Search

Summary Background Debridement is essential in wound treatment to remove necrotic tissue and wound bacteria, but may lead to the transmission of bacteria by aerosolization. Aim To investigate bacterial transmission and wound bacterial reduction induced by debridement using a cold steel curette, plasma-mediated bipolar radiofrequency ablation (Coblation ® ) or hydrodebridement (Versajet ® ) using a wound model inoculated with Staphylococcus aureus . Methods A full-thickness dermal wound was created in fresh porcine joint specimens, inoculated with S. aureus and incubated at 37°C for 24h. The specimens were surgically debrided with a curette, Coblation or Versajet, or were left untreated. During and after each debridement, aerosolized bacteria were measured by active and passive sampling. To assess the bacterial load of the wound, three quantitative swabs and one cylinder scrub sample were taken from each wound at baseline, post incubation and post debridement. Findings Versajet debridement resulted in significant bacterial aerosolization, but this was not the case when using a curette or Coblation. Only Coblation was able to reduce the bacterial load of the wound significantly. Conclusion Extra protective means should be implemented when using Versajet debridement for infected and colonized wounds. The same precautions may be less essential when using a curette or Coblation.

Infection constitutes an important part of wound pathology and impedes wound healing. Plasma-mediated bipolar radiofrequency ablation (Coblation(®)) is a tissue-removal technique suggested for use in wound treatment. The aims of this study were to determine the antimicrobial effect of ablation exposure on bacteria and fungi relevant to wound infection, and how exposure time, temperature and aerobic/anaerobic growth influence the effect. Suspensions of 10(6) colony-forming units/ml of Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Escherichia coli and Candida albicans were exposed to ablation or thermal control for 500, 1000 or 2000 ms, or left untreated, and incubated aerobically. E. coli was also incubated anaerobically. Ablation was significantly (p

The distribution in the skin of orally active antifungals and other drugs claimed to be active in the treatment of skin diseases is of major importance, but to date has been studied only rarely. In the present study the distribution of fluconazole in stratum corneum, epidermis-dermis (without stratum corneum), eccrine sweat and serum was studied in human male volunteers after dosages of 50 mg daily for 12 days and 150 mg once weekly for 2 weeks. In the present study high levels of fluconazole were found especially in the stratum corneum. At a dose of 50 mg once daily the concentration of fluconazole after 12 days was 73.0 micrograms/g and 7 days after cessation of treatment the concentration was still 5.8 micrograms/g. At the 150 mg once a week dose the concentration 7 days after the second dose was still 7.1 micrograms/g in stratum corneum indicating that medication once a week may be effective in the treatment of dermatomycoses. High concentrations, all above the serum concentrations, were also seen in sweat and epidermis/dermis. These results indicate that fluconazole is delivered to the stratum corneum, where it is accumulated, through sweat and by direct diffusion through the dermis-epidermis. These pharmacokinetic results indicate that the drug should be very effective in the treatment of dermatomycoses. An extremely high concentration of the drug in the stratum corneum combined with concentrations from 2.93 to 4.62 micrograms/g in the rest of the epidermis and dermis is important in the treatment of these diseases.

Background Development of the skin barrier continues up to 12 months after birth; therefore, care must be taken when cleansing and bathing infants’ skin. Available guidelines for skin care in newborns are, however, limited. In 2007, the 1st European Round Table meeting on ‘Best Practice for Infant Cleansing’ was held, at which a panel of expert dermatologists and paediatricians from across Europe aimed to provide a consensus on infant bathing and cleansing. Outcomes Based on discussions at the meeting and a comprehensive literature review, the panel developed a series of recommendations relating to several aspects of infant skin care, including initial and routine bathing, safety while bathing, and post-bathing procedures. The panel also focused on the use of liquid cleansers in bathing, particularly relating to the benefits of liquid cleansers over water alone, and the criteria that should be used when choosing an appropriate liquid cleanser for infants. Alkaline soaps have numerous disadvantages compared with liquid cleansers, with effects on skin pH and lipid content, as well as causing skin drying and irritation. Liquid cleansers used in newborns should have documented evidence of their mildness on skin and eyes, and those containing an emollient may have further benefits. Finally, the panel discussed seasonal differences in skin care, and issues relating to infants at high risk of atopic dermatitis. The panel further discussed the need of clinical studies to investigate the impact of liquid cleansers on skin physiology parameters on newborns’ and infants’ skin. Conclusions Bathing is generally superior to washing, provided basic safety procedures are followed, and has psychological benefits for the infant and parents. When bathing infants with a liquid cleanser, a mild one not altering the normal pH of the skin surface or causing irritation to skin or eyes should be chosen. Conflicts of interest M.J. Cork and F. Vanaclocha are advisors to Johnson and Johnson. U. Blume-Peytavi is a member of the advisory board of the ‘Penaten Beirat’, Johnson & Johnson, Germany. J. Faergemann, C. Gelmetti, J. Szczapa declared to have no conflict of interest.

