Joachim J. Schweizer

European multi-centre study on coeliac disease and non-Hodgkin lymphoma.

Introduction Coeliac disease (CD) is associated with an increased risk of non-Hodgkin lymphoma (NHL), but there is little information about whether this is true for clinically silent CD. Objective To investigate the frequency of CD in two European populations; one with NHL and another derived from the general population. Methods A prospective, multi-centre, case–control study in 10 European countries was conducted between May 1998 and April 2001. A total of 1446 consecutive patients with newly diagnosed NHLaged over 18 years was collected. The control group consisted of a population of 9676 individuals who were screened for CD. The number of patients with a previous diagnosis of CD and those with silent CD detected by screening were determined in the two groups. Results The patients with CD had a significantly increased risk of developing NHL [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4–4.9]. This risk was only present in patients with CD diagnosed clinically before the study (OR 3.3, 95% CI 1.4–7.9), but not in those with silent CD detected by screening (OR 1.3, 95% CI 0.6–2.7). Conclusion Patients with CD have an increased risk of developing NHL, although this is lower than previously thought. Clinically silent CD is rare in patients with NHL.

T-cell receptor recognition of HLA-DQ2-gliadin complexes associated with celiac disease

Celiac disease is a T cell–mediated disease induced by dietary gluten, a component of which is gliadin. 95% of individuals with celiac disease carry the HLA (human leukocyte antigen)-DQ2 locus. Here we determined the T-cell receptor (TCR) usage and fine specificity of patient-derived T-cell clones specific for two epitopes from wheat gliadin, DQ2.5-glia-α1a and DQ2.5-glia-α2. We determined the ternary structures of four distinct biased TCRs specific for those epitopes. All three TCRs specific for DQ2.5-glia-α2 docked centrally above HLA-DQ2, which together with mutagenesis and affinity measurements provided a basis for the biased TCR usage. A non–germline encoded arginine residue within the CDR3β loop acted as the lynchpin within this common docking footprint. Although the TCRs specific for DQ2.5-glia-α1a and DQ2.5-glia-α2 docked similarly, their interactions with the respective gliadin determinants differed markedly, thereby providing a basis for epitope specificity.

Cancer in children with celiac disease : A survey of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition

Background In adults, the relation between celiac disease (CD) and cancer has been long recognized. In children, only four cases of CD and cancer have been described in Europe. We made a new inventory of cases with CD and cancer in children that were known by the members of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition between 1989 and 1999. Methods Postal inquiry was made of all European Society for Paediatric Gastroenterology, Hepatology and Nutrition members mentioned on the societys web page. The members were asked if they had seen a child with CD and cancer between 1989 and 1999 and if so, to supply additional clinical data. Also, information on working place, experience, and number of celiac patients under their care was requested. Results Fifty-six percent of the members responded. Sixteen members reported 22 cases of cancer and CD in children. One case had been reported in the literature previously. The tumors that were reported originated from the brain, thyroid, larynx, liver, small bowel, adrenal, lymphoreticular system, and the musculoskeletal system. There were no differences between members reporting a case and those who did not. Conclusions Twenty-one new cases of cancer and CD in children in Europe were found. Cancer and CD in children are underreported. A remarkable number of thyroid and small bowel cancers were found, suggesting a possible relation with CD. It is important to evaluate whether these findings are coincidental. All cases of cancer and CD in children should be reported to the literature.

Recurrent abdominal pain in 200 children: Somatic causes and diagnostic criteria

Aim:  To establish to what extent somatic causes can be found in children referred to secondary care with recurrent abdominal pain.

Coeliac disease and gluten-related disorders in childhood

Gluten-related disorders such as coeliac disease, wheat allergy and noncoeliac gluten sensitivity are increasingly being diagnosed in children. Coeliac disease occurs frequently, affecting 1–3% of the Western population. The condition manifests at a very young age, more so in girls, and is related to the HLA genotype. Coeliac disease might be considered a public health problem and, as primary prevention is not possible, the debate on mass screening should be reopened. Wheat proteins, including gluten, are responsible for one of the most common food allergies in children: wheat allergy. Unlike coeliac disease and wheat allergy, noncoeliac gluten sensitivity is an unclear and controversial entity. These three gluten-related disorders are treated with a gluten-free diet. In coeliac disease, the diet should be strictly followed, whereas wheat allergy only requires wheat elimination and in noncoeliac gluten sensitivity occasional trials of gluten reintroduction can be done. A good diagnostic work-up is important for gluten-related disorders in childhood to avoid unnecessary restrictive diets in children. In this Review, we provide an overview of the pathogenesis, diagnosis and management of the most common gluten-related disorders in children.

