RESUMEN
A severe outbreak of highly virulent and multi-resistant dermatophytosis by species in the Trichophyton mentagrophytes/T. interdigitale complex is ongoing in India. The correct identity of the etiologic agent is a much-debated issue. In order to define species limits, a taxonomic study was undertaken combining molecular, morphological, and physiological characteristics as evidence of classification. Molecular characteristics show that T. mentagrophytes s. str. and T. interdigitale s. str. can be distinguished with difficulty from each other, but are unambiguously different from the Indian genotype, T. indotineae by sequences of the HMG gene. The entities were confirmed by multilocus analysis using tanglegrams. Phenotypic characters of morphology and physiology are not diagnostic, but statistically significant differences are observed between the molecular siblings. These properties may be drivers of separate evolutionary trends. Trichophyton mentagrophytes represents the ancestral, homothallic cloud of genotypes with a probable geophilic lifestyle, while T. indotineae and T. interdigitale behave as anthropophilic, clonal offshoots. The origin of T. indotineae, which currently causes a significant public health problem, is zoonotic, and its emergence is likely due to widespread misuse of antifungals.
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Trichophyton , Antifúngicos/farmacología , Genotipo , Humanos , Trichophyton/genéticaRESUMEN
We report 16 patients of tinea cruris who presented with an asymptomatic red scrotum due to fixed dose combination creams containing antifungal agents and topical steroids applied to the thighs as a treatment of tinea cruris. The erythema resolved upon starting appropriate treatment with single molecule antifungal creams and oral antifungal drugs in about six weeks' time in majority of cases. We propose that this clinical presentation may be akin to red scrotum syndrome (RSS). Due to its asymptomatic nature in most of the cases, we propose that this could be a forme fruste of RSS.
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Antifúngicos , Tiña Cruris , Antifúngicos/uso terapéutico , Eritema/tratamiento farmacológico , Humanos , Masculino , Escroto , EsteroidesRESUMEN
BACKGROUND: The Indian ITS genotype VIII Trichophyton mentagrophytes population shows a high amount of different erg1 (ergosterol) mutants encoding for squalene epoxidase, which catalyses the first step of ergosterol biosynthesis. OBJECTIVES: Illumination of the implication of point mutations at position Ala448Thr in single and double erg1 T mentagrophytes mutants because mutants of this type were abundantly found within the Indian fungal population. METHODS: Growth in fluconazole or terbinafine containing medium was analysed using a microplate-laser-nephelometry (MLN)-based growth assay. RESULTS: Ala 448 Thr erg1 single mutants were terbinafine sensitive, but about 50% of isolates showed an increased fluconazole resistance, whereas 95% of the double mutants (Phe 397 Leu, Ala 448Thr) demonstrated combined terbinafine and increased fluconazole resistance. CONCLUSION: The new Indian T mentagrophytes populations show several point mutations in erg1. Point mutations at position 397 were previously described and cause terbinafine resistance. A large part of the double mutants exhibit resistance to terbinafine and fluconazole, demonstrating a selective advantage of the combination of both mutations.
RESUMEN
BACKGROUND: An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario. OBJECTIVES: The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase (SQLE) gene. PATIENTS/METHODS: We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE. RESULTS: Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine-sensitive and terbinafine-resistant isolates but was associated with increased MICs of itraconazole and voriconazole. CONCLUSIONS: The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.
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Antifúngicos/uso terapéutico , Arthrodermataceae/efectos de los fármacos , Farmacorresistencia Fúngica Múltiple/genética , Proteínas Fúngicas/genética , Adolescente , Adulto , Anciano , Arthrodermataceae/clasificación , Arthrodermataceae/enzimología , Niño , Femenino , Humanos , India , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mutación Missense , Escualeno-Monooxigenasa/genética , Adulto JovenRESUMEN
A 47-year-old male suffered soft tissue injuries 8 years ago that had been covered by meshed split thickness skin graft. During the last 2 years, he developed a chronic eczema (atopic dermatitis) on both recipient and donor sites on the lower extremities. Eczema on skin graft sites has been described rarely. However, this case is unique since both donor and recipient site were involved. We consider our observation as another example of Ruocco's immunocompromised districts of skin.
