Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics.

Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.

[Idiopathic hypereosinophilic syndrome: a case report in an infant]. / Le syndrome d'hyperéosinophilie essentielle: à propos d'un cas chez un nourrisson.

UNLABELLED: We report a case of idiopathic hypereosinophilic syndrome in a young child with favorable outcome after treatment with alpha-interferon. CASE REPORT: A 5-month-old boy presented with major eosinophilia (187 G/l) associated with splenomegaly. There was no evidence for parasitic or allergic disease. Acute leukemia was suspected but bone marrow smear and medullary caryotype were not compatible. Idiopathic hypereosinophilic syndrome was thus diagnosed. Corticotherapy was started and failed. Finally, complete remission was obtained with alpha-interferon treatment. CONCLUSION: Idiopathic hypereosinophilic syndrome is uncommon in children. Significant complications like cardiac dysfunction or hematologic malignancies can occur. Treatment has to be quickly started, in order to reduce eosinophilia. Haematological and echocardiographic follow-up are required.

[Celiac disease in adults: new aspects]. / La maladie coeliaque de l'adulte : aspects nouveaux.

INTRODUCTION: Celiac disease also known as gluten-sensitive enteropathy is a complex disorder where genetically susceptible individuals develop in typical cases signs of malabsorption after ingestion of cereals. Malabsorption is due to total or subtotal atrophy of the small intestinal mucosa regressing after adherence to a gluten-free diet. The only effective therapy is life-long strict abstinence from wheat, rye and barley. CURRENT KNOWLEDGE AND KEY POINTS: During the last two decades spectrum of clinical features of adult celiac disease has been modified. About 60% of cases are now revealed by extraintestinal manifestations. Moreover, recent studies that used serological methods revealed existence of both latent and silent celiac sprue. The finding of the high frequency of atypical celiac sprue contributed to underestimation of the true prevalence of celiac disease until now, and explained that celiac disease could be unknown for a long time, with increased risk of nutritional deficiencies and malignancy. Concurrently, the finding that celiac disease is primarily associated to a few HLA class II molecules, and recent advent of tissue transglutaminase as the main auto-antigen eliciting anti-endomysial antibodies allowed to propose new pathogenesis hypothesis and efficient screening tests for celiac disease diagnosis. FUTURE PROSPECTS AND PROJECTS: New epidemiological data concerning adult celiac disease must incite to a more systematic screening in patients with atypical but evocative features, or in at-risk subjects. Introduction of enzyme linked immunosorbent assays (ELISA) for the detection for anti-tissue transglutaminase antibodies allows to make use of a new available and efficient diagnosis parameter, which could constitute the main screening test in the near future.

[Relevance of anti-tissue transglutaminase antibodies in coeliac disease diagnosis]. / Intérêt des anticorps anti-transglutaminase tissulaire dans le diagnostic de la maladie coeliaque.

Coeliac disease is precipitated upon exposure to the dietary wheat gluten. Definitive diagnosis relies on intestinal biopsy and regression of clinical and histological disorders with adherence to a gluten-free diet. Coeliac disease is usually associated with a malabsorption syndrome. However, both atypical and silent clinical forms have been recently described and prevalence of the disease may be under-estimated. Serological tests have been developed in order to select candidates for intestinal biopsy, but these biological parameters are not suitable for screening in the general population. Indeed, antigliadin IgG antibodies have a poor specificity. antigliadin IgA antibodies a poor sensitivity. The detection of antiendomysial IgA antibodies (EmA) by immunofluorescence, although considered as the "gold standard" of serological coeliac disease markers, could not be automated, depends on a subjective fluorescence display, and may be limited by the degree of training of the observer. In year 1997, tissue transglutaminase (tTg) has been identified as the main autoantigen recognized by EmA. On this basis, solid-phase enzyme-linked immunosorbent assays (Elisa) have been developed in order to potentially replace the EmA assay. Several commercial kits are now available but their diagnostic performances have not yet been compared. We selected 75 sera, including sera from 26 patients with coeliac disease in order to evaluate five commercial anti-tTG Elisa kits. For all patients, treated or not, detection of anti-tTG antibodies with four of the five tested kits correlates with EmA test. Kits using human tTG have the highest specificity, equivalent to the value of EMA test, and widely better than antigliadin antibodies. Anti-tTG Elisa kits using human tTG may be used as an alternative way to the EmA assay in the next future, and may supplant IgA anti-gliadin antibodies for coeliac disease screening.

[Relevance of anti-nucleosome antibodies detected by enzyme-based immunoassays in lupus diagnosis. Comparative analysis of four commercial kits]. / Intérêt de la recherche des anticorps antinucléosome par technique ELISA dans le diagnostic de la maladie lupique. Etude comparative de quatre coffrets commerciaux.

Among the biological assays used for the diagnosis of systemic lupus erythematosus (SLE), the detection of anti-double strand DNA antibodies (dsDNA Ab) is regarded as highly specific. However this biological parameter is negative among 20 to 40% of patients. Recent studies have revealed potential interest of the anti-nucleosome antibodies in the diagnosis of the lupus, in particular when any anti-dsDNA antibody activity could be detected. We selected 80 sera in order to evaluate four commercial anti-nucleosome enzyme-based immunoassays (EIA) kits. Their sensitivity and specificity values were compared with those obtained by the detection of anti-dsDNA Ab, carried out with both a Farr assay and two EIA kits. No anti-nucleosome EIA kits reached performances of the Farr assay for the diagnosis of lupus. On the other hand, our results show an higher diagnostic value for some anti-nucleosome EIA kits compared with 2 anti-dsDNA EIA kits. Apart from SLE, anti-nucleosome antibodies can be observed in others auto-immune diseases, in particular Sjögren's syndromes, the primary antiphospholipid syndrome, the systemic sclerosis and the mixed connective tissue disease. Compared results of the four anti-nucleosome EIA kits highlight many discordances. These variations, testifying to the absence of standardization for this new parameter, must encourage with a careful interpretation of results, according to the clinical context.

[Anesthetic management for delivery of an abdominal pregnancy]. / Prise en charge anesthésique pour accouchement d'une grossesse abdominale.

We report the anaesthetic management of an abdominal pregnancy. The delivery was obtained by laparotomy, under general anaesthesia, by a multi-specialist team. Abdominal pregnancy carries a high foetal and maternal risk for morbidity and lethal outcome. The main complication is sudden haemorrhage which can occur at any time.

[Postoperative management. Critical care in intra-abdominal infection after surgical intervention]. / Prise en charge post-opératoire. Réanimation des sepsis intra-abdominaux après intervention chirurgicale.

UNDERESTIMATED FREQUENCY: Post-operative intraabdominal infections usually appear as abscesses or injury of the bowel, either alone or in combination. These complications of frequently underestimated frequency are characterized by high mortality. Improvement of their prognosis is obtained by early recognition of the complication and a multidisciplinary approach. ALARM SIGNS: In a patient who recently underwent abdominal surgery, the onset of abnormal signs must be considered as an alarm which imposes ruling out intraabdominal complications. Unexplained multiple organ failure or septic shock in the post-operative period of intraabdominal surgery must lead to considering explorative laparotomy. THERAPEUTICS: Etiologic treatment must be ideal and total from the first reoperation. Antibiotic therapy administered from the surgical reoperation must be different from previous treatments. This treatment is aimed at eradicating enterobacteriaceae, non-fermenting Gram negative aerobes, Gram positive cocci, anaerobes and fungi.