Position statement: Recommendations on the diagnosis and treatment of Malassezia folliculitis.

Malassezia is a lipophilic yeast that is a part of the human mycobiome. Malassezia folliculitis appears when the benign colonization of the hair follicles, by the Malassezia yeasts, becomes symptomatic with pruritic papules and pustules. Although Malassezia folliculitis is common in hospital departments, diagnosing and treating it varies among dermatologists and countries. The European Academy of Dermatology and Venereology Mycology Task Force Malassezia folliculitis working group has, therefore, sought to develop these recommendations for the diagnosis and management of Malassezia folliculitis. Recommendations comprise methods for diagnosing Malassezia folliculitis, required positive findings before starting therapies and specific treatment algorithms for individuals who are immunocompetent, immunocompromised or who have compromised liver function. In conclusion, this study provides a clinical strategy for diagnosing and managing Malassezia folliculitis.

Critical synthesis of available data in Malassezia folliculitis and a systematic review of treatments.

Folliculitis is an inflammatory process involving the hair follicle, frequently attributed to infectious causes. Malassezia, an established symbiotic yeast that can evolve to a skin pathogen with opportunistic attributes, is a common source of folliculitis, especially when intrinsic (e.g. immunosuppression) or extrinsic (high ambient temperature and humidity, clothing) impact on the hair follicle and the overlying skin microenvironment. Our aim was to critically review the pathophysiology and clinical characteristics of Malassezia folliculitis, to describe laboratory methods that facilitate diagnosis and to systematically review treatment options. Malassezia folliculitis manifests as a pruritic, follicular papulopustular eruption distributed on the upper trunk. It commonly affects young to middle-aged adults and immunosuppressed individuals. Inclusion into the differential diagnosis of folliculitis is regularly oversighted, and the prerequisite-targeted diagnostic procedures are not always performed. Sampling by tape stripping or comedo extractor and microscopic examination of the sample usually identifies the monopolar budding yeast cells of Malassezia without the presence of hyphae. However, confirmation of the diagnosis with anatomical association with the hair follicle is performed by biopsy. For systematic review of therapies, PubMed was searched using the search string "(malassezia" [MeSH Terms] OR "malassezia" [All Fields] OR pityrosporum [All Fields]) AND "folliculitis" [MeSH Terms] and EMBASE was searched using the search string: 'malassezia folliculitis.mp OR pityrosporum folliculitis.mp'. In total, 28 full-length studies were assessed for eligibility and 21 were selected for inclusion in therapy evaluation. Conclusively Malassezia folliculitis should be considered in the assessment of truncal, follicular skin lesions. Patient's history, comorbidities and clinical presentation are usually indicative, but microscopically and histological examination is needed to confirm the diagnosis. Adequate samples obtained with comedo extractor and serial sections in the histological material are critical for proper diagnosis. Therapy should include systemic or topical measures for the control of the inflammation, as well as the prevention of recurrences.

A survey among dermatologists: diagnostics of superficial fungal infections - what is used and what is needed to initiate therapy and assess efficacy?

BACKGROUND: Superficial fungal infections are common. It is important to confirm the clinical diagnosis by mycological laboratory methods before initiating systemic antifungal treatment, especially as antifungal sensitivity and in vitro susceptibility may differ between different genera and species. For many years, the gold standard for diagnosis of superficial fungal infections has been direct fungal detection in the clinical specimen (microscopy) supplemented by culturing. Lately, newer molecular based methods for fungal identification have been developed. OBJECTIVE: This study was initiated to focus on the current usage of mycological diagnostics for superficial fungal infections by dermatologists. It was designed to investigate whether it was necessary to differentiate between initial diagnostic tests and those used at treatment follow-up in specific superficial fungal infections. METHODS: An online questionnaire was distributed among members of the EADV mycology Task Force and other dermatologists with a special interest in mycology and nail disease. RESULTS: The survey was distributed to 62 dermatologists of whom 38 (61%) completed the whole survey, 7 (11%) partially completed and 17 (27%) did not respond. Nearly, all respondents (82-100%) said that ideally they would use the result of direct microscopy (or histology) combined with a genus/species directed treatment of onychomycosis, dermatophytosis, Candida- and Malassezia-related infections. The majority of the dermatologists used a combination of clinical assessment and direct microscopy for treatment assessment and the viability of the fungus was considered more important at this visit than when initiating the treatment. Molecular based methods were not available for all responders. CONCLUSION: The available diagnostic methods are heterogeneous and their usage differs between different practices as well as between countries. The survey confirmed that dermatologists find it important to make a mycological diagnosis, particularly prior to starting oral antifungal treatment in order to confirm the diagnose and target the therapy according to genus and species.

