Insights on the etiopathogenesis of onychomycosis by dermatophyte, yeast and non-dermatophyte mould in ex vivo model.

Fungal biofilms have been involved in the pathogenesis of onychomycosis, but the aspects contributing to this association need to be enlightened. This study aimed to investigate the ability of three different fungi to form biofilm on the nail. All evaluated fungi were able to grow on the nails, using them as the only nutritional source and formed a structure strongly suggestive of biofilms. However, their architecture and morphology were highly contrasting: Candida albicans showed dense growth, exhibited a well-structured community and a large amount of extracellular matrix (ECM), and FTIR-ATR spectroscopy reinforced these findings revealing components suggestive of the biofilm. For Fusarium oxysporum, these events were also observed, but in lower intensity. Furthermore, while Trichophyton rubrum presented a well-organized architecture, the ECM was not visualized. We hypothesize that these findings are related to the symptomatology of onychomycosis. When it is caused by a non-dermatophyte, it usually is accompanied with paronychia, pain, oedema, inflammation and few signals of keratolysis, while dermatophytes are more associated with intense onycholysis and absence of the inflammatory signals. Biofilm seems to be crucial for non-dermatophytes to cause onychomycosis, but not for T. rubrum.

Epidemiología de la Onicomicosis Pedis en adultos hospitalizados en un servicio de medicina en un hospital de tercer nivel en Chile / Epidemiology of Onychomycosis pedisinhospitalized adults at the internal medicine ward of a high complexity hospital in Chile

La prevalencia global de la onicomicosis pedis es de 4,3%, y en hospitalizados puede llegar hasta 8,9%. Aun así, se propone que está ampliamente subdiagnosticada. Personas añosas con comorbilidades presentan mayor riesgo de onicomicosis pedis y de sus complicaciones. Se examinaron aleatoriamente a 64 pacientes hospitalizados en el Servicio de Medicina del Hospital San José. A aquellos con signos clínicos de onicomicosis pedis se les realizó un examen micológico directo (MD) y estudio histopatológico de un corte de uña teñido con PAS (Bp/PAS). Muestra de 64 pacientes, un 78,1% presentó onicomicosis pedis clínica y en un 70,3% se confirmó el diagnóstico con MD y/o Bp/PAS positivo. De los pacientes con onicomicosis confirmada, el promedio de edad fue de 67,8 +/- 12,3 años. Un 44% correspondió al sexo femenino y un 56% al sexo masculino. La onicomicosis pedis en el servicio de medicina interna del Hospital San José es una condición frecuente. El conjunto de MD y Bp/PAS podría ser considerado como una buena alternativa diagnóstica. (AU)

Onychomycosis of the toenails has a global prevalence of 4,3% and can reach up to 8,9% in hospitalized patients. It has been hypothesized that it is widely under diagnosed. Aged patients with multiple diseases have an increased risk of Onychomycosis and its complications. 64 patients of the internal medicine ward were randomly selected. Those who had clinical signs of onychomycosis of the toenails were tested with direct microscopy and histological study of the nail plate with PAS staining. Of the 64 patients, 78,1% (50) had clinical signs of onychomycosis of the toenails and in 70,3% (45) the diagnosis was confirmed either by direct microscopy and/or by histological study of the nail plate with PAS staining. The mean age for the group with onychomycosis was 67,8 +/- 12,3 ages. 44% were female and 56% were male. Onychomycosis of the toenails is a frequent condition at the internal medicine ward of the San José Hospital. The direct microscopy together with the histological study of the nail plate with PAS staining seem to be a good diagnosis alternative. (AU)

Onychoscopy in a Colombian population with a diagnosis of toenail onychomycosis: an evaluation study for this diagnostic test.

BACKGROUND: Onychoscopy is a technique that uses a dermatoscope for the evaluation of specific features of different skin conditions that are not visible to the naked eye. There are few studies establishing parameters for the diagnosis of onychomycosis based on onychoscopy. Determining the sensitivity and specificity of a potentially new diagnostic test for onychomycosis requires an evaluation study of this new diagnostic test, as there are limited studies reporting onychoscopy results. AIM: To determine the sensitivity, specificity, positive predictive value and negative predictive value of onychoscopy findings in a Colombian population with onychomycosis. METHODS: We assessed outpatients with a diagnosis of toenail onychomycosis confirmed by potassium hydroxide preparation or fungal culture. Onychoscopy was performed using a dermatoscope, and digital images collected using a smartphone. RESULTS: The onychoscopy findings were: longitudinal striae, distal spiked pattern, distal irregular termination, linear edge and ruins aspect, while some patients were confirmed as having traumatic onycholysis. A statistically significant association was found between the clinical symptoms of onychomycosis and both the clinical feature of dyschromia and the onychoscopy feature of longitudinal striae. CONCLUSION: We suggest that this technique is an alternative method that should be used in patients with onychopathies because it has the potential to differentiate onychomycosis from traumatic onycholysis and another nail involvement.

