Capsule Endoscopy Changes Patient Management in Routine Clinical Practice

Our objective was to evaluate the diagnostic yield and effect of capsule endoscopy on patient management in routine clinical practice. Three hundred examinations were performed (176 females; mean age, 51 years), with a median follow-up of 17 months. Indications included overt bleeding (n = 55), anemia (n = 104), suspected Crohn’s disease (n = 68), celiac disease (n = 35), suspected functional symptoms (n = 23), polyposis (n = 5), and miscellaneous (n = 10). The overall diagnostic yield was 39%, but it was notably higher in overt bleeders, 66%, compared to 46% in the anemia group (P<0.025), 32% in the suspected Crohn’s group (P<0.001), and 17% in the functional group (P<0.001). As a result of capsule endoscopy, management was altered in 26% of patients. This study shows that capsule endoscopy has both a high diagnostic yield and an impact on subsequent patient management. These data further support the role of capsule endoscopy in routine clinical practice. R.S. wrote the initial draft; all five authors were involved in the subsequent revisions and final draft. M.E.M. is the guarantor for this paper.     

Pharyngeal dysmotility in a patient with wilson’s disease

Wilson’s disease (WD) is an inherited inborn error of copper metabolism. Patients develop tremor, rigidity, dysarthria, sialorrhea, dysphagia, intracorneal pigmentation, and psychiatric and hepatic disease. Dysphagia may progress to such a degree that the patient is unable to eat. Few reports have detailed the nature of the swallowing dysfunction in patients with WD. Previous reports have shown upper esophageal dysmotility, but none has analyzed pharyngeal motility. We performed a videofluoroscopic swallowing evaluation on a 49-year-old woman with WD who had a history of progressive dysphagia. Videofluoroscopy showed significant pooling of swallowed material in the valleculae and pyriform sinuses, suggesting a reduction in pharyngeal peristalsis. Pooled material in the valleculae was cleared only after repeated swallowing of liquid. These findings suggest that dysphagia in WD may involve pharyngeal as well as esophageal dysmotility. Pharyngeal dysmotility is important to identify, since this places the patient at risk for aspiration pneumonia. Documentation of this finding in these patients is also important for the therapeutic management of their swallowing. Such findings could prove to be of diagnostic value in identifying the disease and monitoring its progression.     

Prevalence of Macrocreatinkinase Type 1 in Patients with Inflammatory Bowel Disease

Macro-creatine-kinases are isoenzymes of creatinine-kinases (CK). They have been classified in two types: type 1 (CK bound to an immunoglobulin) and type 2 (an oligomeric mitochondrial CK). CK type 1 has been found in patients with ulcerative colitis (UC) but not in Crohn’s disease (CD). However, there are no studies evaluating macro-creatinkinase prevalence in inflammatory bowel disease (IBD). We included 159 consecutive patients (72 UC, 85 CD; 2 indeterminate colitis). Creatin-kinase total activity and isoenzymes activities were determined. Twelve (16.7%) patients with UC and one of the two patients with indeterminate colitis had serum macro-creatinkinase type 1 while no CD patients displayed this macromolecule (P < 0,001). Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio were calculated for ulcerative colitis versus Crohn’s disease diagnosis, being 16.7, 98.9, 92.3, 59, 14.5, and 0.84% respectively. There was no correlation with age, gender, time from diagnosis, associated diseases, concomitant medication or disease activity. In conclusion our data suggests that the presence of macro-CK in IBD favors the diagnosis of ulcerative colitis. Further studies are necessary to understand the significance of this finding in a subset of patients with IBD.     

Sargramostim in patients with Crohn’s disease: results of a phase 1–2 study

Background  We aimed to assess the tolerability, pharmacokinetics, safety, and efficacy of sargramostim in Japanese patients with active Crohn’s disease (CD). Methods  Patients with moderately to severely active CD were enrolled. Step 1 was an open-label, phase 1 study of 2 μg/kg per day sargramostim administered subcutaneously (SC) for 4 weeks, with an optional 8-week extension with 6 μg/kg per day. Step 2 was an open-label, phase 1–2 study of the tolerability and pharmacokinetics of SC sargramostim 6 μg/kg per day over 4 weeks and of 8-week efficacy and safety. Efficacy variables were the proportion of patients achieving a clinical response [≥100-point decrease from baseline in the CD activity index (CDAI)] and the proportion achieving clinical remission (CDAI ≤ 150 points). Results  Six patients participated in Step 1; five in Step 2. Serum concentrations of sargramostim peaked within 1 h of administration; mean terminal half-life was 2 h. Maximal serum concentrations increased with the dose. Mean accumulation ratios were 0.998 in Step 1 and 0.673 in Step 2. One of the six patients in the Step-1 extension and none of the five in Step 2 achieved a clinical response. Clinical remission was reported in one patient in each step. A notable decrease in median CDAI scores was observed in the extension and Step 2. In responders, improvement tended to be maintained through the 30-day follow-up. Drug-related adverse events included injection-site reaction, pyrexia, back pain, and bone pain. Conclusion  The systemic exposure of sargramostim increased dose-dependently. No accumulation in systemic exposure was associated with the repeated once-daily administration. SC sargramostim at 6 μg/kg per day improved median CDAI scores. A minority of patients experienced clinical remission or clinical response.     

