[Dynamic diversity of dermatophytes]. / Dynamische Vielfalt der Dermatophyten.

BACKGROUND: Many dermatologists do not understand the perpetual adjustments in the dermatophyte nomenclature. OBJECTIVES: The aim is to explain the background and the development of methods that have led to previous and current changes of dermatophyte taxonomy and to the detection of new dermatophytes. METHODS: In this article we evaluate the recent literature on this topic and our own results in the fields of dermatophyte identification, their detection, and of the associated taxonomic developments. RESULTS: Today, the phylogenetic species concept is the basis of taxonomic classification, including that of dermatophytes. Genetic techniques have decisively advanced this and are state of the art nowadays. The detection of new dermatophyte species was often triggered by clinical observations and by morphologically conspicuous cultures that prompted their subsequent exact mycological characterization. Even today not all species of dermatophytes are unequivocally defined. CONCLUSIONS: By exclusively using selected genetic characteristics for the construction of phylogenetic trees additional taxonomically relevant features are neglected. Therefore it is necessary to better integrate data derived from morphologic, physiologic, ecologic and pathophysiologic observations into phylogenetic analyses. Dermatologists are still asked to contribute such information.

[Tinea faciei caused by Nannizzia persicolor : An underdiagnosed dermatophyte?] / Tinea faciei durch Nannizzia persicolor : Ein unterdiagnostizierter Dermatophyt?

We report on a tinea faciei caused by Nannizzia (N.) persicolor. The 4­year-old boy had probably been infected by a guinea pig. Unambiguous infections caused by N. persicolor are rarely seen in Germany; however, this zoophilic and geophilic dermatophyte may only be rarely identified due to its resemblance to Trichophyton (T.) mentagrophytes. Therefore, the diagnostic attributes of N. persicolor and its differentiation from T. mentagrophytes are described. Particularly in case of contact with rodents, N. persicolor should be kept in mind.

[Primary cutaneous cryptococcosis : Pigeons can carry more than letters !] / Primär kutane Kryptokokkose : Tauben können mehr als Briefe transportieren !

In the event of non-specific epidermal lesions, the importance of a comprehensive anamnesis becomes especially apparent. In the following, we report on a patient case in which only a focused anamnesis was able to bring light into the darkness of numerous differential diagnoses - and to produce the diagnosis of a rare but in this collective common illness: primary cutaneous cryptococcosis.

[Arthroderma benhamiae strains in Germany : Morphological and physiological characteristics of the anamorphs]. / Arthroderma-benhamiae-Stämme aus Deutschland : Morphologische und physiologische Merkmale der anamorphen Formen.

BACKGROUND: Anamorphs of Arthroderma (A.) benhamiae, which can cause inflammatory tinea lesions in humans, have been progressively spreading in Germany. OBJECTIVES: Identification of A. benhamiae anamorphs by conventional methods. MATERIALS AND METHODS: Evaluation of our own results obtained with A. benhamiae anamorphs and from the relevant literature. RESULTS: Infections with A. benhamiae anamorphs are usually transferred by guinea pigs or other animals. A. benhamiae anamorphs can be cultured on growth media used for dermatophytes and can be characterized morphologically and physiologically. In Germany the yellow variant is seen most often but a white variant that equals Trichophyton (T.) interdigitale has also been observed. On Sabouraud agar the yellow variant develops markedly yellow thalli, whereas the white variant produces white aerial mycelium. Microconidia are formed by the yellow variant-if at all-only scarcely and delayed; they are small, roundish, and arranged in a grape-like order. The white variant produces peg-shaped microconidia alongside hyphae as well as roundish ones in grape-like clusters, and subsequently some macroconidia, chlamydospores, and spiral hyphae. In microcultures with both variants circuit-like hyphal structures can consistently be demonstrated. On Trichophyton agars only the yellow variant is clearly dependent on thiamine. The urease test is negative with the yellow variant and positive with the white variant. Most strains of both variants are negative in the hair perforation test. CONCLUSIONS: The characteristics described allow reliable identification of the yellow variant of the A. benhamiae anamorph by conventional methods; a distinction between the white variant and T. interdigitale can be more difficult. Dermatologists should be able to identify this agent in clinical routine.

