Effects of high-dose itraconazole treatment on lipoproteins in men.

OBJECTIVE: Epidemiological studies have convincingly demonstrated a positive association between LDL-cholesterol (LDL-C) and coronary artery disease but, in the case of HDL-C, there is an inverse association. Administration of high doses of the antifungal agent ketoconazole (800 mg/d) reduces serum concentrations of total cholesterol and LDL-C and there is a tendency for an increase in HDL-C. Our goal was to examine whether high-dose itraconazole raises HDL-C in subjects with normal levels of cholesterol. PATIENTS AND METHODS: 8 male patients with onychomycosis received 2 one-week cycles of treatment with itraconazole at a dose of 400 mg once daily in an open, prospective exploratory trial. Serum levels of itraconazole and its active metabolite hydroxyitraconazole were determined using high-performance liquid chromatography at the end of each treatment cycle. Fasting levels of serum lipoproteins and triglycerides were measured twice using routine enzymatic assays at the beginning and end of each cycle. The effects of itraconazole and hydroxyitraconazole on HDL-C metabolism were assessed in vitro using a human Caco-2 cell line and analyzing apoA-I levels with an enzyme-linked immunosorbent assay. RESULTS: During itraconazole treatment total cholesterol and LDL-C decreased on average by 12% (p < 0.001) and 17% (p < 0.001), respectively, whereas HDL-C increased by 21% (p < 0.001). The ratio LDL: HDL-C, an index of atherogenic risk, decreased by 30% (p < 0.001). Incubation of Caco-2 cells in the presence of itraconazole and hydroxyitraconazole for 3 hours resulted in a significant increase in apoA-I concentration in the medium (913 and 412%, respectively) compared with control. CONCLUSION: In addition to its inhibitory effect on cholesterol synthesis, high-dose itraconazole (400 mg/d) causes a significant decrease in serum LDL-C and, in contrast to ketoconazole, a significant increase in HDL-C. In vitro studies with Caco-2 cells indicate that the latter observation might be caused by an increase in apoA-I levels.

Papular palmoplantar hyperkeratosis following chronic medical exposure to arsenic: human papillomavirus as a co-factor in the pathogenesis of arsenical keratosis?

This study presents the case of a 38-year-old patient from Pakistan with vitiligo, who developed multiple verrucous papules on the palms and soles several years after receiving "herbal treatment" from a travelling Indian doctor for a period of 12 months. Histopathological examination showed changes consistent with the diagnosis of arsenical keratosis. Molecularbiological examination of a skin biopsy detected an atypical human papillomavirus. This observation supports the concept of human papillomavirus as a co-factor in the pathogenesis of premalignant arsenic-induced skin tumours.

Flame figures in urticarial lesions accompanying systemic lupus erythematosus.

We present the case of a 38-year-old female patient with systemic lupus erythematosus and atypical urticarial skin lesions with an alteration in shape, but not complete disappearance, within 24 hours. Hematoxylin-eosin-stained sections revealed flame figures. We review urticarial lesions in lupus erythematosus and discuss the possible pathomechanisms.

Association of inclusion body myositis with subacute cutaneous lupus erythematosus.

We present the case of a 71-year-old man with inclusion body myositis combined with subacute cutaneous lupus erythematosus and dysphagia. Although inclusion body myositis is usually resistant to immunosuppressive therapy, this patient improved under treatment with corticosteroids. The presented case is discussed in the context of earlier reports of inclusion body myositis and lupus erythematosus.

Sporotrichoid phaeohyphomycosis due to Alternaria infectoria.

We describe a cardiac transplant patient who had human cutaneous alternariosis with a sporotrichoid distribution of skin lesions. In this patient identification of the causative organism Alternaria infectoria was achieved by sequencing the rDNA internal transcribed spacer domain. Treatment with itraconazole led to clinical resolution within 4 months.

Safety of rush insect venom immunotherapy. The results of a retrospective study in 178 patients.

BACKGROUND: Venom immunotherapy (VIT) is regarded as an established and efficient treatment of Hymenoptera venom allergy. Different frequencies of side-effects have been reported in the literature, depending on the hyposensitization regimen (conventional outpatient programme, rush immunotherapy, ultra rush immunotherapy) and the venom preparation. Aim of this study was to evaluate safety and tolerance of rush VIT in patients treated with a 7-day protocol in our department. METHODS: VIT protocols of 178 patients treated at the Department of Dermatology and Allergy of the University of Bonn were analysed retrospectively. All patients had been treated with a standardized venom preparations (ALK-SQ). We used a modified VIT-protocol with a 2-day break to reduce systemic side-effects. RESULTS: During the course of VIT in 15 patients (8.4%) systemic reactions grade I (Mueller scale) were observed, in seven (3.9%) grade II, in six (3.4%) grade III and in four (2.2%) grade IV. A total of 146 patients (82.1%) had no or only local reactions. CONCLUSIONS: The rate of systemic adverse reactions Mueller Grade I-IV of 17.9% of the 'Bonn rush VIT protocol' appears to be relatively low compared with the data in the literature.

Lymphocytopenia in lupus erythematosus: close in vivo association to autoantibodies targeting nuclear antigens.

BACKGROUND: Leukopenia and lymphopenia are typical features of lupus erythematosus (LE) and correlate with elevated disease activity and higher grades of systemic involvement. Antilymphocyte antibodies are regarded as the most likely rationale for the decreased cell numbers; however, their relevance has not been confirmed so far. OBJECTIVES: Previous investigations at our department have shown a significant correlation between diminished lymphocyte numbers and the presence of antinuclear antibodies (ANA). We wanted to achieve a better understanding of this phenomenon. METHODS: We performed a detailed analysis of autoantibodies and peripheral leucocyte subsets in 82 patients with different subtypes of LE. Leucocyte subsets were measured using flow cytometry (FACScan; Becton Dickinson, Franklin Lakes, NJ, USA.); autoantibodies were detected by indirect immunofluorescence and by enzyme-linked immunosorbent assay. RESULTS: A significant association (P < 0.05) between specific antibodies targeting nuclear antigens (SSA/Ro-52, SSB/La, snRNPs) and lymphocytopenia was found. CONCLUSIONS: We suppose that some of these autoantibodies might have an antilymphocyte effect. Apoptosis induction by specific antinuclear antibodies has already been described earlier, but to the best of our knowledge this is the first study presenting a strong indication of a possible interaction between these antibodies and lymphocyte subsets in vivo.

Annular erythema caused by impending pacemaker extrusion.

A 72-year-old patient with an implanted cardiac pacemaker presented with a circumscribed erythematous area on his chest. It was only several months later, after he had developed positional, localized pain in this area, that the diagnosis of an impending pacemaker extrusion became evident. This case illustrates the diagnostic difficulties in patients with pacemaker-associated skin lesions. Regular follow-up examinations and close co-operation of dermatologists, cardiologists and cardiothoracic surgeons are of major importance in view of the potentially life-threatening complications.