A Promising Strategy for the Treatment of Onychomycosis with Curcumin and Photodynamic Therapy

Onychomycosis is a disease of high incidence in the nail plate and responsible for approximately half of the cases of nail infections. Conventionally, dermatologists prescribe antibiotics and antifungals for long periods for its treatment. The high incidence of this type of infection and the increase of microbial strains resistant to the available drugs have justified the importance of the development of new technologies and treatments. This paper presents the photodynamic therapy as an alternative treatment of onychomycosis. New strategies for the use of curcumin as a photosensitizer and its therapeutic response were investigated in different formulations （gel and emulsion）. Photodynamic therapy is a promising technique by which microorganisms are eliminated by a photosensitizing compound, light and oxygen. It was evaluated in two patients who had developed lesions in the fmgernails caused by onychomycosis for approximately 10 years. The lesions were treated by photodynamic therapy with curcumin. The therapeutic efficacy was observed after a maximum of six photodynamic therapy sessions without any other adjuvant therapy. Curcumin has become more promising than the therapeutic standard as it is a natural and versatible drug for incorporation in different formulations, at low cost and low probability of side effects.

Application of persulfate in low-temperature atmospheric-pressure plasma jet for enhanced treatment of onychomycosis

Fungal infection of human nails,or onychomycosis,affects 10%of the world's adult population,but current therapies have various drawbacks.In this work,we employed a self-made low-temperature plasma(LTP)device,namely,an atmospheric-pressure plasma jet(APPJ)device to treat the nails infected with Trichophyton rubrum(T.rubrum)with the aid of persulfate solution.We found that persulfate solution had a promoting effect on plasma treatment of onychomycosis.With addition of sodium persulfate,the APPJ therapy could cure onychomycosis after several times of treatment.As such,this work has demonstrated a novel and effective approach which makes good use of LTP technique in the treatment of onychomycosis.

Analysis of the Factors Influencing the Therapeutic Effects of Onychomycosis

In order to improve the curative effect of onychomycosis, the factors influencing the therapeutic effects were investigated. 545 cases including 245 males and 300 females, who were diagnosed both clinically and mycologically, were treated by Intraconazole with intermittent pulse therapy. The therapeutic effects were judged by the following observations regularly and analyzed from the factors as follows: age; growing speed of nails; accompanied diseases; family history; trauma of nails; infection ways of the pathogens; manifestation of the injury; pathogens; duration of the treatment. The results showed that the recovery rate was higher in younger patients (P<0.01) with a quicker recovery rate (P<0.001), and a lower recurrent rate (P<0.01), as well as in those with quicker growing speed of new-born nail. Also the patients with WSO and DLSO manifestation had a higher recovery rate. The patients with onychomycosis caused by T. rubrum had a higher recovery rate (P<0 01 to 0.001) no matter whether to prolong the treatment duration. The patients with diabetes mellitus or hyperhidrosis, as well as with positive family history or basic nail diseases such as trauma and paronychia, had a lower recovery rate and the curative effects were not satisfactory. It was concluded that although the single and some DLSO-manifestation nail injury could be cured by internal and external treatments with the help of removing the sick nail and the duration of the treatment could be shortened. The treatment duration should be prolonged in order to increase the curative effects and decrease the recurrence under such conditions as following: old patients above 60 years; patients with low-growing-speed new-borne nails; patients with thumb and big toel injury and ingrowing nai1; patients with diabetes mellitus, hyperhidrosis or Renauld's phenomenon; patients with nail trauma before or during the treatment; patients with PSO or TDO manifestation; patients with onychomycosis caused by Candida or Aspergillus; patients with abnormal new-borne nails of abnormal color, coarse surface or abnormal thickness.

