[Eosinophllic fasciitis (Shulman disease)]. / Fasciite à eosinophiles ou syndrome de Shulman.

Eosinophilic fasciitis is a rare connective tissue disease, described by Shulman in 1974. This syndrome is characterized by a symmetrical swelling of the skin associated with eosinophilia. A progressive induration of the skin replaces the swelling. Arms and legs are the most affected sites. The face and hands are usually not involved and the patients don't complain of Raynaud phenomenon. No circulating autoantibodies are found. Diagnosis is made with history, MRI and histology. MRI detects fascial thickening and contrast enhancement of this fascia. A full thickness skin to muscle biopsy is necessary to confirm the diagnosis. It shows an inflammation and thickening of the fascia with lymphocytes and plasmocytes. High doses of corticosteroids are reported to be effective in more than 70% of the cases. Immunosuppressive drugs are sometimes necessary to induce clinical remission.

Variation in performance in low-volume mammography screening programmes: experience from Switzerland.

BACKGROUND: Reading volume and mammography screening performance appear positively correlated. Quality and effectiveness were compared across low-volume screening programmes targeting relatively small populations and operating under the same decentralised healthcare system. Except for accreditation of 2nd readers (restrictive vs non-restrictive strategy), these organised programmes had similar screening regimen/procedures and duration, which maximises comparability. Variation in performance and its determinants were explored in order to improve mammography practice and optimise screening performance. METHODS: Circa 200,000 screens performed between 1999 and 2006 (4 rounds) in 3 longest standing Swiss cantonal programmes (of Vaud, Geneva and Valais) were assessed. Indicators of quality and effectiveness were assessed according to European standards. Interval cancers were identified through linkage with cancer registries records. RESULTS: Swiss programmes met most European standards of performance with a substantial, favourable cancer stage shift. Up to a two-fold variation occurred for several performance indicators. In subsequent rounds, compared with programmes (Vaud and Geneva) that applied a restrictive selection strategy for 2nd readers, proportions of in situ lesions and of small cancers (≤1cm) were one third lower and halved, respectively, and the proportion of advanced lesions (stage II+) nearly 50% higher in the programme without a restrictive selection strategy. Discrepancy in second-year proportional incidence of interval cancers appears to be multicausal. CONCLUSION: Differences in performance could partly be explained by a selective strategy for second readers and a prior experience in service screening, but not by the levels of opportunistic screening and programme attendance. This study provides clues for enhancing mammography screening performance in low-volume programmes.

[External quality controls for allergy analysis in the Quality Control Center Switzerland from 2006 to 2008]. / Les contrôles de qualité externes pour le laboratoire d'allergologie auprès du Centre suisse de contrôle de qualité de 2006 à 2008.

External assessment of analytical performance is part of the quality assurance in medical laboratory. These external controls are mandatory in Switzerland since 2006 for IgE analysis. The Swiss Society for Immunology and Allergy and the Swiss external quality centers had launched a program for total IgE, IgE specific for cat epithelium, birch pollen and peanut, and multi-specific IgE. They have set up criteria for proficiency assessment. Analysis of data obtained from 2006 to 2008 in the Quality Control Center Switzerland shows that results are very good for all the methods used and that a large number of participants fulfill the requirements to obtain the certificate of QUALAB conformity.

[Goodpasture syndrome associated with p-ANCA microscopic vasculitis: a rare entity to recognize]. / Syndrome de Goodpasture associé à une vasculite microsco- pique à p-ANCA: une entité rare à ne pas méconnaître.

Some autoimmune diseases may be found presenting simultaneously antibodies (Abs) against basal membrane and anti-neutrophil cytoplasm (ANCA). The clinical picture is that of the Goodpasture syndrome with anti-basement membrane Abs associated with an ANCA-associated small-vessel vasculitis (micro-PAN). The arisen of these two pathological entities is nevertheless too frequent to be the fruit of the only fate. The pathophysiological hypothesis remains that of the micro-PAN initially creates lesions of the basement membrane facilitating the formation of Abs against some constituents of this latter. The prognosis remains controversial, leaving open this issue. This article aims to present a recent literature revue dealing with the simultaneous presence of these two auto-immune diseases.

