Delphi consensus on the current clinical and therapeutic knowledge on Anderson-Fabry disease

BACKGROUND: Management of Anderson-Fabry disease (AFD) is contentious, particularly regarding enzyme replacement therapy (ERT). We report results of a Delphi consensus panel on AFD management. METHODS: A survey to gauge consensus among AFD experts was distributed online and responses were analysed. Statements on: 1) diagnosis; 2) when starting ERT; 3) management of ERT infusion and adverse reactions; and 4) follow-up/monitoring response to therapy and progression of disease were included. Responses without consensus were discussed with an enlarged panel and modified to reach consensus. RESULTS: 15 experts responded to the survey. After plenary discussion among the enlarged panel, consensus was reached on most statements. Key points were the use of a target organ biopsy to show Gb3 deposits in symptomatic women with negative molecular analysis, the need for ERT in symptomatic women and in all patients with persistent signs and symptoms±organ damage. It was agreed to assess vital signs before ERT administration and use a 0.2μL filter on infusion to reduce the risk of adverse reactions, that serum should be drawn prior to the first infusion for anti-agalsidase antibody analysis to have a baseline value if a subsequent adverse reaction appears, and that pre-medication is required in those with prior infusion reactions. Holter ECG monitoring, cardiac and brain MRI, renal parameters, and abdominal ultrasound were considered important for the assessment of disease progression and response at ERT. CONCLUSIONS: This consensus supplies guidance to healthcare providers on best practice in the management of patients with AFD and indicates a need for more guidanc

Linear atrophoderma of Moulin.

Firstly described by Moulin et al. in 1992 in 5 patients [1], LAM is a distinct clinical entity characterized by acquired atrophic bandlike skin lesions that often show hyperpigmentation and always follow the lines of Blaschko. No preceding infl ammation is noted, but a transient infl ammatory stage is perhaps often unrecognized, and there is no induration or scleroderma. Usually the condition begins in childhood or adolescence, and there is no evidence of any long-term progression. Histopathologically, an irregular moderate hyperpigmentation of the lower part of the epidermis is found, along with a few perivascular lymphocytes in the dermis and slight thickening of the collagen bundles, as in our case [2]. The existence of LAM is controversial in its possible clinical overlap with linear scleroderma or morphea. Nevertheless, this latter is characterized by one or more linear streaks of progressive induration that can extend through the dermis, subcutaneous tissue, and muscle to the underlying bone, causing signifi cant deformities [3]. The lack of autoantibodies, such as ANA, found in 73% of adult patients with linear scleroderma and the chronic and unvaried course make this diagnosis unlikely in our patient, leading to the more compatible diagnosis of LAM [4]. The cause and pathogenesis of this disorder remain unclea

Electronic nose analysis of urine samples containing blood

In this paper the possible application of an electronic nose to the analysis of urine is presented. In contrast with the conventional applications of sensors and biosensors operating in liquid, the approach discussed here makes use of gas sensors performing an analysis of the headspace. The application deals with urine samples from patients affected by kidney diseases; some of the samples contained traces of blood. Results show the possibility of distinguishing the samples containing blood from the others, and a linear correlation between the first three principal components and the blood content was found. Furthermore, the electronic nose matched with a suitable neural network showed good performance in measuring the pH and the specific weight of the samples

Serum interleukin-18 in children with henoch-schönlein purpura: A promising marker of disease activity?

Henoch-Schönlein purpura (HSp) is the most common systemic vasculitis of childhood with typical skin involvement and concurrent signs involving joints, gastrointestinal tract, and kidney. HSp pathogenesis is still far from being completely understood, though a knotty cytokine complex is believed to contribute to its intimate processes. The aim of our evaluation is to establish the relationship between serum levels of interleukin (IL)-18 and disease outcome and establish its feasibility to provide a marker of disease activity or even a prognostic tool in clinical practice. We examined clinical/laboratory variables and serum IL-18 in 17 children hospitalized during a year for HSp, diagnosed by EULAR/PRINTO/PRES criteria; the same patients were re-evaluated after 6 months. All results were compared with 25 age-matched healthy controls. IL-12 and IL-6 were also evaluated in a cohort of the same patients and compared with controls. General and clinical variables (sex, edema of the extremities, gastrointestinal or renal complications, relapses and renal involvement at 6 months) had no relationship with cytokine levels. Serum IL-18 and IL-6 levels were found significantly increased at diagnosis in HSp patients when compared with healthy controls. After 6 months, serum IL-18 and IL-12 levels were significantly decreased in patients, while IL-12 and IL-6 levels were significantly increased compared to healthy controls. Though preliminary and expecting further confirmation on a larger sample, our data support the conclusion that serum IL-18 levels reflect HSp activity

