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).

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.

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.

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.

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.

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.

Primary hyperhidrosis increases the risk of cutaneous infection: a case-control study of 387 patients.

BACKGROUND: Although primary hyperhidrosis (PHH) has been frequently associated with diminished quality of life, the medical consequences of the condition are less well studied. OBJECTIVE: The objective was to study the clinical presentation of PHH and to determine its relationship to cutaneous infection. METHODS: A retrospective case-control study of patients encountered between 1993 and 2005 with the International Classification of Diseases, Ninth Revision diagnosis code for hyperhidrosis (HH) and meeting criteria for PHH was conducted. RESULTS: Of 387 patients with PHH included, 59% were female and 41% were male; mean age was 27.3 years (range 2-72). Sites of HH included soles (50.1%), palms (45.2%), and axillae (43.4%). Distributional patterns of HH were isolated axillary (27.6%), palmoplantar (24.3%), isolated plantar (15%), axillary/palmoplantar (5.7%), isolated palmar (5.7%), and craniofacial (5.2%). Axillary HH was more common in female patients (P = .004). The mean age of onset (18.6 +/- 12.3 years) indicated a mean duration of untreated symptoms of 8.9 years. Age at onset for palmoplantar HH (11.5 +/- 8 years) was significantly younger than for axillary HH (20.0 +/- 8.3 years; P < .0001), whereas onset of craniofacial HH (25.4 +/- 13.7 years) was older (P < .001). Exacerbating factors included stress/emotion/anxiety (56.7%) and heat/humidity (22%). The overall risk of any cutaneous infection was significantly (P < .0001) increased in HH compared with controls (odds ratio [OR] 3.2; 95% confidence interval [CI] 2.2-4.6). Site-specific risks of fungal infection (OR 5.0; 95% CI 2.6-9.8; P < .0001), bacterial infection (OR 2.6; 95% CI 1.2-5.7; P = .017), and viral infection (OR 1.9; 95% CI 1.2-3.0; P = .011) were all increased. Risks of pitted keratolysis (OR 15.4; 95% CI 2.0-117; P = .0003), dermatophytosis (OR 9.8; 95% CI 3.4-27.8; P < .0001), and verruca plantaris/vulgaris (OR 2.1; 95% CI 1.3-3.6; P = .0077) were particularly increased. Association with atopic/eczematous dermatitis (OR 2.9; 95% CI 1.5-55; P = .019) was observed. LIMITATIONS: Retrospective design and single-institution study are limitations. CONCLUSIONS: Patients with HH are at high risk of secondary infection. Management of HH may have a secondary benefit of decreasing this risk.

Dermatoses affecting desmosomes in animals: a mechanistic review of acantholytic blistering skin diseases.

Failure of desmosomal adhesion with ensuing keratinocyte separation - a phenomenon called acantholysis - can result from genetic, autoimmune or infectious proteolytic causes. Rare hereditary disorders of desmosomal formation have been identified in animals. Familial acantholysis of Angus calves and hereditary suprabasal acantholytic mechanobullous dermatosis of buffaloes appear to be similar to acantholytic epidermolysis bullosa of human beings. A genetic acantholytic dermatosis resembling human Darier disease has been rarely recognized in dogs. In autoimmune blistering dermatoses, circulating autoantibodies bind to the extracellular segments of desmosomal proteins and induce acantholysis. Autoantibodies against desmoglein-3 are found in canine pemphigus vulgaris and paraneoplastic pemphigus. Autoantibodies against desmoglein-1 have been rarely detected in dogs with pemphigus foliaceus. When circulating autoantibodies target desmogleins-1 and -3, mucocutaneous pemphigus vulgaris develops in dogs. Finally, several infectious agents can release proteases that cleave desmosomal bonds. In superficial pustular dermatophytosis of dogs and horses, Trichophyton hyphae colonize the stratum corneum, and acantholysis presumably develops because of proteases secreted by the dermatophytes. In exudative epidermitis of piglets, Staphylococcus bacteria - usually Staphylococcus hyicus- release exfoliatin toxins that bind to and specifically cleave desmoglein-1. Any of the above mechanisms can result in impairment of desmosomal function with subsequent acantholysis. The end point of adhesion failure is identical among these diseases: there is cleft formation where desmosomes are affected. The similarity of mechanisms explains why clinical and microscopic skin lesions overlap between entities, thus leaving clinicians and dermatopathologists with the conundrum of determining whether the acantholysis is of genetic, autoimmune or infectious origin.