Validation of the Rome III criteria and alarm symptoms for recurrent abdominal pain in children

Objectives: Rome criteria were formulated to define functional gastrointestinal disorders (Rome III criteria, 2006) excluding organic diagnoses when alarm symptoms were absent. The aims of the study were to validate the Rome III criteria as to their capacity to differentiate between organic and functional abdominal pain and to assess the role of alarm symptoms in this differentiation. Methods: During 2 years all of the patients (ages 4–16 years) presenting with recurrent abdominal pain (Apley criteria) and referred to secondary care were included. Clinical diagnoses were based on protocolized evaluation and intervention with 6-month follow-up. Alarm symptoms were registered. Rome III criteria for functional pain syndromes were assigned independently. Descriptive statistical analyses were performed. Results: In 200 patients (87 boys, mean age 8.8 years), organic (17%), functional (40%), combined organic and functional (9%), spontaneous recovery (27%), and other (8%) clinical diagnoses were established. Alarm symptoms were found in 57.5% (organic causes 56%, functional causes 61%). The evaluation for Rome symptom clusters revealed symptoms of irritable bowel syndrome in 27%, functional dyspepsia in 15%, functional abdominal pain in 28%, functional abdominal pain syndrome in 14.5%, and no pain syndrome in 15.5%. Rome diagnoses, based on symptoms and absence of alarm symptoms, predicted functional clinical diagnosis with sensitivity 0.35 (95% confidence interval 0.27–0.43), specificity 0.60 (0.46–0.73), positive predictive value 0.71 (0.61–0.82), and negative predictive value of 0.24 (0.17–0.32). Conclusions: The Rome III criteria for abdominal pain are not specific enough to rule out organic causes. Alarm symptoms do not differentiate between organic and functional abdominal pain.

Protozoa as a cause of recurrent abdominal pain in children

Objectives: The aim of this study was to investigate whether protozoa can be identified as a cause of recurrent abdominal pain (RAP), and whether protozoan infections can be recognized by a specific clinical presentation. Methods: For 2 years, all patients (ages 4–16 years) fulfilling the Apley criteria of RAP referred to secondary care were prospectively evaluated for protozoa (Giardia lamblia, Dientamoeba fragilis, Blastocystis hominis) and treated if positive. Re-examination followed at least 10 days after treatment. Disappearance of pain with eradication and a pain-free follow-up of at least 6 months were considered to be indicative of a causal relation with RAP. The predictive value of the characteristics of the pain for protozoan infections was calculated. Results: Of 220 included patients (92 boys, mean age 8.8 years), 215 brought a stool sample; 73 (34%) carried parasites, 10 of whom had 2 parasites, 2 had 3 parasites. Sixty-five patients were treated. Twenty-five (11%) were pain-free after eradication (21 had D fragilis, 8 B hominis, 4 G lamblia), of whom 11 had another infection (2) or constipation (9) as second diagnosis for the pain. Five had recurrence of infection with D fragilis and were again pain-free with eradication. Patients with protozoa as cause of their pain did not show differences with respect to their presentation when compared with patients with an asymptomatic infection and patients without protozoa. Conclusions: Protozoa were found as the cause of pain in 6% to 11% of children with RAP. These patients did not show a characteristic presentation when compared with patients with other causes of abdominal pain.

A toddler with recurrent oral and genital ulcers

In western countries, when a child presents with recurrent oral ulcers and colitis, the diagnosis of Crohn’s disease is mostly made. In our patient, the diagnosis was Behçet’s disease with gastrointestinal manifestations. Behçet’s disease with gastrointestinal manifestations has a similar clinical presentation to Crohn’s disease, but there is more organ involvement and the prognosis is more severe in the former. Because there is limited experience in the treatment of Behçet’s disease in the paediatric population, successful and unsuccessful treatment modalities in both paediatric and adult populations should be reported.

Coeliac Disease in Subfertile Couples in the Netherlands

Background: Subfertility has been assumed as a long-term complication of unrecognized and/or untreated coeliac disease (CD). No data exist on the association between subfertility and CD in The Netherlands. Aims: To determine; 1.) the prevalence of (un)recognized CD in subfertile male-female couples in the Netherlands; 2.) if routine antibody screening for CD should be performed in patients visiting a fertility clinic. Methods: Subjects included 1038 male-female couples (n=2076) who visited the fertility clinic of the Leiden University Medical Centre in the Netherlands, between 2003-2009. All patients were serological screened, and unrecognized CD was defined in cases with simultaneous positive test results for antibodies against anti-tissue transglutaminase and endomysium. Clinical data was collected; gender, age, height, weight and diagnosis of subfertility. All patients were anonymized. The prevalence of unrecognised CD was compared to the one in the general adult population in the Netherlands (0.35%) (1) Results: The prevalence of unrecognized CD in subfertile male-female couples was 0.48% (10/2076), 0.3% female and 0.4% male (p=NS). In 1.5% of the women with an ovulation disorder CD was diagnosed (p=0.04). Compared to the control group, similar CD prevalences were found within the other subfertility categories unexplained subfertility, tuba pathology and androgenic disorder (p=NS). Conclusion: In our well-powered study cohort of subfertile male-female couples, the prevalence of unrecognized CD is comparable to the general population in the Netherlands. Unrecognized CD was 5 times more often detected in women with ovulation disorder compared to the control group, which suggest a possible association between CD and subfertility in females. No association was found in subfertile men and couples with unexplained subfertility. We would suggest performing serological screening for CD in females who are visiting the fertility clinic in the Netherlands.