Dynamics of occurrence of refractory coeliac disease and associated complications over 25 years.

BACKGROUND: Refractory coeliac disease, enteropathy associated T-cell lymphoma and small bowel adenocarcinoma are rare but prognostically important complications in coeliac disease. AIM: To analyse potential changes in occurrence of complicated coeliac disease over the last 25 years. METHODS: One thousand one hundred and thirty eight patients were included and evaluated based on their time of first presentation at the Medical University of Vienna, Austria. Occurrences of refractory coeliac disease and associated malignancies were evaluated for 5-year intervals from January 1990 until December 2014 and were compared over time. RESULTS: 2.6% (n = 29) were diagnosed with refractory coeliac disease (females 65.6%, mean age at diagnosis 62.8 years). The proportion of those patients was 2.6%, 3.1%, 3.3%, 2.7% and 0.5% for the 5 year intervals from 1990 onwards. Thus, the number of refractory cases has been decreasing since 2000 (P = 0.024). The number of patients presenting with lymphoma (n = 7) was 0.6%, 0.4%, 1.1%, 0.8% and 0% from 1990 to 2014. Similarly the number of patients with adenocarcinoma (n = 4) decreased to 0% until 2014. Overall mortality in patients suffering from refractory disease was 48%. Of all patients diagnosed with lymphoma 71.4% died with a 5-year survival rate of 28.6%. CONCLUSIONS: Over the past 15 years the occurrence of complicated coeliac disease has been decreasing. This possibly reflects a higher awareness of coeliac disease and optimised diagnosis and treatment with avoidance of long-term immunological disease activity. Symptomatic disease and a delay in diagnosis are risk factors for refractory coeliac disease and related cancer.

Intraductal papillary mucinous neoplasm of the pancreas in an adult patient with cystic fibrosis after double-lung transplantation.

We report on an adult patient with cystic fibrosis after double-lung transplantation under triple immunosuppression with non-specific abdominal symptoms and a pancreatic cystic tumor, resulting in the diagnosis of an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Pancreatic cysts in adult patients with cystic fibrosis, especially after transplantation, merit close attention and thorough investigation.

[Colorectal cancer: screening and surveillance in inflammatory bowel diseases - consensus of the working group for inflammatory bowel diseases of the Austrian Society of Gastroenterology and Hepatology]. / Kolorektales Karzinom: Screening und Surveillance bei chronisch entzündlichen Darmerkrankungen - Konsensus der Arbeitsgruppe für chronisch entzündliche Darmerkrankungen der ÖGGH.

Patients with ulcerative colitis and Crohn's colitis are at increased risk of colorectal cancer (CRC). This risk is dependent on the duration and extent of disease, inflammatory activity and possible additional risk factors. Thus, the aim is to reduce this risk and to detect dysplastic and malignant lesions at an early stage. The working group for Inflammatory Bowel Diseases (IBD) of the Austrian Society of Gastroenterology and Hepatology (ÖGGH) has developed consensus statements on the following topics: risk of colorectal cancer, screening and surveillance, procedure of surveillance colonoscopy, dysplasia and its management, and chemoprevention. This consensus is intended to increase awareness of the increased risk of CRC in IBD and to support a standardised approach in cancer prevention.

Retesting for latent tuberculosis in patients with inflammatory bowel disease treated with TNF-α inhibitors.

BACKGROUND: Patients treated with TNF-α inhibitors (TNFi) are at high risk of reactivation of latent tuberculosis (LTB). Prospective studies on monitoring of TB reactivation and/or infection in this risk group are lacking. AIM: To test the conversion and reversion rate of screening tests for latent TB serial tuberculin skin test (TST) and interferon-γ release assay (IGRA) under ongoing TNFi therapy. METHODS: We retested consecutive patients with IBD receiving TNFi therapy for a minimum of 5 months for LTB using IGRA and TST. A detailed patient history and concomitant therapy were recorded for each subject. RESULTS: After a median of 34.9 weeks (20.7­177.7), IGRA was retested in 184/227 patients (81.1%; Crohn's disease n = 139, ulcerative colitis n = 45) still under index TNFi. TST was available in 144/184 subjects (78.2%). The majority of patients were TNFi naïve (147/184, 79.9%). In a subgroup of patients who received isoniazid due to diagnosis of latent TB at baseline (n = 32), 6/13 patients (46.2%) with baseline positive IGRA and 3/22 patients (13.6%) with baseline positive TST reverted to negative at retesting. In patients without diagnosis of LTB at baseline no permanent IGRA conversion was observed, but there were 6/144 (4.2%) TST conversions from negative to positive. No single case of TB reactivation or infection was recorded during the observation period. CONCLUSIONS: During treatment TNF-α inhibitors conversion was observed for tuberculin skin test, but not interferon-γ release assay. As compared with tuberculin skin test, interferon-γ release assay reverted in nearly half of isoniazid-treated patients for latent tuberculosis. However, the fact that patients in whom the interferon-γ release assay test result remained positive did not develop active tuberculosis during follow-up questions the utility of interferon-γ release assay as a monitoring tool during chemoprevention.