[Allergen-specific IgE detection methods]. / Detection sérique des IgE spécifiques d'allergènes.

The clinical setting defines the use of different methodology to detect allergen-specific IgE antibodies. In primary care, near the patient detection methods are useful as alternative to skin tests. The use of quantitative screening methods for atopy (Phadiatop) has been shown to improve the allergy diagnosis by the practicionner Such methods are very useful for their negative predictive value. Moreover, the dissociation between seasonal and perennial allergy is easier. For the use of specialist, quantitative results of allergen-specific IgE can be related to the probability of a clinical reaction to a given allergen. Clinical decision points have been established for common food allergens associated with atopic eczema in children.

Dysregulation of IL-2/IL-2R system alters proliferation of early activated CD4+ T cell subset in patients with end-stage renal failure.

BACKGROUND/AIM: Although CD4+ T cells are preactivated in patients with end-stage renal failure (ESRF), these patients present an impairment of T cell immune response, which is partly responsible for the higher incidence of infection in this population. The aim of the present study was to analyze the mechanisms underlying the altered function of activated CD4+ T cells in patients with ESRF. METHODS: Thirty patients undergoing chronic hemodialysis (HD) and 20 patients with ESRF were compared with 15 sex- and age-matched controls. CD4+ T cell early activation (CD69, CD25), interleukin-2 (IL-2)/IL-2 receptor (IL-2R) system, and proliferation capacity of CD69+/CD4+ T cells were assessed ex vivo after blood draw sampling, in culture conditions and after phytohemagglutinin (PHA) stimulation. RESULTS: Although the CD4+ T cell count was lower in chronic HD patients than in predialysis patients and controls (p = 0.007), CD4+ T cells showed a pre-activation state as demonstrated by higher percentage of CD69+/CD4+ T cells and CD25+/CD4+ T cells in chronic HD patients compared with the other groups ex vivo. Furthermore, CD69+/CD4+ T cells from chronic HD patients spontaneously released more IL-2 (22 +/- 6 pg/ml) than those from pre-dialysis patients (12 +/- 4 pg/ml, p = 0.005) and controls (5 +/- 3 pg/ml, p = 0.001). However, after PHA stimulation, CD69+/CD4+ T cells from chronic HD patients expressed lower cell surface CD25 density, and were unable to show further activation. Indeed, these cells produced less IL-2 and released more soluble IL-2R, and correlatively with IL-2 production, they showed lower proliferation capacity compared with predialysis patients (p = 0.001) and controls (p < 0.001). They also displayed decreased responsiveness to exogenous human recombinant IL-2. The restoration of the PHA stimulation index of CD69+/CD4+ T cells from chronic HD patients in the presence of normal human serum as well as the decreased stimulation index of CD69+/CD4+ T cells from control subjects incubated with HD serum, strongly suggest that uremic toxins and mediators induced by HD affect the IL-2/IL-2R pathway. CONCLUSION: These findings demonstrate the presence, in chronic HD patients, and to lesser extent, in predialysis patients, of abnormally high proportion of spontaneously preactivated CD4+ T cells whose proliferation and further activation are blunted due to dysregulation of the IL-2/IL-2R system.

Usefulness of procalcitonin serum level for the diagnosis of bacteremia.

The predictive value of procalcitonin serum levels to detect or rule out bacteremia was investigated prospectively in a case-control study with 200 hospitalized adults from whom blood samples were taken for culture. Fifty bacteremic patients (cases) had higher procalcitonin serum levels than the 150 controls with sterile blood cultures (11.7 vs. 0.7 ng/ml; P=0.0001), a difference that remained significant after controlling for potential confounders in multivariate analysis. At cut-off values of 0.5 and 0.2 ng/ml, the sensitivity of procalcitonin was 56 and 92%, and the specificity was 83 and 43%, respectively. These results yielded low positive (22 and 12%) and high negative predictive values (96 and 99%), reflecting primarily the low prevalence of bacteremia among patients who undergo blood cultures in hospitals (low pretest probability). Although caution is mandatory when using such markers at the individual level, procalcitonin, possibly together with other parameters, could nonetheless prove useful in future studies to rapidly rule out bacteremia.

