommended for moderate to severe onychomycosis and have higher cure rates, while topical antifungals are recommended for mild to moderate disease and have more favorable safety profiles. Oral terbinafine, itraconazole, and griseofulvin and topical ciclopirox 8% nail lacquer, efinaconazole 10% solution, and tavaborole 5% solution are approved by the Food and Drug Administration for treatment of onychomycosis in the United States and amorolfine 5% nail lacquer is approved in Europe. Laser treatment is approved in the United States for temporary increases in clear nail, but clinical results are suboptimal. Oral fluconazole is not approved in the United States for onychomycosis treatment, but is frequently used off-label with good efficacy. Several novel oral, topical, and over-the-counter therapies are currently under investigation. Physicians should consider the disease severity, infecting pathogen, medication safety, efficacy and cost, and patient age, comorbidities, medication history, and likelihood of compliance when determining management plans. Onychomycosis is a chronic disease with high recurrence rates and patients should be counseled on an appropriate plan to minimize recurrence risk following effective antifungal therapy.Keywords: onychomycosis, nail disease, fungal nail infection, diagnosis, management, treatment, recurrence
... Additionally, several essential oils have shown broad-spectrum antifungal activity through in vitro studies, showing promise for a potential role in the treatment of onychomycosis [8]. Halteh et al. [9] published a study in 2015 reviewing over-the-counter and natural remedies for onychomycosis. Authors found both in vitro and clinical evidence for the use of tea tree oil, topical cough suppressants, natural coniferous resin, Ageratina pichinchensis, and ozonized sunflower oil in the treatment of onychomycosis [9]. ...
... Halteh et al. [9] published a study in 2015 reviewing over-the-counter and natural remedies for onychomycosis. Authors found both in vitro and clinical evidence for the use of tea tree oil, topical cough suppressants, natural coniferous resin, Ageratina pichinchensis, and ozonized sunflower oil in the treatment of onychomycosis [9]. In this systematic review, we sought to critically appraise the literature and provide an update to Halteh et al. [9] with a focus on the clinical evidence supporting the use of complementary and alternative therapy for the treatment of onychomycosis. ...
... Authors found both in vitro and clinical evidence for the use of tea tree oil, topical cough suppressants, natural coniferous resin, Ageratina pichinchensis, and ozonized sunflower oil in the treatment of onychomycosis [9]. In this systematic review, we sought to critically appraise the literature and provide an update to Halteh et al. [9] with a focus on the clinical evidence supporting the use of complementary and alternative therapy for the treatment of onychomycosis. ...
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Introduction: Onychomycosis is notoriously difficult to treat. While oral antifungals are the most efficacious treatment for onychomycosis, they are contraindicated in certain patient populations, and patients may desire lower risk and accessible alternatives to systemic agents. In this study, we examine the clinical evidence supporting the use of complementary and alternative therapies in the treatment of onychomycosis. Methods: PubMed, Embase, and Cochrane Library were searched for clinical trials, observational studies, and case reports/case series, examining the efficacy of a complementary or alternative therapy for the treatment of onychomycosis. Results: We identified 17 articles studying a complementary and alternative therapy for onychomycosis, including tea tree oil (n = 5), Ageratina pichinchensis (n = 3), Arthrospira maxima (n = 2), natural coniferous resin lacquer (n = 2), Vicks VapoRub® (n = 2), propolis extract (n = 2), and ozonized sunflower oil (n = 1). Conclusion: Given the rise of antifungal resistance, complementary and alternative therapies should continue to be studied as adjunctive or alternative therapy for onychomycosis. While preliminary evidence exists for several complementary and alternative therapies in the treatment of onychomycosis, large-scale, randomized, placebo-controlled trials are needed prior to endorsing their use to patients.
... Additionally, several essential oils have shown broad-spectrum antifungal activity through in vitro studies, showing promise for a potential role in the treatment of onychomycosis [8]. Halteh et al. [9] published a study in 2015 reviewing over-the-counter and natural remedies for onychomycosis. Authors found both in vitro and clinical evidence for the use of tea tree oil, topical cough suppressants, natural coniferous resin, Ageratina pichinchensis, and ozonized sunflower oil in the treatment of onychomycosis [9]. ...
... Halteh et al. [9] published a study in 2015 reviewing over-the-counter and natural remedies for onychomycosis. Authors found both in vitro and clinical evidence for the use of tea tree oil, topical cough suppressants, natural coniferous resin, Ageratina pichinchensis, and ozonized sunflower oil in the treatment of onychomycosis [9]. In this systematic review, we sought to critically appraise the literature and provide an update to Halteh et al. [9] with a focus on the clinical evidence supporting the use of complementary and alternative therapy for the treatment of onychomycosis. ...
... Authors found both in vitro and clinical evidence for the use of tea tree oil, topical cough suppressants, natural coniferous resin, Ageratina pichinchensis, and ozonized sunflower oil in the treatment of onychomycosis [9]. In this systematic review, we sought to critically appraise the literature and provide an update to Halteh et al. [9] with a focus on the clinical evidence supporting the use of complementary and alternative therapy for the treatment of onychomycosis. ...
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Background: While the Internet remains a popular source of health information, YouTube may contain bias and incomplete information regarding common dermatological conditions. Objective: Our objective was to quantify onychomycosis treatment recommendations on YouTube. Methods: We searched YouTube for "nail fungus," "toenail fungus," "onychomycosis treatment," "onychomycosis," and "nail fungus treatment" in separate searches. The top 30 videos meeting inclusion criteria in each search were viewed for video demographics and treatment recommendations. Results: Analysis was performed on 102 videos. The majority of videos (81.3%) were intended for patient education. Analyzing videos by speaker, 50.0% featured a podiatrist, 13.7% a nondermatologist physician or other medical professional, 10.8% a patient or blogger, 6.9% a dermatologist, and 2.0% a nail technician. Videos recommended FDA-approved therapies, as well as OTC products. The most recommended medical therapies included oral terbinafine and laser therapy, mentioned in 29 and 28 videos, respectively. Various natural remedies were recommended, with tea tree oil being endorsed in 23 videos. Conclusion: YouTube offers patient education on a range of treatment options for onychomycosis. We caution patients against starting treatments based on social media recommendations and encourage dermatologists to utilize social media to educate the public on common dermatological conditions.
... Antifungals available for the treatment of onychomycosis show a range of adverse effects that may cause patients to stop the treatment due to the comorbidities that are usually related to this disorder. The few existing studies indicate that these natural compounds are a promising alternative for treatment of onychomycosis (Halteh et al., 2016). ...
... If the above rate of complete cures is added to the 31.25% rate of partial cures (patients who are still being treated and will be followed for a longer period of time, 12 months), we could report an 87% index of clinical improvement, a superior performance to the results attained with several other natural products (Halteh et al., 2016) for onychomycosis topical treatment. This efficacy may be related to the cumulative effect of the different properties of propolis, such as antimicrobial, biofilm reducer, anti-inflammatory, and scarring effect (Oryan et al., 2018). ...
... Finally, there is concern about the use of over-thecounter and natural remedies for onychomycosis (Halteh et al., 2016), considering the need for standardization and quality control, among other requirements, to produce reliable compounds. These concerns have been allayed for propolis, because the products containing propolis as the active principle are registered, regulated, and approved for use in several pharmaceutical dosage forms in South America (e.g., Brazil and Argentina), the United States, Europe, and Asia (e.g., Japan) (de Toledo et al., 2015(de Toledo et al., , 2016Rosseto et al., 2017). ...
Article
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Onychomycosis is a chronic fungal infection of nails, commonly caused by dermatophyte fungi, primarily species of Trichophyton. Because of the limited drug arsenal available to treat general fungal infections and the frequent failure of onychomycosis treatment, the search for new therapeutic sources is essential, and topical treatment with natural products for onychomycosis has been encouraged. Propolis, an adhesive resinous compound produced by honeybees (Apis mellifera), has shown multiple biological properties including significant antifungal and anti-biofilm activities in vitro. In spite of promising in vitro results, in vivo results have not been reported so far. This study assessed an ethanol propolis extract (PE) as a topical therapeutic option for onychomycosis, including its characterization in vitro and its applicability as a treatment for onychomycosis (from bench to clinic). The in vitro evaluation included analysis of the cytotoxicity and the antifungal activity against the planktonic cells and biofilm formed by Trichophyton spp. We also evaluated the capacity of PE to penetrate human nails. Patients with onychomycosis received topical PE treatments, with a 6-month follow-up period. The results of the in vitro assays showed that PE was non-toxic to the cell lines tested, and efficient against both the planktonic cells and the biofilm formed by Trichophyton spp. The results also showed that PE is able to penetrate the human nail. The results for PE applied topically to treat onychomycosis were promising, with complete mycological and clinical cure of onychomycosis in 56.25% of the patients. PE is an inexpensive commercially available option, easy to obtain and monitor. Our results indicated that PE is a promising natural compound for onychomycosis treatment, due to its ability to penetrate the nail without cytotoxicity, and its good antifungal performance against species such as Trichophyton spp. that are resistant to conventional antifungals, both in vitro and in patients.
