Clinico-mycological validation of dermatophytosis severity score and its correlation with patient-reported outcome measures.

BACKGROUND: Dermatophytosis impacts a significant portion of the global population. Recent shifts in the disease's presentation, severity and response to treatment, primarily due to emerging drug resistance, underscore the need for reliable assessment tools. The Dermatophytosis Severity Score (DSS) aims to standardise the evaluation of the disease's severity and monitor therapeutic responses. METHODS: In a cross-sectional pilot study, 25 adults with clinically diagnosed dermatophytosis were evaluated using the DSS. The study also aimed to establish the correlation of DSS with different stages of treatment, dermatophyte species and patient-reported outcomes. Participants were recruited from a dermatology outpatient clinic, and the DSS was applied at baseline, Weeks 4 and 8. The validity and reliability of the DSS were assessed using statistical measures, including Cronbach's alpha and intraclass correlation coefficient. RESULTS: The study comprised of a near-equal distribution of male (52%) and female (48%) patients, primarily within the age group of 20-39 years. A high recurrence rate of dermatophytosis (60%) was noted, and more than half of the patients (56%) had used topical steroids before presentation. The mean DSS significantly decreased from baseline to the final visit, mirroring the substantial reduction in the 5D itch scale and Dermatology Life Quality Index, with strong positive correlations observed between these measures. CONCLUSION: The DSS demonstrated high inter-rater reliability and internal consistency, indicating its utility as a reliable clinical tool for assessing dermatophytosis severity. The strong correlation of DSS with itch intensity and quality of life validates its role in patient-centered care. Continued use and further validation of the DSS are recommended to enhance dermatophytosis management and treatment outcomes.

Prolonged treatment of dermatophytosis caused by Trichophyton indotinea with terbinafine or itraconazole impacts better outcomes irrespective of mutation in the squalene epoxidase gene.

BACKGROUND: Over the past decades, the increasing incidence of recurrent dermatophytosis associated with terbinafine-resistant Trichophyton has posed a serious challenge in management of dermatophytosis. Independent reports of failure of treatment and high minimum inhibitory concentrations (MIC) of antifungals are available, but data correlating MIC and clinical outcomes is still sparse. Therefore, the present study was conducted to evaluate the outcomes of systemic treatment of dermatophytosis and its correlation with MIC of the etiological agents isolated from such patients. METHODS: Retrospective analysis of 587 consecutive patients with dermatophytosis was done from March 2017 to March 2019. Demographic and clinical details of the patients were noted, along with the results of direct microscopy and fungal culture. The isolates were identified by sequencing the internal transcribed spacer region of rDNA. Antifungal susceptibility testing was performed following the CLSI M38 protocol. Mutation in the squalene epoxidase (SE) gene was detected by DNA sequencing and ARMS-PCR. Based on the culture-positivity and prescribed systemic antifungal, patients were categorised into Group I culture-positive cases treated with systemic terbinafine and Group II culture-positive cases treated with systemic itraconazole, each for a total period of 12 weeks. RESULTS: In the present study, 477 (81.39%) were culture-positive; however, 12 weeks follow-up was available for 294 patients (Group I-157 and Group II-137) who were included for statistical analysis. In both groups [Group I-37/63 (51.4%) and Group II-14/54 (58.3%)], a better cure rate was observed if the initiation of therapy was performed within <6 months of illness. Treatment outcome revealed that if therapy was extended for 8-12 weeks, the odds of cure rate are significantly better (p < .001) with either itraconazole (Odd Ratio-15.5) or terbinafine (Odd Ratio-4.34). Higher MICs for terbinafine were noted in 41 cases (cured-18 and uncured-23) in Group I and 39 cases (cured-16 and uncured-23) in Group II. From cured (Group I-17/18; 94.4% and Group II-14/16; 87.5%) and uncured (Group I-20/23; 86.9% and Group II-21/23; 91.3%) cases had F397L mutation in the SE gene. No significant difference in cure rate was observed in patients with Trichophyton spp. having terbinafine MIC ≥ 1or <1 µg/mL (Group I-p = .712 and Group II-p = .69). CONCLUSION: This study revealed that prolonging terbinafine or itraconazole therapy for beyond 8 weeks rather than the standard 4 weeks significantly increases the cure rate. Moreover, no correlation has been observed between antifungal susceptibility and clinical outcomes. The MIC remains the primary parameter for defining antifungal activity and predicting the potency of antifungal agents against specific fungi. However, predicting therapeutic success based solely on the MIC of a fungal strain is not always reliable, as studies have shown a poor correlation between in vitro data and in vivo outcomes. To address this issue, further correlation of antifungal susceptibility testing (AFST) data with clinical outcomes and therapeutic drug monitoring is needed. It also highlights that initiation of the treatment within <6 months of illness increases cure rates and reduces recurrence. Extensive research is warranted to establish a better treatment regime for dermatophytosis.

