Rare cause of small bowel obstruction: diaphragm disease.

Diaphragm disease is a rare cause of small bowel obstruction, caused by circular fibrotic membranes resulting in a narrowed intestinal lumen. It is associated with prolonged non-steroidal anti-inflammatory drug use, and often requires surgical resection. We report the case of a man in his 50s presenting with recurrent anaemia and intermittent small bowel obstruction. Exploratory laparoscopy identified three distinct areas of congested, thickened and narrowed ileum. Symptoms resolved following small bowel resection. Histological examination found elongated mucosal folds with ulceration and submucosal fibrosis consistent with diaphragm disease. Common radiological findings include small bowel strictures and thickening, mucosal hyperenhancement, and small bowel dilatation. In this case, on retrospective review of the initial CT scan, it is possible to appreciate circumferential mural thickening correlating with the histological findings. This case highlights the importance of rigorous examination of CT imaging and the utility of exploratory laparoscopy in diagnosing diaphragm disease.

Cyclic vomiting syndrome in 28 patients: demographics, features and outcomes.

INTRODUCTION: Cyclic vomiting syndrome (CVS) is a condition characterized by recurrent, stereotyped, attacks of intense nausea and intractable vomiting with no identifiable cause. The diagnosis is made according to the Rome III criteria; however, the condition remains a heterogenous group of symptoms and few studies have analysed patient-reported features in detail. Tricyclic antidepressants may benefit some patients, but there are no data on the long-term outcomes of this condition. METHODS: This is a retrospective cohort study of all patients treated at two London teaching hospitals between 1994 and 2011. Information was obtained by means of inpatient case notes, clinic letters and telephone interviews using a standardized questionnaire. RESULTS: Twenty-eight patients were identified, 17 with adult-onset CVS and 11 with childhood-onset CVS. In the adult-onset CVS cohort, the average age of onset was 30 years; the prevalence of headache was 57.1% and anxiety/depression 21.7%. Vomiting attacks occurred on average 10 times a year with a mean duration of 55.3 h. In the childhood-onset CVS cohort, the average age of onset was 5 years and the prevalence of headaches was 44.4%. Vomiting attacks occurred on average 25.5 times a year with a mean duration of 54.5 h. During acute attacks, patients rated morphine-based medications as the most efficacious. Overall, 65.4% of our patients were not treated with long-term prophylactic medications and, of these, 42.1% felt that their symptoms had improved and 26.3% reported complete resolution. CONCLUSION: CVS is a debilitating illness with frequent attacks of prolonged duration. There is a high association with anxiety/depression as well as headaches. Antimigraine medication, ß-blockers and antiepileptic treatment may be successful at attenuating attacks; however, in this long-term study, the prognosis of patients not treated with these medications was also good. Overall, 61.9% of patients showed a gradual improvement in symptoms and 23.8% had complete resolution after a mean of 7 years.

The management of cyclic vomiting syndrome: a systematic review.

Cyclic vomiting syndrome (CVS) is a rare abnormality of the neuroendocrine system that affects 2% of children. It is a frequently missed diagnosis in the emergency department and may require a number of emergency department visits before the diagnosis is made. The objectives of this review are to identify the clinical features that suggest a diagnosis of CVS and to review the literature on its management. The MEDLINE and EMBASE databases were searched from January 1948 to October 2011 using the keywords 'Cyclic' or 'Vomiting'. Papers were excluded if they did not follow the consensus guidelines or if they were case reports. This review analysed 1093 cases of cyclic vomiting in 25 papers that fulfilled the inclusion criteria. All except one paper were retrospective studies. The size of these cohort studies ranged from three to 181 patients, with a mean patient size of 29. This review found that over 40% of patients have headaches/migraines, with associated anxiety and depression in ≈ 30% of cases. There is a family history of headaches/migraines in 38.9%, and this association was much stronger in the adult CVS cohort compared with the paediatric cohort. Compared with paediatric CVS, adults have a longer duration of attacks and they occur more frequently (5.9 vs. 3.4 days, 14.4 vs. 9.6 episodes/year). Limited data are available on the treatment of the acute phase of CVS, but in adults, sumatriptan has been shown to be effective. For prophylactic treatment, tricyclics are effective in both adult and paediatric CVS, with a clinical response in 75.5 and 67.6% of patients, respectively, in nonplacebo-controlled cohort studies. Furthermore, propranolol has been shown to be useful in children. CVS is an intractable illness with a major impact on the patient's quality of life. There is a long duration between the onset of symptoms and the diagnosis of the condition. There is a high association with headaches/migraines and anxiety/depression. The symptoms are more severe in adult-onset CVS. Tricyclic antidepressants have good efficacy in reducing the frequency/duration or the intensity of attacks. There is limited evidence on the acute management of CVS.

