The role of oxidative stress in onychomycosis: Thiol/disulphide homeostasis.

OBJECTIVES: Onychomycosis is the general term to define fungal nail infections that arise from dermatophytes, non-dermatophytic moulds and yeasts. Thiol/disulphide homeostasis is a new indicator of oxidative stress. In this study, we aimed to investigate the role of thiol/disulphide balance in the pathogenesis of onychomycosis. METHODS: This cross-sectional study included adult patients with onychomycosis who were admitted to the dermatology department and healthy adult volunteers without any dermatologic or systemic condition. The patients and controls were evaluated in terms of native thiol, total thiol, and disulphide levels, and disulphide/native thiol, disulphide/total thiol and native thiol/total thiol ratios. The possible association between these parameters and clinical subtypes of onychomycosis and demographic characteristics was also investigated. RESULTS: A total of 52 patients with onychomycosis and 50 healthy subjects were enrolled in the study. The patient group showed lower levels of total thiol, native thiol and native thiol/total thiol ratio, and higher ratios of disulphide/native thiol and disulphide/total thiol. No statistically significant relationship was found between the parameters, clinical subtypes of onychomycosis and demographic characteristics (p > .05). CONCLUSION: Patients with onychomycosis showed a shifted thiol/disulphide homeostasis towards oxidative stress with a reduction in thiols and an increase in disulphide/native thiol, and disulphide/total thiol ratios. These findings may indicate the role of oxidative stress in the pathogenesis of onychomycosis.

Perspective on Broad-Acting Clinical Physiological Effects of Photobiomodulation.

Research into photobiomodulation reveals beneficial effects of light therapy for a rapidly expanding list of medical conditions and illnesses. Although it has become more widely accepted by the mainstream medicine, the effects and mechanisms of action appear to be poorly understood. The therapeutic benefits of photobiomodulation using low-energy red lasers extend far beyond superficial applications, with a well-described physics allowing an understanding of how red lasers of certain optimum intensities may cross the cranium. We now have a model for explaining potential therapeusis for applications in functional neurology that include stroke, traumatic brain injury, and neurodegenerative conditions in addition to the currently approved functions in lipolysis, in onychomycosis treatment, and in pain management.

Interacción de Pseudomonas aeruginosa y hongos dermatofitos: repercusión en el curso clínico y en el diagnóstico microbiológico de la tinea pedis / Interaction between Pseudomonas aeruginosa and dermatophyte fungi: Repercussions on the clinical course and microbiological diagnosis of tinea pedis

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Utilidad de la terapia fotodinámica en el manejo de la onicomicosis / Usefulness of Photodynamic Therapy in the Management of Onychomycosis

La onicomicosis, o infección fúngica de las uñas, constituye una de las enfermedades micóticas más prevalentes en la población. Su tratamiento tiene una efectividad limitada, además de ser largo y tedioso y, en el caso de los antifúngicos sistémicos, no está exento de efectos adversos. La terapia fotodinámica (TFD) podría ser una buena alternativa para las infecciones cutáneas superficiales, entre ellas la onicomicosis. El presente artículo revisa la experiencia publicada, tanto in vitro como in vivo, acerca de la utilidad de la TFD en las onicomicosis, mostrando el potencial de diversos fotosensibilizantes, así como sus limitaciones. Desde el punto de vista clínico el azul de metileno y el ácido 5-aminolevulínico muestran tasas de curación del 80% y el 43% respectivamente al año de seguimiento. Finalmente, basado en la bibliografía y en la propia experiencia, se propone un protocolo de 3 sesiones de TFD, usando metil-aminolevulinato 16% como fotosensibilizante y luz roja (lambda = 630 nm, 37J.cm−2), separadas por 1 o 2 semanas. Estas irán precedidas de la aplicación de urea 40% durante unos días. Nuevos ensayos clínicos deben optimizar los protocolos y establecer qué pacientes se benefician especialmente de recibir este tratamiento

Onychomycosis, or fungal infection of the nails, is one of the most prevalent fungal diseases in the general population. Treatment is of limited effectiveness, tedious, and must be administered for long periods. Furthermore, systemic antifungal agents are associated with adverse effects. Photodynamic therapy (PDT) may prove to be a viable alternative in the treatment of superficial skin infections, including onychomycosis. We review articles relating to the usefulness of PDT in onychomycosis in both in vitro and in vivo settings and discuss the potential and limitations of various photosensitizing agents. In vivo, methylene blue and 5-aminolevulinic acid have led to cure rates in 80% and 43% of cases, respectively, at 12 months. Finally, based on data in the literature and our own experience, we propose a protocol of 3 PDT sessions, separated by an interval of 1 or 2 weeks, using methyl aminolevulinate 16% as a photosensitizing agent and red light (Lambda = 630 nm, 37J.cm -2). Each session is preceded by the topical application of urea 40% over several days. Clinical trials are needed to optimize PDT protocols and to identify those patients who will benefit most from this treatment

Opportunistic toenail onychomycosis. The fungal colonization of an available nail unit space by non-dermatophytes is produced by the trauma of the closed shoe by an asymmetric gait or other trauma. A plausible theory.