Unusual strains of Microsporum audouinii causing tinea in Europe.

We comment on an unusual strain of Microsporum (M.) audouinii. It was isolated from tinea corporis of a boy who lived in Germany and most likely had acquired his infection during a stay on a farm with animal husbandry in Poland. The strain showed features of M. canis (plenty of markedly rough-walled macroconidia, growth on rice, positive hair perforation) as well as of M. audouinii (white thallus, long macroconidia with central constriction) and in vitro it degraded hair of various mammals. Because its ribosomal internal transcribed spacer region showed 99.9% homology to a M. audouinii reference strain it was finally identified as M. audouinii. We relate these findings with recent observations of M. audouinii causing tinea in Europe. This appraisal suggests that irrespective of an identical ribosomal ITS region distinct M. audouinii strains can display a spectrum of morphological and physiological features that is broader than currently outlined in mycological textbooks. Certain unusual characteristics like an enhanced capacity to utilise keratins may even be associated with unexpected transmission routes. Above all sporadic M. audouinii infections in Europe that bear no relation to an endemic area should be analysed from this perspective.

Dermatomycoses and inflammation: The adaptive balance between growth, damage, and survival.

Dermatomycosis is characterized by both superficial and subcutaneous infections of keratinous tissues and mucous membranes caused by a variety of fungal agents, the two most common classes being dermatophytes and yeasts. Overall, the stepwise process of host infection is similar among the main dermatomycotic species; however, the species-specific ability to elicit a host reaction upon infection is distinct. Yeasts such as Candida albicans elicit a relatively low level of host tissue damage and inflammation during pathogenic infection, while dermatophytes may induce a higher level of tissue damage and inflammatory reaction. Both pathogens can, however, manipulate the host's immune response, ensuring survival and prolonging chronic infection. One common element of most dermatomycotic infections is the disease burden caused by inflammation and associated signs and symptoms, such as erythema, burning and pruritus. There is a strong clinical rationale for the addition of a topical corticosteroid agent to an effective antimycotic therapy, especially in patients who present with inflammatory dermatomycoses (e.g., tinea inguinalis). In this review, we aim to compare the pathogenesis of common dermatomycotic species, including Candida yeasts (Candida albicans), dermatophytes (Trichophyton, Epidermophyton or Microsporum species), and other pathogenic yeasts (Malassezia), with a special focus on unique species-specific aspects of the respective infection processes, the interaction between essential aspects of pathogenic infection, the different roles of the host inflammatory response, and the clinical consequences of the infection-related tissue damage and inflammation. We hope that a broader understanding of the various mechanisms of dermatomycoses may contribute to more effective management of affected patients.

Guideline: vulvovaginal candidosis (AWMF 015/072), S2k (excluding chronic mucocutaneous candidosis).

