[Ulcers in vulva and perineum induced by an anti-anginal drug].

Nicorandil is a type of nicotinamide ester used for the treatment of angina and ischaemic heart disease. A 67-year-old woman was referred to a pelvic floor unit with possible vulvar cancer. She had a painful 2 × 1.5 cm punched-out ulcer. A biopsy showed inflammation, but no evidence of malignancy, infection or dysplasia. She had angina which had been controlled with nicorandil for the past six years. After nearly two years of treatment and examinations nicorandil-induced ulceration was suspected and in liaison with cardiologist, the nicorandil treatment was discontinued. Within a few months, the pain settled, and her ulcers healed.

[Collagenous sprue in a patient with severe diarrhoea, malnutrition and acute renal failure].

Collagenous sprue is a rare enteropathy affecting the small intestinal mucosa and can resemble and coincide with coeliac disease or collagenous colitis. To our knowledge, less than 175 cases of collagenous sprue have been described. Both clinicians and pathologists should be aware of the condition in order to adequately target their investigations and treatment. This is a case report of severe collagenous sprue in a 78-year-old male resulting in severe diarrhoea, weight loss, malnutrition and acute kidney failure. The disorder improved on a lactose and gluten-free diet, loperamide and corticosteroids.

[Genetic HFE-haemochromatosis].

HFE-haemochromatosis is the most frequent genetic disposition for iron overload in ethnic Danes: 20,000 persons are homozygous for the C282Y mutation. The disorder has a long preclinical phase with increasing body iron overload, and 30% of males will develop clinically overt disease, presenting with symptoms of fatigue, arthralgias, reduced libido, erectile dysfunction, cardiac disease, diabetes and liver disease, later progressing into cirrhosis, cardio-myo-pathy, pancreatic fibrosis and osteoporosis. Treatment consists of phlebotomies, which in the preclinical and early clinical phases ensure normal survival.

Symptomatic Patency Capsule Retention in Suspected Crohn's Disease.

The main limitation of capsule endoscopy is the risk of capsule retention. In patients with suspected Crohn's disease, however, this complication is rare, and if a small bowel stenosis is not reliably excluded, small bowel patency can be confirmed with the Pillcam patency capsule. We present two patients examined for suspected Crohn's disease who experienced significant symptoms from a retained patency capsule. Both patients had Crohn's disease located in the terminal ileum. In one patient, the patency capsule caused abdominal pain and vomiting and was visualized at magnetic resonance enterography 9 days after ingestion. Symptoms improved spontaneously. Another patient experienced small bowel perforation with severe peritonitis caused by an intact patency capsule wedged in a small bowel stricture. We conclude that the Pillcam patency capsule is an effective modality for securing small bowel patency prior to capsule endoscopy. However, it should be emphasized that delayed patency capsule degradation and symptomatic capsule retention is a rare but potentially severe complication which should be treated aggressively, either medically or endoscopically.

Circulating microRNAs as biomarkers of adult Crohn's disease.

OBJECTIVE: Previous studies have found a differential expression of microRNAs (miRNAs) in the blood of patients with Crohn's disease (CD) compared with healthy controls. The aim of this study was to identify circulating miRNAs expressed in CD and assess their performance as biomarkers in patients with clinically suspected or known CD. METHODS: The study consisted of two parts: (a) miRNA profiling: The miRNA expression pattern was examined in six patients with CD and six controls using OpenArray miRNA profiling, and the best miRNAs were selected according to their P-value. (b) Validation cohort: In a well-characterized cohort of 102 patients with suspected or known CD, miRNAs identified by miRNA profiling or selected from previously published studies (hsa-miR-16, hsa-miR-21, hsa-miR-106a, and hsa-miR-140-3p) were measured in plasma using reverse transcription PCR. RESULTS: miRNA profiling: hsa-miR-369-3p, hsa-miR-376a, hsa-miR-376, hsa-miR-411#, hsa-miR-411, and mmu-miR-379 were downregulated in CD patients compared with the controls; hsa-miR-200c, hsa-miR-181-2#, and hsa-miR-125a-5p were upregulated (P<0.05). Validation cohort: Only hsa-miR-16 was significantly downregulated in patients with CD compared with patients without CD (fold change 0.83, P=0.02). Receiver operating characteristic analyses showed an area under the curve of 0.65. miRNAs could not discriminate inflammatory from stricturing CD or small bowel CD from CD involving the colon. CONCLUSION: In a clinically relevant cohort of patients, miRNAs in plasma identified in the present and previous studies were inadequate biomarkers for the diagnosis of CD.

