Deep Cutaneous Fungal Infections Research Articles

JAAD Game Changers: "Diagnosis of deep cutaneous fungal infections: Correlation between skin tissue culture and histopathology".

JAAD Game Changers: "Diagnosis of deep cutaneous fungal infections: Correlation between skin tissue culture and histopathology".

Electrically-driven drug delivery into deep cutaneous tissue by conductive microneedles for fungal infection eradication and protective immunity

Fungal infections affect over 13 million people worldwide and are responsible for 1.5 million deaths annually. Some deep cutaneous fungal infections may extend the dermal barriers to cause systemic infection, resulting in substantial morbidity and mortality. However, the management of deep cutaneous fungal infection is challenging and yet overlooked by traditional treatments, which only offer limited drug availability within deep tissue. In this study, we have developed an electrically stimulated microneedle patch to deliver miconazole into the subcutaneous layer. We tested its antifungal efficacy using in vitro and ex vivo models that mimic fungal infection. Moreover, we confirmed its anti-fungal and wound-healing effects in a murine subcutaneous fungal infection model. Furthermore, our findings also showed that the combination of miconazole and applied current synergistically stimulated the nociceptive sensory nerves, thereby activating protective cutaneous immunity mediated by dermal dendritic and γδ-T cells. Collectively, this study provides a new strategy for minimally invasive delivery of therapeutic agents and the modulation of the neuro-immune axis in deep tissue.

First report of deep cutaneous fungal infection caused by Nigrograna hydei

First report of deep cutaneous fungal infection caused by Nigrograna hydei

Deep mycosis mimicking cutaneous squamous cell carcinoma.

Deep cutaneous mycoses (DCMs) and skin fungal infections can cause significant morbidity until diagnosed and treated. In immunocompromised people, Candida spp., Aspergillus spp., and Fusarium spp. fungi can cause these infections, but dermatophytes, especially Trichophyton rubrum and T. mentagrophytes, are the most common. Superficial erythematous lesions become firm subcutaneous nodules, ulcers, abscesses, or sinus tracts. In advanced cases, DCMs can cause osteomyelitis and bone loss. DCM included mycetoma, a chronic infectious disease of the skin, subcutaneous tissues, and bones. In some areas, it is endemic and can mimic cutaneous tuberculosis or cancerous lesions, making diagnosis difficult. Clinical presentation, radiological findings, and microbiological culture are used to diagnose with molecular methods helping in culture-negative cases. An immunocompetent farmer with a wrist lesion initially suspected as cutaneous squamous cell carcinoma was histologically diagnosed as eumycetoma, emphasizing the importance of considering deep mycoses in high-risk individuals and their heterogeneous clinical presentation.

Hyaluronic Acid-Based CuS Nanoenzyme Biodegradable Microneedles for Treating Deep Cutaneous Fungal Infection without Drug Resistance.

Deep cutaneous fungal infection (DCFI) is difficult to be treated by the traditional topical application due to low drug transdermal efficiency, poor fungicidal effect, and easy to develop drug resistance. Here, we report a novel biodegradable microneedle patch (CuS/PAF-26 MN) for DCFI treatment. CuS/PAF-26 MN is composed of hyaluronic acid (HA) and sodium carboxymethylcellulose (CMC-Na), which can simultaneously deliver copper sulfide nanoenzyme (CuS NE) and antimicrobial peptide (PAF-26). CuS NE catalyzes hydrogen peroxide to produce reactive oxygen species (ROS), and PAF-26 directly destroys the cell membrane of fungi. The combination of ROS toxicity produced by CuS NE and the destruction of fungal membrane by PAF-26 shows strong antifungal activities without drug resistance. The antifungal effect of CuS/PAF-26 MN is significantly superior to that of traditional ointment, CuS MN or PAF-26 MN in a DCFI mouse model. Therefore, CuS/PAF-26 MN shows a promising application prospect for treating DCFI.

Bedside Diagnosis for Disseminated Deep Dermatophytosis: a Case Series Study.