Rapid Visible Improvements in Onychomycosis: An Open-Label Clinical Investigation of Kerasal Nail^TM

Traditional treatments for onychomycosis, a fungal disease primarily affecting the toenails, are associated with poor tolerability or inadequate efficacy. Moreover, because many patients find onychomycosis embarrassing, achieving rapid cosmetic improvements is desirable. Kerasal NailTM is a marketed topical treatment containing propylene glycol, urea and lactic acid. The ability of Kerasal Nail to improve the appearance of an affected nail was investigated in a 4-week open-label study. Patients aged ≥21 years and with 25% to 75% of a big toenail or thumbnail (the “target” nail) affected by clinically suspected onychomycosis (n = 65) were instructed to apply Kerasal Nail to all their affected nails once daily for 4 weeks. After 1, 2 and 4 weeks of treatment, they assessed the appearance of the target nail on a 4-point scale, with a score of ≥2 indicating a minimum of some improvement. They also assessed the nail for improvements in thickening, discoloration, brittleness and softness. Adverse events (AEs) occurring between administration of the first dose of Kerasal Nail and the end of the 4-week treatment period were recorded. 85% of patients (95% confidence interval [CI] 74 to 92) achieved some improvement in the target nail at 4 weeks. Improvement of the target nail was reported by 65% of patients (95% CI 52 to 76) after 1 week of treatment and by 82% of patients (95% CI 70 to 90) after 2 weeks. 55% of patients achieved some improvement in discoloration in the first week of treatment. After 4 weeks of treatment, discoloration, thickening, brittleness and softness were each improved in more than half of patients. Treatment-related AEs were limited to two cases of administration site pain. Overall treatment compliance was 99%. In summary, Kerasal Nail produced very rapid improvements in nail appearance in patients with onychomycosis and was well tolerated.

Proximal White Onychomycosis in an Immunocompetent Patient: A Case Report

Objective: Onychomycosis is a diagnosis of fungal organisms in the nail unit. It frequently occurs in both the immunocompetent and immunocompromised patient. A variant of onychomycosis is proxiaml onychomycosis that occurs on the most proximal aspect of the nail. Proximal onychomycosis is known to be commonly associated with immunocompromised status. Study Design: A case report of a veteran who presented a dermatology clinic with complaint of solitary nail discoloration that was recalcitrant to over-the-counter therapy including topical hydrogen peroxide and foot soaks without improvement. Results and Conclusions: This individual case report demonstrates that pedal proximal onychomycosis can be associated with non-dermatophyte organisms, identified as Fusarium species, in immunocompetent individuals. The finding of pedal proximal onychomycosis caused by a Fusarium non-dermatophytic mold has not been reported. The veteran was successfully cured of the condition with treatment via oral terbinafine for a ninety-day course while monitoring patient’s liver function test for any complications.

Early and Visible Improvements after Application of K101 in the Appearance of Nails Discoloured and Deformed by Onychomycosis

Onychomycosis is a fungal infection of the nails of the fingers and toes and is difficult to cure. A previous 24-week, placebo-controlled study demonstrated that a solution containing propylene glycol, urea and lactic acid (K101) was well-tolerated and effective in the treatment of onychomycosis. Patients who received K101 judged that their condition had improved from Week 2 of treatment onwards. The aim of the current study was to further evaluate and document early visible effects on nail appearance after application of topical K101 in an 8-week baseline-controlled study in 75 patients. Patients graded the appearance of their nail compared with baseline using a four-point scale. Compared with baseline, 91.8% (67/73;95% confidence interval (CI): 83.0%, 96.9%) of the patients experienced at least some improvement in their target nail after 8 weeks of treatment. At Week 2, the proportion showing some improvement was 76.7% (56/73;95% CI: 65.4%, 85.8%) with this number increasing to 87.7% (64/73;95% CI: 77.9%, 94.2%) at Week 4. Proportions of patients reporting less thickened, less discoloured, less brittle and softer nails increased over the course of the study. No safety issues were identified. In conclusion, K101 provided early visible improvements in nails affected by onychomycosis.