Efficacious and safe management of moderate to severe scalp seborrhoeic dermatitis using clobetasol propionate shampoo 0·05% combined with ketoconazole shampoo 2%: a randomized, controlled study.

BACKGROUND: Topical antifungals and corticosteroids are the mainstay of treatment for seborrhoeic dermatitis. The short-contact clobetasol propionate 0·05% shampoo (CP) is an efficacious and safe once-daily treatment for scalp psoriasis. OBJECTIVES: To evaluate the efficacy and safety of CP alone and combined with ketoconazole shampoo 2% (KC) in the treatment of moderate to severe scalp seborrhoeic dermatitis. METHODS: This randomized and investigator-blinded study consisted of three phases, each lasting 4 weeks. During the treatment phase, subjects were randomized to receive KC twice weekly (K2), CP twice weekly (C2), CP twice weekly alternating with KC twice weekly (C2 + K2) or CP four times weekly alternating with KC twice weekly (C4+K2). All subjects received KC once weekly during the maintenance phase and were untreated during the follow-up phase. RESULTS: At the end of the treatment phase, all three CP-containing regimens were significantly more efficacious than K2 in decreasing the overall disease severity (P < 0·05). Both combination regimens were also significantly more efficacious than K2 in decreasing each individual sign of the disease (P < 0·05). While the C2 and C4 + K2 groups experienced slight worsening during the maintenance phase, the efficacy of C2 + K2 was sustained and remained the highest among all groups. All regimens were well tolerated without inducing any skin atrophy. Similarly low incidences of telangiectasia, burning and adverse events were observed among the four groups. CONCLUSIONS: The combination therapy of twice-weekly CP alternating with twice-weekly KC provided significantly greater efficacy than KC alone and a sustained effect in the treatment of moderate to severe scalp seborrhoeic dermatitis.

A randomized controlled trial of R-salbutamol for topical treatment of discoid lupus erythematosus.

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.

Bathing and cleansing in newborns from day 1 to first year of life: recommendations from a European round table meeting.

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.

Antibodies to Pityrosporum orbiculare in patients with tinea versicolor and controls of various ages.

Sera from patients with tinea versicolor and controls of various ages were investigated with the indirect immunofluorescence technique for antibodies against Pityrosporum orbiculare, the etiologic agent of tinea versicolor. No differences in titers were observed between patients and adult controls. Also, there were no differences in antibody titers in the patient group with regard to age and sex, or to duration and distribution of lesions. A statistically significant difference in antibody titers was observed between adult controls and children, particularly the youngest. Antibodies against Candida albicans from randomly selected sera from the same groups showed the same tendency, although only statistically significant when children of 5 years or younger were compared with adult controls. This investigation indicates that although P. orbiculare is capable of inducing antibodies, these are not correlated to tinea versicolor but occur when an individual becomes colonized with the organism.

Experimental tinea versicolor in rabbits and humans with Pityrosporum orbiculare.

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.

A new model for growth and filament production of Pityrosporum ovale (orbiculare) on human stratum corneum in vitro.

A new model for the production of hyphae in Pityrosporum ovale in vitro is described. P. ovale was cultured on human stratum corneum pieces placed directly on a culture medium. The highest number of hyphae (24%) was seen after 6 d of incubation at 37 degrees C in a microaerophilic environment. There was a variation between the strains tested. This model opened possibilities to study the filamentous form of P. ovale in vitro. The effect of antimycotics and variation in antigens may be investigated and compared to the yeast form.

