Jan Faergemann

Immune reactions to Pityrosporum ovale in adult patients with atopic and seborrheic dermatitis

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.

Atopic Dermatitis and Fungi

SUMMARY Atopic dermatitis (AD) is a chronic, itching, inflammatory skin disease which is associated with asthma and/or hay fever and a familial occurrence of these conditions. Genetic factors are important in the development of AD, but the exact hereditary pathway is still unknown. Dry skin and the weakened barrier function in patients with AD is very important for the patients reactions to irritants and other external trigger factors including microorganisms. The standard treatments are topical corticosteroids, topical immunomodulating agents, and emollients. If AD cannot be controlled by this type of treatment, systemic immunomodulating agents may be used. UVB, UVA, or psoralen-UVA may also be used for widespread severe lesions. However, some patients do not respond to these standard treatment, and then it is important to consider the role of microorganisms, house dust mites or food. The role of the Malassezia yeasts in AD, especially AD located to the head and neck region, is now documented in several papers. There are also several papers indicating the role of Candida as an aggravating factor in AD. Patients with AD also develop chronic dermatophyte infections more easily, and patients with AD and chronic dermatophyte infections may show improvement in their AD when treated with antifungal drugs.

Pityrosporum folliculitis: A common disease of the young and middle-aged

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.

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.

Seborrhoeic dermatitis and Pityrosporum orbiculare: treatment of seborrhoeic dermatitis of the scalp with miconazole-hydrocortisone (Daktacort), miconazole and hydrocortisone.

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 < 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 <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.

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 µg/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 ≤ 0·03 to 0·125 μg/mL. The recently introduced antifungal, voriconazole, was also very effective, with MIC80 values ≤ 0·03 μg/mL for 80% of strains. MICs of terbinafine against the seven Malassezia species ranged from ≤ 0·03 to 64·0 μg/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.

The prevalence of Malassezia yeasts in patients with atopic dermatitis, seborrhoeic dermatitis and healthy controls

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<0.01). In the patients with atopic dermatitis, fewer positive cultures were found in lesional (28%) than in non-lesional skin (44%, p<0.05), while positive cultures were found in 75% of both lesional and non-lesional skin of patients with seborrhoeic dermatitis (not significant). M. sympodialis dominated in patients with atopic dermatitis (46%) and in healthy controls (69%). In patients with seborrhoeic dermatitis both M. sympodialis and M. obtusa were cultured in 43%. A Malassezia species extract mixture would increase the possibility of detecting IgE sensitization to Malassezia in patients with atopic dermatitis.

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

Summary Background The yeast Malassezia is considered to be one of the factors that can contribute to atopic dermatitis (AD).

Levels of terbinafine in plasma, stratum corneum, dermis–epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once daily for 7 and 14 days

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 μg/g) and stratum corneum (2.5 μg/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 μg/g 1 day after stopping medication; it was still 0.2 μg/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 μg/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.

Double-blind, parallel-group comparison of terbinafine and griseofulvin in the treatment of toenail onychomycosis

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.