Therapeutic preferences and outcomes in newly diagnosed patients with Crohn’s diseases in the biological era in Hungary: a nationwide study based on the National Health Insurance Fund database

Abstract Background Accelerated treatment strategy, including tight disease control and early aggressive therapy with immunosuppressives (IS) and biological agents have become increasingly common in inflammatory bowel disease (IBD). The aim of the present study was to estimate the early treatment strategy and outcomes in newly diagnosed patients with Crohn’s disease (CD) between 2004 and 2008 and 2009–2015 in the whole IBD population in Hungary based on the administrative database of the National Health Insurance Fund (OEP). Methods We used the administrative database of the OEP, the only nationwide state-owned health insurance provider in Hungary. Patients were identified through previously reported algorithms using the ICD-10 codes for CD in the out-, inpatient (medical, surgical) non-primary care records and drug prescription databases between 2004 and 2015. Patients were stratified according to the year of diagnosis and maximum treatment steps during the first 3 years after diagnosis. Results A total of 6173 (male/female: 46.12%/53.87%) newly diagnosed CD patients with physician-diagnosed IBD were found in the period of 2004–2015. The use of 5-ASA and steroids remained common in the biological era, while immunosuppressives and biologicals were started earlier and became more frequent among patients diagnosed after 2009. The probability of biological therapy was 2.9%/6.4% and 8.4%/13.7% after 1 and 3 years in patients diagnosed in 2004–2008/2009–2015. The probability of hospitalization in the first 3 years after diagnosis was different before and after 2009, according to the maximal treatment step (overall 55.7%vs. 47.4% (p = 0.001), anti-TNF: 73%vs. 66.7% (p = 0.103), IS: 64.6% vs. 56.1% (p = 0.001), steroid: 44.2%vs. 36.8% (p < 0.007), 5-ASA: 32.6% vs. 26.7% p = 0.157)). In contrast, surgery rates were not significantly different in patients diagnosed before and after 2009 according to the maximum treatment step (overall 16.0%vs.15.3%(p = 0.672) anti-TNF 26.7%vs.27.2% (p = 0.993), IS: 24.1%vs22.2% (p = 0.565), steroid 8.1%vs.7.9% (p = 0.896), 5-ASA 10%vs. 11% (p = 0.816)). Conclusions IS and biological exposure became more frequent, while hospitalization decreased and surgery remained low but constant during the observation period. Use of steroids and 5-ASA remained high after 2009. The association between the maximal treatment step and hospitalization/surgery rates suggests that maximal treatment step can be regarded as proxy severity marker in patients with IBD

High Prevalence of Silent Celiac Disease in Preschool Children Screened with IgA/IgG Antiendomysium Antibodies

Background: Because of the different sensitivity and specificity of serologic tests, the search for silent celiac disease is usually performed with the combined or sequential use of several tests. Among these, the IgA-class endomysium antibody test has the highest specificity and positive predictive value, but it may overlook IgA-deficient patients. Methods: To test a new one-step screening approach, serum samples from 427 apparently healthy, 3- to 6-year-old Hungarian children were investigated for IEA-class and IgG-class endomysium antibodies using monkey esophagus and human jejunum as substrates. Results: Five new cases with flat mucosa were identified by strong endomysium antibody positivity and subsequent jejunal biopsy, yielding a celiac disease prevalence of 1:85. An additional child may have latent celiac disease (slight histologic changes at present). Two of the screening-detected celiac patients exhibited only IgG-class endomysium antibodies due to associated IgA-deficiency. Despite the young age of the screened population, antigliadin antibodies were positive in only three of the five celiac patients. Conclusions: Prevalence of celiac disease in the study population was much higher than expected on the basis of antigliadin antibody-based studies. The screening system used detected celiac cases in which there was IgA-deficiency and those in which there was not and also those negative for antigliadin antibodies. The findings suggest the importance of the primary testing of autoantibodies in future celiac disease screening policies

Diagnostic significance of HLA-DQ typing in patients with previous coeliac disease diagnosis based on histology alone

Background Coeliac disease is strongly associated with human leukocyte antigen (HLA)-DQ2 or DQ8 genotypes. The diagnosis is based on demonstrating crypt-hyperplastic villous atrophy, endomysial or transglutaminase antibodies and correlation of disease activity with gluten intake. Aim To evaluate the clinical utility of HLA-DQ typing, when coeliac disease diagnosis had previously been established solely by histology. Methods HLA-DQ alleles, endomysial and transglutaminase antibodies were investigated and histology slides reviewed in 70 patients diagnosed 2-25 years earlier by small-intestinal biopsy but without measuring endomysial or transglutaminase antibodies. Patients without DQ2 or DQ8 or without unequivocal villous atrophy were followed-up on free diet by using serology and biopsies. Results All 40 endomysial/transglutaminase antibodies positive patients carried DQ2 or DQ8, and 39 of them had severe villous atrophy. Only 56% of patients without endomysial or transglutaminase antibodies positivity had DQ2 or DQ8 (P < 0.001). Seropositivity and relapse developed in 4 of 11 DQ2 positive but in none of 15 DQ2 and DQ8 negative patients on long-term gluten exposure. Conclusions Coeliac disease diagnosis based solely on histology is not always reliable. HLA-DQ typing is important in identifying DQ2 and DQ8 negative subjects who need revision of their diagnosis, but it does not have additive diagnostic value if endomysial positivity is already known