Host immune responses in dermatophytes infection.

Dermatophytosis is a skin infection caused by keratinophilic, filamentous fungi. These are highly prevalent, common mycoses, affecting approximately 20% of the population. These fungi invade the stratum corneum, and other keratinised tissues, like nails and hair, where they grow by secreting enzymes and degrading keratin to obtain nutrients. Clinical presentation is variable and may depend on many factors, such as the infection site, the host's immunity and the dermatophyte's virulence. Generally, patients with acute superficial dermatophytosis mount cell-mediated immune responses. However, those suffering from chronic or recurrent infections are unable to develop this response, for reasons yet unknown. Several reports have described severe and occasionally life-threatening invasive diseases (deep dermatophytosis) associated with genetic mutations in the innate immunity-associated molecule CARD9, displaying the need to better understand its immune response. These dermatoses have substantial clinical consequences, producing chronic and difficult to treat skin lesions. They also lead to a decline in the patient's quality of life and impact their self-esteem. This review summarises findings on the immune response against dermatophytes.

Phylogenetic investigation of skin sloughing rates in frogs: relationships with skin characteristics and disease-driven declines.

Amphibian skin is highly variable in structure and function across anurans, and plays an important role in physiological homeostasis and immune defence. For example, skin sloughing has been shown to reduce pathogen loads on the skin, such as the lethal fungus Batrachochytrium dendrobatidis ( Bd), but interspecific variation in sloughing frequency is largely unknown. Using phylogenetic linear mixed models, we assessed the relationship between skin turnover rate, skin morphology, ecological traits and overall evidence of Bd-driven declines. We examined skin sloughing rates in 21 frog species from three continents, as well as structural skin characteristics measured from preserved specimens. We found that sloughing rate varies significantly with phylogenetic group, but was not associated with evidence of Bd-driven declines, or other skin characteristics examined. This is the first comparison of sloughing rate across a wide range of amphibian species, and creates the first database of amphibian sloughing behaviour. Given the strong phylogenetic signal observed in sloughing rate, approximate sloughing rates of related species may be predicted based on phylogenetic position. While not related to available evidence of declines, understanding variation in sloughing rate may help explain differences in the severity of infection in genera with relatively slow skin turnover rates (e.g. Atelopus).

Cutaneous mucormycosis caused by Rhizopus microsporus in an immunocompetent patient: A case report and review of literature.

RATIONALE: Cutaneous mucormycosis is an uncommon disease and occurs rarely in immunocompetent patients. PATIENT CONCERNS: We reported the case of a 37-year-old man presenting with a skin lesion on the left side of the chest wall with no history of trauma or primary diseases. He was firstly misdiagnosed as tuberculosis and the proper treatment was thus delayed. DIAGNOSES: Histopathological examination and fungal culture of the lesion confirmed cutaneous mucormycosis. The isolate was identified as Rhizopus microspores by ITS sequencing. INTERVENTIONS: The patient was treated with oral posaconazole 400 mg bid for 150 days. OUTCOMES: The patient recovered satisfactorily. No recurrence was found during the follow-up and no side effect of liver function was found. LESSONS: This case helps doctors to consider the possibility of serious fungal infection in immunocompetent patients. It also suggested that posaconazole could be an alternative choice for the treatment of mucormycosis considering the severe side effect of Amphotericin B.

Malassezia ecology, pathophysiology, and treatment.

Malassezia are lipid dependent basidiomycetous yeasts that inhabit the skin and mucosa of humans and other warm-blooded animals, and are a major component of the skin microbiome. They occur as skin commensals, but are also associated with various skin disorders and bloodstream infections. The genus currently comprises 17 species and has recently been assigned its own class, Malasseziomycetes. Importantly, multiple Malassezia species and/or genotypes may cause unique or similar pathologies and vary in their antifungal susceptibility. In addition to culture-based approaches, culture-independent methods have added to our understanding of Malassezia presence and abundance and their relationship to pathogenicity. Moreover, these novel approaches have suggested a much wider-spread presence, including other human body parts and even other ecosystems, but their role in these arenas requires further clarification. With recent successful transformation and genetic engineering of Malassezia, the role of specific genes in pathogenesis can now be studied. We suggest that characterizing the metabolic impact of Malassezia communities rather than species identification is key in elucidation of pathophysiological associations. Finally, the increasing availability of genome sequences may provide key information aiding faster diagnostics, and understanding of the biochemical mechanisms for Malassezia skin adaptation and the design of future drugs.