An algorithm for family screening for coeliac disease.

AIM: To assess the level of undiagnosed coeliac disease (CD) in relatives of patients affected by the condition. METHODS: We collected blood from 914 relatives of probands. We screened these individuals by ELISA for IgA and IgG tTG antibodies, confirming any positive IgA tTG results with an IgA EMA and looked for evidence of IgA deficiency in those who were IgG tTG positive alone, and performed IgG1 EMA in these individuals. We undertook HLA typing where positive screening was found, and this confirmed a strong prevalence of HLA-DQ2 in the coeliac population. Follow-up small intestinal biopsy was undertaken in cases with positive serological screening, wherever possible. RESULTS: Use of this serological screening algorithm revealed a prevalence of undiagnosed CD in 5%-6% of first degree relatives of probands. CONCLUSION: Our data suggests that first degree relatives of individuals with CD should be screened for this condition.

Transition of care between paediatric and adult gastroenterology. Coeliac disease.

Coeliac disease is a condition in which there is an abnormal mucosa in the small intestine. It improves with a gluten free diet, with avoidance of wheat, rye, barley and possibly oats. The history and epidemiology of this condition are discussed. Diagnosis is based on demonstrating that the characteristic histological abnormalities in the small intestine are dependent on gluten ingestion. Diagnostic pitfalls are discussed. The anti-endomysium and anti-tissue transglutaminase antibodies are specific and sensitive diagnostic tools. The wide variety of clinical symptoms and presentations are discussed including the associated condition of dermatitis herpetiformis. Failure to respond to a gluten-free diet can represent simple dietary problems, an alternative diagnosis or, occasionally, the development of a serious complication of coeliac disease such as ulcerative jejunitis or enteropathy-associated T cell lymphoma. Progress towards the characterization of the toxic epitopes within gluten that exacerbate coeliac disease and our current understanding of the genetics of the disorder are presented.

HLA types in celiac disease patients not carrying the DQA1*05-DQB1*02 (DQ2) heterodimer: results from the European Genetics Cluster on Celiac Disease.

Genetic susceptibility to celiac disease is strongly associated with HLA-DQA1*05-DQB1*02 (DQ2) and HLA-DQA1*03-DQB1*0302 (DQ8). Study of the HLA associations in patients not carrying these heterodimers has been limited by the rarity of such patients. This European collaboration has provided a unique opportunity to study a large series of such patients. From 1008 European coeliacs, 61 were identified who neither carry the DQ2 nor DQ8 heterodimers. Fifty seven of these encoded half of the DQ2 heterodimer. The remaining 4 patients had a variety of clinical presentations. Three of them carried the DQA1*01-DQB*05 haplotype as did 20/61 of those carrying neither DQ2 nor DQ8. This may implicate a role of the DQA1*01-DQB*05 haplotype. None of these four patients carried the DQB1*06 allele that has previously been reported in this sub-group of patients. Of the 16 DQ2 heterodimer negative patients without DRB1*04 or DRB1*07 haplotypes, it was inferred that none encoded the previously implicated DRB4 gene as none had a DRB1*09 haplotype. These results underline the primary importance of HLA-DQ alleles in susceptibility to celiac disease, and the extreme rarity of celiac patients carrying neither the DQ2 or DQ8 heterodimers nor one half of the DQ2 heterodimer alone.

A collaborative European search for non-DQA1*05-DQB1*02 celiac disease loci on HLA-DR3 haplotypes: analysis of transmission from homozygous parents.

The HLA-DQA1*05 with DQB1*02 alleles are a major risk factor for celiac disease (CD). To search for additional human leukocyte antigen (HLA) risk factors, we looked on the DR3-DQ2 risk haplotype, selected because it carries both DQ risk alleles in cis and is the more represented among CD patients. In a European consortium, we identified 109 families with a parent homozygous for DQA1*05-DQB1*02. We typed ten microsatellites in the extended HLA complex, and applied the homozygous-parent transmission disequilibrium test (HPTDT) and extended-TDT to transmissions from homozygous parents. These methods eliminate confounding due to linkage disequilibrium between candidate disease loci and the known risk factor DQA1*05-DQB1*02, and are favorable when sufficient families are available. We did not find evidence of association with any single marker or allele, although weak evidence for additional risk was observed, represented by preferential transmission of six adjacent markers. We tested the largest ever reported HPTDT population in CD, providing unprecedented power. We did not find significant evidence of additional risk-modifying factors on the DR3 haplotype, independent of DQA1*05-DQB1*02, although a weak tendency was observed for the B8-DR3 haplotype. This effect should be tested in large populations with significant representations of both B8-DR3 and non-B8 DR3 haplotypes.