Udgivelsesdato: 2009-Jun-5 Summary Background In a recent open pilot trial, R-salbutamol sulphate, a well-known molecule with anti-inflammatory effects, was tested successfully on patients with therapy-resistant discoid lupus erythematosus (DLE). Objectives To compare the efficacy and safety of R-salbutamol cream 0.5% vs. placebo on DLE lesions in a multicentre, double-blinded, randomized, placebo-controlled phase II trial. Methods Thirty-seven patients with at least one newly developed DLE lesion were randomized - 19 to the R-salbutamol cream 0.5% and 18 to placebo - and treated twice daily for 8 weeks. Efficacy was evaluated through scores of erythema, scaling/hypertrophy and induration as well as pain and itching; general improvement scored by the investigator and global improvement scored by patients' assessment were also evaluated. Results The mean area under the curve of improvement for scaling/hypertrophy, pain, itching and global patient assessment was significantly better for the actively treated patients as compared with placebo (scaling/hypertrophy, P = 0.0262; pain, P = 0.0238; itching, P = 0.0135; global patient assessment, P = 0.045). Moreover, the percentage of patients without induration was significantly higher in the active group compared with the placebo group (P = 0.013), and a statistically significantly greater decrease in the size of the lesional area was also seen in the overall analysis of the R-salbutamol-treated patients (P = 0.0197). No serious adverse events were reported. Conclusions Application of R-salbutamol cream 0.5% was safe and well tolerated. Statistically significant effects were seen on scaling/hypertrophy, induration, pain and itching as well as patient global assessment, suggesting that R-salbutamol could be a promising new topical therapy alternative for DLE.

Balanoposthitis is an inflammatory disorder of the prepuce and glans penis. Microbes involved in balanoposthitis have been investigated, but no single study has covered the growth of both bacteria, Candida and Malassezia. We report here the prevalence of these microbes in 100 patients with balanoposthitis and in 26 control patients. Among patients with balanoposthitis there was a significantly higher frequency of positive cultures than in the control group (59% and 35%, respectively, p

The use of pentane-1,5-diol in topical pharmaceutical products is relatively new compared with, e.g., propane-1,2-diol (propylene glycol), also an aliphatic diol, which has been used for many years. Yet, what are the differences between diols in clinical efficacy, safety and other characteristics?The objective of this overview was to compare the efficacy, safety, chemical and pharmaceutical characteristics of pentane-1,5-diol with other aliphatic diols used in pharmaceutical formulations in dermatology.A survey of the literature was carried out based on searches limited to aliphatic diols.Pentane-1,5-diol was found to be safe and more effective than several other diols with respect to drug delivery-enhancing potency, pharmaceutical and cosmetic properties, antimicrobial spectrum and toxicity. Results from formal clinical trials with pentane-1,5-diol verify its efficacy and safety. These characteristics together with its low cost make pentane-1,5-diol an attractive substance for use in pharmaceutical formulations for topical administration.

Acne vulgaris does not always respond to conventional therapy. Photodynamic therapy (PDT) has been proposed as a treatment option. The aim of this study was to determine the optimal light dose for effective PDT treatment of acne and to investigate whether PDT reduces sebum excretion and the amount of Propionibacterium acnes. Fifteen patients (9 men, 6 women, age range 16-44 years, mean age 25 years) with mild to severe acne were enrolled in an open, unblinded study. Aminolaevulinic acid cream (20% in Unguentum Merck) was applied on two circular areas 3 h before PDT. The areas of investigation were irradiated with red light (635 nm) from a Waldman PDT 1200 lamp. Ten patients with facial acne were treated with a light dose of 50 J/cm(2) on the right cheek and 30 J/cm(2) on the left cheek. Five patients with acne on their back were treated either with 50 J/cm(2) or with 70 J/cm(2). Clinical follow-up was performed for at least 10 weeks. In the patients with facial acne, sebum excretion was determined before PDT and at every follow-up visit. The amount of P. acnes was measured in a skin surface biopsy using a cyano-acrylate polymer to extract the content of the sebaceous follicles. In 9 patients with facial acne the improvement of lesions was the same for the two light doses. According to the patients' own assessment, 8 improved after PDT (p=0.02). No difference was found between the two doses in patients with acne on the back. Hyperpigmentation was more common at higher doses of light, and pain was experienced more often by the patients when higher doses were used. No significant reduction in P. acnes or sebum excretion was found at any time after PDT. It is concluded that PDT could be an alternative treatment of acne lesions. The lowest possible light dose should be used for minimal side-effects. Other mechanisms of action for PDT than eradication of P. acnes and sebosuppression should be considered.