Host-microbe interactions: Malassezia and human skin.

The skin is our first line of defense, protecting us from invasion and evaporation. Its variable structure, changing geography, and complex immune repertoire provide a vast interface for our cutaneous microbial community. Skin is inhabited by many thousands of microbes, but this review focuses on the dominant eukaryote, Malassezia, and its host interaction. Malassezia compromises 17 species with variable niche specificities and differing pathogenic potential. It has been known as a skin inhabitant for over 100 years, and is now accepted to be on all warm-blooded animals. Malassezia occupy healthy and diseased skin, so their role as commensal or pathogenic organisms is complex. Malassezia interact with their host indirectly through immune interplay and directly via chemical mediators. While some interactions are known, many remain to be fully understood.

White-nose syndrome increases torpid metabolic rate and evaporative water loss in hibernating bats.

Fungal diseases of wildlife typically manifest as superficial skin infections but can have devastating consequences for host physiology and survival. White-nose syndrome (WNS) is a fungal skin disease that has killed millions of hibernating bats in North America since 2007. Infection with the fungus Pseudogymnoascus destructans causes bats to rewarm too often during hibernation, but the cause of increased arousal rates remains unknown. On the basis of data from studies of captive and free-living bats, two mechanistic models have been proposed to explain disease processes in WNS. Key predictions of both models are that WNS-affected bats will show 1) higher metabolic rates during torpor (TMR) and 2) higher rates of evaporative water loss (EWL). We collected bats from a WNS-negative hibernaculum, inoculated one group with P. destructans, and sham-inoculated a second group as controls. After 4 mo of hibernation, TMR and EWL were measured using respirometry. Both predictions were supported, and our data suggest that infected bats were more affected by variation in ambient humidity than controls. Furthermore, disease severity, as indicated by the area of the wing with UV fluorescence, was positively correlated with EWL, but not TMR. Our results provide the first direct evidence that heightened energy expenditure during torpor and higher EWL independently contribute to WNS pathophysiology, with implications for the design of potential treatments for the disease.

Common Skin Conditions in Children: Skin Infections.

Skin infections account for a significant subset of dermatologic conditions of childhood. Common cutaneous viral infections in children include warts, molluscum contagiosum, hand-foot-and-mouth disease, and herpes simplex. Although viral infections are self-limited and often only mildly symptomatic, they can cause anxiety, embarrassment, and health care use. Recognition of their common and atypical presentations is necessary to differentiate them from other skin conditions of similar morphology. Impetigo, cellulitis, and abscess comprise the majority of childhood bacterial skin infections and are treated with topical or systemic antibiotics that cover group A Streptococcus and Staphylococcus aureus. Common fungal dermatologic infections in children are oral and genital candidiasis, tinea capitis, and tinea corporis. Management consists of topical and systemic antifungals, including nystatin, triazoles, terbinafine, griseofulvin, and imidazoles. Scabies is the most common parasitic skin infection among children and is managed with topical permethrin. Although serious illness is not common among children returning from international travel, patients presenting with fever and rash, especially petechial or hemorrhagic lesions, require thorough evaluation. Of the numerous reportable conditions that present with childhood rash, tick-borne illnesses, measles, rubella, and varicella are the most common.

Orofacial infection by Conidiobolus coronatus.

