Review of the alternative therapies for onychomycosis and superficial fungal infections: posaconazole, fosravuconazole, voriconazole, oteseconazole.

Terbinafine and itraconazole are the most commonly used oral antifungals to treat onychomycosis and superficial dermatomycoses. Recently, poor response to oral terbinafine has been reported. We have summarized the most appropriate dosing regimens of posaconazole, fosravuconazole, voriconazole, and oteseconazole (VT-1161) to treat onychomycosis and superficial fungal infections. A structured search on PubMed and Google Scholar was conducted. Additionally, the bibliographies of selected articles were searched to identify relevant records. The number of records identified from the searches was 463, with 50 articles meeting the inclusion criteria for review. None of the new azoles are US FDA approved for onychomycosis treatment; however, an increasing number of studies have evaluated these agents. The efficacies (complete cure and mycologic cure) of the antifungal agents for dermatophyte great toenail onychomycosis treatment are terbinafine 250 mg/day × 12 weeks (Phase III trial) (38%, 70%), itraconazole 200 mg/day × 12 weeks (Phase III trial) (14%, 54%), posaconazole 200 mg/day × 24 weeks (Phase IIB) (54.1%, 70.3%), fosravuconazole 100 mg/day ravuconazole equivalent × 12 weeks (Phase III) (59.4%, 82.0%), and oteseconazole 300 mg/day loading dose × 2 weeks (Phase II), followed by 300 mg/week × 10 weeks (maintenance dose) (45%, 70%). Guidelines for monitoring are also presented.

Drug survival and reasons for drug discontinuation in palmoplantar pustulosis: a retrospective multicenter study.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory skin disease-related to psoriasis. Its treatment is challenging, and little is known about the sustainability of different medications. The aim of this study was to analyze drug survival rates and drug discontinuation in the treatment of PPP under real-world conditions. PATIENTS AND METHODS: Patients with PPP treated in the dermatology departments of five German university medical centers between 01/2005 and 08/2017 were included in our retrospective study. Drug survival of systemic therapies was assessed with Kaplan-Meier analysis and multivariate regression. RESULTS: Overall, 347 patients with 935 treatment courses were identified. Within the group of non-biologic systemic agents, apremilast showed the highest median drug survival (15 months), followed by cyclosporine (12 months), the combination of acitretin and topical PUVA (9 months), MTX (8 months), acitretin monotherapy (6 months), alitretinoin (5 months), and fumaric acid esters (3 months). Among biologicals, the highest maintenance rate was detected for certolizumab pegol (restricted mean: 47.4 months), followed by infliximab (median: 26 months), golimumab (22 months), ustekinumab (21 months), adalimumab (18 months), secukinumab (9 months), and etanercept (8 months). CONCLUSIONS: Biologicals and apremilast may serve as second-line options for treatment of PPP and should be further evaluated.

Acquired Acrodermatitis Enteropathica Syndrome in a Kidney Transplant Receipt: A Case Report.

Acrodermatitis enteropathica syndrome (AE) is a clinical entity that results in severe zinc deficiency. It can be genetic or acquired. Acquired AE has been reported in patients with chronic liver disease, malabsorption syndrome, sickle cell anemia, and chronic renal failure. We present a kidney transplant recipient with skin rash and watery diarrhea. The patient had low serum zinc levels, which quickly resolved after zinc supplementation. Skin biopsy showed cytoplasmic pallor and vacuolization and ballooning degeneration of keratinocytes within the superficial epidermis, which may have led to confluent necrosis of keratinocytes. Large amounts of keratinosome-derived lamellae were found in the intercellular spaces in the keratinized area, probably related to disturbance of keratinosome metabolism due to zinc deficiency.

Factors influencing cure rates of non-dermatophyte mold and Candida onychomycosis: analysis of outcomes in 81 patients who completed treatment.