The oestrogenised vagina is colonised by Candida species in at least 20% of women; in late pregnancy and in immunosuppressed patients, this increases to at least 30%. In most cases, Candida albicans is involved. Host factors, particularly local defence mechanisms, gene polymorphisms, allergies, serum glucose levels, antibiotics, psycho-social stress and oestrogens influence the risk of candidal vulvovaginitis. Non-albicans species, particularly Candida glabrata, and in rare cases also Saccharomyces cerevisiae, cause less than 10% of all cases of vulvovaginitis with some regional variation; these are generally associated with milder signs and symptoms than normally seen with a C. albicans-associated vaginitis. Typical symptoms include premenstrual itching, burning, redness and odourless discharge. Although itching and redness of the introitus and vagina are typical symptoms, only 35-40% of women reporting genital itching in fact suffer from vulvovaginal candidosis. Medical history, clinical examination and microscopic examination of vaginal content using 400× optical magnification, or preferably phase contrast microscopy, are essential for diagnosis. In clinically and microscopically unclear cases and in chronically recurring cases, a fungal culture for pathogen determination should be performed. In the event of non-C. albicans species, the minimum inhibitory concentration (MIC) should also be determined. Chronic mucocutaneous candidosis, a rarer disorder which can occur in both sexes, has other causes and requires different diagnostic and treatment measures. Treatment with all antimycotic agents on the market (polyenes such as nystatin; imidazoles such as clotrimazole; and many others including ciclopirox olamine) is easy to administer in acute cases and is successful in more than 80% of cases. All vaginal preparations of polyenes, imidazoles and ciclopirox olamine and oral triazoles (fluconazole, itraconazole) are equally effective (Table ); however, oral triazoles should not be administered during pregnancy according to the manufacturers. C. glabrata is not sufficiently sensitive to the usual dosages of antimycotic agents approved for gynaecological use. In other countries, vaginal suppositories of boric acid (600 mg, 1-2 times daily for 14 days) or flucytosine are recommended. Boric acid treatment is not allowed in Germany and flucytosine is not available. Eight hundred-milligram oral fluconazole per day for 2-3 weeks is therefore recommended in Germany. Due to the clinical persistence of C. glabrata despite treatment with high-dose fluconazole, oral posaconazole and, more recently, echinocandins such as micafungin are under discussion; echinocandins are very expensive, are not approved for this indication and are not supported by clinical evidence of their efficacy. In cases of vulvovaginal candidosis, resistance to C. albicans does not play a significant role in the use of polyenes or azoles. Candida krusei is resistant to the triazoles, fluconazole and itraconazole. For this reason, local imidazole, ciclopirox olamine or nystatin should be used. There are no studies to support this recommendation, however. Side effects, toxicity, embryotoxicity and allergies are not clinically significant. Vaginal treatment with clotrimazole in the first trimester of a pregnancy reduces the rate of premature births. Although it is not necessary to treat a vaginal colonisation of Candida in healthy women, vaginal administration of antimycotics is often recommended in the third trimester of pregnancy in Germany to reduce the rate of oral thrush and napkin dermatitis in healthy full-term newborns. Chronic recurrent vulvovaginal candidosis continues to be treated in intervals using suppressive therapy as long as immunological treatments are not available. The relapse rate associated with weekly or monthly oral fluconazole treatment over 6 months is approximately 50% after the conclusion of suppressive therapy according to current studies. Good results have been achieved with a fluconazole regimen using an initial 200 mg fluconazole per day on 3 days in the first week and a dosage-reduced maintenance therapy with 200 mg once a month for 1 year when the patient is free of symptoms and fungal infection (Table ). Future studies should include Candida autovaccination, antibodies to Candida virulence factors and other immunological experiments. Probiotics with appropriate lactobacillus strains should also be examined in future studies on the basis of encouraging initial results. Because of the high rate of false indications, OTC treatment (self-treatment by the patient) should be discouraged.

Skin irritability to sodium lauryl sulfate is associated with increased positive patch test reactions.

BACKGROUND: As previous observations have indicated an inter-relationship between irritant and allergic skin reactions we analysed data of synchronous allergen and sodium lauryl sulfate (SLS) patch tests in terms of a relationship between SLS responsiveness and allergic patch test reactions. OBJECTIVES: To analyse differences in terms of allergen-specific and overall reaction profiles between patients with vs. those without an irritant reaction to SLS. METHODS: Clinical data of 26 879 patients patch tested from 2008 to 2011 by members of the Information Network of Departments of Dermatology were analysed. After descriptive analyses, including the MOAHLFA index, the positivity ratio and the reaction index, a negative binomial hurdle model was adopted to investigate the correlation between SLS reactivity and positive patch test reactions. RESULTS: Men, patients aged ≥ 40 years and patients with an occupational dermatitis background were over-represented in the SLS-reactive group. Patients with an irritant reaction to SLS showed a higher proportion of weak positive reactions, as well as more questionable and irritant reactions to contact allergens than patients not reactive to SLS. The risk of an additional positive patch test reaction increased by 22% for SLS-reactive patients compared with those who were SLS negative. CONCLUSIONS: The marked association between SLS reactivity and the number of positive reactions in patch test patients may be due to nonspecific increased skin reactivity at the moment of patch testing only. However, increased SLS reactivity could also be due to longer-lasting enhanced skin irritability, which may have promoted (poly-)sensitization. Further studies, for example with longitudinal data on patients repeatedly patch tested with SLS and contact allergens, are necessary.