Nail clipping in onychomycosis and comparison with normal nails and ungual psoriasis.

BACKGROUND: Of all nail disorders seen in dermatology offices, half of them are due to onychomycosis. The main differential diagnosis is nail psoriasis. The objective of this study was to compare the microscopic findings, other than the presence of fungi, in the clipping of onychomycosis versus normal nails and nail psoriasis. METHODS: Cross-sectional study of onychomycosis cases, analyzed by clipping and compared with data on normal nails and those with nail psoriasis. RESULTS: Sixty-two onychomycosis samples were compared with 30 normal nails and 50 nails with psoriasis. In onychomycosis, measurement of subungual region, serous lakes, neutrophils and number of layers of parakeratosis are more intense than in psoriasis. Onychocariosis is less common in psoriasis, while bacteria are more frequent. The nail transition zone is more commonly blurred and irregular in onychomycosis. CONCLUSION: Clipping helps in the differential diagnosis of onychomycosis and nail psoriasis and may be useful even when fungi are not found.

[Evaluation of the usefulness of nail biopsy in the diagnosis of onychomycosis]. / Evaluación de la utilidad diagnóstica de la biopsia ungueal en las onicomicosis.

BACKGROUND: Onychomycosis affects between 2% to 30% of the world population. Nail biopsy may help in making a diagnosis and can distinguish between invasion and colonisation. AIMS: To evaluate the diagnostic usefulness of nail biopsy with Periodic acid-Schiff (PAS) staining for onychomycosis, compared to direct KOH examination, culture and its combination in a reference laboratory in Colombia. METHODS: The study included 66 patients in whom a blind and independent reading of the three tests was performed. The usefulness was defined based on the validity (sensitivity, specificity, Youden's index, likelihood ratios), performance (predictive values) efficiency (proportion of correctly diagnosed patients), and reproducibility (kappa coefficient). RESULTS: The mean age of the patients was 55±16 years, and included 76% women. The direct tests with KOH were positive in 66.7% (n=44), 62.1% (n=41) were positive with culture, and 56.1% (n=37) with the biopsy. The main causal agents were non-dermatophytes moulds in 36.4% (n=24). The most frequent species were Neoscytalidium dimidiatum (n=11), Trichophyton rubrum (n=11), and Candida parapsilosis (n=13). The sensitivity of nail biopsy, when compared to the standard (KOH and/or culture), was 71%, specificity 83%, Youden's index 0.54, positive likelihood ratio 4.25, negative likelihood ratio 0.35, positive predictive value 92%, negative predictive value 52%, efficiency 74% and kappa coefficient 0.45. When biopsy was evaluated only in patients with onycholysis of the nail plate greater than 50%, all the parameters of diagnostic usefulness increased. CONCLUSIONS: The overall usefulness of the biopsy was moderate for patients with more severe symptomatology, which makes its use advisable in cases of extensive onycholysis, and when discriminating colonisation from invasion is required.

Nail clipping in onychomycosis and comparison with normal nails and ungual psoriasis

Abstract: Background: Of all nail disorders seen in dermatology offices, half of them are due to onychomycosis. The main differential diagnosis is nail psoriasis. The objective of this study was to compare the microscopic findings, other than the presence of fungi, in the clipping of onychomycosis versus normal nails and nail psoriasis. Methods: Cross-sectional study of onychomycosis cases, analyzed by clipping and compared with data on normal nails and those with nail psoriasis. Results: Sixty-two onychomycosis samples were compared with 30 normal nails and 50 nails with psoriasis. In onychomycosis, measurement of subungual region, serous lakes, neutrophils and number of layers of parakeratosis are more intense than in psoriasis. Onychocariosis is less common in psoriasis, while bacteria are more frequent. The nail transition zone is more commonly blurred and irregular in onychomycosis. Conclusion: Clipping helps in the differential diagnosis of onychomycosis and nail psoriasis and may be useful even when fungi are not found.

Fusarium oxysporum is an onychomycosis etiopathogenic agent.

