Itraconazole is a broad spectrum triazole antifungal agent. It has favourable pharmacodynamic and pharmacokinetic profiles and is available as both oral and i.v. formulations. Over the last two decades, clinical and animal infection studies have demonstrated the efficacy of itraconazole in a wide range of superficial fungal infections including difficult-to-treat dermatophytoses and onychomycoses. Furthermore, shortened treatment regimens have proven to be effective, ranging from 1-day treatment for vaginal candidosis to 1-week pulse therapy per month, for 2-4 months, in onychomycosis and follicular dermatophytosis. Clinical experience with itraconazole in the treatment of deep mycoses is less comprehensive. However, results in systemic candidosis, sporotrichosis, blastomycosis, paracoccidioiodomycosis, certain types of histoplasmosis and aspergillosis are extremely encouraging. Itraconazole is less effective in the treatment of chromomycosis and coccidioidomycosis. Nevertheless, considering the refractory nature of these diseases, itraconazole has proven to be a valuable addition to the antifungal drugs currently available for treatment. Itraconazole has been well-tolerated with doses of up to 400 mg/day being generally free of serious adverse effects. However, a potential for drug interactions exists, mediated through the cytochrome P450 enzyme 3A4 system, which should be considered when itraconazole is used as part of a multi-drug regimen.
Skin capacitance imaging is a non-invasive, non-optical method that distinguishes three contrasting levels of stratum corneum hydration in psoriatic lesions. The lowest capacitance level probably corresponded to xerotic orthokeratosis. The medium capacitance level presumably identified foci of parakeratosis and clumps of neutrophils. The highest capacitance level suggested exsudation at the site of prominent vessel dilation and dermal inflammation. Impaired sweating in the psoriatic lesions may potentially interfere with body thermoregulation.
Restrictive dermopathy is a rare, lethal autosomal recessive syndrome. We report on 3 unrelated affected stillborn infants of consanguineous parents. Clinical findings include a tight, thin, translucent, taut skin, which tears spontaneously in flexion creases, arthrogryposis multiplex congenita (including the temporomandibular joint), enlarged fontanelles, typical face and dysplasia of clavicles and long bones. Histologic abnormalities include hyperplastic, abnormally keratinized epidermis, reduced tonofilaments, thin, compact dermis with hypoplasia of the elastic fibres, and abnormal subcutaneous fat. Fifteen previous cases are reviewed.
Factor XIIIa-positive dendrocytes present at the periphery and inside epithelial neoplasms are an heterogeneous group of cells. They are subsets of mesenchymal cells, cancer-associated macrophages and antigen-presenting cells. Factor XIIIa, other tissue transglutaminases, alpha 2-macroglobulin and tumour necrosis factor-alpha represent a complex network of mediators influencing tumour progression in the skin. In the present study we searched for the presence of dendrocytes and alpha 2-macroglobulin deposits inside and in the vicinity of cutaneous carcinomas (90 basal cell carcinomas and 46 squamous cell carcinomas) and malignant melanomas (69 primary and 28 metastatic tumours). We also studied the proliferation of the same neoplasms by Ki-67 immunohistochemistry. Dendrocytes were numerous, abutting on and infiltrating most basal cell carcinomas and thin malignant melanomas. In contrast, they were present in only low numbers or even absent in thick primary malignant melanomas and in their metastases. They appeared unmodified around squamous cell carcinomas compared with the surrounding skin. Extracellular deposits of alpha 2-macroglobulin were often found in locations where dermal dendrocytes were numerous. No correlation was found between the Ki-67 indices of carcinomas and the density of peritumoral dendrocytes. In contrast, negative relationships were found between the Ki-67 indices and the number of dendrocytes present inside basal cell carcinomas and thin malignant melanomas. This study has yielded circumstantial evidence to link the density of factor XIIIa-positive dendritic cells and a low proliferative rate of neoplastic cells in basal cell carcinomas and malignant melanomas.
Nail surfaces of toe-nail fragments were analysed by optical profilometry in patients treated with two different dosages of itraconazole: 200 mg continuous dosing for 12 weeks, or a pulse-dose regimen of 1 week per month of 400 mg itraconazole daily for 3-4 months. The use of the latter regimen seemed clinically to increase nail growth, which was accompanied in several patients by the occurrence of nail surface irregularities. This aspect was studied by computerized optical profilometry. Nail beading was characterized by a higher number of peaks and a larger mean roughness value (Ra). Such findings are reminiscent of other nail alterations resulting from a faster matrix turnover. A substantially greater number of peaks and larger Ra were found in the patients receiving the pulse treatment than in those receiving the continuous-dose regimen. Pulse therapy with itraconazole therefore appears to modify the structure of the nail plate, probably as a result of, or in association with, an increased rate of growth.
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