Seborrhoeic dermatitis (SD) is a chronic, inflammatory skin disorder, affecting areas of the head and body where sebaceous glands are most prominent and active. The disorder commonly affects hair-bearing areas of the head, including the scalp. Involvement on the face is usually limited to the hairline, eyebrows, nasolabial folds and ears, and may occur either with or without scalp involvement. Areas of the trunk where SD may occur include the body folds and the presternal area. The aetiology of SD is unknown, although hormones and the Malassezia spp., formerly known as Pityrosporum (naturally occurring yeasts), are thought to be involved in the development of the condition. SD responds to the use of antifungal medications such as ketoconazole, suggesting that the inflammation could be linked to the Malassezia spp. The mechanisms behind the therapeutic effect of ketoconazole for the management of SD form the basis of this review. The broad spectrum activity of Ketoconazole was reported in the early 1980s. Due to its potent effect against Malassezia spp. the development of ketoconazole for the treatment of various skin infections, in which a link was proposed with Malassezia spp., was initiated. Later on, a number of ancillary properties were described for ketoconazole, comprising antibacterial, anti-inflammatory, sebostatic and antiproliferative effects. The incorporation of ketoconazole in an adapted vehicle further promoted its efficacy. Recently, a new anhydrous gel containing 2% ketoconazole (Xolegel) was launched, in which all of the above properties were optimised.

In a double-blind, parallel group study we compared fluconazole 150 mg once weekly with griseofulvin 500 mg once daily for 4-6 weeks in the treatment of tinea corporis or tinea cruris. Eighty-four of 114 patients (74%) (39% after 3 weeks) were clinically cured in the fluconazole group compared with 72 of 116 (62%) (39% after 3 weeks) in the griseofulvin group (P = 0.06). In the fluconazole group 78% were mycological cured compared with 80% in the griseofulvin group. In the fluconazole group nine patients (7.5%) had treatment related adverse events and in the griseofulvin group 15 patients (12.5%) had adverse events. Fluconazole 150 mg once weekly for 6 weeks is both clinically and mycologically effective in the treatment of tinea corporis and tinea cruris and few side-effects were reported.

Pityriasis versicolor is a chronic superficial fungal disease usually located on the upper trunk, neck or upper arms. Terbinafine is an orally and topically active allylamine antifungal derivative with a broad antifungal spectrum. Several studies have documented the high activity of terbinafine (Lamisil) cream in the treatment of pityriasis versicolor, with cure rates of 79-100% after 2-4 weeks of treatment. Lamisil emulsion gel (Lamisil DermGel) is a new topical formulation that remains in the skin in high concentrations for several months after just 1 week of application. Recently, in a prospective, double-blind, placebo-controlled, randomised, parallel-group, comparative, multicentre study, we have treated patients with pityriasis versicolor with either terbinafine 1% emulsion gel (Lamisil DermGel) or placebo gel. Sixty-one patients were included, 31 in the Lamisil DermGel group and 30 in the placebo gel group. The gel was applied once daily for 7 days and the patients were followed up for 8 weeks. Twenty-eight patients in the active and 29 patients in the placebo group were evaluable for efficacy. Using the intent-to-treat efficacy analysis, 21/28 (75%) were cured in the Lamisil-DermGel-treated group compared to 4/29 (14%) in the placebo group. No side-effects were seen. In conclusion, Lamisil DermGel was well tolerated and superior to placebo in the treatment of pityriasis versicolor when applied once daily for 7 days.

Objectives To review methodological approaches used in recent publications in onychomycosis clinical research. To identify key methodological criteria to ensure conclusive and reliable clinical results. Methods A Medline search for recent articles on onychomycosis treatment revealed considerable variation in inclusion criteria, definitions and methodology, rendering comparisons difficult. Results Careful diagnosis at trial entry is critical and predisposing factors affecting overall results are rarely considered at enrolment. Clear definitions are required, notably for the terms mycological, clinical and total cure. A consensus was reached that only studies that are evidence-based, controlled and double-blind with less than 10–15% of patients lost to follow-up should be accepted. Results should be interpreted with caution if a given treatment is found to be less effective than previously reported, even if the results are published in a recognized journal. It was agreed that an explanatory/pilot study should be done initially to determine whether there is a reason to believe that a new therapy is effective. If promising results are obtained, a double-blind, randomized study comparing the new therapy with either an existing therapy (preferably) or a placebo may be initiated. Conclusions Sample size, and inclusion and exclusion criteria should be clearly determined. Efficacy criteria should include mycological, clinical and total cure rates. Finally, studies of toenail and fingernail onychomycosis must last at least 18 and 9 months, respectively.

