白细胞介素17相关生物制剂治疗银屑病过程中浅部真菌感染的发生及应对策略

本文综述白细胞介素（IL）-17与皮肤黏膜真菌感染易感性的基本机制,以及与IL-17相关的生物制剂,如司库奇尤单抗、依奇珠单抗、布罗达单抗、拜莫克珠单抗和乌司奴单抗在治疗银屑病中发生的浅部真菌感染。与IL-17相关生物制剂治疗相关的浅部真菌感染以轻度或中度为主,多呈局限性,且抗真菌治疗效果良好。此外,本文介绍了对相关浅...     

Advances in topical and systemic antifungals

Topical antifungal agents are generally used for the treatment of superficial fungal infections unless the infection is widespread, involves an extensive area, or is resistant to initial therapy. Systemic antifungals are often reserved for the treatment of onychomycosis, tinea capitis, superficial and systemic candidiasis, and prophylaxis and treatment of invasive fungal infections. With the development of resistant fungi strains and the increased incidence of life-threatening invasive fungal infections in immunocompromised patients, some previously effective traditional antifungal agents are subject to limitations including multidrug interactions, severe adverse effects, and their fungistatic mechanism of actions. Several new antifungal agents have demonstrated significant therapeutic benefits and have broadened clinicians' choices in the treatment of superficial and systemic invasive fungal infections.     

Cutaneous Fungal Infections in the Oncology Patient

There are two main types of fungal infections in the oncology patient: primary cutaneous fungal infections and cutaneous manifestations of fungemia. The main risk factor for all types of fungal infections in the oncology patient is prolonged and severe neutropenia; this is especially true for disseminated fungal infections. Severe neutropenia occurs most often in leukemia and lymphoma patients exposed to high-dose chemotherapy. Fungal infections in cancer patients can be further divided into five groups: (i) superficial dermatophyte infections with little potential for dissemination; (ii) superficial candidiasis; (iii) opportunistic fungal skin infections with distinct potential for dissemination; (iv) fungal sinusitis with cutaneous extension; and (v) cutaneous manifestations of disseminated fungal infections. In the oncology population, dermatophyte infections (i) and superficial candidiasis (ii) have similar presentations to those seen in the immunocompetent host. Primary cutaneous mold infections (iii) are especially caused by Aspergillus, Fusarium, Mucor, and Rhizopus spp. These infections may invade deeper tissues and cause disseminated fungal infections in the neutropenic host. Primary cutaneous mold infections are treated with systemic antifungal therapy and sometimes with debridement. The role of debridement in the severely neutropenic patient is unclear. In some patients with an invasive fungal sinusitis (iv) there may be direct extension to the overlying skin, causing a fungal cellulitis of the face. Aspergillus, Rhizopus, and Mucor spp. are the most common causes. We also describe the cutaneous manifestations of disseminated fungal infections (v). These infections usually occur in the setting of prolonged neutropenia. The most common causes are Candida, Aspergillus, and Fusarium spp. Therapy is with systemic antifungal therapy. The relative efficacies of amphotericin B, fluconazole, itraconazole, voriconazole, and caspofungin are discussed. Recovery from disseminated fungal infections is unlikely, however, unless the patient's neutropenia resolves.     

The efficacy and safety of terbinafine in children

In summary, terbinafine is a broad-spectrum allylamine, which has been used to treat superficial fungal infections including onychomycosis, and some systemic mycoses in adults. With a fungicidal activity, low minimum inhibitory concentration value, and high selectivity for fungal squalene epoxidase, terbinafine has demonstrated good efficacy in superficial fungal infections. Its lipophilic nature provides excellent, widespread absorption into hair, skin, and nails where it can eradicate fungal infection. Terbinafine has been shown to be effective and safe in several studies of the treatment of tinea capitis and onychomycosis in children. When treating Trichophyton tinea capitis the length of therapy may be 2 or 4 weeks. Microsporum tinea capitis may require somewhat higher or longer doses of terbinafine for adequate efficacy. These regimens still tend to be shorter than treatment with griseofulvin, and terbinafine may provide a higher compliance and a more cost-effective means of managing tinea capitis. It is possible that even higher cure rates and a shorter duration of therapy may be achieved following further optimization of treatment regimens that use a higher daily dosage of terbinafine than is currently recommended. The evidence is strongly in favor of using terbinafine to treat superficial fungal infections in children.     