Testing for haemochromatosis in a liver clinic population: relationship between ethnic origin, HFE gene mutations, liver histology and serum iron markers.

OBJECTIVE: To identify the most appropriate testing strategy for genetic haemochromatosis in a liver clinic population by determining the ethnic distribution of the HFE mutations and the relationship between serum iron markers, hepatic siderosis and HFE genotype. DESIGN AND SETTING: Observational study of 427 patients being investigated for abnormal liver function tests between 1997 and 2000 attending a liver clinic at a teaching district general hospital in south London, UK. METHODS: All patients were tested for H63D and C282Y gene mutations, and the ethnic origin was determined. Data were available for most patients for non-fasting serum iron, ferritin and transferrin saturation on presentation and fibrosis and siderosis scores from liver biopsy. RESULTS: The C282Y mutation was not detected in any patients of Asian or Afro-Caribbean origin but was found almost exclusively in northern Europeans, especially those classified as Celtic, one in seven of whom were heterozygous for this mutation. Three per cent of all the patients tested were C282Y homozygotes. The H63D mutation was distributed more widely. An elevated serum transferrin saturation was both a more sensitive and a more specific test for genetic haemochromatosis than either serum ferritin or iron. Significantly raised mean siderosis scores were found on liver biopsy in C282Y homozygote and C282Y/H63D compound heterozygote groups but not in wild-type, simple heterozygote, or H63D homozygote groups. Forty-five per cent of the C282Y homozygotes detected already had cirrhosis. CONCLUSIONS: In a multiracial liver clinic population, previously undiagnosed C282Y homozygosity was found to be common (3% in our study) but restricted to those of northern European heritage, particularly those with Celtic ancestry. A serum transferrin saturation proved a better initial test to select patients for genotyping than serum iron or ferritin. Laboratory costs can be minimized with no loss of diagnostic sensitivity by selecting patients for genotyping based on northern European ethnic origin and raised serum transferrin saturation.

A new, highly sensitive assay for C-reactive protein can aid the differentiation of inflammatory bowel disorders from constipation- and diarrhoea-predominant functional bowel disorders.

BACKGROUND: Patients presenting to gastroenterology clinics with symptoms suggestive of lower-bowel disorders often require extensive investigation to differentiate functional from organic disease. C-reactive protein (CRP) is a sensitive marker of systemic inflammation. Levels of CRP are frequently raised in cases of inflammatory bowel disease (IBD). However, using conventional assays, not all cases of IBD have a detectable level. OBJECTIVE: To determine whether a new highly sensitive CRP enzyme-linked immunosorbent assay (ELISA) can aid the differentiation between IBD and functional bowel disorders (FBDs) in gastroenterology outpatients presenting with lower-bowel symptoms. METHODS: Serum was taken from 224 subjects attending a gastroenterology outpatient clinic. Of these, 203 were new patients and 21 were follow-up patients with quiescent colitis. The serum was analysed using a sensitive in-house ELISA. All new patients had a rigid sigmoidoscopy and rectal biopsy. Patients were investigated as deemed appropriate by the attending physician. Notes were reviewed after at least 6 months to determine the final diagnosis. RESULTS: A cut-off value of 2.3 mg/l had a sensitivity of 100% and a specificity of 67% in differentiating FBD from new cases of IBD. The geometric mean CRP was 0.383 mg/l in the constipation-predominant FBD group, 1.435 mg/l in diarrhoea-predominant FBD, 1.455 mg/l in quiescent IBD, 8.892 mg/l in newly presenting cases of ulcerative colitis, and 13.123 mg/l in newly presenting cases of Crohn's disease. CONCLUSION: A new, highly sensitive assay for CRP may help to distinguish FBD from IBD.

Recent developments in celiac disease.

Celiac disease is a common disorder associated with a substantially increased standardized mortality ratio if it is left untreated or if the diagnosis is delayed. Diagnostic sensitivity of serologic testing is improved by the addition of IgG-based testing to standard IgA-based serologic testing for endomysial or transglutaminase autoantibodies. The role of intestinal permeability testing as an additional tool for screening and for monitoring the response to a gluten-free diet is discussed. The importance of diagnosing celiac disease in two clinical situations is considered: first, before immune-stimulating therapy with interferon for viral hepatitis is begun and second, in pregnancy when not only maternal but also paternal celiac disease may affect fetal outcome. The strong genetic component of the etiology of celiac disease is illustrated by a monozygotic twin concordance of nearly 90%, with susceptibility conveyed by human leukocyte antigen (HLA) genotypes DQ2 or DQ8 and one or more non-HLA genes. Progress toward identifying these genes from large linkage and association studies is reviewed.