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Antifungal activity of ketoconazole and other azoles against Malassezia furfur in vitro and in vivo.

The in vitro activity of several antifungal agents (ketoconazole, miconazole, econazole, fenticonazole, itraconazole, fluconazole) in routine clinical use against Malassezia furfur infections has been studied with freshly isolated strains of M. furfur from pityriasis versicolor lesions. The results indicate that the drugs tested exert a good activity, and both ketoconazole and itraconazole appear very active (0.8 mg/l respectively). Hair samples from the beards of volunteer patients affected by pityriasis versicolor but otherwise healthy were examined to determine ketoconazole levels during oral therapy (one or two 200 mg tablets daily). It was shown that the drug progressively accumulates in the beard, reaching levels proportional to the dose administered, although blood levels did not increase in parallel. The study of drug concentration profile has evidenced a long ketoconazole persistence in the beard at therapeutic levels. In conclusion, the possibility of reaching high and lasting ketoconazole levels in the keratin layer of the epidermis indicates that systemic ketoconazole therapy could be useful for eradication of M. furfur in patients affected by pityriasis versicolor.

Adult↗

Oral therapy of common superficial fungal infections of the skin.

Although superficial fungal infections of the skin often respond to topical agents, systemic therapy is sometimes necessary. This article gives a review of the effectiveness of the oral antifungal agents fluconazole, itraconazole, and terbinafine in the treatment of pityriasis versicolor, tinea corporis/cruris, and tinea pedis. Four hundred milligrams fluconazole as a single dose and 200 mg itraconazole daily for 5 to 7 days were effective in the treatment of pityriasis versicolor; terbinafine taken orally appears to be ineffective in pityriasis versicolor. Tinea corporis and tinea cruris were effectively treated by 50 to 100 mg fluconazole daily or 150 mg once weekly for 2 to 3 weeks, by 100 mg itraconazole daily for 2 weeks or 200 mg daily for 7 days, and by 250 mg terbinafine daily for 1 to 2 weeks. Tinea pedis has been effectively treated with pulse doses of 150 mg fluconazole once weekly, with 100 mg itraconazole daily for 2 weeks or 400 mg daily for 1 week, and with 250 mg terbinafine daily for 2 weeks.

Administration, Oral↗

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

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

Adolescent↗

Comparison of a single 400 mg dose versus a 7-day 200 mg daily dose of itraconazole in the treatment of tinea versicolor.

BACKGROUND: Tinea (pityriasis) versicolor is a superficial infection of the stratum corneum by the lipophilic fungus known as Malassezia furfur. OBJECTIVE: To evaluate the efficacy and safety of a 400 mg single dose or 7-day 200 mg daily dose of itraconazole capsules in the treatment of mycologically confirmed pityriasis versicolor. METHODS: A total of 50 patients were entered into a randomized, open, clinical trial comparing a 400 mg single dose (n = 24 for group 1) with a 7-day 200 mg daily dose (n = 26 for group 2) of itraconazole. Clinical signs and symptoms and mycologic evaluation (potassium hydroxide preparation and Wood's lamp) were performed before treatment, and at weeks 3 and 6 after treatment. RESULTS: Both regimens of itraconazole were effective. Our results showed that there were no significant differences in efficacy and safety between the two treatment regimens (chi-square tests, p > 0.05). CONCLUSIONS: On the basis of these findings, a single dose of itraconazole 400 mg/day was as effective as the 7-day 200 mg daily dose in the treatment of pityriasis versicolor.

Adult↗

The spectrum of cutaneous lymphomas in patients less than 20 years of age.