Itraconazole and Nail Scraping in the Treatment of Onychomycosis( A open trial of175 cases)

Objective Itraconazole pulse therapy is at lest as efficient as itraconazole continuous treatment for onychomyocsis, but the long term oral antimycotic therapy has potential hepatotoxicity.Methods\ 40% urea paste was thickly applied to each affected nail which was dressed by three cloth adhesive tapes. The urea paste was changed every day or every other day for 5 to 7 days. The sick softened nails were scraped off thoroughly with razer blade. After sick nails were removed, all patients received 200 mg of itraconazole twice a day for seven consecutive days. Results\ Fingernail onychomycosis were cured in 93% (130/140), markedly improved in 6.4% (9/140). Toenail onychomycosis were cured in 82% (29/35), markedly improved in 17.1(6/35). And in a 18 month follow up period, 16(10 2%) of 147 patients had relapses. Conclusion\ The treatment of onychomycosis with oral itraconazole plus nail scraping is as effective as that of itraconazole pulse therapy but has less side effect and lower cost.\;

Long-pulse Nd：YAG 1064-nm laser treatment for onychomycosis

Background Recent research shows that lasers can inhibit fungal growth and that Nd：YAG 1064-nm lasers can penetrate as deep as the lower nail plate. The aim of this study was to observe the effect of a long-pulse Nd：YAG 1064-nm laser on 154 nails of 33 patients with clinically and mycologically proven onychomycosis. Methods Thirty-three patients with 154 nails affected by onychomycosis were randomly assigned to two groups, with the 154 nails divided into three sub-groups （Ⅱ degree,Ⅲ degree, and IV degree） according to the Scoring Clinical Index of Onychomycosis. The 15 patients （78 nails） in group 1 were given eight sessions with a one-week interval, and the 18 patients （76 nails） in group 2 were given four sessions with a one-week interval. Results In group 1, the effective rates at 8 weeks, 16 weeks, and 24 weeks were 63%, 62%, and 51%, respectively, and the effective rates in group 2 were 68%, 67%, and 53% respectively. The treatment effect was not significantly different between any sub-group pair （P 〉0.05）. Conclusions Long pulse Nd：YAG 1064-nm laser was effective for onychomycosis. It is a simple and effective method without significant complications or side effects and is expected to become an alternative or replacement therapy for onychomycosis.

Self-controlled Study of Onychomycosis Treated with Long-pulsed Nd：YAG 1064-nm Laser Combined with Itraconazole

Background： Onychomycosis is a fungal infection of the nail plate and subungual area. In this study, we examined the efficacy of laser treatment using self-controlled study programs involving a long-pulsed Nd：YAG 1064-nm laser combined with oral medication. Methods： Self-controlled strategies were followed in this study. The patients received treatment with oral itraconazole in conjunction with long-pulsed Nd：YAG 1064-nm laser treatment at the nails of the unilateral limb once a week for a total of four times. A total of 84 affected nails were divided into Group A （mild to moderate） and Group B （severe） according to disease severity. Affected nails with the same Scoring Clinical Index for Onychomycosis scores were selected to compare the therapeutic effects of the pure medication treatment group and the combination treatment group with a 24-week follow-up period. Results： In Group A, at the 8th, 16th, and 24th weeks of follow-up, the efficacies in the pure medication treatment group were 81.0%, 81.0%, and 90.5%, respectively, while those in the combination treatment group were 100%, 95.2%, and 90.5%, respectively. The differences between groups were not significant （8th week： χ2 =4.421, P 〉 0.05; 16th week： χ2 = 2.043, P 〉 0.05; 24th week： χ2= 0.00, P 〉 0.05）. In Group B, at the 8th, 16th, and 24th weeks of follow-up, the efficacies in the pure medication treatment group were 61.9%, 66.7%, and 52.4%, respectively, while those in the combination treatment group were 95.2%, 90.5%, and 100%, respectively. The differences between groups at the 8th and 24th weeks of follow-up were statistically significant （8th week： χ2=6.929, P 〈 0.05; 24th week： χ2=13.125, P 〈 0.05）. Conclusions： For patients with mild or moderate onychomycosis, we recommended a pure medication treatment or combination treatment with medication and laser. For those patients with severe onychomycosis, we recommended a combination of medication and laser therapy.