... Limited sources on the internet advocate several natural remedies, specifically for fungal infection of the nails; however, their efficacy is uncertain [81]. The advocated natural remedies include the use of apple cider vinegar, tea tree oil, essential oil blends, baking soda, mentholated ointments and mouthwashes, and garlic [82,83]. However, most of these treatments show no significant curative effect and do not compare in efficacy to FDA-approved therapies [82,83]. ...
... The advocated natural remedies include the use of apple cider vinegar, tea tree oil, essential oil blends, baking soda, mentholated ointments and mouthwashes, and garlic [82,83]. However, most of these treatments show no significant curative effect and do not compare in efficacy to FDA-approved therapies [82,83]. ...
Article
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Superficial fungal infections affect greater than 20% of the global population. Only a few hundred (of the millions of fungi species) are capable of causing human infections. Moreover, superficial infections respond well to various over-the-counter products. However , resistance to specific anti-fungal medicines is developing. The skin surface is an ideal growth environment for dermatophytes, commonly found around public swimming pools, locker rooms, and showers. Transmission occurs through direct person-to-person contact or indirect contact through the handling of contaminated objects. Immunocompromised patients and those with active illnesses and diseases are at a greater risk for fungal and recurrent fungal infections. An individual's genetic design may predispose them to specific fungal infections. Also, specific factors, such as cosmetics, body soaps, and other hygiene products, can alter the skin microbiome, predisposing the host to pathologic fungal infestation. This article reviews the etiology of external fungal infections and recurrent infections, considers susceptibility factors, and describes and evaluates currently available treatment options.
... The efficacy of current treatments is limited by the slow growth of toenails, nail keratin thickness preventing penetration of topical and systemic drugs, and survival of fungi in surrounding environments (such as footwear) for long periods. Because of their lack of intrinsic immune function and impenetrable nature, nails are a particularly challenging tissue to cure [19]. Individuals with onychomycosis can experience very long-lasting disease, especially in the absence of effective treatment. ...
... Given the challenges associated with available topical and systemic agents, there is a renewed interest in exploring alternative natural treatments for onychomycosis [19]. Natural onychomycosis therapies may have some important advantages over current treatments. ...
Article
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Onychomycosis is an increasingly common fungal nail infection, chiefly caused by dermatophyte fungi. The disease is notoriously difficult to treat due to the deep-seated nature of fungi within the nail plate, prolonged treatment requirements, poor patient adherence and frequent recurrences. Given the poor efficacy of currently available topical and systemic therapies, there is a renewed interest in exploring alternative treatment modalities for onychomycosis. Natural therapies, physical treatments and various combination therapies have all shown potential for the management of onychomycosis, though research on many of these methods is still in preliminary stages. Further large, well-designed, randomised controlled trials are necessary to confirm the efficacy of these novel treatments in order to make formal recommendations regarding their use in the management of onychomycosis.
... • Ciclopirox 8%, • Amorolfine 5% lacquers, and • Efinaconazole 10% solution 47 Systemic antifungals that are commonly used to treat onychomycosis are given below: ...
... Although overall knowledge of superficial fungal infection nomenclature was encouraging, the high treatment failure rate highlights a lack of awareness about the importance of HCP diagnosis and management of superficial fungal infections and the need for comprehensible public education material [7]. The modest use of natural or alternative treatments also supports the need for public education on evidenced-based treatments [8]. ...
Article
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Data about the prevalence, diagnosis, treatment, and public knowledge of superficial fungal infections in the United States are scarce. These infections are a growing concern given the emergence of antifungal drug resistance. We analyzed data from a national survey of nearly 6000 U.S. adults. Overall, 114 (2.7%) participants reported having ringworm and 415 (10.0%) reported a fungal nail infection in the past 12 months; 61.4% of participants with any superficial fungal infection were self-diagnosed. Most patients (55.5%) used over-the-counter antifungals. The common nature of superficial fungal infections and the high rates of self-diagnosis and treatment indicate that community education about these infections should be considered a public health priority.
... It can invade and infect the body systemically and especially dangerous to those that are already immunocompromised or diabetic. Characterized by yellow or white discoloration with flaking, cracked, or crumbling on the nail unit, this fungal infection accounts for 50 percent of all nail diseases [2]. The incidence of TUDO is reported as a percentage of between two to fourteen percent of the American population. ...
Article
The evolution of modern medical advances is often underestimated and that as little as a hundred years ago, none of the formulated antibiotics currently available existed. The germ theory was only substantiated because bacteria had been identified with the refining of microscopic technol-ogy and organisms that did not exist in context or conjunction to human disease. The connection between what appeared through the lens of a microscope slowly became the basis of the medical theories of human health and illness. This included the causative agents within all states of hu-man wellness. Humans started using plants and their essences long before they were able to rec-ord it. The scientific renaissance started the medical movement towards concrete concepts and reproducible results all bound by the scientific methods. This left little room for combinations of chemicals or plant constituents and compartmentalized human health into systems that worked best under strict control negating the concept of synergy. Human medicine is now moving out of the realm of being solely dependent on synthetic chemical formulations. Alternative and modern medical healers alike are starting to understand that both paths to human healing are needed to care for the many microbial assaults caused by bacteria, viruses, and fungi. Combing herbal folk-lore with modern chemistry is not a compromise but a middle way for better human health and illustrated with the use of Melaleuca alternifolia (Australian Tea Tree Oil) and modern antifungal agents used in conjunction to definitively cure the fungal infection starting with the causative fungi Tinea unguim and the condition of onychomycosis as an example.
... TTO is an essential oil that has been used as a medicine since the beginning of the 20th century, when the Bundjalung aborigines of the northern coastal area of New South Wales (Australia) extracted TTO from the dried leaves of the M. alternifolia plant and used it for the treatment of superficial wounds. TTO is widely used in Australia, Europe, and North America for the treatment of tinea pedis and onychomycosis, mainly caused by T. rubrum and T. mentagrophytes in humans, and the treatment of dermatophytosis in horses caused by T. equinum [17,18]. TTO is also effective in inhibiting several fungal isolates, including Candida albicans and Aspergillus niger. ...
Article
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Over the past 20–30 years, Trichophyton rubrum represented the most widespread dermatophyte with a prevalence accounting for 70% of dermatophytosis. The treatment for cutaneous infections caused by Trichophyton spp. are imidazoles (ketoconazole (KTZ)) and triazoles (itraconazole (ITZ)). T. rubrum can develop resistance to azoles after prolonged exposure to subinhibitory concentrations resulting in therapeutic failures and chronic infections. These problems have stimulated the search for therapeutic alternatives, including essential oils, and their potential use in combination with conventional antifungals. The purpose of this study was to evaluate the antifungal activity of tea tree oil (TTO) (Melaleuca alternifolia essential oil) and the main components against T. rubrum and to assess whether TTO in association with KTZ/ITZ as reference drugs improves the antifungal activity of these drugs. We used a terpinen-4-ol chemotype (35.88%) TTO, and its antifungal properties were evaluated by minimum inhibitory and minimum fungicidal concentrations in accordance with the CLSI guidelines. The interaction between TTO and azoles was evaluated through the checkerboard and isobologram methods. The results demonstrated both the fungicide activity of TTO on T. rubrum and the synergism when it was used in combination with azoles. Therefore, this mixture may reduce the minimum effective dose of azole required and minimize the side effects of the therapy. Synergy activity offered a promise for combination topical treatment for superficial mycoses.
... It is important to emphasize that in the last years there has been an increase in cases of fungal infections that result in mortality due to the difficulty of treatment [5]. In addition, the high levels of toxicity presented by some of the available antifungal drugs led to an increase in the interruption of treatment by patients' before complete cure of the infection [6,36]. In view of these facts, this study examined a combination of silver and propolis in an effort to develop an effective antifungal with low toxicity. ...
