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Biomedical subjects

J Faergemann

Publications and source records attributed to J Faergemann.

At least 19 recordsLinked to original sources

Genetic predisposition--understanding underlying mechanisms of onychomycosis.

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.

Antifungal Agents↗

Clinical trial design--towards better practices.

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.

Administration, Oral↗

Prognosis and prognostic factors in adult patients with atopic dermatitis: a long-term follow-up questionnaire study.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing skin disease. Several investigations concerning the long-term prognosis of AD among children and teenagers have been performed but there are only few data among adults. OBJECTIVES: To investigate the prognosis and prognostic factors in adult patients with AD by a long-term follow-up (25-38 years). The prognostic factors were defined as those factors of importance for the persistence of AD. PATIENTS AND METHODS: A follow-up questionnaire was sent in November/December 1998 to 922 AD patients examined in our outpatient clinic between 1960 and 1973 among 1366 registered patients with AD. The patients were aged 20 years or older when they visited the clinic and 45 years or older when they answered the follow-up questionnaire. RESULTS: The response rate was 90.4%. The age range at the time of follow-up was 45-86 years (mean 55 years). Of the 833 patients who responded, 59% reported AD at some time during the last 12 months, which we defined as persistent AD. The mean value of clearance rate per person-years was 18%. One of the most important factors associated with persistence of AD was a head and neck dermatitis with or without other AD locations at the time of examination according to the old patient records. CONCLUSIONS: This study showed that the majority of adults with AD still had AD when they became older. This applies particularly if negative prognostic factors existed.

Adult↗

Pedal dermatophyte infection in psoriasis.

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.

Adolescent↗

Epidemiology, clinical presentation and diagnosis of onychomycosis.

Onychomycosis is a common nail disease, responsible for up to 50% of diseases of the nail. The distribution of different pathogens is not uniform; it depends on various factors such as climate, geography and migration. However, studies have revealed that two dermatophytes, Trichophyton rubrum and Trichophyton mentagrophytes, account for more than 90% of onychomycoses. Onychomycosis can be divided into four major clinical presentations: distal subungal (the most common form of the disease), proximal subungal (the most common form found in patients with human immunodeficiency virus infection), and superficial and total dystrophic onychomycosis. Onychomycosis is a multifactorial disease. Age has a very important effect on the occurrence of onychomycosis, with a correlation between increasing age and infection. Genetics has also been identified as a factor governing the epidemiology of onychomycosis; T. rubrum infection shows a familial pattern of autosomal dominant inheritance. Disease and lifestyle may also play a role in the epidemiology of fungal nail infections. Studies have shown that diabetes, acquired immunodeficiency syndrome and peripheral arterial disease may be independent predictors of onychomycosis. Because of the multifactorial nature of the epidemiology, accurate diagnosis, pertinent treatment and patient education must be paramount when treating the disease.

Adolescent↗

Atopy patch test reactions to Malassezia allergens differentiate subgroups of atopic dermatitis patients.

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.

Adolescent↗

Seborrhoeic dermatitis and Pityrosporum (Malassezia) folliculitis: characterization of inflammatory cells and mediators in the skin by immunohistochemistry.

BACKGROUND: The fact that Pityrosporum ovale plays a part in seborrhoeic dermatitis is well established but the mechanism of this relationship has not been established. OBJECTIVES: To compare the number and type of inflammatory cells and mediators in skin biopsies from normal and lesional skin from the trunk and scalp in patients with seborrhoeic dermatitis, Pityrosporum (Malassezia) folliculitis and in normal skin from healthy controls. METHODS: The skin biopsies were stained using the labelled Streptavidin-biotin METHOD: The following markers were studied: CD4, CD8, CD68, HLA-DR, NK1, CD16, C1q, C3c, IgG, CD54 (ICAM-1), interleukin (IL) -1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, IL-12, tumour necrosis factor-alpha and interferon-gamma. RESULTS: HLA-DR+ cells were seen in the highest number, and were higher in lesional skin compared with normal skin from both patients and healthy volunteers. ICAM-1 expression was also increased in lesional skin. C1q and the interleukins showed an increased cellular and intercellular staining in patients compared with healthy controls and the intercellular staining was often more intense in lesions compared with non-lesional skin. Staining was often more intense when Malassezia (Pityrosporum ovale) yeast cells were present. CONCLUSIONS: An increase in NK1+ and CD16+ cells in combination with complement activation indicates that an irritant non-immunogenic stimulation of the immune system is important. The result with the interleukins showed both an increase in the production of inflammatory interleukins as well as in the regulatory interleukins for both TH1 and TH2 cells. Similarities to the immune response described for Candida albicans infections indicate the role of Malassezia in the skin response in seborrhoeic dermatitis and Pityrosporum folliculitis.