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Eccema/patología , Trasplante de Piel , Piel/patología , Eccema/inmunología , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Piel/inmunologíaRESUMEN
An alarming pan Indian increase in the incidence of superficial dermatophytosis has been noticed over the past 5-6 years. Recent studies have demonstrated emerging predominance of Trichophyton (T.) mentagrophytes as the causative organism in such cases. Interestingly, a distinct Indian genotype of T. mentagrophytes has been identified and recognised with the help of sequencing of the ITS region of the rDNA. That has, however, led to a basic confusion owing to the newly introduced taxonomy of dermatophytes in 2017. According to this most recently suggested classification and new taxonomy of dermatophytes, the former "T. mentagrophytes complex" is differentiated into T. mentagrophytes (zoophilic strains) and T. interdigitale (anthropophilic strains). We have noticed that in some recent studies the causative agent of the chronic, relapsing dermatophytosis outbreak in India has been described as T. interdigitale. In our opinion, it is very likely that these T. interdigitale strains isolated in Delhi and Chennai in India are indeed strains more closely related to the neotype of T. mentagrophytes and not strains of T. interdigitale. We therefore want to underscore the importance of a common nomenclature of species in accordance with the new taxonomy of dermatophytes. This would most likely facilitate better understanding of the issue amongst dermatologists and microbiologists in general. Mistaken identification of Trichophyton isolates not limited to India is very likely to occur due to the lack of appropriate molecular diagnosis which in turn is based on the already published data that presumably wrongly identify one species instead of the other.
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Errores Diagnósticos , Epidemias , Genotipo , Técnicas de Diagnóstico Molecular/métodos , Tiña/microbiología , Trichophyton/clasificación , Trichophyton/aislamiento & purificación , Análisis por Conglomerados , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Humanos , Incidencia , India/epidemiología , Filogenia , Análisis de Secuencia de ADN , Tiña/epidemiología , Trichophyton/genéticaRESUMEN
The disease burden of chronic-relapsing and therapy-refractory superficial dermatophytosis dramatically increased in India within the past 5-6 years. In order to evaluate the prevalence of this trend, 201 skin scrapings were collected from patients from all parts of India and were tested for dermatophytes using both fungal culture and a PCR-ELISA directly performed with native skin scrapings. Fungal culture material was identified by genomic Sanger sequencing of the internal transcribed spacer (ITS) region and the translation elongation factor (TEF)-1α gene. In total, 149 (74.13%) out of the 201 samples showed a dermatophyte-positive culture result. Out of this, 138 (92.62%) samples were identified as Trichophyton (T.) mentagrophytes and 11 (7.38%) as Trichophyton rubrum. The PCR-ELISA revealed similar results: 162 out of 201 (80.56%) samples were dermatophyte-positive showing 151 (93.21%) T mentagrophytes- and 11 (6.79%) T rubrum-positive samples. In this study, we show for the first time a dramatic Indian-wide switch from T rubrum to T mentagrophytes. Additionally, sequencing revealed a solely occurring T mentagrophytes "Indian ITS genotype" that might be disseminated Indian-wide due to the widespread abuse of topical clobetasol and other steroid molecules mixed with antifungal and antibacterial agents.