OBJECTIVES: Onychomycosis shows a poor response to current topical, oral, or device-related antifungal therapies. The aim of this study was to identify factors influencing the cure rates of non-dermatophyte mold and Candida onychomycosis. METHODS: Eighty-one patients who completed treatments were divided into "cured" and "non-cured" groups. The statistical significance of differences between the two groups was studied. RESULTS: Male gender (P < 0.01), long duration of disease before the initiation of treatment (P < 0.02), three or more infected nails (P < 0.0002), continuous exposure to water and detergents (P < 0.05), frequent exposure to mud and soil (P < 0.01), barefoot walking (P < 0.025), concomitant diabetes and hypertension (P < 0.04), eczema (P < 0.03), and associated paronychia (P < 0.01) had negative effects on cure rates of onychomycosis. Patient age, occupation, site of illness (hand, foot or big toe), type of disease (distal and lateral subungual onychomycosis, proximal subungual onychomycosis or total dystrophic onychomycosis), pathogenic fungi, and treatment modality had no statistically significant impact on cure rate. CONCLUSIONS: To minimize the failure rate of antifungal therapies in the treatment of onychomycosis, patients are advised to start treatment as soon as possible, and to avoid predisposing factors such as exposure to water, detergents, mud and soil, and barefoot walking.

The Influence of Two Different Foam Creams on Skin Barrier Repair of Foot Xerosis: A Prospective, Double-Blind, Randomised, Placebo-Controlled Intra-Individual Study.

BACKGROUND/AIMS: Dry skin, or xerosis, is a common condition and a key feature of skin diseases like atopic dermatitis (AD) and ichthyosis vulgaris. Foot xerosis may exist without underlying disease and could be related to very mild forms of AD or ichthyosis vulgaris. The synthesis of important skin lipids (cholesterol, free fatty acids and ceramides) is reduced in xerosis and AD, and reduced lipid synthesis is responsible for a lack of lipids and enzymes in the skin barrier. This slows down reorganisation of the lipid lamellae in the stratum corneum (SC). METHODS: Skin barrier integrity was measured by morphometric analysis of the lipid lamellae in the SC after 4 weeks of treatment with a foam cream (active agent vs. placebo). RESULTS: Significant treatment effects were shown after 2 and 4 weeks by an increasing amount of intercellular lipids in the SC. CONCLUSION: This study shows that a quick reorganisation of the SC lipids initiates a good restoration of the whole skin barrier after 4 weeks of treatment with a foam cream.

[Treatment of interdigital foot Erythrasma with ozonated olive oil]. / Tratamiento de eritrasma interdigital de pies con aceite de oliva ozonificado.

BACKGROUND: Erythrasma is caused by Corinebacterium minutissimum producing a porphyrin that with Wood's light emits a coral-red fluorescence. It is the most common bacterial infection of the feet. Ozonated olive oil decreases the cytoplasm and damages bacterial proteins and lipids. Treatment is with oral erythromycin and there is no consensus regarding the topical therapy of choice. The aim of this paper is to evaluate the therapeutic efficacy of ozonated olive oil in a pilot trial for Erythrasma. METHODS: Experimental, open, observational, descriptive, longitudinal clinical trial at the section of Mycology, of the General Hospital "Dr. Manuel Gea González". PATIENTS: 10 individuals with interdigital feet Erythrasma. INTERVENTION: ozonated olive oil every 12 hours for 10 days was given. RESULTS: All patients had disappearance of coral-red fluorescence, erythema, fissures, pruritus, and maceration; two patients persisted with scaling. A cure was obtained in 100 % of patients, similar to oral erythromycin response. CONCLUSIONS: Ozonated olive oil is a good topical treatment option for interdigital Erythrasma avoiding oral medications. Larger studies are required.

