Treatment of distal subungual onychomycosis with a topical preparation of urea, propylene glycol and lactic acid: results of a 24-week, double-blind, placebo-controlled study.

Onychomycosis is difficult to cure as this requires eradication of the primary infection and protection of new areas of growth from reinfection. A new topical treatment (K101) has been developed. The aim of this study was to assess the efficacy, safety and tolerability of K101 treatment of distal subungual onychomycosis. This was a 24-week (plus 2-week washout), multicentre, randomised, double-blind, placebo-controlled study in 493 patients with distal subungual onychomycosis (K101, n = 346; placebo, n = 147), stratified according to degree of nail involvement. More patients with ≤50% nail involvement achieved the primary endpoint (mycological cure after 26 weeks) in the K101 group (27.2%) than placebo (10.4%; P = 0.0012). Proportions for patients with 51-75% involvement were 19.1% for K101 and 7.0% for placebo (not significant). More patients applying K101 than placebo judged that their condition had improved from week 2 (P = 0.0148) to week 24 (P = 0.0004). No safety issues were identified. K101 provides early visible improvements in nail appearance and a clinically meaningful antifungal activity.

The clinical significance of cutaneous reactions to trichophytin in dermatophytosis.

An intracutaneous test was performed in 114 patients with dermatophytosis verified by culture and in 32 control subjects, unsing purified trichophytin (according to the ethylene glycol method) and commercially available trichophytin. Immediate reactions occurred with both trichophytin antigens at a similar frequency in 12-14% of cases. Delayed reactions occurred significantly more often to the purified trichophytin in patients with dermatophytosis (36%) but in none of the controls. Immediate reactions to purified trichophytin occurred in 26% of the chronically infected patients. Delayed reactions were correlated to patients with tinea cruris (50% positive reactions), to infections with Epidermophyton floccosum (50%) and to patients not chronically infected. Thus, chronic dermatophytosis was characterized by immediate reactions to purified trichophytin and few delayed reactions. In contrast, patients not chronically infected were characterized by delayed reactions and few immediate reactions.

Cell-mediated reactivity in dermatophytosis: differences in skin responses to purified trichophytin in tinea pedis and tinea cruris.

Cell-mediated immune responses were measured in 91 patients with dermatophytosis by means of delayed-type skin hypersensitivity to a purified trichophytin preparation (ethylene glycol method) and to tuberculin (purified protein derivative, PPD). The findings indicate that dermatophytes differ in their sensitizing capacity as measured by trichophytin skin sensitivity. Trichophyton mentagrophytes appeared to be a potent sensitizer compared with Trichophyton rubrum (p < 0.01), whereas Epidermophyton floccosum appeared as a moderate sensitizer. The localization of infection also affected the cell-mediated response to trichophytin, i.e. the frequency of reactions was 44% in tinea cruris and 33% in tinea pedis, while tinea pedis with nail infections elicited delayed-type reactivity in 60% of cases. On the basis of the significant difference (p < 0.001) in cell-mediated reactivity between chronically and non-chronically infected subjects as measured with trichophytin, it is concluded that the cell-mediated response is of importance for the development of host resistance to dermatophytic infections. This study provides further evidenced in support of the view that a partial defect in the cell-mediated system may be responsible for establishment of chronic dermatophytosis.

Ultrastructural studies on experimental hair infections in vitro caused by Trichophyton mentagrophytes and Trichophyton rubrum.

Experimental infections with Trichophyton mentagrophytes and Trichophyton rubrum were performed on human hair in vitro and studied by conventional light microscopy, scanning (SEM) and transmission (TEM) electron microscopy. The penetrations visible by light microscopy in hair infected with T. mentagrophytes appeared at SEM as disrupted surface areas with perforating holes. T. rubrum-infected hair displayed minute perforations and less conspicuous cuticular damages seen at SEM and TEM. In both organisms multiple tiny perforating holes were observed at SEM previously unnoticed in experimental hair infections. From a morphological point of view the differences between the fungi investigated in this experimental system seem to be more of a quantitative nature than involving different mechanisms of action.

Brittle hair in osteogenesis imperfecta: transmission and scanning electron microscopy and mycologic assay.

The brittle hair fibres from a case of osteogenesis imperfecta were studied by scanning and transmission electron microscopy. Normal hair fibres are extremely difficult to infect with T. mentagrophytes. As a tentative assay for biochemical defects of hair fibres, experimental dermatophytic infection of the hair with T. mentagrophytes was performed. The massive growth induced suggested that the experimental fungal infection may indeed indicate a biochemical defect in the hairs from our case of osteogenesis imperfecta.

The changing clinical picture of Microsporum canis infections in Sweden.

All 22 cases of infections with Microsporum canis verified by culture during a five-year period were surveyed. Only tinea corporis was found. The clinical picture was varied and in more than half of the cases the preliminary diagnosis was other than tinea. The classical tinea capitis was not found in any case. Direct KOH-mounts showed poor correlation to the cultural findings (positive in 33%). It is concluded that mycological screening of certain dermatological disorders should be performed by culturing.

Cell mediated cross-reactivity in vivo and in vitro to purified dermatophyte antigen preparations in sensitized guinea pigs.

Guinea pigs were sensitized to either Trichophyton rubrum, Trichophyton mentagrophytes, or Epidermophyton floccosum. Cross-reactivity experiments were performed in vivo and in vitro with purified antigen preparations prepared from the respective dermatophyte according to the ethylene glycol method. All sensitized animals responded with delayed-type skin reactions to all three antigen preparations, although the strongest reactivity observed was to the homologous antigen. Spleen and blood lymphocytes from many (but not all) animals were stimulated by these antigens and the response to the homologous antigen was always more pronounced. The findings indicate the presence of a common group-specific dermatophyte antigen as well as the possibility of species-specific antigens in the experimental system studied.