Background There are numerous factors that predispose to onychomycosis including genetic predisposition, diabetes mellitus, immunosuppression, vascular disease and psoriasis. Objectives The aims of this workshop were to discuss current knowledge of genetic risk factors and the approaches that should be used to investigate underlying mechanisms. Results The high prevalence of onychomycosis within certain families was initially attributed to intrafamilial transmission. However, the low prevalence of infection in people marrying into infected families together with the high prevalence among their offspring suggested a genetic basis. The state-of-the-art pedigree study by Zaias et al. suggested that Trichophyton rubrum infection shows an autosomal dominant pattern of inheritance. A consensus was reached that epidemiological and genetic studies are required to investigate this issue further. For epidemiological studies, families in which two or three generations are infected with T. rubrum should be selected. Patients with T. rubrum on different body sites should be included, and the presence of associated diseases or other common features in these individuals should be investigated to identify trigger factors. Conclusion Genetic studies should explore the mode of inheritance of onychomycosis and look for the disease gene(s). Serum samples from patients and age–sex matched controls must be analysed centrally. The results of these studies will make it possible to develop therapeutic, preventive and prophylatic measures and to provide patients and their families with information.

Multi-resistance to antibiotic therapy and to biocides is becoming increasingly common, which has led to mounting concern worldwide regarding the future use of traditional antimicrobials. Diols or glycols also have antimicrobial effects. Pentane-1,5-diol has low oral toxicity, is essentially non-irritating to the skin and has high antimicrobial activities against bacteria, fungi and viruses. The effect of pentane-1,5-diol against both sensitive and multi-resistant Gram-positive and Gram-negative bacteria was tested in vitro against 85 bacterial strains showing minimal inhibitory concentrations in the range of 2.5 to 15.0% (vol/vol) against both antibiotic-susceptible and multi-resistant aerobic bacteria. The exact mechanism of action is unknown but probably pentane-1,5-diol sucks water out of the bacterial cells which then collapse, a mechanism to which it is probably very difficult to develop resistance. The high activity against multi-resistant bacteria makes pentane-1,5-diol an interesting new compound for topical antimicrobial therapy in humans.

Cultures for Malassezia yeasts were taken from both normal-looking skin and lesional skin in 124 patients with atopic dermatitis, 16 patients with seborrhoeic dermatitis and from normal skin of 31 healthy controls. Positive Malassezia growth was found in fewer patients with atopic dermatitis (56%) than in patients with seborrhoeic dermatitis (88%) or in healthy controls (84%, p

The aim of this study was to confirm findings that vapour-impermeable panty liners might impair skin climate, and to assess their impact on the skin microflora. Temperature, surface pH and aerobic microflora were measured on vulvar skin of 102 women. The mean skin temperature was 1.1 degrees C higher when using a vapour-impermeable panty liner compared with not using one. Use of panty liners with vapour-permeable back sheets and acidic cores resulted in skin temperature, pH and microflora levels that were very close to those observed in persons not using liners. The temperature, pH and total number of microorganisms were significantly lower for users of vapour-permeable panty liners than for users of vapour-impermeable ones (p0.05, p0.001 and p0.001, respectively). The microorganism densities were usually higher when using the vapour-impermeable panty liner, but mean differences were minor. The use of panty liners seems not to imply a microbial risk for normal, healthy women.

Background Dermatophyte infections have been considered rare in psoriasis. However, there are data indicating that tinea unguium is as common or even more common in psoriasis compared with healthy controls. Tinea unguium is generally a secondary event to tinea pedis infection. Objectives To study the prevalence of tinea pedis and tinea unguium in psoriasis compared with a control group. Methods Consecutive psoriasis outpatients aged 18-64 years attending a department of dermatology were examined. Samples for direct microscopy and culture were taken from the interdigital spaces, soles and toenails. Consecutive patients without signs of psoriasis or atopic dermatitis seeking examination of moles constituted the control group. Results In total, 239 patients with psoriasis and 245 control patients were studied. The prevalence of tinea pedis was 8·8%[95% confidence interval (CI) ± 3·6%] in the psoriasis group and 7·8% (95% CI ± 3·4%) in the control group. The corresponding figures for prevalence of tinea unguium were 4·6% (95% CI ± 2·7%) and 2·4% (95% CI ± 1·9%), respectively. The differences found in the psoriasis vs. the control groups were not statistically significant. Conclusions This study does not support the hypothesis that the prevalence of tinea pedis and tinea unguium in patients with psoriasis differs from that in a normal population.