Diagnosis and treatment of unexplained anemia with iron deficiency without overt bleeding.

A general overview is given of the causes of anemia with iron deficiency as well as the pathogenesis of anemia and the para-clinical diagnosis of anemia. Anemia with iron deficiency but without overt GI bleeding is associated with a risk of malignant disease of the gastrointestinal tract; upper gastrointestinal cancer is 1/7 as common as colon cancer. Benign gastrointestinal causes of anemia are iron malabsorption (atrophic gastritis, celiac disease, chronic inflammation, and bariatric surgery) and chronic blood loss due to gastrointestinal ulcerations. The following diagnostic strategy is recommended for unexplained anemia with iron deficiency: conduct serological celiac disease screening with transglutaminase antibody (IgA type) and IgA testing and perform bidirectional endoscopy (gastroscopy and colonoscopy). Bidirectional endoscopy is not required in premenopausal women < 40 years of age. Small intestine investigation (capsule endoscopy, CT, or MRI enterography) is not recommended routinely after negative bidirectional endoscopy but should be conducted if there are red flags indicating malignant or inflammatory small bowel disease (e.g., involuntary weight loss, abdominal pain or increased CRP). Targeted treatment of any cause of anemia with iron deficiency found on diagnostic assessment should be initiated. In addition, iron supplementation should be administered, with the goal of normalizing hemoglobin levels and replenishing iron stores. Oral treatment with a 100-200 mg daily dose of elemental iron is recommended (lower dose if side effects), but 3-6 months of oral iron therapy is often required to achieve therapeutic goals. Intravenous iron therapy is used if oral treatment lacks efficacy or causes side effects or in the presence of intestinal malabsorption or prolonged inflammation. Three algorithms are given for the following conditions: a) the paraclinical diagnosis of anemia with iron deficiency; b) the diagnostic work-up for unexplained anemia with iron deficiency without overt bleeding; and c) how to proceed after negative bidirectional endoscopy of the gastrointestinal tract.

Budesonide is more effective than mesalamine or placebo in short-term treatment of collagenous colitis.

BACKGROUND & AIMS: Studies reporting that budesonide is effective for the treatment of collagenous colitis have been small and differed in efficacy measures. Mesalamine has been proposed as a treatment option for collagenous colitis, although its efficacy has never been investigated in placebo-controlled trials. We performed a phase 3, placebo-controlled, multicenter study to evaluate budesonide and mesalamine as short-term treatments for collagenous colitis. METHODS: Patients with active collagenous colitis were randomly assigned to groups given pH-modified release oral budesonide capsules (9 mg budesonide once daily, Budenofalk, n = 30), mesalamine granules (3 g mesalamine once daily, Salofalk, n = 25), or placebo for 8 weeks (n = 37) in a double-blind, double-dummy fashion. The study was conducted in 31 centers (hospital clinics and private practices) in Germany, Denmark, Lithuania, Spain, and the United Kingdom. The primary end point was clinical remission at 8 weeks defined as ≤ 3 stools per day. Secondary end points included clinical remission at 8 weeks, according to the Hjortswang-Criteria of disease activity, taking stool consistency into account. RESULTS: A greater percentage of patients in the budesonide group were in clinical remission at week 8 than the placebo group (intention-to-treat analysis, 80.0% vs 59.5%; P = .072; per-protocol analysis, 84.8% vs 60.6%; P = .046). Based on the Hjortswang-Criteria, 80.0% of patients given budesonide achieved clinical remission compared with 37.8% of patients given placebo (P = .0006); 44.0% of patients given mesalamine achieved clinical remission, but budesonide was superior to mesalamine (P = .0035). Budesonide significantly improved stool consistency and mucosal histology, and alleviated abdominal pain. The rate of adverse events did not differ among groups. CONCLUSIONS: Oral budesonide (9 mg once daily) is effective and safe for short-term treatment of collagenous colitis. Short-term treatment with oral mesalamine (3 g once daily) appears to be ineffective. ClinicalTrials.gov number, NCT00450086.

High sensitivity of quick view capsule endoscopy for detection of small bowel Crohn's disease.