Patients suffering from non-IgE-mediated cow's milk protein intolerance cannot be diagnosed based on IgG subclass or IgA responses to milk allergens.

BACKGROUND: Cow's milk is one of the most common causes of food allergy. In two-thirds of patients, adverse symptoms following milk ingestion are caused by IgE-mediated allergic reactions, whereas for one-third, the mechanisms are unknown. Aim of this study was to investigate whether patients suffering from non-IgE-mediated cow's milk protein intolerance can be distinguished from persons without cow's milk protein intolerance based on serological measurement of IgG and IgA specific for purified cow's milk antigens. METHODS: We determined IgG(1-4) subclass and IgA antibody levels to purified recombinant αS1-casein, αS2-casein, ß-casein, κ-casein, α-lactalbumin, and ß-lactoglobulin in four patient groups by ELISA: Patients with IgE-mediated cow's milk allergy (CMA, n=25), patients with non-IgE-mediated cow's milk protein intolerance (CMPI, n=19), patients with gastrointestinal symptoms not associated with cow's milk ingestion (GI, n=15) and control persons without gastrointestinal problems (C, n=26). Cow's milk-specific IgE levels were determined by ImmunoCAP. RESULTS: Only CMA patients had IgE antibodies to cow's milk. Cow's milk allergic patients mounted the highest IgG(1) and IgG(4) antibody levels to αS1-casein, αS2-casein, ß-casein, κ-casein, and α-lactalbumin. No elevated levels of IgG(4) , IgA, and complement-binding IgG subclasses (IgG(1) , IgG(2) , IgG(3) ) to purified cow's milk allergens were found within the CMPI patients compared to persons without cow's milk protein intolerance (GI and C groups). CONCLUSION: Cow's milk protein intolerant patients cannot be distinguished from persons without cow's milk protein intolerance on the basis of IgG subclass or IgA reactivity to cow's milk allergens.

IgA autoreactivity: a feature common to inflammatory bowel and connective tissue diseases.

The immunopathogenic mechanisms in inflammatory bowel disease (IBD) are not yet fully established. The aim of this study was to determine the profile and magnitude of IgA and IgG autoantibodies in IBD patients. The autoantigen profile defined by IgA and IgG antibodies from 24 IBD (14 Crohn's disease CD], 10 ulcerative colitis UC]), three coeliac, 12 connective tissue disease (CTD) patients and 10 healthy individuals was studied in human cellular extracts by Western blotting. The magnitude of the IgA and IgG1-4 subclass responses was measured by ELISA. IBD patients could not be distinguished from healthy individuals on the basis of IgG autoantibodies to Western blotted proteins. IgG subclass analysis indicated no clear bias towards Th1 or Th2 immune responses in IBD or CTD. In accordance with previous work, we found that IgA autoreactivity was strongest in coeliac disease patients. Unexpectedly, IBD as well as CTD patients exhibited strong IgA autoantibody reactivities to components of similar molecular weights (16-80 kD) in intestinal and non-intestinal epithelial cell lines. Our data indicate immunopathogenic similarities between IBD and CTD.

Hepatitis B virus DNA in sera and liver tissue of HBsAg negative patients with chronic hepatitis C.