Specificities and sensitivities of four monoclonal antibodies for typing of Borrelia burgdorferi sensu lato isolates.

Borrelia burgdorferi, the agent of Lyme borreliosis, is genetically more heterogeneous than previously thought. In Europe five genospecies have been described from the original B. burgdorferi sensu lato (sl): B. burgdorferi sensu stricto (ss), B. garinii, B. afzelii, B. lusitaniae, and B. valaisiana. In the United States, B. burgdorferi ss as well as B. bissettii in California and B. andersonii on the East Coast were differentiated. In Asia, B. japonica has been identified along, with B. garinii, B. afzelii, and B. valaisiana. In order to evaluate sensitivity and specificity of four species-specific monoclonal antibodies, we analyzed 210 B. burgdorferi sl isolates belonging to eight genospecies by immunoblot and confirmed genospecies by restriction fragment length polymorphism (RFLP) of rrf (5S)-rrl (23S) intergenic spacer amplicon. Monoclonal antibody H3TS had 100% sensitivity for 55 B. burgdorferi ss isolates but showed reactivity with all four isolates belonging to B. bissetii. Monoclonal antibody I 17.3 showed 100% specificity and sensitivity for 45 B. afzelii isolates. Monoclonal antibody D6 was 100% specific for B. garinii but missed 1 of 64 isolates (98.5% sensitivity). Monoclonal antibody A116k was 100% specific for B. valaisiana but was unreactive with 4 of 24 isolates (83.5% sensitivity). Genetic analysis correlated well with results of reactivity and confirmed efficacy of the phenotypic typing of these antibodies. Some isolates showed atypical RFLP. Therefore, both phenotypic and genotypic analyses are needed to characterize new Borrelia isolates.

Scored antibody reactivity determined by immunoblotting shows an association between clinical manifestations and presence of Borrelia burgdorferi sensu stricto, B. garinii, B. afzelii, and B. Valaisiana in humans.

An immunoglobulin G immunoblot was developed with antigenic extracts of Borrelia burgdorferi sensu stricto, B. garinii, B. afzelii, and B. valaisiana genospecies and was reacted with sera from patients with neuroborreliosis, acrodermatitis, and Lyme arthritis. A detailed analysis of the reactivities of the protein bands was performed, and a two-step scoring procedure was selected to determine the preferential reactivity of sera to one particular genospecies. The discriminative potential of 5 proteins (12-kDa, 16-kDa, 18-kDa, OspA, and 66-kDa proteins) was used as a rapid first-step scoring method, followed by scoring of 14 additional protein bands if necessary. The advantage of this procedure is the low percentage of serum samples with inconclusive results for one of the four species (10% for patients with neuroborreliosis, 6% for patients with acrodermatitis chronica atrophicans, and 6% for patients with Lyme arthritis). Among 31 serum samples from patients with neuroborreliosis, 16 were more reactive to B. garinii, 7 were more reactive to B. afzelii, 3 were more reactive to B. valaisiana, and 2 were more reactive to B. burgdorferi sensu stricto. Of 31 serum samples from patients with acrodermatitis, 26 showed a higher level of reactivity to B. afzelii. Of 34 serum samples from patients with Lyme arthritis, 21 were more reactive to B. burgdorferi sensu stricto, 10 were more reactive to B. afzelii, and 1 was more reactive to B. valaisiana. Our results suggest an organotropism of Borrelia species and provide some evidence of a pathogenic potential of B. valaisiana in humans.

Exercise-induced bronchospasm (EIB) in relation to seasonal and perennial specific IgE in young adults.