Article
Aim: Elucidate the antifungal efficacy of biologically synthesized silver nanoparticles with ethanolic propolis extract (AgNPs PE) against the planktonic forms and biofilms of clinically important fungi. Materials & methods: AgNPs were synthesized, characterized and evaluated for cytotoxicity, mutagenicity and antimicrobial activity. Results: AgNPs PE displayed a colloidal appearance, good stability and size of 2.0–40.0 nm. AgNPs PE demonstrated lower cytotoxicity and nonmutagenic potential. In addition, AgNPs PE displayed antifungal properties against all tested isolates, inhibiting growth at concentrations lower than the cytotoxic effect. Mature biofilms treated for 48 h with AgNPs PE showed significant reduction of viable cells, metabolic activity and total biomass. Conclusion: This is the first time that AgNPs have been synthesized from an ethanolic extract of propolis only, proving antifungal, antibiofilm, atoxic and nonmutagenic properties.
... Although, the rate of permeation of the drug per unit of thickness across the nail plate is greater than that in the stratum corneum [68], the major barriers in the delivery of antifungals to the nails are the nail plate thickness and toenails slow growth. The challenge in treatment of nails is due to its impermeable nature and absence of immune function [143]. The longer treatment duration and the high relapse rate of 50% of the disease could be another contributing barrier in its treatment [144][145][146][147][148]. This high Thioglycolic acid A novel method to treat nail mycoses was observed in which the barrier structure of nail weakened on sequential application of reducing agent followed by oxidizing agent thereby facilitate the transport of drugs across the nail A Reducing agent in the form of thioglycolic acid and an oxidizing agent, in the form of hydrogen peroxide applied in liquid form sequentially augmented fungal permeation and increased flux of drug across the nail plate [96] recurrence rate could be attributed to numerous factors like age of the person, genetic predisposition, the social class, inclining factor, the occupation of the person, living conditions and climatic conditions [7]. ...
Article
Onychomycosis is one of the most prevalent and severe nail fungal infection, 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-β-cyclodextrin (HP-β-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.
Article
Ethnopharmacological relevance Genus Melaleuca or tea tree species are well known to be an important source of biological active oils and extracts. The biological significance appears in their usage for treatment of several clinical disorder owing to their traditional uses as anti-inflammatory, antibacterial, antifungal, and cytotoxic activities. Aim of the study: Our study aimed to investigate the metabolic profile of the M. rugulosa polyphenol-rich fraction along with determination of its anti-inflammatory potential, free radical scavenging and antiaging activities supported with virtual understanding of the mode of action using molecular modeling strategy. Materials and methods The anti-inflammatory activity of the phenolic rich fraction was investigated through measuring its inhibitory activity against inflammatory mediators viztumor necrosing factor receptor-2 (TNF-α) and Cyclooxygenases 1/2 (COX-1/2) in a cell free and cell-based assays. Moreover, the radical scavenging activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC) and β-carotene assays, while the antiaging activity in anti-elastase, anti-collagenase, and anti-tyrosinase inhibitory assays. Finally, the biological findings were supported with molecular docking study using MOE software. Results the chromatographic purification of the polyphenol-rich fraction of Melaleuca rugulosa (Link) Craven afforded fourteen phytoconstituents (1–14). The anti-inflammatory gauging experiments demonstrated inhibition of inflammatory-linked enzymes COX-1/2 and the TNFR2 at low μg/mL levels in the enzyme-based assays. Further investigation of the under lying mechanism was inferred from the quantification of protein levels and gene expression in the lipopolysaccharide (LPS)-activated murine macrophages (RAW264.7) in vitro model. The results revealed the reduction of protein synthesis of COX-1/2 and TNF-α with the down regulation of gene expression. The cell free in vitro radical scavenging assessment of the polyphenol-rich fraction revealed a significant DPPH reduction, peroxyl radicals scavenging, and β-carotene peroxidation inhibition. Besides, the polyphenol-rich fraction showed a considerable inhibition of the skin aging-related enzymes as elastase, collagenase, and tyrosinase. Ultimately, the computational molecular modelling studies uncovered the potential binding poses and relevant molecular interactions of the identified polyphenols with their targeted enzymes. Particularly, terflavin C (8) which showed a favorable binding pose at the elastase binding pocket, while rosmarinic acid (14) demonstrated the best binding pose at the COX-2 catalytic domain. In short, natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions. Conclusion Natural polyphenols are potential candidates for the management of free radicals, inflammation, and skin aging related conditions.
Article
Ethnopharmacological relevance Melaleuca species have been used by many ethnic communities for the management and treatment of several ailments as hemorrhoids, cough, skin infections, rheumatism, sore throat, pain, inflammation, and digestive system malfunctions. However, the detailed mechanistic pharmacological effect of Melaleuca rugulosa (Link) Craven leaves in the management of liver inflammation has not been yet addressed. Aim of the study The present study aimed to evaluate the anti-inflammatory, antioxidant, and antiapoptotic capacities of the aqueous methanol extract of M. rugulosa leaves in relevance to their flavonoid content using an appropriate in vivo model. Materials and methods The aqueous methanol extract of M. rugulosa leaves was administered to the rats at three non-toxic doses (250, 500, and 1000 mg/kg) for seven days prior to the initiation of liver-injury induced by paracetamol (3g/kg). Liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated in serum samples. The oxidative stress markers including reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels as well as the inflammatory markers such as tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB), were assessed in liver homogenate. The results were supported by histopathological and immuno-histochemical studies. The phytochemical investigation of the flavonoid-rich fraction of the aqueous methanol extract was accomplished using different chromatographic and spectroscopic techniques. Results The aqueous methanol extract of M. rugulosa leaves showed a powerful hepatoprotective activity evidenced by the significant reduction of MDA and NO levels, as well as increasing GSH and catalase activity. Moreover, the extract has anti-inflammatory and antiapoptotic activities witnessed by decreasing TNF-α, NF-κB, iNOS, p-JNK, caspase-3, BAX, and increasing Bcl-2 levels. Moreover, the pretreatment of rats with all doses of M. rugulosa leaves extract showed a significant decrease in liver weight/body weight (LW/BW) ratio, and total bilirubin induced by paracetamol. On the other hand, the chromatographic separation of the flavonoid-rich fraction afforded twenty known flavonoids namely; iso-orientin (1), orientin (2), isovitexin (3), vitexin (4), quercetin-3-O-β-D-glucuronid methyl ether (5), quercetin 3-O-β-D-mannuronpyranoside (6), isoquercetin (7), quercitrin (8), kaempferol-3-O-β-D-mannuronopyranoside (9), kaempferol-7-O-methyl ether-3-O-β-D-glucopyranoside (10), guaijaverin (11), avicularin (12), kaempferide-3-O-β-D- glucopyranoside (13), astragalin (14), afzelin (15), luteolin (16), apigenin (17), quercetin (18) kaempferol (19), and catechin (20). Conclusion The aqueous methanol extract of M. rugulosa leaves showed potential hepatoprotective, antioxidant and anti-inflammatory activities against paracetamol-induced liver inflammation which is correlated at least in part to its considerable phenolic content.