Experimental infections in rabbits and humans with Pityrosporum orbiculare and P. ovale.

The purpose of this investigation was to produce experimental tinea versicolor in rabbits and humans with Pityrosporum orbiculare and P. ovale. P. orbiculare and P. ovale were inoculated, with and without occlusion, on the inside of the ear in 10 male rabbits and on the upper arm in 10 patients with a history of tinea versicolor, and in 3 healthy volunteers. After 1 week tinea versicolor-like lesions were produced with both P. orbiculare and P. ovale in 8 of 10 rabbits. Likewise experimental infections, similar to those found clinically in tinea versicolor, were seen, after 1 week, in 5 patients with a history of tinea versicolor and in the 3 healthy volunteers. Two of 5 patients inoculated for only 4 days showed identical but less pronounced lesions. Experimental infections could only be produced with occlusion. Microscopically short hyphae and transformation between round and oval forms were seen in both P. orbiculare and P. ovale. This investigation adds to the identity of P. orbiculare and P. ovale and also to the identity of these 2 fungi and the fungus seen in tinea versicolor. Spontaneous healing and the fact that experimental infections were produced only under occlusion illustrates the importance of predisposing factors in tinea versicolor.

Antigenic similarities and differences in genus Pityrosporum.

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.

Pityrosporum ovale and skin diseases.

Pityrosporum ovale is a lipophilic yeast belonging to the normal human cutaneous flora in adults. It is not only a saprophyte but also an opportunistic pathogen associated with: Pityriasis versicolor, Pityrosporum folliculitis, seborrhoeic dermatitis and some forms of atopic dermatitis. Even systemic infections have been described. In pityriasis versicolor P. ovale change from the blastospore to the mycelial form under the influence of predisposing factors such as high temperature, high relative humidity or endogenous factors such as greasy skin, sweating, heredity, immunosuppressive treatment or disorders. Topical treatment is often effective but short term treatment with fluconazole, ketoconazole or itraconazole is also effective. The great problem is recurrence and to avoid this a prophylactic treatment is mandatory. Pityrosporum folliculitis is a chronic disease characterized by pruritic follicular papules and pustules located primarily on the upper trunk, neck and upper arms. Under the influence of the same predisposing factors as in pityriasis versicolor P. ovale increase in numbers in the hair follicles. The main differential diagnosis is acne vulgaris. The effect of antifungal treatment is often dramatic. There are now many studies indicating that P. ovale plays an important role in seborrhoeic dermatitis. Many of these are treatment studies showing a good effect of antimycotics parallelled by a reduction in number of P. ovale. Severe seborrhoeic dermatitis often difficult to treat is associated with AIDS. In a recent study we have evidence for a slight T-cell defect in many patients with seborrhoeic dermatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of triazole derivatives against Pityrosporum orbiculare in vitro and in vivo.

The in vitro antimycotic activity and the in vivo antimycotic activity (in a rabbit model) of itraconazole against P. orbiculare were compared to the corresponding activities of ketoconazole. Fluconazole's in vitro antimycotic activity and in vivo antimycotic activity against P. orbiculare were tested in the same models. The MIC values of itraconazole against P. orbiculare were 0.1-0.2 micrograms/ml compared to 0.02-0.05 micrograms/ml for ketoconazole. For fluconazole, the MIC values were 12.5-50.0 micrograms/ml against P. orbiculare. In a rabbit model, orally administered itraconazole (5 mg/kg) afforded protection against experimental pityriasis (tinea) versicolor in four out of five rabbits. Ketoconazole (1 mg/kg) was effective in all four animals. The in vivo results with fluconazole were in contrast to its low in vitro activity. Fluconazole (5 mg/kg) afforded protection against experimental pityriasis (tinea) versicolor in five out of six animals.

Tinea versicolor with regard to seborrheic dermatitis. An epidemiological investigation.

This is a retrospective study of 232 patients, and a prospective survey of 48 patients, regarding susceptibility factors in tinea versicolor, particularly in association with seborrheic dermatitis. In both surveys, a higher (10.4%) than expected (3.8%) percentage of association with seborrheic dermatitis was found.