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Epidemias , Tiña/epidemiología , Trichophyton/clasificación , Trichophyton/aislamiento & purificación , Adolescente , Adulto , Anciano , Niño , Preescolar , ADN de Hongos/química , ADN de Hongos/genética , ADN Espaciador Ribosómico/química , ADN Espaciador Ribosómico/genética , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Epidemiología Molecular , Factor 1 de Elongación Peptídica/genética , Reacción en Cadena de la Polimerasa , Prevalencia , Análisis de Secuencia de ADN , Trichophyton/genética , Adulto JovenRESUMEN
A 6 month-old-female infant from Bahrain visiting Germany with her family for a holiday was seen by us for extensive dermatophytosis of the back, buttocks, chest and groins. Topical treatment by terbinafine for over 2 months was not successful. Other family members including adults and children were treated in Bahrain with topical antifungals and oral voriconazole which was not helpful. Mycological examination performed in Germany revealed the detection of the zoophilic dermatophyte Trichophyton (T.) mentagrophytes. The newly described genotype VIII within the species T. mentagrophytes was identified by sequencing of the "internal transcribed spacer" (ITS) region of the fungal rDNA. This genotype of T. mentagrophytes is the main causative agent of the current epidemic of chronic recalcitrant dermatophytoses in India. Transmission of this Indian genotype of T. mentagrophytes to other countries due to globalization is a serious issue to be considered. Moreover, a significant percentage of these Indian T. mentagrophytes strains are resistant to terbinafine both in vitro and by the way of genetic point mutations in the squalene epoxidase (SQLE) gene. Some are also found to be partially resistant against itraconazole and voriconazole. The point mutation TTC/TTA was found by SQLE mutation analysis in this particular T. mentagrophyte isolate from Bahrain. This point mutation is closely associated with F397L amino acid substitution of the enzyme indicative of in vitro resistance of the dermatophyte against terbinafine. The girl was successfully treated by topical miconazole and later by ciclopirox olamine. This is the first report on an infection due to a terbinafine-resistant T. mentagrophytes strain of the ITS genotype VIII from India in Germany.
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Antifúngicos/farmacología , Ciclopirox/uso terapéutico , Miconazol/uso terapéutico , Terbinafina/farmacología , Tiña del Cuero Cabelludo/tratamiento farmacológico , Tiña/tratamiento farmacológico , Trichophyton/genética , Trichophyton/aislamiento & purificación , Adulto , Antifúngicos/uso terapéutico , Bahrein , Femenino , Genotipo , Alemania , Humanos , Lactante , ARN de Hongos , Análisis de Secuencia de ARN , Terbinafina/uso terapéutico , Tiña/diagnóstico , Tiña del Cuero Cabelludo/diagnóstico , Trichophyton/clasificaciónAsunto(s)
Enfermedades de la Piel , Estrías de Distensión , Humanos , Cicatriz/etiología , Cicatriz/patologíaRESUMEN
Genital dermatophytosis has been considered rare by most Western authorities. However, to the contrary, Indian reports have shown a higher prevalence of genital dermatophytosis due to warm and humid climate, overcrowding and lack of hygiene. A review is presented for 24 cases of male genital dermatophytosis occurring in patients suffering from tinea cruris in India who have been randomly applying various broad-spectrum steroid antifungal and antibacterial creams containing one or more antifungal and antibiotic in addition to potent corticosteroids, mainly clobetasol propionate. This is such a common phenomenon that Indian dermatologists are witnessing an epidemic of sorts of steroid-modified dermatophytosis and we hereby share various clinical presentations of dermatophytosis of penis and/or scrotum in patients with tinea cruris who have been applying the above-mentioned creams. The review also discusses the bleak scenario that prevails in India regarding the drug regulatory affairs that allow such dangerous and irrational combinations that are sold over the counter because of misinterpretation of the law and lax implementation of existing laws.