Adult↗

Epidemiology of Malassezia yeasts associated with pityriasis versicolor in Ontario, Canada.

The genus Malassezia was recently revised to include seven species, but the clinical significance of each of these species is not clearly understood. To obtain a better understanding of the contribution of individual Malassezia species to the epidemiology of pityriasis (tinea) versicolor, we used Leeming-Notman medium to culture patient skin specimens showing positive evidence of Malassezia infection in direct microscopy. Isolates were identified on the basis of recently published morphological and physiological tests for distinction of the new species. Identification using recently developed molecular criteria was also carried out for the ambiguous cases. Malassezia species were cultured from 111 cases of pityriasis versicolor in the Canadian province of Ontario. The most frequently isolated species were Malassezia sympodialis, M. globosa and M. furfur which respectively made up 59.4%, 25.2% and 10.8% of the isolated etiological agents. M. globosa was commonly isolated from a small number of pityriasis versicolor specimens obtained from investigators outside Canada. A large number of additional Ontario specimens with positive direct microscopy failed to yield a culture; however, it is suggested that this is consistent with the standard sampling practice of scraping the older portions of pityriasis lesions rather than the margins, where viable fungal cells are most likely to occur.

Canada↗

Quantitative culture of Malassezia species from different body sites of individuals with or without dermatoses.

Quantitative cultures were obtained using contact plates to determine whether the quantity and composition of Malassezia species at a given anatomic site in normal individuals differs from that of patients with various cutaneous dermatoses. The sample included 20 clinically healthy individuals (without any dermatosis) and 110 patients with dermatoses (including 31 with atopic dermatitis [AD], 28 with psoriasis [PS], 28 with seborrheic dermatitis [SD] and 23 with pityriasis versicolor [PV]). Contact plates filled with special culture medium were used to obtain a quantitative culture from five body sites (scalp, forehead, arm, trunk and leg) of every individual. The number of cfu were recorded for every plate that grew Malassezia yeasts, and 3-5 colonies were isolated for identification to species level using microscopic, physiological and molecular characteristics. The mean cfu counts observed among patients with AD, PS and SD was significantly lower than normal control subjects (P < 0.05). The mean cfu counts from PV patients was not different from that of healthy control subjects. Overall, for all conditions considered together, the mean cfu counts in lesional sites were significantly lower than in non-lesional sites (P <0.05). Furthermore, the mean cfu counts from lesional sites in patients with AD and PS were significantly lower than the corresponding value in patients with PV (P <0.05). Six Malassezia species were recovered from the different dermatoses. Malassezia sympodialis was the most common species associated with AD and PV patients and healthy control subjects, while M. globosa was most frequently isolated from PS and SD patients. More than one Malassezia species was recovered at any given anatomic site from both controls as well as individuals with dermatoses. M. globosa was equally likely to be recovered from scalp, forehead and trunk, but less likely to derive from arms and legs. M. restricta and M. slooffiae were recovered more frequently from the upper body (scalp and forehead) than from the lower body. Among normal individuals and for patients with AD and PV, M. sympodialis was significantly more likely to affect the forehead than the legs.

Adult↗

In vitro susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine.

Fifty-five strains, either authentic or ex-type, of seven Malassezia species were investigated for in vitro susceptibility to various concentrations (0.03-64.0 microg/mL) of three azole drugs, ketoconazole, voriconazole and itraconazole, as well as the allylamine terbinafine, using the agar dilution method. All strains of the seven Malassezia species were susceptible to the three azole drugs at low concentrations. M. furfur, M. sympodialis, M. slooffiae, M. pachydermatis, M. globosa, M. obtusa and M. restricta were most sensitive to ketoconazole and itraconazole, with minimum inhibitory concentrations (MICs) ranging from < or = 0.03 to 0.125 microg/mL. The recently introduced antifungal, voriconazole, was also very effective, with MIC80 values < or = 0.03 microg/mL for 80% of strains. MICs of terbinafine against the seven Malassezia species ranged from </= 0.03 to 64.0 microg/mL. There were variations in susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine. Strains of M. furfur, M. globosa and M. obtusa were more tolerant to terbinafine than the remaining Malassezia species; M. sympodialis was highly susceptible. M. furfur strains tested with terbinafine ranged from highly susceptible to relatively resistant. Correct identification of Malassezia species could facilitate selection of appropriate antifungal therapy.

Allylamine↗

An open study of efficacy and safety of long-term treatment with mometasone furoate fatty cream in the treatment of adult patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis is a severe chronic skin disease often deteriorated by the presence of microorganisms and often responds well to treatment with potent corticosteroids. However, the long-term use of potent topical corticosteroids are accompanied by side-effects such as skin atrophy. OBJECTIVE: To study the effect and safety of prophylactic treatment with mometasone furoate fatty cream (contains hexylene glycol) for 6 months in patients with atopic dermatitis. RESULTS: Sixty-one of 68 (90%) patients were still free of their disease after 6 months of twice weekly treatment and only one showed possible treatment related signs of skin atrophy. The number of Staphylococcus aureus and Pityrosporum ovale were significantly reduced in cleared patients. CONCLUSIONS: Mometasone furoate fatty cream is effective and safe both for treatment and as a prophylaxis in patients with atopic dermatitis.