Childhood dermatomycoses study in Sfax Hospital, Tunisia.

Mycoses are frequent affections in childhood. Fungal type varies according to the age and the affected organ. The aim of this study was to determine the aetiological agents of childhood dermatomycoses and to draw attention to the diversity of their clinical manifestations. Retrospective study dealing with children's cases with age <16-year old and having dermatomycosis diagnosed between 1991 and 2005 at the Parasitology and Mycology Laboratory of Sfax University Hospital. A total of 4559 children suspected to have superficial mycoses were examined. Dermatomycosis diagnosis was confirmed in 49.3% of cases. Dermatophytes were the most prevalent fungal agents and accounted for 1865 cases (80.6%) dominated by Trichophyton violaceum (54.1%) and Microsporum canis (24.5%). Tinea capitis (69.4%) was the most common type of infection, followed by tinea corporis (20%). Superficial yeast infections (442 cases) were dominated by Malassezia infections (71%). Candida infections were mainly due to Candida albicans (58%). The clinical features of paediatric dermatomycoses vary with the age of the children: tinea capitis and tinea corporis were more frequent before 13 years of age. After this age, tinea versicolor and onychomycoses became more common.

Cutaneous cryptococcosis of the penis.

Disseminated cryptococcosis is a well-known opportunistic infection in AIDS patients. We report an unusual patient who demonstrated an isolated plaque of cryptococcosis on the penis. Resolution of this plaque was obtained after treatment with fluconazole, but subsequent cutaneous dissemination occurred that was responsive to amphotericin B.

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.

Dermatological management of human immunodeficiency virus (HIV).

Atypical presentations of typical dermatological conditions are common in human immunodeficiency virus (HIV). This article will focus on three specific topics: eosinophilic folliculitis, psoriasis, and cutaneous mycoses. Their unique presentations in HIV and treatments are discussed.

Primary aspergillosis of the cheek. A diagnostic dilemma.

Primary cutaneous and subcutaneous aspergillosis is a rare entity and usually occurs secondary to systemic or disseminated aspergillosis. We describe a unique case of primary aspergillosis of the cheek in a 45-year-old male without any evidence of disseminated aspergillosis and recognizable trauma or surgical procedure in the area of cheek.

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.

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.

Increased hair shedding may be associated with the presence of Pityrosporum ovale.

BACKGROUND AND OBJECTIVE: Although the available data show that hair loss is an important cosmetic problem worldwide, the pathogenesis of common hair shedding is not fully understood. The aim of this study was to evaluate the association between hair shedding and cutaneous Malassezia infection. Malassezia fungi have been the suspected cause of dandruff for more than a century. Previously referred to as Pityrosporum ovale or P. orbiculare, these fungi are now known to consist of at least seven species. METHODS: Over a 4-year period, we obtained 300 hair samples from medical students. Based on the clinical history and a hair-pull test, the participants were divided into two groups: normal subjects and subjects with hair shedding. The students' scalp skin was gently scraped, smeared on a slide, colored by methylene blue, and observed under 10x magnification. RESULTS: All participants who had positive smears with >or=3 P. ovale organisms per low-power microscopic field (10x) were defined as 'carriers.' Seventy-six percent of students were Malassezia carriers. The prevalence of positive smears was significantly higher among subjects with hair shedding than among normal subjects (89.92% vs 9.52%, p<0.001). Furthermore, participants with positive smears had a significantly higher frequency of hair loss complaints and positive hair-pull tests. CONCLUSION: The proportion of subjects who were carriers of Malassezia yeasts was significantly higher in the group with hair shedding, and our results therefore raise the possibility of a relationship between this unicellular organism and hair loss. Our study findings should be explored in a larger series of patients.