Fecal microbiota transplantation for severe enterocolonic fistulizing Crohn’s disease

The concept of fecal microbiota transplantation(FMT)has been used in traditional Chinese medicine at least since the 4thcentury.Evidence from recent human studies strongly supports the link between intestinal bacteria and inflammatory bowel disease.We proposed that standardized FMT might be a promising rescue therapy for refractory inflammatory bowel disease.However,there were no reports of FMT used in patients with severe Crohn’s disease(CD).Here,we report the successful treatment of standardized FMT as a rescue therapy for a case of refractory CD complicated with fistula,residual Barium sulfate and formation of intraperitoneal large inflammatory mass.As far as we know,this is the first case of severe CD treated using FMT through mid-gut.     

Pulmonary manifestations of Crohn’s disease

Crohn’s disease(CD)is a systemic illness with a constellation of extraintestinal manifestations affecting various organs.Of these extraintestinal manifestations of CD,those involving the lung are relatively rare.However,there is a wide array of lung manifestations,ranging from subclinical alterations,airway diseases and lung parenchymal diseases to pleural diseases and drug-related diseases.The most frequent manifestation is bronchial inflammation and suppuration with or without bronchiectasis.Bronchoalveolar lavage findings show an increased percentage of neutrophils.Drug-related pulmonary abnormalities include disorders which are directly induced by sulfasalazine,mesalamine and methotrexate,and opportunistic lung infections due to immunosuppressive treatment.In most patients,the development of pulmonary disease parallels that of intestinal disease activity.Although infrequent,clinicians dealing with CD must be aware of these,sometimes life-threatening,conditions to avoid further impairment of health status and to alleviate patient symptoms by prompt recognition and treatment.The treatment of CD-related respiratory disorders depends on the specific pattern of involvement,and in most patients,steroids are required in the initial management.     

Small bowel video capsule endoscopy in Crohn’s disease: What have we learned in the last ten years?

Since its introduction in 2001, capsule endoscopy (CE) has become the most important advance in the study of small bowel disease, including Crohn’s disease (CD). This technique has been demonstrated to be superior to all other current forms of radiological investigation in detecting mucosal abnormalities of small bowel nonstricturing CD. CE has proven to be extremely useful in diagnosing CD in patients with inconclusive findings from ileocolonoscopy and x-ray-based studies. Almost half of all patients with CD involving the ileum also present lesions in proximal intestinal segments, with the small bowel being exclusively involved in up to 30% of all CD cases. Despite the widespread use of CE, several questions concerning the utility of this technique remain unanswered. The lack of commonly agreed diagnostic criteria for defining CD lesions with the aid of CE may have had an influence on the variation in diagnostic re sults for CE reported in the literature. The utility of CE in monitoring CD and in guiding therapy has also been proposed. Furthermore, CE could be a useful second-line technique for patients with an established diagn osis of CD and unexplained symptoms. Finally, as no thres hold for CD diagnosis has been agreed upon, a se verity scale of mucosal disease activity has notbeen universally followed. None of the available activity indexes based on CE findings has been independently validated. This article discusses several cutting-edge aspects of the usefulness of CE in CD 10 years after its introduction as a sensible method to study the small intestine.     

Lifestyle-related disease in Crohn’s disease: Relapse prevention by a semi-vegetarian diet

AIM: To investigate whether semi-vegetarian diet (SVD) has a preventive effect against relapse of Crohn’s disease (CD) in patients who have achieved remission,who are a high-risk group for relapse.METHODS: A prospective,single center,2-year clinical trial was conducted.Twenty-two adult CD patients who achieved clinical remission either medically (n = 17) or surgically (n = 5) and consumed an SVD during hospitalization were advised to continue with an SVD and avoid known high-risk foods for inflammatory bowe...     

Why is damage limited to the mucosa in ulcerative colitis but transmural in Crohn’s disease?

It has been a big puzzle as why the inflammation of ulcerative colitis (UC) is limited to the mucosa, while in Crohn’s disease (CD) the inflammation is transmural and can be seen in all layers of the gut. Here, I give a tentative explanation extended from the unified hypothesis I proposed on the etiology of inflammatory bowel disease. This hypothesis suggested that both UC and CD are caused by weakening of the gut barrier due to damage of the protective mucus layer and the underlying tissue by the poorly inactivated digestive proteases resulting from a reduction of gut bacteria by dietary chemicals like saccharin and sucralose. However, the large amounts of bacteria in the colon make the recruitment of neutrophils and formation of crypt abscess the main manifestation of UC, while the infiltration of antigens and dietary particles in the small and large intestine mainly cause the recruitment of macrophages and formation of granulomas as the main manifestations in CD. The fast reacting and short life span of neutrophils make the fight and damage limited to the surface of the mucosa. In contrast, the long life span and constant movement of macrophages may bring the harmful agents deep into the tissue. Therefore, the pathogenesis of UC may be more like bacterial pneumonia, while CD may be more like pneumoconiosis or tuberculosis of the lung.     