Administration, Topical↗

Pharmacokinetics of fluconazole in skin and nails.

Two studies on the pharmacokinetics of fluconazole in skin and nails are reported here. In 1 study, 12 healthy volunteers received fluconazole 50 mg once daily for 12 days and 11 healthy volunteers received fluconazole 150 mg once weekly for 2 weeks. Fluconazole assays were performed on samples of serum, stratum corneum, dermis-epidermis, and eccrine sweat. In a second study, 36 patients with toenail onychomycosis received either fluconazole 150 mg once weekly or griseofulvin 1000 mg once daily for 12 months. Fluconazole assays were performed on nail clippings and serum samples from the patients receiving fluconazole. Tissue concentrations of fluconazole regularly exceeded plasma concentrations in these studies. In the skin study, the highest concentrations were achieved in stratum corneum, with accumulation occurring up to the end of dosing. Subjects who received 50 mg once daily had higher levels of fluconazole in stratum corneum, sweat, and epidermis-dermis than those subjects who received 150 mg once weekly. In the toenail study, fluconazole concentrations increased for the first 6 months, reaching levels much higher than serum concentrations (P < .001), with no significant difference between healthy and diseased nails.

Administration, Oral↗

Cell-mediated immunity to Malassezia furfur in patients with seborrhoeic dermatitis and pityriasis versicolor.

The lymphocyte transformation response to Malassezia furfur, Candida albicans, phytohaemagglutinin, concanavlin A and tuberculin purified protein derivative of 12 patients with pityriasis versicolor, 15 patients with seborrhoeic dermatitis and matched controls, was studied. Patients with pityriasis versicolor showed a significantly lower response to M. furfur than patients with seborrhoeic dermatitis and controls.

Adult↗

The role of Malassezia species in the ecology of human skin and as pathogens.

The new taxonomic structure of the lipophilic genus Malassezia was presented with key characteristics for the seven described species. Among techniques used for epidemiological surveys, the pulsed field gel electrophoresis (PFGE) was found to be of little value in contrast to randomly amplified polymorphic DNA (RAPD). Immunological studies still yielded conflicting results but at least the immunomodulatory capacity of Malassezia yeasts appeared to be related to the cell wall lipids. A review of Malassezia infections together with the present consensus for their prevention and treatment was also made.

Antibodies, Fungal↗

Quantitative cultures of Candida from mouthwash fluid in HIV-infected patients: a longitudinal study.

The density of Candida colonization in mouthwash fluid of 59 HIV-seropositive patients and 21 controls was determined. No significant difference in colony-forming units was found. No correlation was found between the colonizing density of Candida albicans and the CD4 count among the patients. Twenty-seven of the HIV-seropositive patients were followed for almost 3 years. No difference was found between the number of Candida albicans colony-forming units at the first and second time of sampling. Vaccination with HIV IIIB GP 160 vaccine did not have any influence on the prevalence of Candida albicans.

Adolescent↗

Pityrosporum yeasts--what's new?

The lipophilic yeast Pityrosporum ovale is a member of the normal human cutaneous flora in adults but also associated with several skin diseases. In pityriasis versicolor, under the influence of predisposing factors, P. ovale changes from the round blastospore form to the mycelial form. A great problem in pityriasis versicolor is the high rate of 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. In direct microscopy clusters of round budding yeast cells are found. The disease responds rapidly to antimycotic therapy. 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 paralleled by a reduction in number of organisms. Severe seborrhoeic dermatitis often difficult to treat is associated with AIDS. In peripheral blood from a high number of patients with seborrhoeic dermatitis we found an increase in number of natural killer T-cells and decreased PHA and Con-A stimulation. Secondary we found low serum IgG antibody titres in patients compared to controls. Other studies have found a reduced lymphocyte stimulation reaction when lymphocytes from patients with seborrhoeic dermatitis were stimulated with a P. ovale extract. Additionally, IL-2 and IFN gamma production by lymphocytes from patients was markedly depressed and IL-10 synthesis were increased after stimulation with P. ovale extract. The majority of adult patients with atopic dermatitis localized to the head, neck and scalp are prick-test positive to a protein P. ovale extract. One study showed that p. ovale extracts increased IL-4, IL-10 and IgE synthesis in patients with atopic dermatitis. There are also treatment studies indicating that antifungal treatment may be beneficial in these patients.

AIDS-Related Opportunistic Infections↗