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Corticoesteroides/efectos adversos , Antiinfecciosos Locales/efectos adversos , Enfermedades de los Genitales Masculinos/tratamiento farmacológico , Mal Uso de Medicamentos de Venta con Receta , Esteroides/efectos adversos , Tiña/tratamiento farmacológico , Tiña/epidemiología , Administración Tópica , Adolescente , Corticoesteroides/administración & dosificación , Adulto , Antiinfecciosos Locales/uso terapéutico , Antifúngicos/efectos adversos , Antifúngicos/uso terapéutico , Clobetasol/efectos adversos , Clobetasol/uso terapéutico , Enfermedades de los Genitales Masculinos/epidemiología , Enfermedades de los Genitales Masculinos/microbiología , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Pene/microbiología , Mal Uso de Medicamentos de Venta con Receta/estadística & datos numéricos , Prevalencia , Escroto/microbiología , Esteroides/administración & dosificación , Adulto JovenAsunto(s)
Anetodermia/etiología , Hidróxidos/farmacología , Molusco Contagioso/tratamiento farmacológico , Compuestos de Potasio/farmacología , Anetodermia/tratamiento farmacológico , Anetodermia/fisiopatología , Niño , Humanos , Hidróxidos/metabolismo , Masculino , Molusco Contagioso/complicaciones , Molusco Contagioso/fisiopatología , Compuestos de Potasio/metabolismoRESUMEN
Vulvar malignancies are important tumors of the female reproductive system. They represent a serious health issue with an incidence between 2 and 7 per 100,000 and year. We provide a review about most important cancer entities, i.e., melanoma, squamous cell carcinoma, basal cell carcinoma, neuroendocrine cancer, and skin adnexal malignancies.Squamous cell carcinoma is the most common vulvar malignancy that can develop from vulvar intraepithelial neoplasia or de novo. Basal cell carcinoma represents only 2% of all vulvar cancers. Melanoma of the vulva exists in two major types-superficial spreading and acral lentiginous. A special feature is the occurrence of multiple vulvar melanomas. Of the adnexal cancer types Paget's disease and carcinoma are seen more frequently than other adnexal malignancies. The dermatologist should be aware of this problem, since he might be the first to be consulted by patients for vulvar disease. Treatment should be interdisciplinary in close association to gynecologists, oncologists, and radiologists.
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Neoplasias Cutáneas/patología , Neoplasias de la Vulva/patología , Carcinoma in Situ/patología , Carcinoma Basocelular/patología , Carcinoma de Células Escamosas/patología , Diagnóstico Diferencial , Femenino , Humanos , Melanoma/patología , Estadificación de Neoplasias , Neoplasias de Anexos y Apéndices de Piel/patología , Tumores Neuroendocrinos/patología , Enfermedad de Paget Extramamaria/patología , Pronóstico , Piel/patología , Vulva/patologíaRESUMEN
Dermatomycoses affect free skin, hairy scalp, fingernails and toenails. In addition, oral mucosa and genital mucosa can also be affected by fungal infections. The most common pathogens causing skin fungal infections are dermatophytes. They are responsible for, among others, tinea corporis, tinea capitis and onychomycosis (tinea unguium). Mainly anthropophilic dermatophytes are found as pathogens. In the case of tinea capitis-at least in Europe and in German-speaking countries-zoophilic skin fungi must also be considered. Rarely, geophilic dermatophytes can also be isolated. Yeast infections of the skin, mostly caused by Candida albicans, primarily affect the intertriginous skin areas, for example, the groin region, but also the submammary area and the spaces between the fingers and toes. Elderly patients are often affected, but also infants and, in particular, immunocompromised patients. These patient groups are also more frequently affected by oral mucosal infections caused by Candida albicans and other Candida species. Pseudomembranous candidiasis of the oral mucosa and tongue typically affects patients with HIV/AIDS. Mold infections in dermatology are relevant in onychomycosis of the big toenail. The causative agent is usually Scopulariopsis brevicaulis. Cutaneous mold infections are rare and only occur in immunocompromised patients. The mycological diagnosis of dermatomycoses is based on the microscopic, if possible fluorescence-optical detection of fungal hyphae and spores from skin scales, nail shavings and hair roots. The culture detection of dermatophytes, yeasts and molds allows the identification of the causative fungal species, but often fails, especially in patients who have already been treated with antifungal agents. In view of the high sensitivity and specificity of the molecular methods for fungal detection compared to culture, polymerase chain reaction (PCR) must realistically be regarded as the gold standard for dermatophytosis diagnostics. However, it should not be neglected that the three pillars of diagnostics-preparation, culture, PCR-currently deliver the best results.