[Mycosis caused by Nannizzia incurvata in a traveler returning from Indonesia]. / Mykose durch Nannizzia incurvata bei einem Reiserückkehrer aus Indonesien.

Nannizzia incurvata is a geophilic dermatophyte that is rarely detected in Germany. We report on a 17-year-old traveler returning from Indonesia in whom Nannizzia incurvata was isolated as the causative agent of tinea corporis. Targeted, local antimycotic therapy and clinical follow-up was recommended. This report shows the importance of a detailed travel history and targeted mycological diagnostic workup.

Peritoneal dialysis-associated peritonitis due to infected umbilicus.

We provide the first case report of peritoneal dialysis (PD)-associated peritonitis due to Lasiodiplodia theobromae, a known plant pathogen causing rotting and dieback in post-harvest citrus fruit, in immunocompetent patient with fungal colonization inside the PD catheter lumen. A root cause analysis suspected the patient's umbilical infection as the source of contamination. The fungal infection was established through microscopic examination of the PD catheter lumen and galactomannan testing in both serum and effluent. The species of pathogen was confirmed by DNA barcoding. The patient responded well to timely PD catheter removal and a 2-week course of oral voriconazole. Preventive strategies should prioritize hygiene practices, including umbilical care, to mitigate the risk of contamination and subsequent infections of fungal pathogens.

Efficacy and Safety of Amorolfine Lotion 0.25% w/v Compared to Amorolfine Cream 0.25% w/w in Patients With Superficial Fungal Infections of the Skin: A Multi-center, Randomized, Open-Label, Active-Controlled, Non-inferiority Phase III Clinical Trial.

BACKGROUND: Dermatophytosis, a major cause of superficial fungal infections, requires topical and systemic antifungals. Amorolfine, a morpholine derivative, is a new topical antifungal available in cream and lotion formulations. OBJECTIVE: To evaluate the efficacy and safety of amorolfine lotion 0.25% compared to amorolfine cream 0.25% in patients with dermatophytosis. METHODS: A multi-center randomized, two-arm, active-controlled, parallel, non-inferiority phase III clinical trial involving 284 dermatophytosis patients was conducted, with the test arm using amorolfine lotion and the reference arm using amorolfine cream. The study drugs were applied once daily in the evening for four weeks and patients were followed up for another two weeks. The primary endpoint was clinical cure, while secondary endpoints included mycological cure, composite cure, global efficacy assessment, and post-treatment relapse. Safety and tolerability were assessed. RESULTS: Amongst the enrolled patients, 69.9% and 68.1% of patients had tinea corporis, while 30.1% and 31.9% had tinea cruris. The majority of patients in both groups (99.3% test and 97% reference) achieved a clinical cure at the end of treatment. Mycological cure was achieved by 98.6% and 96.3% respectively. A composite cure was achieved by 98.6% in the test arm versus 96.3% in the reference arm. A total of two AEs were reported in two (1.4%) patients in the test group and three AEs were reported in three (2.1%) patients in the reference group, all of the AEs were mild and resolved within three days without supportive medication. No severe adverse effects were reported in any of the study subjects. CONCLUSION: Amorolfine lotion 0.25% w/v showed a non-inferior clinical, mycological, and composite cure in dermatophytosis patients, was well-tolerated, and had a similar safety profile to amorolfine cream 0.25% w/w.

Recalcitrant dermatophyte infections: identification and risk factors.