T-lymphocyte subpopulations in patients with chronic dermatophytosis.

T lymphocytes with Fc receptors for IgM (Tm cells) or IgG (Tg cells), known under certain conditions to exert help or suppression, and T-helper and T-suppressor cells, defined by fluorescein-isothiocyanate-conjugated monoclonal antibodies, were determined in 7 patients with chronic dermatophytosis. There appeared to be a relation between severity of the disease and decreased proportion of Tm cells with concomitant increase of Tg cells. However, only in 1 severe case there was also a shift of T-helper and T-suppressor cells as defined by monoclonal antibodies.

Dermatophytid--a misdiagnosed entity?

A mycological and immunological survey was performed in 26 patients with clinical signs of dermatophytid. Only 10 patients fulfilled the main criteria of dermatophytid reactions, i.e. positive delayed skin test to trichophytin and dermatophyte isolated by culture. Trichophyton mentagrophytes--especially the zoophilic variant--was found in 9 patients of 10. In the majority of cases, inflammatory tinea pedis caused the dermatophytid reaction which appeared as vesicles localized to the palms. Relying on clinical appearance only implies an obvious risk of erroneously including pyoderma and various eczemas, e.g. pompholyx and contact dermatitis, as dermatophytids. Mycological culture and skin test with a reliable trichophytin antigen preparation ought to be applied in order to avoid misdiagnosis.

Human epidermal Langerhans cells induce cellular immune response to trichophytin in dermatophytosis.

Human epidermal cell suspensions were prepared from patients sensitized to trichophytin. The cells were 75% to 95% viable, and contained 2% to 6% Langerhans cells as judged by immunofluorescence staining with an anti-DR antiserum. T lymphocytes from the same patients were co-cultured with trichophytin, with or without epidermal cells or macrophages. Proliferative T-cell response to trichophytin was obtained in cultures containing epidermal cells or macrophages. Pretreatment of the epidermal cells with anti-DR antiserum abolished the response, but normal rabbit serum did not, indicating that HLA-DR positive Langerhans cells are able to induce the cellular immune response to trichophytin. These data indicate that Langerhans cells play an important role in dermatophytosis.

Juvenile pemphigus vulgaris.

Pemphigus vulgaris is extremely rare in childhood. Only 35 cases of juvenile pemphigus vulgaris have been reported in the literature up until to now. During the pre-steroid era, the outcome of the disease was usually regarded as fatal. Today, the prognosis has improved because of the possibility of early diagnosis by immunofluorescent techniques, determination of antibodies against epidermal intercellular substance and early therapy with systemic steroids. A case of juvenile pemphigus vulgaris with a favourable outcome in a 13-year old girl is described.

In vivo and in vitro immune responses to trichophytin in dermatophytosis.

Cell-mediated immunity in patients with verified dermatophytosis was investigated by means of skin test and lymphocyte stimulation test (LST) using purified trichophytin, prepared by the ethylene glycol method, and commercially available trichophytin. The purified trichophytin seemed to be more specific and sensitive both in skin test and in LST. In the majority of cases skin-positive patients were also positive in LST, especially when T. mentagrophytes or E. floccosum was the causative organism. Patients with non-chronic infections also showed a close correlation between skin reactivity and LST. Patients with chronic mycosis or infected with T. rubrum, on the other hand, were often skin-negative. Their lymphocyte reactivity in vitro, however, was usually positive, thus showing a discrepancy in the ability of these two methods to measure cell-mediated immunity.

Multiple basal cell carcinoma. A clinical evaluation of risk factors.

Basal cell carcinoma (BCC) is the most common malignant skin tumour. There is evidence that the number of patients who develop more than one basal cell carcinoma (mBCC) is increasing. The aim of this study was to elucidate possible risk factors for developing mBCC. Among twelve risk factors considered, skin tumour among relatives was the strongest, with an odds ratio of 10.9 (p < 0.001). The second strongest risk factor was sunburn after the age of 60, odds ratio 4.4 (p < 0.001). The results suggest that the presence of skin tumour in the family and sunburn after age 60 are independent factors associated with mBCC. To our knowledge this has not previously been reported.

Leukoderma syphiliticum: ultrastructural observations on melanocyte function.

A case of genital leukoderma syphiliticum was analysed submicroscopically. No treponema pallidum organisms could be detected intra- or extracellularly in the epidermis or in the dermis. The melanocytes were only slightly reduced in number and had mostly normal outlines. The melanogenesis was impaired and small melanosomes with decreased deposition of melanin were mostly produced at the expense of normal melanin granules. A partial block in the melanin transfer mechanism seems to be in evidence. As no direct destructive action of spirochetes on the melanocytes is observed, an indirect effect is assumed, e.g. by a tyrosinase inhibitor.

An immunohistochemical staining of epidermal Langerhans' cells in tinea cruris.

Epidermal Langerhans' cells (LC) were investigated in fresh cryostat sections of ten biopsies from patients with mycologically proven tinea cruris, using OKT6 monoclonal antibodies and avidin-biotin-immunoperoxidase. Compared to the controls, more epidermal LC and an increased number of LC in the upper half of the epidermis were found in the sections from tinea patients. In a double staining method for both OKT6-positivity and hyphae, a tendency towards a gathering of LC and fungal elements was found. The results of this study are in agreement with the theory that epidermal LC are responsible for the antigen uptake in dermatophytosis.