Opportunistic onychomycosis is defined, when a non-dermatophyte mould is cultured from an abnormal nail unit in the absence of a dermatophyte. The presumption is that the mould has caused the abnormal clinical appearance of the nail unit, yet there are no data available to substantiate this claim. Reports have only identified the mould being recovered from the nail unit niche. A review of the published dermatologic literature describing toenail opportunistic onychomycosis by non-dermatophyte fungi has shown toenails with onycholysis, nail bed (NB) keratosis and nail plate surface abnormalities. The appearance of these clinical changes is indistinguishable from the diagnosis of the Asymmetric Gait Nail Unit Signs (AGNUS). AGNUS is produced by the friction of the closed shoe in patients with an asymmetric gait, resulting primarily from the ubiquitous uneven flat feet. Most commonly, species of Acremonium (Cephalosporium), Aspergillus, Fusarium, Scopulariopsis and rarely species of many different fungi genera are capable of surviving and reproducing in a keratinous environment and change the clinical appearance of the involved nail unit. AGNUS toenails predispose to the colonization by the non-dermatophyte opportunistic fungi but not by dermatophyte fungi.

Oral terbinafine and itraconazole treatments against dermatophytes appear not to favor the establishment of Fusarium spp. in nail.

BACKGROUND: Fusarium onychomycoses are weakly responsive or unresponsive to standard onychomycosis treatments with oral terbinafine and itraconazole. OBJECTIVE: To examine whether the use of terbinafine and itraconazole, which are highly effective in fighting Trichophyton onychomycoses, could be a cause of the high incidence of Fusarium nail infections. METHODS: Polymerase chain reaction methods were used to detect both Fusarium spp. and Trichophyton spp. in nails of patients who had either received treatment previously or not. RESULTS: No significant microbiological differences were found between treated and untreated patients. In 24 of 79 cases (30%), Fusarium spp. was detected in samples of patients having had no previous antifungal therapy and when Trichophyton spp. grew in culture. CONCLUSION: Oral terbinafine and itraconazole treatments do not appear to favor the establishment of Fusarium spp. in onychomycosis.

Nail and skin disorders of the foot.

Disorders of the dermis and the nails on the feet are common. Despite the simplicity of the skin and nail disorders of the foot, they can be debilitating and impact the patient's ability to ambulate and perform activities of daily living. Diagnosis in most cases is confirmed on physical examination alone. Diligent care of skin and nail disorders can prevent further pathology involving the deeper structures of the foot and allow the patient to fully participate in their usual activities.

Procedure to diagnose onychomycosis through changes in emissivity on infrared images.

A noninvasive, quick, reliable, and relatively cheap procedure for the diagnosis of onychomycosis is put forward. It is known that a nail may show an abnormal appearance, although only 50% of all the nails having such an appearance may owe it to the presence of onychomycosis; hence, adequate diagnosis of nail disease is needed for appropriate prescription of medication and treatment of the nail. In order to contribute to the process of improvement in the diagnosis, a procedure based on the analysis of medium-range infrared images is presented in which it is possible to observe energy changes mostly due to the changes in emissivity of the nail. As a nail is more affected by onychomycosis, such changes become more intense. Also, it was found that a nail without onychomycosis has a lower temperature than toe skin, but has a higher emission of energy. Fifty percent of the ailments that may a cause a fingernail or toenail to have an abnormal appearance are not considered in the present work.

Factors associated with presence and severity of toenail onychomycosis in patients with diabetes: a cross-sectional study.