Cheilitis granulomatosa as an early manifestation of Crohn’s disease

Cheilitis granulomatosa (CG) is a rare disease, which presents usually as a persistent swelling of the soft tissues in the orofacial region and is characterized histologically by a granulomatous inflammation. We report the case of a 19-year-old man who suffered from anal fistula. The patient had a 6-year history of asymptomatic and persistent swelling of the lower lip. Examinations for gastrointestinal lesions containing double-balloon total enteroscopy revealed erosions located longitudinally throughout the small intestine and the patient was diagnosed Crohn’s disease (CD). Biopsy of the lower lip showed non-caseating granuloma and confirmed the diagnosis of CG. Despite an elemental diet and mesalazine therapy, the lip swelling persisted. The CG can be the first presenting symptom of CD. CG as a complication of CD is discussed.     

Sarcoidosis in Patients with Celiac Disease

Purpose Several case reports and European studies have suggested an association between sarcoidosis and celiac disease; however, they have been inconsistent. We therefore analyzed a large cohort of celiac-disease patients to assess this association. Methods An anonymized database of patients with celiac disease was reviewed to determine the number of patients with sarcoidosis. Age- and gender-adjusted standardized morbidity ratios with corresponding 95% confidence intervals (CI) were calculated by comparing results to US-population-derived prevalence data. Results Ten patients were found to have a comorbid diagnosis of sarcoidosis, representing an age- and gender-adjusted standardized morbidity ratio of 36.8 (95% CI 26.7–50.9). Conclusions In this cohort of patients with celiac disease, there was a significantly increased risk of sarcoidosis when compared with the American white population. This further strengthens prior associations that have been made suggesting a shared mechanism behind the etiologies of celiac disease and sarcoidosis.     

Correction of copper metabolism is not sustained long term in Wilson’s disease mice post bone marrow transplantation

Purpose Alternative cell sources have been sought for the treatment of liver diseases, since liver cells are in short supply for cell transplantation. Although bone marrow-derived cells have been investigated as an alternative cell source, few studies have demonstrated long-term disease correction. Here we examined bone marrow stem cell transplantation into the toxic milk (tx) mouse model for Wilson’s disease, a mild liver disease characterized by hepatic copper accumulation. The aim of this study was to determine whether bone marrow cells engrafted in the liver could sustain correction of abnormal copper metabolism in the tx mouse. Methods Bone marrow cells were isolated from congenic normal mice, transduced to express enhanced green fluorescent protein, sorted for stem cell (Sca-1) and lineage cell (Lin) surface markers, and then transplanted into sub-lethally irradiated normal or tx mice. Analysis for donor cell activity and distribution was undertaken 5 and 9 months post-transplant to allow for sufficient time to repopulate the liver and demonstrate disease correction. Results Donor bone marrow cells engrafted in both normal and tx mouse liver within 5 months. Significantly reduced liver copper was found in tx mice with donor cell liver engraftment at 5 months post-transplant compared to controls, demonstrating partial correction of abnormal copper metabolism in the short term. However, disease correction was not maintained 9 months post-transplantation. Lin⁻Sca-1⁺ cells were more likely to partially correct disease than Lin⁺Sca-1⁻ cells in the short term. Conclusion These results demonstrate that bone marrow transplants cannot maintain disease correction in a mouse model of mild hepatic damage, although initial copper metabolism correction was observed.     

A case of Crohn’s disease associated with Takayasu’s arteritis and Henoch-Sch?nlein purpura

A 14-year-old Japanese man was diagnosed with Crohn’s disease in October 2001. Four years later, the patient was referred to our institution because of neck pain, fever and asymmetrical blood pressure. Magnetic resonance angiography, computed tomography and ultrasonography revealed findings compatible with Takayasu’s arteritis. In March 2006, the patient developed purpura over bilateral hands and lower extremities, arthralgia, lower abdominal pain and microhematuria. The patient was diagnosed with Henoch-Schönlein purpura. This is the first reported case of Crohn’s disease associated with two types of vascular complications.     

