Causality and gastrointestinal infections: Koch, Hill, and Crohn's

The gastrointestinal tract contains a complex mix of microorganisms. Therefore, the finding of a particular microbe in the gastrointestinal tract or stools of a patient with intestinal disease does not necessarily indicate that the clinical state resulted from the presence of this organism. For this reason, extending from epidemiological association to causality is particularly challenging for gastrointestinal diseases. Most established agents of acute bacterial gastroenteritis (eg, Escherichia coli, Campylobacter jejuni) have been shown to fulfil Koch's postulates of causality in human volunteer studies. For Helicobacter pylori, which can cause both acute and chronic disease, the organism was first linked to an acute syndrome through volunteer studies and then later assessed for a role in chronic disease by use of Hill's epidemiological criteria of causation. However, for agents of chronic intestinal disease, this approach is not ethical and risks overlooking events occurring long after the exposure. We examine the criteria used to judge causality (Koch's postulates and Hill's criteria) and their applicability for chronic gastrointestinal diseases (eg, Whipple's disease and Crohn's disease). We also identify crucial research questions required to advance towards assessing the causal role of candidate microbes in the aetiopathogenesis of Crohn's disease.     

Treatment of extensive subacute portal, mesenteric and ileocolic vein thrombosis with recombinant tissue plasminogen activator.

Portal or/and mesenteric vein thrombosis is a rare condition with high mortality in an acute form. Therapy of thrombosis is not well defined, although there are some general guidelines that differ according to disease onset and clinical presentation. In acute thrombosis with bowel infarction, surgical resection with possible thrombolysis is advised. The best therapy for the subacute form is not known and the approach differs between centers. For chronic disease, prolonged anticoagulant therapy is recommended. Thrombolysis is well recognized in the treatment of acute ischemic coronary or cerebral diseases. Success of treatment is better if therapy is introduced within a few hours after symptoms have begun. We describe a 25-year-old patient with the subacute form of extensive portal, mesenteric and ileocolic vein thrombosis in the setting of underlying liver cirrhosis due to autoimmune disease. An aggressive therapeutic approach is advised, especially in patients who will eventually undergo liver transplantation, since portal and/or mesenteric vein thrombosis is relative contraindication for liver transplantation in the majority of transplant centers.     

Familial intestinal pseudoobstruction dominated by a progressive neurologic disease at a young age

Chronic neuropathic intestinal pseudoobstruction is a rare entity, characterized by recurrent episodes of bowel obstruction without a mechanical obstructive cause. We report five members of two Jewish-Iranian families in whom chronic neuropathic intestinal pseudoobstruction was associated with an identical and unique progressive severe neuronal disease. It appeared within the first two decades of life. The disease consisted of external ophthalmoplegia, ptosis, and severe sensory and motor peripheral neuropathy. Three patients also had neuronal hearing loss. There was no evidence of central nervous system involvement and all patients were mentally intact. The combined disease was confirmed by radiologic, electrophysiologic, and histologic studies. Specific nutritional deficiencies, toxic elements, and systemic diseases affecting both the gastrointestinal tract and the nervous system were ruled out. It seems that these patients suffer from an autosomal recessive, presently unrecognized variant, of chronic neuropathic intestinal pseudoobstruction. In a patient with severe peripheral neuropathy of unknown etiology associated with symptoms suggestive of intestinal obstruction, the possibility of chronic neuropathic intestinal pseudoobstruction has to be considered.     

Bacteria as trigger for chronic gastrointestinal disorders

Apart from acute infections, microorganisms may also induce or perpetuate chronic inflammatory diseases and reversible or irreversible proliferation of various cells in the gastrointestinal tract (the extreme being adenocarcinoma and lymphoma). Helicobacter pylori is not only involved in the pathogenesis of lymphoma and gastric adenocarcinoma. The steps and mechanisms of the carcinogenic process involve host predisposition, environmental factors, and strain virulence. The steps of lymphoma genesis include chronic inflammation, acquisition of mucosa-associated lymphoid tissue in the stomach, proliferation of the B lymphocytes in an inflammatory context, acquisition of genetic anomalies and dysregulation of the NF-κB pathway. The role of Campylobacter jejuni in immunoproliferative small bowel disease has also been shown and eradication of this bacterium can cure the lymphoma at its early stage. The evidence for the role of some bacteria in colon cancer development is discussed. Opportunistic pathogens are detected in the stools or mucosa of a proportion of subjects with Crohn's disease. They include Mycobacterium avium paratuberculosis, adherent invasive Escherichia coli, and Clostridium difficile. A dysbiosis has been repeatedly observed in patients with inflammatory bowel disease. Instability of the dominant microbiota and decreased biodiversity (especially in the firmicutes phylum) are major characteristics. The decrease of Faecalibacterium prausnitzii seems to have a prognostic value to predict relapse of Crohn's disease after surgery. Finally, important perspectives are opened by new tools such as metagenomics and metabolomics of the gastrointestinal ecosystems. Major tracks concern irritable bowel syndrome, colon cancer and obesity.     