INTRODUCTION: Recalcitrant dermatophytosis is an emerging phenomenon that occurs worldwide, and Trichophyton indotineae is currently the prominent cause. MATERIALS AND METHODS: Skin specimens from patients with tinea infection were obtained by scrubbing and then sectioned into three fragments. Two fragments were subjected to direct microscopic examination and culture, while the third portion was utilized in the PCR method. RESULTS: Isolates were morphologically identified as Trichophyton mentagrophytes/interdigitale complex (n = 60 [83.33%]), Microsporum canis (n = 8 [11.11%]), Trichophyton rubrum (n = 3 [4.16%]), and Epidermophyton floccosum (n = 1 [1.38%]). Among 60 T. mentagrophytes complex isolates, 53 (88.33%) were classified as T. indotineae and seven as T. interdigitale genotype II. The disease duration was longer in the T. indotineae group (P = 0.035). Both Gradient PCR and skin-sampling methods yield similar results in terms of positive and negative cases (P = 1.0000). The time patients stopped their medication did not impact the positive case numbers (P = 0.803). Gender had no effects on the frequency (P = 0.699). Familial contamination, dermatologic disorder, and other underlying conditions did not differ in the two group infections (P > 0.05). Steroid usage is strongly associated with the emergence of tinea infection (P < 0.04). The duration of antifungal administration had a substantial effect on the emergence of resistant organisms (P = 0.05). CONCLUSIONS: Steroid usage, T. indotineae involvement, and prolonged exposure to antifungals were the solid and influential factors in recalcitrant involvement. Regarding quick and suitable diagnosis and treatment, which is essential in preventing recalcitrant cases, we suggest that direct skin sample PCR can meet the demands.

Clinico-mycological and therapeutic updates on cutaneous dermatophytic infections in the era of Trichophyton indotineae.

Trichophyton indotineae has emerged as a novel dermatophyte species resulting in treatment recalcitrant skin infections. While the earliest reports came from India, T. indotineae has now spread to many parts of the world and is rapidly becoming a global health concern. Accurate identification of T. indotineae requires elaborate mycological investigations which is beyond the domain of routine microbiology testing. Extensive, non-inflammatory and atypical presentations are commonly seen with this novel species. T. indotineae shows an alarmingly high rate of mutations in the squalene epoxidase gene leading to lowered in vitro susceptibility to terbinafine. This has also translated into a lowered clinical response and requirement of a higher dose and much longer durations of treatment with the drug. Although the species remains largely susceptible to itraconazole, prolonged treatment durations are required to achieve cure with itraconazole. Fluconazole and griseofulvin do not have satisfactory in vitro or clinical activity. Apart from requirement of prolonged treatment durations, relapse postsuccessful treatment is a distressing and yet unexplained consequence of this "species-shift." Use of third generation azoles and combinations of systemic antifungals is unwarranted as both have not demonstrated clear superiority over itraconazole given alone, and the former is an important class of drugs for invasive mycoses.

Atypical and Unpredictable Superficial Mycosis Presentations: A Narrative Review.

While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, or joint); mimicking other skin diseases such as eczema, psoriasis, or mycosis fungoides; and appearing with unexpected color, shape, or distribution. The emergence of such a challenging clinical picture is attributed to the complex interplay of host characteristics (hygiene and aging population), environment (climate change), advances in medical procedures, and agent factors (fungal resistance and species emergence). We aim to provide a better understanding of unusual epidemiological contexts and atypical manifestations of fungal superficial diseases, knowing that there is no pre-established clinical guide for these conditions. Thus, a literature examination was performed to provide a comprehensive analysis on rare and atypical superficial mycosis as well as an update on certain fungal clinical manifestations and their significance. The research and standard data extraction were performed using PubMed, Medline, Scopus, and EMBASE databases, and a total of 222 articles were identified. This review covers published research findings for the past six months.

A clinical prevalence of dermatophytic mycoses with an assessment of its clinical manifestations in a tertiary care hospital at Salem, South India.

BACKGROUND: Dermatophytosis is very common among all age groups throughout the world. The incidence of the same is increasing on a steady basis. AIM: Estimating the clinical prevalence of dermatophytes mycoses among the patients visiting the outpatient unit and assessing its distinct manifestations. METHODOLOGY: A prospective observational study was conducted with the patients attending the Skin and STD outpatient unit of a tertiary care teaching hospital in Salem. A total of 3068 outpatients attended the department, of which 420 patients were diagnosed with dermatophytic mycoses and were taken for investigating the prevalence. RESULTS: A total of 420 dermatophytosis patients were included giving a percentage prevalence of 13.69%. There were more female patients (n = 213, 50.71%) than males (n = 207, 49.29%). The most common afflicted age group was 31-40 years (n = 99, 50.71%). Most of the patients had an atypical lesion called tinea incognita (n = 265, 63.09%) where there was no typical classic appearance of dermatophytic infections. The most prevalent clinical manifestation was tinea corporis (n = 73, 17.38%) followed by tinea cruris (n = 69, 16.43%). There were more newly diagnosed dermatophytosis cases (n = 326) than the previously diagnosed cases (n = 94). CONCLUSION: This study concludes that dermatophytic mycoses were more prevalent among females than males and among the age groups of 31-40 years. The most common clinical presentation was tinea incognita followed by tinea corporis.

Identification of Familial Infections Using Multilocus Microsatellite Typing in Tinea Corporis due to Microsporum canis.