We investigated the relationship between exercise-induced bronchospasm (EIB) and specific IgEs for seasonal (S-IgE) and perennial (P-IgE) allergens. The study, outside the main pollen season, was conducted on 289 20-year-old soldiers, who completed a self-administered questionnaire. A total of 289 subjects had S-IgE and P-IgE measured. The population was divided into subjects with (n = 166) and without (n = 123) history of atopic diseases (HAD). Twenty-three of 289 subjects (8%) had asthma, 70/289 (24%) allergic rhinitis, and 92/289 (32%) atopic siblings. Measured EIB was found in 17/289 subjects (6%). They had significantly higher levels of S-IgE and P-IgE than those without measured EIB (respectively, P < 0.01 and P < 0.05). The odds ratios of having EIB were significantly increased in the entire population in relationship with an increase in both S-IgE and P-IgE (chi-square test for trend = 9.4 and 12.7, P < 0.002 and 0.001, respectively). Interestingly, this highly significant relationship remained true when considering only the no HAD group (chi-square test = 7.4 and 8.8, P < 0.006 and 0.003, respectively). Outside the pollen season, EIB was highly related to the level of both specific seasonal and perennial IgEs in the total population and in the subjects without HAD. This suggests that even in young adults who have been asymptomatic throughout their life EIB appears to be closely linked to seasonal or perennial allergic diathesis as measured by specific IgEs.

Hypersensitivity reactions to drugs: correlation between clinical probability score and laboratory diagnostic procedures.

The in vitro diagnosis of allergic drug reactions have not made significant progress in recent years. Specific stimulation of lymphocytes from allergic patients represents an approach to demonstrating sensitization to the implicated drug. So far, skin tests and RAST can only be applied to a limited number of situations. The purpose of this study was to standardize the clinical criteria in order to establish a clinical probability score for each drug. Independently, the various laboratory procedures mentioned were compared with the established clinical probability score for each drug. The results showed that, for the few common drugs studied, the correlation between the clinical probability score and the results of the in vitro lymphocyte transformation test was significant. A significant correlation between the clinical probability score and the skin tests was only shown for penicillin and its derivatives.

[Music during gastroscopy]. / Musik bei der Gastroskopie.

As part of a project "Music therapy in internal medicine" we investigated 32 consecutive patients undergoing gastroscopy for various reasons. Patients were randomly assigned to two groups, regardless of sex, age or underlying disease. One group listened to music during gastroscopy, while the other did not. The choice of the type of music within the corresponding group was made with the patient and a trained music therapist in a short discussion prior to gastroscopy. The hormones ACTH and cortisol, as well as the catecholamines adrenalin and noradrenaline, were measured in both groups with three blood samples taken before, directly after and one hour after gastroscopy. Parallel measurements included blood pressure and pulse rate as well as questions about the patients' feelings during gastroscopy. The study showed the rise in the plasma levels of the stress hormones ACTH and cortisol to be significantly lower under the influence of music. The subjective feelings of the patients concerning "fear in general" and "fear about gastroscopy" paralleled these findings. Conversely, the plasma adrenalin and noradrenaline levels before and after gastroscopy were virtually unchanged in both groups, as were pulse rate and blood pressure. This study shows the influence of music on human biochemical parameters when used in the setting of a diagnostic procedure.

Imbalance of CD45R and CDw29 helper cell subsets after seven days of culture from penicillin hypersensitive patients.

Specific PBMC proliferation to penicillin represents one of the in vitro diagnostic procedures to show antigenic sensitization. Nine patients with suggestive clinical history of penicillin hypersensitivity, significant stimulation index in the lymphocyte transformation test (LTT), and increased CD25 expression were selected. Their phenotypic expression of T-cell subset markers was compared with that of six normal subjects after 7 days of culture. Higher percentages of CD45R and CDw29 positive cells were found in penicillin-hypersensitive patients. This group of patients showed a significantly (P less than 0.01) higher percentage of CD45R positive cells compared with normal subjects, after 7 days of culture. The percentage of CD45R cells did not differ between patients and normal subjects at day 0, and the progressive decrease of CD45R positive cells in culture of normal subjects was not observable in our patients. These results suggest that the patients with penicillin hypersensitivity have an imbalance of CD45R/CDw29 ratio after 7 days of culture, with a higher expression of CD45R positive cells.