AIM: To evaluate and characterize the etiopathogenesis of the fusarial onychomycosis in an ex vivo study through fragments of sterile human nail, without the addition of any nutritional source. MATERIALS & METHODS: The infection and invasion of Fusarium oxysporum in the nail were evaluated by scanning electron microscopy (SEM), CFU, matrix, histopathology and Fourier Transform Infrared Spectrometer coupled to an equipment with diamond accessory (FTIR-ATR). RESULTS: F. oxysporum infected and invaded across the nail, regardless of application face. However, the dorsal nail surface was the strongest barrier, while the ventral was more vulnerable to infection and invasion process. The fungal-nail interaction resulted in the formation of a dense biofilm. CONCLUSION: F. oxysporum infect and invade the healthy human nail, resulting in biofilm formation. Therefore, F. oxysporum is likely a primary onychomycosis agent.

Meta-analysis of the utility of culture, biopsy, and direct KOH examination for the diagnosis of onychomycosis.

BACKGROUND: Onychomycosis is a highly prevalent disease worldwide. There is no standard test for its diagnosis, which remains costly, wasteful, and is sometimes delayed. The diagnostic tests for this disease are few and discordant. The objective was to evaluate the diagnostic validity, performance, and accuracy of culture, nail clipping with Periodic Acid-Schiff -PAS- staining (biopsy), and direct potassium hydroxide (KOH) examination for the study of onychomycosis. METHODS: A systematic review was conducted via meta-analysis using 5 databases and 21 search strategies. An ex ante protocol was applied with inclusion and exclusion criteria. Quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool, and the sensitivity, specificity, predictive values, likelihood ratios, diagnostic odds ratios, receiver operating characteristic (ROC) curves, and proportion of correctly diagnosed patients were evaluated with the meta-analysis of studies of evaluations of diagnostic and screening tests (Meta-DiSc) and Epidat using a random effects model. RESULTS: The efficiency or accuracy of the three tests is influenced by the methodological quality of the studies. These values are lower for KOH and culture and higher for biopsy in moderate quality studies. CONCLUSION: The diagnostic tests evaluated in this meta-analysis independently showed acceptable validity, performance, and efficiency, with nail clipping with PAS staining outperforming the other two tests.

Tinea Unguium: Diagnosis and Treatment in Practice.

Onychomycosis is caused by dermatophytes, yeasts or non-dermatophyte molds; when caused by dermatophytes, it is called tinea unguium. The main etiological agents are Trichophyton rubrum and Trichophyton interdigitale. The most frequent types are distal and lateral subungual onychomycosis. Diagnosis usually requires mycological laboratory confirmation. Dermoscopy can be helpful and also biopsy is an excellent diagnostic method in uncommon cases or when mycological test is negative. Treatment must be chosen according to clinical type, number of affected nails and severity. The goal for antifungal therapy is the clearing of clinical signs or mycological cure.

Dermoscopy and Onychomycosis: guided nail abrasion for mycological samples

Abstract: Mycological examination is still the cornerstone for the diagnosis of onychomycosis for many dermatologists, but sampling technique interferes on its sensitivity and specificity. Nail abrasion may be used to reach the most proximal part of the lesion and can be easily accomplished with an electric abrasor. We suggest nail plate dermoscopy to identify the best location for localized abrasion to obtain adequate samples for mycological examination.

Scanning electron microscopy of superficial white onychomycosis.

Superficial white onychomycosis is characterized by opaque, friable, whitish superficial spots on the nail plate. We examined an affected halux nail of a 20-year-old male patient with scanning electron microscopy. The mycological examination isolated Trichophyton mentagrophytes. Abundant hyphae with the formation of arthrospores were found on the nail's surface, forming small fungal colonies. These findings showed the great capacity for dissemination of this form of onychomycosis.

Scanning electron microscopy of superficial white onychomycosis

AbstractSuperficial white onychomycosis is characterized by opaque, friable, whitish superficial spots on the nail plate. We examined an affected halux nail of a 20-year-old male patient with scanning electron microscopy. The mycological examination isolated Trichophyton mentagrophytes. Abundant hyphae with the formation of arthrospores were found on the nail's surface, forming small fungal colonies. These findings showed the great capacity for dissemination of this form of onychomycosis.

Fusarium spp. is able to grow and invade healthy human nails as a single source of nutrients.