Adenocarcinoma of the Small Bowel Arising From a Previous Strictureplasty for Crohn’s Disease: Report of a Case

Small-bowel adenocarcinoma is an uncommon tumor, comprising<2 percent of all gastrointestinal tract malignancies. These tumors are known to occur in association with Crohn’s disease. To date, there have been only two documented cases of adenocarcinoma arising at the site of previous strictureplasty reported in the literature. We report the third such case in a patient with no other premalignant conditions affecting the small bowel and question whether we may see an increasing trend in this type of presentation.     

Nasal Septal Perforation in an Adolescent Girl with Crohn’s Disease: A Rare Extraintestinal Manifestation

Crohn's Disease (CD) is a chronic granulomatous inflammatory bowel disease which may also involve the extraintestinal organs such as joints, liver, skin and perianal tissue. Involvement of the aerodigestive tract is quite rare in CD. We report a 16-year-old girl with CD and nasal perforation as an extraintestinal manifestation of the disease.     

Serum Ghrelin Levels in Inflammatory Bowel Disease with Relation to Disease Activity and Nutritional Status

Ghrelin possesses various biological activities -- it stimulates growth hormone (GH) release, plays a major role in energy metabolism, and is one of the hormones that affects body composition. It also plays a role in modulating immune response and inflammatory processes. In this study we aimed to determine whether serum ghrelin levels had correlation with markers associated with disease activation. We also investigated any probable relationship between serum ghrelin level and nutritional status. Serum levels of ghrelin and its relationship with disease activity and nutritional status were evaluated in 34 patients with ulcerative colitis (UC), 25 patients with Crohn's disease (CD), and 30 healthy controls. Serum ghrelin levels, serum IGF-1 and GH levels, and markers of disease activity (sedimentation, C-reactive protein, and fibrinogen) were measured in all subjects. Body composition and nutritional status was assessed by both direct (by anthropometry) and indirect (by bioimpedance) methods. Serum ghrelin levels were significantly higher in patients with active UC and CD than in those in remission (108 +/- 11 pg/ml vs. 71 +/- 13 pg/ml for UC patients, P < 0.001; 110 +/- 10 pg/ml vs. 75 +/- 15 pg/ml for CD patients, P < 0.001). Circulating ghrelin levels in UC and CD patients were positively correlated with sedimentation, fibrinogen and CRP and was negatively correlated with IGF-1, BMI, TSFT, MAC, fat mass (%), and fat free mass (%). This study demonstrates that patients with active IBD have higher serum ghrelin levels than patients in remission and high levels of circulating ghrelin correlate with the severity of disease and the activity markers. Ghrelin levels in inflammatory bowel disease (IBD) patients show an appositive correlation with IGF-1 and bioelectrical impedance analysis, body composition, and anthropometric assessments. Finally, we arrived at the conclusion that ghrelin level may be important in determination of the activity in IBD patients and evaluation of nutritional status.     

Bowel ultrasound in Crohn’s disease: surgical perspective

Background Bowel ultrasound has been proven to be a useful tool in the management of Crohn’s disease, particularly in the assessment of intra-abdominal complications, most of which require surgery. Materials and methods The National Library of Medicine has been searched for articles on the use of bowel ultrasound in Crohn’s disease focusing on aspects of interest to the surgeon. Results and conclusions Several studies have demonstrated that bowel ultrasound may be useful to reduce the risk of unnecessary laparotomy in patients presenting acute abdomen with suspected chronic inflammatory bowel disease. Bowel ultrasound has been proven to be of value in the follow-up of Crohn’s disease patients since allowing early diagnosis of intra-abdominal complications and, therefore, optimising the diagnostic and surgical approach. At follow-up, bowel ultrasound may accurately diagnose early post-operative complications and long-term disease recurrence. In patients submitted to conservative surgery, ultrasonography reveals changes in diseased bowel walls that may be predictive of recurrence of the disease, and hence determinant in the choice of medical treatment.     

Reactivation of hepatitis B in a patient with Crohn’s disease treated using infliximab

We encountered a case of reactivation of hepatitis B virus after administration of infliximab for Crohn's disease. The use of infliximab was considered because the patient displayed abdominal symptoms and perianal lesions. Transaminases were normal, and hepatitis B virus (HBV) DNA was undetectable before treatment, so no antiviral treatment was used, and infliximab and low-dose 6-mercaptopurine were administered. This treatment was effective, but liver dysfunction and reactivation of HBV were observed after the fourth injection of infliximab. This is the first report of Crohn's disease for which infliximab use was continued even after reactivation of HBV was observed. However, liver dysfunction was not improved by lamivudine. Antiviral treatment should be considered before administration of infliximab for patients with HBV.     