Prevention of post-operative recurrence of Crohn’s disease

Endoscopic and clinical recurrence of Crohn’s disease(CD)is a common occurrence after surgical resection.Smokers,those with perforating disease,and those with myenteric plexitis are all at higher risk of recurrence.A number of medical therapies have been shown to reduce this risk in clinical trials.Metronidazole,thiopurines and anti-tumour necrosis factors(TNFs)are all effective in reducing the risk of endoscopic or clinical recurrence of CD.Since these are preventative agents,the benefits of prophylaxis need to be weighed-against the risk of adverse events from,and costs of,therapy.Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF.Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year.Clinical recurrence rates are variable,and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.     

Osteonecrosis of both knees in a woman with Crohn’s disease

Osteonecrosis is a very rare complication of Crohn’s disease(CD).It is not clear if it is related to corticosteroid therapy or if it occurs as an extraintestinal manifestation of inflammatory bowel disease.We present the case of a patient with CD who presented with osteonecrosis of both knees.A 22 years old woman was diagnosed with CD in April 2012(Montreal Classification A2L1 + L4B3p).She was started on prednisolone(40 mg/d),azathioprine(100 mg/d) and messalazine(3 g/d).In July 2012,due to active perianal disease,infliximab therapy was initiated.In September 2012,she had a pelvic abscess complicated by peritonitis and an ileal segmental resection and right hemicolectomy were performed.In December 2012 she was diagnosed with bilateral septic arthritis of both knees with walking impairment.She was treated with amoxicillin-clavulanic acid,started a physical rehabilitation program and progressively improved.However,then,bilateral knee pain exacerbated by movement developed.Magnetic resonance imaging showed multiple osseous medullary infarcts in the distal extremity of the femurs,proximal extremity of the tibiae and patellas and no signs of subchondral collapse,which is consistent with osteonecrosis.The patient recovered completely and maintains therapy with azathioprine and messalazine.A review of the literature is also done.     

Inflammatory bowel disease course in Crohn’s disease: Is the natural history changing?

Crohn’s disease(CD)is a multifactorial potentially debilitating disease.It has a variable disease course,but the majority of patients eventually develop penetrating or stricturing complications leading to repeated surgeries and disability.Studies on the natural history of CD provide invaluable data on its course and clinical predictors,and may help to identify patient subsets based on clinical phenotype.Most data are available from referral centers,however these outcomes may be different from those in population-based cohorts.New data suggest the possibility of a change in the natural history in Crohn’s disease,with an increasing percentage of patients diagnosed with inflammatory disease behavior.Hospitalization rates remain high,while surgery rates seem to have decreased in the last decade.In addition,mortality rates still exceed that of the general population.The impact of changes in treatment strategy,including increased,earlier use of immunosuppressives,biological therapy,and patient monitoring on the natural history of the disease are still conflictive.In this review article,the authors summarize the available evidence on the natural history,current trends,and predictive factors for evaluating the disease course of CD.     

Clinical effects of adalimumab treatment with concomitant azathioprine in Japanese Crohn’s disease patients

AIM:To assess adalimumab’s efficacy with concomitant azathioprine (AZA) for induction and maintenance of clinical remission in Japanese Crohn’s disease (CD) patients. METHODS:This retrospective, observational, singlecenter study enrolled 28 consecutive CD patients treated with adalimumab (ADA). Mean age and mean disease duration were 38.1 ± 11.8 years and 11.8 ± 10.1 years, respectively. The baseline mean Crohn’s disease activity index (CDAI) and C-reactive protein were 177.8 ± 82.0 and 0.70 ± 0.83 mg/dL, respectively. Twelve of these patients also received a concomitant stable dose of AZA. ADA was subcutaneously administered:160 mg at week 0, 80 mg at week 2, followed by 40 mg every other week. Clinical response and remission rates were assessed via CDAI and C-reactive protein for 24 wk. RESULTS:The mean CDAI at weeks 2, 4, 8, and 24 was 124.4, 120.2, 123.6, and 135.1, respectively. The CDAI was significantly decreased at weeks 2 and 4 with ADA and was significantly suppressed at 24 wk with ADA/AZA. Overall clinical remission rates at weeks 4 and 24 were 66.7% and 63.2%, respectively. Although no statistically significant difference in C-reactive protein was demonstrated, ADA with AZA resulted in a greater statistically significant improvement in CDAI at 24 wk, compared to ADA alone. CONCLUSION:Scheduled ADA with concomitant AZA may be more effective for clinical remission achievement at 24 wk in Japanese Crohn’s disease patients.     