Fungal Translocation Marker in People Living with HIV Needing Treatment for Onychomycosis: A Protocol for the Prospective Pilot Study

Increased microbial translocation and chronic immune activation are two critical problems for people living with HIV(PLWH)in the antiretroviral therapy(ART)era.Compared with numerous studies on bacterial microbiomic communities,there are only a limited number of studies focusing on fungal microbiomic composition and products in PLWH.This study protocol is used to evaluate the changes in bacterial and fungal microbiome populations induced by terbinafine treatment,which is an antifungal agent widely used amongst PLWH.Twenty-two PLWH on a stable ART regimen for more than six months,who require treatment for onychomycosis,will be recruited.The participants will be followed-up for a 12-week treatment period(oral terbinafine 250mg daily)and another 12-weeks of terbinafine discontinuation.Plasma and fecal samples will be collected before and after terbinafine treatment,and for 12weeks after the discontinuation of terbinafine.Plasma gut injury and microbial translocation biomarker assays,in addition to testing for gut microbiome composition,will be undertaken.With this pilot study,we will perform formal sample size calculations and test study feasibility for a possible full-scale study.

Advance in application of dermoscopy for onychomycosis diagnosis

IntroductionOnychomycosis refers to all kinds of fumgal infections of nail plate and nail bed,including those caused by dermatophytes,non-dermatophytes,and Candida species[1].Onychomycosis is the most common nail disease in adults,accounting for 10%-30% of all infectious diseases,and 50% of all nail disorders[2-5].The most common tests used to diagnose onychomycosis are direct microscopic examination,mycological culture,histopathologic examination,and polymerase chain reaction-based tests[2,6].Because of the special structure of the sampling area,patients often experience pain during nail abrasion for the collection of samples.Furthermore,the sensitivity of onychomycosis diagnosis is not satisfied.

OSI评分系统在中国甲真菌病患者中的适用性研究

目的:评价onychomycosis severity index(OSI)评分系统在中国甲真菌病患者中的适用性。方法:由11名皮肤科医师应用OSI评分系统,以入选的患者照片资料为依据,对30例远端侧位甲下型患者进行评分。4周后将以上30例患者重新随机编号,由以上11名皮肤科医师对其进行再次评分。结果:两次评分结果的Kendall和谐系数结果分别为0.80、0.81;对11名评分者自身两次所得评分计算Spearman相关系数,结果区间为0.77~0.96。结论:OSI评分系统作为一种新的甲真菌病的评分方法,在中国人群中应用时有较好的客观性、可靠性,可以很好地反应甲真菌病的严重程度,该方法简单易用,并且不同医师使用时一致性良好,值得一试。

Skin disorders in peritoneal dialysis patients:An underdiagnosed subject

AIM： To examine all skin changes in peritoneal dialysis （PD） patients followed up in our unit.METHODS： Patients on PD program for at least three months without any known chronic skin disease were included in the study. Patients with already diagnosed skin disease, those who have systemic diseases that may cause skin lesions, patients with malignancies and those who did not give informed consent were excluded from the study. All patients were examined by the same predetermined dermatologist with all fndings recorded. The demographic, clinical and laboratory data including measures of dialysis adequacy of patients were recorded also. Statistical Package for Social Sciences （SPSS） for Windows 16.0 standard version was used for statistical analysis.RESULTS： Among the patients followed up in our PD unit, those without exclusion criteria who gave informed consent, 38 patients were included in the study with male/female ratio and mean age of 26/12 and 50.3 ± 13.7 years, respectively. The duration of CKD was 7.86 ± 4.16 years and the mean PD duration was 47.1 ± 29.6 mo. Primary kidney disease was diabetic nephropathy in 11, nephrosclerosis in six, uropathologies in four, chronic glomerulonephritis in three, chronic pyelonephritis in three, autosomal dominant polycystic kidney disease in three patients while cause was unknown in eight patients. All patients except for one patient had at least one skin lesion. Loss of lunula, onychomycosis and tinea pedis are the most frequent skin disorders recorded in the study group. Diabetic patients had tinea pedis more frequently （ P = 0.045）. No relationship of skin findings was detected with primary renal diseases, comorbidities and medications that the patients were using.CONCLUSION： Skin abnormalities are common in in PD patients. The most frequent skin pathologies are onychomycosis and tinea pedis which must not be overlooked.