BACKGROUND/AIMS: Hepatitis B virus (HBV) DNA has been detected in HBsAg-negative patients with hepatitis C. We determined the rate and explored the clinical significance of HBsAg negative HBV coinfections in Austrian patients with chronic hepatitis C. METHODS: Sera (n=82, group I) or liver tissue (n=16, group II) from 98 HBsAg negative Austrian patients with chronic hepatitis C were examined for HBV DNA by nested polymerase chain reaction (PCR). For control purposes, sera from 15 patients with chronic HBV infection (8 HBsAg positive, 7 HBsAg negative, all HBV PCR positive) were examined. RESULTS: HBV DNA was detected in 22% of sera and 19% of liver tissue specimens of patients with chronic hepatitis C. No significant difference in mean aminotransferase values, markers of HBV infection, inflammatory disease activity, or degree of hepatic fibrosis was observed in patients with or without HBV DNA. Anti-HBc alone as a marker of past HBV infection was more frequent in chronic hepatitis C patients compared to control individuals. Negative HCV PCR was more common (p=0.009) among patients with positive HBV PCR in serum. When examining repeat sera for HBV DNA, positive results were obtained in previously negative, but also negative results in previously positive patients. CONCLUSIONS: Coinfection with HBV can be demonstrated by PCR in a considerable number of HBsAg negative Austrian patients with chronic hepatitis C. HBV infection seems to suppress HCV replication even in HBsAg negative patients with dual infection. HBV coinfection in HCV infected patients cannot be excluded by negative HBsAg status alone. Repeat PCR examinations are needed to exclude dual infections.

Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy.

BACKGROUND: Type I allergic symptoms in the oropharyngeal mucosa upon contact with plant-derived food in patients with pollen allergies have been termed oral allergy syndrome (OAS). IgE cross-reactivity between pollen and food allergens represents the molecular basis for this phenomenon. The sensitizing allergen source (pollen or plant food) in OAS is a controversial issue. OBJECTIVE: We sought to determine the primary sensitizing molecules in patients with OAS. METHODS: We used recombinant birch pollen (rBet v 1 and rBet v 2) and plant food allergens (apple, rMal d 1; celery, rApi g 1; and carrot, rDau c 1), as well as natural pollen (birch and timothy grass) and plant food (apple, peach, kiwi, hazelnut, celery, and carrot) allergens, to identify cross-reactive allergens by using qualitative immunoblot inhibitions. In addition, we determined the percentage of plant food-specific IgE that can be preadsorbed with recombinant and natural pollen allergens by quantitative RAST inhibitions by using sera from 71 patients with OAS. RESULTS: Preincubation of sera with recombinant and natural pollen allergens led to an almost complete inhibition of IgE binding to plant food allergens in Western blots, as well as in RAST inhibition experiments. In contrast, recombinant plant food allergens poorly inhibited IgE binding to Bet v 1. CONCLUSION: Most IgE epitopes in plant food recognized by patients with OAS are resembled by pollen allergens. Thus pollen allergens may be responsible for the elicitation and maintenance of OAS.

The relation of iron status and hemochromatosis gene mutations in patients with chronic hepatitis C.

BACKGROUND & AIMS: Elevated hepatic iron concentration may affect the response to antiviral therapy in chronic hepatitis C. This study explored the contribution of genetic hemochromatosis to iron accumulation in chronic hepatitis C. METHODS: HFE mutations (C282Y and H63D) were assessed in 184 patients with chronic hepatitis C virus and 487 controls. Liver biopsy specimens were available in 149 patients. Hepatic iron content was measured in 114 patients by atom-absorption spectrophotometry. RESULTS: The C282Y and H63D allele frequencies were 7.06 and 11.6 in patients and 4.83 and 11.09 in controls, respectively. Eight patients were homozygotes (5 C282Y [2.7%] and 3 H63D [1.6%]), 2 compound heterozygotes (1%), and 49 heterozygotes (14 C282Y [7.6%] and 35 H63D [19%]). Biochemical evidence of iron overload was more common in patients with HFE mutations (28 of 47) than in those without (34 of 102; P = 0.0045). Histological iron grading and hepatic iron content overlapped among patients with or without mutations. A hepatic iron index of >1.9 was observed only in 1 of the 4 C282Y homozygotes and 1 of the 3 H63D homozygotes. CONCLUSIONS: HFE mutations contribute to but do not fully explain hepatic iron accumulation in chronic hepatitis C. Furthermore, C282Y or H63D homozygosity in chronic hepatitis C is not necessarily associated with a high hepatic iron content.