Amyloidosis in adult Still's disease. Apropos of 2 cases

Two cases of amyloidosis were observed in a personal series of 42 patients with the adult from of Still's disease. Two other cases have been previously reported in the literature. In the first case, amyloidosis occurred 18 months after the onset of the disease and involved the kidneys and gastrointestinal tract with a fatal outcome in 6 months. In the second case, renal amyloidosis was observed 4 years after the onset of Still's disease and progressed to renal failure in 7 months, necessitating chronic haemodialysis. These cases show that the adult form of Still's disease may rarely be complicated by amyloidosis, the prognosis of which is particularly poor.     

Skin ulcer is a predictive and prognostic factor of acute or subacute interstitial lung disease in dermatomyositis

The aim of this study was to determine whether skin ulcer can be used as a predictive and prognostic factor of acute/subacute interstitial lung disease (ILD) in Japanese patients with dermatomyositis (DM). We reviewed the medical records of 39 consecutive DM patients who were admitted to Tokyo Metropolitan Komagome Hospital from January 2000 to December 2009. The mean follow-up period was 63.9 ± 51.6 months. Fifteen patients had acute/subacute ILD and 11 patients had chronic ILD. Seven out of 15 acute/subacute ILD led to respiratory failure and 3 of them died due to ILD. Skin ulcers were observed in 5 out of 15 patients with acute/subacute ILD (33.3 %) and in 2 out of 24 patients without acute/subacute ILD (8.3 %). The presence of skin ulcers was revealed to be a significant predictive factor for acute/subacute ILD among various parameters by multivariate analysis. In the 15 patients with acute/subacute ILD, the presence of skin ulcers was a significant poor prognostic factor (p = 0.0231) and the cumulative survival rate of patients with skin ulcers was 53.3 % for 12 months. Skin ulcer is a significant predictive and prognostic factor of acute/subacute ILD in patients with DM.     

Alterations of nutritional status in the main gastrointestinal pathologies

An impairment of nutritional status up to real malnutrition can frequently be associated to gastrointestinal diseases. The diseases of the gastrointestinal tract can be divided into five groups: those hampering the nutrient physiological transit (especially neoplastic diseases); those affecting the intestinal mucosa (such as chronic inflammatory bowel disease); those determining intraluminal maldigestion; the hepato-biliary diseases and finally, the diseases of the pancreas. In order to correctly evaluate the nutritional status of an individual, besides the determination of the common biochemical parameters, body composition by direct and indirect techniques and energy metabolism by indirect calorimetry should be measured. Patients affected by Crohn's disease showed a lower fat mass content along with higher lipid oxidation compared to patients affected by ulcerative colitis. Patients with coeliac disease at diagnosis had a reduction in both fat and fat-free mass content along with an increased utilisation of carbohydrates as fuel substrate. There are many factors potentially leading to severe malnutrition in pancreatic diseases, especially in the acute form. Due to the primary role played by the liver in the metabolism of energy substrates, an impaired nutritional status might be commonly found in cirrhotic patients. In this connection, our group reported an increased energy expenditure and lipid oxidation, and an insulin-resistant state in compensated liver cirrhotic patients. These alterations seemed to precede and probably to lead to liver-disease-related malnutrition.     

An inflammatory fibroid polyp (eosinophilic granuloma) and Crohn's disease located in the ileum]

Lower gastrointestinal tract bleeding as a manner of presentation of the Crohn's disease is uncommon. In most cases there is an other concomitant pathology responsible for that bleeding. We report a case of lower gastrointestinal tract bleeding to an inflammatory fibroid bowel polyp in a patient with ileal Crohn's disease. A commentary is made about the etiopathogenic factors of the both diseases.     