The aim of this study was to compare the change in collagen synthesis between topical treatments with two doses of triiodothyroacetic acid (TRIAC), a thyroid hormone analogue, and placebo, after pretreatment with topical betamethasone 17-valerate (BM). Eighteen healthy volunteers were pretreated with BM on abdominal skin for 3 days, and were then treated for 14 days with a cream containing TRIAC (0.03% or 0.1%) or a placebo cream. Collagen production was assessed by quantifying the amino terminal propeptides of human type I and type III procollagen (PINP and PIIINP) in fluids from suction-induced blisters on the treated skin. Three days of treatment with BM led to an average reduction of PINP of 70% and of PIIINP of 50%. Seven days after treatment, the median increase in PINP was 230% (p = 0.03) in the Triac 0.03% group, 148% (p = 0.2) in the TRIAC 0.1% and 5% in the placebo group. The median increase in PINP in the skin area from the start of treatment to the end of treatment was 521% (p = 0.06) in the TRIAC 0.03% group, 339% (p = 0.2) in the TRIAC 0.1% group, and 55% in the placebo group (the p values are related to baseline). Seven days after treatment, the median increase in PIIINP was 24% (p = 0.6) in the Triac 0.03% group, 23% (p = 0.6) in the TRIAC 0.1% group, and -12% in the placebo group. The median increase in PIIINP in the skin area from the start of treatment to the end of treatment was 137% (p = 0.7) in the TRIAC 0.03% group, 230% (p = 0.9) in the TRIAC 0.1% group and 58% in the placebo group (the p values are related to baseline). Histologic examinations of sections from punch biopsies taken at the end of the treatment showed more thickened collagen fibers and increased density of PINP-producing dermal fibroblasts in the TRIAC groups compared to the placebo group. The result suggests a potential role for TRIAC-containing cream concomitant with anti-inflammatory topical treatment with potent glucocorticoids to prevent their suppressive activity on dermal collagen production.

To investigate if there is a synergy between the presence of the Malassezia yeasts and the adverse reaction during treatment of scalp psoriasis with calcipotriol scalp solution, patients were treated with itraconazole to reduce the number of Malassezia yeasts. This study was a double-blind, placebo-controlled parallel group study between oral itraconazole or placebo for 8 weeks in patients with scalp psoriasis. After 2 weeks, calcipotriol scalp solution was applied twice daily for 6 weeks. Altogether 137 patients, 67 in the itraconazole group and 70 in the placebo group, comprised the intention-to-treat population. There were 13 (19.4%) patients with local skin irritation in the itraconazole group compared to 33 (47.1%) in the placebo group (p0.001). The skin irritation was significantly lower in patients with a low number of cultured Malassezia yeasts (p = 0.017). Thus, when Malasessia was eliminated or the numbers reduced, the irritation produced by calcipotriol was significantly diminished.

Pityriasis versicolor is a mild or chronic condition characterized by scaly hypopigmented or hyperpigmented lesions usually affecting the trunk. The lesions vary depending on tropical or temperate climates. The disease seems to occur mainly at adolescence when the sebaceous glands are more active. Malassezia yeasts have been implicated in the pathogenesis of this disease. The mycelial form of the fungus has been suggested to be the cause of lesions. Antifungal preparations have been used to treat the initial presentation effectively, although in a proportion of patients the disease tends to reoccur. They are available in a wide range of formulations and have been shown to be safe.

Background The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD). Objectives To investigate the reactivity to Malassezia allergens, measured as specific serum IgE, positive skin prick test and positive atopy patch test (APT), in adult patients with AD. Methods In total, 132 adult patients with AD, 14 with seborrhoeic dermatitis (SD) and 33 healthy controls were investigated for their reactions to M. sympodialis extract and three recombinant Malassezia allergens (rMal s 1, rMal s 5 and rMal s 6). Results Sixty-seven per cent of the AD patients, but only one of the SD patients and none of the healthy controls, showed a positive reaction to at least one of the Malassezia allergens (extract and/or recombinant allergens) in at least one of the tests. The levels of M. sympodialis-specific IgE in serum correlated with the total serum IgE levels. Elevated serum levels of M. sympodialis-specific IgE were found in 55% and positive APT reactions in 41% of the AD patients with head and neck dermatitis. A relatively high proportion of patients without head and neck dermatitis and patients with low total serum IgE levels had a positive APT for M. sympodialis, despite lower proportions of individuals with M. sympodialis-specific IgE among these groups of patients. Conclusions These results support that Malassezia can play a role in eliciting and maintaining eczema in patients with AD. The addition of an APT to the test battery used in this study reveals a previously overlooked impact of Malassezia hypersensitivity in certain subgroups of AD patients.