BACKGROUND AND AIM: Capsule endoscopy (CE) has a high sensitivity for diagnosing small bowel Crohn's disease, but video analysis is time-consuming. The quick view (qv) function is an effective tool to reduce time consumption. The aim of this study was to determine the rate of missed small bowel ulcerations with qv-CE compared with standard view and the diagnostic accuracy of qv-CE in suspected Crohn's disease. METHODS: This study consisted of two parts: (i) 12 small bowel segments with Crohn's disease of varying severity were selected for a detailed analysis of the number and type of lesions visualized with CE and qv-CE, and (ii) a blinded study of the diagnostic accuracy of qv-CE including 40 patients with suspected Crohn's disease. Ileocolonoscopy and CE served as gold standard. RESULTS: Part 1: CE visualized 171 ulcerations compared with 102 detected with qv-CE (miss rate 40%, P = 0.02). Part 2: qv-CE identified 15 of 16 patients with small bowel Crohn's disease corresponding to a 94% sensitivity, and overall, 39 out of 40 patients were classified correct (diagnostic accuracy 98%). Qv-CE was false negative in one patient because of a leap of 3 min and 20 s in the terminal ileum. Reading times varied from 5 to 18 min (median 10). CONCLUSION: Despite a significant number of missed lesions, qv-CE is a safe and time-reducing method for diagnosing small bowel Crohn's disease. To avoid false negative cases, we recommend viewing the terminal ileum in standard view.

Histiocytic disorders of the gastrointestinal tract.

The morphologic diagnosis of histiocytic lesions of the gastrointestinal tract can be challenging, and several disorders have to be considered in their differential diagnosis. We present one of the most widespread examples of xanthomatosis of the gastrointestinal tract published so far and give a short review on histiocytic disorders of the gastrointestinal tract in general. The primary histiocytic disorders of uncertain origin, Rosai-Dorfman disease, Langerhans cell histiocytosis, and Erdheim-Chester disease, are addressed. Reactive and infectious conditions such as xanthomatosis, xanthogranulomatous inflammation, juvenile xanthogranuloma, Whipple's disease and malacoplakia are discussed as well. We also briefly go into primary histiocytic disorders of neoplastic origin, systemic diseases with secondary gastrointestinal tract involvement like the lysosomal storage disorders, and pigmented lesions. Using a panel of histochemical stains and immunohistochemical markers, together with conventional microscopy, clinical information, and imaging studies, the diagnosis of histiocytic disorders of the gastrointestinal tract can be established in most instances.

Ileoscopy reduces the need for small bowel imaging in suspected Crohn's disease.

INTRODUCTION: In suspected Crohn's disease (CD), current diagnostic guidelines recommend additional small bowel imaging irrespective of the findings at ileocolonoscopy. Magnetic resonance imaging enterography (MRE) and computed tomography enterography (CTE) are regarded first line imaging techniques and should generally precede capsule endoscopy. MATERIAL AND METHODS: This article brings together results from a prospective blinded diagnostic study of MRE, CTE, capsule endoscopy and faecal calprotectin (fCal) in 93 patients undergoing their first diagnostic work-up for CD. RESULTS: In patients with suspected CD, fCal is useful for the identification patients without need for colonoscopy or small bowel imaging. Patients with an elevated fCal should undergo colonoscopy including a persistent attempt to intubate the terminal ileum. CD isolated in the upper small bowel is rare, and in patients with a normal ileocolonoscopy or non-complicated CD in the colon and/or terminal ileum, small bowel imaging provides little extra information compared to ileoscopy alone. Small bowel imaging is primarily indicated if ileoscopy is not achieved and capsule endoscopy is recommended as first line imaging technique. If small bowel stenosis is not ruled out, a preceding test with a patency capsule can be performed to avoid capsule retention. MRE and CTE are complimentary modalities preferably used in patients with stenosis detected at ileocolonoscopy or suspicion of extra-intestinal disease complications. CONCLUSION: Our results suggest that a diagnostic approach different to that described in the guidelines may be expedient. FUNDING: not relevant. TRIAL REGISTRATION: The study was approved by the Ethics Committee of Southern Denmark (S-20070072) and the Danish Data Protection Agency (journal number: 2007-41-0675). ClinicalTrials.gov identifier: NCT01019460.

Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response.