Management of seborrheic dermatitis and pityriasis versicolor.

Pityriasis (tinea) versicolor and seborrheic dermatitis are two very common skin diseases. Pityriasis versicolor is a chronic superficial fungal disease usually located on the upper trunk, neck, or upper arms. In pityriasis versicolor, the lipophilic yeast Malassezia (also know as Pityrosporum ovale or P. orbiculare) changes from the blastospore form to the mycelial form under the influence of predisposing factors. The most important exogenous factors are high temperatures and a high relative humidity which probably explain why pityriasis versicolor is more common in the tropics. The most important endogenous factors are greasy skin, hyperhidrosis, hereditary factors, corticosteroid treatment and immunodeficiency. There are many ways of treating pityriasis versicolor topically. Options include propylene glycol, ketoconazole shampoo, zinc pyrithione shampoo, ciclopiroxamine, selenium sulfide, and topical antifungals. In difficult cases, short term treatment with fluconazole or itraconazole is effective and well tolerated. To avoid recurrence a prophylactic treatment regimen is mandatory. Seborrheic dermatitis is characterized by red scaly lesions predominantly located on the scalp, face and upper trunk. There are now many studies indicating that Malassezia plays an important role in this condition. Even a normal number of Malassezia will start an inflammatory reaction. Mild corticosteroids are effective in the treatment of seborrheic dermatitis. However, the disease recurs quickly, often within just a few days. Antifungal therapy is effective in the treatment of seborrheic dermatitis and, because it reduces the number of Malassezia, the time to recurrence is increased compared with treatment with corticosteroids. Antifungal therapy should be the primary treatment of this disease.

Phototoxicity of skin microorganisms tested with a new model.

A new standardized method for testing phototoxicity of chemicals against microorganisms is described. The inoculum size of the microorganism, application of test chemicals, prediffusion time, incubation time and incubation period are defined. Staphylococcus aureus, S. epidermidis, Candida albicans, and Pityrosporum orbiculare were studied. Both 8-methoxypsoralen and trimethylpsoralen were phototoxic against all microorganisms tested, while tetracycline and doxycycline were not phototoxic. C. albicans may be chosen for phototoxicity testing because it has been used earlier, it is easy to maintain in culture, it grows easily when tested, and its pathogenicity is low. The phototoxicity of S. aureus, S. epidermidis, Pseudomonas aeruginosa, Propionibacterium acnes, C. albicans, and P. orbiculare against each other were also investigated. Only P. orbiculare was inhibitory. It inhibited the growth of S. aureus, S. epidermidis, and Ps. aeruginosa - both in the dark and after irradiation. The growth inhibition was markedly enhanced after UVA irradiation, indicating phototoxicity. The phototoxic effect of P. orbiculare may play a role in the ecology of the human skin flora.

Adherence of Pityrosporum orbiculare to human stratum corneum cells.

This investigation demonstrates the capacity of Pityrosporum orbiculare to adhere to human stratum corneum cells in vitro; this may be an important initial step in its colonization of stratum corneum. Adherence was significantly higher when incubation for 120 min (mean 9.4 adherent yeasts) was compared to 60 min (mean 3.5 adherent yeasts, P less than 0.001), but not to 90 min (mean 8.6 adherent yeasts, P greater than 0.05). Adherence was higher at an incubation temperature of 37 degrees C (mean 10.0 adherent yeasts) as compared with 25 degrees C (mean 4.0, P less than 0.001), but not at 32 degrees C (mean 8.0, P greater than 0.1). There was no significant difference in adherence related to the anatomic area (forearm, back, and chest) from which the stratum corneum cells have been collected. No difference was seen in adherence between different Pityrosporum strains, but it increased significantly with inoculum size of P. orbiculare, being optimal at 10(7) cells ml-1. The adherence of P. orbiculare and Staphylococcus epidermidis to stratum corneum cells was not influenced by incubation of the organisms together or alone. This model opens possibilities to study the influence of: stratum corneum cells from diseased skin compared with controls; antibodies; and types of surface receptors and antimycotics on P. orbiculare adherence to stratum corneum cells.