Deep cutaneous fungal infections including deep dermatophytosis are responsible for significant morbidity and mortality, especially in immunocompromised patients. Variable and longer turnaround time on tissue culture results delay diagnosis. We sought to seek the fast bedside diagnosis for disseminated deep dermatophytosis by direct microscopy using a blunt scalpel or needle aspiration before biopsy. This is a 6-year retrospective review of patients with a diagnosis of disseminated deep dermatophytosis seen at a single tertiary care institution. Trichophyton rubrum was isolated in four patients, and T. mentagrophyte complex in one patient. All the dermatophyte isolates can grow at 37°C. Microscopy of purulence sampling from intact nodules demonstrated abundant septate hyphae, and also isolation from purulence was concordance with skin tissue culture. Ultrasound-guided sampling from non-eroded can yield purulence, and direct microscopy of purulence may facilitate rapid diagnosis of deep dermatophytosis and serve to prevent disease progression and dissemination.

Recent concepts in fungal involvement in skin and soft tissue infections.

The aim of this review is to provide an overview of the most frequent and emerging deep cutaneous fungal infections following either primary inoculation or secondary spread after haematogenous seeding in disseminated infections in different geographical areas. Fungal skin and soft tissue infections (SSTIs) encompass a variety of pathological conditions based on the site of the infection, route of acquisition of the pathogen, epidemiological setting and the virulence of the fungus in relation to the host. The approach to a patient suspected of having a fungal SSTI is complex and usually poses a major diagnostic challenge. The treatment approach should include attempts at immune reconstitution, targeted antifungal therapy and/or aggressive surgical debridement. Fungal SSTIs can be an important cause of morbidity and mortality in both immunocompromised and immunocompetent patients and are being reported with increasing frequency worldwide.

JAAD Game Changers∗: Diagnosis of deep cutaneous fungal infections: Correlation between skin tissue culture and histopathology

JAAD Game Changers∗: Diagnosis of deep cutaneous fungal infections: Correlation between skin tissue culture and histopathology

Beyond Skin Tumors: A Systematic Review of Mohs Micrographic Surgery in the Treatment of Deep Cutaneous Fungal Infections.

Deep cutaneous fungal infections (DCFIs) can cause significant morbidity in immunocompromised patients and often fail medical and standard surgical treatments because of significant subclinical extension. Although rarely considered in this setting, Mohs micrographic surgery (MMS) offers the advantages of comprehensive margin control and tissue conservation, which may be beneficial in the treatment of DCFIs that have failed standard treatment options. To review the benefits, limitations, and practicality of MMS in patients with DCFIs. A systematic review of PubMed and EMBASE was conducted to identify all cases of fungal skin lesions treated with MMS. Eight case reports were identified consisting of a total of 8 patients. A majority of patients had a predisposing comorbidity (75%), with the most common being a solid organ transplant (n = 3, 37.5%). The most commonly diagnosed fungal infection was phaeohyphomycosis (n = 5, 62.5%), followed by mucormycosis (n = 2, 25%). No recurrence or complication post-MMS was noted at a mean follow-up of 11.66 months. Although not a first-line treatment, MMS can be considered as an effective treatment alternative for DCFIs in cases of treatment failure and can be particularly helpful in areas where tissue conservation is imperative.

Deep cutaneous fungal infections in solid-organ transplant recipients

Deepcutaneous fungal infections (DCFIs) are varied in immunosuppressed patients, with few data for such infections in solid-organ transplant recipients (s-OTRs). To determine DCFI diagnostic characteristics and outcome with treatments in s-OTRs. A 20-year retrospective observational study in France was conducted in 8 primary dermatology-dedicated centers for s-OTRs diagnosed with DCFIs. Relevant clinical data on transplants, fungal species, treatments, and outcomes were analyzed. Overall, 46 s-OTRs developed DCFIs (median delay, 13months after transplant) with predominant phaeohyphomycoses (46%). Distribution of nodular lesions on limbs and granulomatous findings on histopathology were helpful diagnostic clues. Treatments received were systemic antifungal therapies (48%), systemic antifungal therapies combined with surgery (28%), surgery alone (15%), and modulation of immunosuppression (61%), leading to complete response in 63% of s-OTRs. Dueto the retrospective observational design of the study. Phaeohyphomycoses are the most common DCFIs in s-OTRs. Multidisciplinary teams arehelpful for optimal diagnosis and management.