Introducción: el eritrasma es causado por Corinebacterium minutissimum que produce una porfirina que con la luz de Wood emite una fluorescencia rojo coral es la infección bacteriana más frecuente en los pies. El aceite de oliva ozononificado disminuye el citoplasma y daña las proteínas y los lípidos bacterianos. El tratamiento es mediante eritromicina oral y no hay consenso respecto a la terapia tópica de elección. El objetivo de este trabajo es evaluar la eficacia terapéutica del aceite de oliva ozonificado en el eritrasma en una prueba piloto. Métodos: estudio clínico experimental, abierto, observacional, descriptivo y longitudinal, llevado a cabo en la sección de Micología del Hospital General "Dr. Manuel Gea González". Se incluyeron 10 pacientes con eritrasma interdigital de pies, a quines se les administró aceite de oliva ozonificado cada 12 horas por 10 días. Resultados: en todos los pacientes hubo desaparición de la fluorescencia rojo coral, eritema, fisuras, prurito y maceración; en dos de ellos persistió la descamación. Se obtuvo una cura clínica en el 100 % de los pacientes, respuesta similar a la eritromicina oral. Conclusiones: el aceite de oliva ozonificado es una buena opción terapéutica tópica para el eritrasma interdigital, que permite evitar la prescripción de medicamentos por vía oral. Se requieren estudios más extensos.

Terbinafine hydrochloride loaded liposome film formulation for treatment of onychomycosis: in vitro and in vivo evaluation.

Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6 ± 3.28, 54.4 ± 4.26, 56.1 ± 7.48 and 46.0 ± 2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16 ± 4.22, 24.81 ± 5.35, 8.17 ± 1.81 and 8.92 ± 3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection.

Broad-band UVB versus paint PUVA for palmoplantar psoriasis treatment.

BACKGROUND: Plaque-type palmoplantar psoriasis (PPTP) is a chronic recalcitrant dermatosis with treatment modalities ranging through topical, phototherapy or systemic. Phototherapy options include various forms of ultraviolet B (UVB) and ultraviolet A with prior psoralen sensitization (PUVA). Currently, few comparative studies have been reported. PURPOSE: To compare Broad-Band UVB (BB-UVB) versus paint PUVA (p-PUVA) in regard to efficacy and safety in the treatment of PPTP. METHODS: A retrospective non-randomized cohort study comprised of all the patients with PPTP treated in our phototherapy centre during 2010-2012, either with BB-UVB or p-PUVA. RESULTS: Among the 248 patients included in this study, 122 received BB-UVB and 126 followed p-PUVA treatment. About 36 (30%) and 53 (42%) had complete remission, 29 (24%) and 59 (47%) responded partially and 57 (47%) and 14 (11%) patients did not improve with BB-UVB and p-PUVA, respectively. The odds ratio for remission (p-PUVA: BB-UVB) was 7.9. Duration of remission was 21.9 ± 1.34 months for p-PUVA and 16.75 ± 1.83 months for BB-UVB. CONCLUSION: Both BB-UVB and p-PUVA are good therapeutic options for PPTP. P-PUVA emerges as the superior treatment modality, yielding a better and more extended response. BB-UVB represents a feasible alternative in patients with milder disease or possible contraindications for p-PUVA.

Potential role of tavaborole for the treatment of onychomycosis.

Systemic antifungal treatments are believed to be more effective than topicals for the treatment of onychomycosis; however, they are associated with more risks of adverse events. Tavaborole is the first member of a new class of antifungals that has been developed as a new topical nail solution for the treatment of toenail onychomycosis caused by dermatophytes. During Phase I-III clinical trials, tavaborole 5.0% nail solution showed a favorable safety and efficacy profile. Tavaborole 5.0% received US FDA market approval on 8 July 2014.

Evidence-based guidelines of the spanish psoriasis group on the use of biologic therapy in patients with psoriasis in difficult-to-treat sites (nails, scalp, palms, and soles).

Psoriatic lesions affecting the scalp, nails, palms, and the soles of the feet are described as difficult-to-treat psoriasis and require specific management. Involvement of these sites often has a significant physical and emotional impact on the patient and the lesions are difficult to control with topical treatments owing to inadequate penetration of active ingredients and the poor cosmetic characteristics of the vehicles used. Consequently, when difficult-to-treat sites are involved, psoriasis can be considered severe even though the lesions are not extensive. Scant information is available about the use of biologic therapy in this setting, and published data generally comes from clinical trials of patients who also had moderate to severe extensive lesions or from small case series and isolated case reports. In this article we review the quality of the scientific evidence for the 4 biologic agents currently available in Spain (infliximab, etanercept, adalimumab, and ustekinumab) and report level i evidence for the use of biologics to treat nail psoriasis (level of recommendation A) and a somewhat lower level of evidence in the case of scalp involvement and palmoplantar psoriasis.