Article
Background Onychomycosis affects approximately 5% of the population worldwide without satisfactory treatment options regarding efficacy and safety. The aim of this first in human study was to compare the safety and efficacy of the novel compound Mycosinate® against an approved toenail lacquer containing 5% Amorolfine. Design A randomized, single-blinded, controlled parallel group study with allocation concealment was carried out. Methods Thirty-eight participants either used the novel compound Mycosinate® or an approved toenail lacquer containing 5% Amorolfine for topical application in their own homes. Outcome measures included a) % change in area of clear visible toenail, b) mycological cure rate and c) safety assessments. Results Statically significant differences for % change in area of clear visible toenail (p<0.05) of 39.8, 40.0 and 70.7 in favour of Mycosinate® were noted at time points 6 weeks, 12 weeks, and 6 months respectively when compared to Amorolfine. No statistically significant differences were noted for mycological cure rates. No adverse events, serious adverse events or deaths occurred for either treatment. Conclusion Mycosinate® is a promising novel topical onychomycosis treatment with high rates of efficacy and excellent safety profile. Further clinical trials are warranted. (EU Clinical Trials Register 2018/000294/78)
Article
Introduction Dandruff and seborrheic dermatitis [SD] are similar skin conditions but have different severities. Because the current therapies are not able to completely remove dandruff, herbal extracts with better effectiveness and fewer side effects are being used in the pharmaceutical and cosmetic industries. Due to the adverse effects of chemical drugs, the use of natural products and traditional medicine has sharply increased over the past few decades. Therefore, in this review, we report herbs used as anti-dandruff agents in traditional medicine around the world. Methods The review was conducted on the literature available on the medicinal utility of certain plants as antidandruff agents using PubMed and Google Scholar and the following search terms: Dandruff and Plants or Medicinal Plant and Dandruff treatment; and Essential oil and Dandruff. Results Because the current therapies are not able to completely remove dandruff, herbal extracts with better effectiveness and fewer side effects are being used in the pharmaceutical and cosmetic industries. Nowadays, there are many different types of herbal antidandruff shampoo. They are effective and safe without the side effects of chemical agents. Recently, a large number of physicians have turned to herbal medicine. Clinical evidence of the therapeutic effects from herbal products has led to the study of many more herbs for their therapeutic roles. Conclusion Herbal are now accepted to act a essential role in the development of favourable therapeutics, either alone or in combination with conventional antibiotics. However, the major challenges to this include finding compounds with satisfactorily lower MICs, low toxicity, and high bioavailability for effective and safe use in humans and animals.
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Introduction Onychomycosis, also called tinea unguium, is a common fungal infection affecting the nails. After dermatophytes, Candida species are recognized as second-line pathogens responsible for this infection. The treatment of onychomycosis requires a long time and is associated with high rates of recurrence. Antifungal medicines which are conjugated with gold (Au-NPs) nanoparticles are the possible platforms for the reduction of drug resistance. Methods In the present study, we reported the in vitro antifungal activity of itraconazole (ITZ) – Au conjugates, time-kill studies, and biofilm-producing ability of six ITZ-resistant C. glabrata. Results 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide (MTT) quantitative results revealed that four out of six resistant isolates studied were able to form biofilms in vitro. ITZ-Au conjugates were more effective than ITZ or Au nanoparticles alone, and the time-kill tests pointed to the suitable effect of ITZ-Au conjugate. Conclusion The present study concluded that ITZ-Au conjugates have an inhibitory effect on the biofilm of resistant C. glabrata isolates. Further studies are needed to compare the ex vivo onychomycosis model.
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Tinea pedis is a common condition seen in clinical practice and has a significant impact on quality of life. Recommendations of over-the-counter antifungal products based on consumer preferences may guide dermatologists in treating patients with tinea pedis and preventing onychomycosis recurrences. Our study aimed to determine consumer preferences of antifungal products for tinea pedis, focusing on features that may guide purchases and usage. A search was performed for antifungal products used to treat athlete’s foot on Amazon.com as of 2018, and the top one percentile of over-the-counter products were sorted by rating and number of reviews. Functionality was the most cited positive feature (42% of comments) followed by cosmetic characteristics (14%). The median price of all products was $1.80 (range $0.33 - $95.42), with solutions and balms associated with higher costs and soaks being the least expensive. Our study showed that the range of antifungal products available online for treatment and prevention of tinea pedis is large and variable in terms of type/vehicle, price, and ingredients. Physicians must counsel patients on the efficacy and Food and Drug Administration approval of listed ingredients, especially for those products associated with numerous supplementary claims.
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Onychomycosis is a common condition and accounts for 50% of all nail diseases. Dermatophyte organisms are responsible for most cases of toenail onychomycosis, with Trichophyton rubrum and Trichophyton mentagrophytes, representing the first and second most commonly isolated organisms in the United States (US). Nondermatophyte molds, such as Fusarium and Acremonium and yeasts such as Candida parapsilosis are responsible for the remaining cases. This chapter will review treatment options for onychomycosis for adults and children, including nail avulsion, available topical therapies, as well as those in clinical trials. Lasers, photodynamic therapy, devices, such as non-thermal plasma, and over the counter treatments will also be discussed.
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Background Norway spruce (Picea abies) produces resin to protect against decomposition by microbial pathogens. In vitro tests showed that spruce resin has antifungal properties against dermatophytes known to cause nearly 90% of onychomycosis in humans.Objectives To confirm previous in vivo observations that a topical resin lacquer provides mycological and clinical efficacy, and to compare this lacquer with topical amorolfine hydrochloride lacquer and systemic terbinafine for treating dermatophyte toenail onychomycosis.Methods In this prospective, randomized, controlled, investigator-blinded study, 73 patients with onychomycosis were randomized to receive topical 30% resin lacquer once daily for 9 months, topical 5% amorolfine lacquer once weekly for 9 months, or 250 mg oral terbinafine once daily for 3 months. Primary outcome measure was complete mycological cure at 10 months. Secondary outcomes were clinical efficacy, cost-effectiveness, and patient compliance.ResultsAt 10 months, complete mycological cure rates with resin, amorolfine, and terbinafine treatments were 13% (95% confidence interval [CI] 0–28), 8% (95%CI 0–19), and 56% (95% CI 35–77), respectively (P≤0.002). At 10 months, clinical responses were complete in 4 (16%) patients treated with terbinafine and partial in 7 (30%), 7 (28%), and 9 (36%) patients treated with resin, amorolfine, and terbinafine, respectively (P<0.05). Resin, amorolfine, and terbinafine treatments cost €41.6, €56.3, and €52.1, respectively, per patient (P<0.0001).Conclusions Topical 30% resin lacquer and topical 5% amorolfine lacquer provided similar efficacy for treating dermatophyte toenail onychomycosis. However, orally administered terbinafine was significantly more effective in terms of mycological cure and clinical outcome than either topical therapy in 10-month follow-up.This article is protected by copyright. All rights reserved.
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Onychomycosis is a common disorder, and high prevalence figures are commonly cited in the literature. Evaluate the prevalence of onychomycosis based on published studies. Relevant studies were identified in Medline by using specific search criteria. Eleven population-based and 21 hospital-based studies were identified. The mean prevalence in Europe and North America was 4.3% [95% Confidence Interval (CI): 1.9-6.8] in the population-based studies, but it was 8.9% (95% CI: 4.3-13.6) for the hospital-based studies. Both population-based and hospital-based studies showed that onychomycosis is more common in toenails and is seen more frequently in males. The main causative agent was a dermatophyte in 65.0% (95% CI: 51.9-78.1) of the cases. Trichophyton rubrum was the single most common fungus and was cultured on average in 44.9% of the cases (95% CI: 33.8-56.0). Moulds were found on average in 13.3% (95% CI: 4.6-22.1) and yeasts in 21.1% (95% CI: 11.0-31.3). We may not have been able to locate all studies. Onychomycosis is a common disorder, but it may not be as common as cited in the literature, because hospital-based studies might overestimate the prevalence of onychomycosis. It is more frequent in males, and toenails are more commonly affected. Dermatophytes, particularly T. rubrum, are the main causative agents.
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The "in vitro" antifungal activity of ozonized sunflower oil (Bioperoxoil®) was tested on 101 samples of yeasts originating from onychomycosis using the disk diffusion method. The oil was efficacious against several clinical fungal strains: Candida parapsilosis, Candida albicans, Trichosporon asahii, Candida tropicalis and Candida guilliermondii.
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In in vitro tests, natural coniferous resin from the Norway spruce (Picea abies) is strongly antifungal. In this observational study, we tested the clinical effectiveness of a lacquer composed of spruce resin for topical treatment of onychomycosis. Thirty-seven patients with clinical diagnosis of onychomycosis were enrolled into the study. All patients used topical resin lacquer treatment daily for 9 months. A mycological culture and potassium hydroxide (KOH) stain were done from nail samples in the beginning and in the end of the study. Treatment was considered effective, if a mycological culture was negative and there was an apparent clinical cure. At study entry, 20 patients (20/37; 54%; 95% CI: 38-70) had a positive mycological culture and/or positive KOH stain for dermatophytes. At study end, the result of 13 patients was negative (13/19; 68%; 95% CI: 48-89). In one case (1/14; 7%; 95% CI: 0-21) the mycological culture was initially negative, but it turned positive during the study period. By 14 compliant patients (14/32; 44%; 95% CI: 27-61), resin lacquer treatment was considered clinically effective: complete healing took place in three cases (9%) and partial healing in 11 cases (85%). The results indicate some evidence of clinical efficacy of the natural coniferous resin used for topical treatment of onychomycosis.