Entomophtoramycosis is a type of subcutaneous mycosis which includes both basidiobolomycosis and conidiobolomycosis; the latter is caused by Conidiobolus coronatus, a saprophytic fungus which lives in tropical soils. This mycosis characteristically affects the paranasal sinuses and oropharynx, with the potential to deform the face in patients without apparent immunodeficiency. It has a chronic course of infection with a tendency to form granulomas visible using histology. We present the case of a 28 year-old male agricultural worker, with a clinical profile of 6 months' evolution of rhinofacial tumefaction, nasal obstruction and post-nasal drip who was diagnosed with conidiobolomycosis by means of tissue culture after multiple biopsies of the facial area. The patient received antifungal treatment with amphotericin B and subsequently with itraconazol, resulting in a dramatic improvement without the need for surgical treatment; itraconazol was administered for one year and there was no evidence of relapse at the end of this period. Due to the low frequency of this disease there is no established treatment strategy; however, the use of azoles such as itraconazol with or without adjuvant surgical treatment is increasingly seen in case reports. The present report adds to the clinical experience in Colombia of this rare mycosis and also describes the long-term clinical and therapeutic response.

Dermatomycosis frequency and localization sites.

INTRODUCTION: Since the prevalence of skin mycotic infections is changing and is area depended we aimed to analyze the frequency of the skin myocotic infections and the appearance sites. MATERIAL AND METHODS: There were involved 560 patients referred to the Dermatology Clinic of University Clinical Center of Kosova during a period of one year. RESULTS: The mean age of our study group was around thirties with a predominance of female and rural patients. Although most of cases presented with single site disease localization, we observed the increase in number of cases with more than one site localization with age. CONCLUSION: The increased prevalence skin mycotic infections, as well as more than one place of localization deserve a multidimensional approach.

Acute toxicity and risk of infection during total skin electron beam therapy for mycosis fungoides.

BACKGROUND: Detailed rates of acute toxicity and skin infection during total skin electron beam therapy (TSEBT) for mycosis fungoides have not been reported in a large, modern series. OBJECTIVE: We sought to demonstrate the rates of acute toxicity and skin infection during TSEBT. METHODS: We retrospectively reviewed 89 consecutive courses of TSEBT. In all, 82 courses were prescribed a dose of 30 to 36 Gy and were included in the toxicity analysis. We recorded the types and grades of acute treatment toxicities and the incidence of infection during TSEBT for comparison with the previously documented baseline incidence of infection in mycosis fungoides. RESULTS: The most common toxicities included erythema/desquamation (76%), blisters (52%), hyperpigmentation (50%), and skin pain (48%). The worst reported toxicity grade per patient was grade 1 in 21%, grade 2 in 67%, and grade 3 in 10%, with no grade 4 or 5 toxicities. According to the previously reported rate, a total of 2.4 infections were expected for our cohort at baseline. The number with skin infection was 26 (32%) (relative risk 10.8, P < .01), and of these, 12 (15%) were culture confirmed (relative risk 5.0, P < .01). LIMITATIONS: This was a retrospective study design. CONCLUSION: The risk of cutaneous infection is significant during TSEBT.

A comprehensive pathophysiology of dandruff and seborrheic dermatitis - towards a more precise definition of scalp health.

Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the pathophysiological understanding is still incomplete but suggests a role of Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal responses. The objective of this report is to review published literature from in vivo studies of D/SD populations to provide a more complete description of overall scalp health. New biomolecular capabilities establish a depth of pathophysiological understanding not previously achievable with traditional means of investigation. Biomarkers representing inflammation, hyper-proliferation and barrier function are all perturbed by the D/SD condition and robustly respond to therapeutic resolution. These biomarkers can be sampled noninvasively, enabling their use in routine clinical evaluations as either surrogate endpoints or complementary ones to classical signs/symptoms to broaden the etiological learning.

Pathophysiology in mountain yellow-legged frogs (Rana muscosa) during a chytridiomycosis outbreak.

The disease chytridiomycosis is responsible for declines and extirpations of amphibians worldwide. Chytridiomycosis is caused by a fungal pathogen (Batrachochytrium dendrobatidis) that infects amphibian skin. Although we have a basic understanding of the pathophysiology from laboratory experiments, many mechanistic details remain unresolved and it is unknown if disease development is similar in wild amphibian populations. To gain a better understanding of chytridiomycosis pathophysiology in wild amphibian populations, we collected blood biochemistry measurements during an outbreak in mountain yellow-legged frogs (Rana muscosa) in the Sierra Nevada Mountains of California. We found that pathogen load is associated with disruptions in fluid and electrolyte balance, yet is not associated with fluctuations acid-base balance. These findings enhance our knowledge of the pathophysiology of this disease and indicate that disease development is consistent across multiple species and in both laboratory and natural conditions. We recommend integrating an understanding of chytridiomycosis pathophysiology with mitigation practices to improve amphibian conservation.