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Dermatitis , Onicomicosis , Tiña del Cuero Cabelludo , Anciano , Lactante , Humanos , Piel , Candida albicans , CandidaRESUMEN
Trichophyton (T.) indotineae is a newly identified dermatophyte species that has been found in a near-epidemic form on the Indian subcontinent. There is evidence of its spread from the Indian subcontinent to a number of countries worldwide. The fungus is identical to genotype VIII within the T. mentagrophytes/T. interdigitale species complex, which was described in 2019 by sequencing the Internal Transcribed Spacer (ITS) region of ribosomal DNA of the dermatophyte. More than 10 ITS genotypes of T. interdigitale and T. mentagrophytes can now be identified. T. indotineae causes inflammatory and itchy, often widespread, dermatophytosis affecting the groins, gluteal region, trunk, and face. Patients of all ages and genders are affected. The new species has largely displaced other previously prevalent dermatophytes on the Indian subcontinent. T. indotineae has become a problematic dermatophyte due to its predominantly in vitro genetic resistance to terbinafine owing to point mutations of the squalene epoxidase gene. It also displays in vivo resistance to terbinafine. The most efficacious drug currently available for this terbinafine-resistant dermatophytoses, based on sound evidence, is itraconazole.
RESUMEN
We report four cases of ulcerated striae following misuse of fixed dose combinations creams containing clobetasol propionate with antifungal and antibacterial agents.
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Antialérgicos , Estrías de Distensión , Corticoesteroides/efectos adversos , Clobetasol/efectos adversos , Humanos , Estrías de Distensión/inducido químicamente , ÚlceraRESUMEN
Trichophyton (T.) mentagrophytes now accounts for an overwhelming majority of clinical cases in India, a new "Indian genotype" (T. mentagrophytes ITS genotype VIII) having been isolated from skin samples obtained from cases across a wide geographical distribution in this country. The conventional diagnostic methods, like fungal culture, are, however, inadequate for diagnosing this agent. Thus, molecular methods of diagnosis are necessary for proper characterization of the causative agent. The shift in the predominant agent of dermatophytosis from T. rubrum to T. mentagrophytes, within a relatively short span of time, is without historic parallel. The apparent ease of transmission of a zoophilic fungus among human hosts can also be explained by means of mycological phenomena, like anthropization.
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Tiña/diagnóstico , Trichophyton/clasificación , ADN de Hongos/genética , Dermoscopía , Epidemias , Genotipo , Humanos , India , Filogenia , Reacción en Cadena de la Polimerasa , Tiña/epidemiología , Tiña/transmisión , Trichophyton/genéticaRESUMEN
One of the canonical features of the current outbreak of dermatophytosis in India is its unresponsiveness to treatment in majority of cases. Though there appears to be discordance between in vivo and in vitro resistance, demonstration of in vitro resistance of dermatophytes to antifungals by antifungal susceptibility testing is essential as it may help in appropriate management. The practical problem in the interpretation of antifungal susceptibility testing is the absence of clinical breakpoints and epidemiologic cutoff values. In their absence, evaluation of the upper limit of a minimal inhibitory concentration of wild type isolates may be beneficial for managing dermatophytosis and monitoring the emergence of isolates with reduced susceptibility. In the current scenario, most of the cases are unresponsive to standard dosages and duration of treatment recommended until now. This has resulted in many ex-cathedra modalities of treatment that are being pursued without any evidence. There is an urgent need to carry out methodical research to develop an evidence base to formulate a rational management approach in the current scenario.