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Detailed GC and GC-MS analyses of oil of Melaleuca have identified several constituents not previously reported from Melaleuca alternifolia and clarified some earlier assignments. The range, mean, and coefficient of variation for the principle constituents in 800 typical samples are presented along with the compositions of several substandard oils. Isolation and storage procedures affecting the chemical composition of the oil are reported. Ethanolic extraction of mature leaves gave solutions suitable for direct injection into a gas chromatograph for the qualitative determination of tea tree oil. Comparison with conventional steam distillation showed that this technique was suitable for preliminary analysis of tea tree oil yield and quality.
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This review presents an overview about pharmaceutical and cosmetic topical products containing polymeric nanoparticles (nanospheres and nanocapsules), reporting the main preparation and characterization methods and the studies of penetration and transport of substances through the skin. The penetration and transport extent of those systems through the skin depends on the ingredients chemical composition, on the encapsulation mechanism influencing the drug release, on the size of nanoparticles and on the viscosity of the formulations. The polymeric nanoparticles are able to modify the activity of drugs, delay and control the drug release, and increase the drug adhesivity or its time of permanence in the skin. Briefly, the nanoparticles can be useful as reservoirs of lipophilic drugs to deliver them in the stratum corneum becoming an important strategy to control their permeation into the skin.
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The results of the use of ozonised sunflower oil (OLEOZON(®)) in the treatment of onychomycosis, based on its known antimycotic action and good skin tolerance, by means of a controlled randomised phase III assay are presented. A total of 400 outpatients were randomly divided into two groups: experimental, treated with topical OLEOZON(®), two times per day and control, treated also two times per day, with ketoconazole cream 2%, for 3 months. A patient was considered cured when the sick nails regained the normal colour, growth and thickness, with a negative mycological study. In the experimental group, a regression of signs was achieved from the first month of treatment, while in the control group, it was obtained after the third month of treatment. All patients treated with OLEOZON(®) had improvement in their condition (9.5%) or were cured (90.5%). However, in the control group, only 13.5% of patients were cured, 27.5% improved and 59% remained the same, with significant differences between both the groups. After 1 year of follow-up, experimental and control groups presented 2.8% and 44.4% of relapses, respectively. Topical OLEOZON(®) demonstrated effectiveness in the treatment of onychomycosis, superior to that of ketoconazole. No side effects were observed.
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Resin salve prepared from Norway spruce (Picea abies) has been used for centuries in traditional medicine to treat skin diseases. The authors studied with transmission and scanning electron microscopy, and with electron physiology, changes in cell wall and cell membrane of Staphylococcus aureus after exposure of the bacterial cultures to resin. After exposure, cell wall thickening, cell aggregation, changed branching of fatty acids, and dissipation of membrane potential of the bacterial cells were observed. The authors conclude that spruce resin affects the cell viability via changes in the cell wall and membrane, and impairs, thereby, the synthesis of energy in the bacteria.
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The prevalence of onychomycosis, the most frequent cause of nail disease, ranges from 2% to 13%. Standard treatments include debridement, topical medications, and systemic therapies. This study assesses the efficacy and tolerability of topical application of 1% clotrimazole solution compared with that of 100% Melaleuca alternifolia (tea tree) oil for the treatment of toenail onychomycosis. A double-blind, multicenter, randomized controlled trial was performed at two primary care health and residency training centers and one private podiatrist's office. The participants included 117 patients with distal subungual onychomycosis proven by culture. Patients received twice-daily application of either 1% clotrimazole (CL) solution or 100% tea tree (TT) oil for 6 months. Debridement and clinical assessment were performed at 0, 1, 3, and 6 months. Cultures were obtained at 0 and 6 months. Each patient's subjective assessment was also obtained 3 months after the conclusion of therapy. The baseline characteristics of the treatment groups did not differ significantly. After 6 months of therapy, the two treatment groups were comparable based on culture cure (CL = 11%, TT = 18%) and clinical assessment documenting partial or full resolution (CL = 61%, TT = 60%). Three months later, about one half of each group reported continued improvement or resolution (CL = 55%; TT = 56%). All current therapies have high recurrence rates. Oral therapy has the added disadvantages of high cost and potentially serious adverse effects. Topical therapy, including the two preparations presented in this paper, provide improvement in nail appearance and symptomatology. The use of a topical preparation in conjunction with debridement is an appropriate initial treatment strategy.
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The essential oil of Melaleuca alternifolia (tea tree) exhibits broad-spectrum antimicrobial activity. Its mode of action against the Gram-negative bacterium Escherichia coli AG100, the Gram-positive bacterium Staphylococcus aureus NCTC 8325, and the yeast Candida albicans has been investigated using a range of methods. We report that exposing these organisms to minimum inhibitory and minimum bactericidal/fungicidal concentrations of tea tree oil inhibited respiration and increased the permeability of bacterial cytoplasmic and yeast plasma membranes as indicated by uptake of propidium iodide. In the case of E. coli and Staph. aureus, tea tree oil also caused potassium ion leakage. Differences in the susceptibility of the test organisms to tea tree oil were also observed and these are interpreted in terms of variations in the rate of monoterpene penetration through cell wall and cell membrane structures. The ability of tea tree oil to disrupt the permeability barrier of cell membrane structures and the accompanying loss of chemiosmotic control is the most likely source of its lethal action at minimum inhibitory levels.
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The effect of tea tree oil (TTO) on the formation of germ tubes by Candida albicans was examined. Two isolates were tested for germ tube formation (GTF) in the presence of TTO concentrations (% v/v) ranging from 0.25% (1/2 minimum inhibitory concentration [MIC]) to 0.004% (1/128 MIC). GTF at 4 h in the presence of 0.004 and 0.008% (both isolates) and 0.016% (one isolate) TTO did not differ significantly (P > 0.05) from controls. At all other concentrations at 4 h, GTF differed significantly from controls (P < 0.01). A further eight isolates were tested for GTF in the presence of 0.031% TTO, and at 4h the mean GTF for all 10 isolates ranged 10.0-68.5%. Two isolates were examined for their ability to form germ tubes after 1 h of pre-exposure to several concentrations of TTO, prior to induction of germ tubes in horse serum. Cells pre-exposed to 0.125 and 0.25% TTO formed significantly fewer germ tubes than control cells at 1 h (P < 0.05), but only those cells pre-exposed to 0.25% differed significantly from control cells at later time points (P < 0.01). GTF by C. albicans is affected by the presence of, or pre-exposure to, sub-inhibitory concentrations of TTO. This may have therapeutic implications.
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The ozonised sunflower oil, Bioperoxoil, was tested for its antimicrobial activity against some pathological strains in vitro together with its healing potential against Staphylococcus aureus in vivo. Bioperoxoil was tested against S. aureus, Pseudomonas aeroginosa, Candida albicans, S. typhimurium and Escherichia coli suspensions using the agar diffusion method. Healing experiments were carried out with Wistar rats through topical application of 3.5 mg/ml of the ozonised oil up to the 7th day after inoculation with S. aureus. Bioperoxoil showed anti-inflammatory effects against all strains tested, with MIC values ranging from 2.0 to 3.5 mg/ml. Bioperoxoil also demonstrated protective effects on skin connective tissue and to enhance wound healing during the treatment, as compared to a neomycin-clostebol association used as a positive control. The overall results indicated a significant antimicrobial activity, anti-inflammatory and wound-healing properties for Bioperoxoil, as compared to other antimicrobial agents commercially available.
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Resin salve made from Norway spruce (Picea abies) is traditionally used in folk medicine to heal skin ulcers and infected wounds. Its antimicrobial properties were studied against certain human bacteria important in infected skin wounds. The sensitivity of the resin against Gram-positive and Gram-negative bacteria was studied in vitro by methods that are routinely used in microbiology laboratories. The resin salve exhibited a bacteriostatic effect against all tested Gram-positive bacteria but only against Proteus vulgaris of the Gram-negative bacteria. Interestingly, the resin inhibited the growth of bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE), both on agar plates and in culture media. The study demonstrated antimicrobial activity of the resin salve and provided objective evidence of its antimicrobial properties. It gives some explanations why the traditional use of home-made resin salve from Norway spruce is experienced as being effective in the treatment of infected skin ulcers.