The role of Malassezia furfur adherence to human stratum corneum cells in vitro was studied. The adherence assay was performed with one strain of M. furfur and stratum corneum cells from 30 healthy individuals and from 28 patients with seborrhoeic dermatitis. Stratum corneum cells from patients with seborrhoeic dermatitis contained significantly lower numbers of adherent M. furfur cells than cells from healthy individuals. No correlation was found with sex or age. The adherence assay was also performed with stratum corneum cells from one healthy individual and M. furfur strains from 15 patients with seborrhoeic dermatitis and 13 healthy controls. Malassezia furfur strains from patients with seborrhoeic dermatitis showed the same in vitro capacity for adherence to stratum corneum cells as strains from healthy individuals. This in vitro study does not indicate that M. furfur adherence to human stratum corneum cells is of importance in the pathogenesis of seborrhoeic dermatitis.

Summary Several studies indicate that Pityrosporum ovale plays an important role in seborrhoeic dermatitis. Many of these are treatment studies which describe the effectiveness of antimycotics, paralleled by a reduction in the number of P. ovale colonies and then recolonization, leading to a recurrence of seborrhoeic dermatitis. In this study 20 patients with seborrhoeic dermatitis of the scalp were treated with terbinafine (Lamisil®) 1% solution once daily for 4 weeks. Eleven of 18 patients (61%) were cured and they were still free of lesions 2 weeks after stopping treatment. No side-effects related to treatment were seen. There was also a significant reduction in the number of P. ovale colonies. This may explain both the good clinical effect and the observation that all patients who were cleared of P. ovale were still free of lesions 2 weeks after stopping treatment.

Twenty patients with onychomycosis secondary to paronychia or to onycholysis were examined for causative fungal agents. The role of yeasts in these diseases is critically discussed.

Background: Griseofulvin has been used in the treatment of toenail onychomycosis with limited success. Evidence suggests that terbinafine may be more effective. Objective: In a double-blind, parallel-group study we compared 250 mg/day terbinafine for 16 weeks with 500 mg/day griseofulvin for 52 weeks (or for shorter periods in cured patients) in patients with toenail onychomycosis. Methods: Eighty-nine patients with culture-proved tinea unguium were included, and 43 in the terbinafine group and 41 in the griseofulvin group were assessable for efficacy. Patients who had not improved after 16 weeks were entered into an open study and were given 250 mg/day terbinafine for 16 weeks with the study code still blinded and were then followed up for 20 weeks. Results: Terbinafine was significantly more effective than griseofulvin, with 42% being completely cured and 84% mycologically cured compared with only 2% with total cure and 45% with mycologic cure in the griseofulvin-treated group. The number of side effects was significantly lower in the terbinafine group (11%) compared with the griseofulvin group (29%). Conclusion: Terbinafine is significantly more effective than griseofulvin in the treatment of toenail onychomycosis.

In earlier skin pharmacokinetic studies we have shown that terbinafine is rapidly delivered to the stratum corneum, nails and hair both through sebum and by direct diffusion through dermis-epidermis. In the present study the skin pharmacokinetic profile of terbinafine was studied in two groups of eight human male volunteers during and after 250 mg orally once daily for 7 and 14 days. In the 7-day study high terbinafine levels were found in sebum (19.0 micrograms/g) and stratum corneum (2.5 micrograms/g), and a concentration in stratum corneum above the minimal inhibitory concentration for most dermatophytes was still found 48 days after the last day of medication. Terbinafine was found in peripheral nail clippings after 7 days of medication and the concentration was, in the 7-day study, 0.5 microgram/g 1 day after stopping medication; it was still 0.2 microgram/g 90 days after stopping treatment. The results in the 14-day study were in parallel with, but higher than, in the 7-day study. The elimination of terbinafine from several compartments is biphasic, with a faster initial elimination followed by a slower secondary elimination. For nails, the elimination is slower compared with the other compartments. The results indicate that terbinafine may be effective in short-term treatment of several dermatophytoses. The concentration of 0.2 microgram/g of terbinafine found in nails 90 days after stopping medication, following 7 days of treatment, indicates that the duration of therapy, even in tinea ungium, may be shorter than is currently the case.