Inoculation of bats with European Geomyces destructans supports the novel pathogen hypothesis for the origin of white-nose syndrome.

White-nose syndrome (WNS) is an emerging disease of hibernating bats associated with cutaneous infection by the fungus Geomyces destructans (Gd), and responsible for devastating declines of bat populations in eastern North America. Affected bats appear emaciated and one hypothesis is that they spend too much time out of torpor during hibernation, depleting vital fat reserves required to survive the winter. The fungus has also been found at low levels on bats throughout Europe but without mass mortality. This finding suggests that Gd is either native to both continents but has been rendered more pathogenic in North America by mutation or environmental change, or that it recently arrived in North America as an invader from Europe. Thus, a causal link between Gd and mortality has not been established and the reason for its high pathogenicity in North America is unknown. Here we show that experimental inoculation with either North American or European isolates of Gd causes WNS and mortality in the North American bat, Myotis lucifugus. In contrast to control bats, individuals inoculated with either isolate of Gd developed cutaneous infections diagnostic of WNS, exhibited a progressive increase in the frequency of arousals from torpor during hibernation, and were emaciated after 3-4 mo. Our results demonstrate that altered torpor-arousal cycles underlie mortality from WNS and provide direct evidence that Gd is a novel pathogen to North America from Europe.

Dermatomicosis en ancianos institucionalizados y estudios de sensibilidad in vitro a los antifúngicos sistémicos / Dermatomycosis in institutionalized elderly patients and in vitro sensitivity study to systemic antifungus

Se determinó la prevalencia de dermatomicosis en ancianos institucionalizados de Ciudad Bilívar, Estado Bolívar, Venezuela, y se evaluó la sensibilidad in vitro de los aislamientos clínicos a los antifúngicos itraconazol, fluconazol y terbinafina mediante el método de microdilución en medio líquido, recomendado por el Comité Internacional de Laboratorios Clínicos (M38-P), con algunas modificicaciones. Los hongos fueron identificados mediante métodos tradicionales. Las levaduras se identificaron mediante pruebas bioquímicas, sistema Api 20 C AUX (Biomérieux SA®, France) y crecimiento en medio de Staib. Se estudiaron 74 ancianos, todos recluidos en el Asilo "San Vicente de Paúl" y el Geriátrico "Carlos Fragachán" quienes dieron consentimiento por escrito para participar en el estudio. La edad de los pacientes estuvo comprendida entre 63 y 98 años (80 ± 8,4 años), la mayoría eran hombres (73%). Todos los pacientes tenían lesiones sugestivas de onicomicosis en los pies. El único dermatofito aislado fue Trichophyton rubrum (n=2) el cual resultó sensible al Itraconazol, terbinafina y sensibilidad variable a flucozazol. Asimismo se logró aislar Aspergillus niger (n=5; 6,7%) demostrándose sensible a terbinafina y fluconazol con sensibilidad variable a itraconazol. Candida albicans (n=3; 4,1%) fue sensible a fluconazol, resistentes a itraconazol y variable a la terbinafina. Aspergillus flavus fue aislado en dos casos (2,7%). Además de Geomyces sp, Fusarium oxysporum y Pseudeurotium ovale. Se concluye que existe una prevalencia baja de dermatomicosis en los ancianos institucionalizados de Ciudad Bolívar y que las lesiones clinicamente observadas son debidas a los cambios degenerativos propios de la edad.