Cutaneous lymphomas are rare in young patients and are mostly represented by mycosis fungoides and its variants and CD30+ lymphoproliferative disorders (lymphomatoid papulosis [LYP] and anaplastic large T-cell lymphoma). We report our observations in a series of 69 patients less than 20 years of age who presented either with primary cutaneous lymphoma (n = 62) or with secondary manifestations of extracutaneous disease (n = 7). Clinicopathologic features permitted classification of the cases into the following diagnostic categories: mycosis fungoides (n = 24, all primary cutaneous), anaplastic large T-cell lymphoma (n = 13, all primary cutaneous), LYP (n = 11, all primary cutaneous), subcutaneous "panniculitis-like" T-cell lymphoma (n = 1, primary cutaneous), small-medium pleomorphic T-cell lymphoma (n = 2, all primary cutaneous), natural killer (NK)/T-cell lymphoma, nasal-type (n = 1, secondary cutaneous), follicle center cell lymphoma (n = 1, primary cutaneous), marginal zone B-cell lymphoma (n = 7, all primary cutaneous), B-lymphoblastic lymphomas (n = 6, 3 primary and 3 secondary cutaneous), specific cutaneous manifestations of Hodgkin disease (n = 1, secondary cutaneous), and acute myeloid leukemia (n = 2, both secondary cutaneous). Cutaneous lymphoma in children should be differentiated from benign skin disorders that may simulate them. In particular, mycosis fungoides and LYP in this age group may present with clinicopathologic features reminiscent of inflammatory disorders such as pityriasis alba, vitiligo, pityriasis rosea, and pityriasis lichenoides et varioliformis acuta. Even in secondary cutaneous lymphomas, skin manifestations may be the first sign of the systemic disease, and a diagnosis may be achieved on examination of histopathologic specimens of a cutaneous lesion. Our study illustrates the wide spectrum of cutaneous lymphomas and leukemias in patients less than 20 years of age and underlines the need for proper interpretation of these lesions by dermatologists and dermatopathologists.

Adolescent↗

Synthesis of fluorochromes and pigments in Malassezia furfur by use of tryptophan as the single nitrogen source.

A new minimal medium consisting only of L-tryptophan (L-Trp) and a lipid source induced formation of brown pigmentation only in the species Malassezia furfur, which diffuses into the agar. Strains of the species M. sympodialis and M. pachydermatis failed to grow on this medium. On mDixon medium, however, after replacement of peptone by L-Trp, growth of all three Malassezia species was achieved. Under these conditions pigment production was observed with all M. furfur strains tested, although the results for M. pachydermatis strains were inconsistent. M. sympodialis strains showed no pigment production. On the minimal medium pigmentogenesis was induced in M. furfur by only 0.01 g% tryptophan; the pH optimum was pH 5. In all M. furfur strains, alternative amino nitrogen sources given concurrently with Trp suppressed pigmentogenesis. Furthermore, there were differences in the optimal temperature among the individual M. furfur strains. CBS 7019, CBS 6000 and CBS 6001 failed to produce pigment at 37 degrees C. The extract of the culture exhibited remarkable fluorescence, and several indole derivatives with a broad spectrum of colours were detected. This finding may have an impact on the clinical appearance of pityriasis versicolor, a very common skin disease caused by lipophilic yeasts of the genus Malassezia. We hypothesize that in pityriasis versicolor metabolic adaptation of Malassezia yeasts to altered nitrogen conditions on superficial skin might be of patho-physiological importance. Tryptophan as an inducer of pigmentogenesis probably accumulates during excessive sweating, a well-known manifestation of pityriasis versicolor.

Fluorescent Dyes↗

[Synthesis of fluorochromes and pigments in Malassezia furfur by using tryptophan as the single source of nitrogen].

A new minimal medium consisting only of L-tryptophan (L-trp) and a lipid source induced formation of brown pigmentation only in the species Malassezia furfur. Strains of the species M. sympodialis and M. pachydermatis failed to grow on this medium. Pigmentogenesis was already induced in M. furfur by 0.01 g% tryptophan, the pH optimum was pH = 5. Alternative amino nitrogen sources given concurrently with trp suppressed pigmentogenesis. The extract of the culture exhibited remarkable fluorescence, and several indole derivatives with a broad spectrum of colors were detected by means of mass spectroscopy and NMR. This finding may have an impact on the clinical appearance of pityriasis versicolor, a very common skin disease caused by lipophilic yeasts of the genus Malassezia. We hypothesize that in pityriasis versicolor metabolic adaptation of Malassezia yeasts to altered nitrogen conditions on superficial skin might be of pathophysiological importance. Tryptophan as inductor of pigmentogenesis probably cumulates during excessive sweating, a well known manifestation factor of pityriasis versicolor.