A Case of Deep Cutaneous Fungal Infection Caused by a Wood Foreign Body

A Case of Deep Cutaneous Fungal Infection Caused by a Wood Foreign Body

Antimicrobial Microneedle Patch for Treating Deep Cutaneous Fungal Infection

AbstractSubcutaneous fungal infection is often difficult to be treated by the conventional topical application or oral intake of antifungal agents because of low drug bioavailability to the infection site, lack of sustained therapeutic effect, and development of drug resistance. Here, a new strategy using polymeric microneedle (MN) patches to overcome the skin barrier is reported. MN is made of a biocompatible and biodegradable chitosan–polyethylenimine copolymer, which possesses antimicrobial property immune to drug resistance and allows sustained drug release. Using a fungal infection mouse model, it is demonstrated that MN patches encapsulated with antifungal agent amphotericin B offer outstanding treatment effectiveness. It is attributable to the high bioavailability of therapeutics and synergistic actions of the antifungal polymer and drug.

A Case of Deep Cutaneous Purpureocillium lilacinum Fungal Infection in an Immunocompetent Patient

Purpureocillium is a genus of saprophytic fungi that is commonly found in soil or rotting material. Although rarely a pathogen in humans, it can cause serious infections in immunocompromized patients. An 85-year-old woman presented with a 2-week history of pruritic erythematous plaques with yellowish crusts on her right forearm and dorsal hand. Histopathological analysis identified fungal hyphae and spores in the dermis, and Purpureocillium lilacinum was identified through tissue culture, polymerase chain reaction, and DNA sequencing. The skin lesion barely responded to 4 weeks of itraconazole treatment but improved upon the addition of terbinafine. The skin lesion was completely cured after 12 weeks, with no recurrence to date. Here, we report a rare deep cutaneous fungal infection caused by P. lilacinum in an immunocompetent patient and postulate that, in this case, the patient's agricultural lifestyle increased the possibility of P. lilacinum infection.

Deep cutaneous fungal infection in tropical regions: A retrospective study from a referral center in southern Taiwan

Deep cutaneous fungal infection in tropical regions: A retrospective study from a referral center in southern Taiwan

Cutaneous manifestations of subcutaneous and systemic fungal infections in tropical regions: a retrospective study from a referral center in southern Taiwan.

Deep cutaneous fungal infections, including subcutaneous mycoses and systemic fungal infection with cutaneous involvement, cause significant morbidity and mortality in light of increasing immunocompromised patients and global warming. Although a few studies reviewed deep fungal infections in temperate regions, a relevant study in tropical regions is lacking. We evaluated features of deep cutaneous fungal infections in southern Taiwan among the tropical regions. We retrospectively reviewed all histopathological specimens with deep cutaneous fungal infections in a single referral center from 2001 to 2014 and successfully identified 23 cases. Medical chart review revealed patient demographic data, clinical presentation, underlying disease, microbiological culture reports, and treatment outcomes. The average patient age was 52 years. Fourteen cases had primary subcutaneous mycoses, and nine had systemic mycoses. Fifteen patients were immunocompromised, including hematological malignancies. Acquired immune deficiency syndrome (AIDS) and long-term steroid use were most commonly associated with deep fungal infections. The positive culture growth rate was 63%. Fonsecaea sp. was most frequently identified by tissue culture. Aspergillosis, mucormycosis, and disseminated cryptococcosis were particularly fatal. Diabetes and long-term steroid use appear as major risk factors for advanced mycoses in this region. Rapid diagnosis with skin biopsy and tissue culture along with appropriate treatment of deep cutaneous fungal infection are necessary.

Infekcje grzybicze skóry i tkanki podskórnej u chorych po transplantacji narządów

Infekcje grzybicze skóry i tkanki podskórnej u chorych po transplantacji narządów

Epidemiology of deep cutaneous fungal infections in Korea (2006-2010).