The efficacy and safety of terbinafine in children

Terbinafine is an allylamine antifungal agent that has been effective and safe in the treatment of superficial and some deep mycotic infections in adults. An increasing amount of data is available where terbinafine has been used in the paediatric population to treat superficial fungal infections, in particular tinea capitis. The data suggest that terbinafine is effective and safe using treatment regimens that involve short duration therapy, leading to an increased compliance and providing a cost-effective means of treating paediatric superficial fungal infections such as tinea capitis. Terbinafine has been approved for the treatment of tinea capitis in many countries worldwide, and provides good efficacy rates for Trichophyton tinea capitis using shorter regimens than the gold standard griseofulvin. The adverse events profile for children is similar to that in adults with few adverse effects associated with its use. The evidence favours the use of terbinafine in the treatment of superficial infections in children.     

Superficial fungal infections in 102 renal transplant recipients: a case-control study

BACKGROUND: Renal transplant recipients are predisposed to superficial fungal infections caused by graft-preserving immunosuppressive therapy. Reports have documented a wide range of prevalence rates for superficial fungal infections in this patient group. OBJECTIVE: The aim of this study was to determine the prevalence and clinical and mycological features of superficial fungal infections in renal transplant recipients at our center. METHODS: One hundred two consecutively registered renal transplant recipients (34 women, 68 men) and 88 healthy age- and sex-matched persons acting as controls (30 women, 58 men) underwent screening for the presence of superficial fungal infection. Skin scrapings and swabs were obtained from the dorsum of the tongue, upper part of the back, toe webs, and any suspicious lesions. Nail clippings were also collected. All samples were examined by direct microscopy and were stained with calcofluor white. The samples were cultured in Sabouraud dextrose agar, mycobiotic agar, and dermatophyte test medium. Candida species were identified on the basis of germ-tube production, spore formation in cornmeal agar, and results of biochemical testing. Dermatophytes were identified on the basis of colonial and microscopic morphologic features in conjunction with results of physiologic evaluation (in vitro hair perforation test, urease activity, temperature tolerance test, and nutritional test). RESULTS: Sixty-five (63.7%) of the 102 renal transplant recipients had cutaneous-oral candidiasis, dermatophytosis, or pityriasis versicolor, whereas only 27 (30.7%) of controls had fungal infection. Pityriasis versicolor was the most common fungal infection in the patient group (36.3%), followed by cutaneous-oral candidiasis (25.5%), onychomycosis (12.7%), and fungal toe-web infection (11.8%). Pityriasis versicolor and oral candidiasis were significantly more common among the renal transplant recipients, whereas the frequency of dermatophytosis in patients and controls was similar. Candida albicans was the main agent responsible for oral candidiasis, and Trichophyton rubrum was the most common dermatophyte isolated. Analysis showed that age, sex, and duration of immunosuppression did not significantly affect the prevalence of superficial fungal infection. Cyclosporine treatment and azathioprine therapy were identified as independent risk factors for superficial fungal disease. CONCLUSIONS: The prevalence of opportunistic infections with Pityrosporum ovale and C albicans is increased among renal transplant recipients, probably owing to the immunosuppressed state of this patient population. However, renal transplant recipients are not at increased risk of dermatophytosis.     

Multilokuläres vegetierendes Pyoderma gangraenosum

Vegetative pyoderma gangrenosum is a nonaggressive, chronic, superficial variant of pyoderma gangrenosum. Unlike classic ulcerative pyoderma gangrenosum, the lesions are less deep and not painful, and the borders are not undermined. The base of ulcers usually shows granulation tissue. The histopathologic findings are characterized by superficial granulomas. Cultures for fungal or bacterial infections normally are negative. Vegetative pyoderma gangrenosum is seldom associated with systemic diseases and often responds to simple modes of therapy. Our patient had a 10 years history of superficial ulcers on face, trunk and upper arms, whose general health was not impaired. A broad diagnostical evaluation showed no systemic diseases. The histologic pattern demonstrated a granulomatous dermatitis. After exclusion of other causes, we believe the patient has the vegetative form of pyoderma gangraenosum. There was no improvement with local treatment. Only systemic therapy with corticosteroids and later on cyclosporine led to healing.     