OBJECTIVE: To identify the factors associated with toenail onychomycosis in patients with diabetes. METHODS: In this cross-sectional, observational study, the presence and severity (area of nail involvement and nail thickness) of toenail onychomycosis and related factors were examined. One hundred and thirteen patients with diabetes were surveyed at the Diabetic Foot Outpatient Clinic at the University hospital. Toenails of all patients enrolled in the survey were examined whether onychomycosis was present or absent by mycological examination. The severity of onychomycosis was assessed by clinical evaluation, using the area of nail involvement and the nail thickness. RESULTS: Fifty eight (51.3%) patients had toenail onychomycosis. The presence of onychomycosis was significantly associated with not washing of feet every day (the unadjusted model, OR: 3.45, 95% CI: 1.24-9.65, P=0.018). The median area of nail involvement was 50.0% (range 5.0-100.0%). A larger area of involvement was significantly related to a lower toe brachial index (ß=-67.46, P=0.040). The median nail thickness with onychomycosis was 1.14 mm (range 0.68-9.86 mm). Increasing thickness was significantly correlated with higher hemoglobin A(1)c levels (ß=0.98, P=0.003). CONCLUSIONS: This study suggested that daily washing of feet may reduce the risk of onychomycosis in patients with diabetes. This suggested that education regarding the importance of the washing of feet every day and support for continuous self-care might be effective in the prevention of onychomycosis in patients with diabetes. Furthermore, good control of blood glucose might prevent increasing nail thickness. This study may highlight importance of early nursing educational intervention to improve patients' daily life style for prevention of onychomycosis induced diabetic foot ulcers.

CD4+CD25+ Treg cells in patients with toenail onychomycosis.

The essential role played by CD25+CD4+ regulatory T (Treg) cells in the control of immunity against some pathogens such as Helicobacter pylori is now well established. But their role in cutaneous fungal infections is still unknown. Onychomycosis is the chronic fungal infection of the nails, which is very common. The aim of this study was to evaluate possible relationship of CD4+CD25+ Treg cells and onychomycosis. Peripheral blood samples were investigated for CD4+CD25+ Treg cells using flow cytometry analysis in 43 toenail onychomycosis patients and in 30 healthy controls. We have found that onychomycosis patients had a higher expression of CD25+CD4+ Treg cells than controls, with values of 8.45 +/- 4.47% versus 4.64 +/- 1.59%, respectively (P = 0.001). The results of this study suggests that increased numbers of CD4+CD25+ Treg cells may play a role in failure of clearance of dermatophytes from skin by preventing the protective inflammation which is leading to development of onychomycosis. Accordingly, we address the possibility that CD4+CD25+ Treg cells may play a role in immune pathogenesis of other superficial fungal infections.

Role of omalizumab in a patient with hyper-IgE syndrome and review dermatologic manifestations.

Hyper-IgE syndrome (HIES) is a rare idiopathic primary immunodeficiency. It is characterized by a triad of findings, including high levels of serum IgE, recurrent skin abscesses and pneumonia and leads to pneumatocele formation. The diagnosis of HIES is complicated by a diversity of clinical and immunological spectrums and a heterogeneous set of genetic defects. The National Institute of Health (NIH) developed a scoring system for HIES in which a score greater than 14 indicates a probable diagnosis. Our patient presented with recurrent multiple abscesses on her scalp, recalcitrant eczema, candida onychomycosis, alopecia universalis, and highly elevated levels of serum IgE. Using the NIH scoring system, a 30 total-point score in this patient indicated the likelihood of carrying the HIES genotype. To our knowledge, there are no specific treatments of HIES. The humanized recombinant monoclonal antibody against IgE, subcutaneous omalizumab, was successfully used in this patient.

The OnyCOE-t questionnaire: responsiveness and clinical meaningfulness of a patient-reported outcomes questionnaire for toenail onychomycosis.

BACKGROUND: This research was conducted to confirm the validity and reliability and to assess the responsiveness and clinical meaningfulness of the OnyCOE-t, a questionnaire specifically designed to measure patient-reported outcomes (PRO) associated with toenail onychomycosis. METHODS: 504 patients with toenail onychomycosis randomized to receive 12 weeks of terbinafine 250 mg/day with or without target toenail debridement in the IRON-CLAD trial completed the OnyCOE-t at baseline, weeks 6, 12, 24, and 48. The OnyCOE-t is composed of 6 multi-item scales and 1 single-item scale. These include a 7-item Toenail Symptom assessment, which comprises both Symptom Frequency and Symptom Bothersomeness scales; an 8-item Appearance Problems scale; a 7-item Physical Activities Problems scale; a 1-item Overall Problem scale; a 7-item Stigma scale; and a 3-item Treatment Satisfaction scale. In total, 33 toenail onychomycosis-specific items are included in the OnyCOE-t. Clinical data, in particular the percent clearing of mycotic involvement in the target toenail, and OnyCOE-t responses were used to evaluate the questionnaire's reliability, validity, responsiveness, and the minimally clinical important difference (MCID). RESULTS: The OnyCOE-t was shown to be reliable and valid. Construct validity and known groups validity were acceptable. Internal consistency reliability of multi-item scales was demonstrated by Cronbach's alpha > .84. Responsiveness was good, with the Treatment Satisfaction, Symptom Frequency, Overall Problem, and Appearance Problem scales demonstrating the most responsiveness (Guyatt's statistic of 1.72, 1.31, 1.13, and 1.11, respectively). MCID was evaluated for three different clinical measures, and indicated that approximately an 8.5-point change (on a 0 to 100 scale) was clinically meaningful based on a 25% improvement in target nail clearing. CONCLUSION: The OnyCOE-t questionnaire is a unique, toenail-specific PRO questionnaire that can be used with confidence in future studies of toenail onychomycosis. MCID was evaluated for three different clinical measures, and indicated that approximately a 7-point change (on a 0 to 100 scale) was clinically meaningful based on a 12.5% improvement in target nail clearing.