A study determine prevalence of dermatomycosis in 74 institutionalized elderly patients was conductted in Ciudad Bolivar, state of Bolivar, Venezuela. Clinical isolates were assayed for in vitro sensitivity to itraconazole, fluconazole, and terbinafine using a slightly modified version of the microdilution method in liquid medium recommended by the International Committee of Clinical Laboratory (M38-P). Traditional methods were used to identify the fungi. The yeasts were identified by Api 20C AUX biochemical testing (bioMérieux SA®, France) and growth on Staib media. The elders, mostly men (73%), from the "San Vicente de Paúl" Nursing Home and the "Carlos Fragachan" Geriatric Hospital, were aged between 63 and 98 (80 ± 8.4 years). All the patients, whose written consent was secured, had lesions suggestive of onychomycosis. Trichophyton rubrum was the only isolated dermatophyte (n=2), which resulted sensitive to itraconazole and terbinafine, with variable sensitivity to fluconazole. Aspergillus niger (n=5;6.7%) was sensitive to terbinafine and fluconazole with variable itraconazole sensitivity. Candida albicans (n=3; 4.1%) was fluconazole sensitive, resistant to itraconazole, and variable to terbinafine. Aspergillus flavus was isolated in two cases 2.7%). Geomyces sp., Fusarium oxysporum, and Pseudeurotium ovale were also isolated. It is concluded that there is a low prevalence of dermatomycosis among institutionalized elders in Ciudad Bolivar, and that the lesions clinically observed were due to degenerative changes naturally occurring with aging.

White-nose syndrome: is this emerging disease a threat to European bats?

White-nose syndrome (WNS) is a newly emergent disease that potentially threatens all temperate bat species. A recently identified fungus, Geomyces destructans, is the most likely causative agent of this disease. Until 2009, WNS and G. destructans were exclusively known from North America, but recent studies have confirmed this fungus is also present in Europe. We assembled an international WNS consortium of 67 scientists from 29 countries and identified the most important research and conservation priorities to assess the risk of WNS to European bats. Here, we review what is known about WNS and G. destructans and detail the conservation and research recommendations aimed at understanding and containing this emerging infectious disease.

Differential host susceptibility to Batrachochytrium dendrobatidis, an emerging amphibian pathogen.

The amphibian fungal pathogen Batrachochytrium dendrobatidis (Bd) has received considerable attention due to its role in amphibian population declines worldwide. Although many amphibian species appear to be affected by Bd, there is little information on species-specific differences in susceptibility to this pathogen. We used a comparative experimental approach to examine Bd susceptibility in 6 amphibian species from the United States. We exposed postmetamorphic animals to Bd for 30 days and monitored mortality, feeding rates, and infection levels. In all species tested, Bd-exposed animals had higher rates of mortality than unexposed (control) animals. However, we found differences in mortality rates among species even though the amount of Bd detected on the different species' bodies did not differ. Of the species tested, southern toads (Anaxyrus terrestris) and wood frogs (Lithobates sylvaticus) had the highest rates of Bd-related mortality. Within species, we detected lower levels of Bd on individuals that survived longer and found that the relationship between body size and infection levels differed among species. Our results indicate that, even under identical conditions, amphibian species differ in susceptibility to Bd. This study represents a step toward identifying and understanding species variation in disease susceptibility, which can be used to optimize conservation strategies.

[Role of cytokine secretion of human keratinocytes in dermatophytosis].

The clinical presentation of dermatophytosis depends on species of the infecting fungus. The infections caused by the anthropophilic species tend to be chronic and intractable, and the resultant inflammation is minimal. On the other hand, the infections caused by the geophilic and zoophilic species tend to be self-healing, and the resultant inflammation is more severe. We investigated the role of cytokine secretion of human keratinocyte during dermatophyte infections: Arthroderma benhamiae, a zoophilic dermatophyte, and Trichophyton tonsurans, an anthropophilic dermatophyte. The results demonstrate that keratinocytes secrete a broad spectrum of cytokines including proinflammatory cytokines, chemokines, and immunomodulatory cytokines in response to A. benhamiae infection, whereas T.tonsurans infection stimulates the production of only a limited number of cytokines. Such differential cytokine secretion of the keratinocytes in response to infection by dermatophyte species may reflect the distinct inflammatory responses in the skin.