Candida infections today--how big is the problem?

Thirty years ago, superficial fungal infections were common, but systemic fungal infections were not as frequent as today. Since that time incidence in both superficial and systemic fungal infection has been increasing. The reasons are many. Due to advances in medicine, human life span is extended and many people suffer from various immunodeficiencies. Transplantation of organs and tissues, wide application of parenteral feeding and parenteral administration of drugs, infection with human immunodeficiency virus (HIV), and long-term peroral administration of antibiotics are the main reasons for appearance of many immunologic dysfunctions and thereby systemic fungal infections. The most usual predisposing factors for systemic fungal infection are skin and mucosal damage, hypofunction of T-cell-mediated immunity, decreased function of neutrophiles, long-term administration of corticosteroids, as well as dysfunction of microbial flora. Systemic fungal infections are a great problem, because they are very difficult to prove and to treat. This is why prevention of systemic infections is extremely important today, including the removal of predisposing factors as well as rational drug administration.     

Fungal melanonychia

Fungal melanonychia is a relatively rare nail disorder caused by nail infection that produces brown-to-black pigmentation of the nail unit. The number of organisms implicated as etiologic agents of fungal melanonychia is increasing, and the list currently tops 21 species of dematiaceous fungi and at least 8 species of nondematiaceous fungi. These superficial infections may clinically mimic subungual melanoma and are often not responsive to traditional antifungal therapy. This article reviews the literature on fungal melanonychia and the role of fungal melanin in infection.     

Efficacy and safety of itraconazole use in children

Current dosing regimens for itraconazole are effective, safe, and versatile for use in superficial fungal infections in children, particularly tinea capitis. Good efficacy rates have been noted in both Trichophyton and Microsporum tinea capitis infections. Itraconazole has a high affinity for keratin, and accumulates to high levels at the site of superficial fungal infections. A pulse regimen may be chosen over continuous dosing, because the accumulation persists after dosing of itraconazole has been stopped. An oral solution of itraconazole is available, and may be more convenient for children who cannot swallow capsules. The oral solution also produces good rates of efficacy, but may be associated with a somewhat higher potential for gastrointestinal adverse events than the capsules. The range of adverse events noted with itraconazole capsules or oral solution use in children is similar to the range in adults. Events are generally mild and transient. Attention must be taken to note any medications that the child is using, because itraconazole is associated with a range of potential drug interactions. This safety of use, in combination with itraconazole's wide antifungal spectrum and pharmacokinetic properties, which allow for shorter dosing regimens, may make itraconazole a suitable alternative to griseofulvin for pediatric superficial fungal infections.     

The use of fluconazole to treat superficial fungal infections in children

Fluconazole has excellent absorption and good persistence in tissues that suggests it may be useful in superficial fungal infections. The predominant use in pediatric superficial fungal infection has been for tinea capitis, and successful treatment has been shown with both daily and weekly fluconazole regimens. The data regarding fluconazole use in superficial fungal infections in children are somewhat limited; however, it seems that there is good potential for the safe use of fluconazole to treat tinea capitis in children. Further studies need to be conducted, particularly in cases of tinea capitis (both T. tonsurans and M. canis), to determine the optimal treatment regimens using fluconazole.     

Clinicopathologic presentations of dermatomycoses in cancer patients

Many of the skin fungal infections in cancer patients may look similar to those infections in non-cancer patients. However, in some cases, they become more extensive and even life threatening. Prolonged and severe neutropenia is the main risk factor for the dramatic issue of fungal infections. The dermatomycoses in cancer patients can be classified in four broad groups: primary superficial dermatophytoses, primary superficial yeast infections, opportunistic mold infections with distinct potential for dissemination and secondary cutaneous manifestations of fungaemia. Occasionally, more than one fungus are found inside a given skin lesion. A special condition is represented by the mycotic colonization of mucosal squamous cell carcinomas. Angio-invasion by fungi accounts for the frequency of disseminated infections prevailing in immunocompromised cancer patients. In case of skin involvement, the dermatologist may assist by recognizing subtle semiological signs and performing biopsies for swift histological examination, molecular biology and/or culture.     