Transungual delivery of efinaconazole: its deposition in the nail of onychomycosis patients and in vitro fungicidal activity in human nails.

BACKGROUND: Effective transungual delivery of topical antifungal agents in onychomycosis has been hampered by poor nail permeation. To be effective they must have antifungal efficacy, and effectively permeate through the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. The therapeutic efficacy of efinaconazole topical solution, 10% has been established in two phase 3 clinical trials in distal lateral subungual onychomycosis. OBJECTIVE: To investigate the transungual delivery of efinaconazole in onychomycosis patients and its fungicidal activity in the toenail. METHODS: Concentrations of efinaconazole were determined as part of a multi-center, open label study in forty onychomycosis patients following repeated application of efinaconazole topical solution, 5% and 10% to the toenails over 28 days, with a 2-week follow-up. Fungicidal activity against T. rubrum in the ventral layer of human nails was determined using an in vitro human nail infection model (ChubTur®). RESULTS: Efinaconazole concentrations in the nail were four orders of magnitude higher than MIC values of efinaconazole against dermatophytes. Further, nail drug concentrations were not influenced by the presence of disease or nail thickness, and maintained at high antifungal levels post-treatment. Efinaconazole was effective in reducing fungal viability, suggesting that sufficient amounts of efinaconazole were being delivered into the ventral layer of the nail plate.
CONCLUSIONS: Effective transungual delivery of efinaconazole was demonstrated. The high efinaconazole concentrations in patient toenails and fungicidal activity in vitro potentially contribute to the clinical efficacy reported in phase 3 studies.

Is Trichophyton simii endemic to the Indian subcontinent?

Trichophyton simii is considered to be prevalent only in the Indian subcontinent where it was isolated from soil, as well as from infections of humans and animals. We have investigated a case of onychomycosis caused by this exotic dermatophyte, not traceable to endemic areas. This case, as in others due to this fungus in man or animals, that have been previously and sporadically reported worldwide, suggests infections caused by T. simii might be underestimated, especially outside its primary geographic areas. Indeed, there are isolates that do not show species-specific morphology, as in our case isolate, and as a result may be misidentified by classical methods. By checking the identity of some strains preserved in the collection BCCM/IHEM, we found several that proved to be T. simii, originating from non-endemic areas (Belgium, France and Ivory Coast). Therefore, the natural distribution of T. simii is probably not as restricted as has previously been proposed.

Comparison of clobetasol propionate cream plus coal tar vs. topical psoralen and solar ultraviolet A therapy in palmoplantar psoriasis.

AIM: Palmoplantar psoriasis (PPP) produces significant morbidity and requires prompt treatment. Topical agents form the mainstay of therapy. We compared the efficacy and side-effect profile of a steroid/coal-tar combination with topical psoralen and solar ultraviolet A (PUVAsol) in PPP. METHODS: In total, 52 patients with PPP were randomized to receive either a combination of clobetasol propionate cream and coal tar daily (group 1) or topical PUVAsol on alternate days (group 2) for 16 weeks. Response was assessed as change in Psoriasis Activity and Severity Index (PASI) and Patient Global Assessment (PGA). RESULTS: Of the 52 patients, 43 completed the treatment phase. There was a reduction in PASI for the palms and soles in both treatment groups throughout the treatment period until week 16. There was a greater reduction in PASI in palmar psoriasis with topical PUVAsol, and a greater reduction in psoriasis of the soles with the steroid/coal-tar combination. In both groups, patients perceived 'good improvement'. Improvement or cure in palmar lesions was observed in 90% of cases in the topical steroid/coal-tar group and in 75% of cases in the topical PUVAsol group; for the soles, these figures were 76% and 79%, respectively. No adverse effects were experienced with the steroid/coal-tar combination, whereas for the topical PUVAsol, phototoxicity occurred in 22% of cases. CONCLUSION: Both treatments had comparable efficacy. In both groups, patients experienced 'good improvement' after 16 weeks of therapy.