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Section I: The Normal Nail. Historical Aspects of Nail Disease. Structure and Function. Embryology. Basic Science of the Nail Unit. Histology and Histopathology. Section II: The Abnormal Nail. An Approach to Initial Examination of the Nail. Pediatric Disease. The Nail in Older Individuals. Onychomycosis. Nonfungal Infections and Paronychia. Dermatologic Diseases of the Nail Unit. Pigmentation Abnormalities. Nails in Systemic Disease. Nail Changes Secondary to Systemic Drugs and Ingestants. Tumours. Nail Cosmetics. Occupational Disease. Podiatric Approach to Onychomycosis. Pedal Biomechanics and Toenail Disease. Subungual Exostosis and Nail Disease and Radiologic Aspects. Surgery. Advanced Surgery. Appendix I: Glossary. Appendix II: The Possibility of HIV Transmission By Manicure.
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The aim of this study was to evaluate, for the first time, the antifungal efficacy of nanocapsules and nanoemulsions containing Melaleuca alternifolia essential oil (tea tree oil) in an onychomycosis model. The antifungal activity of nanostructured formulations was evaluated against Trichophyton rubrum in two different in vitro models of dermatophyte nail infection. First, nail powder was infected with T. rubrum in a 96-well plate and then treated with the formulations. After 7 and 14 days, cell viability was verified. The plate counts for the samples were 2.37, 1.45 and 1.0 log CFU mL(-1) (emulsion, nanoemulsion containing tea tree oil and nanocapsules containing tea tree oil, respectively). A second model employed nails fragments which were infected with the microorganism and treated with the formulations. The diameter of fungal colony was measured. The areas obtained were 2.88 ± 2.08 mm(2), 14.59 ± 2.01 mm(2), 40.98 ± 2.76 mm(2) and 38.72 ± 1.22 mm(2) for the nanocapsules containing tea tree oil, nanoemulsion containing tea tree oil, emulsion and untreated nail, respectively. Nail infection models demonstrated the ability of the formulations to reduce T. rubrum growth, with the inclusion of oil in nanocapsules being most efficient.
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This in vitro study assessed the antifungal activity of a well-known and widely used essential oil, Melaleuca alternifolia (Australian tea tree oil), against the ubiquitous dermatophyte Trichophyton rubrum. The literature has reported the antifungal properties of M. alternifolia citing the minimum inhibitory concentration needed to secure this effect. Following a study which determined that the oil was a potent antifungal and that the inverse relationship between essential oil concentration and fungal growth was not influenced by random variability (P = 0.05); the minimum inhibitory concentration (MIC) was then determined at 0.1% (v/v). This MIC is approximately 10% lower than results from other similar studies, and could have important therapeutic significance.
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Resins (rosin, pitch) are natural products of the coniferous trees and are antimicrobial against a wide range of microbes. The antifungal effectiveness of resin, purified from Norway spruce (Picea abies), was studied against human pathogenic fungi and yeasts with the agar plate diffusion tests and electron microscopy (EM). The fungistatic effect of these resin mixtures (resin salves) was tested against a set of Candida yeasts, dermatophytes, and opportunistic fungi. Transmission and scanning EM was done from samples of fungi (Trichophyton mentagrophytes). In agar diffusion tests, the resin was strongly antifungal against all dermatophytes tested, e.g., against all fungi of the genus Trichophyton, but it was not antifungal against the Candida yeasts or against the opportunistic fungi tested. According to EM, resin caused damages in the cell hyphae and cell wall structures. We conclude that, in the agar plate diffusion test, coniferous resins are strongly fungistatic against the dermatophytic fungi only.
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Sipponen A, Laitinen K. Antimicrobial properties of natural coniferous rosin in the European Pharmacopoeia challenge test. APMIS 2011; 119: 720–24. Rosins (resins) are natural products of the coniferous trees. Purified rosin from the trunk of Norway spruce (Picea abies) is antibacterial against the gram-positive bacteria, but not against the gram-negative bacteria in agar plate diffusion test. In this study, we examined the antimicrobial properties of the coniferous rosin against bacteria and yeasts using the European Pharmacopoeia (EP) challenge test. The microbes tested were Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, and Candida albicans. To prepare challenge media, purified rosin was mixed with a biologically inert salve in varying concentrations. The microbes were inoculated (5 × 105 microbes (bacteria) or 5 × 104 microbes (yeast, C.albicans)) into 10 g of the rosin-containing challenge medium for 14 days at maximum. Samples were taken from the media for re-cultivation of the microbes at time intervals of 1 h, 24 h, 4, 7, and 14 days. The microbicidal efficacy of the challenge media was estimated by reduction of the number of the colony forming units (CFU) of microbes in the test samples. A reduction of more than 103 CFU for bacteria and 102 CFU for fungi in 7 days was considered to indicate a significant microbicidal action. Pure rosin was antimicrobial within 24 h against all microbes tested. The 0.5% rosin-salve medium (w/w) did not differ in microbicidal effects from the rosin-free salve medium (control). A raise of the rosin concentration resulted in increase of the microbicidal effect of the rosin-salve medium against all micro-organisms tested. Rosin concentration of 10% (w/w) in the medium significantly reduced the colonization of S. aureus (including MRSA) within 24 h and significantly reduced the colonization of all other micro-organisms within 4 days. Rosin is strongly microbicidal against a wide range of microbes, against both gram-positive and gram-negative bacteria, and against C. albicans, in the EP challenge test. The minimum concentration of rosin is 10% (w/w) to prevent the preservation of the microbes in the rosin-salve media.
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The classification of onychomycosis, infection of the nail apparatus caused by fungi, has changed over time with the recognition of new pathways of nail infection, new organisms, and new variations in the appearance of diseased infected nail. Taking into account published descriptions of nail morphology in fungal infection, the following forms of onychomycosis are recognized: distal and lateral subungual, superficial, endonyx, proximal subungual, mixed, totally dystrophic, and secondary onychomycosis. These can be subdivided, where appropriate, by color and pattern of nail plate change. The purpose of the revised classification is to provide a framework to assist selection of treatment, estimate prognosis, and evaluate new diagnostic methods.
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current medication treatments for onychomycosis have less than full cure-rate efficacy and have the potential for adverse side effects. Vicks VapoRub (The Proctor & Gamble Company, Cincinnati, OH) has been advocated in the lay literature as an effective treatment for onychomycosis. This pilot study tested Vicks VapoRub as a safe, cost-effective alternative for treating toenail onychomycosis. eighteen participants were recruited to use Vicks VapoRub as treatment for onychomycosis. Participants were followed at intervals of 4, 8, 12, 24, 36, and 48 weeks; digital photographs were obtained during initial and follow-up visits. Primary outcome measures were mycological cure at 48 weeks and clinical cure through subjective assessment of appearance and quantifiable change in the area of affected nail by digital photography analysis. Patient satisfaction was a secondary outcome, measured using a single-item questionnaire scored by a 5-point Likert scale. fifteen of the 18 participants (83%) showed a positive treatment effect; 5 (27.8%) had a mycological and clinical cure at 48 weeks; 10 (55.6%) had partial clearance, and 3 (16.7%) showed no change. All 18 participants rated their satisfaction with the nail appearance at the end of the study as "satisfied" (n = 9) or "very satisfied" (n = 9). Vicks VapoRub seems to have a positive clinical effect in the treatment onychomycosis.
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The plant species Ageratina pichinchensis has been used, for many years, in Mexican traditional medicine for the treatment of superficial mycosis. This study compared the therapeutic effectiveness and tolerability of two concentrations of the standardized extract from Ageratina pichinchensis (12.6 and 16.8%) on patients with clinical and mycological diagnosis of mild and moderate onychomycosis. Two identical phytopharmaceuticals (containing the standardized extract from Ageratina pichinchensis) in nail lacquer solution for topical administration were evaluated in a double-blind clinical trial. Treatments were administered for 6 months to patients distributed in two groups. Of 122 patients who agreed to participate in the study, 103 (84.4%) concluded the treatment. The therapeutic effectiveness exhibited by the 12.6% Ageratina pichinchensis extract was 67.2%, while that of the 16.8% Ageratina pichinchensis extract was 79.1%. Regarding clinical evolution, analysis of results at the end of treatment evidenced that the 16.8% concentration possesses higher therapeutic effectiveness with a significant statistical difference (p=0.010). No treatment produced side effects. Both concentrations of phytopharmaceuticals possess high rates of effectiveness on patients with mild and moderate onychomycosis, and the formulation with a 16.8% concentration possesses higher effectiveness.