Expression of antimicrobial peptides and toll-like receptors is increased in tinea and pityriasis versicolor.

In superficial tinea and pityriasis versicolor, the causative fungi are for the most part confined to the stratum corneum which is barely reached by leukocytes. Therefore, a role of non-cellular components in the epidermal antifungal defence was suggested. To investigate the presence of such factors in these infections, the expression of human beta defensins 2 and 3 (hBD-2, hBD-3), RNase 7, psoriasin, toll-like receptors 2, 4 and 9 (TLR2, TLR4 and TLR9) and dectin 2 was analysed by use of immunostainings in skin biopsies. We found that hBD2, hBD3, psoriasin, RNase7, TLR2 and TLR4 were significantly more often expressed in distinct layers of lesional epidermis as compared with uninfected epidermis. In both infections but not in normal skin, hBD2 and hBD3 were commonly expressed within the stratum corneum and in the stratum granulosum. Similarly, psoriasin was seen more often in the upper skin layers of both infections as compared with normal skin. No significant differences between normal and infected skin were found for the expression of TLR9 and dectin 2. Our findings clearly show the expression of specific antimicrobial proteins and defence-related ligands in superficial tinea as well as in pityriasis versicolor, suggesting that these factors contribute to fungal containment.

Randomized, double-blind, placebo-controlled study of safety and efficacy of miltefosine in antihistamine-resistant chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU), a mast cell-driven condition, is debilitating, common, and hard to treat. Miltefosine, a lipid raft modulator, can inhibit mast cell responses in vivo. OBJECTIVE: To study the safety and efficacy of systemic miltefosine treatment in CSU patients resistant to standard-dosed antihistamines. METHODS: In this investigator-initiated multicentre, randomized, double-blind, placebo-controlled study, CSU patients were treated for 4 weeks with daily doses of up to 150-mg miltefosine (n = 47) or placebo (n = 26). Disease activity was assessed using the urticaria activity score. Safety and tolerability of miltefosine were also assessed. RESULTS: After 4 weeks of treatment, Urticaria Activity Score (UAS7) levels were substantially more reduced in miltefosine-treated patients (-6.3 vs. -3.5 in placebo-treated patients; P = 0.05). Also, the number of weals, but not the intensity of pruritus, was significantly reduced in miltefosine-treated patients vs. placebo-treated patients (P = 0.02). In general, adverse events were frequent in both groups (miltefosine: 88%, placebo: 65% of patients) but mostly mild to moderate in severity. We did not observe any serious adverse events. CONCLUSIONS: The results of this study indicate that miltefosine is an effective and safe treatment option for CSU patients who do not respond to standard-dosed antihistamines.

[Skin infections caused by Fusarium]. / Dermatomykosen durch Fusarien.

Under favorable conditions even molds can cause skin infections. Fusarium spp. belong to this group of agents. Onychomycoses due to Fusarium spp. are regularly encountered and cannot be clinically distinguished from nail infections triggered by dermatophytes. They can occur in otherwise healthy persons. Skin lesions caused by Fusarium spp. may be necrotizing, ulcerating, pustular, vasculitis-like, panniculitis-like or granulomatous. Single lesions can develop after fungal inoculation into damaged tissue; multiple ones are often due to a septic dissemination of Fusarium in severely immunocompromised patients. An immediate verification of the agents can be life-saving in such cases. Pathogenic Fusarium spp. should be identified at the species level and need to be tested for their susceptibility to antimycotics. In case of multiple lesions, systemic therapy is required. Many strains of Fusarium spp. are susceptible to amphotericin B, voriconazole and posaconazole; itraconazole and terbinafine may be helpful in certain cases.