Onychomycosis caused by Fusarium spp. is emerging, but some factors associated with its development remain unclear, such as whether this genus is keratinolytic. The main aim of the present study was to evaluate the ability of Fusarium to use the human nail as a single source of nutrients. We also performed an epidemiological study and antifungal susceptibility testing of Fusarium spp. that were isolated from patients with onychomycosis. The epidemiological study showed that Fusarium species accounted for 12.4 % of onychomycosis cases, and it was the most common among nondermatophyte molds. The most frequent species identified were F. oxysporum (36.5 %), F. solani (31.8 %), and F. subglutinans (8.3 %). Fluconazole was not active against Fusarium spp., and the response to terbinafine varied according to species. Fusarium was able to grow in vitro without the addition of nutrients and invade healthy nails. Thus, we found that Fusarium uses keratin as a single source of nutrients, and the model proposed herein may be useful for future studies on the pathogenesis of onychomycosis.

Dermoscopy and Onychomycosis: guided nail abrasion for mycological samples.

Mycological examination is still the cornerstone for the diagnosis of onychomycosis for many dermatologists, but sampling technique interferes on its sensitivity and specificity. Nail abrasion may be used to reach the most proximal part of the lesion and can be easily accomplished with an electric abrasor. We suggest nail plate dermoscopy to identify the best location for localized abrasion to obtain adequate samples for mycological examination.

Fast elimination of onychomycosis by hematoporphyrin derivative-photodynamic therapy.

Onychomycosis is a fungal nail disease and is one of the major onychopathy worldwide. Topical or oral antifungal therapies are used to treat this disease, but often they are inefficient and oral medications can even cause several side effects. Photodynamic therapy (PDT) is a well established technique and hence, may represent an alternative non invasive technique for the treatment of onychomycosis. In this work, we present a case of onychomycosis that was completely cured by using the porphyrin-photodynamic therapy. A 59-year-old patient, who had two nails with onychomycosis (the right and the left hallux, with more than thirty and ten years, respectively) caused by fungi was treated once a week for a period of six weeks. The nails were first treated and prepared by a specialist. An hour after the photosensitization, the nail was illuminated using a light source based on light emitting diodes (LEDs) in the red wavelength (630 nm, at a total dose of 54 J/cm(2)).

Aspergillus terreus complex: an emergent opportunistic agent of Onychomycosis.

The incidence of onychomycosis due to non-dermatophyte moulds (NDM) is increasing. Aspergillus terreus is relatively undocumented as an agent of this fungal infection. The aim of this work is to show the prevalence of onychomycosis caused by A. terreus and to describe its clinical features. Nail samples were collected for microscopic examination and culturing in selective media. All cases of onychomycosis due to NDM were confirmed by a second sample. Aspergillus terreus isolates were identified through their morphological characteristics and using molecular methods. A total of 2485 samples were obtained. Positive cultures were obtained in 1639 samples. From 124 NDM confirmed cultures, 23 were identified as A. terreus (18.5%). Superficial white onychomycosis was the most frequent clinical pattern. A high percentage was found in fingernails. The prevalence of A. terreus in this study considerably exceeded the percentages reported by other authors. Onychomycosis due to A. terreus presents similar clinical patterns to those caused by dermatophytes, but is difficult to eradicate and is associated with less predictable treatment outcomes. Better knowledge of the aetiology of A. terreus may be important for accomplishing more accurate and effective treatment.

Intermittent therapy with terbinafine and nail abrasion for dermatophyte toe onychomycosis: a pilot study.

Onychomycosis constitutes up to 50% of all nail disorders. Toenails are generally affected, mostly due to dermatophytes. Terbinafine is the most potent antifungal agent in vitro against dermatophytes. There are few randomised controlled trials using a non-continuous dose of terbinafine. The aim of this open-label pilot study was to reduce the total drug amount, the collateral effects and, specially, the costs; albeit maintaining the same efficacy of the standard regimens. Compare the outcomes of two different intermittent regimens with the same total amount of the medication (42 tablets in 6 months). Forty-one patients were divided into the following groups: terbinafine 250 mg day(-1) , for 7 days, monthly or terbinafine 500 mg day(-1) , once daily, for 7 days, every 2 months, both plus nail abrasion during 6 months. The efficacy was evaluated at months 6, 12 and 18 using the disease free nail criteria. Total cure = group I: eight patients (44.4%) and group II: eight patients (44.4%). Partial cure = group I: five patients (27.8%) and group II: four patients (22.2%). Treatment failure = group I: five patients (27.8%) and group II: three patients (16.7%). Recurrence = group I: zero patients (0.0%) and group II: three patients (16.7%). Two intermittent dosing regimens of terbinafine plus nail abrasion proved to be an alternative statistically effective, safe and with reduced drug costs for dermatophytes toenail onychomycosis.