The Impact of Subungual Osteochondroma Deformans on Severely Mycotic Toenails

Background: We examined 94 toenails exhibiting clinical signs of severe onychomycosis taking into account multiple contributing factors, not the least of which was Subungual Osteochondroma Deformans (SOD). We hypothesize that SOD plays a significant role in both the etiology and treatment of onychomycosis. Methods/Results: A retrospective post-treatment outcome analysis was performed comparing two groups of severely mycotic toenails. The first group of 25 fungal nails showed 54.31% improvement following treatment by both surgical nail avulsion and a 1064 YAG laser-based Nail Restoration algorithm. The second group of 69 fungal nails was not only treated using the same nail avulsion/laser-based algorithm but was also evaluated for SOD lesions which were surgically removed when present, resulting in 95.31% improvement. The overall incidence of SOD lesions in the second group of severely mycotic toenails was 73.91%. Conclusion: We submit that at 73.91% Subungual Osteochondroma Deformans has an under-reported and under-appreciated association with toenail fungus. Generally, we find that our success rates in treating severe toenail fungus using our laser-based Nail Restoration Protocols are much higher when SOD lesions are surgically removed.

Homozygous Nonsense Mutation in SDR9C7 in a Chinese Patient With Autosomal Recessive Congenital Ichthyosis

Introduction:Autosomal recessive congenital ichthyosis(ARCI)is a heterogeneous group of cornification disorders.To date,14 genes have been found to be related to ARCI.Case presentation:A 23-year-old woman developed generalized erythroderma and scales over her trunk and limbs shortly after birth,followed by recurrent blisters and nail deformities.A diagnosis of ARCI was made based on her clinical manifestations,family history,and genetic analysis,which revealed a homozygous mutation inSDR9C7(c.187C>T,p.Q63X).Discussion:Most genes responsible for ARCI are associated with epidermal lipid metabolism,which contributes to the cutaneous barrier.SDR9C7,which encodes short-chain dehydrogenase/reductase family 9C member 7,has also been recently found to play vital roles in this process by regulating ceramide binding to the epidermal cornified cell envelope.For patients clinically suspected to have ARCI,recurrent onychomycosis is a strong indication that they carry aSDR9C7 gene mutation.Conclusion:Remarkable phenotypic and genotypic heterogeneity exists among patients with ARCI.Genetic analysis is an effective tool in diagnosing this and other hereditary diseases.Our patient developed recurrent onychomycosis,a typical presentation of ARCI caused bySDR9C7 mutation,and the unusual blisters further expand the clinical phenotypic spectrum of ARCI.

Nail Psoriasis: Treatment Options and Management Strategies in Special Patient Populations

Nail involvement is common in psoriasis and is considered a risk factor for and a predictor of the development of psoriatic arthritis.The treatment of nail psoriasis is challenging because of the unique anatomical structure of nails and the absence of standardized treatment protocols.Herein,we provide an up-to-date overview of the treatment options for nail psoriasis,including topical drugs and penetration enhancement strategies,traditional and novel oral drugs,and biologic agents.In addition,we highlight the available individualized management strategies in special patient populations such as pediatric patients,geriatric patients,women of childbearing age,and patients with concomitant onychomycosis or psoriatic arthritis.