[Diagnostics and exclusion of hereditary angioedema : a standarized approach for the practice]. / Diagnostik und Ausschluss des hereditären Angioödems : Ein standardisierter Ansatz für die Praxis.

The differentiation between mast cell mediator-mediated and bradykinin-mediated forms of angioedema can be difficult. Bradykinin-mediated hereditary angioedema is a rare autosomal dominant hereditary disease which is characterized by recurrent edema attacks of varying magnitude. The edema occurs in the skin and mucous membranes and can be temporarily disfiguring, very painful and life-threatening by attacks in the laryngeal region. Because of the multitude of differential diagnoses, a final diagnosis is only achieved after an average duration of more than 10 years. The anamnestic and laboratory diagnostic algorithm presented here is designed to assist a simpler differentiation of the various forms of angioedema and to reach the correct diagnosis more quickly.

Guideline vulvovaginal candidosis (2010) of the German Society for Gynecology and Obstetrics, the Working Group for Infections and Infectimmunology in Gynecology and Obstetrics, the German Society of Dermatology, the Board of German Dermatologists and the German Speaking Mycological Society.

Candida (C.) species colonize the estrogenized vagina in at least 20% of all women. This statistic rises to 30% in late pregnancy and in immunosuppressed patients. The most often occurring species is Candida albicans. Host factors, especially local defense deficiencies, gene polymorphisms, allergic factors, serum glucose levels, antibiotics, psychosocial stress and estrogens influence the risk for a Candida vulvovaginitis. In less than 10% of all cases, non-albicans species, especially C. glabrata, but in rare cases also Saccharomyces cerevisiae, cause a vulvovaginitis, often with fewer clinical signs and symptoms. Typical symptoms include premenstrual itching, burning, redness and non-odorous discharge. Although pruritus and inflammation of the vaginal introitus are typical symptoms, only less than 50% of women with genital pruritus suffer from a Candida vulvovaginitis. Diagnostic tools are anamnesis, evaluation of clinical signs, the microscopic investigation of the vaginal fluid by phase contrast (400 x), vaginal pH-value and, in clinically and microscopically uncertain or in recurrent cases, yeast culture with species determination. The success rate for treatment of acute vaginal candidosis is approximately 80%. Vaginal preparations containing polyenes, imidazoles and ciclopiroxolamine or oral triazoles, which are not allowed during pregnancy, are all equally effective. C. glabrata is resistant to the usual dosages of all local antimycotics. Therefore, vaginal boric acid suppositories or vaginal flucytosine are recommended, but not allowed or available in all countries. Therefore, high doses of 800 mg fluconazole/day for 2-3 weeks are recommended in Germany. Due to increasing resistence, oral posaconazole 2 × 400 mg/day plus local ciclopiroxolamine or nystatin for 15 days was discussed. C. krusei is resistant to triazoles. Side effects, toxicity, embryotoxicity and allergy are not clinically important. A vaginal clotrimazole treatment in the first trimester of pregnancy has shown to reduce the rate of preterm births in two studies. Resistance of C. albicans does not play a clinically important role in vulvovaginal candidosis. Although it is not necessary to treat vaginal candida colonization in healthy women, it is recommended in the third trimester of pregnancy in Germany, because the rate of oral thrush and diaper dermatitis in mature healthy newborns, induced by the colonization during vaginal delivery, is significantly reduced through prophylaxis. Chronic recurrent vulvovaginal candidosis requires a "chronic recurrent" suppression therapy, until immunological treatment becomes available. Weekly to monthly oral fluconazole regimes suppress relapses well, but cessation of therapy after 6 or 12 months leads to relapses in 50% of cases. Decreasing-dose maintenance regime of 200 mg fluconazole from an initial 3 times a week to once monthly (Donders 2008) leads to more acceptable results. Future studies should include candida autovaccination, antibodies against candida virulence factors and other immunological trials. Probiotics should also be considered in further studies. Over the counter (OTC) treatment must be reduced.