Die lipophile Hefe Pityrosporum ovale ist ein Keim der normalen Hautflora und kann von der Haut fast aller Erwachsenen kultiviert werden [1]. Die Kolonisierung beginnt in der Pubertat. P. ovale kann jedoch auch von der Haut kleiner Kinder, sogar von Sauglingen isoliert werden. Bei Personen mittleren Alters und bei alteren Personen wird die Anzahl von P. ovale geringer, vielleicht wegen einer Reduzierung der Hautlipide [2]. Die groste Anzahl von Hefen findet man am oberen Rumpf, im Gesicht und an der Kopfhaut. An diesen Stellen sind auch die Talgdrusen am haufigsten. Die Form des Organismus hat man als rund und oval beschrieben, mehrere Aussagen bezeugen, das die beiden Formen identisch sind und nur verschiedene Stufen eines Zellzyklus desselben Organismus sind.

Summary Sera from 10 patients with seborrhoeic dermatitis and from 10 age-matched healthy individuals were examined for IgG activity against Pityrosporum ovale. The IgG activity was analysed using the following techniques: an enzyme-linked immunosorbent assay (ELISA) against whole P. ovale cells, purified cell-wall carbohydrate or protein extract, an indirect slide-immunofluorescence assay and fluorescence-activated flow cytometry using the whole organism as antigen. The ELISA method using the protein antigen was the only technique that showed a significant difference between patients and controls; a lower antibody response was found in the seborrhoeic dermatitis patients compared to healthy controls.

Pityrosporum ovale is a lipophilic yeast commonly present in the seborrheic areas of the skin of adults. Fifty-five young adult patients with atopic dermatitis, 19 patients with seborrheic dermatitis, and 19 healthy control subjects were examined for immune reactions to P. ovale, including tests for specific IgE antibodies (prick test, histamine release), IgG antibodies and epicutaneous testing. IgE antibodies against P. ovale were found in two thirds of the patients with atopic dermatitis and were more frequent in patients with lesions predominantly in the seborrheic areas. In addition, some atopic patients had positive reactions to epicutaneous tests, which suggest that delayed allergic reactions to P. ovale may also be important. In patients with seborrheic dermatitis, no evidence of immediate or delayed hypersensitivity to P. ovale was found. IgG antibody levels were low in all groups.

Serum IgG antibodies against Pityrosporum orbiculare were detected by enzyme-linked immunosorbent assay (ELISA). Preliminary experiments with different microtiter plates, various techniques for coating, incubation and washing indicated that the following procedures were most suitable. Titertec P.V.C. Microplates, high activated (HAC) (Flow, England) were used. Wells were coated with whole P. orbiculare cells suspended in a 0.05 M carbonate buffer (107 cells ml−1), pH 9.6 for 3h at 37°C. After each incubation step the wells were washed 3 times with phosphate buffered saline (PBS) con-taining 0.05% Tween 20 (PBS-Tw), pH 7.4. The wells were filled with bovine serum albumin (BSA) 20 g L-1 in PBS and left overnight at 4°C. The plates were incubated for 2.5h at 37°C with serum diluted in PBS-Tw. Alkaline phosphatase-conjugated rabbit anti-human IgG (Dako-Pads, Denmark) diluted in PBS-Tw was added and left overnight at 4°C. Finally 4-nitrophenyl phos-phate (Sigma, USA) 1 mg ml−1 in 1 M diethanolamine buffer, pH 9.8 (Merck, West Germany) was allowed to react. The absorbance was read after 50 min with a Titertec-Multiscan MCC photometer (Flow, England). Ten sera from healthy adult volunteers were used. The experiment was done with 4 different samples from each of the sera and each sample was run in triplicate. The ELISA-method was compared with the indirect immunofluorescent technique.

Die lipophile Hefe Pityrosporum ovale ist ein Keim der normalen Hautflora bei Erwachsenen [1]. Die Kolonisierung startet in der Prapubertat wegen eines Anstiegs der Sebumproduktion. P. ovale kommt uberwiegend an der Kopfhaut, im Gesicht und am oberen Rumpf vor.

The antimycotic activity of ethane-1,2-diol, propane-1,2-diol, butane-1,3-diol, pentane-1,5-diol, and hexane-2,5-diol in vitro against Pityrosporum orbiculare, Candida albicans, Trichophyton rubrum, T. mentagrophytes var. interdigitale and Epidermophyton floccosum was studied. Ethane-1,2-diol had the lowest activity (MIC of 40-100 g 1(-1)), and hexane-2,5-diol the highest activity (MIC of 10-40 g 1(-1)). Among, the higher diols there can be both effective antifungal agents and substances with a lower risk of allergic and irritative skin reactions than propane-1,2-diol.

Pityrosporum orbiculare, P. ovale, and P. pachydermatis showed the same luxuriant growth when cultured under aerobic conditions, in an aerobic milieu with 7 % CO2, and under micro-aerophilic conditions. The species survived and even multiplied under strictly anaerobic conditions. These findings may explain how P. orbiculare and P. ovale can survive in the deeper parts of hair follicles.On a medium that enhanced the production of filaments in Pityrosporum, filaments were more pronounced in the micro-aerophilic environment. Macroscopically, P. ovale showed a more luxuriant growth than P. orbiculare on this medium, but microscopically the same type of filaments were produced.