Dermatomycoses↗

[Identification of causative species in malassezia-associated dermatoses].

The Tween test was used to identify Malassezia species isolated from patients with pityriasis versicolor and seborrhoeic dermatitis, and suckling infants with seborrhoeic dermatitis. The most common species isolated from cases of pityriasis versicolor was M. globosa (55%), and this species was surmised to be the principal causative organism of this disease. In both adult and suckling infant cases of seborrhoeic dermatitis, M. globosa and M. furfur were isolated at high incidences compared with the healthy control subjects, indicating the possibility that one or both of these species are the causative organisms of these diseases. In addition, scales were collected from lesions of pityriasis versicolor for use as the template, and the involved Malassezia species were identified by the PCR method using the DNA sequences of nuclear ribosomal internal transcribed spacer l. The most commonly detected species was M. globosa, found in 97% of the cases, and this was followed in frequency by M. restricta (79%) and M. sympodialis (68%). It was also elucidated that multiple Malassezia species can be detected in the same specimen.

Adolescent↗

[Species of Malassezia associated with various dermatoses and healthy skin in the Mexican population].

At the present, eight Malassezia species have been described and their distribution in normal skin and in several skin diseases appears variable. The aim of the present study was to determine the frequency and distribution of Malassezia species in patients with psoriasis, seborrhoeic dermatitis and pityriasis versicolor attended in a Hospital from Mexico City, in addition to a healthy individual group. Scales of abnormal and healthy skin were grown in modified Dixon agar and the species identification was performed by macroscopic and microscopic features; by catalase and urease reaction; growth at 32, 37 and 40 degrees C; and Tween 20, 40, 60 and 80 assimilation. The cultures from 63 persons were included: forty six patients (20 psoriasis, 15 seborrhoeic dermatitis, 11 pityriasis versicolor) and 17 healthy individuals (external auditory canal). A total of 96 isolates were obtained. The more frequently isolated species were: M. sympodialis (38.2%) and M. furfur (26.5%) in psoriasis; M. sympodialis (38.5%) and M. slooffiae (34.6%) in seborrhoeic dermatitis; M. globosa (46.7%) and M. sympodialis (26.7%) in pityriasis versicolor; and M. restricta (47.6%) and M. globosa (23.8%) in normal skin. The number of isolates, the species diversity and association were higher in the patients group than in the healthy individuals group.

Humans↗

Malassezia yeast species isolated from patients with dermatologic lesions.

INTRODUCTION: Yeasts of the genus Malassezia form a normal component of skin flora, but are also associated with several dermatological disorders. Since 1996, the description of new species in this genus have led to new questions about their epidemiology and pathogenicity. OBJECTIVE: Herein, the frequency of Malassezia species in individuals with pityriasis versicolor, atopic dermatitis, seborrhoeic dermatitis, seborrhoeic dermatitis was compared in HIV patients and healthy individuals. Three body sites were selected for examination--head, thorax, and upper and lower extremities. MATERIAL AND METHODS: The 154 Malassezia species were isolated from 112 individuals and grouped as follows: 39 with seborrhoeic dermatitis (20 were HIV-positive patients), 18 with pityriasis versicolor, 18 with atopic dermatitis and 37 without dermatological leisions. HIV patient samples were examined microscopically, and specimens from both patients and healthy subjects were cultured on modified Dixon agar medium. Subsequently, isolates were identified by macroscopic, microscopic and physiological characteristics. RESULTS: The most commonly isolated species were Malassezia globosa (37.5%), M. sympodialis (31.3%) and M. furfur (31.3%). Malazzerzia globosa predominated in patients with pityriasis versicolor (67%) and in HIV-positive patients with seborrhoeic dermatitis (85%). In non-HIV patients with atopic dermatitis or seborrhoeic dermatitis, M. furfur and M. restricta were isolated in 72% and 26% of the cases, respectively. CONCLUSION: Several conclusions were evident. First, Malassezia species was present in subjects with and without dermatological pathologies. Second, the species frequency in the sampled population differed from frequencies reported from other geographic areas. Third, Malassezia globosa was involved at high frequency in patients with dermatological pathologies, suggesting a higher pathogenicity of this species. Additional studies on each species are recommended to clarify their pathogenic roles in association with HIV-positive and normal subjects.

