Treatment of human cutaneous sporotrichosis with itraconazole

Eighteen adult white male patients with cutaneous sporotrichosis were treated with itraconazole following different daily dose schemes. Cure was obtained in all cases after periods of 15-75 days (median 44 days) with total doses between 3.1 and 14.8 g (median 8.4 g). No serious side effects were observed and no relapses occurred in the follow-up period of between 1 and 26 months (median 14.7). These results show that itraconazole represents a safe and effective drug for the treatment of sporotrichosis. Comparison with other studies leads us to consider a daily dose of 200 mg as the most appropriate. A concomitant warming of the affected limbs should be recommended.     

Treatment of head and neck dermatitis comparing itraconazole 200 mg and 400 mg daily for 1 week with placebo

BACKGROUND: Head and neck dermatitis (HND) is a variant of atopic dermatitis often seen in young adults. A hypersensitivity to Malassezi antigens is considered to be of pathogenic importance. Previous mostly uncontrolled studies have shown that oral antimycotics might be of use in this condition. OBJECTIVE: To evaluate the efficacy of itraconazole in the treatment of HND in a randomized, double-blind, placebo-controlled trial. PATIENTS: Adult patients with HND were included. Systemic steroids and oral/topical antimycotics were avoided 1 and 2 months prior to the trial. Topical steroids were not allowed in the head and neck area within 2 weeks. Patients in generally good health were included and female patients had to have had a negative urine pregnancy test. The patients signed an informed consent. STUDY DESIGN: The study included a 7-day treatment period and a follow-up period of 105 days. Control visits were carried out on days 3, 7 and 14 and after 15 weeks. METHODS: The SCORAD index (one for the head and neck area and one for the remaining surface area) and global evaluations by patient and investigator were used for clinical evaluation at each visit. Prick tests with Malassezia antigens and Candida albicans antigen were carried out at the start of the trial and included positive and negative controls. The patients were randomized into three groups, which were treated with 400 mg itraconazole daily, 200 mg itraconazole daily or placebo, respectively, for 7 days. RESULTS: The number of patients included was 53: 18 had 200 mg itraconazole daily, 17 had 400 mg itraconazole daily and 18 placebo. At days 7 and 14, significant improvement was seen in the SCORAD of the head and neck area for the groups given 400 mg itraconazole daily (P = 0.0385 and P = 0.0134), and 200 mg daily (P = 0.0104 and P = 0.0006). Patients in the placebo group improved slightly (P = 0.0785). At day 14, comparison of improvement of SCORAD of the head and neck area between all three groups showed a significant difference in favour of the 200 mg itraconazole group compared to the placebo group (P = 0.0318). The prick test was positive for Pityrosporum ovale in 37% and negative for C. albicans in all patients. CONCLUSIONS: One week of treatment with 200 or 400 mg itraconazole as a single treatment has a significant effect on the head and neck area. Compared to placebo there was a significant improvement in SCORAD of the head and neck area in favour of the 200 mg itraconazole group after 14 days. The important observation seems to be that antifungal systemic treatment has a significant SCORAD reduction of atopic dermatitis, irrespective of the presence of allergy.     

C1GALT1 in health and disease

O-linked glycosylation (O-glycosylation) and N-linked glycosylation (N-glycosylation) are the two most important forms of protein glycosylation, which is an important post-translational modification. The regulation of protein function involves numerous mechanisms, among which protein glycosylation is one of the most important. Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 (C1GALT1) serves an important role in the regulation of O-glycosylation and is an essential enzyme for synthesizing the core 1 structure of mucin-type O-glycans. Furthermore, C1GALT1 serves a vital role in a number of biological functions, such as angiogenesis, platelet production and kidney development. Impaired C1GALT1 expression activity has been associated with different types of human diseases, including inflammatory or immune-mediated diseases, and cancer. O-glycosylation exists in normal tissues, as well as in tumor tissues. Previous studies have revealed that changes in the level of glycosyltransferase in different types of cancer may be used as potential therapeutic targets. Currently, numerous studies have reported the dual role of C1GALT1 in tumors (carcinogenesis and cancer suppression). The present review reports the role of C1GALT1 in normal development and human diseases. Since the mechanism and regulation of C1GALT1 and O-glycosylation remain elusive, further studies are required to elucidate their effects on development and disease.     

Reduction in incidence of invasive fungal infection in patients receiving allogeneic stem cell transplantation using combined diagnostic‐driven approach and itraconazole oral solution

Invasive fungal infections are an important cause of morbidity and mortality after allogeneic haematopoietic stem cell transplantation. We evaluated, in our allogeneic stem cell transplant patients, the effect on the incidence of invasive fungal infection during neutropenia of a strategy combining a diagnostic‐driven approach with chemoprophylaxis during higher risk periods of graft vs. host disease and prolonged neutropenia, using itraconazole oral solution with parenteral voriconazole bridging. One hundred and thirty patients admitted for allogeneic stem cell transplantation within two predefined 20 month periods were included in the study. Data for all patients were collected prospectively. Implementation of the protocol resulted in the administration of more prophylactic antifungals to more patients. Following implementation, there was a non‐significant decrease in the overall number of invasive fungal infections (IFI) [11 of 65 patients (17.2%) vs. 4 of 65 patients (6.2%, P = 0.051)], as well as in the occurrence of invasive mould infections [8 of 65 patients (12.5%) vs. 2 of 65 patients (3.1%, P = 0.054)]. Survival rates at three and 6 months were not significantly affected. A combined diagnostic‐driven approach and antifungal prophylaxis with oral itraconazole and an intravenous voriconazole bridging protocol, was associated with a reduced, albeit non‐statistically significant, number of IFI in our medical centre.     