Topical preparations for the treatment of psoriasis: results of a retrospective study over 15 years.

Psoriasis requires lifelong treatments that depend on the extent, clinical forms and associated conditions.To retrospectively analyze which topical treatments were used, their efficacy, and potential advantages and disadvantages.A total of 666 patients admitted for the first time over 15 years who were topically treated were retrospectively reviewed and subdivided using clinical forms and PASI into four groups and four subgroups for the applied treatments. For each treatment the mean PASI was calculated daily: on the first, third and sixth day. An X sample statistical analysis and Mann--Whitney U-test were performed. The hospitalization time and correlation with the response to treatment were analyzed.A statistically significant response was recorded for every regimen. The best combination was clobetasol propionate plus eosin on alternate days with eosin plus cade oil. The highest score was recorded for the 'en plaques' psoriasis. The average length of treatment was of 7.5 days in the best combination. No statistically significant difference among the groups was recorded with respect to the length of hospitalization and PASI.The statistically significant response for all the topical treatments analyzed and recorded in this study does not exclude a potential benefit due to hospitalization per se

Vascular Endothelial Growth Factor (VEGF-a) in Fabry disease: Association with cutaneous and systemic manifestations with vascular involvement

Fabry disease is an X-linked inherited metabolic disorder characterized by the deficiency of lysosomal \u3b1-galactosidase A enzyme. This leads to the accumulation, into lysosomes through the body, of glycosphingolipids, mainly Gb3. Skin involvement and progressive multi-organ failure are usually observed. Endothelium is the preferential target of the Gb3 storage that determines endothelial dysfunction and vasculopathy leading to the clinical manifestations of the disease. The serum levels of Vascular Endothelial Growth Factor-A (VEGF-A), a specific endothelial cell mitogen, were analyzed in Fabry patients to explore a possible association to the clinical manifestations with vascular involvement

Influence of β-carotene on lysosomal hydrolases and their natural substrates in major salivary glands of hamsters treated with 7,12-dimethylbenzanthracene (DMBA)

We evaluated the effects of P-carotene, a precursor of vitamin A, on the activity of some lysosomal hydrolases and on the levels of their natural substrates in hamster major salivary glands during experimental oral 7,12-dimethylbenzanthracene (DMBA) carcinogenesis. Sixtyfour hamsters (Cricetus auratus) were divided into four groups-group 1: untreated control; group 2: DMBA was painted three times a week in the left buccal pouch; group 3: beta-carotene was painted three times a week in the left buccal pouch; group 4: DMBA and beta-carotene were painted alternatively in the left buccal pouch. After 16 weeks, the animals were sacrificed and the activities of some lysosomal hydrolases and their natural substrates in the major salivary glands were measured. beta-Carotene when administered topically in DMBA treated animals (group 4) reduced the levels of the majority of enzymes and substrates closer to those of the untreated control group, thus outlining a mild protective effect of beta-carotene towards the DMBA carcinogenic stress. Nevertheless, the presence of some enzymes which responded negatively to the combined administration of DMBA and beta-carotene suggests the necessity.for future studies on the effect of beta-carotene at different concentrations, the systemic administration and the possibility to combine the topical beta-carotene administration with other chernopreventive drugs. (C) 2004 Elsevier Inc. All rights reserved

The impact of fever and dystermia in Fabry disease diagnosis: a retrospective analysis

The occurrence of fever in patients with Fabry disease has been discussed in this report