Adolescent↗

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)

Dermatitis, Atopic↗

Koebnerization as a cutaneous manifestation of immune complex-mediated vasculitis.

Two unusual examples of the cutaneous manifestations of vasculitis are presented. In both cases lesions occurred on previously traumatized skin and on normal skin of the dependent areas. Lesional skin biopsy specimens obtained from the koebnerized sites and from the other dependent sites revealed evidence of vascular injury in both patients. A diagnosis of leukocytoclastic vasculitis was made in one patient and pityriasis lichenoides et varioliformis acuta in the other. Direct immunofluorescence microscopy of lesional skin specimens from both patients demonstrated dermal vascular immune deposits. Raji cell assay detected a significant elevation of circulating immune complexes in the serum of both patients. Neither koebnerizing leukocytoclastic vasculitis nor koebnerizing pityriasis lichenoides et varioliformis acuta has been reported previously.

Adult↗

Febrile ulceronecrotic Mucha-Habermann disease with clonality: a cutaneous T-cell lymphoma entity?

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a severe variant of pityriasis lichenoides et varioliformis acuta (PLEVA). PLEVA patients only very rarely have systemic signs; the cutaneous lesions are usually asymptomatic, but may be pruritic and may heal with scarring. FUMHD often starts out as classic PLEVA, but goes on to develop widespread ulceronecrotic lesions and is associated with a high mortality rate. Whether Pityriasis lichenoides chronica (PLC) and PLEVA form a spectrum rather than single entities of clonal lymphoproliferative diseases has been discussed. Recently, it has been proposed that FUMHD, too, is a clonal lymphoproliferative disorder. Here, we report two cases of FUMHD with monoclonal T-cell population, as detected by Southern blot analysis. We propose that clonal FUMHD represents a cutaneous T-cell lymphoma entity.

Adult↗

Disorders of hypopigmentation in children.

The most common disorders of hypopigmentation in children are pityriasis alba, vitiligo, nevus depigmentosus, and tinea versicolor. Pityriasis alba usually presents as ill defined, scaly patches of hypomelanosis on the cheeks of children with an atopic diathesis. The face is also a favored site for vitiligo, but the distribution is periorificial, and the pigment loss is complete because of a destruction of melanocytes. Vitiligo is an acquired, progressive disorder in contrast to nevus depigmentosus, which is a stable, congenital leukoderma. The localized form of nevus depigmentosus must be distinguished from an ash leaf spot, the earliest cutaneous manifestation of tuberous sclerosis, whereas the systematized form may be confused with hypomelanosis of Ito, another neurocutaneous disorder. The lesions of tinea versicolor favor the upper trunk of adolescents, and potassium hydroxide examination of the associated scale reveals hyphal and yeast forms of P. orbiculare. Any inflammatory process in the skin such as dermatitis or psoriasis can resolve with areas of hypopigmentation.

Adolescent↗

The prevalence of skin conditions in Romanian school children.