[New apects in the diagnosis and therapy of dermatomycoses]. / Neues zu Diagnostik und Therapie bei Mykosen der Haut.

Recent observations indicate that Arthroderma benhamiae can cause bullous tinea, that onychomycosis increasingly occurs in children and that molds can cause tinea-like lesions. If a mycotic infection is suspected, the pathogen needs to be identified. The first genetic assays for the detection of dermatophytes have successfully been tested under routine conditions. Using appropriate techniques, genetic diagnosis is faster and more sensitive than a culture. Laboratory standards that would facilitate widespread implementation of genetic identification of dermatophytes have not yet been established. For the identification of yeasts, MALDI-TOF has already been established in many laboratories. This method is being refined for the diagnosis of hyphomycetes too. Newer antimycotics that are approved for certain systemic mycoses such as the triazoles voriconazole and posaconazole and the echinocandines caspofungin, micafungin und anidulafungin may be considered for dermatomycoses that cannot be treated by other therapies. Thermotherapy and photodynamic therapy are additional options in particularly difficult cases.

Toenail infection by Cladophialophora boppii.

Cladophialophora boppii is a black yeast-like fungus that up to now has been only rarely described as a cause of human infection and whose role as a pathogen was not established despite its repeated isolation and genetic identification in these reports. Here we report the first case of a verified toenail infection caused by this fungus in a woman without any systemic disease or evidence of immunodeficiency. Identical dark molds were isolated from the same toenail at three points of time. Species identification was performed by scrutinizing the isolates morphologic, physiologic and genetic characteristics which resulted in their identification as Cladophialophora boppii. Oral treatment with terbinafin plus topical ciclopiroxolamine was effective.

Fast and sensitive detection of Trichophyton rubrum in superficial tinea and onychomycosis by use of a direct polymerase chain reaction assay.

Detection of Trichophyton rubrum in superficial skin infections by conventional methods is time consuming and not always successful. However, with modern molecular methods, an alternative is in sight. The aim of this study was to compare the detection of T. rubrum by conventional methods and by a direct specific PCR assay under routine conditions. Skin scrapings (n = 464) and nail samples (n = 230) collected from suspected tinea lesions were equally divided for KOH-mounts, cultures and PCR-analysis. For the latter, DNA was extracted and PCR was performed with T. rubrum-specific primers. Of the scale samples, 16% were positive for T. rubrum in the culture and PCR as well, 9% were positive in the PCR only and 3% in the culture only, whereas 5% were only KOH-positive. The corresponding results for nail samples were 17%, 20%, 3% and 7%. PCR results were available after 2-5 days, culture results after 2-3 weeks. Our results show that a specific PCR assay can successfully be used to detect T. rubrum directly in samples collected from superficial skin lesions and nails under routine conditions. Compared with conventional methods, it is faster and more sensitive. We recommend its complementary use.

Tinea corporis caused by an unusual strain of Microsporum audouinii that perforates hair in vitro.

We report on a dermatophyte infection acquired by a young woman from Germany who had worked in Ghana. The strain isolated from her skin lesions showed morphological and physiological features compatible with Microsporum audouinii but a clearly positive hair perforation test made its definite identification by conventional methods equivocal. A genetic analysis finally unambiguously revealed Microsporum audouinii. This is the first observation of a Microsporum audouinii strain with a positive hair perforation test. The ability to perforate hair may be related to attributes favouring an inflammatory host response.

Nail infection by Aspergillus ochraceopetaliformis.

Aspergillus ochraceopetaliformis is a rare fungal species that has not yet been identified as a proven human pathogen. Here we report a case of a toenail infection in a healthy woman caused by this fungus. Species identification was performed by scrutinizing the phenotypic and genetic characteristics of distinct isolates obtained at different times during the course of the infection. Treatment with terbinafine plus ciclopiroxolamine was effective.