The purpose of this investigation was to produce experimental tinea versicolor in rabbits and humans with Pityrosporum orbiculare . Inoculation with P. orbiculare under plastic occlusion on the glabrous follicle-rich inside of the rabbit ear resulted in a tinea versicolor-like lesion after 1 week in 3 of 4 animals. One week after inoculation with P. orbiculare under plastic occlusion, experimental infections similar to those found clinically in tinea versicolor were seen in 10 of 12 patients with a history of tinea versicolor and in 3 of 6 normal volunteers. It was not possible to produce experimental infections without occlusion. Spontaneous healing usually occurred.

Seventy patients (36 males and 34 females) with seborrhoeic dermatitis of the scalp were treated in a double-blind controlled study, for a maximum of 6 weeks, with 2% miconazole base and 1% hydrocortisone (Daktacort), 2% miconazole base, or 1% hydrocortisone. Patients who were cured were treated with the same formulation prophylactically twice monthly for 3 months or until recurrence. Nineteen of 21 patients were cured in the Daktacort group, 15 of 22 in the miconazole group and 17 of 24 in the hydrocortisone group. The number of cultured Pityrosporum orbiculare was significantly lower in all groups after treatment, but in the hydrocortisone group was still significantly higher than in the two other groups. After 3 months of prophylactic treatment, both Daktacort (16 of 19 patients clear) and miconazole (10 of 15 patients clear) were significantly better than hydrocortisone (3 of 17 patients clear) (P less than 0.01). The numbers of P. orbiculare remained low in the Daktacort and miconazole groups and also significantly lower than in the hydrocortisone-treated group (P less than 0.01). In patients with recurrence, the numbers returned to pre-treatment levels. This study demonstrates the aetiological significance of the Pityrosporum yeasts in seborrhoeic dermatitis. Both Daktacort and miconazole were effective in treatment and as prophylactic agents.

Using the indirect immunofluorescence technique no differences were observed in intensity of staining when antisera against Pityrosporum orbiculare and P. ovale or IgG fractions of these were incubated with P. orbiculare and P. ovale cells. However, a weaker reaction was observed with these antisera and P. pachydermatis cells. With IgG fractions the nonspecific fluorescence was minimized. Fungal cells in biopsies from tinea versicolor lesions showed a brilliant staining with the IgG fractions of antisera against P. orbiculare . This investigation indicates a close antigenic relationship between all of the 3 Pityrosporum species. A common antigenicity was found between P. orbiculare and P. ovale cells as well as between P. orbiculare cells from culture and the fungal cells in biopsies from tinea versicolor lesions. This strongly suggests that these 2 species are identical with each other and with the organism found in tissue.

SUMMARY Twenty children (mean age 9 weeks) with infantile seborrhoeic dermatitis (ISD) were investigated with cultures for bacteria, Pityrosporum ovale and other fungi, and 20 healthy children served as controls. P. ovale and Staphylococcus aureus were the dominant organisms. P. ovale was cultured in 18 of 20 infants with ISD as compared to 4 of 20 controls. S. aureus was cultured in 14 of 20 infants with ISD as compared to 1 of 20 controls. The role of S. aureus in ISD is not known, but it could be a secondary invader as is supposed in atopic dermatitis (AD). Even if P. ovale may be suspected as the aetiological agent of ISD further studies are needed to clarify the exact role of the organism in ISD.

Fifty-one patients, thirty-nine women and twelve men, with Pityrosporum folliculitis are described. This investigation clearly demonstrates that Pityrosporum folliculitis is a real entity. The diagnosis is based primarily on the clinical picture, direct microscopy, histopathology, and the effect of antimycotic treatment. The typical patient is a woman of 30 years with itching follicular papules and pustules localized to the upper trunk or upper arms. Direct microscopy reveals round yeast cells and sometimes even hyphae. In biopsy specimens, abundant round budding yeast cells and occasionally hyphae are seen in a dilated follicle. Yeast growth is obtained only on lipid-enriched media. Twenty-five patients were treated with selenium sulfide shampoo, twelve with 50% propylene glycol in water, and ten with topical econazole cream with good results. Cure or marked improvement was seen after 3 to 4 weeks, but symptoms and lesions recurred if treatment was not continued intermittently. Predisposing factors such as occlusion and greasy skin are probably important, and future studies should focus on fungal hypersensitivity, quantitative variations in the number of Pityrosporum orbiculare, lipid composition of the skin, and extended epidemiologic data.