Microsporum canis is a type of dermatophyte that causes zoonotic dermatophytosis in cats and dogs. We report three cases of tinea corporis due to M. canis from a single household with a domestic cat as a pet. The cases included a woman in her thirties (mother), a girl in her teens (older sister), and a girl in her teens (younger sister). Following sudden hair loss in the domestic cat, annular erythema with pruritus and scales appeared on the face, neck, and limbs of the older sister, younger sister, and mother, sequentially; they subsequently visited our hospital. Potassium hydroxide direct microscopy revealed filamentous fungi on all three women. In addition, short-haired colonies with a white to yellowish-white color and extending in a radial manner were found in cultures using a flat plate agar medium. A slide culture with the same medium indicated pointed spindle-shaped macroconidia with 7-8 septa. Therefore, the cases were diagnosed as tinea corporis due to M. canis. Genetic analysis of the cells of the cat and the mother, older sister, and younger sister using multilocus microsatellite typing (MLMT) indicated that all cases were classified into the same genotype, suggesting that the transmission route of these cases was familial. Here, we show that MLMT is useful in identifying the infection route in cases of tinea corporis due to M. canis.

Progress in the diagnosis and treatment of superficial cutaneous fungal infections in children / 中华实用儿科临床杂志

Superficial cutaneous fungal infections are caused by fungi infections that only invade fully keratinized tissues, such as the stratum corneum, hair, and nails.In clinical practice, tinea capitis is the most prevalent superficial cutaneous fungal infections in children, whereas the incidence of tinea corporis/cruris, tinea manuum/pedis, onychomycosis, and pityriasis versicolor is relatively low.This article aims to comprehensively discuss the clinical manifestations, diagnosis, and advancements in the treatment of superficial cutaneous fungal infections in children, focusing on each specific infection individually.

Tinea corporis intrafamilial infection in pets due to Microsporum canis

ABSTRACT Microsporum canis, one of the most widespread dermatophytes worldwide, is a zoonotic microorganism that transmits infection from reservoirs such as cats and dogs to humans. This microorganism is associated with Tinea corporis and other clinical manifestations; however, few studies have used genetic surveillance to determine and characterize the process of zoonotic transmission. In this study, we show a clear example of zoonotic transmission from a cat to an intrafamilial environment, where it caused Tinea corporis by infection with M. canis. Molecular characterization using the b-tubulin gene and Random Amplified Polymorphic DNA analysis made it possible to determine that the six isolates of M. canis obtained in this study belonged to the same genetic variant or clone responsible for reservoir-reservoir or reservoir-human transmission.

Therapeutic Updates on the Management of Tinea Corporis or Cruris in the Era of Trichophyton Indotineae: Separating Evidence from Hype-A Narrative Review.

The emergence and spread of Trichophyton indotineae (T. indotineae) has led to a sea change in the prescription practices of clinicians regarding the management of dermatophytic skin infections. An infection easily managed with a few weeks of antifungals, tinea corporis or cruris, is now often chronic and recurrent and requires prolonged treatment. Rising resistance to terbinafine, with documented squalene epoxidase (SQLE) gene mutations, and slow clinical response to itraconazole leave clinicians with limited treatment choices. However, in these testing times, it is essential that the tenets of antifungal stewardship be followed in making therapeutic decisions, and that the existing armamentarium of antifungals be used in rationale ways to counter this extremely common cutaneous infection, while keeping the growing drug resistance among dermatophytes in check. This review provides updated evidence on the use of various systemic antifungals for dermatophytic infection of the glabrous skin, especially with respect to the emerging T. indotineae species, which is gradually becoming a worldwide concern.

A Case of Tinea Corporis Caused by Trichophyton benhamiae var. luteum from a Degu and Evolution of the Pathogen's Taxonomy.

BACKGROUND: Trichophyton benhamiae, an anthropophilic dermatophyte, can cause dermatophytosis in humans and animals with rising zoonotic infections through pets, primarily in Europe. Dermatophytosis from T. benhamiae is often misdiagnosed due to its inflammatory symptoms. We report a case of tinea corporis from T. benhamiae var. luteum in a Japanese woman, contracted from pet Czech degus. CASE: The 40-year-old patient developed neck papules resembling acne. Initial treatment with topical antibiotics and steroids exacerbated the rash. Fungal elements were not detected by direct potassium hydroxide examination. Skin biopsy confirmed fungal elements in the stratum corneum and hair follicles, and tinea corporis was diagnosed. Oral terbinafine 125 mg was initiated without topical agents. Erythematous papules appeared on her limbs, determined as a trichophytid reaction. After two months, her skin improved significantly. Fungal culture identified T. benhamiae var. luteum colonies with a yellowish hue. Mating tests classified the strain as Americano-European race (-) with MAT1-1 genotype. This was diagnosed as tinea corporis from T. benhamiae var. luteum, likely transmitted from pet Czech degus. CONCLUSIONS: The incidence rate of pet-transmitted cutaneous fungal infections may increase in Japan with the trend to keep exotic pets. Dermatologists must recognize dermatophytosis clinical features from anthropophilic dermatophytes to prevent misdiagnosis and understand evolving nomenclature and pathogenesis.