Cartilage proteoglycan-induced arthritis in BALB/c mice. Antibodies that recognize human and mouse cartilage proteoglycan and can cause depletion of cartilage proteoglycan with little or no synovitis.

Human fetal cartilage proteoglycan (PG) induces the development of an erosive polyarthritis and spondylitis in BALB/c mice. We have examined the properties of 3 monoclonal antibodies (MAb) to human fetal cartilage PG isolated from immunized mice that cross-react with mouse cartilage PG. Compared with sera from arthritic mice, which contain antibodies reactive with keratan sulfate, MAb 202 (IgG1) reacted only with a protein-related epitope that is distributed on both hyaluronic acid-binding and chondroitin sulfate-attachment regions. MAb 813 (IgG1) reacted with the same fragments and recognized an epitope with the immunologic characteristics of keratan sulfate. MAb 945 (IgM) remains to be further characterized. Introduction of hybridomas secreting MAb 202 and MAb 945 into irradiated mice resulted in the loss of PG from articular cartilage and from growth plate cartilage (with MAb 202 only), as revealed by a loss of staining with toluidine blue. There was no synovial hyperplasia with MAb 202, but some hyperplasia and mononuclear cell infiltration was seen with MAb 945. This was accompanied by the binding of immunoglobulins to articular cartilage, as demonstrated by immunofluorescence. The hybridoma secreting MAb 813 produced no cartilage changes or synovitis, and there was no immunoglobulin binding to cartilage. Polymorphonuclear leukocyte infiltration was never observed with these antibodies. These studies indicate that MAb reactive with mouse cartilage PG can cause the depletion of PG from hyaline cartilage by mechanisms that may be both complement dependent and complement independent. Antibodies may serve to release and expose PG antigen to immune cells, as well as causing a loss of the mechanical properties of cartilage that are PG dependent.

Quantitation of retroviral gp70 antigen, autoantibodies, and immune complexes in extravascular space in arthritic MRL-lpr/lpr mice. Use of a subcutaneously implanted tissue cage model.

MRL-lpr/lpr (MRL/l) mice spontaneously develop a disease that is characterized by glomerulonephritis, diffuse vasculitis, and arthritis associated with high levels of autoantibodies that include IgG rheumatoid factor (RF). To define the immunopathogenic mechanisms that lead to the development of extravascular lesions such as arthritis, we implanted a tissue cage subcutaneously in arthritic MRL/l mice and compared components of the tissue cage fluid, which resembles the extravascular fluid, with those of sera. When compared with those of sera, tissue cage fluids from arthritic MRL/l mice had similar levels of RF and one-third the amount of C1q immune complexes. In contrast, anti-DNA activities in tissue cage fluids corresponded to only 10% of the serum activities and, most strikingly, nephritogenic retroviral gp70-anti-gp70 immune complexes were almost undetectable in tissue cage fluids. This was also the case for another strain of autoimmune mice, (New Zealand black X New Zealand white)F1 mice, although they did not produce RF. The absence of gp70 immune complexes in tissue cage fluids could be due to markedly limited diffusion of gp70 antigen in these fluids. These results strongly suggest that serum proteins, including autoantigen and autoantibodies, appear in extravascular fluid in a selective manner, depending on their size and charge. Their specific properties in sera or extravascular fluid could partly account for the different manifestations of vascular and extravascular lesions observed in autoimmune mice.

Capacity to solubilize immune complexes in sera and synovial fluids from patients with rheumatoid arthritis.

Fifty-six sera and 33 synovial fluids from rheumatoid arthritis patients were studied to evaluate their capacity to solubilize immune complexes. A decreased function was found in 65% of rheumatoid synovial fluids when compared with 13 osteoarthritis synovial fluids. The decrease of immune complex solubilization capacity correlated with the decrease of hemolytic activity of the alternative complement pathway (P less than 0.001) and inversely with the level of immune complexes (P less than 0.05). Synovial fluids with low and normal immune complex solubilization capacity were compared; the results confirmed a possible role of the synovial complement system in modulating the size and thus the diffusion and clearance of locally generated immune complexes.