Hematopoietic cell transplantation for Crohn＇s disease; is it time？

AIM: To review all studies in the literature that have assessed Hematopoietic cell transplantation (HCT) and Crohn's disease (CD) with the ultimate aims of determining if this is a viable treatment option for those with CD. A secondary aim was to review the above literature and determine if the studies shed further light on the mechanisms involved in the pathogenesis of CD. METHODS: An extensive Medline search was performed on all articles from 1970 to 2005 using the keywords; bone marrow transplant, stem cell, hematopoietic cell, Crohn's disease and inflammatory bowel disease. RESULTS: We identified one case in which a patient developed CD following an allogeneic HCT from a sibling suffering with CD. Evidence for transfer of the genetic predisposition to develop CD was also identified with report of a patient that developed severe CD following an allogeneic HCT. Following HCT it was found that the donor (that had no signs or symptoms of CD) and the recipient had several haplotype mismatches in HLA class III genes in the IBD3 locus including a polymorphism of NOD2/CARD15 that has been associated with CD. Thirty three published cases of patients with CD who underwent either autologous or allogeneic HCT were identified. At the time of publication 29 of these 33 patients were considered to be in remission. The median follow-up time was seven years, and twenty months for allogeneic and autologous HCT respectively. For patients who underwent HCT primarily for treatment of their CD there have been no mortalities related to transplant complications. CONCLUSION: Overall these preliminary data suggest that both allogeneic and autologous HCT may be effective in inducing remission in refractory CD. This supports the hypothesis that the hematolymphatic cells play a key role in CD and that resetting of the immune system may be a critical approach in the management or cure of CD.     

Wireless capsule endoscopy and proximal small bowel lesions in Crohn’s disease

AIM: To investigate the prevalence of proximal small bowel (SB) lesions detected by wireless capsule endoscopy (WCE) in Crohn's disease (CD). METHODS: WCE was performed in 64 patients: 32 with CD of the distal ileum, and 32 controls with iron-deficiency anemia (IDA) or diarrhea. WCE was performed using the Given SB-WCE, followed by small intestine contrast ultrasonography (SICUS). Findings compatible with CD by using WCE included erosions, aphthoid or deep ulcers, and strictures/stenosis. RESULTS: WCE detec...     

Why interleukin-10 supplementation does not work in Crohn’s disease patients

Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) or ulcerative colitis are chronic intestina disorders, which are on the increase in Westernised countries. IBD can be caused by both genetic and environmental factors. Interleukin-10 (IL-10) is an immunoregulatory cytokine that has been identified as being involved in several diseases including IBD. Studies have shown that polymorphisms in the promoter region reduce serum levels of IL-10 and this reduction has been associated with some forms of IBD. Mouse models have shown promising results with IL-10 supplementation, as such IL-10 supplementation has been touted as being a possible alternative treatment for CD in humans. Clinical trials have shown that recombinant human IL-10 is safe and well tolerated up to a dose o 8 μg/kg. However, to date, the results of the clinica trials have been disappointing. Although CD activity was reduced as measured by the CD activity index IL-10 supplementation did not result in significantly reduced remission rates or clinical improvements when compared to placebo. This review discusses why IL-10supplementation is not effective in CD patients currently and what can be addressed to potentially make IL-10 supplementation a more viable treatment option in the future. Based on the current research we conclude that IL-10 supplementation is not a one size fits all treatment and if the correct population of patients is chosen then IL-10 supplementation could be of benefit.     

Lymphangitic spread from appendiceal adenocarcinoma to ileocecal valve,mimicking Crohn’s disease

Due to the anatomical peculiarity of the appendix,diagnosis of tumors arising from this area can be challenging by clinicoradiologic means.We report a case of a rare primary appendiceal signet ring carcinoma with an uncommon presentation.An 86-year-old woman was admitted toour hospital with subacute epigastric pain.Computed tomography demonstrated bowel wall thickening with fat stranding in the ileocecal region.The leading diagnostic consideration was inflammatory bowel disease.Upon colonoscopy,a swollen,distorted ileocecal valve was identified.The remaining colon was otherwise unremarkable.Extensive biopsy sampling of the ileocecal region and colon was performed.A lymphangitic signet ring carcinoma within the ileocecal region was diagnosed on biopsy;there was no dysplasia or carcinoma of the remaining biopsies.By cytomorphology and immunoprofile,a lymphangitic signet ring carcinoma of appendiceal origin was the primary consideration,further confirmed upon subsequent laparotomy.This case represents an unusual pattern of appendiceal tumor spread with localized,lymphangitic involvement,creating a milieu which closely simulates Crohn’s disease on imaging modalities.     