High-resolution ultrasonography in gastrointestinal graft-versus-host disease

Gastrointestinal graft-versus-host disease (GVHD) is one of the main causes of therapy-related death after allogeneic hemopoietic stem cell transplantation. Early diagnosis and immediate treatment are probably essential for improving clinical outcome. High-resolution sonography allows the evaluation of single bowel wall layers throughout the small and large bowel. We report the sonographic findings of seven consecutive patients with histologically confirmed GVHD grade II–IV of the gastrointestinal tract. The patients were examined sonographically within the 1st week after onset of clinical symptoms. Dilatation of the colon and striking bowel wall thickening were early and common features in these patients. Sonography may become a useful tool for diagnosis of patients with gastrointestinal GVHD. Its role for preclinical diagnosis, grading of severity of disease, and guiding therapy of patients with gastrointestinal GVHD warrants evaluation in prospective studies.     

Update in the Management of Extraintestinal Manifestations of Inflammatory Bowel Disease

Inflammatory bowel disease, comprised of Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of the gastrointestinal tract. Up to 40 % of patients with inflammatory bowel disease can develop inflammation in other organ systems of the body. These extraintestinal manifestations (EIM) can affect the musculoskeletal, ocular, mucocutaneous, and hepatobiliary systems. Symptoms related to EIM can result in impaired quality of life, and complications of EIM can lead to disfigurement, functional deficits, and even life-threatening organ dysfunction. Some EIM parallel the activity of IBD, and respond to treatment of the underlying disease. Others, however, follow an independent course and require targeted treatment.     

Irritable bowel syndrome

Irritable bowel syndrome is a frequent functional disorder of gastrointestinal tract. Its high incidence represents an important socioeconomic concern. The diagnosis of irritable bowel syndrome is indirect and requires exclusion of an organic lesion within as well as outside the gastrointestinal tract. No algorithms--so called treatment guidelines--are available for pharmacological or non-pharmacological treatment of the irritable bowel syndrome. Long-term and comprehensive care of patients with functional diseases is an important component of the management of patients with irritable bowel syndrome.     

提高缺血性肠病的临床认识

缺血性肠病是一组因小肠、结肠血液供应不足导致的不同程度的肠壁局部组织坏死和一系列症状的疾病,可分为急性肠系膜缺血（AMI）、慢性肠系膜缺血（CMI）及缺血性结肠炎（IC）,以IC最多见。临床表现主要为腹痛、血性腹泻、血便及腹胀等消化道症状。该病与动脉粥样硬化、肠系膜动静脉栓塞及血栓形成、心搏量减少及血管炎等有关,患者可同时存在高血压、糖尿病及急性心肌梗死等老龄化疾病。DSA及CT检查对于诊断AMI及CMI价值较高,而IC则主要依赖于结肠镜的诊断。预后也各不相同,AMI病情凶险,死亡率高,须早期诊断及手术治疗;而IC临床症状多为自限性,预后良好。缺血性肠病临床误诊率较高,应引起临床医师重视。     

New genes in inflammatory bowel disease: lessons for complex diseases?

The chronic inflammatory bowel diseases Crohn's disease and ulcerative colitis are common causes of gastrointestinal disease in northern Europe, affecting as many as one in 250 people. Although mortality is low, morbidity associated with these diseases is substantial. We review the recent advances in the genetics of inflammatory bowel disease, with particular emphasis on the data that have been generated since the discovery of the CARD15 (NOD2) gene in 2001.     

Presymptomatic Crohn's Disease in a Young Patient Diagnosed Just After the Onset of Idiopathic Acute Pancreatitis

Acute pancreatitis is an extraintestinal manifestation of inflammatory bowel disease. There have been few reports describing acute pancreatitis preceding a diagnosis of inflammatory bowel disease. We herein report a rare case of a 16-year-old boy with presymptomatic Crohn''s disease that was newly diagnosed just after the onset of idiopathic acute pancreatitis. Crohn''s disease of any stage, much less in the presymptomatic stage, is rarely diagnosed just after the development of acute pancreatitis. The present case suggests that acute pancreatitis without an apparent cause in young or pediatric population can precede a diagnosis of presymptomatic Crohn''s disease.     

Diagnostic value of faecal calprotectin in paediatric gastroenterology clinical practice