Allergic bronchopulmonary aspergillosis: new concepts of pathogenesis and treatment

Allergic bronchopulmonary aspergillosis (ABPA) is a condition that results from a hypersensitivity reaction to the fungus Aspergillus fumigatus. The purpose of the present review is to examine the pathogenesis of this condition and the evidence for treatments available. Allergic bronchopulmonary aspergillosis is characterized by an intense airway inflammation with eosinophils and the formation of mucus plugs. Clinically, there are periods of exacerbation and remission that may lead to proximal bronchiectasis and fibrotic lung disease. New evidence confirms the role of intense airway inflammation with eosinophils, but also suggests a role for interleukin (IL)-8/neutrophil-mediated inflammation in this process, and the potential deficiency of anti-inflammatory cytokines such as reduced IL-10. Treatment for ABPA has so far focused on corticosteroids to suppress eosinophilic airway inflammation. An expanding knowledge of the pathology of ABPA also suggests other therapies may be of potential benefit, particularly the use of azole antifungal agents. Allergic bronchopulmonary aspergillosis is itself an important complication of asthma and cystic fibrosis. A greater understanding of the condition is required to improve management and well-designed clinical trials need to be carried out to critically assess new and current treatments. In addition, the information gained from the studies of its pathogenesis has the potential to benefit our understanding of the disease processes in asthma and bronchiectasis.     

Fungal infections of the skin and nail: new treatment options

Knowledge of the currently available antifungal agents, along with clinical, microbiologic and histopathologic methods, can help the medical professional optimally manage skin and nail fungal infections. With regards to treatment of fungal disease of the skin or nail, there are a variety of systemic antifungal agents, including several newer agents that have different formulations, tolerability, adverse effect profiles and spectrum of activity. This review will highlight the clinically important fungal infections of the skin and nail and describe the activity and role of antifungal treatment.     

口服伊曲康唑引起过敏性休克1例

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Therapie von Infektionen durch Schwärzepilze

Zusammenfassung. Da Schwärzepilze zu den seltenen Erregern von Mykosen zählen, begründen sich Therapieempfehlungen vorwiegend auf Einzelfallbeobachtungen. Bei Eumyzetomen und herdförmigen Phaeohyphomykosen des Zentralnervensystems (z. B. durch Cladophialophora bantiana, Exophiala dermatitidis ) und in bestimmten Fällen einer Chromoblastomykose ist die Resektion in toto Therapie der Wahl, ggf. mit antimykotischer Begleitmedikation. Zur antimykotischen Therapie ex juvantibus bei Phaeohyphomykosen ist z. Z. ein Therapicerfolg mit einer Kombinationsbehandiung aus Itraconzol und 5-Fluorcytosin am ehesten zu erwatten. Eine ausreichende Therapiedauer ist für den Erfolg maßgebend.
Summary. Since dematiaceous fungi belong to the group of rare infectious agents causing mycoses, therapeutic recommendations are mainly deduced from observations of single cases. In cases of eumycetoma or focal phaeohyphomycoses of the central nervous system (e.g. caused by Cladophialophora bantiana or Exophiala dermatitidis ) and in certain cases of chromoblastomycoses, the resection in loto is the therapy of choice, which may be accompanied by antimycotic medication. As antimycotic therapy ex juvantibus in case of phaeohyphomycoses, a simultaneous application of itraconazole and 5-fluorocytosine is presently most promising. The success depends on an adequate duration of therapy.     

Effect of food on the absorption and pharmacokinetics of prednisolone from enteric-coated tablets

Summary We have studied the influence of food and dose (50, 100, 200 mg) on the oral systemic availability of the broad spectrum antifungal itraconazole and the pharmacokinetics after repeated dosing of 100 mg in six healthy volunteers.The relative systemic availability of itraconazole capsules compared with solution averaged 39.8% in the fasting state but 102% in the post-prandial state. Food did not significantly affect the t_max of the capsules. Itraconazole AUC at single doses of 50, 100, and 200 mg had a ratio of 0.3:1:2.7, and the steady-state AUC (0–24) after 15 days of 100 mg was five times the single-dose AUC.These findings suggest non-linear itraconazole pharmacokinetics in the range of therapeutically used doses. Furthermore, capsules should be given shortly after a meal to ensure optimal oral systemic availability.     

The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis

Background and objective:   Very little is known about the response rates to or appropriateness of treatment for patients with allergic fungal diseases of the lung. This study assessed the effect of antifungal therapy in patients with severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA).
Methods:   A retrospective cohort study of 33 adult patients who fulfilled the criteria for either SAFS ( n  = 22) or ABPA ( n  = 11) was conducted. All patients had received antifungal therapy for at least 6 months. The primary study end point was the effect of antifungal therapy on patients' lung function.
Results:   Overall, total IgE values and radioallergosorbent test (RAST) for A. fumigatus markedly decreased after 6 months of therapy in both SAFS and ABPA patients ( P  = 0.004 and P  = 0.005, respectively). Reduction was seen in the eosinophil count ( P  = 0.037), dose of oral steroids ( P  = 0.043) and courses of systemic steroids required ( P  = 0.041). Lung function also improved ( P  = 0.016). Four of 10 patients discontinued oral steroids after 6 months of therapy. Reduction in IgE levels ( P  = 0.015) and RAST for A. fumigatus was also observed ( P  = 0.006) for those patients treated for at least 1 year with antifungal drugs.
Conclusions:   Both ABPA and SAFS patients benefited from oral antifungal therapy. The antifungal therapy may act by reducing the antigenic load, interacting with corticosteroids or by a direct immunological effect.