Article
The composition and antifungal activity of clove essential oil (EO), obtained from Syzygium aromaticum, were studied. Clove oil was obtained commercially and analysed by GC and GC-MS. The EO analysed showed a high content of eugenol (85.3 %). MICs, determined according to Clinical and Laboratory Standards Institute protocols, and minimum fungicidal concentration were used to evaluate the antifungal activity of the clove oil and its main component, eugenol, against Candida, Aspergillus and dermatophyte clinical and American Type Culture Collection strains. The EO and eugenol showed inhibitory activity against all the tested strains. To clarify its mechanism of action on yeasts and filamentous fungi, flow cytometric and inhibition of ergosterol synthesis studies were performed. Propidium iodide rapidly penetrated the majority of the yeast cells when the cells were treated with concentrations just over the MICs, meaning that the fungicidal effect resulted from an extensive lesion of the cell membrane. Clove oil and eugenol also caused a considerable reduction in the quantity of ergosterol, a specific fungal cell membrane component. Germ tube formation by Candida albicans was completely or almost completely inhibited by oil and eugenol concentrations below the MIC values. The present study indicates that clove oil and eugenol have considerable antifungal activity against clinically relevant fungi, including fluconazole-resistant strains, deserving further investigation for clinical application in the treatment of fungal infections.
Article
Diabetes mellitus may be associated with serious sequelae, such as renal disease, retinopathy, and diabetic foot. A recent large prospective study has shown that onychomycosis is among the most significant predictors of foot ulcer. As the severity of onychomycosis may be associated with the length of time the individual has had the infection, early intervention is advisable owing to the progressive nature of the fungal infection. If left untreated, toenails can become thick, causing pressure and irritation, and thus act as a trigger for more severe complications. In the treatment of onychomycosis, compliance and drug interactions are important considerations, as diabetic patients frequently take concomitant medications. Terbinafine and itraconazole have been investigated for the treatment of onychomycosis in diabetic patients and have been shown to have efficacy and safety profiles comparable to those in the nondiabetic population. Data from clinical trials and postmarketing surveillance suggest that drug interactions resulting in hypoglycemia may not be an important issue when itraconazole and terbinafine are used to treat diabetic patients receiving concomitant hypoglycemic medications. Patient advice and education in improved foot care are an integral part of onychomycosis management, and help achieve long-term cure and reduce the complications of diabetic foot.
Article
The nails serve several important functions and, when they are infected by fungal organisms, these functions are severely impaired. In addition, the quality of life, in terms of self-esteem and social interaction, is adversely affected when fungal nail infections are present. Finally, when finger and/or toenails are abnormal this may interfere with patients' occupations.
Article
Investigation on the roots of Helianthella quinquenervis (Hook.) A. Gray (Asteraceae), led to the isolation of one new benzofuran (6-methoxy-tremetone (1)) and a new prenylacetophenone (4-beta-D-(glucopyranosyloxy)-3-[3-methoxy-trans-isopenten-1 -yl] acetophenone (3)). In addition, 6-hydroxy-3-methoxytremetone (2), encecalin (6), euparin (5), demethylencecalin (4), and angelic acid were obtained. Structural assignments of the isolated compounds were based on spectroscopic and spectrometric analysis. Natural products 1-4 showed marginal cytotoxicity against three human tumor cell lines [MCF-7, A-549, and HT-29]. Compounds 4 and 6 inhibited the radicle growth of Amaranthus hypochondriacus and Echinochloa crusgalli. Furthermore, substances 4-6 exhibited antifungal activity against Trichophyton mentagrophytes.
Article
Tea-tree oil (oil of Melaleuca alternifolia) has recently received much attention as a natural remedy for bacterial and fungal infections of the skin and mucosa. As with most naturally occurring agents, claims of effectiveness have been only anecdotal; however, several published studies have recently demonstrated tea-tree oil's antibacterial activity. This study was conducted to determine the activity of tea-tree oil against 58 clinical isolates: Candida albicans (n = 10), Trichophyton rubrum (n = 8), Trichophyton mentagrophytes (n = 9), Trichophyton tonsurans (n = 10), Aspergillus niger (n = 9), Penicillium species (n = 9), Epidermophyton floccosum (n = 2), and Microsporum gypsum (n = 1). Tea-tree oil showed inhibitory activity against all isolates tested except one strain of E floccosum. These in vitro results suggest that tea-tree oil may be useful in the treatment of yeast and fungal mucosal and skin infections.
Article
The prevalence of onychomycosis, a superficial fungal infection that destroys the entire nail unit, is rising, with no satisfactory cure. The objective of this randomized, double-blind, placebo-controlled study was to examine the clinical efficacy and tolerability of 2% butenafine hydrochloride and 5% Melaleuca alternifolia oil incorporated in a cream to manage toenail onychomycosis in a cohort. Sixty outpatients (39 M, 21 F) aged 18-80 years (mean 29.6) with 6-36 months duration of disease were randomized to two groups (40 and 20), active and placebo. After 16 weeks, 80% of patients using medicated cream were cured, as opposed to none in the placebo group. Four patients in the active treatment group experienced subjective mild inflammation without discontinuing treatment. During follow-up, no relapse occurred in cured patients and no improvement was seen in medication-resistant and placebo participants.
Article
Although ozone therapy has been used as an alternative medical approach for four decades, it has encountered scepticism, if not outright objection, by orthodox medicine. This prejudice is not unjustified because ozone therapy often has been used without rational basis or appropriate controls. With the advent of precise medical ozone generators, it is now possible to evaluate some mechanisms of action and possible toxicity. In contrast with the respiratory tract, human blood exposed to appropriate ozone concentrations is able to tame its strong oxidant properties and neither acute nor chronic side effects have ensued in millions of patients treated with ozonated autohaemotherapy. This paper summarises studies aimed at clarifying biological effects, defining any possible damage, the therapeutic window, and suitable doses able to express therapeutic activity. Although an unfashionable and unpopular approach, it is hoped that orthodox medicine will help to critically assess the validity of ozone therapy.
Article
To evaluate the antimicrobial effect of the ozonized sunflower oil (Oleozon) on different bacterial species isolated from different sites. The effect of Oleozon on Mycobacteria, staphylococci, streptococci, enterococci, Pseudomonas and Escherichia coli was tested. The sunflower oil was ozonized at the Centro de Investigaciones del Ozone (CENIC, Havana, Cuba) by an ozone generator. MICs were determined by the agar dilution method. For Mycobacteria, the MIC of Oleozon was determined on solid medium by a microdrop agar proportion test. Oleozon showed antimicrobial activity against all strains analysed, with an MIC ranging from 1.18 to 9.5 mg ml-1. Oleozon showed a valuable antimicrobial activity against all micro-organisms tested. Results suggest that Mycobacteria are more susceptible to Oleozon than the other bacteria tested. The wide availability of sunflower oil makes Oleozon a competitive antimicrobial agent. These results should prompt the setting up of some clinical trials to compare Oleozon with other antimicrobial agents.
Article
The antifungal activity of Melaleuca alternifolia Maiden (Myrtaceae) essential oil against yeasts (Candida spp., Schizosaccharomyces pombe, Debaryomyces hansenii) and dermatophytes (Microsporum spp. and Tricophyton spp.) is reported. We focused on the ability of tea tree oil to inhibit Candida albicans conversion from the yeast to the pathogenic mycelial form. Moreover we carried out broth microdilution test and contact tests to evaluate the killing time. M. alternifolia essential oil inhibited the conversion of C. albicans from yeast to the mycelial form at a concentration of 0.16% (v/v). The minimum inhibitory concentrations (MICs) ranged from 0.12% to 0.50% (v/v) for yeasts and 0.12% to 1% (v/v) for dermatophytes; the cytocidal activity was generally expressed at the same concentration. These results, if considered along with the lipophilic nature of the oil which enables it to penetrate the skin, suggest it may be suitable for topical therapeutic use in the treatment of fungal mucosal and cutaneous infections.