BACKGROUND: Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose-doubling. METHODS: A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose-doubling (10 mg/kg/8 weeks). RESULTS: In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose-doubling and 56 received interval-halving strategy. Early response to dose-escalation was experienced by 86/112 (77%) patients in the dose-doubling group compared with 37/56 patients (66%) in the interval-halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8-3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose-doubling group compared with 39% in the interval-halving group (OR 1.5, 95% CI 0.8-2.9, P = 0.2). On multivariate analysis, predictors of long-term response to escalation were a nonsmoking status, CD diagnosis between 16-40 years of age, and normal C-reactive protein (CRP). CONCLUSIONS: Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose-doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose-doubling strategy may be preferable to the interval-halving strategy.

Diagnostic accuracies of MR enterography and CT enterography in symptomatic Crohn's disease.

OBJECTIVE: In patients, with symptomatic Crohn's disease (CD), valid information about the presence or absence of small bowel disease activity and stenosis is clinically important. Such information supports decisions about medical or surgical therapy and can be obtained with MR enterography (MRE) or CT enterography (CTE). MATERIALS AND METHODS: A total of 50 patients with symptomatic pre-existing CD and a demand for small bowel imaging to support changes in treatment strategy were included in this prospective and blinded study. MRE and CTE were performed on the same day in alternating order and subsequently compared with the gold standard: pre-defined lesions at ileoscopy (n = 30) or surgery with (n = 12) or without (n = 3) intra-operative enteroscopy. RESULTS: A total of 35 patients had active small bowel CD (jejunum 0, ileum 1, (neo)-terminal ileum 34) and 20 had small bowel stenosis. The sensitivity and specificity of MRE for detection of small bowel CD was 74% and 80% compared to 83% and 70% with CTE (p ≥ 0.5). MRE and CTE detected small bowel stenosis with 55% and 70% sensitivities, respectively (p = 0.3) and 92% specificities. CONCLUSIONS: MRE and CTE have comparable diagnostic accuracies for detection of small bowel CD and stenosis. In symptomatic patients with CD and high disease prevalence, positive predictive values are favorable but negative predictive values are low. Consequently, MRE and CTE can be relied upon, if a positive result is obtained whereas a negative enterography should be interpreted with caution.

Fecal calprotectin is equally sensitive in Crohn's disease affecting the small bowel and colon.

OBJECTIVE: The utility of fecal calprotectin (fCal) in small bowel Crohn's disease (CD) remains to be clarified. The primary aim of this study was to determine levels of fCal in CD restricted to the small bowel compared with CD affecting the colon, in patients undergoing their first diagnostic work-up. In addition, the study assessed the sensitivity and specificity of fCal in suspected CD. MATERIAL AND METHODS: A total of 83 patients referred to gastroenterology out-patient clinic with suspected CD were included in this prospective, blinded study, and fCal was measured during diagnostic work-up. Ileo-colonoscopy + capsule endoscopy/surgery (n = 81), ileo-colonoscopy + upper endoscopy (n = 1), and ileo-colonoscopy (n = 1) served as gold standard for the presence and location of CD. RESULTS: A total of 40 patients were diagnosed with CD: small bowel 13, colonic 16, and ileo-colonic 11. Levels of fCal were equal in patients with small bowel or colonic CD: median 890 mg/kg and 830 mg/kg, respectively (p = 1.0). With a 50 mg/kg cut-off, CD in the small intestine and colon was diagnosed with 92% and 94% sensitivities, respectively, and the overall sensitivity and specificity of fCal was 95% and 56%. In this cohort, CD was ruled out with a negative predictive value of 92%. CONCLUSIONS: This is the first study to show that fCal is equally sensitive in colonic and small bowel CD. In patients suspected of CD, fCal is an effective marker to rule out this diagnosis and select patients for endoscopy.

Diagnostic accuracy of capsule endoscopy for small bowel Crohn's disease is superior to that of MR enterography or CT enterography.

BACKGROUND & AIMS: Capsule endoscopy (CE) detects small bowel Crohn's disease with greater diagnostic yield than radiologic procedures, although there are concerns that CE has low specificity. We compared the sensitivity and specificity of CE, magnetic resonance imaging enterography (MRE) and computed tomography enterography (CTE) in patients with suspected or newly diagnosed Crohn's disease. METHODS: We performed a prospective, blinded study of 93 patients scheduled to undergo ileocolonoscopy, MRE, and CTE and subsequently CE if stenosis was excluded. Physicians reporting CE, MRE, and CTE results were blinded to patient histories and findings from ileocolonoscopy and other small bowel examinations. Results were compared with those from ileoscopy (n = 70), ileoscopy and surgery (n = 4), or surgery (n = 1). RESULTS: Twenty-one patients had Crohn's disease in the terminal ileum. The sensitivity and specificity for diagnosis of Crohn's disease of the terminal ileum were 100% and 91% by CE, 81% and 86% by MRE, and 76% and 85% by CTE, respectively. Proximal Crohn's disease was detected in 18 patients by using CE, compared with 2 and 6 patients by using MRE or CTE, respectively (P < .05). Small bowel stenosis was observed in 5 patients by using CTE and 1 patient by using MRE. Cross-sectional imaging results indicated additional stenoses in only 2 of the patients who received complete ileocolonoscopies. CONCLUSIONS: In suspected or newly diagnosed Crohn's disease, MRE and CTE have comparable sensitivities and specificities. In patients without endoscopic or clinical suspicion of stenosis, CE should be the first line modality for detection of small bowel Crohn's disease beyond the reach of the colonoscope.