Serum Mannan-Binding Lectin Levels in Patients with Celiac Disease: An Analysis of Clinical and Autoimmune Features

Mannan-binding lectin (MBL) is the central protein in the activation of complement through the lectin pathway. MBL plasma concentration is genetically determined and varies significantly among individuals. Recent findings suggest that MBL is associated with the pathogenesis of celiac disease (CD). In this study, MBL and C-reactive protein (CRP) levels were determined in 101 celiac patients and 120 controls, with the aim to associate with the presence of gluten in the diet, disease severity, and the presence of concomitant autoimmune diseases. MBL concentration was determined by ELISA and CRP by nephelometry, using a high-sensitivity method. EmA-IgA and other autoantibodies were tested by indirect imunofluorescence. Although a significant increase in MBL levels was observed in male patients compared to female (P = 0.024), the absence of any other association suggests that circulating MBL and CRP concentrations are not associated with clinical and autoimmune CD features in Brazilian patients.     

Prevalence of Silent Celiac Disease in Patients with Dyspepsia

Celiac disease (CD) has become more common than in the past, although it frequently remains undetected for long periods of time. One reason for this is failure by health care professionals to recognize the variable clinical manifestations of CD and to perform the appropriate tests to make the diagnosis. Although dyspepsia may be part of a clinical spectrum in CD patients, there are scarce data about its prevalence in silent CD. We aimed to determine the prevalence of CD in otherwise healthy dyspeptic patients by means of serologic screening followed by endoscopic biopsies if appropriate. Anti-endomysium antibody assay was positive in 3 of 196 patients. All 3 were female, ages ranged from 19–52 years (mean ± SD age, 36±16 years). Duodenal biopsies were compatible with CD in all, whereas abnormal endoscopic findings were noted in 2. Therefore, a 1.5% prevalence of CD was observed in this study group. The odds ratio for CD was 2.57 (95% confidence interval) in comparison with the general population. CD should be kept in mind as a cause of dyspepsia during clinical activities. The association between these 2 conditions is, at most, weak, but a gluten-free diet may still bring symptomatic relief for dyspeptic symptoms in CD. During endoscopic examination for dyspepsia, if indicated, endoscopists should carefully inspect the duodenum for CD findings. Although routine serologic screening can not be recommended, it may be appropriate for the patients with refractory dyspepsia, especially females.     

Response to Hepatitis B Vaccination in Patients with Celiac Disease

Abnormal immune response to gliadin, genetic, and environmental factors play a role in the pathogenesis of celiac disease (CD). Non-responsiveness to hepatitis B virus (HBV) vaccination is related to genetic features. Certain human leukocyte antigen (HLA) genotypes are more prevalent among non-responders to HBV vaccination. There is also a strong relationship between CD and these HLA genotypes. This study investigates the relationship between CD and non-responsiveness to HBV vaccination, with an emphasis on genotypic co-incidence. No statistically significant difference was noted between the ages and gender of CD patients and control subjects. Baseline serum IgA, IgM, and IgG levels of all CD patients were normal. Responsiveness to HBV vaccination was observed in 17 (68%) CD patients and all (100%) control subjects (P = 0.006). In conclusion, CD should also be sought in unresponders to HBV vaccine who are not immunosuppressed.     

IL-15 Gene Polymorphism in Celiac Disease Patients and Their Siblings

BackgroundCeliac disease (CD) is an immune-mediated enteropathy characterized by lifelong gluten intolerance. Interleukin-15 (IL-15) is a proinflammatory cytokine that is considered a key component in the immune reaction triggered by gluten. Our aim of this study was to evaluate the influence of IL-15 gene polymorphisms on CD development and clinical presentation.MethodsThe study was enrolled-with 90 CD patients (49 female/41 male, median years of age 11), their 38 siblings (20 female/18 male, median years of age 8), and 99 healthy controls (66 female/33 male, median years of age 13). Their demographic findings, symptoms, and signs histopathological grade, Human Leukocyte Antigen (HLA) types were recorded. IL-15 gene polymorphisms rs2857261, rs10519613, and rs1057972 were analyzed through PCR.ResultsThere was a significantly higher frequency of GG genotype in rs2857972 polymorphisms and TT genotype in rs1057972 polymorphisms in celiac families compared to controls [41% vs. 23% (P = .0008), 36% vs. 11% (P = .001), respectively]. Without considering their HLA status, there was not any difference between celiacs and healthy siblings. However, when stratified according to their HLADQ2 status, rs2857972 GG polymorphism was 1.5 times prominent in celiacs than siblings at homozygous state, whereas rs1057972 TT genotype was found to be 2.5 times prominent in celiac siblings at heterozygous state. There was no association between these polymorphisms and clinical presentation.Conclusionrs2857972 GG and rs1057972 TT variants of IL 15 are more prominent in celiac families than controls. However, the impact of IL-15 gene polymorphism on CD development is dependent on HLADQ2 status.