Article
Tea tree oil has been shown to have activity against dermatophytes in vitro. We have conducted a randomized, controlled, double-blinded study to determine the efficacy and safety of 25% and 50% tea tree oil in the treatment of interdigital tinea pedis. One hundred and fifty-eight patients with tinea pedis clinically and microscopy suggestive of a dermatophyte infection were randomized to receive either placebo, 25% or 50% tea tree oil solution. Patients applied the solution twice daily to affected areas for 4 weeks and were reviewed after 2 and 4 weeks of treatment. There was a marked clinical response seen in 68% of the 50% tea tree oil group and 72% of the 25% tea tree oil group, compared to 39% in the placebo group. Mycological cure was assessed by culture of skin scrapings taken at baseline and after 4 weeks of treatment. The mycological cure rate was 64% in the 50% tea tree oil group, compared to 31% in the placebo group. Four (3.8%) patients applying tea tree oil developed moderate to severe dermatitis that improved quickly on stopping the study medication.
Article
Eighteen plant extracts from nine traditional Mexican medicinal plants were tested for antifungal activity against two dermatophyte fungal species (Trichophyton mentagrophytes and Trichophyton rubrum), one non-dermatophyte (Aspergillus niger), and one yeast (Candida albicans). The strongest effect was manifested by the hexane extracts from Eupatorium aschenbornianum and Sedum oxypetalum, as well as the methanol extracts from Lysiloma acapulcensis and Annona cherimolia.
Article
To investigate the in vitro antifungal activity of the components of Melaleuca alternifolia (tea tree) oil. Activity was investigated by broth microdilution and macrodilution, and time kill methods. Components showing the most activity, with minimum inhibitory concentrations and minimum fungicidal concentrations of < or =0.25%, were terpinen-4-ol, alpha-terpineol, linalool, alpha-pinene and beta-pinene, followed by 1,8-cineole. The remaining components showed slightly less activity and had values ranging from 0.5 to 2%, with the exception of beta-myrcene which showed no detectable activity. Susceptibility data generated for several of the least water-soluble components were two or more dilutions lower by macrodilution, compared with microdilution. All tea tree oil components, except beta-myrcene, had antifungal activity. The lack of activity reported for some components by microdilution may be due to these components becoming absorbed into the polystyrene of the microtitre tray. This indicates that plastics are unsuitable as assay vessels for tests with these or similar components. This study has identified that most components of tea tree oil have activity against a range of fungi. However, the measurement of antifungal activity may be significantly influenced by the test method.
Article
The treatment of onychomycosis has improved in recent years and many patients can now expect a complete and lasting cure. However, for up to 25% of patients, persistent disease remains a problem, thus presenting a particular challenge to the clinician. For these patients, it is obviously important to ensure that a correct diagnosis of onychomycosis has been made, as misdiagnosis will inevitably jeopardize the perception of therapeutic effectiveness. Although onychomycosis accounts for about 50% of all nail diseases seen by physicians, nonfungal causes of similar symptoms include repeated trauma, psoriasis, lichen planus, local tumours vascular disorders and inflammatory diseases. Predisposing factors that contribute to a poor response to topical and/or oral therapy include the presence of a very thick nail, extensive involvement of the entire nail unit, lateral nail disease and yellow spikes. However, poor penetration of systemic agents to the centre of infection, or the inability of topical agents to diffuse between the surface of the nail plate and the active disease below, probably contributes to this.
Article
The increasing recognition and importance of fungal infections, the difficulties encountered in their treatment and the increase in resistance to antifungals have stimulated the search for therapeutic alternatives. Essential oils have been used empirically. The essential oils of Thymus (Thymus vulgaris, T. zygis subspecies zygis and T. mastichina subspecies mastichina) have often been used in folk medicine. The aim of the present study was to evaluate objectively the antifungal activity of Thymus oils according to classical bacteriological methodologies - determination of the minimal inhibitory concentration (MIC) and the minimal lethal concentration (MLC) - as well as flow cytometric evaluation. The effect of essential oils upon germ tube formation, an important virulence factor, was also studied. The mechanism of action was studied by flow cytometry, after staining with propidium iodide. The chemical composition of the essential oils was investigated by gas chromatography (GC) and gas chromatography/mass spectroscopy (GC/MS). The antifungal activity of the major components (carvacrol, thymol, p-cymene and 1,8-cineole) and also possible interactions between them were also investigated. The essential oils of T. vulgaris and T. zygis showed similar antifungal activity, which was greater than T. mastichina. MIC and MLC values were similar for all the compounds tested. At MIC values of the essential oils, propidium iodide rapidly penetrated the majority of the yeast cells, indicating that the fungicidal effect resulted primarily from an extensive lesion of the cell membrane. Concentrations below the MIC values significantly inhibited germ tube formation. This study describes the potent antifungal activity of the essential oils of Thymus on Candida spp., warranting future therapeutical trials on mucocutaneous candidosis.
Article
The antibiotic effect of the active ingredients in Meijer medicated chest rub (eucalyptus oil, camphor and menthol) as well as the inactive ingredients (thymol, oil of turpentine, oil of nutmeg and oil of cedar leaf) were studied in vitro using the fungal pathogens responsible for onychomycosis, such as the dermatophytes Tricophyton rubrum, Trichophyton mentagrophytes, Microsporum canis, Epidermophyton fl occosum and Epidermophyton stockdale. The zones of inhibition data revealed that camphor (1). menthol (2). thymol (3). and oil of Eucalyptus citriodora were the most efficacious components against the test organisms. The MIC(100) for mixtures of these four components in various carrier solvents revealed that formulations consisting of 5 mg/mL concentrations of each have a potential to be efffective in controlling onychomycosis.
Article
Ageratina pichinchensis has been used for many years in Mexican traditional medicine for the treatment of superficial mycosis. Previous studies have demonstrated the antifungal effectiveness of a hexane extract from aerial parts of this plant on in vitro cultures of Candida albicans, Aspergillium niger, Trichophyton mentagrophytes, and Trichophyton rubrum. To compare the effectiveness and tolerability of A. pichinchensis with ketoconazole in patients with the clinical and mycological diagnosis of tinea pedis, we carried out a double-blind pilot study. The experimental group was treated topically with a cream containing A. pichinchensis standardized extract (10 %), while the control group was administered a similarly colored cream containing 2 % ketoconazole. All patients were clinically followed weekly for 4 weeks. By means of a mycological examination (direct microscopic detection), the mycological diagnosis of tinea pedis was performed. This technique was also used for evaluating the mycological effectiveness at the end of treatment. A total of 120 patients were included, 60 in each treatment group. Of these, 97 patients were included in the statistical analysis, 51 from the experimental group and 46 controls. The remainder of the patients withdrew from the study due to non-medical causes. Clinical effectiveness was reached in 80.3 and 76 %, while therapeutic success was achieved in 80.3 and 71.7 % of the experimental and control groups, respectively. There were no statistical differences between groups (p = 0.31). Our results suggest the effectiveness and tolerability of a standardized extract from A. pichinchensis in treatment of patients with tinea pedis. Abbreviations MIC:Minimal inhibitory concentration PII:Primary irritation index HPLC:High performance liquid chromatography
Article
Onychomycosis is the most frequent nail disease, which could impair the patient's quality of life. The present study was undertaken to evaluate the impact of toenail onychomycosis on quality of life among Polish population. Three thousand nine-hundred and four (3904: 2269 females and 1635 males) individuals fulfilled an international onychomycosis-specific quality-of-life questionnaire consisting of statements regarding social, emotional and symptoms problems. All patients had toenail onychomycosis confirmed by the positive direct microscopic examination and/or by the positive mycologic culture. Seven hundred and sixty-seven patients simultaneously had fingernail onychomycosis. All patients were divided into subgroups according to sex, age, education level, place of living, type of onychomycosis, number of involved toenails, fingernails involvement, duration of illness and previously used antimycotic therapy. Most of the patients demonstrated significantly reduced quality of life. The degree of life impairment varied between analysed subgroups. Patients with more advanced toenail onychomycosis and with fingernail involvement were more seriously affected. Both social and emotional impairments were more pronounced in female than in male patients, although there were no differences according to symptoms. Moreover, patients with better educational level and people living in towns or cities were more emotionally and socially affected by onychomycosis, although people living in the country or with poorer education level presented with significantly more severe symptoms. Toenail onychomycosis is still a serious medical problem, which can significantly reduce the patient's quality of life.
  • Kerydin
Kerydin [package insert]. Palo Alto, CA: Anacor Pharmaceuticals, Inc; 2014 WWW.CUTIS.COM [published online May 5, 2015]. J Am Acad Dermatol. 2015;73:62-69.