BACKGROUND: Faecal calprotectin (FC) is a new marker of intestinal inflammation. Data on FC in paediatric gastroenterology clinical practice are still scarce. AIMS: To assess FC values in different paediatric gastrointestinal diseases comparing them with those obtained in healthy children. PATIENTS: Two hundred and eighty-one children (age range 13-216 months) consecutively referred for gastrointestinal symptoms. Seventy-six healthy controls (age range 13-209 months). The exclusion criteria in healthy children were the following: any known underlying chronic disease or a history of abdominal pain, diarrhoea, acute respiratory tract infection, intake of non-steroidal anti-inflammatory drugs, gastric acidity inhibitors, antibiotics, drugs influencing gut motility, and menstrual or nasal bleeding in the last 3 weeks. METHODS: Stool samples stored, prepared and analyzed by an ELISA assay. RESULTS: In healthy children the median FC value was 28.0 microg/g (15-57 interquartile range) with a 95th percentile value of 95.3 microg/g. An increase in FC concentration was observed in all diseases characterized by gastrointestinal mucosa inflammation, and the active inflammatory bowel disease patients showed the higher FC values. All children affected by functional bowel disorders or by non-inflammatory diseases showed normal values. We calculated an optimized FC cut off value of 102.9266 microg/g (revealed by the receiver operating characteristic curve) to distinguish patients with active organic/inflammatory disorders from healthy subjects and from patients with functional bowel disorders. CONCLUSIONS: Calprotectin is a sensitive, but not disease specific, marker to easily detect inflammation throughout the whole gastrointestinal tract. It may help in identifying an organic disease characterized by intestinal mucosa inflammation and in the differential diagnosis of functional bowel disorders.     

Inflammatory bowel disease in the dog:Differences and similarities with humans

Inflammatory bowel diseases (IBD) represent important chronic conditions affecting the gastrointestinal tract in man.However,similar disorders are found in several animal species and the IBD affecting dogs are particularly important.These are encompassed by an umbrella of probably several different entities with common symptoms,some of which seem to share striking similarities with human conditions.This review will focus on the actual knowledge of IBD in dogs,and attempt to identify differences and similarities with human IBD conditions.     

Gut-lung crosstalk in pulmonary involvement with inflammatory bowel diseases

Pulmonary abnormalities,dysfunction or hyper-reactivity occurs in association with inflammatory bowel disease(IBD) more frequently than previously recognized.Emerging evidence suggests that subtle inflammation exists in the airways among IBD patients even in the absence of any bronchopulmonary symptoms,and with normal pulmonary functions. The pulmonary impairment is more pronounced in IBD patients with active disease than in those in remission. A growing number of case reports show that the IBD patients develop rapidly progressive respiratory symptoms after colectomy,with failure to isolate bacterial pathogens on repeated sputum culture,and often request oral corticosteroid therapy. All the above evidence indicates that the inflammatory changes in both the intestine and lung during IBD. Clinical or subclinical pulmonary inflammation accompanies the main inflammation of the bowel.Although there are clinical and epidemiological reports of chronic inflammation of the pulmonary and intestinal mucosa in IBD,the detailed mechanisms of pulmonaryintestinal crosstalk remain unknown. The lung has no anatomical connection with the main inflammatory site of the bowel. Why does the inflammatory process shift from the gastrointestinal tract to the airways? The clinical and subclinical pulmonary abnormalities,dysfunction,or hyper-reactivity among IBD patients need further evaluation. Here,we give an overview of the concordance between chronic inflammatory reactions in the airways and the gastrointestinal tract. A better understanding of the possible mechanism of the crosstalk among the distant organs will be beneficial in identifying therapeutic strategies for mucosal inflammatory diseases such as IBD and allergy.     

A case of multiple gastrointestinal stromal tumor of the jejunum which was diagnosed by capsule endoscopy

More than 90% cases of chronic gastrointestinal bleeding can be diagnosed by upper endoscopy and/or colonoscopy, and therefore, obscure gastrointestinal bleeding has been defined as bleeding of unknown origin that persists after these conventional endoscopic evaluation. Gastrointestinal stromal tumors (GISTs) are rare tumors, but the most common form of mesenchymal tumors of the gastrointestinal tract. Small bowel is the second most common primary site for GISTs, and accounts for 2-10% of chronic bleeding sites. GISTs usually present as a sporadic and solitary tumor, and a minority of the cases of multiple GISTs are discovered as forms of hereditary or idiopathic tumor syndromes. Small bowel tumor has been difficult to diagnose because of absence of accurate and proper diagnostic tools. Recently developed wireless capsule endoscopy helps in the diagnostic work-up of small bowel diseases. We report a case of multiple jejunal GISTs presenting melena in a 39-year-old male, which was diagnosed with wireless capsule endoscopy.     

Breastfeeding and genetic factors in the etiology of inflammatory bowel disease in children

Inflammatory bowel disease is a chronic, debilitating disorder of the gastrointestinal tract. The etiology of inflammatory bowel disease has not been elucidated, but is thought to be multifactorial with both environmental and genetic influences. A large body of research has been conducted to elucidate the etiology of inflammatory bowel disease. This article reviews this literature, emphasizing the studies of breastfeeding and the studies of genetic factors, particularly NOD2 polymorphisms.