Deep cutaneous fungal infections (DCFI) occur worldwide and their prevalence is influenced by personal factors of the affected patients and the geographic and cultural features. Surveillance studies of DCFI with respect to the various clinical backgrounds of affected patients can ultimately help to improve their outcome. Expanding on our previous study, we performed a retrospective analysis of patients with DCFI who were treated in a group of university teaching hospitals in Korea to determine the trends within a 5-year period. A retrospective medical record review of patients with DCFI treated between 2006 and 2010 at 16 university teaching hospitals located throughout Korea was performed. Among the 51 cases of DCFI (median patient age, 47.0years), opportunistic infections in immunocompromised hosts accounted for half. Patients in this group included 11 who were transplant recipients and 12 with malignancies. Overall, Candida (13/51) was the most common causative organism, followed by Sporothrix (12) and Aspergillus (6). Papuloplaques and nodular lesions were the typical presentation, with maculopatches and ulcers also occurring in considerable numbers. Ten patients had systemic involvement. Eight immunocompromised patients did not recover from the disease despite systemic antifungal treatment. Our results highlight the equal involvement of opportunistic and primary pathogens in DCFI, as determined in cases from a 5-year period. Especially in immunocompromised hosts with non-specific skin findings, clinical suspicion is important because failure to diagnose a DCFI causes significant morbidity and possibly even death.

DA 5505: A Novel Topical Formulation of Terbinafine That Enhances Skin Penetration and Retention

Topical fungal infections can become severe if left untreated. Efficient treatment modalities for topical fungal infections aid the penetration of antifungal agents deep into viable skin layers. Terbinafine is a fungicidal agent that inhibits ergosterol, an essential fungal component. The main objective of this study was to evaluate skin permeation and retention of a terbinafine-loaded solution containing chitosan as a film former. Comparative assessment of skin permeation and retention was performed using a prepared formulation (DA 5505) and marketed formulations of terbinafine in murine and porcine skin. To mimic fungal infection of skin, keratinized skin was induced in NC/Nga mice. In comparison with the marketed formulations, DA 5505 exhibited significantly better skin permeation. The flux, permeation coefficient, and enhancement ratio of terbinafine were remarkably increased by DA 5505 in comparison with the marketed formulations, and lag time was dramatically reduced. DA 5505 significantly increased cumulative terbinafine retention in viable skin layers in comparison with the marketed solution, suggesting enhanced efficacy. Furthermore, DA 5505 exhibited superior skin permeation in normal skin and keratinized skin. Thus, the DA 5505 formulation has the potential to effectively deliver terbinafine to superficial and deep cutaneous fungal infections.

Morphological findings of deep cutaneous fungal infections.

Cutaneous fungal infections used to be rare in most developed countries. However, they have become more common due to immunosuppression and globalization. In this report, we summarize the histopathologic findings of the main cutaneous fungal infections that are commonly seen in daily practice, including eumycetoma, sporotrichosis, histoplasmosis, cryptococcosis, coccidioidomycosis, aspergillosis, zygomycosis, phaeohyphomycosis, alternariosis, blastomycosis, paracoccidioidomycosis, lobomycosis, and chromoblastomycosis. We also include protothecosis (despite the fact that the infectious agent of this disease is algal and not fungal) and rhinosporidiosis (despite being caused by mesomycetozoea, which are not fungi).

Diagnosis of deep cutaneous fungal infections: Correlation between skin tissue culture and histopathology

Deep cutaneous fungal infections (DCFIs) are responsible for significant morbidity and mortality, particularly in immunocompromised patients. Although a direct correlation between histopathologic examination and culture is expected, discordant findings may be seen, presenting a unique diagnostic and therapeutic challenge. We sought to determine the correlation between skin tissue cultures and histopathologic examination in patients with DCFI. This is a 10-year retrospective review (2003-2012) of patients with a diagnosis of DCFI seen at a single tertiary care institution. Tissue cultures and histopathologic findings were reviewed. In 8 of 33 cases, fungal elements were seen on routine histopathologic sections but skin cultures were negative. Three of 8 of the discordant cases had concurrent positive non-skin tissue cultures that correlated with the pathology interpretation, and 3 of 8 patients in the discordant group died of systemic fungal infection. This was a retrospective study design and a single tertiary care institution experience. The histopathologic interpretation of skin tissue specimens is critical for rapid and accurate diagnosis of DCFI. Despite the identification of fungal organisms on histopathologic assessment of skin tissue specimens, skin tissue culture may fail to show fungal growth. A diagnosis of a DCFI and initiation of appropriate treatment should always be considered in spite of discordant results.