A Terbinafine Sensitive Trichophyton indotineae Strain in Italy: The First Clinical Case of tinea corporis and onychomycosis.

Trichophyton indotineae is an emerging dermatophyte species that plays a relevant role in human healthcare. It has been associated with severe chronic skin infections and a high level of terbinafine resistance. T. indotineae is endemic to India, Iran, and Iraq but several cases have been reported in Europe, recently. In this manuscript, the authors report the first clinical description of a tinea corporis and onychomycosis due to T. indotineae. The patient was a 42-year-old female from India that has lived in Umbria (Central Italy) for the last two years. Firstly, a dermatological examination suggested dermatophytosis: mycology isolation from cultures and macro- and microscopical features identified the colonies as belonging to the T. mentagrophytes/T. interdigitale species complex. Subsequently, ITS1/ITS4 end-point PCR and Sanger sequencing identified the strain as T. indotineae. Lastly, a DermaGenius® Resistance Multiplex real-time PCR assay was carried out, targeting the mutations in the SQLE gene to establish terbinafine resistance or susceptibility of the strain. The melting curve observed was compatible with wild-type positive control, identifying the strain as T. indotineae terbinafine-sensitive. An oral terbinafine treatment was associated with a topical ciclopirox nail solution, resulting in remission in its clinical manifestation. On 3 July 2023, the local Prevention Service notified the case to the Ministry of Health that then reported the information at national and international levels.

An update on the myriad antifungal resistance mechanisms in dermatophytes and the place of experimental and existential therapeutic agents for Trichophyton complex implicated in tinea corporis and cruris.

INTRODUCTION: There is an epidemic emergence of increased resistance in dermatophytes with to antifungal drugs with ergosterol1 (Erg1) and Erg11 mutations to terbinafine and azoles. Apart from mutations, mechanisms that predict clinical failure include efflux pumps, cellular kinases, heat shock proteins (Hsp), and biofilms. Apart from itraconazole and SUBATM (Super-Bioavailable) itraconazole, measures that can be used in terbinafine failure include efflux-pump inhibitors, Hsp inhibitors and judicious use of antifungal drugs (topical + systemic) combinations. AREAS COVERED: A PubMed search was done for the relevant studies and reviews published in the last 22 years using keywords dermatophytes OR Trichophyton, anti-fungal, resistance, mechanism and fungal AND resistance mechanisms. Our aim was to look for literature on prevalent species and we specifically researched studies on Trichophyton genus. We have analyzed varied antifungal drug mechanisms and detailed varied experimental and approved drugs to treat recalcitrant dermatophytosis. EXPERT OPINION: Apart from administering drugs with low minimum inhibitory concentration, combinations of oral and topical antifungals (based on synergy data) and new formulations of existing drugs are useful in recalcitrant cases. There is a need for research into resistance mechanism of the existent Trichophyton strains in therapeutic failures in tinea corporis & cruris instead of data derived from laboratory strains which may not mirror clinical failures.

Towards an Early Clinical and Biological Resistance Detection in Dermatophytosis: About 2 Cases of Trichophyton indotineae.

Trichophyton indotineae causes resistant dermatophytosis to terbinafine. The global spread of terbinafine-resistant Trichophyton indotineae strains with mutations in the squalene epoxidase gene is a major issue. This emerging species is now more frequently isolated in Europe and we report here two cases of T. indotineae tinea corporis in Switzerland, one with in vitro resistance to terbinafine and a second with in vitro susceptibility but a clinical resistance. Mycology isolation from cultures and sequencing ITS gene were used to confirm T. indotineae infection. In vitro antifungal susceptibility was tested in a microplate with a colorimetric detection of fungal viability for the determination of the minimal inhibitory concentration (MIC). Facing these emerging resistances and since there are a limited number of antifungal agents available to treat dermatophytosis, the early detection of terbinafine resistance should be a prerequisite in the management of T. indotineae infections.