Evaluation and management of fungal infections in immunocompromised patients

As the population of chronically immunosuppressed individuals continues to grow, the prevalence of fungal infections is increasing. Fungal infections in this patient population represent challenges in diagnosis and management. This article will review the common superficial and invasive mycoses that occur in the solid organ transplant and HIV-infected populations. Disease presentations are reviewed, but emphasis is placed on cutaneous manifestations. Recent advances in antifungal therapy and their direct application to specific diseases provide important new approaches to this complex and often seriously ill patient population.     

Optimal Management of Fungal Infections of the Skin, Hair, and Nails

Superficial fungal infections are chronic and recurring conditions. Tinea capitis is a scalp infection, primarily affecting prepubescent children. Ringworm infections, such as tinea corporis and tinea cruris, involve the glabrous skin. Tinea nigra is a rare mycotic infection that may be related to travel abroad. Piedra, black or white, is limited to the hair shaft without involvement of the adjacent skin. Pityriasis (tinea) versicolor and seborrheic dermatitis are dermatoses associated with yeasts of the genus Malassezia that affect the lipid-rich areas of the body. The taxonomy of the Malassezia yeasts has been revised to include nine species, eight of which have been recovered from humans. Tinea pedis, an infection of the feet and toes, is one of the most common forms of dermatophytosis. Onychomycosis is a fungal infection affecting the nail bed and nail plate; it may be chronic and can be difficult to treat. In instances where the superficial fungal infection is severe or chronic, an oral antifungal agent should be considered. Terbinafine, itraconazole, and fluconazole are oral antifungals that are effective in the treatment of superficial mycoses.     

五种新型唑类抗真菌药物

唑类药物是目前治疗浅部和深部真菌感染的一线用药.按照其结构的不同,该药可以分为咪唑类和三唑类.3种咪唑类新药卢立康唑、拉诺康唑和氟曲乌唑已在国外上市,外用治疗皮肤癣菌等浅部真菌病疗效明显且局部无明显不良反应.2种三唑类新药普拉康唑和雷夫康唑则仍在临床试验阶段,但从目前研究来看,两者用于治疗浅部和深部真菌感染亦较安全有效,有望作为新型抗真菌药应用于临床.

Abstract：

Azoles are a primary treatment choice for superficial and deep fungal infections. They can be divided into two groups, i.e., imidazoles and triazoles, according to chemical structure. Three new imidazoles including luliconazole, lanoconazole and flutrimazole have been on the medical market abroad and shown notable efficacy with no obvious local side effects in the treatment of superficial fungal infection including dermatophytosis. Two triazoles including pramiconazole and ravuconazole are still in clinical trials, although they have proved to be safe and effective in the treatment of superficial and deep fungal infection, and have shown some potential as new antifungal agents.     

Cutaneous Fungal Infection in a Neonatal Intensive Care Unit Patient: A Case Report and Literature Review

Fungal skin infections are not uncommon in healthy, premature or immunocompromised newborns. Healthy neonates usually develop fungal skin infections caused by dermatophytes, Candida and Malassezia species, whereas immunocompromised neonates are more susceptible to skin infections with opportunistic pathogens (Aspergilus, Zygomycetes). Therefore neonatal fungal skin infections can range from generally benign superficial lesions to potentially fatal, deep, necrotic forms with dissemination. We present the case of a premature neonate twin with cutaneous fungal infection in a neonatal intensive care unit. Because there were doubts concerning the correspondence of the clinical features with the cultured species in the newborn, a literature review was performed searching for similar clinical cases.     

Chronic infection due to Fusarium oxysporum mimicking lupus vulgaris: case report and review of cutaneous involvement in fusariosis.

A 67-year-old female presented with a 20-year-old lesion involving the right ear and preauricular area mimicking tuberculous lupus. Fusarium oxysporum infection was confirmed by biopsy studies and cultures. The biopsy specimen showed an unusually extensive dermal invasion with fungal hyphae. This is an uncommon clinical presentation for Fusarium infection in a healthy patient. When referred to us, the patient had received antifungal therapy with itraconazole without any benefit. Improvement was obtained with fluconazole therapy. The spectrum of cutaneous involvement related to Fusarium spp. includes toxic reactions, colonization, superficial indolent infection, deep cutaneous or subcutaneous infections and disseminated infection.     