[Characteristic changes of skin and its accessories in type 2 diabetes mellitus].

The different changes are seen on skin and it's accessories in Diabetes Mellitus, some of which represent the prognostic indicator of complicated diabetes and some directly contribute in development of them. Numerous problems concerned with the diabetic foot could be avoided due to early detection and treatment of these changes. The objective data on foot examination of 195 patient with Type 2 Diabetes Mellitus were analyzed considering the grade of severity of Diabetic Peripheral Neuropathy (DPN). It was revealed that the skin humidity is dependent on DPN, particularly, the DPN 2-4 times raises the dryness of the skin on the foot; the risk of callus development is significantly high in case of painless and complicated DPN, accordingly, the possibility of neuropathy ulcer is also high in this group. The high incidence of onychomycosis and Yellow nails syndrome was noted, accordingly in 28.7% and 39.4% of cases; the Melin's shin spots were found in fourth of the patients, mainly in men; a few cases of rubeosis plantarum and bulbosis diabeticorum were revealed; the cases of necrobiosis were not noted. Thus, the prevalence of the characteristic changes of skin and it's accessories in Type 2 Diabetes Mellitus is sufficiently high and it depends on the severity of DPN, using early detection of them may avoid many problems related to diabetic foot and its complications.

Study of oral itraconazole and terbinafine pulse therapy in onychomycosis.

In this open, randomized and comparative study, the safety and efficacy of systemic intermittent itraconazole and terbinafine was examined in 30 patients with onychomycosis. The patient with positive mycological culture and also the patients with positive microscopy and negative culture were investigated. Patients were randomly assigned: 15 patients in each group received either 200mg itraconazole or 250 mg terbinafine twice daily during the first week of a 4 weeks cycle. The treatment duration was 16 weeks and was followed-up for 36 weeks. Both the treatment regimen showed significant reduction in onychomycosis affected areas after 8 weeks and maximum reduction was observed at the end of 36 weeks. At the end point of the follow-up period, the clinical cure rates (no residual deformity or with some deformity) were 86.7% in the itraconazole group and 100% in the terbinafine group. The mycological cure rates were 86.7% and 100% respectively. However, no statistically significant differences between the treatment groups were seen in clinical, mycological (P= 0.864) and severity assessment (P= 0.220). Nausea, abdominal cramp, headache, back pain and flu like syndrome are the adverse effects more frequently reported. At least one adverse effect was reported by 17 patients, of them 12 belonged to itraconazole group and 5 to terbinafine group and the difference was statistically significant (P= 0.027). The overall therapeutic effectiveness, safety and cost affectivity were in favor of Terbinafine pulse therapy.

Pharmacotherapy of onychomycosis.

Fungal infections of the nails are frequent in some segments of the population. Dermatophytes, yeasts and moulds are potential pathogens. A series of antifungal treatments are available to the clinician, differing by both their mechanistic nature and mode of administration. The pharmacodynamic and pharmacokinetic properties of each antifungal agent are distinct. This review focuses on the characteristics of amorolfine, bifonazole, ciclopirox, fluconazole, griseofulvin, itraconazole, ketoconazole, ravuconazole, R126638 and terbinafine. Single drug treatments and combined therapies are presented. None of the current drug regimens have demonstrated reliable efficacy against all cases of onychomycosis. Treatment failures, relapses and reinfections remain stubborn problems in the management of onychomycosis.

Nail changes and disorders among the elderly.

Nail disorders are frequent among the geriatric population. This is due in part to the impaired circulation and in particular, susceptibility of the senile nail to fungal infections, faulty biomechanics, neoplasms, concurrent dermatological or systemic diseases, and related treatments. With aging, the rate of growth, color, contour, surface, thickness, chemical composition and histology of the nail unit change. Age associated disorders include brittle nails, trachyonychia, onychauxis, pachyonychia, onychogryphosis, onychophosis, onychoclavus, onychocryptosis, onycholysis, infections, infestations, splinter hemorrhages, subungual hematoma, subungual exostosis and malignancies. Awareness of the symptoms, signs and treatment options for these changes and disorders will enable us to assess and manage the conditions involving the nails of this large and growing segment of the population in a better way.