Mutifactorial analysis of risk factors for reduced bone mineral density in patients with Crohn’s disease

INTRODUCTION Osteoporosis is now recognised as a common complication of inflammatory bowel disease (IBD) and in particular Crohn’s disease (CD). Estimates of prevalence vary but those studies employing the World Health Organisation[1] diagnostic criteria…     

Surgery for luminal Crohn’s disease

Many patients with Crohn’s disease(CD)require surgery.Indications for surgery include failure of medical treatment,bowel obstruction,fistula or abscess formation.The most common surgical procedure is resection.In jejunoileal CD,strictureplasty is an accepted surgical technique that relieves the obstructive symptoms,while preserving intestinal length and avoiding the development of short bowel syndrome.However,the role of strictureplasty in duodenal and colonic diseases remains controversial.In extensive colitis,after total colectomy with ileorectal anastomosis(IRA),the recurrence rates and functional outcomes are reasonable.For patients with extensive colitis and rectal involvement,total colectomy and end-ileostomy is safe and effective;however,a few patients can have subsequent IRA,and half of the patients will require proctectomy later.Proctocolectomy is associated with a high incidence of delayed perineal wound healing,but it carries a low recurrence rate.Patients undergoing proctocolectomy with ileal pouch-anal anastomosis had poor functional outcomes and high failure rates.Laparoscopic surgery has been introduced as a minimal invasive procedure.Patients who undergo laparoscopic surgery have a more rapid recovery of bowel function and a shorter hospital stay.The morbidity also is lower,and the rate of disease recurrence is similar compared with open procedures.     

Chronic pancreatitis as presentation of Crohn’s disease in a child

It is reported that a pancreatic disease may precede the diagnosis of inflammatory bowel disease(IBD) both in children and in adults.Idiopathic chronic pancreatitis,however,occasionally co-exists with the IBD,mainly at pediatric age.We report a case of a patient who progressively developed the features of a chronic pancreatitis,before the diagnosis of Crohn’s Disease(CD).Ten months after the onset of the first episode of pancreatitis the patient developed bloody diarrhea,mucus stools and biochemical findings of inflammation.The colonoscopy revealed a diffuse colitis without involvement of the last loop and the gastroscopy showed inflammation of the iuxta-papillary area.The histological findings confirmed the diagnosis of CD that involved the colon and the duodenum.In conclusion,in children the idiopathic chronic pancreatitis may be an unusual presentation of CD.Thus,if other known cause of chronic pancreatitis are not found,a not invasive work up to exclude the IBD should be warranted.An early coincidental diagnosis of the IBD may delay the progression of the pancreatic disease.     

Crohn’s disease complicated by multiple stenoses and internal fistulas clinically mimicking small bowel endometriosis

We report a 31-year-old woman with Crohn's disease complicated by multiple stenoses and internal fistulas clinically misdiagnosed as small bowell endometriosis, due to the patient's perimenstrual symptoms of mechanical subileus for 3 years; at first monthly, but later continuous, and gradually increasing in severity. We performed an exploratory laparotomy for small bowel obstruction, and found multiple ileal strictures and internal enteric fistulas. Because intraoperative findings were thought to indicate Crohn's disease, a right hemicolectomy and partial distal ileum resection were performed for obstructive Crohn's ileitis. Histopathology of the resected specimen revealed Crohn's disease without endometrial tissue. The patient made an uneventful recovery from this procedure and was discharged home 10 d post-operatively. The differential diagnosis of Crohn's diease with intestinal endometriosis may be difficult pre-operatively. The two entities share many overlapping clinical, radiological and pathological features. Nevertheless, when it is difficult to identify the cause of intestinal obstruction in a woman of child-bearing age with cyclical symptoms suggestive of small bowel endometriosis, Crohn's disease should be included in the differential diagnosis.     

Crohn’s disease:Innate immunodeficiency?

iNtRODuCtiON Over a period of many years Crohn’s Disease (CD) has been thought to result predominantly from excessive activation of type 1 helper T cells (TH1) with a characteristic cytokine profile including elevated interferon-γ and IL-2. However the …     

Crohn’s disease complicated by intestinal infection with methicillin-resistant Staphylococcus aureus

We report on a 24-year-old male patient with history of bloody diarrhea, abdominal pain and vomiting. Endoscopy revealed massive ulcerative discontinuous proctosigmoiditis with deep, sharply demarcated epithelial denudations and enterotoxigenic methicillin-resistant Staphylococcus aureus (MRSA) was detected in mucosal biopsies. After treatment with linezolide and steroids, a significant amelioration of colitis was detected and testing for MRSA became negative. In face of the case presented here, we suggest that in patients with refractory inflammatory bowel disease (IBD), microbiological assessment should be performed to detect a possible Staphylococcus aureus infection in order to initiate an antimicrobial treatment in addition to IBDspecific treatment.