Virtually nothing is known about the prevalence of skin conditions in children in the general population. Although we know something about the relative frequency of skin conditions seen by dermatologists, we do not know how such referrals are influenced by factors such as social class, accessibility to medical services or educational and cultural background. In order to estimate the burden and relative frequency of dermatological disease in children in the community, we measured the point prevalence of skin conditions in 1114 Romanian schoolchildren aged 6-12 years, using the British Association of Dermatologists diagnostic index. The overall point prevalence of children with one or more skin diseases was 22.8%, with no significant differences according to age group or sex, except for pityriasis alba which showed a male predominance (P = 0. 007). The most common diseases were infectious dermatoses such as viral warts and insect bites (6.3%), dermatitis/eczema (5.1%), pityriasis alba (5.1%), keratosis pilaris (4.0%) and urticaria (1. 9%). Together, these five groups accounted for more than 84% of the cases. Of the 1114 children, 213 (19.1%) had only one skin disease and 41 (3.7%) had two skin diseases. While acknowledging the limitations in defining which skin conditions can benefit from medical care, this study suggests that skin disorders are common in Romanian schoolchildren, affecting about one-quarter of 6-12 year olds. Such a point prevalence is likely to be conservative because of the tendency of prevalence estimates to exclude many other dermatoses of short duration. The finding that over 80% of the disorders can be grouped into fewer than six categories is important in informing training programmes and delivery of service for primary health care teams. This study provides a baseline for further studies into the morbidity and use of health care services by children with skin disease in the community.

Age Distribution↗

Phototherapy in pediatric patients.

The treatment of children with psoriasis, atopic dermatitis (AD), pityriasis lichenoides, and scleroderma poses a therapeutic problem because all therapeutic options are associated with numerous side effects. Therefore ultraviolet A and B (UVA and UVB) phototherapy is presented as a possible alternative to some of these therapies, primarily topical and systemic corticosteroids, in children. Our results in treating children with phototherapy and psoralen plus UVA (PUVA) bath phototherapy over the past 5 years are reported. UVB therapy (TL01) was used in 20 psoriatic children (6 boys, 14 girls; ages 6-14 years) during the stage of disease exacerbation and in 9 children (3 boys, 6 girls; ages 8-16 years) with pityriasis lichenoides. Combined UVA/UVB phototherapy was applied in 21 AD children (7 boys, 14 girls; ages 4-15 years). Photochemotherapy with local application of a PUVA bath was used in six children (2 boys, 4 girls; ages 9-16 years) with circumscribed scleroderma and in one girl with systemic scleroderma. All children received short courses of phototherapy with either no maintenance or short maintenance. All three therapeutic protocols resulted in a certain degree of improvement in most of the study patients. None of the patients exhibited any early phototherapy side effects. We conclude that phototherapy and PUVA bath are valuable and safe therapeutic options for selected children who do not respond to other treatments.

Adolescent↗

An unusual presentation of dermatomyositis: the type Wong variant revisited.

We describe a 53-year-old white woman with dermatomyositis (DM) who had additional clinical findings of pityriasis rubra pilaris (type Wong dermatomyositis) with histopathologic features of both pityriasis rubra pilaris (PRP) and porokeratosis. Type Wong dermatomyositis was originally described in 11 patients by Wong in 1969 and has been reported in 5 additional patients. This is a rarely described phenomenon in which patients with DM develop cutaneous hyperkeratotic lesions that resemble PRP and histologically show follicular hyperkeratosis and hair follicle destruction. Arrector pilorum muscles also show degenerative findings and myositis. We believe that this is the first reported case of a patient with type Wong DM who also has clinical and histologic features suggestive of porokeratosis. This is important because of the association of adult-onset dermatomyositis with internal malignancy and the well-documented association of porokeratosis with immunosuppression. These clinical and histologic findings serve as markers for malignancy in patients with DM. These patients warrant a complete review of systems and investigation for age-appropriate neoplasms as well as close long-term follow-up by dermatologists to ensure that these cutaneous eruptions are not overlooked.

Dermatomyositis↗

Hair casts.

The literature on hair casts suggests they are rare even though Kligman intimated in 1957 that in some scalp diseases they might well be common. In this study, casts have been looked for in a group of orthokeratotic and parakeratotic scalp conditions. Hair casts are indeed common in psoriasis, pityriasis amiantacea, pityriasis capitis and seborrhoeic dermatitis. No casts were seen in women with traction hair styles or in those regularly using hair sprays.

Dermatitis, Seborrheic↗