Wood灯在皮肤浅表真菌感染诊断中应用价值评估

目的 评估Wood灯在皮肤常见浅表真菌感染诊断中的应用价值.方法 对129例根据临床病史及体征初步诊断为皮肤浅表真菌感染患者进行Wood灯和真菌实验室检查.结果 花斑糠疹、马拉色菌毛囊炎患者Wood灯检查的阳性率分别为84%、85.7%,同时阳性病例的真菌培养或镜检的阳性率达92.9%、87.5%,两者有高度的一致性.而临床诊断手足癣和体股癣者其荧光阳性率只有8.3%.真菌总检出率却高达85.4%(41/48),两者不具有一致性.结论 Wood灯在花斑糠疹、马拉色菌毛囊炎的检查上有较高的特异性和敏感性,临床诊断上有应用价值,而对手足癣和体股癣诊断则无意义.

Abstract：

Objective To estimate the performance of Wood's lamp examination in the diagnosis of superficial cutaneous fungal infections. Methods Totally, 129 patients, who were diagnosed with superficial cutaneous fungal infections according to clinical medical history and signs, were enrolled in this study. Wood's lamp examination of lesions was carried out. Cutaneous samples were obtained from the patients and subjected to microscopic examination and fungal culture. Results Wood's lamp examination was positive in 84% and 85.7% of patients with tinea versicolor and malassezia folliculitis, respectively; among these patients positive for Wood's lamp examination, 92.9% were positive for fungal culture, and 87.5% for microscopic examination. In patients clinically diagnosed with tinea manus and pedis, tinea corporis or tinea cruris, 8.3% were positive for Wood's lamp examination, while 85.4% were positive for fungal examination. There was a high consistency between Wood's lamp examination and fungal examination in patients with tinea versicolor and malassezia folliculitis, but not in those with tinea manus and pedis, tinea corporis or tinea cruris. Conclusions Wood's lamp examination shows a high specificity and sensitivity and is useful in the diagnosis of tinea versicolor and malassezia folliculitis, but seems unapplicable for the diagnosis of tinea manus and pedis, tinea corporis or tinea cruris.     

五种新型唑类抗真菌药物

唑类药物是目前治疗浅部和深部真菌感染的一线用药。按照其结构的不同,该药可以分为咪唑类和三唑类。3种咪唑类新药卢立康唑、拉诺康唑和氟曲马唑已在国外上市,外用治疗皮肤癣菌等浅部真菌病疗效明显且局部无明显不良反应。2种三唑类新药普拉康唑和雷夫康唑则仍在临床试验阶段,但从目前研究来看,两者用于治疗浅部和深部真菌感染亦较安全有效,有望作为新型抗真菌药应用于临床。     

Topical Therapy for Dermatophytoses

Dermatophytoses, commonly known as ringworm or tinea, represent superficial fungal infections caused by dermatophytes, which are among the most common infections encountered in medicine. The use of corticosteroid-containing combinations in dermatophyte infections that are usually treated with topical medications is still a much-debated issue. The addition of a corticosteroid to local antifungal therapy may be of value in reducing local inflammatory reaction and thus carries the theoretical advantage of rapid symptom relief in acute dermatophyte infections associated with heavy inflammation. However, the use of such combinations requires caution as they have some potential risks, especially with long-term use under occlusive conditions. Corticosteroid-induced cutaneous adverse effects have been reported primarily in pediatric patients due to inappropriate application of these preparations on diaper areas. Additionally, the corticosteroid component may interfere with the therapeutic actions of the antifungal agent, or fungal growth may accelerate because of decreased local immunologic host reaction, such that underlying infection may persist, and dermatophytes may even acquire the ability to invade deeper tissues. Analysis of the literature documenting clinical study data and adverse reactions related to combination therapy, drew the following conclusions: (i) combination products containing a low potency nonfluorinated corticosteroid may initially be used for symptomatic inflamed lesions of tinea pedis, tinea corporis, and tinea cruris, in otherwise healthy adults with good compliance; (ii) therapy should be substituted by a pure antifungal agent once symptoms are relieved, and should never exceed 2 weeks for tinea cruris and 4 weeks for tinea pedis/corporis; and (iii) contraindications for the use of these combinations include application on diaper or other occluded areas and facial lesions, as well as in children <12 years of age and in immunosuppressed patients for any reason.