Skin occlusion: effect on Pityrosporum orbiculare, skin PCO2, pH, transepidermal water loss, and water content.

The effect of 8 days skin occlusion on Pityrosporum orbiculare, bacteria, skin PCO2, pH, transepidermal water loss (TEWL), and water content (WC) was studied. P. orbiculare counts increased from a baseline of 2.1 X 10(2)/cm2 to 2.3 X 10(3)/cm2 after 3 days occlusion; bacterial counts increased from 2.9 X 10(3)/cm2 to 1.8 X 10(5)/cm2 after 8 days occlusion. pH increased during occlusion from 5.6 to a maximum at day 3 of 6.7; TEWL increased to a maximum of 11.74 g m-2 h- after 3 days occlusion compared with 4.39 g m-2 h-1 before. P. orbiculare counts, pH, and TEWL were lower at 8 days than at 3 days occlusion. WC and PCO2 remained high after 8 days; relative WC was then 60.6% compared with 52.5% before occlusion; PCO2 was 63.1 mm Hg compared with 53.1 mm Hg before occlusion. The increased levels of these factors may partially explain the higher risk of infection in occluded compared with non-occluded skin.

Tinea versicolor and Pityrosporum orbiculare: mycological investigations, experimental infections and epidemiological surveys.

In patients with tinea versicolor, Pityrosporum orbiculare was cultured from tinea versicolor lesions in 100%, from normal-looking skin in 80%, and from apparently healed lesions in 69%. P. orbiculare was isolated from normal skin in 85% of patients with seborrheic dermatitis and in 90% of volunteers. The best substrate for isolation of P. orbiculare was a peptone-glucose-yeast extract medium containing glycerol monostearate and Tween 80, overlaid with olive oil. Germ tubes were produced when P. orbiculare was incubated in an atmosphere containing air with 7% CO2. Cultures of P. orbiculare and P. ovale did not show any fluorescence in Wood's light. The in vitro activity of miconazole, clotrimazole, econazole, sodium omadine, and sodium thiosulphate against P. orbiculare was found to correlate to the good clinical effect of these drugs in tinea versicolor. In addition several substances used as solvents or in vehicles had an inhibitory activity against P. orbiculare in vitro. 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 I 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. In a retrospective study of 232 patients and prospective survey of 48 patients regarding susceptibility factors in tinea versicolor a higher (10.4%) than expected (3.8%) connection to seborrheic dermatitis was found.

Current treatment of cutaneous Pityrosporum and Candida-infections.

Pityrosporum and Candida-yeasts are opportunistic pathogens and infections require predisposing factors. These factors are also of major importance in treatment and the reason for recurrence and sometimes chronicity of the disease caused by these yeasts. Pityrosporum orbiculare and P.ovale are both lipophilic, probably identical, and both are members of the normal human cutaneous flora. In pityriasis versicolor they change from the blastospore form to the mycelial form. My favourite treatment for pityriasis versicolor is propylene glycol 50% in water applied with a gauze pad twice daily for 2 weeks. This will clear 95-100%. Other treatment modalities are: zinc pyrithione shampoo, selenium sulfide shampoo and the imidazoles. For extensive cases, patients who frequently relapse, and infections refractary to other treatments ketoconazole orally may be an effective alternative both therapeutically and prophylactically. In another disease caused by these yeasts, Pityrosporum folliculitis, both propylene glycol and ketoconazole are effective. Although Candida species are only seldom found on normal-looking skin predisposing factors are still the main reason for disease. Under the influence of these factors the organism changes from the blastospore to the mycelial form. The main predisposing factors important to control are: occlusion, underlying skin diseases, diabetes mellitus and immunodeficiency diseases. The imidazoles in a cream vehicle are very effective for many infections and applied for 2-3 weeks they will clear most lesions. The addition of a corticosteroid to the imidazole will not shorten the time of treatment but will give a more prompt symptomatic relief. In extensive cutaneous lesions and lesions refractary to other treatments ketoconazole is an effective alternative.