Familial Mediterranean fever--a not so unusual cause of abdominal pain

Familial Mediterranean fever is a hereditary syndrome characterised by recurrent episodes of fever and serositis, resulting in pain in the abdomen, chest, joints and muscles. It is primarily diagnosed in people of Jewish, Arabic, Turkish or Armenian ancestry and is caused by mutations in the gene encoding for pyrin. Abdominal FMF attacks resemble the clinical presentation of 'acute abdomen', with severe abdominal pain and rigidity, but in FMF symptoms always resolve spontaneously. It is important to distinguish these regular pain episodes from small bowel obstruction due to adhesions to prevent life-threatening bowel strangulation. In most cases, colchicine will prevent new painful attacks. This seminar also discusses other causes of abdominal pain in FMF patients.     

A study in three European IBD cohorts confirms that the ATG16L1 c.898A > G (p.Thr300Ala) variant is a susceptibility factor for Crohn’s disease

Background and aimsA recent study reported that a nonsynonymous SNP rs2241880 (c.898A > G, p.Thr300Ala) within ATG16L1 confers susceptibility to Crohn's disease (CD). We analyzed ATG16L1 c.898A > G in three independent European inflammatory bowel disease (IBD) cohorts from Germany, Hungary and the Netherlands.MethodsIn total, we included 910 European IBD patients and compared the ATG16L1 c.898A > G genotype frequency with 707 ethnically matched healthy controls. We included patients from 3 populations originating from Germany (CD n = 310; ulcerative colitis [UC] n = 179), Hungary (CD n = 147; UC n = 117), and the Netherlands (CD n = 157). Subtyping analysis was performed in respect to CARD15 alterations and clinical characteristics.ResultsWe found a highly significant association of c.898A > G to CD. The association was significant (p = 0.0005) for the total CD cohort but also for the individual populations from Germany (p = 0.02) and Netherlands (p = 0.02) whereas in the Hungarian CD patients a clear trend was observed (p = 0.19; OR 1.227, 95% CI 0.910; 1.654). No association was found between c.898A > G and UC. No statistical interactions were observed between ATG16L1 c.898A > G and CARD15 variants. Furthermore no association to a CD subphenotype was detected.ConclusionsWe confirm that ATG16L1 variant c898A > G confers a risk variant for CD but is not associated with a distinct CD phenotype.     

Chronic yersiniosis due to defects in the TLR5 and NOD2 recognition pathways

Infection with Yersinia enterocolitica leads to a self-limiting disease, but in a small number of cases a protracted course can develop. The host genetic factors contributing to the advancement of the disease to the chronic phase are not known. We describe a patient suffering from an abdominal inflammatory mass due to chronic yersiniosis. Functional assays revealed defects in the recognition of flagellin by Toll-like receptor 5 (TLR5) and of muramyl dipeptide by NOD2, leading to a defective inflammatory response to Yersinia enterocolitica. Genetic sequencing showed that the patient was compound heterozygous for five different mutations in TLR5, while being homozygous for the 3020insC NOD2 mutation. In conclusion, we describe a patient in whom specific defects in the TLR5 and NOD2 recognition pathways led to chronic yersiniosis.     

Training innovations in gastroenterology and educational resources: a new vision of gastrointestinal education across Europe

To define a new educational strategy for the United European Gastroenterology Federation (UEGF) to be followed and implemented in the near future. UEGF organized a consensus-based strategy meeting with stakeholders and key decision makers in European Gastroenterology on Training Innovations in Gastroenterology and Educational Resources. In May 2010, in an 'open-face conference' at Starnberg, Germany, 59 specialists in gastroenterology, hepatology, and related fields from 15 countries and 16 societies participated. Breakout sessions identified the key problem areas, possible solutions, and formulated statements subsequently voted upon in plenum. A majority of the formulated statements (59%) reached a strong agreement. Topics in which UEGF should focus are the future educational activities that include developing ways to advocate multidisciplinarity and integration between levels of care and specialties, ways to improve quality of care, and the development of training tools. The successful outcome of the Training Innovations in Gastroenterology and Educational Resources conference was achieved with the production of a strategy layout for new UEGF educational activities. There was an agreement that improvement in topics related to multidisciplinarity and professionalism, which is crucial for further development. An open-face conference, such as that embodied by the Training Innovations in Gastroenterology and Educational Resources meeting, was shown to be an effective tool in identifying the key problem areas in education and in formulating new strategies.     

Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome

Hereditary periodic fever syndromes are characterized by incapacitating attacks of fever and generalized inflammation. While the mutated genes for the major syndromes in this group are known, the pathogenesis remains unclear. The aim of this study was to investigate apoptosis in patients with periodic fever as a possible pathogenic factor. We measured anisomycin-induced apoptosis with annexin-V flow cytometry and caspase-3/7 activity in peripheral-blood lymphocytes from symptom-free patients with hyper-IgD and periodic fever syndrome (HIDS; n = 10), TNF-receptor-associated periodic syndrome (TRAPS; n = 7), and familial Mediterranean fever (FMF; n = 2). HIDS lymphocytes showed a decreased percentage of apoptosis during remission by both methods compared with controls (17.8% vs 55.4%), whereas no difference was observed in TRAPS or FMF lymphocytes. This defective apoptosis of lymphocytes may be a central pathogenic mechanism in HIDS, since dysfunction of one of the inhibitory mechanisms to curtail the immunologic response could cause an unbridled generalized inflammation after a trivial stimulus.     

Polycystic liver: clinical characteristics of patients with isolated polycystic liver disease compared with patients with polycystic liver and autosomal dominant polycystic kidney disease

Aim: The goal of this study was to compare the clinical features of patients with isolated polycystic liver disease (PCLD) with those of patients with polycystic liver and autosomal dominant polycystic kidney disease (ADPKD). Methods: Cases were identified from clinical records at the University of Colorado Hospital in Denver (USA) and at the Radboud University Hospital in Nijmegen (the Netherlands) by ICD‐10 codes. To be included in this analysis, patients had to have an initial diagnosis of PCLD within six years of presentation to our clinics. Medical records were reviewed for demographic information, medical history, physical examination, symptoms, complications, laboratory and imaging results, therapy and outcomes. Results: Out of a total of 94, 53 patients met our criteria for entering this study, 19 with PCLD and 34 with ADPKD. The mean time interval from diagnosis of PCLD to presentation in our clinics was 1.21 years for PCLD and 2.76 years for ADPKD (P=NS). PCLD was associated with female gender in both PCLD and ADPKD. Patients with PCLD had greater numbers (P=0.031), and larger sizes of liver cysts (P=0.0051), but had less associated morbidities than patients with ADPKD. Liver cyst decompressions were performed more frequently in PCLD patients (57.9 vs. 23.5%, P=0.012). However, serious hepatic complications, sufficient to require consideration of liver transplantation, were more frequent in patients with ADPKD (0/19 vs. 6/34, P<0.0001). Conclusions: Although PCLD in patients with PCLD is characterized by larger and greater number of hepatic cysts, the clinical course is relatively benign compared with ADPKD.     

Dysregulation of innate immunity: hereditary periodic fever syndromes

The hereditary periodic fever syndromes encompass a rare group of diseases that have lifelong recurrent episodes of inflammatory symptoms and an acute phase response in common. Clinical presentation can mimic that of lymphoproliferative disorders and patients often go undiagnosed for many years. These syndromes follow an autosomal inheritance pattern, and the major syndromes are linked to specific genes, most of which are involved in regulation of the innate immune response through pathways of apoptosis, nuclear factor κΒ activation and cytokine production. In others, the link between the protein involved and inflammation is less clear. The recurrent inflammation can lead to complications, such as renal impairment due to amyloidosis and vasculitis, visual impairment, hearing loss, and joint destruction, depending on the specific syndrome. In recent years, treatment options for these diseases have improved significantly. Early establishment of an accurate diagnosis and start of appropriate therapy improves prognosis in these patients.     

Recurrent idiopathic pancreatitis in familial adenomatous polyposis: Report of a case-series and review of the literature

Familial adenomatous polyposis (FAP) is characterized by the development of multiple adenomatous polyps predominantly in the colon but also in the duodenum. Scattered case reports indicate that there is a risk for pancreatitis in FAP. The most likely cause of pancreatitis in FAP is obstructing ampullary adenomas. We describe 7 FAP patients who experienced one or more episodes of pancreatitis. Two patients experienced pancreatitis after endoscopic treatment of ampullary adenoma. The cause of the pancreatitis in 5 of 7 patients could not be determined, as none of the patients had obstruction of the ampulla. Furthermore, other risk factors for pancreatitis such as pancreatic serine protease inhibitor Kazal type I (SPINK1) gene mutations were ruled out. A review of literature identified 20 FAP patients who developed the first episode of pancreatitis at a mean age of 45 years (range 23–72 years). Some 55% had recurrent episodes of pancreatitis. Eight patients had (peri) ampullary adenomas or carcinomas. In most cases, the course of pancreatitis was mild with an uneventful outcome, but one patient died after an episode of acute pancreatitis. Grant support: Joost P.H. Drenth is a recipient of a NWO-VIDI grant