Inter-observer agreement for detection of small bowel Crohn's disease with capsule endoscopy.

OBJECTIVE: Compared to other modalities, capsule endoscopy (CE) has a high diagnostic yield for diagnosing small bowel Crohn's disease (CD). The aim of this study was to determine the inter-observer agreement for detection of small bowel CD with predefined diagnostic criteria. MATERIAL AND METHODS: Thirty patients with suspected or known CD were included in the study. Observers were blind to patient histories, the results of ileo-colonoscopies, and small bowel examinations. More than three ulcerations (aphthous lesions or ulcers) or the presence of stenosis caused by inflammation or fibrosis was diagnostic of small bowel CD. Three observers with experience in gastrointestinal endoscopy and CE participated in the study. RESULTS: The presence or absence of small bowel CD was determined with complete agreement in 23 patients, nine patients with and 14 without small bowel CD. The inter-observer agreement was substantial for the diagnosis (kappa = 0.68) and moderate for the localization of CD (kappa = 0.44). Aphthous lesions were detected with only fair agreement (kappa = 0.38). The time intervals to passage of the pylorus and ileo-caecal valve were detected with excellent intra-class correlation. CONCLUSIONS: CE is performed with substantial inter-observer agreement for detection of small bowel CD. In the majority of patients, the presence or absence of small bowel CD is unequivocal. However, in patients with few or minor lesions, the diagnosis is observer dependent.

Incidental findings at MRI-enterography in patients with suspected or known Crohn's disease.

AIM: To determine the frequency and clinical impact of incidental findings detected with magnetic resonance imaging (MRI)-enterography in patients with suspected or known Crohn's disease (CD). METHODS: Incidental findings were defined as unexpected lesions outside the small intestine, not previously known or suspected at the time of referral, and not related to inflammatory bowel disease. Through a systematic review of medical charts we analyzed the clinical impact of incidental findings, and compared the MRI findings with subsequent diagnostic procedures. RESULTS: A total of 283 patients were included in the analysis, and MRI detected active CD in 31%, fistula in 1.4% and abscess in 0.7%. Extra-intestinal findings not related to CD were recorded in 72 patients (25%), of which 58 patients (20%) had 74 previously unknown lesions. Important or incompletely characterized findings were detected in 17 patients (6.0%). Incidental findings led to 12 further interventions in 9 patients (3.2%) revealing previously unknown pathological conditions in 5 (1.8%). One patient (0.4%) underwent surgery and one patient was diagnosed with a malignant disease. MRI detected incidental colonic lesions in 16 patients of which additional work-up in 4 revealed normal anatomy. Two patients (0.7%) benefitted from the additional examinations, whereas incidental findings led to unnecessary examinations in 9 (3.2%). CONCLUSION: In a minority of patients with suspected or known CD, important incidental findings are diagnosed at MRI-enterography. However, a substantial number of patients experience unnecessary morbidity because of additional examinations of benign or normal conditions.

[Diagnostic imaging and endoscopic methods in Crohn's disease of the small intestine]. / Billeddiagnostiske og endoskopiske metoder ved Crohns sygdom i tyndtarmen.

Diagnosing Crohn's disease in the small intestine can be troublesome. Traditionally, the small bowel is evaluated by ileocolonoscopy and small bowel follow-through or enteroclysis. In recent years MRI, CT, ultrasound and capsule endoscopy have emerged. All are validated and implemented in clinical practice. Double-balloon enteroscopy, PET-CT and SPECT are newer methods, which are still being evaluated in clinical trials. The purpose of this article is to review clinical studies focusing on the validity of modalities for diagnosing Crohn's disease of the small intestine.